Biomedical subjects

Giovanni Coppola

Publications and source records attributed to Giovanni Coppola.

8 recordsLinked to original sources

PubMed2006

Microarrays and the microscope: balancing throughput with resolution.

The cellular complexity of the brain is a major issue in the planning, execution and interpretation of microarray studies. Recent technical advances allow for high-throughput study of specific cell populations and circuits. Here we review representative examples of currently available methods that allow high resolution and specificity in brain microarray studies, while maintaining the goal of comprehensive, high-throughput analysis.

Animals↗

PubMed2006

Neuropsychological assessment, quantitative MRI and ApoE gene polymorphisms in a series of MS patients treated with IFN beta-1b.

Few trials issued the effect of disease-modifying medications on cognitive functions in multiple sclerosis. We designed an open-label longitudinal study to evaluate, during 2 years, cognitive performance and its relationship with MRI data and ApoE polymorphism findings in a group of relapsing-remitting (RR) multiple sclerosis (MS) Interferon (IFN) beta-1b-treated patients (median age 30 years, median disease duration 3.4 years). Complete neuropsychological battery was grouped into attention, information learning/memory, language and visuo-spatial functions. Fifty-two patients (33 females) were enrolled in the study. Six patients (11.5%) dropped out, mainly due to side effects. At baseline neuropsychological evaluation, we found 54% normal, 42% mildly impaired and 4% moderately impaired patients. At 2 years follow-up, cognitive status was stable in 65%, improved in 33% and worsened in 2% of patients. No significant relations were found between global cognitive outcome vs. EDSS change, clinical disease activity, MRI data or ApoE gene polymorphisms over the 2 years follow-up. EDSS and MRI fractional volumes were found to correlate with the performance at single tests. Twenty-one patients (45.6%) showed active MRI scans throughout the study, without any worsening at the corresponding neuropsychological examination. This ongoing trial suggests a possible beneficial effect of IFN beta-1b treatment on cognitive functions in RRMS patients. Extension of follow-up and further data analyses are needed to confirm and clarify these findings.

Adolescent↗

PubMed2006

Gene expression profiling in frataxin deficient mice: microarray evidence for significant expression changes without detectable neurodegeneration.

Friedreich's ataxia (FRDA) is caused by reduction of frataxin levels to 5-35%. To better understand the biochemical sequelae of frataxin reduction, in absence of the confounding effects of neurodegeneration, we studied the gene expression profile of a mouse model expressing 25-36% of the normal frataxin levels, and not showing a detectable phenotype or neurodegenerative features. Despite having no overt phenotype, a clear microarray gene expression phenotype was observed. This phenotype followed the known regional susceptibility in this disease, most changes occurring in the spinal cord. Additionally, gene ontology analysis identified a clear mitochondrial component, consistent with previous findings. We were able to confirm a subset of changes in fibroblast cell lines from patients. The identification of a core set of genes changing early in the FRDA pathogenesis can be a useful tool in both clarifying the disease process and in evaluating new therapeutic strategies.

Animals↗

PubMed2006

Technology Insight: querying the genome with microarrays--progress and hope for neurological disease.

The ability to perform large-scale analysis of the genome at the level of gene sequence, gene copy number and messenger RNA transcript expression characterizes the post-genomic era. In the past decade, the microarray-based approach has emerged as one of the major tools in this area of genome biology, contributing to advances in the understanding of Mendelian and complex neurological disorders. Despite technical issues regarding design, data analysis and validation that have to be addressed in the planning and interpretation of a microarray study, microarray-based approaches for studying transcript expression, single-nucleotide-polymorphism genotyping and gene resequencing are becoming more widely adopted. Genomic microarrays are providing an unprecedented opportunity to dissect the genetic risk for complex neurological disorders. Numerous clinical and preclinical applications are likely to dominate the ambitious microarray agenda within the next decade.

Genome, Human↗

PubMed2005

Autosomal recessive progressive myoclonus epilepsy with ataxia and mental retardation.

We describe two couples of sibs from a southern Italian family affected by epilepsy, myoclonus, mental retardation and slight ataxia. Onset was between 4 and 12 years and the course slowly progressive. The clinical picture suggested the diagnosis of Unverricht-Lundborg disease. Molecular study excluded linkage to EPM1. Other possible causes of progressive myoclonus epilepsy were also excluded.

Adult↗

PubMed2004

Reduced striatal [123 I]FP-CIT binding in SCA2 patients without parkinsonism.

Degeneration of substantia nigra has been described in spinocerebellar ataxia type 2 (SCA2). In this study, dopamine transporter (DAT) density with [123 I]FP-CIT SPECT was studied in six SCA2 patients with no parkinsonian signs, six Parkinson's disease (PD) patients, and six controls. Marked striatal DAT loss was found in both SCA2 and PD patients. However, a more severe reduction in the caudate and a higher putamen to caudate ratio distinguished SCA2 from PD patients, suggesting a more uniform nigrostriatal impairment in SCA2. Striatal DAT density of SCA2 patients correlated with the severity of cerebellar ataxia.

Adult↗

PubMed2004

A pathogenetic classification of hereditary ataxias: is the time ripe?

Harding's classification takes credits for defining the homogeneous phenotypes that have been essential for the genetic linkage studies and it is still useful for didactic purposes. The advances in pathogenetic knowledge make it now possible to modify Harding's classification. Five main pathogenetic mechanisms may be distinguished: 1) mitochondrial; 2) metabolic; 3) defective DNA repair; 4) abnormal protein folding and degradation; 5) channelopathies. The present attempt to classify ataxia disorders according to their pathogenetic mechanism is a work in progress, since the pathogenesis of several disorders is still unknown. A pathogenetic classification may be useful in clinical practice and when new therapeutic strategies become available.

Ataxia↗

PubMed2003

Variable phenotype in a P102L Gerstmann-Sträussler-Scheinker Italian family.

BACKGROUND: Gerstmann-Sträussler-Scheinker disease is an autosomal dominant prion disease. The clinical features include ataxia, dementia, spastic paraparesis and extrapyramidal signs. METHODS: We report a new large Italian family affected by Gerstmann-Sträussler-Scheinker disease. RESULTS: The four generation pedigree includes 11 patients. The mean age at onset +/- SD was 41.4 +/- 16.2 years. Mean disease duration to death in four patients was 5.5 +/- 1.7 years. Two clinical patterns were evident: cognitive impairment with scarce neurological features or ataxia followed by cognitive impairment. Molecular analysis showed P102L mutation in PRNP gene. CONCLUSION: Three Italian families have been reported to date. The variable phenotype has already been reported, and does not appear related to the codon 129 polymorphism.

Adult↗