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Biomedical subjects

G Meola

Publications and source records attributed to G Meola.

103 records · Page 6Linked to original sources
PubMedDate not supplied

[Expression of a defect in the respiratory chain in cultured human cells].

Large scale deletions of mitochondrial DNA (mtDNA) or altered inter-genomic regulation in skeletal muscle have been demonstrated in patients with mitochondrial encephalomyopathies due to Cytochrome C oxidase (COx) deficiency. We have analyzed by Southern blotting and Polymerase Chain Reaction (PCR) the mtDNA in primary muscle cultures (myoblast-myotube stages and at clonal densities) and in fibrogenic subclones obtained from 9 patients with partial COx deficiency who had in their muscle biopsy a subpopulation of mtDNA showing deletions of variable size (between 2.1 and 6.5 Kb). Only in the cultures from one patient, southern analysis revealed in myoblasts and myotubes a mtDNA almost identical to that found in the original muscle biopsy and persistence of deletion in muscle cells grown at clonal densities. The deletion was detectable in fibrogenic lineage only by PCR amplification. The deleted mtDNA molecules were detectable in myogenic or fibrogenic cultures from other patients only by PCR amplification. The different amounts of deleted mtDNA in the various tissues could be due either to an unequal distribution of the altered mtDNA during embryogenesis with amplification of deleted molecules in myogenic lineage or could result from negative selection against the altered mtDNA in rapidly proliferating cells, such as fibroblasts.

Blotting, Southern↗
PubMedDate not supplied

Apoptosis induced by proteasome inhibition in human myoblast cultures.

Dysfunction of the ubiquitin-proteasome system has recently been implicated in the pathogenesis of some untreatable myodegenerative diseases characterized by the formation of ubiquitinated inclusions in skeletal muscles. We have developed an in vitro model of proteasomal dysfunction by applying inhibitors of the proteasome to primary adult human skeletal muscle cultures. Our data show that proteasome inhibition causes both cytoplasmic accumulation of ubiquitinated inclusions and apoptotic death, the latter through accumulation of active caspase-3.

Adult↗
PubMedDate not supplied

Central nervous system involvement in HCV-related mixed cryoglobulinemia.

An involvement of the peripheral nervous system is frequent in patients with HCV-related mixed cryoglobulinemia (HCV-MC), whereas central nervous system (CNS) impairment has been rarely reported. To investigate the possible CNS involvement in MC, we evaluated 18 patients by neurophysiological, neuroradiological and neuropsychological methods. Three patients (16.7%) had clinically evident neurological central signs, ten (55.5%) complained of mild symptoms, possibly indicative of CNS impairment, and five (27.8%) did not have any CNS symptom. Evoked potentials (EPs) were abnormal in 83% of the cases (SSEPs in 72%, VEPs in 44%, MEPs in 39% and BAERs in 22%). Brain magnetic resonance imaging (MRI) showed abnormal findings in 83% (small T2-weighted hyperintense lesions in 72%, focal or diffuse atrophy in 50%). Cognitive impairment was detected in 22% of the patients. A mild or subclinical CNS involvement is frequent in MC patients. Neuropsychological, neurophysiological and neuroradiological examination are useful to detect CNS involvement also in asymptomatic subjects.

Aged↗
PubMedDate not supplied

Muscleblind-like protein 1 nuclear sequestration is a molecular pathology marker of DM1 and DM2.

Myotonic dystrophies (DM) are repeat expansion diseases in which expanded CTG (DM1) and CCTG (DM2) repeats cause the disease. Mutant transcripts containing CUG/CCUG repeats are retained in muscle nuclei producing ribonuclear inclusions, which can bind specific RNA-binding proteins, leading to a reduction in their activity. The sequestration of muscleblind-like proteins (MBNLs), a family of alternative splicing factors, appears to be involved in splicing defects characteristic of DM pathologies. To determine whether MBNL1 nuclear sequestration is a feature of DM pathologies, we have examined the in vivo distribution of MBNL1 in muscle sections from genetically confirmed DM1 (n=7) and DM2 (n=9) patients, patients with other myotonic disorders (n=11) and from patients with disorders caused by repeat expansions, but not DM1/DM2 (n=3). The results of our immunofluorescence study indicate that, among patients examined, MBNL1 nuclear sequestration in protein foci is a molecular pathology marker of DM1 and DM2 patients where ribonuclear inclusions of transcripts with expanded CUG/CCUG repeats are also present. These findings indicate that MBNLs might be important targets for therapeutic interventions to correct some of the specific features of DM pathology.

Cell Nucleus↗
PubMedDate not supplied

[Present-day clinico-genetic framework of Duchenne's muscular dystrophy].

The authors emphasize the importance of adding a genetic criterion to the definition of Duchenne dystrophy. The clinical characteristics, however, on the basis of recent molecular genetic studies, are sufficiently precise to make the condition heterogeneous: two types of Duchenne dystrophy, with or without mental retardation in affected boys; muscular dystrophy in girls with mild symptomatic weakness in "manifesting carriers" up to severe myopathy in girls, found to be associated with reciprocal chromosomal translocation (X-autosome), always at the same site, Xp21. Diagnostic use of Xp21 probes is now as necessary as EMG, muscle biopsy and serum CK assay for the definition of Duchenne muscular dystrophy.

Creatine Kinase↗
PubMedDate not supplied

[Prevention of duchenne's muscular dystrophy: methodological problems in the detection of carriers (author's transl)].

In the last five years 48 possible carries and 13 known carriers of the gene for the Duchenne type of muscular dystrophy were studied in the Neurological Institute of the University of Milan. To achieve the most accurate detection, the following tests are recommended: a) the serum creatine kinase (CPK) estimation; b) quantitative EMB test on 3 muscles (deltoid, biceps and vastus medialis), in case of normal CPK level; c) histological and histochemical studies, only if tests a) and b) are uniformative.

Adolescent↗
PubMedDate not supplied

Neural regulation of acid maltase in an unusual adult onset deficiency.

In a 48-year-old female, the first symptoms apparently manifested themselves 18 years before, with occasional tripping and weakness in both legs. During the next 18 years, weakness progressed and the patient developed a waddling gait; she became unable to rise from a lying or seated position unassisted and the shoulder girdle also became affected. Neurological examination revealed limb and shoulder girdle predominantly involving the lower extremities. We established cell cultures from muscle biopsy specimens obtained from our patient and carried out morphological analysis which, although aspecific, demonstrated clear signs of neurogenic suffering. This was confirmed in EMG studies performed. Biochemical analysis revealed very low acid maltase residual activity. We describe an unusual case of adult-onset acid maltase deficiency (AMD) with neurogenic atrophy and low residual activity. Innervated myofibres prepared by co-culturing the patient's myoblasts, with spinal cord foetal mouse explants were not associated with an abnormal in vitro maturation of the innervated myofibres as expected by the very low residual enzymatic activity found both in the muscle biopsy specimens and in the muscle cultures. There is strong suggestion that factors other than the amount of residual activity must be involved to determine the clinical manifestation of this disease.

Animals↗
PubMedDate not supplied

Muscle surface mechanical and electrical activities in myotonic dystrophy.

The dimensional changes of the muscle fibres of the active motor units generate a signal, labelled as mechanomyogram (MMG), related to the number and firing rate of the active fibres. Aim of the study was to evaluate if the root mean square (RMS) of the surface EMG, of the MMG and their relationship (electromechanical coupling efficiency, EMCE) are related to the clinical stage of patients affected by myotonic dystrophy. The EMG and the MMG were recorded during isometric contractions at 20%, 40% and 60% of the maximal voluntary contraction (MVC), in less (elbow flexors, EF) and more (finger flexors, FF) affected muscles in 10 myotonic dystrophy (DM) patients (duration of disease: 15-22 yr.; MDRS scale: 3-4) and in 10 age matched controls (C). It resulted that I) the MVC was only 30% lower in DM than in C (P > 0.05) for the EF but 74% lower (P < 0.001) for the FF; II) at the same relative force the MMG-RMS and the EMG-RMS in DM were significantly lower than in C (P < 0.05); III) the EMCE was almost the same in DM and C for EF but dramatically lower for FF. In conclusion these findings provide evidence that the EMCE changes due to the dystrophic process can be monitored by this new and non invasive technique. A good concurrence of clinical findings and experimental results was observed.

Adult↗