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Biomedical subjects

M Suárez

Publications and source records attributed to M Suárez.

At least 37 records · Page 2Linked to original sources
PubMed2000

SmcL, a novel membrane-damaging virulence factor in Listeria.

We describe here the fourth listerial membrane-damaging virulence factor, a sphingomyelinase C (SMase) that is produced specifically by the ruminant pathogen Listeria ivanovii. Its coding gene, smcL, is a monocistron expressed independently of PrfA. The smcL product, SmcL, is highly similar to the staphylococcal beta-toxin and is responsible for the differential hemolytic properties of L. ivanovii (bizonal hemolysis and CAMP-like reaction with R. equi). The role of SmcL in virulence was assessed by gene disruption and complementation. Our data show that SmcL mediates disruption of the membrane of primary phagosomes, thereby promoting bacterial intracellular proliferation. They also suggest that SmcL may play a role in host tropism. smcL is located in LIPI-2, a novel 18-kb pathogenicity island which also contains a cluster of internalin genes. LIPI-2 is unstable, L. ivanovii-specific and required for full virulence in mice and lambs.

Amino Acid Sequence↗
PubMed2000

Promoting social competence in deaf students: the effect of an intervention program.

The aim of this study was to determine the effects of a social skills training program on the social skills and social behaviors of deaf children in a mainstream setting. The study used a pretest/posttest design. The participants consisted of 18 severely and profoundly hearing-impaired children (ages ranged from 9;1 to 13;6) who were enrolled in three elementary schools in the Canary Islands. Results indicated that the intervention succeeded in improving students' social problem-solving skills, especially in making comprehensible the steps implied in the solution of interpersonal problems; the intervention also led to significant improvement of deaf students' assertive behavior as rated by their teachers and by themselves. Significant differences in social or academic integration as judged by companions in a sociometric questionnaire were not found.

Journal Article↗
PubMed2000

Peripubertal prolactinomas: clinical presentation and long-term outcome with different therapeutic approaches.

UNLABELLED: The evolution of prolactinomas in children and adolescents continues to be controversial. We report on the long-term evolution (2-20 yr) of prolactinomas in 40 patients (29 F, 11 M). In females, the age for the onset of symptoms ranged between 8 and 16 yr and the age at which diagnosis was made ranged from 15 to 19 yr; in males, ages ranged from 8 to 17 yr and from 13.8 to 19 yr, respectively. In females, there was predominance of microprolactinomas (22/ 29) and the symptomatology resulted from functional disorders, whereas in males there was predominance of macroprolactinomas (8/11) and symptoms were caused by tumor mass disorders. Surgery was used as primary therapy in nine patients and as supplemental therapy in six patients. Twenty-four patients were treated primarily with bromocriptine and seven with cabergoline. Of the nine patients treated primarily with surgery, only one achieved gonadotropic axis restoration; in 25/31 patients receiving drug therapy gonadotropic function was restored to normal. Fifteen patients showed complete resolution or substantial shrinkage of tumor. CONCLUSION: In pediatric and adolescent age, there seem to be age- and sex-dependent differences in the clinical presentation of prolactinomas that cannot be accounted for only in terms of time of evolution. Drug therapy can control the disease, normalize prolactin levels and achieve gonadotropic axis restoration in most patients.

Adolescent↗
PubMed2000

[Usefulness of spect with 99mTc-tetrofosmin and stimulus with dipyridamole in patients with left bundle branch block of His].

BACKGROUND: In patients with left bundle branch block, the 201Tl scintigraphic studies show high sensitivity, but with low specificity, in the diagnosis of coronary artery disease. OBJECTIVE: [corrected] To assess the value of 99mTc-tetrofosmin Single Photon Emission Computed Tomography (SPECT) and dipyridamole administration in patients with left bundle branch block. METHODS: 22 patients with angina and left bundle branch block were retrospectively studied by cardiac catheterization and Tc-Tf after dipyridamole administration (0,142 mg/kg/min. i.v.) and at rest. RESULTS: The mean number of territories with perfusion defects was 1.5+/-1.0, and the average number of diseased vessels in the coronariographic study was 1.6+/-1.3 (r = 0.77, p<0.001). Sensitivity, specificity, positive predictive value, negative predictive value, total predictive value and Kappa index in the diagnosis of multivessel disease were 92%, 90%, 92%, 90%, 91% and 0.82, respectively. In the diagnosis of anterior descending artery disease, these values were 83%, 70%, 77%, 78%, 77%, and 0.54, respectively. CONCLUSION: In patients with angina and left bundle branch block, SPECT with Tc-Tf-dipyridamole is of great value in the study of coronary artery disease extension. Sensitivity and specificity for the diagnosis of anterior descending artery disease were similar to that shown in series with thallium-dipyridamole.

Bundle of His↗
PubMed1999

The smcL gene of Listeria ivanovii encodes a sphingomyelinase C that mediates bacterial escape from the phagocytic vacuole.

The ruminant pathogen Listeria ivanovii differs from Listeria monocytogenes in that it causes strong, bizonal haemolysis and a characteristic shovel-shaped co-operative haemolytic ('CAMP-like') reaction with Rhodococcus equi. We cloned the gene responsible for the differential haemolytic properties of L. ivanovii, smcL. It encodes a sphingomyelinase C (SMase) highly similar (> 50% identity) to the SMases from Staphylococcus aureus (beta-toxin), Bacillus cereus and Leptospira interrogans. smcL was transcribed monocistronically and was expressed independently of PrfA. Low-stringency Southern blots demonstrated that, within the genus Listeria, smcL was present only in L. ivanovii. We constructed an smcL knock-out mutant. Its phenotype on blood agar was identical to that of L. monocytogenes (i.e. weak haemolysis and no shovel-shaped CAMP-like reaction with R. equi ). This mutant was less virulent for mice, and its intracellular proliferation was impaired in the bovine epithelial-like cell line MDBK. The role of SmcL in intracellular survival was investigated using an L. monocytogenes mutant lacking the membrane-damaging determinants hly, plcA and plcB, being thus unable to grow intracellularly. Complementation of this mutant with smcL on a plasmid was sufficient to promote bacterial intracellular proliferation in MDBK cells. Transmission electron microscopy showed that SmcL mediates the disruption of the phagocytic vacuole and the release of bacteria into the cytosol. Therefore, L. ivanovii possesses a third phospholipase with membrane-damaging activity that, together with PlcA and PlcB, may act in concert with the pore-forming toxin Hly to mediate efficient escape from the vacuolar compartment. The 5' end of smcL is contiguous with the internalin locus i-inlFE, which is also specific to L. ivanovii and is required for full virulence in mice. Thus, smcL forms part of a novel virulence gene cluster in Listeria that is species specific.

Amino Acid Sequence↗
PubMed1999

Synthesis and antiprotozoan properties of new 3,5-disubstituted-tetrahydro-2H-1,3,5-thiadiazine-2-thione derivatives.

In a search for antiprotozoan compounds, 34 new 3,5-disubstituted-tetrahydro-2H-1,3,5-thiadiazine-2-thione derivatives were synthesized and tested in vitro against Trypanosoma cruzi and Trichomonas vaginalis. Some of them showed important antiprotozoan activity. In vivo assays of compounds which showed remarkable in vitro activity against T. vaginalis were carried out.

Animals↗
PubMed1999

Medullo adrenal response to lesion of anterodorsal thalamic nuclei in rats.

Anterodorsal thalamic nuclei (ADTN) exert an inhibitory influence on hypophyso-adrenal system (HAS) in rats. With the purpose of evaluating if ADTN are also involved in the control of medullo adrenal activity, experiments were conducted on female rats with bilateral lesion of these nuclei. Thirty days after lesion, plasma epinephrine (E) concentration in lesioned rats was higher than that in sham-lesioned control group (P < 0.02). Meanwhile, adrenal E content was significantly lower in lesioned animals than that found in the control group (P < 0.005). Plasma norepinephrine (NE) values in lesioned rats were not significantly different from those in the control ones, however, there was a significant decrease in adrenal NE when compared to the control one (P < 0.02). Basal values of plasma ACTH and plasma and adrenal corticosterone (C) were signicantly higher than those in sham lesioned rats (P < 0.05; P < 0. 001; P < 0.001 respectively). These findings demonstrate that the ADTN in rats are involved in the regulation of both cortico and medullo adrenal activity.

Adrenal Medulla↗
PubMed1999

[Clinical course of cytomegalovirus infection in renal transplant recipients].

BACKGROUND: The incidence of cytomegalovirus infection or reactivation is 8 times more frequent in transplant recipients than in the general population. AIM: To evaluate the prevalence and usefulness of different diagnostic techniques for cytomegalovirus infection in renal transplant recipients. PATIENTS AND METHODS: Twenty nine renal transplant recipients were followed for at least five months. Cytomegalovirus infection was assessed by the presence of serum antibodies against the virus using ELISA and viral detection in urine and lymphocytes, using classical viral isolation, shell vial assay, and detection of viral genome by polymerase chain reaction. RESULTS: Prior to transplantation, 23 of 27 patients had IgG type anti cytomegalovirus antibodies. In 40%, IgM type antibodies were detected in some moment of the follow up. Three of these corresponded to seroconversion. Cytomegalovirus was detected in urine in 41% of patients and it was not detected in lymphocytes. Shell vial assay detected the virus in 5 of 13 urine samples and in 1 of 7 lymphocyte samples. Polymerase chain reaction was positive in 12 of the 29 patients. In six patients, an acute rejection was postulated and there was no relation of rejection episodes with viral detection. In two patients, a disease caused by cytomegalovirus was postulated. One of these patients had a seroconversion during follow up. CONCLUSIONS: The prevalence of positive serum indices of cytomegalovirus infection was similar to that reported in the general population. However, the frequency of reactivation and viral disease was lower than that reported elsewhere. The techniques used in this study can be useful to confirm the suspicion of cytomegalovirus disease. However they do not predict the occurrence or evolution of the disease caused by the virus nor viral reactivation in renal transplant recipients.

Adolescent↗
PubMed1999

[Preventing HIV infection: an exercise in evaluating scientific evidence in public health].

BACKGROUND: Evidence-based medicine (EBM) analyses scientific evidence for the efficacy/effectiveness of health interventions. It aims to identify and implement available interventions that have proved to be the best. This concept is now soundly established for clinical interventions, but just breaking for prevention, particularly when--as in HIV infection--transmission is associated to private behaviour. METHODS: A search for studies evaluating the effects of HIV prevention interventions. All studies were critically evaluated. RESULTS: Relevant evidence for the effects of the main specific HIV prevention interventions is reviewed, according to transmission group and study design, focusing on its methodological strength and weakness, and paying special attention to experimental research. CONCLUSIONS: A wider debate on scientific evidence for public health interventions is proposed, trying to promote feasible and efficient EBM methods in HIV prevention research.

Adult↗
PubMed1999

Influence of anterodorsal thalamic nuclei on the hypophyseal-adrenal axis and cardiac beta receptors in rats submitted to variable chronic stress.

The limbic structures play an important role in the control of the neuroendocrine and sympathical adrenal function in basal and stress conditions. This work was undertaken to evaluate plasma ACTH, adrenocortical activity, cardiac adrenoceptors density and affinity response to variable chronic stress (VCS) in anterodorsal thalamic nuclei (ADTN) lesioned rats. Thirty days after lesion, shamlesioned stressed animals increased plasma ACTH and corticosterone as compared to sham-lesioned unstressed animals (p < 0.05); lesioned rats increased ACTH levels after VCS (p < 0.05) as compared to unstressed-lesioned rats. Whereas in sham-lesion plasma corticosterone (C) increased after stress, in lesioned animals(C) remained unchanged as compared to unstressed-lesioned animals. In the stressed groups, adrenal C contents were below those found in unstressed rats. beta-receptors affinity, in all the experimental groups, was similar, but VCS sham-lesioned animals underwent a significant increase in cardiac D-adrenergic receptors density when compared with basal and lesioned groups (P < 0.001). Our findings would demonstrate that the increment in cardiac beta adrenoceptors density appears as a consequence of the increase in ACTH, plasma corticosterone and sympathetic response provoked by chronic stress situations. ADTN lesion attenuated this hipophisoadrenal system response to chronic stress as well as the above mentioned cardiac beta adrenoceptors density increment.

Adrenocorticotropic Hormone↗
PubMed1998

The bovine IFN-omega 1 is biologically active and secreted at high levels in the yeast Pichia pastoris.

The gene coding for bIFN-omega 1 was isolated from bovine genomic DNA by polymerase chain reaction (PCR). Recombinant bIFN-omega 1 was expressed in the yeast Pichia pastoris and high levels of the recombinant protein (0.4 mg ml-1) were secreted to the culture media. The obtained bIFN-omega 1 showed a cross-species antiviral activity on four mammalian cell lines of calf, pig, hamster and human origin, but this activity was absent on Madin-Darby canine kidney (MDCK) cells. A delivery carrier was developed to permit a better release of bIFN-omega 1. When compared with a control group, an increase in 6 days in the corpus luteum lifespan was obtained in cyclic ewes following three interferon (IFN) intrauterine administrations on days 9, 10 and 11 post-estrus. In summary, these results demonstrated for the first time that biologically active recombinant bIFN-omega 1 was highly secreted by P. pastoris showing antiviral activity in different cell lines and an antiluteolytic effect in cyclic ewes, with no detrimental effects on the animals.

Amino Acid Sequence↗
PubMed1998

Involvement of the anterodorsal thalami nuclei on the hypophysoadrenal response to chronic stress in rats.

Anterodorsal thalami nuclei (ADTN) exert an inhibitory influence on the hypophysoadrenal system (HAS) under basal and acute stress conditions; however, after chronic stress, the effect is different. The response to chronic immobilization stress (IMO) (forced immobilization for 15 min/day for 12 days) and variable chronic stress (V) (24-day exposure to different stressors per day) of plasma ACTH and corticosterone (C) in rats with anterodorsal thalami nuclei lesions was studied. In sham-lesioned rats, chronic immobilization stress and variable chronic stress induced a significant increase in plasma ACTH and C and a reduction of adrenal C content. After exposure of lesioned rats to chronic immobilization stress, there was a decrease of plasma ACTH compared to that in unstressed lesioned rats. In contrast, there was significant increase in ACTH levels after variable chronic stress, this increase being smaller than the variable increase elicited in sham-lesioned rats. In all stressed lesioned animals, plasma C remained unchanged. However, adrenal C content decreased significantly compared to that in unstressed lesioned rats. These findings demonstrate that anterodorsal thalami nuclei lesions attenuated the hypophysoadrenal system response to chronic stress. These data are in contrast to those obtained in previous studies under basal and acute stress conditions. The reason for this discrepancy is at present unknown, and its elucidation will require further studies.

Adaptation, Physiological↗
PubMed1998

Molecular mechanisms of Salmonella invasion: the type III secretion system of the pathogenicity island 1.

Salmonella spp. are facultative intracellular pathogens which are able to enter into non-phagocytic cells as an essential step in their pathogenic life cycle. The majority of the molecular determinants involved in this entry process are encoded in a pathogenicity island located at the centisome 63 of the bacterial chromosome, and belong to a specialized protein secretion system termed "type III" or "contact-dependent". This secretion system is used by Salmonella spp. and several other bacterial pathogens to translocate bacterial effector proteins into the eukaryotic cell. Thus, a bidirectional biochemical cross-talk with the host cell is initiated, which leads to several responses such as membrane ruffling, bacterial internalization and the activation of various transcription factors.

Bacterial Proteins↗
PubMed1997

Glucose-1-phosphate utilization by Listeria monocytogenes is PrfA dependent and coordinately expressed with virulence factors.

Virulence genes of the facultative intracellular pathogen Listeria monocytogenes are coordinately regulated by the activator protein PrfA, encoded by prfA, a member of the cyclic AMP receptor protein family of bacterial transcription factors. We found that prfA* mutants that constitutively overexpress the virulence regulon due to a Gly145Ser substitution in PrfA (M.-T. Ripio, G. Domínguez-Bernal, M. Lara, M. Suárez, and J.-A. Vázquez-Boland, J. Bacteriol. 179:1533-1540, 1997) rapidly utilized glucose-1-phosphate (G-1-P) as a carbon source for growth, in contrast to wild-type strains, which characteristically do not. Wild-type strains acquired the capacity for readily metabolizing G-1-P upon exposure to environmental conditions that activate the expression of prfA and PrfA-dependent virulence genes (i.e., culture at 37 degrees C in charcoal-treated medium). In these strains, G-1-P utilization followed an expressional pattern identical to that of virulence genes controlled by PrfA, with repression at 20 degrees C. Tn917 insertions in L. monocytogenes mutants selected for G-1-P utilization deficiency mapped to the plcA-prfA operon, a deltaprfA strain was totally unable to utilize G-1-P, and trans complementation with prfA constructs restored the ability to efficiently metabolize and grow on G-1-P to these mutants. Thus, G-1-P utilization by L. monocytogenes is under the tight positive control of the central virulence regulator, PrfA, and is coexpressed with PrfA-dependent pathogenicity determinants. It was recently reported that readily utilized carbohydrates, such as glucose or cellobiose, repress virulence genes in L. monocytogenes. We confirmed this but, interestingly, found that G-1-P does not inhibit expression of the PrfA regulon, indicating that this sugar follows a catabolic pathway that bypasses the repressor mechanism triggered by other readily metabolized carbon sources. PrfA dependence and coexpression with virulence genes suggest that utilization of exogenous G-1-P may be relevant to Listeria pathogenesis. G-1-P is the precursor metabolite and primary degradation product of glycogen and is therefore available within the mammalian cell. Based on our results, we hypothesize that G-1-P could play an important role as a growth substrate for intracellular Listeria.

Amino Acid Substitution↗
PubMed1997

A Gly145Ser substitution in the transcriptional activator PrfA causes constitutive overexpression of virulence factors in Listeria monocytogenes.

Virulence genes in Listeria monocytogenes are coordinately expressed under the control of the transcriptional activator PrfA, encoded by prfA, a member of the cyclic AMP (cAMP) receptor protein (CRP)/FNR family of bacterial regulators. Strain P14-A is a spontaneous mutant of L. monocytogenes serovar 4b which produces elevated levels of virulence factors (M. T. Ripio, G. Domínguez-Bernal, M. Suárez, K. Brehm, P. Berche, and J. A. Vázquez-Boland, Res. Microbiol. 147:371-384, 1996). Here we report that P14-A and other variant strains with the same phenotype carry a point mutation in codon 145 of prfA, leading to a Gly-->Ser substitution. trans-complementation experiments with PrfA-deficient mutants demonstrated that the Gly145Ser prfA allele causes overexpression of virulence factors in L. monocytogenes, to the levels found in the virulence factor-overexpressing variants. In strain P14-A with a chromosomal Glyl45Ser prfA background, transcription of prfA and of PrfA-dependent virulence genes remained constitutively high under culture conditions in which virulence factor expression is downregulated in wild-type L. monocytogenes. The Glyl45Ser substitution is located in a PrfA stretch (residues 141 to 151) showing high sequence similarity to the D alpha-helix of CRP. Interestingly, well-characterized crp* mutations, which make CRP functionally active in the absence of cAMP, map in this region (i.e., Gly141Ser and Ala144Thr substitutions). By analogy with the CRP model, the phenotype conferred to L. monocytogenes by the Gly145Ser substitution in PrfA could be due to the mutant regulatory protein being locked in a transcriptionally active, cofactor-independent conformational state. Our observations allow the construction of a model for PrfA-dependent virulence gene regulation in which the levels of virulence factor expression depend primarily on the conformational state of the PrfA protein, which alternates between active and inactive forms according to its interaction with an environmentally regulated signal molecule or cofactor.

Amino Acid Sequence↗