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Biomedical subjects

M Pineda

Publications and source records attributed to M Pineda.

At least 19 recordsLinked to original sources
PubMed2006

[Orientation of mental retardation from neurometabolic diseases].

INTRODUCTION AND DEVELOPMENT: Isolated mental retardation is rarely caused by metabolic factors. The application of a standardised protocol offers low diagnostic performance. There is no international agreement about what type of metabolic examination must be applied in patients with unspecific mental retardation. Nevertheless, and although they are infrequent, there are a number of inborn errors of metabolism that can present in this way. Urea cycle disorders, different forms of homocystinuria, creatine transport deficiency, 4-hydroxybutyric aciduria, Sanfilippo disease, adenylosuccinate lyase deficit and certain extraordinarily rare congenital disorders of the glycosylation of proteins are some examples of them. It is important first to consider those for which treatment is available and that could be diagnosed genetically for possible family counselling. CONCLUSIONS: Rather than applying a standardised study protocol it is essential is to perform a thorough appraisal of the signs and symptoms associated with the mental retardation (psychiatric disorders, autistic traits, predominant compromise of language, signs of cerebellar dysfunction, epilepsy, dysmorphic traits), since in most disorders it is necessary to apply specific analyses, which are not included in conventional metabolic studies and are only available in certain reference centres.

Algorithms↗
PubMed2006

Niemann-Pick C disease in Spain: clinical spectrum and development of a disability scale.

OBJECTIVES: To describe the clinical evolution of Niemann-Pick C disease to identify possible factors involved in the diagnosis and severity of the disease. METHODS: A clinical database and a severity scale was created to evaluate 45 patients diagnosed with Niemann-Pick type C in the last 28 years in Spain. RESULTS: Complete clinical data were obtained from 30 patients, all were confirmed to have mutations in the NPC1 gene. Regarding clinical form, 3 were perinatal, 7 severe infantile, 6 late infantile, 11 juvenile and 3 adult. Biochemical phenotype was classic in 26. Splenomegaly was present in 28 patients (93%) with a wide range of age at detection. The first symptom of neurological disease was clumsiness, followed in 2-4 years by cerebellar signs. Ophthalmoplegia appeared 2-4 years later and became complete 1-2 years after onset. Dysarthria appeared by the time of complete ophthalmoplegia. Diagnosis was made before the onset of neurological signs in patients with the severe infantile form, at the time of onset of cerebellar signs in the late infantile form and complete ophthalmoplegia in late onset forms. CONCLUSIONS: In our series, splenomegaly is present in 96% of patients, even in late onset forms during the first years of life. Clumsiness in children with otherwise normal motor development precedes the onset of ataxia by 2-4 years in Niemann Pick type C. A disability scale could be useful for monitoring evolution, establishing possible phenotypic correlations and evaluating future therapies.

Adolescent↗
PubMed2006

Theoretical analysis of internal fluctuations and bistability in CO oxidation on nanoscale surfaces.

The bistable CO oxidation on a nanoscale surface is characterized by a limited number of reacting molecules on the catalytic area. Internal fluctuations due to finite-size effects are studied by the master equation with a Langmuir-Hinshelwood mechanism for CO oxidation. Analytical solutions can be found in a reduced one-component model after the adiabatic elimination of one variable which in our case is the oxygen coverage. It is shown that near the critical point, with decreasing surface area, one cannot distinguish between two macroscopically stable stationary states. This is a consequence of the large fluctuations in the coverage which occur on a fast time scale. Under these conditions, the transition times between the macroscopic states also are no longer separated from the short-time scale of the coverage fluctuations as is the case for large surface areas and far away from the critical point. The corresponding stationary solutions of the probability distribution and the mean first passage times calculated in the reduced model are supported by numerics of the full two-component model.

Journal Article↗
PubMed2006

Abel inversion applied to a small set of emission data from a microwave plasma.

In this work we propose a criterion to apply the Abel inversion in the case of a small set of experimental data to be used in laboratory plasmas. The Nestor-Olsen method, spline interpolation, and Fourier transform Abel inversion have been compared in order to study the influence of statistical noise and the number of sampled data. The application of this criterion permits us to obtain a radial distribution of the plasma parameters (densities and temperatures) from the spectral line profiles emitted by the discharge. The proposed criterion has been tested using the lateral intensities of several lines emitted by a microwave helium plasma column generated at atmospheric pressure.

Algorithms↗
PubMed2005

Synchronization in driven versus autonomous coupled chaotic maps.

The phenomenon of synchronization occurring in a locally coupled map lattice subject to an external drive is compared to the synchronization process in an autonomous coupled map system with similar local couplings plus a global interaction. It is shown that chaotic synchronized states in both systems are equivalent, but the collective states arising after the chaotic synchronized state becomes unstable can be different in these two systems. It is found that the external drive induces chaotic synchronization as well as synchronization of unstable periodic orbits of the local dynamics in the driven lattice. On the other hand, the addition of a global interaction in the autonomous system allows for chaotic synchronization which is not possible in a large coupled map system possessing only local couplings.

Journal Article↗
PubMed2005

Muscle coenzyme Q10 concentrations in patients with probable and definite diagnosis of respiratory chain disorders.

Coenzyme Q(10) (CoQ) deficiency syndrome is a disorder of unknown ethiology that may cause different forms of mitochondrial encephalomyopathy. In the present study our aim was to analyse CoQ concentration and mitochondrial respiratory chain (MRC) enzyme activities in muscle biopsies of patients with clinical suspicion and/or biochemical-molecular diagnosis of a mitochondrial disorder. We studied 36 patients classified into 3 groups: 1) 14 patients without a definitive diagnosis of mitochondrial disease, 2) 13 patients with decreased CI + III and II + III activities of the MRC, and 3) 9 patients with definitive diagnosis of mitochondrial disease. Only 1 of the 14 patients of group 1 showed slightly reduced CoQ values in muscle. Six of the 13 patients from group 2 showed partial CoQ deficiency in muscle and 1 of the 9 cases from group 3 presented a slight CoQ deficiency. Significantly positive correlation was observed between CI + III and CII + III activities with CoQ concentrations in the 36 muscle homogenates from patients (r = 0.555; p = 0.001; and r = 0.460; p = 0.005, respectively). In conclusion, measurement of MRC enzyme activities is a useful tool for the detection of CoQ deficiency, which should be confirmed by CoQ quantification.

Adolescent↗
PubMed2005

Cerebrospinal fluid concentrations of folate, biogenic amines and pterins in Rett syndrome: treatment with folinic acid.

BACKGROUND: Previous studies in Rett syndrome (RS) patients suggested various abnormalities in biogenic amines, pterins, and folate values in cerebrospinal fluid (CSF). Our aim was to analyse these metabolites in CSF of 16 RS patients (age range: 2 - 23 years). Biogenic amines, pterins, and 5-methyltetrahydrofolate were measured by HPLC with electrochemical and fluorescence detection. RESULTS: CSF values of 5-methyltetrahydrofolate were decreased in 8 out of 16 RS patients (average: 53.6 nmol/L; range: 19 - 92) when compared with our reference values (average: 74.6 nmol/L; range: 45 - 127). These eight patients had epilepsy, while 4 out of 16 RS patients who did not have epilepsy showed normal CSF 5-methyltetrahydrofolate concentrations. Values of biogenic amines or pterins were decreased in four of the patients with low values of 5-methyltetrahydrofolate. No correlation was observed between CSF values of 5-methyltetrahydrofolate and pterins, biogenic amines, or age. Supplementation with folinic acid was applied in six out of the eight patients with CSF 5-methyltetrahydrofolate deficiency. An improvement was noticed in all cases. CONCLUSIONS: An important percentage of RS patients showed 5-methyltetrahydrofolate concentrations under the reference values. Therefore, analysis of CSF 5-methyltetrahydrofolate seems advisable in RS, especially in patients with epilepsy and those resistant to antiepileptic drugs.

Adolescent↗
PubMed2005

Identification of 25 new mutations in 40 unrelated Spanish Niemann-Pick type C patients: genotype-phenotype correlations.

To better characterize Niemann-Pick type C (NPC) in Spain and improve genetic counselling, molecular analyses were carried out in 40 unrelated Spanish patients. The search identified 70/80 alleles (88%) involving 38 different NPC1 mutations, 26 of which are described for the first time. No patient with NPC2 mutations was identified. The novel NPC1 mutations include 14 amino acid substitutions [R372W (c.1114C>T), P434L (c.1301C>T), C479Y (c.1436G>A), K576R (c.1727G>A), V727F (c.2179G>T), M754K (c.2261T>A), S865L (c.2594C>T), A926T (c.2776G>A), D948H (c.2842G>C), V959E (c.2876T>A), T1036K (c.3107C>A), T1066N (c.3197C>A), N1156I (c.3467A>T) and F1224L (c.3672C>G)], four stop codon [W260X (c.780G>A), S425X (c.1274C>A), C645X (c.1935T>A) and R1059X (c.3175C>T)], two donor splice-site mutations [IVS7+1G>A (g.31432G>A) and IVS21+2insG (g.51871insG)], one in-frame mutation [N961_F966delinsS (c.2882del16bpins1bp)] and five frameshift mutations [V299fsX8 (c.895insT), A558fsX11 (c.1673insG), C778fsX10 (c.2334insT), G993fsX3 (c.2973_78delG) and F1221fsX20 (c.3662delT)]. We also identified three novel changes [V562V (c.1686G>A), A580A (c.1740C>G) and A1187A (c.3561G>T)] in three independent NPC patients and five polymorphisms that have been described previously. The combination of these polymorphisms gave rise to the establishment of different haplotypes. Linkage disequilibrium was detected between mutations C177Y and G993fsX3 and specific haplotypes, suggesting a unique origin for these mutations. In contrast, I1061T mutation showed at least two different origins. The most prevalent mutations in Spanish patients were I1061T, Q775P, C177Y and P1007A (10, 7, 7 and 5% of alleles, respectively). Our data in homozygous patients indicate that the Q775P mutation correlates with a severe infantile neurological form and the C177Y mutation with a late infantile clinical phenotype.

Adolescent↗
PubMed2004

The effect of genotype on the natural history of eIF2B-related leukodystrophies.

BACKGROUND: Recessive mutations in the five eucaryotic initiation factor 2B (eIF2B) subunits have been found in leukodystrophies of variable age at onset and severity. OBJECTIVES: To evaluate the clinical spectrum of eIF2B-related disorders and search for a phenotype-genotype correlation. METHODS: Ninety-three individuals (78 families) with an undetermined leukodystrophy were selected on MRI-based criteria of childhood ataxia with central hypomyelination/vanishing white matter (CACH/VWM) for EIF2B genes analysis. RESULTS: Eighty-nine percent of individuals with MRI criteria of CACH/VWM have a mutation in one of the eIF2B beta to epsilon subunits. For 83 individuals (68 families), 46 distinct mutations (90% missense) in four of the five eIF2B subunits (beta, gamma, delta, epsilon) were identified. Sixty-four percent were in the epsilon subunit, a R113H substitution was found in 71% of eIF2B epsilon-mutated families. A large clinical spectrum was observed from rapidly fatal infantile to asymptomatic adult forms. Disease severity was correlated with age at onset (p < 0.0001) but not with the type of the mutated subunit nor with the position of the mutation within the protein. Mutations R113H in the epsilon subunit and E213G in the beta subunit were significantly associated with milder forms. CONCLUSIONS: The degree of eIF2B dysfunction, which is involved in the regulation of protein synthesis during cellular stress, may play a role in the clinical expression of eIF2B-related disorders.

Adolescent↗
PubMed2004

Cerebrospinal fluid concentrations of idebenone in Friedreich ataxia patients.

We studied plasma and cerebrospinal fluid (CSF) concentrations of idebenone in five Friedreich ataxia patients on treatment with this antioxidant, and plasma and CSF ubiquinone-10 (Q (10)) concentrations in 15 controls. CSF idebenone concentrations were below the detection limit in 3 Friedreich ataxia patients and no association could be demonstrated between plasma and CSF idebenone values. Q (10) CSF concentrations (median: 2.25 nmol/L) were approximately 300 times lower than those of plasma (median: 0.77 micro mol/L). No correlation was observed between plasma and CSF Q (10) concentrations. A significantly positive correlation was observed between CSF total protein values (range 8.1 - 107.5 mg/dL; median: 29.5) and CSF Q (10) concentrations (Spearman test: r = 0.664; p = 0.01). Our findings suggest that less idebenone is distributed to the brain than to other tissues, although CSF does not appear to be an appropriate material for treatment monitoring of idebenone and other quinoid compounds.

Adolescent↗
PubMed2003

Emergence of patterns in driven and in autonomous spatiotemporal systems.

The relationship between a driven extended system and an autonomous spatiotemporal system is investigated in the context of coupled map lattice models. Specifically, a locally coupled map lattice subjected to an external drive is compared to a coupled map system with similar local couplings plus a global interaction. It is shown that, under some conditions, the emergent patterns in both systems are analogous. Based on the knowledge of the dynamical responses of the driven lattice, we present a method that allows the prediction of parameter values for the emergence of ordered spatiotemporal patterns in a class of coupled map systems having local coupling and general forms of global interactions.

Journal Article↗
PubMed2003

CblE type of homocystinuria: mild clinical phenotype in two patients homozygous for a novel mutation in the MTRR gene.

Patients with the cblE type of homocystinuria usually present with megaloblastic anaemia, feeding difficulties, developmental delay and cerebral atrophy. We present a 14-year-old Spanish girl (patient 1) and a 10-year-old Portuguese boy (patient 2) with cblE disease and mild clinical phenotype. The main clinical feature in both patients was persistent megaloblastic anaemia observed at 3 years and at 2 months of age, respectively. Diagnosis was made at the ages of 9 and 7 years, respectively, owing to persistent macrocytosis despite cobalamin treatment. Plasma total homocysteine values at diagnosis were 91 micromol/L and 44 micromol/L, respectively, in the absence of methylmalonic aciduria. Neurological and neurophysiological examinations were normal except for two small lesions on brain MRI suggestive of ischaemia and slight abnormalities in somatosensitive evoked potentials. Enzymatic analysis, complementation studies and clearly reduced production of methylcobalamin from 57Co-labelled cyanocobalamin indicated functional methionine synthase reductase deficiency due to the cblE defect. Genetic analysis confirmed that both patients are homozygous for a novel mutation c.1361C>T in the methionine synthase reductase gene leading to a replacement of serine by leucine (S454L) in a highly conserved FAD-binding domain. We propose that homozygosity for this novel mutation may be associated with a mild phenotype, although its long-term deleterious neurological consequences remain possible. Furthermore, we propose that even in the absence of apparent neurological involvement, total homocysteine should be investigated in patients with resistant megaloblastic anaemia to detect possible mild forms of the cblE type of homocystinuria.

Adolescent↗
PubMed2002

Congenital microcephaly and seizures due to 3-phosphoglycerate dehydrogenase deficiency: outcome of treatment with amino acids.

Congenital microcephaly, intractable seizures and severe psychomotor retardation characterize 3-phosphoglycerate dehydrogenase (3-PGDH) deficiency, a disorder of L-serine biosynthesis. The enzyme defect results in low concentrations of serine and to a variable degree of glycine in plasma and cerebrospinal fluid. Short-term beneficial effects have been reported of oral treatment with the deficient amino acids. In this paper, we report the first follow-up data of amino acid therapy in five patients treated for 3-7.5 years. Different treatment regimes were used, but a favourable response to amino acids was observed in all patients. A major reduction in seizure frequency occurred in all patients; two patients became free of seizures. Amino acids were well tolerated and no adverse effects were documented. A progress of psychomotor development was only observed in one patient, diagnosed early and treated with a high dosage of L-serine. A favourable outcome of 3-PGDH deficiency depends on early diagnosis and treatment.

Carbohydrate Dehydrogenases↗
PubMed2002

Friedreich's ataxia: idebenone treatment in early stage patients.

BACKGROUND: Antioxidant therapy has been applied to Friedreich's ataxia patients. We assessed the effect of idebenone treatment in patients with Friedreich's ataxia. METHODS DESIGN: open-label trial. Nine Friedreich's ataxia patients (age range 11 - 19 years) were treated with idebenone (5 mg/kg/day). Patients were evaluated before the start of the therapy and throughout one year of treatment by International Cooperative Ataxia Rating Scales (ICARS) scores, neurophysiological investigations and echocardiographic measurements. Serum idebenone concentrations were measured by HPLC with electrochemical detection. The number of GAA repeats at the frataxin gene was analyzed by PCR. RESULTS: Serum idebenone concentrations ranged between 0.04 - 0.37 micro mol/L. Significantly positive correlation was observed between idebenone values and the percentage of difference between the ICARS scores before and 12 months after the start of the therapy (r = 0.883; p = 0.002). Significant reduction was observed comparing the ICARS scores in baseline conditions and after 3 months of treatment (p = 0.017). No differences were observed in echocardiographic measurements after the start of the therapy. CONCLUSIONS: Cerebellar improvement was notable in mild patients after the first 3 months of therapy. Idebenone treatment at early stages of the disease seems to reduce the progression of cerebellar manifestations. Further blind trials with a greater number of patients and higher doses are needed to fully assess the therapeutic potential of idebenone in Friedreich's ataxia.

Adolescent↗
PubMed2001

Identification and characterisation of human xCT that co-expresses, with 4F2 heavy chain, the amino acid transport activity system xc-.

We have identified a new human complementary deoxyribonucleic acid (cDNA), for the xc- amino acid transporter (HGMW-approved name SLC7A11; also known as human xCT), that, when co-expressed with the heavy chain of surface antigen 4F2 (4F2hc, also termed CD98), but not with rBAT, (related to the bo,+ amino acid transporter), induces system xc- transport activity in Xenopus oocytes. Human xCT is the seventh human member of the family of amino acid transporters that are subunits of 4F2hc or rBAT and, inview of its amino acid sequence identity (89%) with mouse xCT, is most probably the human orthologue thereof. The amino acid transport activity induced by the co-expression of human 4F2hc and xCT in Xenopus oocytes was sodium independent and specific for L-cystine, L-glutamate and L-aspartate. This activity also functioned in an exchange mode (e.g. cystine/glutamate) with a substrate stoichiometry of 1:1. Expression of human xCT alone in oocytes did not induce amino acid transport activity and the expressed xCT protein was localised intracellularly. When human xCT was co-expressed with 4F2hc, the former localised to the oocyte plasma membrane. Tissue-expression studies showed that human SLC7A11 mRNA is expressed mainly in the brain, but also in pancreas and in cultured cell lines. The transport characteristics of human xCT and the distribution of its tissue expression strongly suggest that it corresponds to the human amino acid transporter system xc-.

Amino Acid Sequence↗
PubMed2001

Cloning, characterization and mRNA expression analysis of PVAS1, a type I asparagine synthetase gene from Phaseolus vulgaris.

A gene encoding a putative asparagine synthetase (AS; EC 6.3.5.4) has been isolated from common bean (Phaseolus vulgaris L.). A 2-kb cDNA clone of this gene (PVAS1) encodes a protein of 579 amino acids with a predicted molecular mass of 65,265 Da, an isoelectric point of 6.3, and a net charge of -9.3 at pH 7.0. The PVAS1 protein sequence conserves all the amino acid residues that are essential for glutamine-dependent AS, and PVAS1 complemented an Escherichia coli asparagine auxotroph, which demonstrates that it encodes a glutamine-dependent AS. The PVAS1 protein showed the highest similarity to soybean SAS1, and piled up with other legume ASs to form an independent dendritic group of type-I AS enzymes. Northern blot analyses revealed that the expression pattern of PVAS1 resembles that of PVAS2, another AS previously described in the common bean. Unlike PVAS2, however, PVAS1 was not expressed in the nodule and was not repressed by light, suggesting different functions for these two AS genes.

Amino Acid Sequence↗