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Biomedical subjects

E Muñoz

Publications and source records attributed to E Muñoz.

At least 73 records · Page 4Linked to original sources
PubMed2000

Yersinia enterocolitica O:8 and O:5 lipopolysaccharide arthritogenicity in hamsters.

OBJECTIVE: To assess the arthritogenicity of Yersinia enterocolitica O:8 and O:5 lipopolysaccharide (LPS) administered separately as single antigens in hamsters. METHODS: Male hamsters of the Syria strain were intramuscularly injected into each of the hind paws with two doses of Y. enterocolitica LPS O:8 or O:5. The measurement of swelling using a plethysmometer, the analysis of histological changes by routine techniques and the kinetics of LPS-specific antibodies and autoantibodies evaluated by enzyme-linked immunosorbent assay (ELISA) were performed. RESULTS: LPS O:8 was demonstrated to be more arthritogenic than LPS O:5, inducing acute arthritis on day 3 post-injection as well as more significant and longer lasting joint swelling after a second dose. LPS O:8 caused severe histopathological changes in the joints. Important LPS O:8-specific IgG responses and antibodies against type I and II collagen were observed. CONCLUSION: LPS O:8 administered alone has arthritogenic power and induces activation of autoreactive clones. This study supports the key role of LPS in the development of reactive arthritis.

Animals↗
PubMed2000

Trichomoniasis in a Bonelli's eagle population in Spain.

During 1980-97, trichomoniasis was detected in nestlings of Bonelli's eagle Hieraaetus fasciatus in Catalonia (Spain). In 1993 Trichomonas gallinae was isolated in 36% of nestlings (n = 39) and affected 41% of broods (n = 22). Overall, trichomoniasis was one of the most important single nestling mortality factor, accounting for 22% of total chick mortality, and causing the death of 2% of chicks. Trichomoniasis deaths took place during the second half of the nestling period. The median age at death was 45.5 days. Although the presence of the parasite was not related to the composition of the diet or parental age, pairs that developed the disease ate more pigeons and included more often non-adult birds. At present trichomoniasis apparently has little demographic impact on the Bonelli's eagle population in Catalonia, but the eventual spread of this disease in chicks and its unknown effects on adults might be of concern.

Age Factors↗
PubMed2000

Significant association between the tau gene A0/A0 genotype and Parkinson's disease.

A significant association between the tau gene A0/A0 genotype and progressive supranuclear palsy has been reported recently. To determine if the presence of a tau polymorphism could constitute a risk factor for the development of sporadic and familial Parkinson's disease, a dinucleotide repeat marker at intron 11 was genotyped in 152 patients with PD, 52 patients with Alzheimer's disease, and 150 healthy controls. We detected a significant difference in A0 allelic frequency in the Parkinson's disease group (79.27%) compared with the control group (71%) and the Alzheimer's disease group (73.07%). Individuals homozygous for the A0 allele were also detected significantly more frequently in the Parkinson's disease group (63.8%) compared with the control group (52.66%) and the Alzheimer's disease group (48.07%). These results suggest a possible involvement of the tau gene in the pathogenesis of some cases of Parkinson's disease.

Aged↗
PubMed2000

[Advantages of primary rhinoplasty in the treatment of lip fissure].

Congenital cleft lip is always associated to nasal deformity. The classical approach has been not to treat the severe nose defects during childhood, in the fear that early surgery would interfere with nasal growth. However, long term follow-up in patients with early conservative rhinoplasty has shown the nose to hold its new shape and its growth to be normal. During the period between november 1996 and november 1998, 22 infants affected with cleft lip underwent early rhinoplasty according to McComb's technique. During the follow-up period (6 months to 30 months) the children had a good nasal growth. The nose tip is in the medial position in all cases, and only the inferior view of the nose shows a discrete nosetril assimetry in some patients.

Cleft Lip↗
PubMed1999

Susceptibility of HIV-1-TAT transfected cells to undergo apoptosis. Biochemical mechanisms.

The effects of HIV-1 Tat protein on mitochondria membrane permeability and apoptosis were analysed in lymphoid cells. In this report we show that stable-transfected HIV-Tat cells are primed to undergo apoptosis upon serum withdrawal. This effect was observed in both the Jhan T cell line and the K562 cells, the latter expressing the bcr-abl chimeric gene, which confers resistance to apoptosis induced by different stimuli. Using a cytofluorimetric approach we have determined that serum withdrawal induces a disruption of the transmembrane mitochondrial potential (Deltapsim) followed by an increase of reactive oxygen species (ROS) and the subsequent DNA nuclear loss in K562-Tat cells but not in the K562-pcDNA cell line. These pre-apoptotic events were associated with the cleavage of the caspase-3, while the expression of Bcl-2, Bcl-XL and Bax proteins was not affected by the presence of Tat. Regardless of the steady state of the Bax protein, we found that in both K562 and K562-Tat cells, this protein is located in the nucleus, but after serum withdrawal its localization was mainly in the cytoplasm. The activity of caspase-3 detected in K562-Tat cells after serum withdrawal paralleled with the mitochondria permeability transition. Nevertheless, in Jhan-Tat cells the inhibition of this caspase with the specific inhibitor, z-DEVD-cmk, did not affect the disruption of the mitochondria potential induced by serum withdrawal. Interestingly, we found that HIV-Tat protein accumulates at the mitochondria in the K562-Tat cells cultured under low serum conditions, and this mitochondrial localization correlated with the Deltapsim disruption detected in these cells. In addition, HIV-1 Tat protein synergies with protoporphyrin IX (PPIX), a ligand of the mitochondrial benzodiazepine receptor, in the induction of apoptosis in both Jhan and K562 cells. Thus, HIV-1 Tat protein may induce apoptosis by a mechanism that involves mitochondrial PT and may contribute to the lymphocyte depletion seen in AIDS patients.

Apoptosis↗
PubMed1999

Dopamine receptor D2 intronic polymorphism in patients with Parkinson's disease.

An association between the intronic allele 3 of the dopamine receptor D2 (DRD2) gene and European Parkinson's disease (PD) cases has been reported recently. We initiated the present work in order to determine whether this association between the DRD2 locus and PD is also present in our population from Spain. The DRD2 gene polymorphism has been genotyped in 154 patients and in 125 controls. The allele 3 is present in 60.3% of the patients and in 55.2% of the controls. The genotype 3/3 is present in 36.3% of the patients and in 34.4% of the controls. No statistical differences in the genotype and allelic frequencies between the two groups have been found. No differences were also found when the patients were classified according to different criteria such as onset, family history, gender or clinical presentation. Thus our results do not support a role for the DRD2 locus to develop PD.

Adult↗
PubMed1999

Extracellular HIV type 1 Tat protein induces CD69 expression through NF-kappaB activation: possible correlation with cell surface Tat-binding proteins.

The HIV-1 Tat protein, essential for HIV-1 gene expression and viral replication, is known to be secreted by infected cells and has pleiotropic effects on various cell functions. It seems that extracellular Tat may exert its functions on cellular targets by at least two different mechanisms, namely, by adsorptive endocytosis, and by a possible interaction with cell surface receptor(s). Here we report that extracellular Tat activates AIM/CD69 gene transcription through an NF-kappaB-dependent pathway in the erythroleukemia cell line K562. Tat induces NF-kappaB binding to DNA as a result of IkappaBalpha phosphorylation and degradation, which depend on the intracellular redox state. We found that the second Tat-coding exon is required for CD69 gene trans-activation, but not for HIV LTR gene transcription. Fluorescein-labeled Tat proteins were used to study cell surface binding sites and cellular uptake of the proteins. Full-length Tat protein has specific binding sites on the surface of K562 cells, whereas truncated Tat1-48, which is efficiently internalized by the cells, does not bind to the cell surface. Our results suggest that extracellular Tat may activate a cell surface-mediated pathway that induces intracellular signal transduction in K562 cells, leading to the activation of NF-kappaB and the transcription of NF-kappaB-dependent genes, such as CD69.

Antigens, CD↗
PubMed1999

Prevalence of haematozoa in birds of prey in Catalonia, north-east Spain.

Blood samples from birds of prey, 95 Strigiformes and 190 Falconiformes, were examined for the presence of haematozoan parasites. The birds had been admitted to a raptor recovery centre in Catalonia, north-east Spain. Parasites were counted in positive smears. A second blood sample was obtained from 99 birds at least seven days after their arrival at the centre. Haematozoa were detected in all seven species of Strigiformes and in nine of 19 species of Falconiformes. The overall prevalences in the two groups were significantly different, 30.5 per cent and 46.3 per cent in the nocturnal and diurnal raptors, respectively. Eleven species of haematozoan parasites were identified. The genus most commonly detected in members of the nocturnal Strigiformes was Leucocytozoon, followed by Haemoproteus, Plasmodium and Trypanosoma. In the diurnal Falconiformes only Leucocytozoon and Haemoproteus were detected. The highest infection rates were found in Accipiter nisus (sparrow hawks), Accipiter gentilis (goshawks) and Athene noctua (little owls). Relapses were detected in 9 per cent of the birds sampled twice. The highest intensity of infection (6.2 per cent) was observed in a Buteo buteo (buzzard) infected with Haemoproteus.

Animals↗
PubMed1999

Patterned ballistic movements triggered by a startle in healthy humans.

1. The reaction time to a visual stimulus shortens significantly when an unexpected acoustic startle is delivered together with the 'go' signal in healthy human subjects. In this paper we have investigated the physiological mechanisms underlying this effect. If the commands for the startle and the voluntary reaction were superimposed at some level in the CNS, then we would expect to see alterations in the configuration of the voluntary response. Conversely, if the circuit activated by the startling stimulus is somehow involved in the execution of voluntary movements, then reaction time would be sped up but the configuration of the motor programme would be preserved. 2. Fourteen healthy male and female volunteers were instructed to react as fast as possible to a visual 'go' signal by flexing or extending their wrist, or rising onto tiptoe from a standing position. These movements generated consistent and characteristic patterns of EMG activation. In random trials, the 'go' signal was accompanied by a very loud acoustic stimulus. This stimulus was sufficient to produce a startle reflex when given unexpectedly on its own. 3. The startling stimulus almost halved the latency of the voluntary response but did not change the configuration of the EMG pattern in either the arm or the leg. In some subjects the reaction times were shorter than the calculated minimum time for processing of sensory information at the cerebral cortex. Most subjects reported that the very rapid responses were produced by something other than their own will. 4. We conclude that the very short reaction times were not produced by an early startle reflex adding on to a later voluntary response. This would have changed the form of the EMG pattern associated with the voluntary response. Instead, we suggest that such rapid reactions were triggered entirely by activity at subcortical levels, probably involving the startle circuit. 5. The implication is that instructions for voluntary movement can in some circumstances be stored and released from subcortical structures.

Acoustic Stimulation↗
PubMed1999

Alpha1-antichymotrypsin gene polymorphism and susceptibility to Parkinson's disease.

OBJECTIVE: To determine whether the alpha1-antichymotrypsin AA genotype (ACT-AA) confers susceptibility for developing Parkinson's disease (PD) in the Spanish population. BACKGROUND: A correlation between the ACT-AA genotype and the risk of developing PD has been recently reported in the Japanese population. METHODS: The ACT genotypes of 71 patients diagnosed with clinically definite PD were compared with those of 109 age-matched healthy control subjects. RESULTS: The authors found that the ACT-AA polymorphism frequency was not increased significantly in the PD group (31%) compared with the control group (28.4%). The ACT allelic distribution was also similar for familial and sporadic PD, for female and male patients, and for the different clinical subtypes of PD. The age at onset of PD was significantly lower in the ACT-AA patients compared with non-ACT-AA patients. When the actual age was considered, the ACT-AA frequency was higher in PD patients < or =50 years old (50%) compared with that present in patients >50 years old (26.8%), but the same effect was found in control subjects. CONCLUSIONS: The ACT-AA polymorphism is not related to an increased risk of developing PD in the Spanish population. The ACT-AA overrepresentation in PD and control subjects < or =50 years old suggests that this polymorphism could be associated with life-threatening conditions other than PD.

Adult↗
PubMed1999

Reflex excitability of facial motoneurons at onset of muscle reinnervation after facial nerve palsy.

We studied 18 patients with complete unilateral denervation of the facial muscles after idiopathic facial nerve palsy to determine whether motoneuronal excitability is enhanced in the few motor units that are active at onset of muscle reinnervation. The study was carried out between 75 and 90 days after the facial nerve lesion. We used two needle electrodes to record simultaneously the spontaneous and voluntary activity of the orbicularis oris (OOris) and orbicularis oculi (OOculi) muscles, as well as the responses to ipsilateral and contralateral facial and supraorbital nerve stimuli. All patients showed involuntary firing of motor unit action potentials (MUAPs) in at least one of the muscles. Synkinetic activation of motor units in the OOris was induced by spontaneous blinking in all patients, and by inhalation and swallowing in some. Electrical stimulation of the ipsilateral facial nerve induced a direct M response in only 4 patients. In contrast, long-latency reflex responses were induced in both muscles by electrical stimulation of ipsilateral and contralateral facial and supraorbital nerves in all patients, at latencies ranging between 44 and 132 ms. The shape of such MUAP reflex responses was the same as that of the MUAPs seen to fire at rest. These findings provide evidence of enhanced excitability of facial motoneurons in our patients. Such hyperexcitability may be partly responsible for the postparalytic motor dysfunction syndrome that occurs after facial palsy with severe axonal damage.

Action Potentials↗
PubMed1999

p27KIP1 is abnormally expressed in Diffuse Large B-cell Lymphomas and is associated with an adverse clinical outcome.

Cell cycle progression is regulated by the combined action of cyclins, cyclin-dependent kinases (CDKs), and CDK-inhibitors (CDKi), which are negative cell cycle regulators. p27KIP1 is a CDKi key in cell cycle regulation, whose degradation is required for G1/S transition. In spite of the absence of p27KIP1 expression in proliferating lymphocytes, some aggressive B-cell lymphomas have been reported to show an anomalous p27KIP1 staining. We analysed p27KIP1 expression in a series of Diffuse Large B-cell Lymphoma (DLBCL), correlating it with the proliferative index and clinical outcome, to characterize the implications of this anomalous staining in lymphomagenesis in greater depth. For the above mentioned purposes, an immunohistochemical technique in paraffin-embedded tissues was employed, using commercially available antibodies, in a series of 133 patients with known clinical outcomes. Statistical analysis was performed in order to ascertain which clinical and molecular variables may influence outcome, in terms of disease-free survival (DFS) and overall survival (OS). The relationships between p27KIP1 and MIB-1 (Ki-67) were also tested. An abnormally high expression of p27KIP1 was found in lymphomas of this type. The overall correlation between p27KIP1 and MIB-1 showed there to be no significant relationship between these two parameters, this differing from observations in reactive lymphoid and other tissues. Analysis of the clinical relevance of these findings showed that a high level of p27KIP1 expression in this type of tumour is an adverse prognostic marker, in both univariate and multivariate analysis. These results show that there is abnormal p27KIP1 expression in DLBCL, with adverse clinical significance, suggesting that this anomalous p27KIP1 protein may be rendered non-functional through interaction with other cell cycle regulator proteins.

Cell Cycle Proteins↗
PubMed1999

Induction of apoptosis in human mitogen-activated peripheral blood T-lymphocytes by the ether phospholipid ET-18-OCH3: involvement of the Fas receptor/ligand system.

1. Activated T-cells constitute a target for treatment of autoimmune diseases. We have found that the antitumour ether phospholipid 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3; edelfosine) induced dose- and time-dependent apoptosis in human mitogen-activated peripheral blood T-lymphocytes, but not in resting T-cells. T-lymphocytes were stimulated with phytohemagglutinin and interleukin-2 or with concanavalin A. Apoptosis was assessed by DNA fragmentation through cell cycle and TUNEL analyses, as well as through visualization of internucleosomal DNA fragmentation in agarose gels. 2. The ET-18-OCH3-mediated apoptotic response in activated T-lymphocytes was less intense than in human leukaemic T cell lines, such as Jurkat cells and Peer cells; namely about 25% apoptosis in activated T-cells versus about 46-61% apoptosis in T leukaemic cells after 24 h treatment with 10 microM ET-18-OCH3. 3. The ET-18-OCH3 thioether analogue BM 41.440 (ilmofosine) showed a similar apoptotic capacity to that found with ET-18-OCH3 in activated T-cells, whereas the phospholipid analogue hexadecylphosphocholine (miltefosine) failed to promote this response. 4. The uptake of [3H]-ET-18-OCH3 was much larger in activated T-cells than in resting lymphocytes. 5. Using a cytofluorimetric approach we have found that ET-18-OCH3 induced disruption of the mitochondrial transmembrane potential and production of reactive oxygen species in activated T-cells, but not in resting lymphocytes. 6. ET-18-OCH3 induced an increase in Fas (APO-1/CD95) ligand mRNA expression in activated T-cells, and incubation with a blocking anti-Fas (APO-1/CD95) antibody partially inhibited the ET-18-OCH3-induced apoptosis of activated T-lymphocytes. 7. These results demonstrate that mitogen-activated T-cells, unlike resting lymphocytes, are able to take up significant amounts of ET-18-OCH3, and are susceptible to undergo apoptosis by the ether lipid via, in part, the Fas (APO-1/CD95) receptor/ligand system. This ET-18-OCH3 apoptotic action can be of importance in the therapeutic action of this ether lipid in certain autoimmune diseases.

Antineoplastic Agents↗
PubMed1999

Selective induction of apoptosis by capsaicin in transformed cells: the role of reactive oxygen species and calcium.

Capsaicin is a vanilloid quinone analog that inhibits the plasma membrane electron transport (PMOR) system and induces apoptosis in transformed cells. Using a cytofluorimetric approach we have determined that capsaicin induces a rapid increase of reactive oxygen species (ROS) followed by a subsequent disruption of the transmembrane mitochondrial potential (DeltaPsim) and DNA nuclear loss in transformed cell lines and in mitogen activated human T cells. This apoptotic pathway is biochemically different from the typical one induced by either ceramide or edelfosine where, in our system, the DeltaPsim dissipation precedes the generation of reactive oxygen species. Neither production of ROS nor apoptosis was found in capsaicin-treated resting T cells where the activity of the PMOR system is minimal when compared with mitogen activated or transformed T cells. Capsaicin also induces Ca2+ mobilization in activated but not in resting T cells. However, preincubation of cells with BAPTA-AM, which chelate cytosolic free calcium, did not prevent ROS generation or apoptosis induced by capsaicin, suggesting that ROS generation in capsaicin treated cells is not a consequence of calcium signaling and that the apoptotic pathway may be separated from the one that mobilizes calcium. Moreover, we present data for the implication of a possible vanilloid receptor in calcium mobilization, but not in ROS generation. These results provide evidence that the PMOR system may be an interesting target to design antitumoral and anti-inflammatory drugs.

Apoptosis↗