Acute meningoencephalitis associated with seroconversion to "Afipia felis".
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Acute Disease↗
Biomedical subjects
J Pelletier
Publications and source records attributed to J Pelletier.
A dominant mutation in the Wilms tumor gene WT1 cooperates with the viral oncogene E1A in transformation of primary kidney cells.
Wilms tumor is a pediatric kidney cancer that has been linked to the inactivation of a tumor-suppressor gene at chromosome locus 11p13. The WT1 gene, mapping to this locus, is developmentally regulated in the kidney and encodes a putative transcription factor that has been shown to be mutated in Wilms tumor specimens. We have suggested that one such altered product of the WT1 gene may be capable of trans-dominant suppression, since the mutated allele was found to be coexpressed with the wild-type allele in a sporadic Wilms tumor. We therefore tested the ability of this mutant WT1 allele, containing an in-frame deletion within the DNA-binding domain, to transform primary baby rat kidney cells. The mutant WT1 gene was found to cooperate with the adenoviral E1A gene in transforming baby rat kidney cells, as demonstrated by growth in soft agar and tumorigenicity in nude mice. The wild-type WT1 gene in all of its alternatively spliced forms neither suppressed E1A-induced focus formation nor cooperated with E1A. Our results indicate that impairment of DNA binding of the WT1 tumor-suppressor gene product can result in a dominant negative mutation.
Adenovirus Early Proteins↗
Effect of a 2-month light cycle regimen on testicular parameters of adult Ile-de-France rams.
This experiment was conducted in Ile-de-France adult rams to examine the target point of a 2-month light cycle regimen on seminiferous tubule functions, on intertubular compartment and on Leydig cell parameters. Eight rams were subjected to a 2-month light cycle regimen and were compared to sexually active or inactive rams. In light-treated rams, testis weight was maintained equal or was higher than that of sexually active rams. Both tubular and intertubular tissues were found significantly higher in light-treated than in sexually active rams. The mean ratio of basement membrane area of the seminiferous tubules per Sertoli cells and the daily productions of A1 spermatogonia and of leptotene primary spermatocytes were significantly increased in light-treated rams as compared with sexually active or inactive rams. Meanwhile, the dairy productions of diplotene primary spermatocytes, of round spermatids, of spermatozoa and of the rete testis fluid were not significantly increased in light-treated as compared with sexually active rams but significantly greater than those of sexually inactive rams. Total volume, total numbers, and individual volumes of Leydig cells were at least equal or higher in light-treated than in sexually active rams.
Animals↗
Localization of luteinizing hormone beta-mRNA by in situ hybridization in the sheep pars tuberalis.
The localization of luteinizing hormone beta (LH beta)-mRNA was studied by in situ hybridization in the pars tuberalis of sheep using a homologous sheep double-stranded 32P- or 35S-cDNA. The labelled cDNA probe detected one mRNA sequence in the pars tuberalis by Northern blot analysis; this sequence was similar to that detected in the pituitary. In situ, the labelling of LH beta-mRNA in the horizontal and sagittal tissue sections was found throughout the pars tuberalis. This labelling was prevented by adding an excess of cold probe or treating the sections by ribonuclease before in situ hybridization. Controls showed a labelling in the pars distalis, but not in the median eminence, hypothalamus, cerebral cortex and liver sections. Double labelling by in situ hybridization followed by immunohistochemistry using a specific LH beta-antiserum indicated that the labelling of LH beta-mRNA appeared more intense in LH-containing cells that were found only in the ventral part of the pars tuberalis. These results suggest that the entire pars tuberalis is able to produce the LH beta subunit, but that the level of translation greatly varies according to the location of the cells.
Animals↗
Monoclonal antibody to MALA-2 (ICAM-1) reduces acute autoimmune nephritis in kdkd mice.
Hereditary tubulointerstitial nephritis is a prominent cause of renal failure in humans. A variety of animal models utilizing immunologically induced nephritis have been developed. The kdkd congenic variant of the CBA/Ca mouse has normal kidneys at birth but develops progressive, lethal autoimmune nephritis beginning at approximately Week 8. The destruction of renal tubular epithelium in mediated by a population of antigen-specific, H-2Kk-restricted, Lyt-2+, L3T4- T cells. The present experiments demonstrate that systemic treatment with anti-ICAM-1 monoclonal antibody reduces kidney disease in kdkd mice. Anti-ICAM-1 mab localizes to inflammatory sites in the kidney and effects a significant reduction in leukocyte infiltration. Concomitantly, urine protein levels of anti-ICAM-1-treated mice are significantly reduced. The use of anti-adhesion molecule monoclonal antibodies that alter leukocyte activity and/or trafficking may be useful therapies for certain autoimmune disorders.
Animals↗
Germline intronic and exonic mutations in the Wilms' tumour gene (WT1) affecting urogenital development.
Denys-Drash syndrome is a rare human developmental disorder affecting the urogenital system and leading to renal failure, intersex disorders and Wilms' tumour. In this report, four individuals with this syndrome are described carrying germline point mutations in the Wilms' tumour suppressor gene, WT1. Three of these mutations were in the zinc finger domains of WT1. The fourth occurred within intron 9, preventing splicing at one of the alternatively chosen splice donor sites of exon 9 when assayed in vitro. These results provide genetic evidence for distinct functional roles of the WT1 isoforms in urogenital development.
Alternative Splicing↗
Putaminal necrosis after methanol intoxication.
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Adult↗
Pulsatile secretion of LH in the ram: a re-evaluation using a discrete deconvolution analysis.
The purpose of the present experiment was to characterize LH secretion pulsatility in rams by analysing the instantaneous secretion rate profile obtained by deconvoluting the plasma concentration profile. Plasma LH concentration profiles were obtained by collecting blood samples every 6 min for 24 h during two different sessions separated by an interval of 15 days. Individual kinetic parameters of ovine LH (oLH) were determined following i.v. injection of oLH. By deconvoluting the plasma concentration profile, it was shown that a pulse has an effective duration of only 20.41 +/- 7.69 (S.D.) min whereas the mean duration estimated from measurement of plasma concentrations was 61.00 +/- 15.16 min. The number of pulses was similar before and after deconvolution (7.80 +/- 1.99 vs 9.70 +/- 3.44 pulses/24 h respectively). Using deconvolution the calculated production rate was 2.26 +/- 0.94 micrograms/kg per 24 h, about 50% of this production being located in the pulses. Statistical analysis of pulsatility revealed that pulse occurrence was a nonperiodic event and that the amplitude of LH pulses and the associated amount of LH released were correlated with the duration of the preceding quiescence period, but had no statistically significant influence on the duration of the following quiescence period.
Animals↗
[Interhemispheric transfer in multiple sclerosis. Morphofunctional correlations].
Signs of cerebral disconnection, especially left ear suppression to dichotically presented verbal stimuli, have been reported in multiple sclerosis patients and found to be correlated to morphological atrophy of the corpus callosum on magnetic resonance imaging. To reinvestigate this issue, 26 patients satisfying criteria for definite multiple sclerosis were proposed 3 tasks aimed at evaluating interhemispheric function: a dichotic listening task, a motor finger-tapping task and a sensory transfer task. Performance at these tasks suggested impaired callosal function in MS patients, compared to normal controls. Callosal morphology was assessed on midsagittal MRI sections using a digitalised method of partition of the callosal area into 6 subregions and automatized surface measurements. Results of correlations between task performance and callosal areas showed a significant correlation between total callosal atrophy and severity of interhemispheric impairment on each functional task. Moreover, impaired motor transfer was specifically related to atrophy of the anterior callosal regions. These results suggest that MS patients may constitute a suitable population to studying interhemispheric transfer of information through the callosal commissure and that this approach may be useful in the clinical management of MS patients.
Adolescent↗
[Sterilization by the plasma procedure].
Plasma sterilisation of heat sensitive materials appears as an attractive substitute for ethylene oxide processing which leaves adsorbed toxic residues. In oxygen-based plasmas, the de-activation of pathogenic organisms is assumed to be due to their slow combustion with the active species which produces CO2 and H2O. In the absence of ion bombardment, the concentration of oxygen atoms is an important parameter entering the plasma sterilisation efficiency. Means for achieving high production of oxygen atoms are reviewed and discussed. In particular, an initial improvement would be to generate the plasma in the sterilisation volume itself. Uniform plasma excitation at electron cyclotron resonance (ECR) which allows resonant coupling in the whole treatment volume (no shadowing) and requires reduced electric fields to sustain the discharge (no heating of biomaterials) is particularly adapted to this purpose.
Oxygen↗
[Intervention framework of the Quebec Healthy Heart Demonstration Project].
Cardiovascular diseases are Canada's primary cause of death and hospitalisation, and are the second major cause of restricted physical activity. Quebec province, with a mortality rate of 399/100,000, has figures even higher than the national average of 323/100,000, and 7 out of every 10 Quebecois present at least one of the major cardio-vascular risk factors. Following an exploratory task force on this question, the Canadian government initiated a partnership programme with the provinces wherein the federal government and provincial governments would each contribute one million Canadian dollars over a five year period for heart disease prevention programmes. Quebec province selected three different projects in which multifactorial, multisectorial community-based programmes were to be implemented. The sites chosen for the projects were: a rural region situated on the banks of the St. Laurence River, a Montreal suburban district, and a multi-ethnic, socio-economic disadvantaged community in downtown Montreal. Despite a common public health approach and the ultimate goal of improving heart health through the lowering of risk factors, each project had its own specific major intervention strategy and primary target population. The projects were linked by a study design to evaluate community and family mechanisms which favour the adoption of low risk behaviours. A coordinating committee was formed to supervise the overall project which included strategic planning, consultancy services to project staff, methodology, development and implementation, and evaluation. Each specific project team was free, however, to choose its particular orientations.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiovascular Diseases↗
Alternative splicing and genomic structure of the Wilms tumor gene WT1.
The chromosome 11p13 Wilms tumor susceptibility gene WT1 appears to play a crucial role in regulating the proliferation and differentiation of nephroblasts and gonadal tissue. The WT1 gene consists of 10 exons, encoding a complex pattern of mRNA species: four distinct transcripts are expressed, reflecting the presence or absence of two alternative splices. Splice I consists of a separate exon, encoding 17 amino acids, which is inserted between the proline-rich amino terminus and the zinc finger domains. Splice II arises from the use of an alternative 5' splice junction and results in the insertion of 3 amino acids between zinc fingers 3 and 4. RNase protection analysis demonstrates that the most prevalent splice variant in both human and mouse is that which contains both alternative splices, whereas the least common is the transcript missing both splices. The relative distribution of splice variants is highly conserved between normal fetal kidney tissue and Wilms tumors that have intact WT1 transcripts. The ratio of these different WT1 mRNA species is also maintained as a function of development in the mouse kidney and in various mouse tissues expressing WT1. The conservation in structure and relative levels of each of the four WT1 mRNA species suggests that each encoded polypeptide makes a significant contribution to normal gene function. The control of cellular proliferation and differentiation exerted by the WT1 gene products may involve interactions between four polypeptides with distinct targets and functions.
Amino Acid Sequence↗
Germline mutations in the Wilms' tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome.
Denys-Drash syndrome is a rare human condition in which severe urogenital aberrations result in renal failure, pseudohermaphroditism, and Wilms' tumor (nephroblastoma). To investigate its possible role, we have analyzed the coding exons of the Wilms' tumor suppressor gene (WT1) for germline mutations. In ten independent cases of Denys-Drash syndrome, point mutations in the zinc finger domains of one WT1 gene copy were found. Nine of these mutations are found within exon 9 (zinc finger III); the remaining mutation is in exon 8 (zinc finger II). These mutations directly affect DNA sequence recognition. In two families analyzed, the mutations were shown to arise de novo. Wilms' tumors from three individuals and one juvenile granulosa cell tumor demonstrate reduction to homozygosity for the mutated WT1 allele. Our results provide evidence of a direct role for WT1 in Denys-Drash syndrome and thus urogenital system development.
Acute Kidney Injury↗
WT1 mutations contribute to abnormal genital system development and hereditary Wilms' tumour.
Wilms' tumour (WT), aniridia, genitourinary abnormalities and mental retardation form a symptom group (WAGR syndrome) associated with hemizygous deletions of DNA in chromosome band 11p13 (refs 1,2). However, it has not been clear whether hemizygosity at a single locus contributes to more than one phenotype. The tumour suppressor gene for Wilms' tumour, WT1, has been characterized: it is expressed at high levels in the glomeruli of the kidney, as well as the gonadal ridge of the developing gonad, the Sertoli cells of the testis and the epithelial and granulosa cells of the ovary, suggesting a developmental role in the genital system in addition to the kidney. We now report constitutional mutations within the WT1 genes of two individuals with a combination of WT and genital abnormalities as evidence of a role for a recessive oncogene in mammalian development.
Amino Acid Sequence↗
The effect of poliovirus proteinase 2Apro expression on cellular metabolism. Inhibition of DNA replication, RNA polymerase II transcription, and translation.
Infection of cells with poliovirus results in a rapid inhibition of host RNA and protein synthesis. Concordant with this shutoff, the p220 subunit of the cap-binding protein complex is cleaved, probably indirectly, by the poliovirus proteinase p2A (2Apro). To elucidate the mechanism of action of 2Apro in inhibiting protein synthesis in vivo, we studied the effect of transient expression of 2Apro in COS-1 monkey kidney cells. In cells transfected with a 2Apro expression plasmid, p220 was cleaved and the 2Apro mRNA was reduced 30-fold compared to an identical plasmid containing a translation termination codon within the 2Apro coding region. The reduced expression from the 2Apro vector results from a 4-fold reduction in DNA replication and 22-fold reduction in transcription by RNA polymerase II from the adenovirus major late promoter/SV40 enhancer utilized in this vector. In contrast, no decrease in transcription of the adenovirus virus-associated I RNA gene by RNA polymerase III was observed. The effect of 2Apro expression on cap-dependent mRNA translation was studied by producing a dicistronic beta-globin mRNA harboring the encephalomyocarditis virus leader and 2Apro coding region within the 3' end of the mRNA to mediate cap-independent translation of 2Apro. Expression of this mRNA was also reduced 25-fold compared to an identical plasmid harboring a termination codon within the 2Apro coding region. Translation of the beta-globin marker gene from this mRNA was reduced 3-fold when corrected for mRNA level. These results suggest that p220 cleavage itself is not sufficient for complete inhibition of host translation and that an important effect of 2Apro expression on host protein synthesis is a reduction in RNA polymerase II transcription and to a lesser extent, DNA replication. This reduction could be a primary effect of 2Apro, or a secondary effect caused by the inhibition of translation.
Animals↗
Multiple mRNAs encode the murine translation initiation factor eIF-4E.
All eukaryotic cellular mRNAs (except organellar) possess at their 5' end the structure m7GpppX (where X is any nucleotide) termed the "cap." The cap structure facilitates the melting of mRNA 5' secondary structure through the action of initiation factor-4F (eIF-4F) in conjunction with eIF-4B. eIF-4F consists of three subunits of which one, eIF-4E (eIF-4E has recently been designated eIF-4 alpha according to the Nomenclature Committee of the International Union of Biochemistry (NC-IUB) (Safer, B. (1989) Eur. J. Biochem. 186, 1-3)), contains the cap binding site. Several lines of evidence suggest that eIF-4E regulates the rate of translation initiation. Consequently, changes in cellular eIF-4E levels could control growth and differentiation. To investigate the possibility that eIF-4E expression is regulated, we studied the pattern of eIF-4E expression in several cell lines. Here, we show the existence of multiple mRNAs for eIF-4E that are generated by differential polyadenylation. In addition, we show tissue-specific differences in eIF-4E mRNA expression and utilization of polyadenylation sites.
Animals↗
Melatonin binding sites in the brain of sheep exposed to light or pinealectomized.
The binding sites of [125I]melatonin were identified in the sheep brain using a specific and sensitive autoradiographical method. Rams were either untreated (controls) or exposed to light before slaughter or pinealectomized (px). In all animals labelling was intense in the pars tuberalis (PT) and absent in the suprachiasmatic nucleus (SCN). In light-treated and in px rams, but not in controls, we demonstrated melatonin binding sites in the intermediate and ventrolateral septum and in the stratum lacunosum of the hippocampus. Labelling was less marked in nervous tissues than in PT cells and did not seem to be different between treatments. These results indicate the presence of light-dependent melatonin binding sites in the septum and hippocampus of sheep, but rise the question of the involvement of melatonin in the SCN activity in this species.
Animals↗
Assignment of two of the translation initiation factor-4E (EIF4EL1 and EIF4EL2) genes to human chromosomes 4 and 20.
The eukaryotic translation initiation factor (eIF-4E) has recently been cloned from human, mouse, and yeast. This polypeptide is the rate-limiting component of the eukaryotic translation apparatus and is involved in the mRNA-ribosome binding step of eukaryotic protein synthesis. We have designed oligonucleotide primers to the 3' untranslated region of the gene encoding eIF-4E and specifically amplified the human gene in human/rodent somatic cell hybrids using the polymerase chain reaction. By this method, one of the human eIF-4E genes (EIF4EL1, eukaryotic translation initiation factor 4E-like 1) has been mapped to human chromosome 4qter-4p15. In addition, we have localized a second eIF-4E gene (EIF4EL2, eukaryotic translation initiation factor 4E-like 2) to human chromosome 20 by Southern blot analysis of mapping panels established from human/rodent somatic cell hybrids.
Animals↗