Supernumerary marker 15 chromosome in a patient with Prader-Willi syndrome.
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Adolescent↗
Biomedical subjects
I Szijan
Publications and source records attributed to I Szijan.
Genotypic and phenotypic characterization of the histoblood group ABO(H) in primary bladder tumors.
The ABO(H) histoblood group genes have been mapped by linkage analysis to 9q34.1-34.2, an area of common deletions in bladder cancer. Lack of ABO(H) antigen expression in bladder tumors is a frequent and well-documented event. In bladder neoplasms the loss of A and B transferase activity is due to down-regulation of the ABO gene transcripts. Our study was undertaken in order to determine the presence of structural alterations of the ABO(H) gene-encoding locus in primary bladder tumors, to estimate the extent of allelic deletions and to characterize further the pattern of histoblood group antigen expression. Fifty-three primary bladder tumors were analyzed by immuno-histochemistry (IHC) using a panel of well-characterized antibodies and fresh frozen tissue sections. Normal and tumor DNA also were analyzed by PCR coupled with restriction enzyme analysis in order to establish the ABO genotype. Results obtained from these analyses were then compared to allelotyping data at the 9q34.1-4 region by Southern blotting. IHC data showed undetectable levels of antigen expression on neoplastic cells in 59% of informative cases. PCR-based genotypic results revealed allelic losses in 27% of heterozygous cases. Four of the 16 pheno- and/or genotypically altered cases (25%) presented loss of heterozygosity at D9S10 or D9S7 loci. Our data indicate that the lack of ABO antigen expression in certain bladder tumors is due to the allelic loss of the ABO glycosyltransferase-encoding genes and that in some of these tumors the loss involves the surrounding chromosomal region at 9q34.1-4.
ABO Blood-Group System↗
Clinical, cytogenetic, and molecular testing of Argentine patients with retinoblastoma.
PURPOSE: The purpose of this study is to determine the clinical, chromosomal, and molecular characteristics of Argentine patients with unilateral and bilateral retinoblastoma. STUDY DESIGN: Eighty-six patients belonging to 82 families were studied; 59% of them were examined during the first year of life. Leukocoria was the most common reason for consultation. Other presenting signs were strabismus and glaucoma. Enucleation of the affected eye was performed in 85% of the cases and the complication rate was 13%. RESULTS: An appropriate therapy allowed the survival of 84 of the 86 patients. Two children with malformations and growth retardation had an abnormal karyotype with a deletion in 13q14. Segregation analysis of polymorphic sites within the retinoblastoma gene and the parental origin of the allele lost in the tumor were analyzed in 30 of the 82 families. Five mutant alleles transmitted through the germline and six de novo germline mutant alleles were identified in 12 patients with hereditary retinoblastoma. Most de novo germline mutant alleles were paternally derived. Molecular analysis of nonhereditary retinoblastoma showed loss of heterozygosity in three of eight cases. From these, two maternal alleles and one paternal allele were lost, thus not indicating a significant difference in the parental origin for the lost allele. CONCLUSIONS: These data are useful for deoxyribonucleic acid diagnosis of susceptibility to retinoblastoma in relatives of hereditary patients, even if mutations have not been identified.
Alleles↗
Deletion patterns in Argentine patients with Duchenne and Becker muscular dystrophy.
The identification of mutations in Duchenne or Becker muscular dystrophy (DMD/BMD) patients is important for carrier detection in these families. We present the patterns of deletions of the dystrophin gene in Argentine population. DNA from 75 patients with DMD/BMD was analyzed by multiplex PCR and, in some cases, cDNA/Southern. Deletions were detected in 24 patients (32%) and were mainly clustered in two areas of the dystrophin gene: the 5' end (exons 3-12) and the central part (exons 44-53). 64% of the deletion endpoints lay in the middle region and 34% in the 5' end of the gene. The most frequent sites for deletion-endpoints were in the introns 47 (13.6%), 44 (11%), 2 (9%) and 12 (7%). Thus, the proportion and distribution of deletions in our DMD/BMD patients differ from those reported for other populations. Furthermore, a higher proportion of deletions was observed in familial cases (40%) than in isolated ones (30%), in contrast to previously reported data. The effect of the deletion on the reading frame agree with the phenotype in almost all the patients studied. This study will be useful in prenatal diagnosis and diagnosis of other Argentine DMD patients.
Adolescent↗
Carrier detection in Duchenne and Becker muscular dystrophy Argentine families.
In order to offer carrier detection, genetic counseling, and prenatal diagnosis to families with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) in our country, segregation analysis of highly polymorphic short tandem repeats (STR) (dC-dA)n: (dG-dT)n loci was utilized. The risks to females of 15 DMD BMD families (9 familial and 6 sporadic) were evaluated on STR, pedigree and serum creatine kinase (SCK) data. From the 36 females at risk of being carriers (not including 8 obligate carriers), results of STR analysis were compatible with carrier status in 7 and not compatible in 20. In 9 females, no information regarding carriership was derived from the STR analysis. Prenatal diagnosis is now possible on the carrier females. Previously identified deletions in the central part of the gene were confirmed by STR analysis in 3 families. Five new alleles were identified in Argentine individuals; allele frequencies differed from those of North American people. Results derived from this study are useful for carrier detection and genetic counseling in DMD/BMD. One case of probable mosaicism in an unaffected father was detected on a pedigree basis in a family with DMD patients.
Alleles↗
Patient with an Xp21 contiguous gene deletion syndrome in association with agenesis of the corpus callosum.
The so-called Xp21 contiguous deletion syndrome or complex glycerol kinase deficiency (GKD) usually presents with classical Duchenne muscular dystrophy (DMD) or a milder dystrophic myopathy, adrenal hypoplasia, and GKD. A number of syndromic and nonsyndromic cases of agenesis of the corpus callosum (ACC) also map to that location. To date, none of the cases of complex GKD have been associated with ACC. Here, we report on a patient with a complex phenotype as a result of the Xp21 contiguous deletion syndrome in association with ACC. Biochemical, cytogenetic, and molecular analyses were performed to detect and establish the size of the genomic deletion. It is at least 3 million base pairs in length; however, exact limits could not be determined in the present study. Nevertheless, we suggest the presence of a primary gene involved in the embryogenesis of the corpus callosum between Xp21.1 and Xp22.11.
Agenesis of Corpus Callosum↗
Four new polymorphisms in the human dystrophin gene from an Argentinian population.
Duchenne muscular dystrophy and its allelic disorder Becker muscular dystrophy are among the most common hereditary human pathologies (1:3500). Two thirds of the genomic alterations responsible for these diseases involve gross gene rearrangements such as deletions, and less frequently duplications. The remaining one third includes point mutations such as deletions, insertions, and substitutions. This study describes four nonpreviously reported polymorphisms in the dystrophin gene by using the polymerase chain reaction/single-strand conformation polymorphism technique and subsequent nonisotopic silver staining.
Adolescent↗
Identification of RB1 germline mutations in Argentinian families with sporadic bilateral retinoblastoma.
Hereditary predisposition to retinoblastoma is caused by germline mutations in the RB1 gene. Most of these mutations occur de novo and differ from one patient to another. DNA samples from 10 families with a child presenting sporadic bilateral retinoblastoma have been analysed for the causative mutation. Using intragenic DNA polymorphisms we detected large deletions in two patients. Heteroduplex and DNA sequence analysis of PCR products from each exon and the promoter region showed small mutations in four patients: a C to T transition in exon 18; 1 bp and 2 bp deletion in exons 20 and 19 respectively; and a 4 bp insertion in exon 7. All these mutations are likely to result in premature termination of transcription. In one of these families, an unaffected carrier was detected. This emphasises the importance of detection of the causative mutation for predictive diagnosis in families with sporadic bilateral retinoblastoma.
Argentina↗
Localization of RC3 (neurogranin) in rat brain subcellular fractions.
Previous studies have shown that RC3 (neurogranin) is a postsynaptic, protein kinase C (PKC)/calmodulin-binding substrate that accumulates throughout the perikaryal and dendritic cytoplasm and is often closely associated with the postsynaptic density (PSD) in dendritic spines of neostriatal neurons. Here Western immunoblotting studies of rat brain subcellular fractions confirm that RC3 is predominantly a cytosolic protein but is found in lower amounts in membrane-enriched microsomes and synaptosomes. Solubilization of synaptosomes suggests that RC3 may only be loosely associated with the PSD.
Animals↗
Expression of c-myc and c-fos protooncogenes in the anterior pituitary gland of the rat. Effect of estrogen.
Thymidine incorporation into the DNA of the anterior pituitary gland is stimulated by estrogen. We studied the relationship between this effect and expression of the protooncogenes c-myc and c-fos. Within one hour after estrogen administration, the level of c-myc and c-fos mRNA increased in the anterior pituitary gland and remained high throughout the experimental period (16 to 22 hrs). Transcription of the prolactin gene, one of the targets of estrogen action, was stimulated at the same time intervals. There were no modifications in the growth hormone mRNA level. Thus, estrogen induced the expression of c-myc and c-fos in the anterior pituitary gland in an early period.
Animals↗
Expression of c-myc and c-fos oncogenes in different rat brain regions during postnatal development.
We have studied the expression of c-myc and c-fos proto-oncogenes in various areas of the central nervous system during postnatal development. c-myc mRNA levels increased during the first 5 days and then decreased over the next 15 days in all nervous regions studied. c-fos mRNA levels changed in a different way in four brain areas. While in cerebral cortex and cerebellum there was a sharp decrease during the first 10 days, in white matter and hypothalamus c-fos transcript levels remained high during the same period, decreasing at a later stage. Changes in oncogenes mRNA levels are related to various developmental events, such as neurite growth, myelination and cell proliferation. The dissimilar patterns of c-myc and c-fos expression suggests that they play different functions in CNS maturation. c-myc mRNA levels are temporally related to active neurite growth and to cell proliferation. Changes in c-fos mRNA correlate in time with early developmental processes and also with those occurring at later stages, such as myelination.
Animals↗
Effect of dopamine agonists and antagonists on the binding of [3H]estradiol to its receptors in the anterior pituitary gland of male rats.
The synthesis of PRL and DNA in PRL cells is regulated by estrogens and dopamine. To investigate a possible relationship between these two components, we studied the influence of dopamine agonists and antagonists on the binding of [3H]estradiol ([3H]E2) to its receptors in the anterior pituitary gland of estrogenized male rats. The administration of sulpiride (dopamine antagonist) or bromocriptine (dopamine agonist) decreased the binding of [3H]E2 to cytosolic receptors when the concentration of [3H]E2 in the assay mixture was 1 nM. Both drugs also diminished the binding of [3H]E2 when they were added in vitro to the incubation media, apparently in a competitive way. Dopamine and alpha-methyltyrosine also inhibited competitively the binding of [3H]E2 to cytosolic receptors. The inhibition constants were determined by the Lineweaver-Burk plot. To overcome the competitive inhibition of dopamine agonists and antagonists, the concentration of the titrated steroid in the incubation mixture was increased to 16 nM. This concentration was established by saturation analysis. The administration of alpha-methyltyrosine increased the binding of [3H]E2 to nuclear receptors without modifying the binding to cytosolic receptors. This increase paralleled an increment in the levels of plasma PRL. Bromocriptine prevented the increase in [3H]E2 binding produced by alpha-methyltyrosine and had no effect on the binding when administered to nontreated rats. These results suggest that dopamine can regulate the biological effects of estradiol in the anterior pituitary gland by decreasing the binding of this hormone to its receptors.
Animals↗
The influence of estrogen administration on the subcellular receptors distribution and its biological effect in the rat anterior pituitary gland.
We studied the effects of estrogen administration in the anterior pituitary gland (APG) of male rats. The subcellular distribution of estradiol receptors, and some biological responses, such as prolactin secretion and progestine receptors were examined. In the presence of circulating estrogens, the binding of [3H]-estradiol decreased in the cytosol and increased in nuclei. The total binding augmented significantly (P less than 0.05). These changes were dose and time dependent. So, in long chronic treatment, the changes in subcellular receptor distribution were greater, in accordance with higher serum estrogen level. Serum prolactin concentration and progestin receptor in the APG increased continuously as a function of time of the estrogen treatment. They were related to the presence of nuclear estradiol receptors, which remained elevated throughout the entire experimental period.
Animals↗
Effect of haloperidol on the synthesis of DNA in the pituitary gland of the rat.
The administration of haloperidol increased serum prolactin and decreased the pituitary concentration of prolactin 15 min after its administration. Concomitantly there was a stimulation in the synthesis of DNA and the activity of DNA polymerase alpha in the anterior pituitary gland that was greater in oestrogenized than in non-oestrogenized male rats. Both these effects were greatly reduced by clomiphene in the oestrogenized male rats, although it did not affect the release of prolactin produced by haloperidol. In non-oestrogenized animals clomiphene abolished the stimulatory effect of haloperidol on the synthesis of DNA. These results suggest that the reduction in the intracellular levels of prolactin are a primary event in the oestrogen mediated stimulation of cell proliferation by prolactin releasing agents.
Animals↗
Relationships among release of prolactin, synthesis of DNA and growth of the anterior pituitary gland of the rat: effects of oestrogen and sulpiride.
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Animals↗
Studies on estrogen receptors in the cytosol and nuclei of the rat anterior pituitary gland. Determination of specific sites by [3H]-estradiol exchange assay.
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Animals↗
DNA polymerases in the rat pituitary gland. Effect of oestrogens and sulpiride.
Changes in the activity of DNA polymerase and [3H]thymidine incorporation into the DNA of the anterior pituitary gland were studied in oestrogenized male and pregnant rats. The activities of DNA polymerases alpha and beta, extracted in Tris--HCl or in sodium phosphate buffer were characterized according to their optimum pH and sensitivity to N-ethyl-maleimide. In the Tris-soluble fraction DNA polymerase activity is almost exclusively alpha, while in the phosphate soluble fraction it is a mixture of alpha and beta. The administration of oestrogens to male rats increases [3H]thymidine incorporation and enhances the activity of DNA polymerases in the Tris-soluble fraction, while the activity of the phosphate-soluble enzyme does not change. Sulpiride administration results in a further increment of [3H]thymidine incorporation and of DNA polymerase activity in the Tris-soluble fraction. In pregnant rats sulpiride also produces an increment of DNA polymerase activity only in the Tris-soluble fraction. Thus, the activity of the Tris-soluble fraction from APG behaves as DNA polymerase alpha. This activity changes in parallel with [3H]thymidine incorporation into DNA which is an indication of cell proliferation in the gland. This is discussed with respect to a negative feedback mechanism between intracellular prolactin concentration and DNA synthesis in the APG.
Animals↗
DNA synthesis in the pituitary gland of the rat: effect of sulpiride and clomiphene.
Sulpiride administration to rats releases prolactin and increases DNA replication in the anterior pituitary gland. Clomiphene prevents the stimulation of DNA synthesis produced by sulpiride, but does not affect prolactin release from the gland. These findings suggest that the intracellular prolactin content of the anterior pituitary gland plays a role in the regulation of DNA synthesis through a mechanism mediated by oestrogens.
Animals↗