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Biomedical subjects

G Novelli

Publications and source records attributed to G Novelli.

At least 55 records · Page 3Linked to original sources
PubMed2000

Absence of correlation between BMP-4 polymorphism and postmenopausal osteoporosis in Italian women.

Several studies have demonstrated that bone has the power of regeneration and repair. BMPs (bone morphogenetic proteins) are involved in the determination of osteoblast phenotype and bone turnover, therefore genes coding for these proteins, like BMP-4, could be considered potential candidate genes for osteoporosis. We investigated the association of BMP-4 gene polymorphism with osteoporosis in a cohort of 72 osteoporotic, postmenopausal women and 82 unrelated controls. We failed to detect any significant association between this genetic marker and the disease.

Bone Morphogenetic Protein 4↗
PubMed2000

Fine mapping of a distinctive autosomal dominant vacuolar neuromyopathy using 11 novel microsatellite markers from chromosome band 19p13.3.

We previously mapped a distinctive autosomal dominant vacuolar neuromyopathy on human chromosome 19p13 in an 8cM region, delimited by D19S209 and D19S177 markers. We now report the fine mapping of the disease locus within an interval of 250 Kb by haplotype analysis performed using a set of 11 novel microsatellite markers isolated from the candidate region.

Chromosome Mapping↗
PubMed2000

T cell receptor repertoire and function in patients with DiGeorge syndrome and velocardiofacial syndrome.

DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS) are associated with chromosome 22q11.2 deletion. Limited information is available on the T cell receptor (TCR) Vbeta repertoire. We therefore investigated TCR Vbeta families in lymphocytes isolated from blood and thymic samples of seven patients with DGS and seven patients with VCFS, all with 22q11.2 deletion. We also studied activities related to TCR signalling including in vitro proliferation, anti-CD3-induced protein tyrosine phosphorylation, and susceptibility to apoptosis. Reduced CD3+ T cells were observed in most patients. Spontaneous improvement of T cell numbers was detected in patients, 3 years after the first study. Analysis of CD4+ and CD8+ TCR Vbeta repertoire in peripheral and thymic cells showed a normal distribution of populations even if occasional deletions were observed. Lymphoproliferative responses to mitogens were comparable to controls as well as anti-CD3-induced protein tyrosine phosphorylation. Increased anti-CD3-mediated apoptosis was observed in thymic cells. Our data support the idea that in patients surviving the correction of cardiac anomalies, the immune defect appears milder than originally thought, suggesting development of a normal repertoire of mature T cells.

Abnormalities, Multiple↗
PubMed2000

Protective effects of N-acetylcysteine and rutin on the lipid peroxidation of the lung epithelium during the adult respiratory distress syndrome.

This study investigates the effects of N-acetylcysteine (NAC) and rutin on the lung oxidative burden of patients with early adult respiratory distress syndrome (ARDS). The protection was evaluated by measuring expired ethane and malondialdehyde (MDA), and oxidized (GSSG) and reduced glutathione (GSH) in the epithelial lining fluid of 36 patients who developed ARDS less than 24 hours before enrollment in the study. The patients were randomly assigned to 3 groups, receiving 250 mL 5% dextrose in water (group 1), NAC 50 mg/kg body weight in 5% dextrose (group 2), and NAC 50 mg/kg + rutin 5 mg/kg in 5% dextrose (group 3). Ethane and MDA concentrations were significantly reduced in the treatment groups after day 6. GSH was 30% increased in the treatment groups. No significant variations were observed in the control group until day 9. The trial confirms that NAC and rutin are efficient in protecting the lungs of patients with ARDS.

APACHE↗
PubMed2000

Evidence for an association between the SRD5A2 (type II steroid 5 alpha-reductase) locus and prostate cancer in Italian patients.

We have investigated the contributions of three polymorphic markers in the SRD5A2 gene to prostate cancer in a group of Italian patients. We have genotyped cases and controls for a polymorphic (TA)n dinucleotide repeat and two functional substitutions, A49T and V89L, substituting respectively alanine with threonine at codon 49, and valine to leucine at codon 89. We found a substantially increased but not significant risk associated with the 49T mutation and a reduction of risk for the V89L substitution. In conclusion, we report on preliminary evidence for both increased and decreased risk associated with separate markers at this locus.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2000

The effect of glutathione and N-acetylcysteine on lipoperoxidative damage in patients with early septic shock.

Both the hyperproduction of oxygen free radicals (OFR) and the weakening of natural scavenging mechanisms have been implicated as contributors to multiple organ failure in septic shock. This study examined whether the antioxidants glutathione (GSH) and N-acetyl-L-cysteine (NAC) play a protective role against damage by OFR in early septic shock. We randomly entered 30 patients with septic shock into one of three groups within 24 h of diagnosis. All of the patients received septic shock therapy, including parenteral nutrition, antibiotics, and volume-expanding and inotropic agents. One group (Group B) also received 70 mg/kg/d of intravenous GSH, and a second group (Group C), 70 mg/kg/d of intravenous GSH and 75 mg/kg/d of intravenous NAC. The protection against OFR damage was evaluated by measuring expired ethane, plasma malondialdehyde, erythrocyte deformability, complement activation, and clinical scores at admission and on Days 3 and 5 of treatment. A significant decrease in peroxidative indexes was observed at Day 5 in Group B as compared with both the control group and basal values. The decrease in peroxidative indexes was even more marked in Group C. Clinical scores in this group were also significantly improved. In conclusion, the administration of high doses of NAC added to GSH significantly decreased the peroxidative stress of patients with septic shock.

APACHE↗
PubMed2000

Transfer and expression of foreign genes in mammalian cells.

The transfer of foreign genes into eukaryotic cells, in particular mammalian cells, has been essential to our understanding of the functional significance of genes and regulatory sequences as well as the development of gene therapy strategies. To this end, different mammalian expression vector systems have been designed. The choice of a particular expression system depends on the nature and purpose of the study and will involve selecting particular parameters of expression systems such as the type of promoter/enhancer sequences, the type of expression (transient versus stable) and the level of desired expression. In addition, the success of the study depends on efficient gene transfer. The purification of the expression vectors, as well as the transfer method, affects transfection efficiency. Numerous approaches have been developed to facilitate the transfer of genes into cells via physical, chemical or viral strategies. While these systems have all been effective in vitro they need to be optimized for individual cell types and, in particular, for in vivo transfection.

Animals↗
PubMed1999

Expression analysis and protein localization of the human HPC-1/syntaxin 1A, a gene deleted in Williams syndrome.

The HPC-1/syntaxin 1A (STX1A) gene maps to the Williams syndrome (WS) commonly deleted region on chromosome 7q11.23 and encodes a protein implicated in the docking of synaptic vesicles with the presynaptic plasma membrane. To assess the potential role of STX1A in the WS phenotype, we carried out expression studies at the RNA and protein levels, in fetal and adult human tissues. RNA in situ hybridization on human embryo sections showed strong STX1A expression in spinal cord and ganglia. However, in adulthood, this gene was preferentially expressed in brain, as shown by Northern blot and RT-PCR experiments. Marked expression levels were observed in cerebellum and cerebral cortex. The STX1A protein was prevalently distributed in the molecular layer of the cerebellar cortex. A qualitative and quantitative analysis using a specific anti-STX1A antibody did not disclose any significant difference among frontal, temporal, and occipital poles of the human adult cortex in the two hemispheres. This is the first study focused on STX1A expression in humans. Our results indicate that this gene is strongly expressed in cerebral areas involved in cognitive process, supporting a likely role in the neurological symptoms of WS.

Antigens, Surface↗
PubMed1999

A distinctive autosomal dominant vacuolar neuromyopathy linked to 19p13.

OBJECTIVE: To characterize a kindred with a distinctive autosomal dominant neuromuscular disorder. BACKGROUND: The authors studied a large Italian family affected by a progressive neuromyopathy. Ten individuals over three generations were affected. The disease was characterized by onset from the late teens to early 50s with distal leg weakness and atrophy, development of generalized muscle weakness with distal-to-proximal progression sparing facial and ocular muscles, dysphonia and dysphagia, pes cavus and areflexia, variable clinical expression ranging from subclinical myopathy to severely disabling weakness, and mixed neurogenic and myopathic abnormalities on electromyography. METHODS: Morphologic, immunocytochemical, and ultrastructural studies were performed in muscle biopsies from three affected patients. A genomewide linkage analysis through the genotyping of 292 microsatellite markers spanning the 22 autosomes was undertaken to map the disorder segregating in this family. RESULTS: All muscle biopsies showed variation of fiber size, panesterase-positive angular fibers, mild to severe fibrosis, and numerous "rimmed vacuoles." Electron microscopy failed to demonstrate the nuclear or cytoplasmic filamentous inclusions specific of inclusion-body myopathies and, accordingly, immunohistochemistry did not show any positivity with SMI-31 antibodies detecting hyperphosphorylated tau. Preliminary analysis of 292 microsatellite markers provided evidence for linkage to chromosome 19p13. CONCLUSIONS: This distinctive autosomal dominant disorder is characterized by a vacuolar neuromyopathy. Localization to chromosome 19p13 will allow the genetic relationship between this disease and inherited myopathies with rimmed vacuoles, in particular autosomal dominant inclusion-body myopathies, to be defined.

Adult↗
PubMed1999

Gene transfection efficiency of tracheal epithelial cells by DC-chol-DOPE/DNA complexes.

We evaluated the transfection efficiency of five different cationic liposome/plasmid DNA complexes, during the in vitro gene transfer into human epithelial tracheal cell lines. A dramatic correlation between the transfection efficiency and the charge ratio (positive charge of liposome to negative charge of DNA) has been found. DC-Chol-DOPE was found to be the most effective liposome formulation. Therefore, a morphological and structural analysis of DC-Chol-DOPE liposomes and DC-Chol-DOPE/DNA complexes, has been performed by transmission electron microscopy (TEM) and by confocal laser scanning microscopy (CLSM), respectively. The process of interaction between DC-Chol-DOPE/DNA complexes and human epithelial tracheal cells has been studied by CLSM. These results raise some issues for in vivo gene therapy.

Benzothiazoles↗
PubMed1999

Classical galactosemia and mutations at the galactose-1-phosphate uridyl transferase (GALT) gene.

Classical galactosemia is caused by a deficiency in activity of the enzyme galactose-1-phosphate uridyl transferase (GALT), which, in turn, is caused by mutations at the GALT gene. The disorder exhibits considerable allelic heterogeneity and, at the end of 1998, more than 150 different base changes were recorded in 24 different populations and ethnic groups in 15 countries worldwide. The mutations most frequently cited are Q188R, K285N, S135L, and N314D. Q188R is the most common mutation in European populations or in those predominantly of European descent. Overall, it accounts for 60-70% of mutant chromosomes, but there are significant differences in its relative frequency in individual populations. Individuals homoallelic for Q188R tend to have a severe phenotype and this is in keeping with the virtually complete loss of enzyme activity observed in in vitro expression systems. Globally, K285N is rarer, but in many European populations it can be found on 25-40% of mutant chromosomes. It is invariably associated with a severe phenotype. S135L is found almost exclusively in African Americans. In vitro expression results are discrepant, but some individuals carrying S135L appear to exhibit GALT activity in some tissues. Duarte 1 (or Los Angeles) and Duarte 2 (or Duarte) variants carry the same amino acid substitution, N314D, even though D1 is associated with increased erythrocyte GALT activity and D2 with reduced activity. N314D is in linkage disequilibrium with other base changes that differ on the D1 and D2 alleles. N314D does not impair GALT activity in in vitro expression systems. However, there are differences in the abundance of GALT protein in lymphoblastoid cells lines from D2 and D1 individuals. It is unclear whether the specific molecular changes that distinguish the D1 and D2 alleles account for the different activities. The considerable genetic heterogeneity documented to date undoubtedly contributes to the phenotypic heterogeneity that is observed in galactosemia. The additional effects of nonallelic variation and other constitutional factors on phenotypic variability remain to be elucidated.

Alleles↗
PubMed1999

Diagnosis of DiGeorge and Williams syndromes using FISH analysis of peripheral blood smears.

We describe the use of a FISH protocol for detecting chromosome microdeletions in peripheral blood smear leukocytes. This method has the advantage of a smaller sample requirement than classical metaphase chromosome analysis and the potential for analysis of a larger number of chromosome microdeletions using a routine blood smear. A selected series of 10 DiGeorge syndrome (DGS) and 12 Williams-Beuren syndrome (WBS) patients were correctly diagnosed by this method confirming results obtained by molecular cytogenetic metaphases. These results support effectiveness of interphase FISH analysis on peripheral blood smears as a focused, single-step method for the detection of chromosome microdeletions.

Adolescent↗
PubMed1999

Isolation and characterization of a novel transcript embedded within HIRA, a gene deleted in DiGeorge syndrome.

We have isolated a few cDNAs from different human tissues, transcribed from the first intron of HIRA, a gene deleted in the DiGeorge syndrome. These cDNAs are produced by an intronic gene (22k48) which is transcribed by the HIRA opposite strand and is itself arranged in exons and subjected to alternative splicing. The longest continuum cDNA sequence we obtained is 3.6 kb long and contains 3 different exons and 2 introns. 22k48 cDNA is composed of several tandemly arranged repeated elements (Alu, LINEs, CAn) surrounding a unique sequence. In situ hybridization showed the presence of 22k48 RNA in the cytoplasm of CNS and PNS neurons. 22k48 RNA is able to bind cytoplasmic proteins in the range of 45 to 60 kDa. 22k48 is a new member of the small group of genes that are transcribed but not translated, and its haploinsufficiency could contribute to the pathogenesis of the DiGeorge syndrome.

Adult↗
PubMed1999

Genomic structure, promoter characterisation and mutational analysis of the S100A7 gene: exclusion of a candidate for familial psoriasis susceptibility.

We have recently assigned a locus for familial psoriasis (PS) susceptibility to the region containing the epidermal differentiation complex gene cluster on chromosome 1q21. Gene S10OA7 maps within this cluster and is reported to be markedly over-expressed in the skin lesions of psoriatic patients. In order to analyse S100A7 as a candidate for PS susceptibility, we have determined its genomic structure regarding exon-intron boundaries and the transcription start site. The gene is organised in three exons and two introns, spanning 2.7 kb. The 5' flanking region contains AP1- and Sp1-binding motifs and a TATA box. We have performed functional assays by using the beta-galactosidase gene as a reporter and have confirmed that this region has strong promoter activity. To search for nucleotide variation within S100A7, we have designed a set of primers to amplify each exon and the gene promoter. Polymerase chain reaction products from 15 unrelated PS patients selected from 1q-linked pedigrees and 25 normal controls have been characterised by single-strand conformation polymorphism and direct sequencing techniques. These analyses have revealed the presence of two polymorphisms in the promoter region (-559G/A and -563 A/G), neither of which shows preferential association with the disease. Our results indicate that S100A7 can be excluded as a candidate for PS susceptibility.

Base Sequence↗