PubMed Health⌕ Search

Biomedical subjects

N Romero

Publications and source records attributed to N Romero.

At least 19 recordsLinked to original sources
PubMed2006

[Thiamine retention as a function of thermal processing conditions: canned salmon].

The present work studied the effect of different treatments at high temperatures on the nutritional properties of thiamine retention and color measurement experimentally. Canned salmon (Salmo salar) was processed under different temperatures and time conditions (110 degrees C for 135 minutes; 114 degrees C for 89 minutes; 118 degrees C for 69 minutes and 121 degrees C for 62 minutes). Thiamine was determined by HPLC before and after the process. Color changes, due to processing conditions, were also measured utilizing a Hunter colorimeter. The canning was prepared in 300 x 407 cans and sterilized until Fo value reached 6 min. The nutritional value or index represented by the B1 vitamin or thiamine was affected by high temperature and time exposition. The lowest loss of thiamine of 19.2% was obtained in the canned salmon sterilized at 114 degrees C for 89 minutes. The color in canned salmon was different from the raw material, with a severe loss of red color and a greater clarity of the meat.

Animals↗
PubMed2004

A novel missense mutation, c.584A > C (Y195S), in two unrelated Argentine patients with hypoxanthine-guanine phosphoribosyl-transferase deficiency, neurological variant.

The hypoxanthine-guanine phosphoribosyl-transferase (HPRT) deficiency is an inborn error of purine metabolism, responsible for classic Lesch-Nyhan disease and its neurological and hyperuricemic variants. We report a novel mutation in the HPRT gene, c.584A > C (Y195S), in two unrelated Argentine patients affected with the neurological variant with no HPRT activity in lysed erythrocytes. Using PCR plus DNA sequencing and/or restriction enzyme digestion we were able to confirm the diagnosis and identify new cases and potential carriers.

Adolescent↗
PubMed2004

Danon's disease as a cause of hypertrophic cardiomyopathy: a systematic survey.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease caused by mutations in sarcomeric genes. However, extensive genetic screening failed to identify a mutation in about a third of cases. One possible explanation is that other diseases, caused by other genes, may mimic HCM. OBJECTIVE: To investigate the possible involvement of Danon's disease, an X linked lysosomal disease, in a large population of patients with HCM. METHODS: A population of 197 index cases was considered; 124 were subsequently excluded because of a mutation in sarcomeric genes and 23 because of autosomal dominant inheritance. Fifty index cases were therefore included in molecular analysis (direct sequencing) of the lysosome associated membrane protein 2 (LAMP2) gene responsible for Danon's disease. RESULTS: Two new mutations leading to premature stop codons were identified in patients who evolved towards severe heart failure (< 25 years old): 657C>T and 173_179del. The prevalence was therefore 1% of the total population (two of 197) or 4% of enrolled index cases (two of 50). Interestingly, Danon's disease was responsible for half of the cases (two of four) with HCM and clinical skeletal myopathy but was not involved in isolated HCM (none of 41). CONCLUSIONS: Danon's disease may be involved in patients with previously diagnosed as HCM. A diagnosis strategy is proposed. To distinguish HCM from Danon's disease is important because the clinical evolution, prognosis, mode of inheritance, and therefore genetic counselling are very different.

Adolescent↗
PubMed2001

Mutations in the fukutin-related protein gene (FKRP) identify limb girdle muscular dystrophy 2I as a milder allelic variant of congenital muscular dystrophy MDC1C.

The limb girdle and congenital muscular dystrophies (LGMD and CMD) are characterized by skeletal muscle weakness and dystrophic muscle changes. The onset of symptoms in CMD is within the first few months of life, whereas in LGMD they can occur in late childhood, adolescence or adult life. We have recently demonstrated that the fukutin-related protein gene (FKRP) is mutated in a severe form of CMD (MDC1C), characterized by the inability to walk, leg muscle hypertrophy and a secondary deficiency of laminin alpha2 and alpha-dystroglycan. Both MDC1C and LGMD2I map to an identical region on chromosome 19q13.3. To investigate whether these are allelic disorders, we undertook mutation analysis of FKRP in 25 potential LGMD2I families, including some with a severe and early onset phenotype. Mutations were identified in individuals from 17 families. A variable reduction of alpha-dystroglycan expression was observed in the skeletal muscle biopsy of all individuals studied. In addition, several cases showed a deficiency of laminin alpha2 either by immunocytochemistry or western blotting. Unexpectedly, affected individuals from 15 families had an identical C826A (Leu276Ileu) mutation, including five that were homozygous for this change. Linkage analysis identified at least two possible haplotypes in linkage disequilibrium with this mutation. Patients with the C826A change had the clinically less severe LGMD2I phenotype, suggesting that this is a less disruptive FKRP mutation than those found in MDC1C. The spectrum of LGMD2I phenotypes ranged from infants with an early presentation and a Duchenne-like disease course including cardiomyopathy, to milder phenotypes compatible with a favourable long-term outcome.

Adolescent↗
PubMed2001

Expanded CAG repeats in exon 1 of the Huntington's disease gene stimulate dopamine-mediated striatal neuron autophagy and degeneration.

Huntington's disease (HD) is caused by an expanded CAG repeat in exon 1 of the gene coding for the huntingtin protein. The cellular pathway by which this mutation induces HD remains unknown, although alterations in protein degradation are involved. To study intrinsic cellular mechanisms linked to the mutation, we examined dissociated postnatally derived cultures of striatal neurons from transgenic mice expressing exon 1 of the human HD gene carrying a CAG repeat expansion. While there was no difference in cell death between wild-type and mutant littermate-derived cultures, the mutant striatal neurons exhibited elevated cell death following a single exposure to a neurotoxic concentration of dopamine. The mutant neurons exposed to dopamine also exhibited lysosome-associated responses including induction of autophagic granules and electron-dense lysosomes. The autophagic/lysosomal compartments co-localized with high levels of oxygen radicals in living neurons, and ubiquitin. The results suggest that the combination of mutant huntingtin and a source of oxyradical stress (provided in this case by dopamine) induces autophagy and may underlie the selective cell death characteristic of HD.

Animals↗
PubMed2001

Mutations in SEPN1 cause congenital muscular dystrophy with spinal rigidity and restrictive respiratory syndrome.

One form of congenital muscular dystrophy, rigid spine syndrome (MIM 602771), is a rare neuromuscular disorder characterized by early rigidity of the spine and respiratory insufficiency. A locus on 1p35-36 (RSMD1) was recently found to segregate with rigid spine muscular dystrophy 1 (ref. 1). Here we refine the locus and find evidence of linkage disequilibrium associated with SEPN1, which encodes the recently described selenoprotein N (ref. 2). Our identification and analysis of mutations in SEPN1 is the first description of a selenoprotein implicated in a human disease.

Amino Acid Sequence↗
PubMed2001

Mice transgenic for exon 1 of the Huntington's disease gene display reduced striatal sensitivity to neurotoxicity induced by dopamine and 6-hydroxydopamine.

Huntington's disease is an autosomal dominant hereditary neurodegenerative disorder characterized by severe striatal cell loss. Dopamine (DA) has been suggested to play a role in the pathogenesis of the disease. We have previously reported that transgenic mice expressing exon 1 of the human Huntington gene (R6 lines) are resistant to quinolinic acid-induced striatal toxicity. In this study we show that with increasing age, R6/1 and R6/2 mice develop partial resistance to DA- and 6-hydroxydopamine-mediated toxicity in the striatum. Using electron microscopy, we found that the resistance is localized to the cell bodies and not to the neuropil. The reduction of dopamine and cAMP regulated phosphoprotein of a molecular weight of 32 kDa (DARPP-32) in R6/2 mice does not provide the resistance, as DA-induced striatal lesions are not reduced in size in DARPP-32 knockout mice. Neither DA receptor antagonists nor a N-methyl-d-aspartate (NMDA) receptor blocker reduce the size of DA-induced striatal lesions, suggesting that DA toxicity is not dependent upon DA- or NMDA receptor-mediated pathways. Moreover, superoxide dismutase-1 overexpression, monoamine oxidase inhibition and the treatment with the free radical scavenging spin-trap agent phenyl-butyl-tert-nitrone (PBN) also did not block DA toxicity. Levels of the antioxidant molecules, glutathione and ascorbate were not increased in R6/1 mice. Because damage to striatal neurons following intrastriatal injection of 6-hydroxydopamine was also reduced in R6 mice, a yet-to-be identified antioxidant mechanism may provide neuroprotection in these animals. We conclude that striatal neurons of R6 mice develop resistance to DA-induced toxicity with age.

Aging↗
PubMed2001

Late-onset mitochondrial DNA depletion: DNA copy number, multiple deletions, and compensation.

Through a report of 4 late-onset cases with mitochondrial DNA (mtDNA) depletion, we address the specificity of the clinical entities associated with a very low residual amount of mtDNA. Three of the patients met the diagnostic criteria of Kearns Sayre syndrome, which has never been associated with mtDNA depletion. The fourth patient had an isolated skeletal myopathy. Deleted mtDNA molecules were found by long-range polymerase chain reaction (PCR) only in the Kearns Sayre syndromes, which strengthens the clinical differences between the two types of patients. All patients had extremely low residual amounts of mtDNA as shown by Southern blot analysis. Using an original method based on competitive PCR, we were able to measure the number of mtDNA copies per diploid genome. These results demonstrated the severity of the depletion in the patients by comparison not only to normal controls but also to patients with mtDNA disorders. Despite the severity of the depletion, in situ hybridization using two mtDNA transcripts revealed a normal steady-state level of transcription. Such compensation provides clues to the striking contrast between the severity of mtDNA depletion and the late onset and slowly progressive disease.

Age of Onset↗
PubMed2000

Delaying caspase activation by Bcl-2: A clue to disease retardation in a transgenic mouse model of amyotrophic lateral sclerosis.

Molecular mechanisms of apoptosis may participate in motor neuron degeneration produced by mutant copper/zinc superoxide dismutase (mSOD1), the only proven cause of amyotrophic lateral sclerosis (ALS). Consistent with this, herein we show that the spinal cord of transgenic mSOD1 mice is the site of the sequential activation of caspase-1 and caspase-3. Activated caspase-3 and its produced beta-actin cleavage fragments are found in apoptotic neurons in the anterior horn of the spinal cord of affected transgenic mSOD1 mice; although such neurons are few, their scarcity should not undermine the potential importance of apoptosis in the overall mSOD1-related neurodegeneration. Overexpression of the anti-apoptotic protein Bcl-2 attenuates neurodegeneration and delays activation of the caspases and fragmentation of beta-actin. These data demonstrate that caspase activation occurs in this mouse model of ALS during neurodegeneration. Our study also suggests that modulation of caspase activity may provide protective benefit in the treatment of ALS, a view that is consistent with our recent demonstration of caspase inhibition extending the survival of transgenic mSOD1 mice.

Actins↗
PubMed2000

Myoneurin, a novel member of the BTB/POZ-zinc finger family highly expressed in human muscle.

Initially characterized as Drosophila developmental regulators, the BTB/POZ and zinc finger proteins (BTB/POZ-ZF) constitute a growing family of proteins with gene expression regulatory functions since they have been shown to be involved in both transcriptional activation and repression of various genes in a broad range of species, including mammals. Here we report the cloning of a novel human transcript, coding for a 68-kDa deduced BTB/POZ-ZF protein. This molecule, called myoneurin on the basis of its prevalent expression in the neuromuscular system, contains an amino-terminal BTB/POZ domain and eight tandemly repeated zinc-finger motifs of the C(2)H(2) type. The murine myoneurin, identified in the mouse embryo, is highly homologous to the human protein.

Aging↗
PubMed2000

Gallium-67 scintigraphy in macrophagic myofasciitis.

OBJECTIVE: To evaluate gallium-67 (67Ga) uptake and the value of 67Ga scintigraphy for diagnosis of macrophagic myofasciitis (MMF), a recently identified inflammatory myopathy. METHODS: Twelve consecutive patients with MMF confirmed by muscle biopsy, 10 with polymyositis, 10 with sarcoidosis, 8 with fibromyalgia, and 10 with lymphoma without muscle symptoms (serving as normal controls for muscle) were included. Patients received 1.8 MBq 67Ga per kg body weight by intravenous injection, and scintigraphy was performed with a 2-head gamma camera. The various views were acquired for the 3 main photopeaks of 67Ga 48 hours after infusion, and were analyzed in 2 blinded experiments by nuclear physicians. A semiquantitative scale was used to compare the uptake of 67Ga in the vascular soft tissue background with that in the muscles or joints of MMF patients, and with that in the normal controls. RESULTS: The MMF patients (4 men and 8 women, mean +/- SD age 47.8 +/- 8.7 years) had chronic myalgia (n = 11; predominantly in the lower limbs), asthenia (n = 10), arthralgia (n = 7), mild muscle weakness (n = 5), and high serum creatine kinase levels (n = 6). All MMF patients had significantly higher levels of 67Ga uptake in the muscle and para-articular areas than that recorded for the soft tissue background and for the controls. Muscle uptake was bilateral, symmetric, and homogeneous, and predominantly localized in the legs. No linear enhancement corresponding to fascias or synovial involvement was observed. In patients with polymyositis, symmetric, but heterogeneous, 67Ga uptake was observed in muscle, but not in the fascia. In patients with sarcoidosis, 67Ga uptake was nodular and heterogeneous in muscle, was not detected in the fascia, and was suggestive of synovial involvement in the joints. The uptake of 67Ga in fibromyalgic patients was similar to that in normal controls and to that in the soft tissue background. CONCLUSION: MMF is a new condition involving characteristic changes that can be detected by deltoid muscle biopsy. It usually manifests as a weakly specific, chronic arthromyalgic syndrome that predominates in the lower limbs. 67Ga scintigraphy is a noninvasive method that may make it easier to differentiate MMF from fibromyalgia and sarcoidosis.

Adult↗
PubMed2000

[Fatty acids composition and proximate of 7 fish species of Isla de Pascua].

During the last years the study of fatty acids belonging to omega 3 family in marine foods has been emphasized due to their beneficial effects on cardiovascular diseases, which are the main cause of death in occidental countries, as described by literature. In order to obtain more information about the fatty acid composition of the main marine species fat constituent, usually consumed by Eastern Island population, seven fish species were analyzed: Maito (Acanthurus leucopareius), Matuko (Bodianus vulpinus), Marau (Myripristis tiki), Nanue (Kiphosus bigibus). Moki (Mori and Marari, Anampses caeruleopunctatus), Puia (Girellops nebulosus) and Raea (Cheilodactilus plessisi). Fatty acid profile and proximate analysis were determined for each species. According to its fat content, Nanue and Marari showed the highest lipid percentage, with values of 2.8 and 3.6% respectively. Fatty acid profile expressed as methyl esters percentage indicated that the most important group was that of the saturated fatty acids (SFA 35.1-54%), followed by the polyunsaturated fatty acids group (PUFA, 22-42.5%). Palmitic acid was the most important between saturated fatty acids, while oleic acid was the main fatty acid between the monounsaturated group. In omega-3 family fatty acids, eicosapentaenoic acid (EPA, C20:5w3) and docosahexaenoic acid (DHA, C22:6w3) were the most important, with values in a range between 2.0-12% and 1.8-18.3%, respectively. Omega-6 family showed a higher content in arachidonic acid (AA, C20:4w6) with values between 1.9 and 10%. Considering the fatty acid composition and the fat content, Marari was the highest in w-3 and w-6 fatty acid contribution, with values of 850 and 240 mg per one hundred grams of edible portion respectively.

Animals↗
PubMed1999

Diffusion of peroxynitrite in the presence of carbon dioxide.

Peroxynitrite, the reactive species formed in vivo by the reaction of nitric oxide with superoxide anion, is capable of diffusing across erythrocyte membranes via anion channels and passive diffusion (A. Denicola, J. M. Souza, and R. Radi, Proc. Natl. Acad. Sci. USA 95, 3566-3571, 1998). However, peroxynitrite diffusion could be limited by extracellular targets, with the reaction with CO(2) (k(2) = 4.6 x 10(4) at 37 degrees C and pH 7.4) the most relevant. Herein, we studied the influence of physiological concentrations of CO(2) on peroxynitrite diffusion across intact red blood cells. The presence of CO(2) inhibited the oxidation of intracellular oxyhemoglobin by externally added peroxynitrite. However, the inhibition by CO(2) decreased at increasing red blood cell densities. At 45% hematocrit, 1.3 mM CO(2) (in equilibrium with 24 mM bicarbonate, at pH 7.4 and 25 degrees C) only inhibited 30% of intracellular oxyhemoglobin oxidation. This partial inhibition was also observed in red blood cells pretreated with the anion exchanger inhibitor 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, ruling out a competition between peroxynitrite and bicarbonate for the transport through the anion channel. A theoretical model was developed to estimate the diffusion distance and half-life of extracellular peroxynitrite before reacting with intracellular oxyhemoglobin, at different red blood cell densities, and in the presence or absence of CO(2). The theoretical model correlated well with the experimental data. Our results indicate that, even in the presence of CO(2), peroxynitrite is able to diffuse and reach the inside of the erythrocyte.

Biological Transport, Active↗
PubMed1999

Inducible nitric oxide synthase up-regulation in a transgenic mouse model of familial amyotrophic lateral sclerosis.

Mutations in copper/zinc superoxide dismutase (SOD1) are associated with a familial form of amyotrophic lateral sclerosis (ALS), and their expression in transgenic mice produces an ALS-like syndrome. Here we show that, during the course of the disease, the spinal cord of transgenic mice expressing mutant SOD1 (mSOD1) is the site not only of a progressive loss of motor neurons, but also of a dramatic gliosis characterized by reactive astrocytes and activated microglial cells. These changes are absent from the spinal cord of age-matched transgenic mice expressing normal SOD1 and of wild-type mice. We also demonstrate that, during the course of the disease, the expression of inducible nitric oxide synthase (iNOS) increases. In both early symptomatic and end-stage transgenic mSOD1 mice, numerous cells with the appearance of glial cells are strongly iNOS-immunoreactive. In addition, iNOS mRNA level and catalytic activity are increased significantly in the spinal cord of these transgenic mSOD1 mice. None of these alterations are seen in the cerebellum of these animals, a region unaffected by mSOD1. Similarly, no up-regulation of iNOS is detected in the spinal cord of age-matched transgenic mice expressing normal SOD1 or of wild-type mice. The time course of the spinal cord gliosis and iNOS up-regulation parallels that of motor neuronal loss in transgenic mSOD1 mice. Neuronal nitric oxide synthase expression is only seen in neurons in the spinal cord of transgenic mSOD1 mice, regardless of the stage of the disease, and of age-matched transgenic mice expressing normal SOD1 and wild-type mice. Collectively, these data suggest that the observed alterations do not initiate the death of motor neurons, but may contribute to the propagation of the neurodegenerative process. Furthermore, the up-regulation of iNOS, which in turn may stimulate the production of nitric oxide, provides further support to the presumed deleterious role of nitric oxide in the pathogenesis of ALS. This observation also suggests that iNOS may represent a valuable target for the development of new therapeutic avenues for ALS.

Alanine↗
PubMed1999

Bax and Bcl-2 interaction in a transgenic mouse model of familial amyotrophic lateral sclerosis.

It has been proposed that mutations in copper/zinc-superoxide dismutase (SOD1), the only proven cause of amyotrophic lateral sclerosis (ALS), induce the disease by a toxic property that promotes apoptosis. Consistent with this, we have demonstrated that overexpression of Bcl-2, a protein that inhibits apoptosis, attenuates neurodegeneration produced by the familial ALS-linked SOD1 mutant G93A (mSOD1). Herein, we assessed the status of key members of the Bcl-2 family in the spinal cord of transgenic mSOD1 mice at different stages of the disease. In asymptomatic transgenic mSOD1 mice, expression of Bcl-2, Bcl-XL, Bad, and Bax does not differ from that in nontransgenic mice. In contrast, in symptomatic mice, expression of Bcl-2 and Bcl-XL, which inhibit apoptosis, is reduced, whereas expression of Bad and Bax, which stimulate apoptosis, is increased. These alterations are specific to affected brain regions and are caused by the mutant and not by the normal SOD1 enzyme. Relevant to the neuroprotective effects of Bcl-2 in transgenic mSOD1 mice, overexpression of Bcl-2 increases the formation of Bcl-2:Bax heterodimers, which abolish the Bax proapoptotic property. This study demonstrates significant alterations in the expression of key members of the Bcl-2 family associated with mSOD1 deleterious effects. That these changes contribute to the neurodegenerative process in this model of ALS is supported by our observations in double transgenic mSOD1/Bcl-2 mice in which the pernicious increase of Bax is tempered by an increase in formation of Bcl-2:Bax heterodimers. Based on these findings, it may be concluded that Bcl-2 family members appear as invaluable targets for the development of new neuroprotective therapies in ALS.

Animals↗