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Biomedical subjects

L Chiadò-Piat

Publications and source records attributed to L Chiadò-Piat.

At least 19 recordsLinked to original sources
PubMed2002

Alpha-sarcoglycan deficiency featuring exercise intolerance and myoglobinuria.

An 8-year-old boy was referred for recent onset of easy fatigue. He showed hyperCKemia and mild scapular winging. Muscle biopsy on the quadriceps muscle demonstrated slight fibre size variability. Dystrophin was normally distributed, carnitine palmitoyl transferase and glycolytic enzymes had normal activities. In the following years the patient developed exercise intolerance and myoglobinuria. Immunohistochemistry showed marked reduction of alpha-sarcoglycan, confirmed by Western blotting. Molecular analysis revealed compound heterozygosity with Arg284Cys and Glu137Lys substitutions, corresponding to nucleotide changes C850 T and G409 A in the gene. At present the patient, 20 years old, shows mild proximal weakness with prominent involvement of the paraspinal muscles, dorsal kyphosis and lumbar hyperlordosis. Exercise intolerance and myoglobinuria, already described in Becker muscular dystrophy, should be also considered among the possible presentations of sarcoglycan deficiencies.

Biopsy↗
PubMed2001

Distribution of activated caspase-3 in relation with apoptosis in human malignant gliomas.

Activated caspase-3has been immunohistochemically studied in 30glioblastomas. Its distribution has been compared with that of apoptotic nuclei demonstrated by terminal dUTP nick-end labeling (TUNEL) and morphology. The best procedure for the demonstration of caspase-3 requires formalin fixation, followed by Carnoy fixation, with microwave irradiation. The number of positive cells is lower than that of apoptotic nuclei shown by TUNEL technique, especially in perinecrotic pseudo-palisadings, and there are also qualitative variations. Positive staining occurs in nuclei, cytoplasms or in both cell compartments. The interpretation of Caspase-3 positive staining is based on its crucial position in the final pathway to apoptosis and on the mechanisms by which it cleaves cytoplasmic and nuclear proteins among which inhibitory/caspase-activated DNase system is included.

Apoptosis↗
PubMed2001

CDKN2A/p16 in ependymomas.

Sixteen cases of ependymoma were studied for CDKN2A/p16 inactivation by immunohistochemistry using a p16 monoclonal antibody, by homozygous deletion (HD) assay and 5'CpG promoter methylation assay (methylation-specific PCR). Three out of 16 cases were p16 immuno-negative: two corresponded to grade II ependymomas and one to grade III. The latter ependymoma, characterized by a high Ki-67/MIB-1 LI, was the only one of the whole series to show CDKN2A HD. No promoter methylation was found in the two immuno-negative cases without CDKN2A HD. Alternative mechanisms, such as point mutations or alterations in p16 post-translational regulation, may be responsible for p16 inactivation. Since in our series just one out of eight anaplastic cases showed negative immunostaining and CDKN2A HD, p16/CDKN2A inactivation may not play an important role in the malignant transformation of ependymomas. Amplification of CCNDI and CDK4, p27/Kipl degradation and TP53 mutations were previously studied by other authors and were demonstrated not to correlate with anaplasia. Up to date, molecular genetic studies have not been useful in recognizing the anaplastic variant in ependymomas.

Adolescent↗
PubMed2001

Cyclin D1 expression in normal oligodendroglia and microglia cells: its use in the differential diagnosis of oligodendrogliomas.

Cyclin D1 regulates G1-S progression. In many carcinomas it is overexpressed and it might even correlate with prognosis. However, the amplification of CCND1 contributes to the loss of cell cycle control only in a small fraction of malignant gliomas. Cyclin D1 can be immunohistochemically demonstrated by DCS-6 mAb. In astrocytic gliomas the fraction of tumor cells with positive nuclei is almost null in well differentiated tumors and increases with the increase of proliferation rate that occurs in anaplasia. The correct evaluation of this fraction is hindered by the positive staining of normal oligodendrocytes and microglia cells. The cyclin D1-positive staining of normal oligodendrocytes and microglia cells has been studied in a series of 20 oligodendrogliomas, five diffuse astrocytomas and five oligoastrocytomas and in 10 samples of normal cortex and white matter, using cyclin D1 DCS-6 mAb, Feulgen reaction and CR3.43 mAb for microglia cells. As well as microglial nuclei, the nuclei of normal oligodendrocytes of the cortex and white matter, including peri-neuronal satellites and pericapillary cells, were immunostained by DCS-6 mAb. In infiltrative areas of oligodendrogliomas, normal, cyclin D1-positive oligodendrocytes and cyclin D1-negative tumor cells coexisted. In anaplastic oligodendrogliomas, cycling tumor oligodendrocytes may regain the capacity to express cyclin D1, which is thus positive in some tumor cells. The occurrence of positive oligodendrocytes in the peripheral parts of tumors can be useful in distinguishing astrocytomas from oligoastrocytomas.

Antibodies, Monoclonal↗
PubMed2000

CDKN2A/p16 inactivation in the prognosis of oligodendrogliomas.

The cell-cycle regulator p16 inhibits the complex cdk4-cyclin D1 and controls G1-S transition. In human tumors, p16 inactivation is often accomplished by homozygous deletion (HD) of its encoding gene, CDKN2A. Methylation of the 5' CpG island promoter has been proposed as an alternative mechanism of inactivation. Expression of p16, CDKN2A HD and 5' CDKN2A CpG island methylation was studied in 25 oligodendrogliomas by immunohistochemistry and PCR amplification. Ten oligodendrogliomas were p16-immunonegative, and CDKN2A HD was determined in 8 of these cases. In the 2 immunonegative cases without HD, no CpG island methylation was found. The absence of CpG island methylation in the p16-immunonegative cases without HD suggests either non-genetic regulation of p16 or different genetic changes. CDKN2A HD did not correlate with histological grading (p = n.s.); however, it showed a correlation with survival (p = 0.03), supporting an important role of CDKN2A in the prognosis of oligodendrogliomas.

Brain Neoplasms↗
PubMed1999

Variable histological expression of dystrophinopathy in two females.

We report two carriers of Xp21 muscular dystrophy with unusual clinical manifestations and striking variability of dystrophin deficiency within the same muscle biopsy. The first patient was a 60-year-old nun with recent onset of cramps and proximal weakness, mimicking an acquired myopathy. Muscle biopsy disclosed slight alterations in one sample and severe dystrophic changes in another; dystrophin was absent in 7% fibers in the former specimen and in 60% in the second. X inactivation was skewed with 90% cells inactivating the same X chromosome. The second patient was a 17-year-old girl with hyperCKemia, learning disability and a family history of X-linked muscular dystrophy. Muscle biopsy displayed slight fiber size variability and some internal nuclei; dystrophin was absent only in one muscle fiber. A second sample with the same morphological features demonstrated dystrophin deficiency with mosaic distribution. The pattern of X inactivation was normal. These cases emphasize the variability of histopathological changes and dystrophin deficiency in Xp21 muscular dystrophy carriers and the risk of sampling errors in muscle biopsy.

Adolescent↗
PubMed1999

Unusual clinical expression of dystrophinopathy in a female, mimicking a congenital myopathy.

A 25-year-old woman with negative family history and delayed motor development presented hypotrophy of the right lower limb and calf hypertrophy since age 7 and she complained of muscle weakness since 23. Neurological examination showed a thin elongated face, high-arched palate, high-pitched voice, proximal wasting and weakness, impairment of distal muscles in the lower limbs. CK was 3, 034 U/l, EMG showed a myopathic pattern. Muscle biopsy displayed dystrophic features with diffuse dystrophin deficiency; immunoblotting demonstrated quantitative reduction of the protein and normal molecular weight. Lyonization study showed skewed X-inactivation with the maternal X active. Seven years' follow-up did not show progression of the disease.

Adult↗
PubMed1997

Muscle apoptosis in humans occurs in normal and denervated muscle, but not in myotonic dystrophy, dystrophinopathies or inflammatory disease.

Recent data suggest that death of muscle cells during development and in selected pathological conditions occurs via apoptosis. We investigated the occurrence of apoptosis in normal and pathological human skeletal muscle, using in situ end-labeling (ISEL) to detect DNA fragmentation, and immunohistochemistry for the expression of tissue transglutaminase and interleukin-1beta-converting enzyme (ICE)-like proteases. In normal subjects, apoptotic myonuclei were occasionally observed as evidence of normal tissue turnover. Myonuclear apoptosis due to a deficit of trophic support from nerve cells also occurred in spinal muscular atrophies. No apoptosis of muscle cells was found in dystrophinopathies, myotonic dystrophy and inflammatory myopathies, suggesting that death of myofibers in those conditions is not due to activation of a gene-directed program of death. In dystrophinopathies and inflammatory myopathies, apoptosis was found in interstitial mononuclear cells, as a likely mechanism of clearance of the inflammatory infiltrates.

Adolescent↗
PubMed1997

Systematic use of dystrophin testing in muscle biopsies: results in 201 cases.

We studied dystrophin with both immunohistochemistry and immunoblotting in 201 muscle biopsies stored in liquid nitrogen during the period 1985-92. The systematic use of dystrophin testing combined with DNA analysis and with 3-10 years follow-up of the patients yielded a significant modification of the diagnoses made previously and identified dystrophinopathies with unusual expression and course. Seventeen out of 152 (11.18%) diagnoses in males and 8 out of 49 (16.32%) in females were modified by dystrophin testing. Most diagnostic errors (9 out of 27 diagnoses) were in the group Becker muscular dystrophy-limb girdle muscular dystrophy, confirming the clinical overlap of the two diseases. Unusual expressions of dystrophinopathy included muscular dystrophy with early elbow contractures (two patients), recurrent myoglobinuria (one patient), dilating cardiomyopathy (two patients), myoglobinuria and associated dilating cardiomyopathy (one patient), very late-onset benign myopathy (two patients and one manifesting carrier) and congenital myopathy (one manifesting carrier). In the group 'idiopathic hyper-CKaemia', we did not find any dystrophinopathy in 34 males, whereas five out of nine females were found to be carriers. Immunohistochemical analysis of dystrophin using the monoclonal antibody against the C-terminus detected 99% of protein defects and was found to be the most cost-effective way of revealing dystrophinopathies. The combined use of immunohistochemical analysis with the antibody against the C-terminus and immunoblotting with the antibody against the core of the protein appears to be a highly reliable diagnostic approach (100% detection rate).

Biopsy↗
PubMed1996

Bcl-2 distribution in neuroepithelial tumors: an immunohistochemical study.

Bcl-2 proto-oncogene prevents apoptosis in many conditions. First detected in lymphomas, it has been also described in non-lymphoid tissues. The immunohistochemical distribution of bcl-2 protein in 100 neuroepithelial tumors is presented. Bcl-2 was positive in some neurons of normal nervous tissue, in reactive astrocytes and variably in all neuroepithelial tumor. The reaction product was either diffuse or granular, due to bcl-21 protein localization on cytoplasmic, nuclear and mitochondrial membranes. The positivity was high in medulloblastomas and in astrocytic tumors. In the latter, the strongest staining was found in cells retaining the astrocytic aspect. Oligodendroglial cells were minimally stained. No correlation of bcl-2 staining with survival was found in each tumor type. The interpretation of the results is based on the one side on the constitutive role played by bcl-2 in the nervous tissue and its neoplastic derivatives. On the other side, in tumors bcl-2 acts by preventing tumor cells from undergoing apoptosis. BCl-2 expression in brain tumors, therefore, receives a dual interpretation. For this reason and for the lacking of correlation with survival, bcl-2 expression cannot be regarded as a prognostic factor.

Astrocytoma↗
PubMed1996

Quantitative and qualitative alterations of dystrophin are expressed in muscle cell cultures of Xp21 muscular dystrophy patients (Duchenne and Becker type).

The authors studied skeletal muscle cell cultures from four control subjects, two patients with Duchenne muscular dystrophy, two Duchenne carriers and three patients with Becker muscular dystrophy with different phenotypes. Western blotting was performed on well-differentiated myotubes and compared with the results obtained in muscle tissue. In all cultures the band of dystrophin closely corresponded to the one observed in muscle tissue: both quantitative and qualitative defects were observed. This confirms the early expression of the Xp21 gene defect in uninnervated muscle cultures and supports the usefulness of muscle cultures both in diagnostic procedure and as a model to study the disease.

Adult↗
PubMed1994

Unusual expression and very mild course of Xp21 muscular dystrophy (Becker type) in a 60-year-old man with 26 percent deletion of the dystrophin gene.

A 54-year-old farmer with a negative family history had had mild proximal weakness for the previous 4 years. Clinical examination showed marked scoliosis, barrel-shaped chest, diffuse hypotrophy, and mild proximal weakness. Creatine kinase was 938 U/l; electrocardiography and echocardiography were normal. EMG disclosed myopathic changes. Muscle biopsy showed slight, nonspecific alterations. Dystrophin was present and normally distributed with antibodies against the C-terminal and N-terminal, whereas it was not recognized by the antibody against the rod domain. Western blotting detected an abnormal molecular weight protein of 320 kd (normal, 427 kd). Southern blot analysis revealed a deletion from exon 21 to exon 44, corresponding to 26% of the coding region of dystrophin. Six years' follow-up did not disclose progression of the muscle disease.

Dystrophin↗
PubMed1994

Metachromatic dye-Ca++ATPase method in pathological muscle: a study of 382 muscle biopsies.

The metachromatic dye-Ca++ATPase method, that in normal muscle distinguishes fiber types on the basis of their metachromatic or orthochromatic staining, was applied to 382 pathological muscle biopsies. Results were compared in serial sections with those obtained with the conventional ammonium sulphide method. In pathological muscle the metachromatic dye-Ca++ATPase method confirms the advantages already showed in normal muscle: fast and easy performance, neat fiber typing, simultaneous staining of nuclei. Moreover in pathological muscle the metachromatic dye-Ca++ATPase method showed some muscle changes which are missed by the conventional ammonium sulphide one, namely central nuclei, macrophagic invasion and some structural abnormalities. This allows immediate correlation between those alterations and fiber typing.

Biopsy↗
PubMed1993

Exercise intolerance and recurrent myoglobinuria as the only expression of Xp21 Becker type muscular dystrophy.

A 9-year-old boy complained of exertional myalgias and described two episodes of myoglobinuria. His family history was negative for neuromuscular diseases. The findings of a neurological examination were normal. Serum creatine kinase was increased, ECG was normal, EMG showed slight "myopathic" signs. Muscle biopsy disclosed a small group of basophilic fibres as the only abnormality. Muscle glycolytic enzymes and carnitine palmitoyl transferase were normal. Immunoblotting using antidystrophin antibody demonstrated a protein with low molecular weight. Genomic DNA analysis showed a deletion of the HindIII fragments spanning from exon 45 to exon 48. Eight years after the first observation the patient has diffuse muscle hypertrophy without muscle weakness.

Biopsy↗
PubMed1993

Clinical spectrum of McArdle disease: three cases with unusual expression.

Three cases of myophosphorylase deficiency with unusual clinical expression are presented. The 1st had clinical characteristics suggesting a mild congenital myopathy, and the patient never experienced cramps or myalgias. The 2nd had a slowly progressive myopathy without cramps or myoglobinuria which was detected by chance. The 3rd presented with myoglobinuria and acute renal failure, unrelated to a triggering effort, and with permanent weakness and wasting. In all cases, muscle biopsy demonstrated a vacuolar myopathy with free glycogen increase and absence of myophosphorylase activity, confirmed by biochemical assays. The cases confirm the wide clinical spectrum of McArdle disease.

Biopsy↗
PubMed1993

Congenital muscular dystrophy associated with familial junctional epidermolysis bullosa letalis.

A 20-year-old patient was born with epidermolysis bullosa and a severe, slowly progressive muscle disease. Skin biopsy demonstrated junctional epidermolysis bullosa. Muscle biopsy demonstrated degenerative changes with increase in connective tissue, fibre size variability, rods and cytoplasmic bodies, central nuclei. In muscle biopsy dystrophin, chondroitin unsulphate, chondroitin 4-sulphate, chondroitin 6-sulphate, heparan sulphate, collagen III, collagen IV and VI, laminin, and fibronectin were normally distributed. This is the first report of the association of a form of congenital muscular dystrophy with junctional epidermolysis bullosa and, together with the previous reports of muscle involvement in epidermolysis bullosa simplex and dystrophica, it suggests the existence of a syndrome characterized by the contemporaneous presence of skin and muscle involvement.

Adult↗
PubMed1992

Dilating cardiomyopathy as the expression of Xp21 Becker type muscular dystrophy.

A 35-year-old man with severe progressive dilating cardiomyopathy and no clinical signs of muscle disease underwent muscular investigations because of markedly increased serum creatine kinase. Muscle biopsy demonstrated Becker type muscular dystrophy with dystrophin of low molecular weight. Genetic analysis showed a deletion spanning from exon 45 to exon 46 in the Xp21 region. Xp21 Becker type muscular dystrophy must be considered in the differential diagnosis of dilating cardiomyopathy.

Adult↗