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C Angelini

Publications and source records attributed to C Angelini.

At least 163 records · Page 9Linked to original sources
PubMed1992

Variability of the expression of muscle mitochondrial damage in ocular mitochondrial myopathy.

In this study we comparatively analysed deltoid histochemistry, biochemistry and mitochondrial DNA (mtDNA) in two groups of ten sporadic ocular mitochondrial myopathies (OMM), respectively with and without ragged red fibres (RRF). (1) All but one RRF--patients presented the mild form of OMM with blepharoptosis but without ophthalmoplegia; (2) the occurrence of cytochrome c oxidase deficient (COX-) fibres was significantly higher in the RRF+ group, but four RRF- cases also showed COX- fibres; (3) no difference was observed in biochemical findings between the groups; (4) two RRF- patients without COX- fibres showed mtDNA heteroplasmy; (5) in two RRF- patients without deltoid mtDNA deletion, biopsy of an eyelid muscle showed significant mitochondrial alterations. These results suggest that the expression of a mitochondrial defect can vary and that the absence of RRF in a skeletal muscle biopsy does not necessarily rule out the diagnosis of OMM, if other data support that.

Adolescent↗
PubMed1992

Screening for mutations in the muscle promoter region and for exonic deletions in a series of 115 DMD and BMD patients.

Mutations in the muscle promoter region and exonic deletions were screened in a series of 115 unrelated DMD and BMD patients from north-east Italy. No gross mutations of the promoter region were found. In three cases in which dystrophin of normal size was expressed at low levels, the analysis of DNA sequences of the promoter region failed to detect abnormalities. The majority of deletions in coding sequences, detected by cDNA probes, occur in the deletion hot spot identified by the probe P20. Intrafamilial variability in the severity of the disease is reported and discussed.

Adolescent↗
PubMed1992

Epidemiology of spinal muscular atrophies in a sample of the Italian population.

In the course of an epidemiological survey in four provinces of Veneto (northeastern Italy) 67 spinal muscular atrophy (SMA) cases (types I, II and III) were recorded. The survey spanned the period 1960-1983 and involved 859,891 consecutive live-born infants in a population of 2,635,800 inhabitants. The overall prevalence at birth for SMA types I, II and III was 7.8/100,000 live births. Type I alone accounted for 4.1/100,000 live births. If the hypothesis that SMA types I, II and III are clinical manifestations of allelic mutations is assumed, the mutation rate would be about 70 x 10(-6) and the frequency of the heterozygotes 1 in 57.

Female↗
PubMed1992

Clinical and biochemical aspects of carnitine deficiency and insufficiency: transport defects and inborn errors of beta-oxidation.

Carnitine is required for entry of long chain fatty acids into mitochondria where beta-oxidation occurs. Primary carnitine deficiency, due to a generic defect in cellular carnitine transport, exists in myopathic and systemic forms. Secondary carnitine deficiency may be due to multiplicity of inherited abnormalities, including deficiencies in carnitine palmitoyl-transferase acyl-CoA dehydrogenases, electron transfer flavoprotein, and 3-ketoacyl-CoA-thiolase. The clinical features, diagnosis, and treatment of these conditions are described.

Biological Transport, Active↗
PubMed1992

Percutaneous pinning of displaced supracondylar fractures of the humerus in children. Case report.

The authors report their experience with closed reduction and percutaneous pinning of twenty-two supracondylar fractures of the humerus in children. In cases with neurovascular complications there was a marked regression within six hours following reduction. The results after 15 months to 13 years were satisfactory (excellent + good) in 90% of the cases, avoiding the risks and possible cicatricial complications of incisions and the discomfort of orthopaedic treatment in traction and subsequent thoracic-brachial plaster cast.

Adolescent↗
PubMed1991

L-carnitine uptake in differentiating human cultured muscle.

We studied carnitine uptake in human skeletal muscle growing in culture for up to 30 days, and correlated it to the degree of muscle differentiation revealed by myotube formation and muscle-specific creatine-kinase isozyme accumulation. In our study carnitine uptake was a saturable specific process with two distinct components: a high affinity uptake at carnitine concentration between 0.5 and 10 microM and a low affinity uptake at carnitine concentration between 25 and 200 microM. High affinity uptake (Km 4.17-5.50 microM, Vmax 11.78-19.6 pmol/h per mg protein) did not change during muscle maturation in culture. Low affinity uptake showed significant changes in Km and Vmax in the various stages of muscle differentiation. Our studies suggest the existence of a muscle-specific system, operating at physiological carnitine concentration, which gradually develops during muscle maturation in culture. We hypothesize that a defect of the low affinity muscle-specific uptake might be the cause of the primary muscle carnitine deficiency syndrome.

Adult↗
PubMed1991

Is the carboxyl-terminus of dystrophin required for membrane association? A novel, severe case of Duchenne muscular dystrophy.

Duchenne muscular dystrophy is a lethal X-linked recessive disorder caused by the deficiency of a component of the muscle fiber membrane cytoskeleton called dystrophin. Becker muscular dystrophy, a clinically milder disorder, results from dystrophin abnormalities rather than deficiency. We identified the first patient who is clearly an exception to these established clinical and biochemical correlates. The patient described clinically had particularly severe Duchenne dystrophy. Biochemically, his muscle contained substantial amounts of abnormal dystrophin (Becker-like). Characterization of the dystrophin protein and gene revealed a unique intragenic gene deletion resulting in a dystrophin protein missing the carboxyl-terminal domain. This patient's dystrophin seemed to have a deleterious "dominant" effect on his muscle: The presence of this abnormal protein was more damaging to the myofibers than the absence of dystrophin would have been. This patient challenges the current hypothesis that dystrophin associates with the plasma membrane solely via its carboxyl-terminus, yet supports the hypothesis that an intact carboxyl-terminus is crucial for correct dystrophin function.

Chromosome Deletion↗
PubMed1991

Congenital muscular dystrophy: brain alterations in an unselected series of Western patients.

The typical form of congenital muscular dystrophy (CMD) described in Western countries is generally considered different from its Japanese variant because of the absence of CNS involvement. Evaluations from both a clinical and a neuroradiological point of view were made of the CNS functions of 12 unselected Western children affected by CMD. In five patients, clinical observation and intelligence tests showed a mild to severe mental retardation. One of these patients suffered also from a severe form of epilepsy. In the same five patients, various degrees of white matter hypodensity, ventricular enlargement and cerebral atrophy were also detected. Similar neuroradiological abnormalities were also found in five of the seven children who did not have clinical symptoms or signs of CNS involvement. In one of these cases, necropsy neuropathological examination showed the gyral anomalies characteristic of the Japanese type of CMD. This study clearly indicates the high frequency of subclinical CNS alterations in typical Western CMD, suggesting that it should be considered a type of myoencephalopathy like its Japanese counterpart.

Adolescent↗
PubMed1991

Muscle carnitine deficiency in patients with severe peripheral vascular disease.

BACKGROUND: This study was designed to evaluate the effect of severe peripheral arterial insufficiency on carnitine concentrations and carnitine acetyltransferase and palmitoyltransferase activities in the ischemic skeletal muscles of patients with severe peripheral vascular disease. METHODS AND RESULTS: Nine biopsy specimens of ischemic muscles were obtained from five patients undergoing reconstructive vascular surgery. Biopsies from 35 normal subjects served as controls. Ischemic muscles showed a significant reduction in total carnitine from the control value of 20.9 +/- 5.2 to 11.6 +/- 6.2 nmol/mg noncollagen protein (p less than 0.01). A significantly lower free carnitine and acylcarnitine content contributed to this reduction. Similarly, carnitine acetyltransferase activity was reduced in the ischemic muscles from the control value of 102.1 +/- 41.2 to 52.9 +/- 22.1 nmol/min/mg noncollagen protein (p less than 0.01). On the contrary, carnitine palmitoyltransferase activity did not show any change (0.29 +/- 0.05 nmol/min/mg noncollagen protein in the ischemic muscles and 0.28 +/- 0.07 nmol/min/mg noncollagen protein in controls). Carnitine, acylcarnitines, and enzyme activities were also measured in the ischemic muscles in four additional patients 2 days after intravenous administration of L-propionylcarnitine (1.5 g as a single bolus followed by an infusion of 1 mg/kg/min for 30 minutes). Treatment restored normal levels of carnitine and its esters in the ischemic muscles but did not affect enzyme activities. CONCLUSIONS: Demonstration of carnitine deficiency in severe peripheral vascular disease substantiates previous findings showing the efficacy of carnitine supplementation to ischemic muscles. Furthermore, the feasibility of restoring carnitine homeostasis with L-propionylcarnitine provides the basis for clinical trials aimed at assessing the efficacy of this carnitine ester in the treatment of peripheral vascular disease.

Aged↗
PubMed1991

Echocardiographic and pulsed Doppler features in glycogen storage disease type II of the heart (Pompe's disease).

Two cases of cardiac glycogen storage disease type II are described: the first one, male aged 3 months, presented with generalized muscular hypotonia and decreased deep tendon reflexes; a 2/6 systolic murmur was audible at the left sternal border; chest X-ray and ECG were consistent with left ventricular hypertrophy; an echocardiogram disclosed an impressive and diffuse cardiac hypertrophy; the pump function appeared preserved and the estimated ejection fraction was about 70%. Pulsed wave Doppler demonstrated a normal envelope of mitral flow with E/A ratio = 1.27 in averaged 20 beats. The patient died suddenly at 6 months of age. The second patient was a female 4 months old with generalized muscular hypotonia. ECG and chest X-ray were consistent with left ventricular hypertrophy; 2D echocardiogram showed diffuse hypertrophy with estimated ejection fraction of 68% and an almost normal aspect of the mitral flow curve, with E/A ratio of 1.18. This child died at 13 months of age of cardiopulmonary insufficiency. In both cases the diagnosis was made by muscular biopsy and biochemical tests (alpha 1-4 glucosidase deficiency). We stress the fact that, despite the severe and diffuse hypertrophy, the pump function and the ventricular filling did not seem compromised.

Cardiomegaly↗
PubMed1991

Multicenter trial with ubidecarenone: treatment of 44 patients with mitochondrial myopathies.

Fourty four patients with mitochondrial myopathies were treated with Ubidecarenone (CoQ10) for six months in an open multicentric trial. No side effects due to the drug administration were observed. Sixteen patients showing at least 25% decrease of post exercise lactate levels were selected as responders. Responsiveness was apparently not related to CoQ10 level in serum and platelets or to the presence or absence of mtDNA deletions. The responders were further treated for 3 months with CoQ10 or placebo in the second blind part of the trial; no significant differences between the 2 groups were observed. It is not clear why CoQ10 had therapeutic effects in some patients and not in others with the same clinical presentation and biochemical defect, and we failed to identify candidate responders before treatment. At the dosage of CoQ10 used in the study (2 mg/kg/day) the therapy requires long administration time before a response is demonstrable.

Adolescent↗
PubMed1991

Exploring the molecular basis for variability among patients with Becker muscular dystrophy: dystrophin gene and protein studies.

Becker muscular dystrophy (BMD) often results from in-frame mutations of the dystrophin gene that allow production of an altered but partially functional protein. To address potential structure-function relationships for the various domains of dystrophin, we examined both the dystrophin gene and protein in 68 patients with abnormal dystrophin. Eighty-six percent of BMD patients with dystrophin of altered size have deletions or duplications, and the observed sizes of dystrophin fit well with predictions based on DNA data. Deletions within the amino-terminal domain I tended to result in low levels of dystrophin and a more severe phenotype. The phenotypes of patients with deletions or duplications in the central rod domain were more variable. This region can be divided into three portions based on differences in clinical presentations of patients. Deletions around exons 4553 were most common and generally caused typical BMD; however, phenotypic variability among patients with similar mutations suggests that epigenetic and/or environmental factors play an important role in determining the clinical progression. In contrast, deletions or duplications in the proximal portion of this domain tended to cause severe cramps and myalgia. Finally, loss of the middle of this region probably causes a very mild phenotype, as only one such patient was found and his only symptom was elevated serum creatine phosphokinase levels.

Adolescent↗
PubMed1990

Ubidecarenone in the treatment of mitochondrial myopathies: a multi-center double-blind trial.

Forty-four patients with mitochondrial myopathies were treated with Ubidecarenone (CoQ10) for 6 months in an open multi-center trial. No side effects of the drug were observed. Sixteen patients showing at least 25% decrease of post-exercise lactate levels were selected as responders. Responsiveness was apparently not related to CoQ10 level in serum and platelets or to the presence or absence of mtDNA deletions. The responders were treated for a further 3 months with CoQ10 or placebo in the second blind part of the trial; no significant differences were observed between the 2 groups. It is not clear why CoQ10 had therapeutic effects in some patients and not in others with the same clinical presentation and biochemical defect, and we failed to identify candidate responders before treatment. At the dose of CoQ10 used in this study (2 mg/kg/day) the therapy requires a long administration time before a response is seen.

Blood Platelets↗
PubMed1990

Defects of fatty-acid oxidation in muscle.

Long-chain fatty acids (LCFA) are oxidized by muscle mitochondria after transport in the cytosol by fatty-acid-binding protein(s) and their activation by a thiokinase. Carnitine, two forms of carnitine palmitoyltransferase(s) and carnitine acylcarnitine translocase are involved in LCFA gating. A primary genetic carnitine deficiency occurs in children with dilated cardiomyopathy, hypoglycaemia and low carnitine content in plasma, liver and muscle, owing to a defect in a common high-affinity transport system. This high-affinity transport in muscle differs from a low-affinity transport that has modifications during muscle maturation. The genetic enzyme defects of beta-oxidation (long-chain acyl-CoA dehydrogenase, medium- and short-chain acyl-CoA-dehydrogenase) present with Reye-like attacks that may lead to non-ketotic hypoglycaemia, coma and sudden infant death syndrome. There is elevated urinary excretion of dicarboxylic acids, acylcarnitines and acylglycines. Secondary carnitine deficiency may occur. ETF and ETF dehydrogenase deficiencies may present in a neonatal form with congenital anomalies, or in a later-onset form with ethylmalonic adipic aciduria. A still-unidentified defect leads to LCFA accumulation in fibroblasts, bone marrow, liver and muscle cells in a multisystem triglyceride disorder.

Acyl-CoA Dehydrogenase, Long-Chain↗
PubMed1990

Serum lipids, lipoprotein analysis and apoprotein A-I, A-II and B levels in Friedreich's ataxia.

Serum lipid, lipoprotein and apoprotein parameters were evaluated in 15 patients (7 males and 8 females) with Friedreich's ataxia. Serum lipid levels in patients showed no significant differences compared to controls. Small reduction in serum phospholipid and in total HDL and HDL3 cholesterol levels were observed, and the female patients presented a slight reduced total cholesterol level; among the serum apoproteins, apo B was reduced only in the males. The most interesting findings concerned the lipoproteins, since both lipid and protein masses of the VLDL, LDL and HDL2 fractions were reduced. In reference to lipoprotein composition, however, HDL2 was the most modified fraction, showing an important protein reduction. From this point of view, this lipoprotein seems the most responsible for the changes observed in our patients. The meaning of this modified lipoprotein pattern in the pathophysiology of Friedreich's ataxia is not clear.

Adolescent↗
PubMed1990

Enormous dystrophin in a patient with Becker muscular dystrophy.

We describe a patient with a duplication of more than 400,000 bp of the dystrophin gene. The duplication is completely contained within the gene, and the duplicated exons are predicted to be "in frame" with the rest of the gene. Dystrophin protein is detected in the patient's muscle as a single species of approximately 600 kDa (normal, approximately 400 kDa), indicating that the resulting mutated gene codes for a translatable mRNA of over 100 exons (normal, approximately 70 exons). The patient's mother carries the duplicated gene as determined by both DNA and protein analysis. The described duplication of the dystrophin gene is by far the largest characterized to date. This observation is of significant biologic interest in that, despite the gross alteration of the gene and the encoded protein, the patient has a relatively mild clinical progression compatible with a diagnosis of Becker muscular dystrophy.

Adolescent↗
PubMed1990

Evolution of cardiac involvement in progressive ophthalmoplegia with deleted mitochondrial DNA.

A 43-year-old woman with progressive external ophthalmoplegia developed a bifascicular block and dilatation of the right ventricle during 4 years of follow-up. Histochemical and electron microscopy studies detected mitochondrial abnormalities in ocular, skeletal muscle and cardiac biopsies. This case registers disease progression from the external ocular to the skeletal and cardiac muscles. Mitochondrial DNA was deleted in relation to the morphological abnormality.

Adult↗