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J Pelletier

Publications and source records attributed to J Pelletier.

At least 37 records · Page 2Linked to original sources
PubMed2002

Melatonin and seasonal reproduction: understanding the neuroendocrine mechanisms using the sheep as a model.

The mechanisms by which melatonin controls seasonal reproduction are poorly understood. The use of a large animal model, namely the sheep, has allowed progress in the understanding of these mechanisms, and is the subject of this review. Firstly, the contribution made by large animal models to demonstrating that melatonin acts in the hypothalamus and the identification of this hypothalamic target is reviewed. Secondly, the way in which large animal models have facilitated the demonstration of a specific mechanism of release of melatonin in the cerebrospinal fluid and, thus, raised the question of the route used by melatonin to reach its central targets is discussed. Finally, the human and agricultural relevance of the data presented is considered.

Animals↗
PubMed2001

Functional characterization of WT1 binding sites within the human vitamin D receptor gene promoter.

The Wilms' tumor suppressor gene, wt1, encodes a zinc finger transcription factor that can regulate gene expression. It plays an essential role in tumorigenesis, kidney differentiation, and urogenital development. To identify WT1 downstream targets, gene expression profiling was conducted using a cDNA array hybridization approach. We confirm herein that the human vitamin D receptor (VDR), a ligand-activated transcription factor, is a WT1 downstream target. Nuclear run on experiments demonstrated that the effect of WT1 on VDR expression is at the transcriptional level. Transient transfection assays, deletion mutagenesis, electrophoretic mobility shift assays, and chromatin immunoprecipitation assays suggest that, although WT1 is presented with a possibility of three binding sites within the VDR promoter, activation of the human VDR gene appears to occur through a single site. This site differs from a previously identified WT1-responsive site in the murine VDR promoter (Maurer U, Jehan F, Englert C, Hübinger G, Weidmann E, DeLucas HF, and Bergmann L. J Biol Chem 276: 3727-3732, 2001). We also show that the products of a Denys-Drash syndrome allele of wt1 inhibit WT1-mediated transactivation of the human VDR promoter. Our results indicate that the human VDR gene is a downstream target of WT1 and may be regulated differently than its murine counterpart.

Alleles↗
PubMed2001

LEAFY COTYLEDON2 encodes a B3 domain transcription factor that induces embryo development.

The Arabidopsis LEAFY COTYLEDON2 (LEC2) gene is a central embryonic regulator that serves critical roles both early and late during embryo development. LEC2 is required for the maintenance of suspensor morphology, specification of cotyledon identity, progression through the maturation phase, and suppression of premature germination. We cloned the LEC2 gene on the basis of its chromosomal position and showed that the predicted polypeptide contains a B3 domain, a DNA-binding motif unique to plants that is characteristic of several transcription factors. We showed that LEC2 RNA accumulates primarily during seed development, consistent with our finding that LEC2 shares greatest similarity with the B3 domain transcription factors that act primarily in developing seeds, VIVIPAROUS1/ABA INSENSITIVE3 and FUSCA3. Ectopic, postembryonic expression of LEC2 in transgenic plants induces the formation of somatic embryos and other organ-like structures and often confers embryonic characteristics to seedlings. Together, these results suggest that LEC2 is a transcriptional regulator that establishes a cellular environment sufficient to initiate embryo development.

Amino Acid Sequence↗
PubMed2001

Low-temperature sterilization using gas plasmas: a review of the experiments and an analysis of the inactivation mechanisms.

Utilizing an ionized gas (plasma) to achieve sterilization is an alternative to conventional sterilization means as far as sterilization of heat-sensitive materials and innocuity of sterilizing agents are concerned. The literature on plasma sterilization is reviewed. A major issue of plasma sterilization is the respective roles of UV photons and reactive species such as atomic and radicals. Insight into this matter is obtained by analyzing the survival curves of microorganisms. In contrast to classical sterilization where such plots show a unique straight line, plasma sterilization yields survival diagrams with two or three different linear segments. Three basic mechanisms are involved in the plasma inactivation of microorganisms: (A) direct destruction by UV irradiation of the genetic material of microorganisms; (B) erosion of the microorganisms atom by atom, through intrinsic photodesorption by UV irradiation to form volatile compounds combining atoms intrinsic to the microorganisms; (C) erosion of the microorganisms, atom by atom, through etching to form volatile compounds as a result of slow combustion using oxygen atoms or radicals emanating from the plasma. In some cases, etching is further activated by UV photons, increasing the elimination rate of microorganisms. These mechanisms make plasma sterilization totally different from classical sterilization techniques and suggest its use to inactivate nonconventional infectious agents such as the abnormal prions.

Bacillus subtilis↗
PubMed2001

Full-length cDNAs: more than just reaching the ends.

The development of functional genomic resources is essential to understand and utilize information generated from genome sequencing projects. Central to the development of this technology is the creation of high-quality cDNA resources and improved technologies for analyzing coding and noncoding mRNA sequences. The isolation and mapping of cDNAs is an entrée to characterizing the information that is of significant biological relevance in the genome of an organism. However, a bottleneck is often encountered when attempting to bring to full-length (or at least full-coding) a number of incomplete cDNAs in parallel, since this involves the nonsystematic, time consuming, and labor-intensive iterative screening of a number of cDNA libraries of variable quality and/or directed strategies to process individual clones (e.g., 5' rapid amplification of cDNA ends). Here, we review the current state of the art in cDNA library generation, as well as present an analysis of the different steps involved in cDNA library generation.

Automation↗
PubMed2001

A longitudinal study of callosal atrophy and interhemispheric dysfunction in relapsing-remitting multiple sclerosis.

OBJECTIVES: To determine if callosal atrophy and interhemispheric dysfunction can be detected in the early stages of relapsing-remitting multiple sclerosis (MS) and to evaluate their progression in relation to the disability and evolution of lesions seen on magnetic resonance imaging during a 5-year period. METHODS: We compared 30 patients who had clinically definite early-onset replasing-remitting MS and mild disability with control subjects. Regional and segmental callosal size and extent of white matter abnormalities on magnetic resonance imaging, as well as performance on tasks exploring interhemispheric transfer of motor, auditory, and sensory information were assessed. Patients with MS were evaluated at baseline and after 5 years. Physical disability was determined at both times using the Expanded Disability Status Scale score. RESULTS: Patients with MS were seen with significant callosal atrophy and functional impairment of interhemispheric transfer at baseline that worsened during the 5-year study. A significant correlation was found between the magnitude of disability and the severity of morphological and functional callosal involvement at baseline. This association persisted at year 5. Baseline clinical characteristics such as age and prestudy relapse rate were unrelated to callosal size or interhemispheric performance. However, the number of baseline T2-weighted lesions was correlated with callosal involvement and this relation persisted at year 5. CONCLUSION: Patients who had relapsing-remitting MS in the early stages of the disease and mild disability had significant callosal involvement that progressed over time. The relationship between disability, T2-weighted lesions load, and degree of morphological and functional callosal impairment confirm the potential value of using callosal dysfunction as a surrogate marker of disease progression in MS.

Adult↗
PubMed2001

Assessment of the total number of human transcription units.

Variation in the estimates of the number of genes encoded by the human genome (28,000-120,000) attests to the difficulty of systematically identifying human genes. Sequencing of human chromosome 22 (Chr22) provided the first comprehensive, unbiased view of an entire human chromosome, and intensive analysis of this sequence identified 545 genes and 134 pseudogenes that had similarity or identity to known proteins and/or ESTs and which were listed in the gene annotation (http://www.sanger.ac.uk/HGP/Chr22). This analysis yielded an estimate of approximately 36,000 functional expressed genes in the human genome (and 9000 pseudogenes). However, a key uncertainty in this estimate was that hundreds of additional genes beyond those annotated in the Chr22 sequence are predicted by the gene prediction program Genscan, an unknown number of which might represent additional expressed genes. To determine what fraction of these "predicted novel genes" (PNGs) represents expressed human genes, we used a sensitive RT-PCR assay to detect predicted transcripts in 17 tissues and one cell line. Our results indicate that at least 5000-9000 additional human genes which lack similarity to known genes or proteins exist in the human genome, increasing baseline gene estimates to approximately 41,000-45,000.

Chromosomes, Human, Pair 22↗
PubMed2001

Regional metabolite levels of the normal posterior fossa studied by proton chemical shift imaging.

MR spectroscopy of the posterior fossa is pitted with numerous technical difficulties. It is, however, of great clinical interest in the study of the degenerative diseases and tumors of this area. We have developed a method to perform 2D CSI of this area, by using a sagittal slice and a careful positioning of outer volume saturation. We performed this acquisition in 30 healthy volunteers to determine the normal metabolic ratios in five voxels of this area (mesencephalon, pons, medulla oblongata, vermis, cerebellar white matter). The main technical difficulty was magnetic field inhomogeneity in the lower brainstem generated by dental alloys. However, 88% of the voxels were of sufficient quality to be analyzed. The statistically significant regional variations were a higher NAA/Cr ratio in the pons than in the medulla oblongata, higher Cho/Cr in the pons than in the mesencephalon and higher Cho/Cr in the cerebellar white matter than in the vermis. We conclude that 2D CSI of the brainstem, although technically delicate can be performed in most patients.

Brain↗
PubMed2001

Mapping protein-protein interactions with combinatorial biology methods.

Extremely diverse, DNA-encoded libraries of peptides and proteins have been constructed that include a linkage between each polypeptide and the encoding DNA. Library members can be selected by virtue of a particular binding specificity, and their protein sequence can be deduced from the sequence of the cognate DNA. Such combinatorial biology methods have proven invaluable in both identifying natural protein-protein interactions and also in mapping the specificities and energetics of these interactions in fine detail.

Amino Acid Sequence↗
PubMed2001

Novel (4-piperidin-1-yl)-phenyl sulfonamides as potent and selective human beta(3) agonists.

A series of novel (4-piperidin-1-yl)-phenyl sulfonamides was prepared and evaluated for their biological activity on the human beta(3)-adrenergic receptor (AR). Replacement of the 3,4-dihydroxyl group of the catechol moiety with 4-hydroxyl-3-methyl sulfonamide on the left-hand side of the compounds resulted in a number of potent full agonists at the beta(3) receptor. Modification of the right-hand side of the compounds by incorporation of a free carboxylic acid resulted in a few potent human beta(3) agonists with low affinities for beta(1)- and beta(2)-ARs. N-Alkyl substitution on the 4-piperidin-1-yl-phenylamine further increased the beta(3) potency while maintaining the selectivity. For example, sulfonamide 48 is a potent full beta(3) agonist (EC(50)=0.004 microM, IA=1.0) with > 500-fold selectivity over beta(1)- and beta(2)-ARs.

Adrenergic beta-3 Receptor Agonists↗
PubMed2001

Central nervous system disease in patients with macrophagic myofasciitis.

Macrophagic myofasciitis (MMF), a condition newly recognized in France, is manifested by diffuse myalgias and characterized by highly specific myopathological alterations which have recently been shown to represent an unusually persistent local reaction to intramuscular injections of aluminium-containing vaccines. Among 92 MMF patients recognized so far, eight of them, which included the seven patients reported here, had a symptomatic demyelinating CNS disorder. CNS manifestations included hemisensory or sensorimotor symptoms (four out of seven), bilateral pyramidal signs (six out of seven), cerebellar signs (four out of seven), visual loss (two out of seven), cognitive and behavioural disorders (one out of seven) and bladder dysfunction (one out of seven). Brain T(2)-weighted MRI showed single (two out of seven) or multiple (four out of seven) supratentorial white matter hyperintense signals and corpus callosum atrophy (one out of seven). Evoked potentials were abnormal in four out of six patients and CSF in four out of seven. According to Poser's criteria for multiple sclerosis, the diagnosis was clinically definite (five out of seven) or clinically probable multiple sclerosis (two out of seven). Six out of seven patients had diffuse myalgias. Deltoid muscle biopsy showed stereotypical accumulations of PAS (periodic acid-Schiff)-positive macrophages, sparse CD8+ T cells and minimal myofibre damage. Aluminium-containing vaccines had been administered 3-78 months (median = 33 months) before muscle biopsy (hepatitis B virus: four out of seven, tetanus toxoid: one out of seven, both hepatitis B virus and tetanus toxoid: two out of seven). The association between MMF and multiple sclerosis-like disorders may give new insights into the controversial issues surrounding vaccinations and demyelinating CNS disorders. Deltoid muscle biopsy searching for myopathological alterations of MMF should be performed in multiple sclerosis patients with diffuse myalgias.

Adult↗
PubMed2001

[Tremor and abnormal movement in multiple sclerosis: symptomatic therapeutic indications].

Tremor and movement disorders in multiple sclerosis (MS) patients cause a severe functional impairment. The different types of tremor observed in MS are: cerebellor tremor with a dominant intention component, Holmes tremor characterized by the addition of rest and postural components and palatal tremor. When no medication can improve the functional status, it is acceptable to discuss the deep brain stimulation in the VIM thalamus, thus making possible a partial attenuation of the rest and postural component, mainly affecting the proximal part of the affected limb. Among the movement disorders, paroxysmal dyskinesias are not rare and a good therapeutic response is obtained with carbamazepine: dystonia and parkinsonism are usually coincidental features during MS.

Electric Stimulation Therapy↗
PubMed2000

A set of canine interrepeat sequence PCR markers for high-throughput genotyping.

One hundred and sixteen interspersed repetitive DNA sequence (IRS)-PCR markers have been developed and characterized from Canis familiaris for high-throughput filter-based genotyping. We present a detailed analysis of markers produced by amplification using primers directed to the conserved regions of the C. familiaris short interspersed nuclear element (Can-SINE). The majority of IRS-PCR markers developed were moderately to highly polymorphic with mean heterozygosity (HET) and polymorphism information content (PIC) values of approximately 0.6. The HET value for 22.3% of the markers exceeded 0.7. We also demonstrate that sequence variation of Can-SINEs between breeds is significant and also represents a rich source of polymorphisms. Mapping of 73 of the markers to the existing integrated linkage-radiation hybrid map enriches the map as well as establishes the utility of the markers. The significance and utility of this new class of IRS-PCR Can-SINE-based markers for high-throughput genotyping is discussed. This method can also be extended to other species that are currently map-poor but have a sufficiently high density of SINEs to allow IRS-PCR.

Animals↗
PubMed2000

Modulation of EWS/WT1 activity by the v-Src protein tyrosine kinase.

Desmoplastic small round cell tumor (DSRCT) is a malignant human cancer that is associated with a specific t(11;22) chromosome translocation, where 265 amino acids from the EWS amino-terminus are fused to the DNA binding domain of the WT1 tumor suppressor gene. We have noticed the presence of several SH3 interacting domains within the amino-terminus of EWS and have assessed the potential of EWS/WT1 to interact with such motifs. We find that EWS/WT1 can associate with the SH3 domain of several proteins, including v-Src. Ectopic expression of v-Src phosphorylates EWS/WT1 in vivo, as well as enhances the transactivation ability of the EWS amino-terminal domain. Structural alteration of the v-Src SH2 or SH3 domains produced mutants that could not interact with EWS/WT1 nor augment the transcriptional properties of EWS. Taken together, our results suggest the possibility that some transcriptional properties of EWS/WT1 may be regulated by a cytoplasmic signaling pathway.

Amino Acid Motifs↗