Biomedical subjects

G Meola

Publications and source records attributed to G Meola.

At least 37 records · Page 2Linked to original sources

PubMed1999

Proximal myotonic myopathy (PROMM) presenting as myotonia during pregnancy.

Proximal myotonic myopathy is a recently described autosomal dominant condition characterized by proximal myopathy, cataracts, intermittent myotonia, and myalgia. We report a further family with this condition. The proband and her two sisters presented with myotonia during pregnancy which resolved after each delivery. Two sisters experienced myalgia between each pregnancy. This relationship between pregnancy and symptom exacerbation suggests an intriguing hormonal influence in PROMM.

Adult↗

PubMed1997

Andersen's syndrome: a distinct periodic paralysis.

A previous study of 4 patients defined Andersen's syndrome (AS) as a triad of potassium-sensitive periodic paralysis, ventricular dysrhythmias, and dysmorphic features. AS appears to be distinct in terms of its genetic defect from the alpha-subunit of skeletal muscle sodium channel and the cardiac potassium channel responsible for most long QT syndromes (LQT1). We studied 11 additional patients with AS from 5 kindreds. Spontaneous attacks of paralysis were associated with hypokalemia, normokalemia, or hyperkalemia. All 11 patients had similar dysmorphic features. The QT interval was prolonged in all patients although only 4 were symptomatic. Genetic linkage studies excluded linkage to the alpha-subunit of the skeletal muscle sodium channel and to four distinct LQT loci. In addition, none of the common dihydropyridine receptor mutations responsible for hypokalemic periodic paralysis were present. We conclude that (1) AS is a genetically unique channelopathy affecting both cardiac and skeletal membrane excitability, (2) attacks of paralysis may be either hypokalemic or hyperkalemic, (3) a prolonged QT interval is an integral feature of this syndrome, and (4) a prolonged QT interval may be the only sign in an individual from an otherwise typical AS kindred. This may be confused with more common, potentially lethal LQT syndromes.

Adolescent↗

PubMed1997

Oculopharyngeal muscular dystrophy in Italy.

Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant myopathy particularly frequent in Québec. The few Italian cases thus far described with bilateral ptosis, dysphagia and variable muscle weakness, show non-specific dystrophic findings on muscle biopsies by light microscopy. We describe a 70-year-old Italian woman with an adult-onset ptosis, mild dysphagia and proximal muscle weakness belonging to a family segregating OPMD according to an autosomal dominant mode of inheritance. Clinical features of four of her relatives are reviewed. Muscle biopsy studied by electron microscopy showed the typical 8.5 nm in diameter intranuclear filamentous inclusions (INI). To our knowledge, this is the first Italian report of OPMD with INI. The identification of nuclear inclusions is mandatory in order to confirm the diagnosis prior to linkage analysis.

Aged↗

PubMed1997

De novo 14484 mitochondrial DNA mutation in monozygotic twins discordant for Leber's hereditary optic neuropathy.

Monozygotic twin brothers, clinically discordant for Leber's hereditary optic neuropathy (LHON), had a heteroplasmic point mutation at position 14484 in the mitochondrial DNA that was not detected in their mother. Moreover, the mutation occurred on the rare European haplogroup X, rather than the haplogroup J commonly associated with the 14484 mutation. These data indicate that the 14484 mutation in this family was a new mutation, indicating that it was the de novo occurrence of a common, primary LHON mutation.

Adolescent↗

PubMed1996

Computerized tomography and magnetic resonance muscle imaging in Miyoshi's myopathy.

We describe clinical, pathological, and muscle imaging findings in a patient with an early adult-onset progressive muscular weakness in association with atrophy beginning in the legs and involving both gastrocnemi in particular. Muscle biopsy findings showed a severe dystrophic process with no vacuoles, consistent with Miyoshi's myopathy. Computerized tomography and magnetic resonance imaging scans were used to provide an ongoing permanent record of the various stages of the disease.

Adult↗

PubMed1996

A newly-described myotonic disorder (proximal myotonic myopathy--PROMM): personal experience and review of the literature.

The aim of this study is to describe the essential characteristics of a family affected by the newly-described proximal myotonic myopathy (PROMM) The clinical, laboratory and genetic findings are described and compared with those reported in the literature, and the clinical spectrum of the manifestations that are similar to but distinct from myotonic dystrophy (MD) is also explored. This has practical implications because the cases so far described suggest that the long-term prognosis with PROMM seems to be more favourable than that of patients with MD.

Adult↗

PubMed1996

A family with an unusual myotonic and myopathic phenotype and no CTG expansion (proximal myotonic myopathy syndrome): a challenge for future molecular studies.

Myotonic dystrophy (DM) is a well-defined autosomal dominant disorder characterized by myotonia, muscle weakness, cardiac conduction defects, cataracts, and endocrine abnormalities. Recently a newly recognized disorder, similar to but distinct from DM, has been observed with multisystem findings including intermittent myotonia, proximal myopathy, and occasional cardiac conduction disturbances. This disorder has been called proximal myotonic myopathy (PROMM). No history of anticipation is present and there is no linkage to the gene locus for DM or to the loci for the muscle sodium or chloride channels. This report describes a family with a normal size of the CTG trinucleotide repeat expansion of the DM gene in which affected individuals have myotonia (intermittent, exacerbated by cold), bilateral cataracts, mild hypogonadism and mild temporal atrophy. Affected individuals also have proximal muscle weakness, facial involvement, nonspecific abnormalities on muscle biopsy, normal cardiac conduction, and no glucose intolerance. The absence of trinucleotide repeat expansion in the DM gene is consistent with this family being affected by a disorder distinct from DM, possibly a form of PROMM.

Adult↗

PubMed1995

Cardiac involvement in patients with myotonic dystrophy: characteristic features of magnetic resonance imaging.

Structural alterations of the myocardium, such as fibrosis and fatty infiltration, were observed in post-mortem examinations in patients with myotonic dystrophy, a familial multisystem neuromuscular disease with frequent cardiac involvement. To identify structural and anatomical abnormalities of the heart, 14 patients, aged 45 +/- 14 years, belonging to seven families, suffering from myotonic dystrophy were studied. Twelve-lead ECG, high resolution signal-averaged ECG, 24 h Holter monitoring, bidimensional echocardiography and cardiac magnetic resonance (MRI) were performed in all patients. Atrioventricular and/or intraventricular conduction disturbances were present in 11 patients; no major arrhythmias were recorded by Holter monitoring. Ventricular late potentials were present in four patients, absent in eight and not assessed in two (due to left bundle branch block). Echocardiogram showed abnormal findings (left ventricular hypertrophy, mitral valve prolapse, wall motion abnormalities) in eight patients. MRI revealed various cardiac alterations in 11 cases, specifically: left ventricular hypertrophy in seven, right ventricular hypertrophy in two, right ventricular enlargement in six, area of fatty infiltration and fibrosis in the right ventricle in six and in both ventricles in three. Although no clear correlations between the extent of fibro-lipomatous infiltrations and severity of cardiac dysfunction were found, fatty infiltrations were always observed in the most severely diseased patients and were frequently associated with the presence of more advanced conduction disturbances.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

Expression of the low-affinity NGF receptor during human muscle development, regeneration, and in tissue culture.

The expression of the low-affinity NGF receptor (LNGFR) during human muscle development, regeneration, and in tissue culture was analyzed using a murine monoclonal antibody to human LNGFR (MAb ME 20.4). Muscle cells from 12-22-week fetuses stained strongly for LNGFR. In adult normal muscle, only intramuscular nerve endings showed immunoreactivity with MAb ME 20.4, but no staining was detected in muscle fibers. In Duchenne muscular dystrophy, immunohistologically demonstrable LNGFR was present in regenerating muscle fibers. In these fibers, LNGFR gene expression was also demonstrated at the transcriptional level using in situ hybridization with riboprobes coding with human LNGFR. Cultures from human fetal and adult muscle were studied by double label indirect immunofluorescence microscopy with MAb ME 20.4 and antisera against human fetal myosin. Most myosin-positive cells, both at the myoblast and myotube stages, displayed surface LNGFR immunostaining. In cells from fetal muscle, LNGFR was detected during the first 2 weeks in vitro, whereas in cells from adult muscle the expression of LNGFR was observed for up to 7 weeks. These findings suggest a potential involvement of LNGFR in human muscle development and regeneration.

Culture Techniques↗

PubMed1994

Muscle phosphoglycerate mutase (PGAM) deficiency in the first Caucasian patient: biochemistry, muscle culture and 31P-MR spectroscopy.

Muscle phosphoglycerate mutase (PGAM) deficiency has been so far identified in only six patients, five of these being African Americans. We report the results of clinical, morphological, biochemical, muscle culture and 31P-MR spectroscopy studies in the first Caucasian patient with muscle PGAM deficiency. A 23-year-old man had a 10-year history of cramps after physical exertion with one episode of pigmenturia. Neurological examination and EMG study were normal. ECG and echocardiography revealed hypertrophy of the interventricular septum and slight dilation of the left chambers of the heart. Muscle biopsy revealed increased glycogen content and some accumulation of mitochondria. Muscle PGAM activity was markedly decreased (6.5% and 9.7% of control value in two different biopsies). Citrate synthase and other mitochondrial respiratory chain enzyme activities were much higher than normal. In contrast to the marked decrease of PGAM activity observed in muscle biopsy, total enzyme activity in the patient's aneural muscle culture was normal, being represented exclusively by BB isoenzyme. The deficiency of PGAM-MM isoenzyme was reproduced in the patient's innervated muscle culture. Muscle 31P-MR spectroscopy showed accumulation of phosphomonoesters only on fast "glycolytic" exercise. On "aerobic" exercise, Vmax, calculated from the work-energy cost transfer function, showed an increase consistent with the morphological and biochemical evidence of mitochondrial proliferation. This might represent a sort of compensatory aerobic effort in an attempt to restore muscle power.

Adult↗

PubMed1994

Mutation in the S4 segment of the adult skeletal sodium channel gene in an Italian paramyotonia congenita (PC) family.

The periodic paralyses are a group of autosomal dominant muscle diseases sharing the common feature of episodic stiffness and weakness, usually occurring with muscle cooling (as in the case of paramyotonia congenita, PC phenotype) or changes in extracellular K+ levels resulting from various precipitating factors (hyperkalemic periodic paralysis, HYPP and hypokalemic periodic paralysis, HypoPP). It is now known that HYPP maps to chromosome 17q, and that PC and a form of myotonia congenita without periodic paralysis also map to the 17q locus, thus indicating that they derive from allelic variants. So far, these disorders have been described in various ethnic groups but, to our knowledge, have never been reported in Italy. We describe a mutation in an S4 segment of the adult skeletal muscle sodium channel in a clinically-defined Italian family that leads to the paramyotonia congenita (PC) phenotype with dominant autosomal inheritance and temperature-related symptoms (regional weakness following cooling and exercise), present since childhood in all of the affected family members.

Adult↗

PubMed1994

Sodium channel mutations in acetazolamide-responsive myotonia congenita, paramyotonia congenita, and hyperkalemic periodic paralysis.

Hyperkalemic periodic paralysis (hyperKPP) and paramyotonia congenita (PC) are genetic muscle disorders sharing the common features of myotonia and episodic weakness. In hyperKPP, patient symptoms and signs are worsened by elevated serum potassium, whereas in PC, muscle cooling exacerbates the condition. There are patients in whom features of both hyperKPP and PC are present. These diseases result from molecular alterations in the adult skeletal muscle sodium channel. This report summarizes our sodium channel mutation analysis in 25 families with hyperKPP and PC. We also report the putative disease-causing mutation in acetazolamide-responsive myotonia congenita, a related disease in which myotonia is worsened by potassium but in which episodic weakness does not occur. This missense mutation (I1160V) occurs at a very highly conserved position in the sodium channel, cosegregates with the disease, and was not present in any of a large panel of normal DNAs. Electrophysiologic characterization of specific mutations will lead to better understanding of the biophysics of this voltage-gated ion channel.

Acetazolamide↗

PubMed1994

Enzymatic activity and morphological differentiation in de novo innervated human muscle cultures.

In the present series of experiments, we studied the effects of developmental neural control on morphological differentiation and on the activity of muscle-specific (creatine kinase, CK; phosphoglycerate mutase, PGAM; phosphorylase, PPL; and phosphofructokinase, PFK) and non-specific (acid maltase, AM; glucose-6-phosphate dehydrogenase, G6PD), human muscle enzymes in de novo innervated muscle cultures. Following innervation of muscle cultures, we noted an increase in the activity of CK, PPL, PFK and AM along with a reduction in G6PD activity. There was also a change of the CK isoenzymes present in the myotubes, i.e. BB and MB are the major isoenzymes in non innervated cultures, but MM becomes predominant following innervation. In the case of PGAM, the only isoenzyme present in the non innervated cultures was BB while the MM isoform appeared only after a prolonged innervation period in most cases--with the exception of AM--these changes in enzyme activity and in the type of isoenzymes present, demonstrate that innervated cultures are more similar to mature muscle. This maturation of enzymatic activity correlates well with the morphological maturation of the myotubes observed following innervation. Such innervated cultures therefore represent a better model with which to study the morphological and biochemical abnormalities associated with neuromuscular diseases.

Creatine Kinase↗

PubMed1993

Muscle glucose-6-phosphate dehydrogenase deficiency: restoration of enzymatic activity in hybrid myotubes.

A high level of glucose-6-phosphate dehydrogenase (G6PD) activity was observed in myoblasts and myotubes from normal human and mouse cell cultures. However, only a residual amount of activity was observed in myoblasts and myotubes obtained from G6PD-deficient patients (G6PD Mediterranean). Hybrids were formed by the fusion of normal (from human and mouse) and G6PD-deficient myoblasts (from the patients). These hybrids contained a high level of G6PD activity. Hoechst staining permitted to confirm that the enzymatic activity was not restrained to a domain near the competent nuclei. These results suggest that myoblast transplantation could be used to restore normal enzymatic activity in metabolic myopathies.

Adult↗

PubMed1993

Clinical and biochemical evidence of skeletal muscle involvement in galactose-1-phosphate uridyl transferase deficiency.

An 8-year-old boy with galactose-1-phosphate uridyl transferase (GALT) deficiency presented with hypotonia, muscle hypotrophy, hepatomegaly, bilateral cataract and mild mental retardation. Two brothers showed a GALT activity consistent with a homozygotic condition and both parents were found to be heterozygotes for this defect. Histological and ultrastructural examination of muscle biopsy specimens showed several necrotic fibres. GALT activity was undetectable in skeletal muscle and muscle tissue cultures; myotubes converted galactose to CO2 at a lower rate than controls. Galactose-1-phosphate was increased in the patient's red cells and muscle tissue. GALT deficiency, not previously described in muscle, may be of pathogenic relevance in determining the myopathic features present in GALT deficiency syndrome.

Biopsy↗

PubMed1993

Stable hybrid myotubes: a new model for studying re-expression of enzymatic activities in vitro.

Heterokaryons represent a stable and reproducible model system for the study of biochemical and molecular aspects responsible for muscle gene activation. Previous experiments have used this fusion system to demonstrate human gene activation in hybrids formed between human and non-human cells. The aim of this research was to apply this experimental model to the correction of a cytoplasmic activity, namely glucose-6-phosphate dehydrogenase (G6PD), in vitro, in hybrid myotubes formed between G6PD-negative and positive myoblasts. Different identification methods were used (Hoechst stain and Fluorescent Latex Microspheres, FLMs) to identify hybrid myotubes formed. We demonstrated the restoration of G6PD activity in all hybrid myotubes formed; we then tried to elucidate the mechanisms underlying the restoration of this specific activity and apply the results obtained to the understanding of more complex mechanisms involved in muscle gene activation.

Animals↗

PubMed1993

Cytoplasmic restoration and persistence of glucose-6-phosphate dehydrogenase activity in stable hybrid myotubes.

In previous experiments, we obtained an in vitro restoration of a cytosolic enzyme glucose-6-phosphate dehydrogenase (G6PD) in hybrid myotubes formed between G6PD-deficient and human or murine myoblasts. In the present series of experiments, the degree of restoration was observed and the persistence of the restored activity was evaluated in the hybrids formed. Quantitative measurements of enzymatic activity in single human-human or human-mouse myotubes, identified by using either fluorescent latex microspheres or Hoechst stain 33258, were made by using a computer-controlled Leitz photometer. Histospectrophotometry and statistical analysis showed a 50% restoration of enzymatic activity in human-human hybrids compared to deficient and normal myotubes. The restored activity was uniformly distributed throughout the cytoplasm and persisted in long-term cultures. No nuclear domain was observed for G6PD. Knowledge of the degree of restoration, of the extent of distribution of the products of "competent" nuclei and the demonstration that the correction is not a transitory event in vitro, supports the potential usefulness of myoblast transfer therapy for this type of myopathy.

Animals↗

PubMed1991

Increased acetylcholine sensitivity in Duchenne muscular dystrophy myotubes.

Monolayer cultures were established from explants of muscle obtained from 6 patients with Duchenne muscular dystrophy (DMD) and 9 controls. Electrophysiological studies were made after 3-4 weeks in vitro, when many myotubes had formed. An intracellular electrode was used to record cell membrane potential, and acetylcholine was applied by ionophoresis. The myotubes grown from Duchenne muscle showed greater acetylcholine sensitivity than controls.

Acetylcholine↗