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Biomedical subjects

E Muñoz

Publications and source records attributed to E Muñoz.

At least 37 records · Page 2Linked to original sources
PubMed2002

Distribution of HLA-DRB1 genes in patients with sporadic ankylosing spondylitis in the south of Spain.

OBJECTIVE: To evaluate the relationship between the presence of different HLA-DRB1 genes and predisposition to develop a sporadic form of ankylosing spondylitis (AS) in a demographically well-defined population. METHODS: One hundred fifteen selected patients with sporadic (non-familial) forms of AS from six different cities and 748 bone marrow donors as control group. All individuals were typed for HLA-B27 by flow cytometry with monoclonal antibodies and PCR -SSP, as well as for HLA-DRB using the Dynal ELI SSO HLA-DRB Test (Dynal AS, Oslo, Norway). The Inno-Lipa DRB Decoder (Innogenetics NV Zwijndrecht, Belgium), was used for high-resolution HLA-DRB typing. RESULTS: The presence of the DRB1*01 antigen in the studied population is significantiy higher in B27 positive healthy individuals (bone marrow donors) than in B27 positive AS patients; also, DRB1*01 is higher in B27 negative AS patients than 827 negative controls. The frequency of DRB1*03 is higher in B27 negative controls than B27 negative AS patients. CONCLUSION: The results of this study suggest that DRB1*01 antigens might be involved in the development of sporadic forms of ankylosing spondylitis in HLA-B27 negative individuals in the studied area.

Adult↗
PubMed2002

SCA8 in the Spanish population including one homozygous patient.

Controversial data have been reported about SCA8 since its description in 1999. The most accepted hypothesis is that CTG expansions within the CTA/CTG combined repeat expansion in the SCA8 locus causes SCA8. It is inherited as a dominant trait with reduced penetrance. The present study, reports the first data regarding SCA8 in the Spanish population and the clinical findings in patients carrying expanded alleles, including one homozygous patient. Two hundred and forty-six individuals from the Spanish population, including controls (149) and ataxic patients (97), were studied. DNA was extracted from blood samples using standard methods. Amplification of the CTA/CTG 3'untranslated region was achieved by PCR using primers SCA8-F3 and SCA8-R4 and conditions described previously. Neurological reevaluation was done in individuals carrying the expanded allele. We detected five unrelated expanded alleles corresponding to three affected patients (one of them homozygous) and one healthy individual. SCA8 represents 4% of the total dominant spinocerebellar ataxias studied in our group (Spanish population) (three index patients out of 75 dominant ataxic independent nucleus). The patient that resulted homozygous for the expansion is a 25-year-old man with a clinical picture of progressive ataxia and dysarthria that began at the age of 12. On neurological examination, he showed ataxia, slight dysarthria and nystagmus to the extreme lateral gaze. A cranial MRI showed global atrophy of cerebellum but the brainstem was spared. Family history showed the presence of ataxia in his grandfather and father. His mother is healthy at the age of 52 and a molecular study of SCA8 reveals one allele that could be considered as premutated. She has no ataxia antecedents in her family. Our results provide additional information about the SCA8 expansion, within the Spanish population. These results are in agreement with the hypothesis of the CTG expansion in the SCA8 locus being responsible for the SCA8 ataxia showing reduced penetrance. Besides homozygous status, advancing age at onset (as previously described for other SCAs) supports this idea.

Adult↗
PubMed2002

Implications on human fertility of the 677C-->T and 1298A-->C polymorphisms of the MTHFR gene: consequences of a possible genetic selection.

Mutant alleles with the 677C-->T and 1298A-->C polymorphisms of the MTHFR gene, and consequent lower methylentetrahydrofolate reductase enzyme activity, have been related to higher plasma homocysteine levels, which are associated with cardiovascular diseases. We assessed the genotype frequencies, degrees of fertility and homocysteine levels, and discuss a possible genetic selection for the gene polymorphisms studied. A total of 1777 subjects (897 women and 880 men), divided into four age groups, were genotyped by PCR and restriction fragment length polymorphism. The total homocysteine concentration in plasma was determined by fluorescence polarization immunoassay. Based on random pairs and linkage disequilibrium of the two polymorphisms, we estimated the rate of fetal non-viability according to the combinations of these two polymorphisms to be 4.63% for the group >24 years old and 6.31% for the group <24 years old. We detected an increased frequency of mutant alleles in the youngest age group, coincident with a generally increased folate intake by pregnant women in Spain. The genetic selection detected leads to an increase in mutated individuals, the number of whom could increase four-fold over the next 75 years. Although generally reduced in the younger age groups, the homocysteine plasma levels were shown to increase in individuals according to the number of mutations, especially those of the 677T allele.

Adult↗
PubMed2002

Relative high frequency of the c.255delA parkin gene mutation in Spanish patients with autosomal recessive parkinsonism.

BACKGROUND: Autosomal recessive juvenile parkinsonism is a neurodegenerative disorder associated with mutations in the parkin gene. OBJECTIVES: To search for the presence of parkin gene mutations in Spanish patients with Parkinson's disease (PD) and characterise the phenotype associated with these mutations. METHODS: Thirty seven PD patients with either early onset or autosomal recessive pattern of inheritance were selected for genetic study. RESULTS: Mutations were identified in seven index patients (19%). Homozygous mutations were detected in six patients and a heterozygous mutation in one. The age at onset was lower in patients with mutations than in patients without mutations. Dystonia at onset was present in two patients with parkin gene mutations. The disease began in two patients with postural tremor in the upper limbs mimicking essential tremor. Four patients exhibited a long term response to dopamine agonists. The c.255delA mutation was identified in four unrelated families. This is a frameshift mutation leading to protein truncation. CONCLUSIONS: Parkin gene mutations are present in Spanish patients with early onset and/or an autosomal recessive parkinsonism. The c.255delA is the most frequent mutation found, suggesting a relative high prevalence in the Spanish population.

Adult↗
PubMed2002

[Antithrombotic treatment of fusiform aneurysms of the basilar artery].

Fusiform aneurysms are unusual, and they are most found in the vertebrobasilar system. Although the presence of such aneurysms has been related to atheromatous degeneration of the arterial wall, in many cases the cause of their formation is unknown. The clinical manifestations of fusiform aneurysms of the vertebrobasilar system are generally due to mass effect with compression of adjacent structures or to ischemic events; exceptionally they are due to subarachnoidal haemorrhage. We present the case of a patient with symptoms suggestive of brainstem ischemic damage, in which neuroimaging showed a fusiform aneurysm of the basilar artery with an intraaneurysmatic thrombus. Antiaggregation did not prevent new ischemic events, so anticoagulation therapy was initiated. The patient remained asymptomatic at 8 months of follow-up. The treatment of fusiform aneurysms is controversial; however, there are some evidences in the literature supporting that patients with ischemic events may be treated with long term anticoagulation, especially in cases of non-giant aneurysms of the vertebrobasilar system not accompanied by aneurysms in other sites.

Anticoagulants↗
PubMed2002

[Cerebrotendinous xanthomatosis without tendinous xanthomas: presentation of two cases].

Cerebrotendinous xanthomatosis (CTX) is a genetic disorder caused by a 27-hydroxilase enzyme deficiency, leading to beta-cholestanol storage in many body tissues. Clinically, the disease is characterised by the presence of tendinous xanthomas, juvenile cataracts and progressive neurologic dysfunction. The diagnosis requires beta-cholestanol quantification in serum. We report two siblings with a history of photosensitive epilepsy of childhood onset, who developed progressive spastic paraparesis and cataracts in their third decade of life. They were diagnosed to have CTX in spite of the absence of tendinous xanthomas. Cranial and spinal MRI only showed bilateral high intensity signal in the dentate nuclei in the T2-weighted and proton-density sequences. Our patients presented with a progressive spastic paraparesis. The delay in the diagnosis in our case could be due to the absence of tendinous xanthomas and late-onset cataracts. The recognition of the disease is important, because the treatment with chenodeoxycholic acid induces a decrement of beta-cholestanol levels in serum and could prevent the progression of the disease.

Adolescent↗
PubMed2002

[Creation of a model for myelomeningocele in rabbit embryos].

UNLABELLED: Spinal dysraphism causes paraplegia, fecal incontinence, neurogenic bladder, sexual dysfunction, hydrocephalus and skeletal abnormalities in newborns. Its ethiology and pathogenesis are still not known, and probably multifactorial. AIM: To determine whether spinal cord exposition to the amniotic space causes a functional (impairment) and anatomic lesion similar to that of human myelomeningocele. MATERIAL AND METHODS: Forty-eight fetal rabbits underwent to create spina bifida on the 23rd gestational day (term is 31 days). The procedure consisted of lumbosacral skin excision and posterior laminectomy. The fetuses are allowed to continue their gestation. On the 30th gestational by the operated fetuses were harvested, together with a group of nonoperated littermates for control. A clinical and neurologic evaluation was done, as well a study of somato-sensorial evoked potentials in the upper and lower limb and histologic study of the affected vertebral and cordial segment. RESULTS: The 26 surviving animals had deformity and lack of movement of the lower limbs. Evoked potentials showed absent response to stimuli in the lower limbs of animals with spina bifida, whereas upper limbs and control animals did respond. Histologically the spinal cord of the operated rabbits was uncovered and flattened. CONCLUSION: This model of myelomeningocele in fetal rabbit reproduces a variety of features similar to human spinal dysraphism, and hence can be used to study the pathophysiology of spina bifida.

Animals↗
PubMed2001

Changes in the cochlear dopaminergic system of the aged rat.

The levels of dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) have been quantified in cochleae of male and female rats aged 3, 6, 9, 12, 19 and 24 months. Animals were exposed for 1 h, under general anesthesia, to: (1) silence (basal conditions) or (2) white noise at 90 dB SPL. Afterwards, the concentrations of DA, DOPAC and HVA were determined by HPLC with electrochemical detection in homogenates of individual cochleae. In basal conditions, the cochlear concentrations of DA, DOPAC and HVA in aged females were higher than in adult ones. The concentrations of DA and DOPAC were also higher in aged males with respect to adult ones. A decrease in DA and an increase in DOPAC and HVA concentrations, with respect to silence, were detected when adult animals were exposed to noise. Meanwhile, aged animals showed either a noise-induced increase or no modification of DA and DOPAC with respect to basal levels. Present results suggest age-related failures in DA release and metabolizing mechanisms within the cochlea, together with a compensatory DA synthesis increase. However, the possibility of an initial damage in the primary auditory neurons which could also stimulate the synthesis of DA must not be excluded. Present age-related changes could indicate that the cochlear dopaminergic innervation is affected during the aging process. Since this innervation plays an important role in both the modulation and the protection of the primary auditory neurons, its metabolic alteration could profoundly modify the auditory process.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2001

[Sporadic and familial Parkinson's disease: comparative study].

BACKGROUND: Several studies have shown that 13 to 33% of patients with Parkinson's disease (PD) exhibit a positive familial history. The goals of this work were to identify patients with familial PD and to analyse whether there existed distinctive features between familial and sporadic cases. PATIENTS AND METHOD: 402 patients with PD from the Hospital Clínic i Universitari of Barcelona were evaluated prospectively. Clinical assessment was done using different scales in 169 patients. The disease was classified as tremorigenic, rigid or mixed according to the predominant symptoms. RESULTS: The frequency of familial PD was 13%. The age at onset was not different between familial and sporadic cases but it was significantly higher in females (57.4 [13] years) than in males (54.8 [11.4] years) (p < 0.05). The tremorigenic type of PD was more common in familial cases (35.5%) (p < 0.05). In familial PD cases, the age at onset was lower in descendents (53 [13] years) than in parents (68 [7.8] years) (p = 0.001). CONCLUSIONS: Genetic factors may play an important role in the development of PD and gender-associated factors may modulate the age at onset. Familial PD cases differ from sporadic cases in the higher frequency of predominantly tremorigenic forms. The lower age at onset in descendents than in parents suggests the existence of a genetic anticipation phenomenon in familial PD.

Adult↗
PubMed2001

Focal limb dystonia in a patient with a cerebellar mass.

BACKGROUND: Focal dystonia of acute onset is indicative of a structural lesion in the nervous system. Cerebellar lesions have rarely been associated with dystonia. CASE DESCRIPTION: A 42-year-old woman was admitted to the neurology ward because of fever, confusion, and gait unsteadiness. She was diagnosed as having tuberculous meningitis, and, after a few days of antituberculous treatment, she developed prominent dystonia of the left upper limb. Cranial nuclear magnetic resonance imaging showed an isolated lesion compatible with a tuberculoma in the left cerebellar hemisphere. Both the limb dystonia and the tuberculoma resolved with maintained antituberculous treatment. CONCLUSIONS: In the patient described, the presence of upper-limb dystonia ipsilateral to a focal cerebellar lesion and the resolution of the dystonia and the mass lesion following treatment suggest that the cerebellum or its connections to the thalamus and/or basal ganglia could be involved in the pathophysiology of the dystonia.

Acute Disease↗
PubMed2001

Analysis of the coding and the 5' flanking regions of the alpha-synuclein gene in patients with Parkinson's disease.

Missense mutations of the alpha-synuclein gene have been reported to explain a few kindreds with autosomal dominant Parkinson's disease (PD). In order to identify mutations in our PD patients, we have screened the coding region and 5'flanking region of the gene. DNA samples from 50 patients with familial PD were screened via single-strand conformation polymorphism (SSCP) for mutations in the alpha-synuclein gene. The 5' flanking region was examined in 117 additional PD patients (27 patients with unclear family history for PD, and 90 patients without family history) and in 169 control subjects. We found one change (G199A) in exon 4 in one family with a pattern of autosomal dominant PD. However, this mutation did not result in an amino acid substitution (valine) and did not segregate completely with PD. The analysis of the 5' flanking region also showed a new polymorphism, a nucleotide insertion (- 164insA) linked to a nucleotide substitution (C-116G), in patients and in controls. The -164insA/C-116G allele was present in 52.3% of the patients and in 47.6% of the controls. We did not find significant differences regarding the allelic and genotype frequencies between PD and control groups. These results suggest that mutations in the alpha-synuclein gene are a very rare cause of familial PD and that the novel -164insA/C-116G polymorphism in the 5' flanking region does not confer susceptibility to develop PD.

Aged↗
PubMed2001

Cellular redox state and activating protein-1 are involved in ascorbate effect on calcitriol-induced differentiation.

Ascorbate has been related to the differentiation of several mesenchymal cells including haematopoietic cells. We have previously demonstrated that ascorbate enhances the activity of 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3) on monocytic differentiation of HL-60 cells. Here, we show that ascorbate-mediated modification of cellular redox state and AP-1 (activating protein-1) DNA binding during early phases are related to the enhancing effect of ascorbate on differentiation. Ascorbate, but not its fully oxidized form, dehydroascorbate, or an ascorbate analogue with a low rate of oxidation, ascorbate-2-phosphate, enhanced the differentiation induced by 1 alpha,25(OH)2D3, modified cytosolic reactive oxygen species levels and mitochondrial redox potential (delta psi m), and modulated AP-1 DNA binding in HL-60 cells. Ascorbate itself increased AP-1 binding to DNA in noninduced cells, whereas it inhibited AP-1 binding in 1 alpha,25(OH)2D3-induced cells. However, ascorbate increased the mRNA levels of c-jun, junB, and c-fos in 1 alpha,25(OH)2D3-induced cells. Taken together, these results suggest that the enhancing effect of ascorbate on HL-60 differentiation induced by 1 alpha, 25(OH)2D3 is related to its effect on the cellular redox state and the modulation of AP-1 activity.

Ascorbic Acid↗
PubMed2001

Ingenol esters induce apoptosis in Jurkat cells through an AP-1 and NF-kappaB independent pathway.

BACKGROUND: Ingenol derivatives have received constant and multidisciplinary attention on account of their pleiotropic pattern of biological activity. This includes activation of protein kinase C (PKC), tumour-promotion, anticancer, and anti-HIV properties, and the possibility of dissecting co-cancerogenic and clinically useful activities has been demonstrated. Certain ingenol esters show powerful anticancer activity, and a structure-activity relationship model to discriminate between their apoptotic and non-apoptotic properties has been developed. RESULTS: The polyhydroxylated southern region of ingenol was selectively modified, using the anticancer and PKC activator ingenol 3,20-dibenzoate (IDB) as a lead compound. The evaluation of IDB analogues in apoptosis assays showed strict structure-activity relationships, benzoylation of the 20-hydroxyl being required to trigger apoptosis through a pathway involving caspase-3 and occurring at the specific cell cycle checkpoint that controls the S-M phase transition. Conversely, a study on the activation of the PKC-dependent transcription factors AP-1 and NF-kappaB by IDB analogues showed significant molecular flexibility, including tolerance to changes at the 3- and 20-hydroxyls. IDB-induced apoptosis was independent of activation of PKC, since it was not affected by treatment with the non-isoform-selective PKC inhibitor GF 109230X0. CONCLUSIONS: Remarkable deviations from the tumour-promotion pharmacophore were observed for both the apoptotic and the PKC-activating properties of IDB analogues, showing that ingenol is a viable template to selectively target crucial pathways involved in tumour promotion and development. Since the apoptotic and the PKC-activating properties of ingenoids are mediated by different pathways and governed by distinct structure-activity relationships, it is possible to dissect them by suitable chemical modification. In this context, the esterification pattern of the 5- and 20-hydroxyls is critical.

Apoptosis↗
PubMed2001

Enhanced gain of blink reflex responses to ipsilateral supraorbital nerve afferent inputs in patients with facial nerve palsy.

OBJECTIVES: Patients with peripheral facial palsy (PFP) may present with transient hyperkinetic movement disorders in the side contralateral to the paralysis. One possible cause of such enhanced motor activity is sensitization of reflex responses to afferent inputs from the unprotected cornea. We hypothesized that if this sensitization occurs, the size of the orbicularis oculi (OOc) responses induced by afferents from the ophthalmic branch of the paralyzed side would be larger than those induced by afferents from the contralateral side. METHODS: In 68 patients with complete PFP and in a group of 30 age-matched control subjects we recorded the response of the OOc muscle of one side to electrical stimulation of the supraorbital nerve of both sides, and calculated the ratio between R2c and R2 (R2c/R2). RESULTS: The mean R2c/R2 ratio was significantly larger in patients than in control subjects (unpaired t test, P<0.05). Larger R2c than R2 responses were observed in 23.1% of control subjects and in 80.9% of patients (chi(2)=13.3, P<0.01). CONCLUSIONS: Our results suggest that patients with PFP have an enhanced blink reflex gain to inputs from the paralyzed side compared to those of the non-paralyzed side. Sensitization of the blink reflex polysynaptic pathways to inputs carried by afferent fibers from the ophthalmic branch of the paralyzed side can play a role in inducing an abnormal facial motor behavior after PFP.

Adult↗
PubMed2001

New glycosides from Capsicum annuum L. var. acuminatum. Isolation, structure determination, and biological activity.

Investigation of polar extracts from ripe fruits of Capsicum annuum L. var. acuminatum yielded three new glycosides, capsosides A (1) and B (2) and capsianoside VII (3), along with seven known compounds (4-10). The chemical structures were elucidated mainly by extensive nuclear magnetic resonance methods and mass spectrometry, and the biological activities of icariside E(5) (4) were tested by different assays. Icariside E(5), in contrast to capsaicin, neither induces an increase in the intracellular levels of reactive oxygen species nor affects the mitochondria permeability transition, and it does not signal through the vanilloid receptor type 1. Interestingly, this compound protects Jurkat cells from apoptosis induced by the oxidative stress mediated by serum withdrawal. These results suggest that icariside E(5) may have antioxidant properties that strengthen the importance of peppers in the Mediterranean diet.

Capsicum↗
PubMed2001

Ectopic transposition of a group II intron in natural bacterial populations.

Self-splicing group II introns are thought to be the evolutionary progenitors of eukaryotic spliceosomal introns. The invasion of novel (ectopic) sites by group II introns is considered to be a key mechanism by which spliceosomal introns may have become widely dispersed. However, the dynamics of these events in populations are unknown. In bacteria, only two group II introns have been shown to splice and to be mobile in vivo. One of these introns, RmInt1 from Sinorhizobium meliloti, which encodes a protein with no endonuclease domain, has been shown to invade the ectopic oxi1 site independently of recombinase. In this study, we analysed ectopic transposition of the RmInt1 intron in a natural population of S. meliloti. We characterized S. meliloti isolates by polymerase chain reaction amplification of a gene, dapB, which is found only on the pRmeGR4b plasmid diagnostic of GR4-type strains. The diversity within this specific field population of bacteria was analysed by restriction fragment length polymorphism using ISRm2011-2 (homing site of RmInt1) and RmInt1 as probes. We found that ectopic transposition of RmInt1 to the oxi1 site occurred in this natural bacterial population. This ectopic transposition was also the most frequent genetic event observed. This work provides further evidence that the ectopic transposition of group II introns is an important mechanism for their spread in natural bacterial populations.

DNA Transposable Elements↗
PubMed2001

Mesorhizobium chacoense sp. nov., a novel species that nodulates Prosopis alba in the Chaco Arido region (Argentina).

Low-molecular-weight RNA analysis was performed for the identification and classification of 20 Argentinian strains isolated from the root nodules of Prosopis alba. SDS-PAGE of total cellular proteins, determination of the DNA base composition, DNA-DNA reassociation experiments and physiological and biochemical tests were also carried out for these strains and the whole 16S rRNA gene was sequenced from one of the strains, strain LMG 19008T. Results of the genotypic and phenotypic characterization showed that the strains isolated in this study belong to a group that clustered in the genus Mesorhizobium. The results of DNA-DNA hybridizations showed that this group is a novel species of this genus. The name Mesorhizobium chacoense sp. nov. is proposed for this species. The type strain is LMG 19008T (= CECT 5336T).

Anti-Bacterial Agents↗