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J Arenas

Publications and source records attributed to J Arenas.

At least 55 records · Page 3Linked to original sources
PubMed2001

[Fasciola hepatica. study of a series of 37 patients].

BACKGROUND: To analyze the clinical, bacteriologic, diagnostic and therapeutic features of patients with Fasciola hepatica (FH) in our hospital. PATIENTS AND METHOD: We reviewed all the patients with a diagnosis of fascioliasis from 1975 to 1999 in the Aranzazu Hospital in San Sebastián (Guipúzcoa, Spain). Diagnosis was made by direct vision of adult parasites during surgery and/or the presence of ova in stool examinations and/or positive serologic tests in patients with symptoms consistent with parasitosis. RESULTS: Thirty-seven patients were included (23 men and 14 women), aged 19 to 71 years. Ingestion of watercress was confirmed in 27. Seven cases occurred as part of familiar outbreaks. Thirty-two were in the liver invasive stage and in 5 the biliary tree was invaded. The most common features were eosinophilia (91.8%), malaise and weight loss (75.6%), elevated alkaline phosphatase (74.2%), and abdominal pain (72.9%). Adult worms in the biliary ducts were observed in 3 patients and ova in feces were observed in 6. In 13 of 27 patients indirect hemagglutination test was ( 1/1,280. Data significant to confirmation of liver involvement were provided by laparoscopy in 12 of 13 patients and by imaging techniques in 13 of 31 patients. Four patients had cholelithiasis and of these, 2 also showed adult parasites in the common bile duct. Three patients underwent surgery. Therapy with dehydroemetine and/or bithionol was followed by complete remission in 30 patients, although 6 required repeat treatment cycles. The remaining 4 patients were cured by praziquantel. CONCLUSIONS: Most of the patients in these series reported consumption of watercress and all patients showed the symptoms typical of parasite disease. Imaging techniques proved to be of great utility in confirming the diagnosis of hepato-biliary disease. In most of the patients therapy with dehydroemetine and/or bithionol (in one or several cycles) was followed by complete remission.

Adult↗
PubMed2001

A new mtDNA mutation in the tRNA(Leu(UUR)) gene associated with ocular myopathy.

We studied a patient with ptosis, ophthalmoparesis, and exercise intolerance who showed in her muscle biopsy ragged-red fibers and combined defects of the complexes I and IV of the mitochondrial respiratory chain. Molecular analysis revealed a T3273C transition in the mitochondrial DNA tRNA(Leu(UUR)) gene. The mutation was heteroplasmic and very abundant in muscle from the proposita, less abundant in her other tissues studied, and still less abundant in blood from her maternal relatives. Single muscle fiber analysis showed significantly higher levels of mutant genomes in ragged-red fibers than in normal fibers. The T3273C mutation affects a strictly conserved base pair in the anticodon stem and was not found in controls, thus satisfying the accepted criteria for pathogenicity.

Base Sequence↗
PubMed2001

Resolution of a mispaired secondary structure intermediate could account for a novel micro-insertion/deletion (387 insA/del 8 bp) in the PYGM gene causing McArdle's disease.

We report two siblings with McArdle's disease who are both compound heterozygotes for two non-identical frameshift mutations in the PYGM gene; a previously reported 753 delA in exon 18 and a novel 387 insA/del 8 bp in exon 10. The novel mutation is predicted to result in premature termination of translation 33 amino acids downstream of the site of mutation, potentially encoding a severely truncated protein of 419 amino acids instead of 841 amino acids. The complete lack of myophosphorylase activity observed in muscle derived from one sibling suggests that this mutation has deleterious functional consequences. The underlying mechanism of mutagenesis may have been slipped mispairing mediated by the formation of a Moebius loop-like secondary intermediate.

Adult↗
PubMed2001

Thyroid hormone regulates oxidative phosphorylation in the cerebral cortex and striatum of neonatal rats.

We have previously shown that thyroid hormone (T(3)) regulates mitochondrial gene expression, morphology and transmembrane potential in the developing brain. Here, we have analysed the effect of thyroid hormone on mitochondrial function in different brain regions. For this purpose we have determined, in control, hypothyroid and T(3)-treated hypothyroid neonatal rats, the rate of oxidative phosphorylation in isolated mitochondria and the activity of the respiratory complexes in tissue homogenates. Our results showed a decrease in oxidative phosphorylation rate (only in the presence of NADH-generating substrates) and mitochondrial complexes I and III activity in the cerebral cortex and striatum of hypothyroid neonates, but not in the other areas analysed (hippocampus, cerebellum, thalamus, mid brain and brain stem). In parallel with mitochondrial activity, the levels of mitochondrially encoded transcripts were decreased only in the cerebral cortex and striatum of hypothyroid rats. The administration of T(3) corrected all these parameters. In summary, this study showed a down-regulation of mitochondrial gene expression accompanied by a decrease in mitochondrial activity in the cerebral cortex and striatum of developing hypothyroid neonatal rats.

Adenosine Triphosphatases↗
PubMed2001

Mitochondrial disease and stroke.

BACKGROUND AND PURPOSE: It is well known that some mitochondrial disorders are responsible for ischemic cerebral infarction in young patients. Our purpose was to determine, in this prospective ongoing study, whether ischemic stroke is the only manifestation of a mitochondrial disorder in young patients. METHODS: Patients aged </=50 years, admitted to the Stroke Unit from January 1999 to May 2000 with a diagnosis of ischemic stroke of unknown origin, were included in the study. All of them had full biochemical and hematologic tests, neuroimaging studies, transesophageal echocardiography, and extracranial and transcranial Doppler sonography. Patent foramen ovale was ruled out. Lactic acid concentrations were measured after anaerobic exercise of the forearm, and a morphological, biochemical, and molecular study after biceps muscle biopsy was performed. RESULTS: Of the 18 patients so far included, 3 (17%) presented lactic acid hyperproduction after physical exercise, and 6 (33%) showed deficit of the mitochondrial respiratory chain complexes. The molecular analyses have confirmed mitochondrial mutations at base pairs 3243 (characteristic of mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes [MELAS]), 4216, and 15 928. CONCLUSIONS: These results suggest that ischemic stroke may be the only manifestation or the initial manifestation of a mitochondrial disorder.

Adolescent↗
PubMed2001

Congenital hydranencephalic-hydrocephalic syndrome with proliferative vasculopathy: a possible relation with mitochondrial dysfunction.

We report the case of a fetus aborted at gestation week 20 because of hydranencephalic-hydrocephalic syndrome. The fetus was the third pregnancy of a nonconsanguineous couple whose first child exhibited congenital hydranencephalic-hydrocephalic syndrome associated with muscle histology findings consistent with mitochondrial cytopathy and deficiency of complexes III and IV of the respiratory chain and whose second pregnancy had terminated in an elective abortion on detection of progressive hydrocephalus at gestation week 19. The third pregnancy had a normal course according to obstetric and ultrasonography examinations performed at gestation weeks 5, 10, and 15, and negative results were obtained in standard serologic and polymerase chain reaction (PCR) tests for prenatal infections of the mother. However, the ultrasonography examination at gestation week 18 revealed hydrocephalus, in response to which the parents requested an abortion, which was performed at gestation week 20; the fetus was male and with no evident external malformations. Histopathologic studies of the brain and medulla oblongata revealed proliferative vasculopathy (glomeruloid vessels, intracytoplasmic inclusions, and microcalcifications) and intracytoplasmic inclusions in the voluntary muscle. Microbiologic and PCR tests of hepatic and spleen tissue were negative for prenatal infections. In view of the precedent of a sister with mitochondrial dysfunction, these findings raise the pos sibility that at least some cases of familial syndrome of congenital hydranencephalic-hydrocephalic syndrome with proliferative vasculopathy can be attributed to alterations in the mitochondrial respiratory chain.

Abortion, Induced↗
PubMed2001

Molecular heterogeneity of myophosphorylase deficiency (McArdle's disease): a genotype-phenotype correlation study.

We report on 54 Spanish patients with McArdle's disease from 40 unrelated families. Molecular analysis revealed that the most common R49X mutation was present in 70% of patients and 55% of alleles. The G204S mutation was less frequent and found in 14.8% of patients and 9% of mutant alleles. The W797R mutation was observed in 16.5% of patients, accounting for 13.7% of mutant alleles. Moreover, 78% of mutant alleles among Spanish patients can be identified by using polymerase chain reaction-restriction fragment length polymorphism analysis for the R49X, G204S, and W797R mutations, which makes noninvasive diagnosis possible through molecular genetic analysis of blood DNA. Six novel mutations were found. Three were missense mutations, E348K, R601W, and A703V; two nonsense mutations, E124X and Q754X; and one single base pair deletion, 533 delA. No clear genotype-phenotype correlation emerges from our study. Most of the mutations of uncharged and solvent inaccessible residues and the truncations must disrupt the basic structure of the protein. The mutations of charged residues would be expected to interfere with internal hydrogen bonding networks, introducing severe incompatible partnering that is caused by poor packing or electrostatic repulsions.

Adolescent↗
PubMed2000

Myocardial carnitine and carnitine palmitoyltransferase deficiencies in patients with severe heart failure.

We studied myocardial tissue from 25 cardiac transplant recipients, who had end-stage congestive heart failure (CHF), and from 21 control donor hearts. Concentrations of total carnitine (TC), free carnitine (FC), short-chain acylcarnitines, long-chain acylcarnitines (LCAC) as well as carnitine palmitoyltransferase (CPT) activities were measured in myocardial tissue homogenates and referred to the concentration of non-collagen protein. Compared to controls, the concentrations of TC and FC as well as total CPT activities were significantly lower in patients. LCAC levels and the LCAC to FC ratio values were significantly greater in patients than in controls. While the malonyl-CoA sensitive fraction of CPT, which represents CPT I activity, was similar in patients and controls, the residual CPT activity after inhibition by malonyl-CoA, representing CPT II activity, was significantly reduced in patients compared to controls. Moreover, the activity of CPT in the presence of Triton X-100, which also represents the activity of CPT II, was significantly lower in patients than in controls. Malonyl-CoA concentrations required for half-maximal inhibition of CPT activity were significantly greater in patients than in controls. There was a linear relationship between ejection fraction (EF) values and concentrations of TC, FC, or total CPT activities. Values for LCAC and the LCAC to FC ratio were inversely related to EF values. We conclude that failing heart shows decreased total CPT and CPT II activities and carnitine deficiency that may be related to ventricle function.

Biopsy↗
PubMed2000

[The use of cardiopulmonary exercise test in patients with mitochondrial myopathies].

BACKGROUND: Exercise tests has been used in the diagnosis of metabolic myopathies. If there is an abnormal response pattern in mild mitochondrial myopathy (MM) and her role in the initial suspect diagnostic is unknown. SUBJECTS AND METHODS: Prospective study of 26 patients with mitochondrial myopathy (15 men, 11 women) and a control group of 14 sedentary volunteers (9 men, 5 woman) with similar antropometric characteristics. We have made pulmonary function tests and treadmill exercise with serial venous sampling of blood lactate, piruvate, ketone bodies, free fatty acids and creatinkinase. RESULTS: Patients with MM showed exercise limitation with lower maximal power (MM = 143 [47] vatts, C = 187 [40] vatts, p = 0.006), maximal oxygen uptake (MM = 27 [8] ml/min/kg, C = 40 [7] ml/min/kg, p = 0.001) and maximal oxygen pulse (MM = 11 [3] ml/beat, C = 14 [3] ml/beat, p = 0.006). For the same oxygen uptake the heart rate was higher and the anaerobic threshold was earlier in MM patients (MM = 48% [14], C = 62% [12], p = 0.01). We found a considerable slower maximal oxygen uptake in patients with lipid increase in muscle biopsy (n = 15). Acetoacetate curves, beta-hydroxybutyrate, free fatty acids and creatinkinase were similar in both groups. The exercise test was pathologic in 17/26 of the patients. The sensitivity of the exercise test for maximal oxygen uptake was 0.65. CONCLUSIONS: The cardiopulmonary exercise test is a useful test in the suspect initial diagnostic of patients with mild mitochondrial myopathy because the majority of patients show a pathologic test.

Adolescent↗
PubMed2000

A missense mutation W797R in the myophosphorylase gene in a Spanish patient with McArdle's disease.

We identified a novel missense mutation in the myophosphorylase gene (PYGM) in a Spanish patient with McArdle's disease. This homozygous T-to-C transition results in the replacement of a highly conserved tryptophan at amino acid position (aa) 797 with an arginine in the C-terminal domain of the PYGM protein. The lack of enzyme activity in the proband's muscle is consistent with a crucial role of the aa 797 in the normal function of the PYGM protein. Our data further expand the genetic heterogeneity in patients with McArdle's disease.

Adult↗
PubMed2000

Lipomatosis, proximal myopathy, and the mitochondrial 8344 mutation. A lipid storage myopathy?

Multiple symmetric lipomatosis (MSL) has been related in some cases to the 8344 point mutation of the tRNA-lysine gene of the mitochondrial DNA, mainly in the context of families with classic myoclonic epilepsy with ragged-red fibers (MERRF) and exceptionally in patients with proximal myopathy as the only manifestation of mitochondrial disease. We report on two families harboring the 8344 mutation. The patients presented with MSL and myopathy, expressed as limb girdle weakness in index cases and as exercise intolerance in the others. All muscle biopsies performed showed lipid storage apart from RRF and respiratory chain complexes deficiency. A possible explanation for both adipose proliferation and lipid storage myopathy in these cases is a disturbance in intermediary lipid metabolism secondary to mitochondrial respiratory chain deficiency that could be related via carnitine deficiency.

Adolescent↗
PubMed2000

Two homozygous mutations (R193W and 794/795 delAA) in the myophosphorylase gene in a patient with McArdle's disease.

We report two novel homozygous mutations in the myophosphorylase gene (PYGM) in a patient with McArdle's disease. A C-to-T transition that changed an arginine to tryptophan at codon 193 (R193W) in exon 5, and a deletion of two adenine base pairs in exon 20 at codon 794/795 (794/795 delAA) were identified. Several lines of evidence suggest the pathogenicity of both mutations: (i) they were the only nucleotide alteration in the coding region and adjacent exon/intron boundaries of the PYGM gene; (ii) the R193W mutation leads to the replacement of a highly conserved amino acid residue involved in glucose-6-P binding, and the 794/795 delAA mutation predicts a frameshift and premature termination of the protein; (iii) 60 normal controls and 20 disease controls did not have the mutations in their 160 alleles. Hum Mutat 15:294, 2000.

Adolescent↗
PubMed2000

Molecular analysis of Spanish patients with AMP deaminase deficiency.

We found six patients with AMPD deficiency in muscle who were homozygous for the most common mutation, Q12X in the AMPD gene (AMPD1), associated with this disease. Three patients had AMPD deficiency alone, showing a mild clinical phenotype. Two patients showed a defect of PPL in muscle, and were homozygous for the most common mutation associated with McArdle's disease, R49X in the muscle PPL gene (PYGM). In one of these patients, the clinical phenotype was more severe than usually seen in patients with McArdle's disease. The remaining patient harbored the mtDNA A3243G mutation, showing one of the usual clinical patterns associated with this mutation. We conclude that the Q12X mutation in AMPD1 may result in a mild clinical effect; that it is frequent in the Spanish population, and therefore frequently associated with other metabolic diseases; and that the effect of the association of AMPD and PPL deficiencies seems to be neutral.

AMP Deaminase↗
PubMed2000

Identification of novel mutations in Spanish patients with muscle carnitine palmitoyltransferase II deficiency.

Carnitine palmitoyltransferase II (CPT II) deficiency is the most common recessively inherited disorder of lipid metabolism affecting skeletal muscle and the most frequent cause of hereditary myoglobinuria. We studied 5 Spanish patients with CPT II deficiency from four unrelated families. Four patients had the typical clinical phenotype of muscle CPT II deficiency with recurrent episodes of myoglobinuria, triggered by prolonged exercise, fasting, or fever, and marked elevation of creatine kinase values during metabolic crisis. One patient had exercise-related myalgia, cramps and moderate elevation of serum CK values, but had never had myoglobinuria. Molecular analysis showed that three patients were heterozygous for the S113L mutation and one patient heterozygous for the P50H substitution. To identify the mutations in the other alleles of our patients we amplified and sequenced genomic DNA fragments encompassing the entire coding region and intron/exon boundaries of the CPT2 gene. We found the recently reported 178 insT/del 25 bp in one patient. Three novel mutations were identified: a Y120C substitution that leads to a nonconservative amino acid replacement; a 36-38 insGC mutation that results in premature termination of the translation; and an I502T substitution that affects a conserved amino acid residue in the CPT II protein. Our data confirm the molecular heterogeneity of patients with CPT II deficiency, and suggest that the ethnic origin has to be taken into account before performing mutation analysis in these patients.

Adolescent↗
PubMed2000

The pathogenic role of point mutations affecting the translational initiation codon of mitochondrial genes.

The mutation T3308C results in a Met --> Thr change at the highly conserved amino acid position 1 of the mtDNA ND1 gene (M1T). To study its potential pathogenic effect we have carried out a combination of mitochondrial protein synthesis and Northern and Western analyses. Our data demonstrate that M1T mutation does not affect the efficiency of the synthesis of the ND1 polypeptide and suggest that any codon specifying methionine located close to the 5' end of mitochondrial mRNAs may be used as translational initiator.

Blotting, Northern↗