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Biomedical subjects

J Pelletier

Publications and source records attributed to J Pelletier.

At least 127 records · Page 7Linked to original sources
PubMed1994

Anaplastic Wilms' tumour, a subtype displaying poor prognosis, harbours p53 gene mutations.

The genetics of Wilms' tumour (WT), a paediatric malignancy of the kidney, is complex. Inactivation of the tumour suppressor gene, WT1, is associated with tumour aetiology in approximately 10-15% of WTs. Chromosome 17p changes have been noted in cytogenetic studies of WTs, prompting us to screen 140 WTs for p53 mutations. When histopathology reports were available, p53 mutations were present in eight of eleven anaplastic WTs, a tumour subtype associated with poor prognosis. Amplification of MDM2, a gene whose product binds and sequesters p53, was excluded. Our results indicate that p53 alterations provide a molecular marker for anaplastic WTs.

Alleles↗
PubMed1994

Mutations in the muscle sodium channel gene (SCN4A) in 13 French families with hyperkalemic periodic paralysis and paramyotonia congenita: phenotype to genotype correlations and demonstration of the predominance of two mutations.

Hyperkalemic periodic paralysis (hyperPP), paramyotonia congenita (PC) and PC with myotonia permanens are closely related muscle disorders of genetic origin due to allelic mutations in the muscle sodium channel gene, SCN4A. Seven families of French origin with hyperPP were studied. Five of these had the Thr704Met mutation, but 2 families, genetically linked to SCN4A, failed to show any of the known mutations of SCN4A. Correlations between the phenotype and the genotype were made for patients with the Thr704Met mutation. All 12 patients over 30 years old with the Thr704Met mutation presented muscle weakness due to degeneration of muscle fibers in addition to periodic paralysis. Only approximately 12.5% of patients with the Thr704Met mutation presented with clinical myotonia and about 50% with hyperkalemia. One family with PC displayed the Gly1306Val mutation with a phenotype similar to the one already reported for this mutation. Five families with either PC or PC with myotonia permanens had the Thr1313Met mutation indicating that the severity of myotonia and its permanence were variable. Two mutations of SCN4A were found to be predominant in these 13 families: the Thr704Met and the Thr1313Met mutations. Only 2 families with the Thr704Met mutation and 3 families with the Thr1313Met shared the same SCN4A haplotype determined with intragenic dinucleotide repeats. Recurrent mutations of SCN4A may contribute to the predominance of these two mutations in the French population.

Adolescent↗
PubMed1994

[Spinal dural fistula with peri-medullar venous drainage].

Clinical and neuroradiological findings of 8 patients with a spinal dural arteriovenous fistula are reviewed. Disturbance of micturition or defecation and weakness of the legs were always present and the most frequent initial symptom was a progressive spastic paraparesis. Duration of symptoms before diagnosis was 2 years. Lumbar puncture showed elevation of proteins and myelography demonstrated dilated perimedullar posterior veins. In every case, magnetic resonance imaging of the spinal cord (T2- weighted images) revealed intramedullary high signal intensity of the conus medullaris and selective angiography confirmed the site of the dural fistula. Each patient was treated with endovascular method consisting in liquid adhesive embolization (0.2 cc of N-butyl cyanoacrylate) with hyperselective catheterism of the dorsospinal artery. Embolization procedure was successful in 6 cases with large improvement of leg weakness and partial regression of disturbed micturition and defecation. The pathophysiological mechanisms explaining the clinical signs are discussed.

Aged↗
PubMed1994

[Scanner in a medical emergency test of the nervous system].

Computed tomography is the essential examination in patients with severe manifestations of neurological disorders. We discuss emergency situations involving the central nervous system due to vascular and infections lesions. Trauma and acute complications of brain tumours, usually seen within a neurosurgical context, are not discussed here.

AIDS-Related Opportunistic Infections↗
PubMed1994

[Familial deficiency of C7 associated with adrenomyeloneuropathy].

A 24-year old man presented with recurrent meningitis resulting from familial deficiency of a late component of the complement system (C7). Five years later, he developed gait disturbance, mental impairment and loss of hearing. Adrenomyeloneuropathy was diagnosed by a raised plasma long chain fatty acids level.

Adrenoleukodystrophy↗
PubMed1994

Molecular genetics of Wilms' tumor: insights into normal and abnormal renal development.

Wilms' tumor is a pediatric malignancy of the kidney. Studies of the genetics of this disease have revealed a limited number of genes implicated in tumor initiation. The identification and characterization of these genes and their products represents an immediate challenge to further our understanding of the molecular events involved in tumor progression. Understanding the events leading to deregulation of cell growth and proliferation in Wilms' tumor has lead to the ability to predict a group of individuals at risk for this malignancy.

Adolescent↗
PubMed1993

Absence of p53 gene mutations in primary neuroblastomas.

Neuroblastoma is a common childhood malignancy of the sympathetic nervous system. Mutations in p53, a tumor suppressor gene located on the short arm of chromosome 17, are one of the most common genetic lesions in human cancers. The evidence for trisomies of 17q with loss of 17p in some cases of neuroblastoma led us to consider whether p53 mutations might contribute to the onset and progression of this malignancy. In this study, primary tumors from 38 neuroblastoma patients were screened for mutations within the coding exons of the p53 gene by single-strand conformation polymorphism analysis, and potential mutations were further analyzed by nucleotide sequence analysis. Previously described sequence variations were detected in many of the tumors, including a silent polymorphism at codon 213 (CGA to CGG) and the nontransforming Pro to Arg substitution at codon 72 (CCC to CGC). However, no other sequence variations were detected within the coding portions of the p53 gene. This finding suggests that p53 mutations do not contribute to the etiology of neuroblastoma and that the chromosome 17 alterations observed in neuroblastoma involve genes which are distinct from the p53 locus.

Base Sequence↗
PubMed1993

WT-1 is required for early kidney development.

In humans, germline mutations of the WT-1 tumor suppressor gene are associated with both Wilms' tumors and urogenital malformations. To develop a model system for the molecular analysis of urogenital development, we introduced a mutation into the murine WT-1 tumor suppressor gene by gene targeting in embryonic stem cells. The mutation resulted in embryonic lethality in homozygotes, and examination of mutant embryos revealed a failure of kidney and gonad development. Specifically, at day 11 of gestation, the cells of the metanephric blastema underwent apoptosis, the ureteric bud failed to grow out from the Wolffian duct, and the inductive events that lead to formation of the metanephric kidney did not occur. In addition, the mutation caused abnormal development of the mesothelium, heart, and lungs. Our results establish a crucial role for WT-1 in early urogenital development.

Alkaline Phosphatase↗
PubMed1993

Effects of a high-density intramammary device on mammary glands, production, and reproductive performance in dairy cows.

A clinical field trial was undertaken to determine the influence of an intramammary device (IMD) on environmental mastitis and production. On 4 central California dairies, 200 Holstein first-lactation cows were randomly assigned to 2 groups. Cows in the treatment group were fitted with an IMD, and cows in the control group were not. The incidence of clinical mastitis for the 2 groups was determined during the study period. Bacteriologic monitoring at intervals over 2 lactations (lactation 2 and through 60 days of lactation 3) was used to determine the incidence of subclinical infection. In addition, data were collected to determine whether the groups differed in milk production, butterfat production, post-milking and test-day somatic cell counts, and reproductive efficiency. Total milk production and butterfat production over the 2 lactation periods did not vary significantly between the groups. Also, the groups did not differ in calving-to-conception interval, duration of lactation, calving interval, and calving-to-first service interval. Cows with IMD were significantly less likely to develop clinical mastitis (5% vs 13%) than control cows. The IMD did not appear to affect subclinical infection rates (minor pathogens only) except at day 300 of lactation 2 and at day 10 of lactation 3, when prevalence was greater in the cows with IMD. The minor pathogens were predominately (80%) coagulase-negative staphylococci. It was unusual to have coagulase-negative staphylococci in the same quarter at 2 consecutive samplings, prompting the speculation that during lactation, the duration of coagulase-negative staphylococci infection is short (resolves without intervention).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Functional and magnetic resonance imaging correlates of callosal involvement in multiple sclerosis.

To investigate functional and anatomical features of callosal involvement in multiple sclerosis (MS), performances of 90 patients with definite MS and 25 matched normal control subjects were compared on three tasks exploring interhemispheric transfer of auditory, sensory, and motor information: a verbal dichotic listening task, a crossed tactile finger localization task, and an alternate finger tapping task. Each patient also underwent a magnetic resonance imaging (MRI) scan (1) to appreciate the extent of white-matter changes by a semiquantitative evaluation of hemispheric brain MRI hyperintensities and (2) to measure the degree of total and regional callosal atrophy using an automatized method of partition of the midsagittal callosal area. Interhemispheric transfer and/or integration was impaired in patients with MS for all modalities explored and proportional to both degree of callosal atrophy and diffusion of white-matter lesions. Moreover, in good agreement with data obtained from partial commissurotomy studies, performance on each functional task was predominantly associated with atrophy of one part of the callosum, namely left-ear dichotic suppression with the posterior callosal region, alternate finger tapping with the anterior region, and cross-localization with midanterior and posterior regions. Finally, a subgroup of patients without MRI white-matter hyperintensities also showed significant impairment of callosal function and relative atrophy of the callosum. These findings suggest the potential clinical value of callosal involvement in MS and the usefulness of MS as a model of interhemispheric disconnection.

Adolescent↗
PubMed1993

Size heterogeneity of affinity-labeled estrogen receptor in the ram hypothalamo-pituitary axis.

The presence of multiple monomeric forms of estrogen receptor (ER) has been described in different target tissues. Using [3H]tamoxifen aziridine (TA) to covalently label ER and SDS-PAGE to analyze labeled products, ER forms were investigated in ram pituitary and hypothalamus. A major labeled protein of M(r) 60,000-65,000 and a minor species of 50,000-55,000 were found in the pituitary cytosol covalently labeled with [3H]TA. In the hypothalamic cytosol, the major TA-labeled species was the M(r) 50,000 form while the 65,000 ER was difficult to detect. Comparison of ER forms after in vitro translocation of the ER complex in purified nuclei of ram pituitary or hypothalamus again showed major ER forms of M(r) 65,000 and 50,000 for the glandular and nervous tissue respectively, suggesting a biological significance for the M(r) 50,000 species. A similar heterogeneity was also observed in male rats used as controls. Moreover, covalent labeling of cytosol from the pars tuberalis/median eminence area showed the presence of ER in this part migrating with a pattern between those of the hypothalamus and the pituitary. The ER heterogeneity was thus demonstrated in the hypothalamo-pituitary axis. The source of this heterogeneity could be: (1) different ER mRNAs according to tissue type; (2) a specific posttranslational processing such as a specific proteolytic activity within the nervous tissue.

Affinity Labels↗
PubMed1993

Melatonin receptors in the lamb pars tuberalis/median eminence throughout the day.

After validation of the methodology, melatonin receptors have been measured by binding of (125I)-melatonin to membranes of individual pars tuberalis/median eminence of lambs at different times of the day in the course of three experiments. Plasma melatonin was assessed by radioimmunoassay 60 min, 30 min and just before slaughter. Kd was found in the range of 10-25 pM and did not vary with the time of slaughter. Particularly, the mean Kd values were identical and equal to 17 pM in animals slaughtered either during the light or the dark phase of the day. The pattern of Bmax changes was similar in the three experiments and varied significantly (p < 0.001) with the time of the day. The apparent numbers of receptors were found to be the highest at the end of the day and at the onset of the night and to be the lowest at the end of the night: 63.4 +/- 6.3, 61.4 +/- 6.5 and 34.4 +/- 2.8 fmol/mg protein (mean +/- SEM), respectively. Values were found to be intermediary either at the middle of the day (51.1 +/- 5.3 fmol/mg protein) or at the middle of the night (40.4 +/- 6.3 fmol/mg protein). Furthermore, plasma melatonin was positively correlated to the melatonin receptor number (p < 0.02) but only at the onset of the night. In conclusion, the results are strongly suggestive of the existence of a circadian rhythm in the apparent number of melatonin receptors in the lamb pars tuberalis/median eminence with a possible downregulation occurring during the night.

Animals↗
PubMed1993

Nuclear localization of the protein encoded by the Wilms' tumor gene WT1 in embryonic and adult tissues.

The human Wilms' tumor gene WT1 encodes a putative transcription factor implicated in tumorigenesis and in specifying normal urogenital development. We have studied the distribution of WT1 protein and mRNA using immunohistochemistry and in situ hybridization. Monoclonal antibodies were raised against a peptide specific to the first alternative splice site of WT1. Two antibodies specifically reacted on Western blot to this WT1 isoform. Immunofluorescence localized WT1 protein to podocytes during mesonephric and metanephric development. In situ hybridization revealed a similar pattern of expression except that WT1 mRNA was also present in metanephric blastema and renal vesicles. Messenger RNA expression was most pronounced in the kidneys during early fetal development and declined thereafter. In contrast, WT1 protein was readily detectable in glomerular podocytes throughout adulthood. WT1 protein in Wilms' tumor was present in blastema and glomeruloid structures. Expression in the female gonad was linked to the different stages of granulosa cell development. In the male gonad, expression was restricted to Sertoli cells and their precursors, the embryonic tunica albuginea and the rete testis. The intracellular distribution of the WT1 protein was investigated by confocal laser microscopy and was demonstrated to be exclusively nuclear. The nuclear distribution and the selective pattern of expression support the proposed role of WT1 as a transcription factor active during urogenital development. The persistence of WT1 expression in the adult kidney suggests a role in homeostasis of the podocyte.

Blotting, Western↗
PubMed1993

Analysis of the 11p13 Wilms' tumor suppressor gene (WT1) in ovarian tumors.

We have examined the status of the Wilms' tumor suppressor gene (WT1), residing at chromosome 11 band p13, in a total of 40 cancers of the female reproductive tract. Northern blot analysis revealed that the WT1 gene is expressed in a large percentage of ovarian tumors (75%) analyzed. Single-strand conformation polymorphism analysis was performed on all the tumors in this study in an attempt to detect mutations within the WT1 gene. Only silent mutations were detected within intron 7 of WT1 using this method. Loss of heterozygosity studies were performed at the WT1 locus in several ovarian tumors and revealed that in the informative cases, heterozygosity was retained.

Base Sequence↗