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Y Campos

Publications and source records attributed to Y Campos.

At least 73 records · Page 4Linked to original sources
PubMed1998

[Molecular genetics of alterations in the mitochondrial respiratory chain].

Mitochondrial biogenesis is the result of the coordinated action of two genomes, nuclear (nDNA) and mitochondrial (mtDNA). Therefore respiratory chain defects are divided into alterations of mtDNA and of nDNA. The former may be due to sporadic isolated deletions and specific duplications and mutations, which are both transmitted maternally. The nDNA disorders are inherited following a mendelian pattern and may affect genes which codify enzymes, genes which take part in the process of importing proteins, or genes involved in intergenomic communication. In the latter case, the alterations are seen in the mtDNA as multiple deletions or depletion. The characteristics of mitochondrial genetics are maternal inheritance, polyplasmia, heteroplasmia, mitotic segregation and threshold effect and largely explain the characteristic phenotype behaviour specific to these changes.

DNA, Mitochondrial↗
PubMed1997

Bilateral striatal necrosis and MELAS associated with a new T3308C mutation in the mitochondrial ND1 gene.

We found a novel maternally inherited T3308C mutation in the mtDNA ND1 gene in a patient with bilateral striatal necrosis and stroke-like episodes. Muscle biopsy from the proband showed mitochondrial proliferation in blood vessels and normal respiratory chain activities. The mutation, which was not present in 100 normal controls or in 30 patients with mitochondrial disease, was heteroplasmic in both muscle and blood of the proband and in blood from her asymptomatic mother. This mutation results in a Met --> Thr change at the highly conserved amino acid position 1. The T3308C mutation may alter the hydrophobicity and antigenicity of the N-terminal peptide of ND1.

Adult↗
PubMed1997

Cerebrospinal fluid carnitine levels in patients with Parkinson's disease.

We assessed free carnitine (FC) and acyl-carnitine esters (AC) in both CSF and plasma from 29 patients with diagnostic criteria for PD, and from 29 healthy matched-controls. FC and AC levels in both CSF and plasma did not differ significantly between PD patients and controls, they were not influenced significantly by anti-parkinsonian drugs, and did not correlate with age at onset, duration and severity of PD. These results suggest that CSF carnitine levels are apparently unrelated with the risk for PD.

Acylation↗
PubMed1997

Syndrome of encephalopathy, petechiae, and ethylmalonic aciduria.

We report a boy 20 months of age with encephalopathy, petechiae, and ethylmalonic aciduria (EPEMA). Other clinical features were severe hypotonia, orthostatic acrocyanosis, and chronic diarrhea. Magnetic resonance imaging (MRI) of the brain demonstrated bilateral lesions in the lenticular and caudate nuclei, periaqueductal region, subcortical areas, white matter, and brainstem. Short and medium chain Acyl-CoA dehydrogenase and cytochrome c oxidase (COX) activities in fibroblasts were normal. Muscle histochemistry disclosed diffuse COX deficiency, and respiratory chain activities in muscle disclosed severe COX deficiency. Twelve other patients with similar clinical features have been reported. Muscle COX activity, studied only in four, demonstrated a clear-cut defect.

Brain↗
PubMed1997

Association of genetically proven deficiencies of myophosphorylase and AMP deaminase: a second case of 'double trouble'.

We studied a 25-year-old man with paresis of the limbs and neck, scapular atrophy, facial weakness, exercise intolerance and frequent episodes of myoglobinuria. Muscle histochemistry and biochemistry revealed a combined defect of myophosphorylase and AMP deaminase. Molecular genetic analysis showed that the patient was homozygous for the two most common mutations associated with myophosphorylase and AMP deaminase deficiencies. This is the second documented case of genetic 'double trouble', which should be looked for in patients with unusual severe phenotypes.

AMP Deaminase↗
PubMed1997

Gene dosage effect in one family with myoclonic epilepsy and ragged-red fibers (MERRF).

OBJECTIVES: We analyzed the percentage of mitochondrial DNA (mtDNA) heteroplasmy in blood samples of 13 individuals belonging to a three family generation of myoclonic epilepsy with ragged-red fibers (MERRF) and compared the 5 affected patients and the 8 unaffected relatives. MATERIAL AND METHODS: DNA was extracted from blood and muscle of the proband and from blood of 12 maternal relatives. A PCR restriction analysis method was used to detect the mutation. RESULTS: The proband had the complete MERRF phenotype. The phenotype in three other individuals in the maternal lineage was consistent with the MERRF syndrome. The remaining were asymptomatic. The np 8344 mutation was observed in muscle and blood of the proband, and in blood from every one of 12 maternal relatives, ranging from 44% to 83% of mutated genomes. Symptomatic individuals had higher levels (P < 0.001) of mutated mtDNA than asymptomatic maternal relatives. However, high proportions of mutant genomes (up to 63%) were found in asymptomatic relatives. CONCLUSIONS: Although there seems to be a gene dosage effect in MERRF, we found no absolute relationship between the relative proportion of mutant genomes in blood and clinical severity. Factors other than gene dosage in blood may account for the differences in clinical phenotype.

Adult↗
PubMed1997

Respiratory chain enzyme activities in isolated mitochondria of lymphocytes from patients with Alzheimer's disease.

We studied respiratory chain enzyme activities in lymphocyte mitochondria from 33 patients with Alzheimer's disease (AD) and from 30 age- and sex-matched healthy controls. The respiratory chain enzyme activities did not differ significantly between patients and controls. No patient showed any value for respiratory chain enzyme levels below normal range. Values for activities of complexes in the AD group did not correlate with age at onset or duration of the disease. Our finding of normal mitochondrial function in lymphocyte mitochondria suggests that this tissue cannot be used to demonstrate the involvement of oxidative phosphorylation in AD and, thus, to develop a diagnostic test for AD.

Aged↗
PubMed1997

Leigh syndrome associated with the T9176C mutation in the ATPase 6 gene of mitochondrial DNA.

A child with clinical and neuroradiologic evidence of Leigh syndrome (LS) had the T-to-C transition at nt 9176 in the ATPase 6 gene of mtDNA. The mutation was homoplasmic in muscle and maternally inherited. The proband's mother had ataxia and harbored 93% of mutant genomes in blood, whereas three clinically unaffected maternal relatives had varying degrees of heteroplasmy in blood. These data confirm the association of the T9176C mutation with LS and extend the clinical heterogeneity of mutations in the ATPase 6 gene.

Adenosine Triphosphatases↗
PubMed1996

Sporadic MERRF/MELAS overlap syndrome associated with the 3243 tRNA(Leu(UUR)) mutation of mitochondrial DNA.

We studied a patient with a mitochondrial encephalomyopathy characterized by the presence of all the cardinal features of both myoclonic epilepsy and ragged-red fibers (MERRF) and mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS) syndromes. Muscle biopsy showed ragged-red fibers (RRF). Some RRF were cytochrome c oxidase (COX)-negative while some others stained positive for COX. Muscle biochemistry revealed defects of complexes I and IV of the respiratory chain. Both muscle and blood mitochondrial DNA from the patient showed the presence of the mutation at nucleotide position 3243 in the tRNA(Leu(UUR)) gene and the absence of point mutations related to MERRF syndrome. The proportions of mutant mtDNA were 70% in muscle and 30% in blood. The mutation was absent in blood from all maternal relatives, in hair follicles from the mother, and in muscle from one sister of the proband. Therefore, there was no evidence of maternal inheritance.

Adolescent↗
PubMed1996

Abnormal carnitine distribution in the muscles of patients with idiopathic inflammatory myopathy.

OBJECTIVE: To analyze the levels of free carnitine and carnitine esters in the muscles of patients with inflammatory myopathies. METHODS: Six men and 7 women with inflammatory myopathy and 25 age-matched healthy controls were studied. Free carnitine and carnitine esters in muscle homogenates were measured by a radiochemical procedure. Muscle histochemical staining and measurement of respiratory chain enzyme activity were also performed. RESULTS: Eleven patients had muscle carnitine insufficiency. Five of them had subsarcolemmal oxidative accumulations, 5 had lipid droplets, and 4 had defects of the respiratory chain enzyme complexes. CONCLUSION: Abnormal distribution of muscle carnitine is present in patients with inflammatory myopathies and could impair muscle function. Coexistent mitochondrial dysfunction may contribute to carnitine insufficiency.

Adolescent↗
PubMed1996

Leber's congenital amaurosis associated with mitochondrial dysfunction.

We report the case histories of two 6-month-old girls, both with young, nonconsanguineous parents, referred to us for suspected blindness. In both cases, Leber's congenital amaurosis was diagnosed. Due to persistently high lactic acid levels in blood, muscle biopsies were taken. Analysis of biopsies revealed that both patients had low levels of complex IV of the mitochondrial respiratory chain; one patient additionally had low levels of complex III. Microscopic and ultrastructural alterations of muscle, typically observed in mitochondrial disorders, were observed only in the second patient. These observations raise the possibility that at least some cases of Leber's congenital amaurosis may be due to alterations in the mitochondrial respiratory chain.

Age of Onset↗
PubMed1996

Respiratory-chain enzyme activities in isolated mitochondria of lymphocytes from untreated Parkinson's disease patients. Grupo-Centro de Trastornos del Movimiento.

We studied respiratory-chain enzyme activities in lymphocyte mitochondria from 36 untreated Parkinson's disease (PD) patients and in 30 age- and sex-matched healthy controls. The respiratory-chain enzyme activities did not differ significantly between patients and controls. Moreover, no patient showed respiratory-chain enzyme levels below normal range. Values for activities of complexes in the PD group did not correlate with age at onset, duration, scores of the Unified Parkinson's Disease Rating scales, or Hoehn and Yahr staging. These results suggest that the presence of defects of respiratory-chain complexes could depend on methodologic aspects, and that determinations of respiratory-chain enzymes in cell homogenates are not generally appropriate for evaluating abnormal mitochondrial dysfunction, especially when the amount of the specific enzyme is relatively low, as is the case of blood cells. In addition, the method of measuring complex I activity is critical for evaluating the results. In conclusion, our finding of normal mitochondrial function in lymphocyte mitochondria suggests that this tissue cannot be used to develop a diagnostic test for PD.

Citrate (si)-Synthase↗
PubMed1996

Single large-scale mitochondrial DNA deletion in a patient with mitochondrial myopathy associated with multiple symmetric lipomatosis.

In a nonalcoholic woman with multiple symmetric lipomatosis (MSL), muscle histochemistry showed ragged-red fibers and cytochrome c oxidase negative fibers. Southern blot analysis revealed a single deletion of mitochondrial DNA (mtDNA). We suggest that MSL is an uncommon manifestation of the wide clinical spectrum of mitochondrial disorders, in particular of those associated with single mtDNA deletions.

Blotting, Southern↗
PubMed1995

Mitochondrial DNA deletion in a patient with mitochondrial myopathy, lactic acidosis, and stroke-like episodes (MELAS) and Fanconi's syndrome.

Large-scale mitochondrial DNA deletion was found in a 5-year-old girl with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) and Fanconi's syndrome. Muscle biopsy disclosed ragged-red fibers and cytochrome c oxidase negative fibers. Respiratory chain studies were normal. Southern blot analysis demonstrated a 10.5-Kb heteroplasmic deletion in both muscle and blood. Deleted genomes represented 40% of total mitochondrial DNA in muscle and 63% in blood. There was no evidence of point mutations characteristic of MELAS. We suggest that not only patients with progressive external ophthalmoplegia syndromes, but also those with defined syndromes [e.g., MELAS or myoclonic epilepsy and ragged-red fibers (MERRF)] without characteristic point mutations, be screened for mitochondrial DNA deletions.

Biopsy↗
PubMed1995

Clinical heterogeneity in two pedigrees with the 3243 bp tRNA(Leu(UUR)) mutation of mitochondrial DNA.

We studied two pedigrees with a mutation at the nucleotide 3243 of mitochondrial DNA (mtDNA). The proband from the first pedigree had clinically defined MELAS plus maternally transmitted insulin-dependent diabetes mellitus (IDDM). The propositus of the other pedigree had exercise intolerance, lactic acidosis and ragged-red fibers (RRF). In the first pedigree, both the mother and the sister's proband harbored the point mutation in their muscle. The mother had 40% of mutant mitochondrial genomes and the sister 70%. In the second pedigree, the mutation was present in both muscle and blood from the proband as well as in blood from all other members studied. Proportion of mutant mtDNA was 90% in muscle and ranged from 40% to 90% in blood.

Adult↗
PubMed1995

Respiratory chain enzyme defects in patients with idiopathic inflammatory myopathy.

OBJECTIVE: To analyse muscle respiratory chain enzymes in idiopathic inflammatory myopathy. METHODS: Four consecutive female patients seen at our hospital with idiopathic inflammatory myopathy were studied. Muscle histochemical staining included NADH tetrazolium reductase and succinate dehydrogenase tests. Activity of rotenone sensitive NADH cytochrome c reductase (complex I and III) succinate dehydrogenase (complex II), succinate cytochrome c reductase (complex II and III), cytochrome c oxidase (complex IV), and citrate synthase (a mitochondrial matrix enzyme), was measured spectrophotometrically in muscle homogenates. Free carnitine, and short and long chain acylcarnitine esters were determined in muscle homogenates by a radiochemical procedure. RESULTS: Three patients had mitochondrial proliferation in nonregenerating muscle fibres; these patients had defects of respiratory chain enzyme complexes. Carnitine concentrations, measured in two of the four patients, revealed carnitine deficiency in one. CONCLUSION: Our results suggest that mitochondrial dysfunction may be present in patients with inflammatory myositis.

Adolescent↗