Biomedical subjects

C Angelini

Publications and source records attributed to C Angelini.

At least 145 records · Page 8Linked to original sources

PubMed1994

Prevalent cardiac involvement in dystrophin Becker type mutation.

Myocardial involvement is frequently present in Xp21-linked muscular dystrophy, due to a lack of dystrophin in cardiac fibres. We describe a 41-yr-old man affected by dilated cardiomyopathy with sporadic episodes of myoglobinuria induced by effort and increased levels of serum creatine kinase. Very mild signs of skeletal myopathy were clinically evident. His mother was affected by an indefinite cardiopathy and suddenly died when she was 36 yr old. Muscle biopsy of the patient showed a dystrophic process. Dystrophin analysis together with a genetic DMD locus study led us to diagnose Becker type muscular dystrophy, with truncated dystrophin and a gene deletion extending from exon 45 to 48. Prevalent cardiac involvement in a Becker type mutation of the dystrophin gene further confirms clinical variability of dystrophinopathies.

Adult↗

PubMed1994

Non-radioactive detection of 17p11.2 duplication in CMT1A: a study of 78 patients.

Charcot-Marie-Tooth disease type 1 (CMT1) is a peripheral neuropathy characterised by progressive distal muscular atrophy and sensory loss with markedly decreased nerve conduction velocity, mostly inherited as an autosomal dominant trait. The most common form, type 1A, is associated with a 1.5Mb DNA duplication in region p11.2-p12 of chromosome 17 in many patients. In this study a non-radioactive test for detection of the CMT1A duplication based on an RM11-GT microsatellite polymorphism is presented. Although different methods have been devised for this purpose, the present method has the advantage of being rapid, informative, economical, easily interpretable, and, therefore, it represents a very useful tool for diagnosis of CMT1A, especially before clear manifestation of clinical symptoms. Seventy-eight patients diagnosed clinically as having CMT and evaluated by electrophysiological methods were tested with an RM11-GT microsatellite and with probe pVAW409R3. The CMT1A duplication was found in 76% of the 56 unrelated patients. RM11-GT was the most informative marker with a heterozygosity of 89%.

Base Sequence↗

PubMed1994

Single muscle fibre analyses in 2 brothers with succinate dehydrogenase deficiency.

We report 2 brothers with hypertrophic cardiomyopathy, lipid storage and skeletal mitochondrial myopathy. Biochemical analyses detected complex II (succinate dehydrogenase) deficiency of the respiratory chain. Single fiber analyses using a microphotometer were performed and revealed reduced succinate dehydrogenase activity in all muscle fibers. This report shows the validity of kinetic microphotometric analysis in revealing complex II defects.

Adult↗

PubMed1994

[Description of two cases of retrobrachiocephalic thymus gland].

We report two rare cases of thymus gland found behind the left brachiocephalic vein, in young women undergoing thymectomy for myasthenia gravis. Our observations are included among the thymic anatomical variants. After a review of the literature on the subject, we discuss both the diagnostic role of new radiological techniques (CT, NRM) and the choice of surgical approach to these variants.

Adult↗

PubMed1993

Multifactorial study of inflammatory myopathies. Report of 29 cases.

We made a comparative clinical, immunopathological and therapeutic evaluation in 17 patients with polymyositis (PM) and 12 patients with dermatomyositis (DM), followed up at our Neuromuscular Center. DM can be distinguished by its clinical appearance and pathological changes. Current evidence suggests that it results from vasculopathy. For studying these inflammatory myopathies we used multifactorial diagnostic criteria, evaluating the therapeutic response by means of a composite clinical and functional score in a longitudinal study. In muscle biopsy specimens we characterized with monoclonal antibodies T lymphocyte subpopulations (CD4, CD8), macrophages, IgG, IgM, C1q, C3, C4 complement fractions, MHC-I, MHC-II. In PM the cell-mediated immunity was more pronounced and in some cases both MHC-I and MHC-II molecules were found on the surface or within muscle fibers. Our patients were treated with steroids; in resistant cases azathioprine, cyclophosphamide, plasmapheresis, high-dose intravenous immunoglobulins (ivIgG) and total body irradiation were added to the therapeutic schedule.

Adolescent↗

PubMed1993

Hypertension after renal transplantation.

In 212 cyclosporine-treated renal transplant recipients with stable graft function at 1 year and with potential follow-up of 5 years the prevalence of arterial hypertension was 81.6% at 1 year and 81.2% at 5 years. The logistic regression analysis showed that the presence of hypertension before transplantation (P = 0.0001; odds ratio 3.5), a plasma creatinine level higher than 2 mg/dL at 1 year (P = 0.0001; odds ratio 3.8), and a maintenance therapy with corticosteroids (P = 0.008; odds ratio 3.3) were positively associated with hypertension at 1 year after transplantation. The mean number of graft failures between 1 and 5 years was significantly higher and the mean reciprocal of plasma creatinine was significantly worse at 1 and 5 years in patients with noncontrolled hypertension than in normotensive patients or in patients with hypertension well controlled by drugs. We also investigated the potential protective role of nifedipine. The episodes of acute tubular necrosis (four versus three), of acute rejections (28 versus 29), the mean arterial pressure at 1 year (105 +/- 9 versus 104 +/- 9 mm Hg) and 5 years (105 +/- 10 versus 108 +/- 12 mm Hg), and the mean plasma creatinine level at 1 year (1.4 +/- 0.4 versus 1.6 +/- 0.4 mg/dL) and 5 years (1.8 +/- 1 versus 1.9 +/- 1 mg/dL) were similar in 52 patients who were given nifedipine for at least 4 years and 58 hypertensive patients who never took calcium channel blockers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Cardiac involvement in Becker muscular dystrophy.

OBJECTIVES: The purpose of this study was to assess the incidence of myocardial involvement and the relation of cardiac disease to the molecular defect at the deoxyribonucleic acid (DNA) or protein level in Becker muscular dystrophy. BACKGROUND: Dystrophin gene mutations produce clinical manifestations of disease in the heart and skeletal muscle of patients with Becker muscular dystrophy. METHODS: Thirty-one patients underwent electrocardiographic and echocardiographic examination and 24-h Holter monitoring. The diagnosis was established by neurologic examination, dystrophin immunohistochemical assays or Western blot on muscle biopsy, or both, and DNA analysis. RESULTS: Electrocardiographic and echocardiographic findings were abnormal in 68% and 62% of the patients, respectively. Right ventricular involvement was detected in 52%. Left ventricular impairment was observed either as an isolated phenomenon (10%) or in association with right ventricular dysfunction (29%). Right ventricular disease was manifested in the teenagers, and an impairment of the left ventricle was observed in older patients. Right ventricular end-diastolic volumes were significantly increased compared with those in a control group. The left ventricular ejection fraction was significantly lower in older patients than in control subjects or younger patients. Life-threatening ventricular arrhythmias were detected in four patients. No correlations were found between skeletal muscle disease, cardiac involvement and dystrophin abnormalities. In our patients, exon 49 deletion was invariably associated with cardiac involvement. Exon 48 deletion was associated with cardiac disease in all but two patients. CONCLUSIONS: The cardiac manifestation of Becker muscular dystrophy is characterized by early right ventricular involvement associated or not with left ventricular impairment. Exon 49 deletion is associated with cardiac disease.

Adolescent↗

PubMed1993

Dystrophin-positive myotubes in innervated muscle cultures from Duchenne and Becker muscular dystrophy patients.

Nerve-muscle co-cultures from five Duchenne muscular dystrophy (DMD) patients and one Becker (BMD) patient, were studied by immunocytochemistry with antibodies against different portions of dystrophin. Four DMD patients had a deletion in the dystrophin gene. Some dystrophin-positive myotubes were detected in a few samples of all DMD cases. PCR amplification of exon 8 of the dystrophin gene ruled out a contamination from rat spinal cord during innervation. Our results in three DMD cases, may be explained by a clonal selection of dystrophin-positive fibers observed in muscle biopsies, while in the other two cases, a "frame-restoring" mutation might account for the presence of dystrophin-positive myotubes. The possible expression of "dystrophin-related protein" or dystrophin immature isoform was considered. In the BMD case an abnormal truncated dystrophin was found in innervated muscle cultures, as well as in muscle biopsy.

Adolescent↗

PubMed1993

Reappraisal of the incidence rate of Duchenne and Becker muscular dystrophies on the basis of molecular diagnosis.

The incidence rates of Duchenne and Becker muscular dystrophies (X-linked recessive) in a given sample of the Italian population were recalculated using the results of DNA and dystrophin analysis. While the incidence rate of Duchenne muscular dystrophy remained unchanged, the new figure for the incidence of Becker muscular dystrophy (7.2 per 100,000 male live births) was much higher than previously reported, since molecular diagnosis revealed additional cryptic cases, but this incidence is still an underestimate.

Blotting, Western↗

PubMed1993

Expression of muscle-type phosphorylase in innervated and aneural cultured muscle of patients with myophosphorylase deficiency.

Patients with McArdle's myopathy lack muscle glycogen phosphorylase (M-GP) activity. Regenerating and cultured muscle of patients with McArdle's myopathy presents a glycogen phosphorylase (GP) activity, but it is not firmly established whether M-GP or non-M-GP isoforms are expressed. We have cultured myoblasts from biopsy specimen of five patients with McArdle's myopathy. Skeletal muscle was cultured aneurally or was innervated by coculture with fetal rat spinal cord explants. In the patients' muscle biopsies and in their cultured innervated and aneural muscle we studied total GP activity, isoenzymatic pattern, reactivity with anti-M-GP antiserum, and presence of M-GP mRNA. There was no detectable enzymatic activity, no immunoreactivity with anti-M-GP antiserum, and no M-GP mRNA in the muscle biopsy of all patients. GP activity, M-GP isozyme, and anti-M-GP antiserum reactivity were present in patients' aneural cultures, increased after innervation, and were undistinguishable from control. M-GP mRNA was demonstrated in both aneural and innervated cultures of patients and control by primer extension and PCR amplification of total RNA. Our studies indicate that the M-GP gene is normally transcribed and translated in cultured muscle of patients with myophosphorylase deficiency.

Adult↗

PubMed1993

Hypertrophic cardiomyopathy with mitochondrial myopathy. A new phenotype of complex II defect.

Two brothers, 25 and 19 years old, were affected by asymmetrical hypertrophic cardiomyopathy. The older brother had waddling gait and weakness of the proximal girdle muscles, while the younger had a broad-based gait and weakness of selected limb girdle muscles. EMG exam was myopathic. Serum enzyme, CPK and aldolase were elevated. Histochemical reactions in muscle revealed "core-like" areas, subsarcolemmal rims of mitochondria and lipid accumulation. Succinate-dehydrogenase stain showed a lack of activity in both biopsies, with the exception of intrafusal fibers. Microphotometric quantitative measurements confirmed the defect in both biopsies. Biochemical measurements of several mitochondrial enzymes in muscle showed a reduced activity of succinate-dehydrogenase (33%) and succinate-cytochrome C reductase (36-47%) which are both components of complex II. On myocardial biopsy lipid and mitochondrial abnormalities were found. This mitochondriopathy represents a new phenotype of partial complex II defect.

Adult↗

PubMed1992

Differential DNA binding properties of three human homeodomain proteins.

The products of three human homeobox containing (HOX) genes, 2C, 3C and 4B, were produced in insect cells using the Baculovirus expression system and purified to near homogeneity. In this system we observed that the DNA binding forms of the three proteins are not glycosylated. HOX 3C and 4B are phosphorylated in insect cells, while HOX 2C is not. The three HOX proteins bind to a DNA sequence known to be a target site for Antennapedia protein with a very similar affinity (Kd = 1-2 x 10(-9) M). We then measured their binding properties to four human sequences present in the HOX 3D, 4C, 1C and 4B promoters. Two of these sequences have been reported to be binding sites for HOX proteins. HOX 2C, 3C and 4B behaved quite differently, showing low affinity for promoters of genes located upstream from their own gene in the HOX clusters and a higher affinity for regulatory sequences of their own gene and downstream HOX genes.

Animals↗

PubMed1992

MELAS mutation in mtDNA binding site for transcription termination factor causes defects in protein synthesis and in respiration but no change in levels of upstream and downstream mature transcripts.

The pathogenetic mechanism of the mitochondrial tRNA(LeuUUR) gene mutation responsible for the MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) syndrome was investigated in transformants obtained by transfer of mitochondria from three genetically unrelated MELAS patients into human mitochondrial DNA (mtDNA)-less (rho 0) cells. Marked defects in mitochondrial protein synthesis and respiratory activity were observed in transformants containing virtually pure mutant mtDNA, as compared to the parent of the rho 0 cells (the 143B cell line) or to transformants containing exclusively wild-type mtDNA, derived from one of the patients or a maternally related asymptomatic individual. A striking protective effect against the mutation was exerted in the transformants by levels of residual wild-type mtDNA above 6%. The MELAS mutation occurs within the mtDNA binding site for a protein factor (mTERF) that promotes termination of transcription at the 16S rRNA/tRNA(LeuUUR) gene boundary. A marked decrease in affinity of purified mTERF for the mutant target sequence was observed in in vitro assays. By contrast, RNA transfer hybridization experiments failed to show any significant change in the steady-state amounts of the two rRNA species, encoded upstream of the termination site, and of the mRNAs encoded downstream, in the transformants carrying the MELAS mutation.

Acidosis, Lactic↗

PubMed1992

MELAS: clinical features, biochemistry, and molecular genetics.

We studied 23 patients with clinically defined mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), 25 oligosymptomatic or asymptomatic maternal relatives, and 50 mitochondrial disease control subjects for the presence of a previously reported heteroplasmic point mutation at nt 3,243 in the transfer RNA(Leu(UUR)) gene of mitochondrial DNA. We found a high concordance between clinical diagnosis of MELAS and transfer RNA(Leu(UUR)) mutation, which was present in 21 of the 23 patients with MELAS, all 11 oligosymptomatic and 12 of 14 asymptomatic relatives, but in only five of 50 patients without MELAS. The proportion of mutant genomes in muscle ranged from 56 to 95% and was significantly higher in the patients with MELAS than in their oligosymptomatic or asymptomatic relatives. In subjects in whom both muscle and blood were studied, the percentage of mutations was significantly lower in blood and was not detected in three of 12 asymptomatic relatives. The activities of complexes I + III, II + III, and IV were decreased in muscle biopsies harboring the mutation, but there was no clear correlation between percentage of mutant mitochondrial DNAs and severity of the biochemical defect.

Acidosis, Lactic↗

PubMed1992

Further evidence of a duplication in 17p11.2 in families with recurrence of HMSN Ia (Charcot-Marie-Tooth neuropathy type Ia).

Five Italian families with recurrence of cases of Charcot-Marie-Tooth disease (type Ia) were analysed using three closely linked DNA probes that detect polymorphisms in the region 17p11.2. The probe pVAW409R3 detected the presence of a duplication in all the affected subjects, but not in the subjects with normal electromyographic (EMG) findings. This observation confirms previous data indicating the association of the duplication with the disease, suggesting that, at least in populations of European origin, the duplication might be the molecular feature diagnostic of the pathological trait.

Charcot-Marie-Tooth Disease↗

PubMed1992

Cognitive and psychiatric evaluation of 40 patients with myotonic dystrophy.

We evaluated 40 patients suffering from a severe form a myotonic dystrophy (MD) with neuropsychological (WAIS-R, MMSE) and psychiatric tests (SADS, SRT) for the assessment of cognitive and psychiatric symptoms. We tested 20 normal volunteers as control group. Patients with MD scored significantly, lower on WAIS Full Scale (p less than 0.001), Verbal Scale (p less than 0.001), and Performance Scale (p less than 0.001) and on the MMSE (p less than 0.05) than the controls. 35% of patients met the Research Diagnostic Criteria for a psychiatric diagnosis; 17.5% of them had a depressive disorder. The scores on SADS subscales and on the SRT scale of depression were also significantly higher in patients than in controls. Our data confirm that mental impairment and psychiatric disorders are important clinical manifestations of CNS dysfunction in the severe form on MD.

Adult↗

PubMed1992

Correlation between clinical and molecular features in two MELAS families.

We describe the clinical, morphological, biochemical presentation in two MELAS families, and correlate it with the distribution and proportion of mitochondrial DNA carrying the A to G transition at nt 3243. Family A was characterized by late onset MELAS in two members, CPEO in one, and mild CNS involvement in another. 20-61% of mtDNA of affected and unaffected individuals was mutated in muscle, 2-18% in blood. There was no obvious correlation between clinical picture and proportion of mutated mtDNA. In family B full MELAS syndrome appeared only in the third generation, but the mutation was also detected in muscle of asymptomatic individuals of the first and second generation. The proportion of mutated mtDNA in blood, and to a lesser extent in muscle, correlated with the severity of the clinical presentation. The MELAS mutation is consistently detected in all asymptomatic maternal relatives of MELAS patients. We conclude that different clinical presentations of mitochondrial encephalomyopathy may coexist in the same family, and correlation between clinical severity and molecular abnormality is not always recognizable. Presence of the MELAS mutation in muscle and blood is a necessary but not sufficient condition for the expression of the typical MELAS phenotype.

Adult↗

PubMed1992

Prevalence of dystrophin-positive fibers in 85 Duchenne muscular dystrophy patients.

The prevalence of dystrophin-positive fibers in Duchenne muscular dystrophy (DMD) muscle was estimated by direct counting on immunostained sections in a series of biopsy specimens from 85 patients, 42 of which were also screened for intragenic deletions by cDNA probes. Dystrophin-positive fibres are normotrophic and occur in muscle sections at a frequency between 0.01 and 6.81%. Frequencies over 1% were found only in patients older than 6 yr. The prevalence of dystrophin-positive fibers is about the same in patients with detectable and with undetectable deletions. The occurrence of positive fibers in small clusters supports the hypothesis of their clonal origin, suggesting that they may result from genetic reversion. No clinical differences were noticed in DMD patients of similar age with respect to the occurrence of dystrophin-positive fibres in their muscle biopsies.

Aging↗