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S Varrone

Publications and source records attributed to S Varrone.

At least 19 recordsLinked to original sources
PubMed1999

The length of polyglutamine tract, its level of expression, the rate of degradation, and the transglutaminase activity influence the formation of intracellular aggregates.

A common feature of CAG-expansion neurodegenerative diseases is the presence of intranuclear aggregates in neuronal cells. We have used a synthetic fusion protein containing at the NH2 terminus the influenza hemoagglutinin epitope (HA), a polyglutamine stretch (polyQ) of various size (17, 36, 43 CAG) and a COOH tail encoding the green fluorescent protein (GFP). The fusion proteins were expressed in COS-7 and neuroblastoma SK-N-BE cells. We found that the formation of aggregates largely depends on the length of polyglutamine tracts and on the levels of expression of the fusion protein. Moreover, transglutaminase overexpression caused an increase of insoluble aggregates only in cells expressing the mutant expanded protein. Conversely, treatment of cells with cystamine, a transglutaminase inhibitor, reduced the percentage of aggregates. We found also that the inhibition of the proteasome ubiquitin-dependent degradation increased the formation of intranuclear aggregates. These data suggest that length of polyglutamine tract, its expression, unbalance between cellular transglutaminase activity, and the ubiquitin-degradation pathway are key factors in the formation of intranuclear aggregates.

Acetylcysteine↗
PubMed1996

Transglutaminase activity is related to CAG repeat length in patients with Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disorder associated with CAG repeat expansion. We measured transglutaminase (TGase) activity in lymphocytes from 35 HD patients and from healthy individuals to ascertain whether it was altered in this condition. TGase activity was above maximum control levels in 25% of HD patients; it was correlated with the age of the patient and inversely correlated with the CAG repeat length. These results suggest that: (1) HD could be biochemically heterogeneous, and (2) the length of the CAG repeat expansion/TGase ratio could be important in the manifestation of HD.

Adult↗
PubMed1995

Double autosomal/gonosomal mosaic aneuploidy: study of nondisjunction in two cases with trisomy of chromosome 8.

We report cytogenetic and molecular investigations performed in two cases of mosaic trisomy 8 combined with mosaic sex chromosome aneuploidy. In a 35-year-old female, presenting with short stature, gonadal dysgenesis, and a multiple congenital anomalies/mental retardation syndrome typical of trisomy 8, chromosome analysis from peripheral lymphocytes showed the presence of three cell lines, whose karyotypes were 45,X (59.2%), 46,X,+8 (1.2%), and 47,XX,+8 (39.6%), respectively. The same cell lines were found in a skin fibroblast culture, though in different proportions. The second patient, a 9-month-old male with multiple skeletal abnormalities, showed a 47,XY,+8 and a 47,XXY cell line in both peripheral lymphocytes (61.7% and 38.3%, respectively) and skin fibroblasts (92.8% and 7.2%, respectively). To determine the events underlying the origin of these complex karyotypes we performed Southern blot and polymerase chain reaction (PCR) analysis using polymorphic DNA markers from the X chromosome and from chromosome 8. Both supernumerary chromosomes 8, and, in case 2, the two X chromosomes, appeared to be identical, lacking detectable recombination events. We conclude that, in both cases, the most likely mechanism underlying the origin of the mosaic cell lines was formation of a normal zygote, followed by mitotic errors during early divisions.

Abnormalities, Multiple↗
PubMed1994

Late onset Friedreich's disease: clinical features and mapping of mutation to the FRDA locus.

Twenty two patients from 17 families with Friedreich's disease phenotype but with onset ranging from the ages of 21 to 36 are described. Comparison with "typical" Friedreich's disease with onset before 20 years of age showed only a lower occurrence of skeletal deformities. The peripheral and central neurophysiological findings, sural nerve biopsy, and the neuroradiological picture did not allow the differentiation between "late onset" and "typical" Friedreich's disease. Duration of disease from onset to becoming confined to a wheelchair was five years longer in late onset patients. Sixteen patients and 25 healthy members from eight families were typed with the chromosome 9 markers MLS1, MS, and GS4 tightly linked to the FRDA locus. All families showed positive lod scores with a combined value of 5.17 at a recombination fraction of theta = 0.00. It is concluded that "late onset" Friedreich's disease is milder than the "typical" form and that it maps to the same locus on chromosome 9.

Adaptor Proteins, Signal Transducing↗
PubMed1990

A pilot study for neonatal screening of congenital adrenal hyperplasia due to 21-hydroxylase and 11-beta-hydroxylase deficiency in Campania region.

A neonatal screening for both 21-hydroxylase and 11-beta-hydroxylase deficiencies, responsible for congenital adrenal hyperplasia (CAH), has been conducted in Campania Region, Southern Italy. In 4380 neonates, aged 2-10 days, capillary blood from a heel prick was collected on microfilter paper, and 17-alpha-hydroxyprogesterone (17OHP) measured by radioimmunoassay (RIA) using a highly specific antibody (Ab A). In addition, in 295 of these samples, both 17OHP and 11-deoxycortisol (S) were measured using an anti-deoxycortisol antibody (Ab B) cross-reacting with 17OHP 100%. All results were compared with plasma 17OHP and S levels in 21 patients with diagnosed 21-hydroxylase deficiency and in 5 healthy volunteers on metyrapone test used for blocking the 11-beta-hydroxylase activity. CAH due to 21-hydroxylase deficiency was diagnosed in a female newborn. The assay, based on the antibody reacting with both 17OHP and S, is particularly suitable for wide-scale screening programs enabling the simultaneous detection of two congenital enzyme defects.

Adolescent↗
PubMed1988

Polymorphism at the 5' end flanking region of the insulin gene is associated with reduced insulin secretion in healthy individuals.

Sixty-four unrelated healthy subjects were studied for the detection of a DNA polymorphism at the 5' end of the insulin gene. No significant difference between the groups was found in blood glucose values at fasting and after an oral glucose load. A significant association was found between fasting (P less than 0.05) and after load plasma C-peptide levels (P less than 0.01) and the presence of a 1.6 Kb insertion at the 5' end of the insulin gene. A gene dose-dependent effect was noted, class 3/3 individuals having the lowest after-load C-peptide concentration and class 1/3 an intermediate level (F for the linear trend: P = 0.007). This might suggest that insulin gene polymorphism affects insulin secretion in healthy individuals. In order to confirm this, a subgroup of six class 3/3 and eight class 1/1 individuals subsequently underwent a hyperglycaemic clamp. The tissue sensitivity to insulin was similar in the two groups but glucose-stimulated insulin secretion was markedly impaired in homozygotes for the class 3 allele. In this group, insulin secretion was, on average, only one-third of that in class 1/1 individuals (P less than 0.02). Similarly impaired in class 3/3 persons was the glucose + arginine-stimulated insulin secretion (P less than 0.05). We conclude that the polymorphism at the 5' end of the insulin gene is associated with variations in insulin secretion in healthy humans.

Adult↗
PubMed1987

Increased level of thyroglobulin mRNA in a human familial goiter.

Thyroglobulin (Tg) and its specific mRNA were analyzed in the thyroid gland of two cases of familial goiter. A three-fold increase in the level of stable protein and functional Tg mRNA was found in the goiter of one of the two patients in whom a desiodase defect was demonstrated. Normal concentrations of both Tg and its mRNA were found in the other goiter in which no enzymatic defect could be shown. Our results suggest that the increase of Tg mRNA levels found in the goiter with a desiodase defect was due to a chronic stimulation of the gland by TSH.

Adolescent↗
PubMed1985

Mapping of human thyroglobulin gene on the long arm of chromosome 8 by in situ hybridization.

We report the structural organization of a segment of the human thyroglobulin gene, located 70kb from the 3' end of the gene, containing the exons 8 and 9 starting from the 3' end. Selected probes from this region have been used for the chromosomal mapping of the thyroglobulin gene by in situ hybridization techniques. Only one site in the human haploid karyotype is labeled with the genomic DNA probes. Twenty percent of the grains are localized on the long arm of chromosome 8, mostly in the subregion q-2-23 q-2-24 of the long arm of chromosome 8. The localization of the autoradiographic grains suggests a subregional assignment of the human thyroglobulin gene locus to 8q 2-23 or 8q 2-24.

Base Sequence↗
PubMed1978

[In vitro expression of the thyroid gland genome. Difference between chromatin and DNA].

In vitro, transcription by thyroid chromatin has been compared to that carried out by deproteinized DNA prepared from the same tissue. The chromatin-primed transcripts are represented by 4S and 10S RNAs, whereas the DNA-primed transcript is heterogenous and polydisperse. The sequences expressed in vitro have been analyzed by hydridization of 4S and 10S RNA to the total native thyroid DNA. Most of the sequences transcribed are represented by intermediate repetitive-associated an unique sequence. Furthermore, they are expressed only by chromatin and not by DNA. Thus, thyroid chromatin very likely holds in vitro the same fonctional restriction exhibited in vivo, whereas the transcriptional behaviour of thyroid DNA is totally aspecific.

Animals↗