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Biomedical subjects

M Montes

Publications and source records attributed to M Montes.

At least 55 records · Page 3Linked to original sources

SDF-1-induced activation of ERK enhances HIV-1 expression.

Chemokine receptors are not only able to bind chemokines but, together with CD4, they serve as an entry door for the human immunodeficiency virus type 1 (HIV-1). The signalling capacity of chemokine receptors, which is of fundamental importance for chemokine-induced chemotaxis, is not used by HIV-1 to enter a target cell, nor by chemokines or chemokine-derived ligands to inhibit viral entry. In addition, an ill-defined signal triggered by chemokines can, under some circumstances, lead to an increase in HIV-1 expression. We show here that, in infected cells, exposure to SDF-1 leads to an increased expression of a X4 strain of HIV-1. A similar increase can be induced by an N-terminal peptide of SDF-1 which had previously been shown to elicit an intracellular calcium response and to inhibit the entry of X4 strains of HIV-1. We demonstrate the involvement of extracellular signal-regulated kinases (ERK) in this phenomenon. SDF-1 activates ERK-1 and ERK-2 in Jurkat cells. In HeLa cells, ERK-2 only is activated by SDF-1 or by a SDF-derived peptide. This ERK activation can be blocked by pertussis toxin and by the MEK inhibitor U0126. Most importantly, SDF-1-dependent HIV-1 expression is abolished by pretreating the cells with pertussis toxin or with U0126. The consequences of this SDF-1-induced, ERK-dependent modulation of HIV-1 expression in infected cells may have a clinical relevance for eradicating latent viruses.

Anti-HIV Agents↗

[Effects of competitive substrates ans insulin on glucose uptake and utilization in isolated perfused hearts of dyslipemic rats].

Rats chronically fed (15 weeks) a sucrose-rich diet (SRD) developed hypertriglyceridemia (hyperTg), increased plasma free fatty acids (FFA), impaired glucose homeostasis and insulin insensitivity. An increase of Tg and glycogen (Gly) in heart muscle was also observed. HyperTg with altered glucose metabolism could have profound effects on myocardial glucose utilization. To test this hypothesis male Wistar rats were fed a semi-synthetic SRD (w/w: 62.5% sucrose, 8% corn-oil, 17% protein), and the control group (CD) received the same semi-synthetic diet, except that sucrose was replaced with starch for 90 days. At that time, the hearts from these animals were isolated and perfused for 30 min in the presence or absence of insulin (30 mU/ml). Levels of the exogenous substrates were similar to those found in the plasma of the animal in vivo in both dietary groups (glucose 8.5 mM, palmitate 0.8 mM in SRD and glucose 5-5 mM, palmitate 0.3 mM in CD). In the absence of insulin glucose uptake was reduced (40%) and lactate release was increased (50%) in SRD hearts. Glucose oxidation was depressed mainly due to both, an increase of PDH kinase and a decrease of 60% of PDHa (active form of PDHc). Insulin in the perfusion medium improved only glucose uptake. The results suggest that at least two different mechanisms might contribute to insulin resistance and to impaired glucose metabolism in the perfused hearts of dyslipemic SRD fed rats: 1) reduced basal and insulin-stimulated glucose uptake and its utilization and 2) increased availability and oxidation of lipids (low PDHa and PDH kinase activities), which in turn decreased glucose uptake and utilization. Thus, this experimental model may be useful to study how impaired glucose homeostasis, increased plasma FFA and hyperTg could contribute to heart tissue malfunction.

Analysis of Variance↗

Stromal cell-derived factor-1alpha associates with heparan sulfates through the first beta-strand of the chemokine.

Biological properties of chemokines are believed to be influenced by their association with glycosaminoglycans. Surface plasmon resonance kinetic analysis shows that the CXC chemokine stromal cell-derived factor-1alpha (SDF-1alpha), which binds the CXCR4 receptor, associates with heparin with an affinity constant of 38.4 nM (k(on) = 2.16 x 10(6) M(-1) s(-1) and k(off) = 0.083 x s(-1)). A modified SDF-1alpha (SDF-1 3/6) was generated by combined substitution of the basic cluster of residues Lys(24), His(25), and Lys(27) by Ser. SDF-1 3/6 conserves the global native structure and functional properties of SDF-1alpha, but it is unable to interact with sensor chip-immobilized heparin. The biological relevance of these in vitro findings was investigated. SDF-1alpha was unable to bind in a CXCR4-independent manner on epithelial cells that were treated with heparan sulfate (HS)-degrading enzymes or constitutively lack HS expression. The inability of SDF-1 3/6 to bind to cells underlines the importance of the identified basic cluster for the physiological interactions of SDF-1alpha with HS. Importantly, the amino-terminal domain of SDF-1alpha which is required for binding to, and activation of, CXCR4 remains exposed after binding to HS and is recognized by a neutralizing monoclonal antibody directed against the first residues of the chemokine. Overall, these findings indicate that the Lys(24), His(25), and Lys(27) cluster of residues forms, or is an essential part of, the HS-binding site which is distinct from that required for binding to, and signaling through, CXCR4.

Animals↗

Incidence and risk factors for developing cytomegalovirus retinitis in HIV-infected patients receiving protease inhibitor therapy. Spanish CMV-AIDS Study Group.

OBJECTIVE: To assess the incidence and risk factors for cytomegalovirus (CMV) retinitis in HIV-infected patients who initiated protease inhibitor-containing antiretroviral therapy. DESIGN AND SETTING: Prospective, multicentre study. PATIENTS: A cohort of 172 HIV-infected patients with a CD4 cell count below 100x10(6) cells/l at the time of protease inhibitor introduction. MAIN OUTCOME MEASURES: Confirmed CMV retinitis and mortality, according to CD4 cell count, HIV load, and CMV viraemia. RESULTS: The cumulative incidence of CMV retinitis was 5% at 1 year and 6% at 2 years. Only a positive CMV polymerase chain reaction (PCR) test at therapy initiation was significantly associated with the development of disease (relative hazard, 4.41; 95% confidence interval, 2.12-8.93; P<0.00001). The 12-month Kaplan-Meier CMV retinitis event rate was 38% in patients who were CMV PCR-positive compared with 2% in those who were CMV PCR-negative (P<0.001). Mean CMV load was significantly higher in those individuals who went on to develop CMV retinitis (3700 versus 384 copies/ml, P = 0.002). Only 2% of patients remained CMV PCR-positive after 3 months of protease inhibitor therapy, and CMV viraemia was not associated with a worse therapy response or shorter survival. Transient CMV positivity without a higher risk of disease was observed in 7% of patients at the first month on therapy. CONCLUSIONS: Protease inhibitor-containing antiretroviral therapy significantly reduces the incidence of CMV viraemia and disease. Although a positive CMV PCR test identifies those patients on therapy at highest risk of CMV retinitis, it is not associated with an increased risk of death or a worse response to protease inhibitor therapy.

AIDS-Related Opportunistic Infections↗

Outcomes of retreatment after laser in situ keratomileusis.

OBJECTIVE: To evaluate the safety and efficacy of retreatment after myopic laser in situ keratomileusis (LASIK). DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: A total of 962 eyes of 566 patients underwent LASIK for up to -20.0 diopters (D) of myopia, of which 53 eyes (5.5%) were retreated. INTERVENTION: Retreatments were performed by lifting the original flap and using the Nidek EC-5000 excimer laser (Nidek Inc., Tokyo, Japan). MAIN OUTCOME MEASURES: Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BCVA), fogged manifest refraction, and complications were evaluated 6 months after retreatment. RESULTS: Overall, 53 (5.5%) of 962 eyes underwent LASIK retreatment. Before retreatment, the mean spherical equivalent (MSE) was -1.7 +/- 1.1 D (range, +0.3 to -5.0 D), UCVA ranged from 20/25 to 20/400, and BCVA ranged from 20/20 to 20/50. Six months after retreatment, the MSE was -0.09 +/- 0.29 D, 48 (90.6%) eyes were within +/-0.5 D, and all eyes were within +/-1.0 D of the attempted correction. The UCVA improved to 20/20 or better in 21 (39.6%) eyes and 20/40 or better in 51 (96.2%) eyes. The BCVA was maintained in 33 eyes (62.3%), 15 eyes (28.3%) gained 1 line or more of vision, whereas 5 eyes (9.4%) lost 1 line. All eyes had a BCVA of 20/50 or better. No retreated eye lost two or more lines of BCVA. No complications were observed. CONCLUSION: Retreatment for low amounts of residual myopia performed by lifting the original flap within the first year after surgery after myopic LASIK is safe, effective, and predictable.

Adolescent↗

Numerical taxonomy of gram-negative, facultative anaerobic bacteria isolated from skin of turbot (Scophthalmus maximus) and surrounding water.

A numerical taxonomic study of 473 gram negative heterotrophic facultative anaerobic bacteria isolated from skin of turbot (Scophthalmus maximus) and its culture water was performed. The study included 53 type and reference strains belonging to the genera Vibrio, Aeromonas and Listonella. The strains were characterized using 90 tests and data were examined by Simple Matching coefficient (S(SM)) and Jaccard coefficient (S(J)). UPGMA (unweighted pair group method, arithmetic average) defined 66 phena at S(SM) values > or = 84% and 27 groups at S(SM) > or = 80%. Six phena were defined as Vibrio albensis, V. (Listonella) anguillarum, V. splendidus biotype I, V. fischeri, V. ordalii and V. scophthalmi including reference strains. Some groups clustered different phena for one species, although others as the V. anguillarum related strains and inactive Vibro group required S(SM) > or = 84% to define species. More studies are necessary to identify the Vibrio spp. strains and to confirm some species identifications.

Animals↗

Characterization by numerical taxonomy and ribotyping of Vibrio splendidus biovar I and Vibrio scophthalmi strains associated with turbot cultures.

Twelve Vibrio strains were examined phenotypically in 91 biochemical characters and genotypically by ribotyping. Ten were isolated from sea water and two from diseased turbot (Scophthalmus maximus). All isolates originated from one experimental system located in Ría de Vigo (Galicia, north-west Spain). Different type strains were used for comparative purposes. The taxonomic position was analysed with the NTSYST-pc and similarities among strains were calculated by the Simple Matching coefficient (SSM). rRNA gene restriction patterns were performed with the HindIII enzyme. The SSM coefficient separated the 12 Vibrio strains into two groups which included strains that showed a SSM coefficient quite similar to V. splendidus biovar 1 (ATCC 33125) and V. scophthalmi (CECT 4638). None of 91 phenotypical characters were specific in distinguishing both species. The ribotyping confirmed the taxonomic classification of strains. The pathogenicity of each strain was evaluated; 10 environmental strains were avirulent and two, isolated from diseased turbot, were virulent. Different biotypes and ribotypes were found among the avirulent isolates. This work showed ribotyping to be a valuable tool for identification and confirmed the necessity of extending the ribotype database within closely related Vibrio species in order to clarify the taxonomic position.

Animals↗

Composition and antimicrobial activity of the essential oil of Peumus boldus leaves.

The composition and the antimicrobial activity of the essential oil from the leaves of Peumus boldus is investigated. Analyses of the oil obtained by hydrodistillation were carried out by GC and GC-MS using columns of two different stationary phases. Fractionation of the essential oil by column chromatography on silica gel was performed to improve identification of some constituents. More than 90% of the total oil (46 components) was identified, major constituents being monoterpenes (90.5%), among which limonene (17.0%), p-cymene (13.6%), 1.8-cineole (11.8%), and beta-phellandrene (8.4%) reached the highest percentages. Determination of the minimal bactericidal or fungicidal concentration against several microorganisms showed interesting activities towards Streptococcus pyogenes, Micrococcus sp., and Candida sp.

Anti-Infective Agents↗

Calcium responses elicited in human T cells and dendritic cells by cell-cell interaction and soluble ligands.

The interactions between a human CD4+ T cell clone and monocyte-derived human dendritic cells (DC) were analyzed with an imaging system. The first question addressed was the relationship between the formation of a contact zone and the triggering of a Ca2+ response in the T cells, in the presence or absence of antigen. Interaction of T cells with DC pulsed with the antigen led to the formation of a stable contact zone, followed by the appearance in the T cells of large and sustained Ca2+ oscillations. In the absence of antigen, contact zones formed normally and, surprisingly, Ca2+ responses were also observed, characterized by rare and small transients. Antigen-independent Ca2+ responses were not MHC restricted. The possible influence of Ca2+ responses in the DC on the efficiency of antigen presentation was then Investigated. In DC, Ca2+ responses can be elicited by a variety of stimuli: cell adhesion, platelet-activating factor, UTP and chemotactic molecules (formyl-Met-Leu-Pro, RANTES, MIP-1beta and SDF-1alpha). Importantly, Ca2+ responses were also induced in approximately 30% of DC as a result of their interaction with T cells. However, the efficiency of antigen presentation (as judged by the percentage of T cells presenting a Ca2+ response) was independent of the Ca2+ level in DC. Thus, imaging the interactions between human T cells and DC led us to observe two novel phenomena: DC-induced but antigen-independent Ca2+ responses in T cells and T cell-induced Ca2+ responses in DC.

Antigen Presentation↗

A Brunner's gland adenoma as a cause of anemia.

Benign tumors of the small bowel are rare. They present with many different manifestations depending on the size and location, and also cause a variety of symptoms that are often nonspecific. These include abdominal pain, dyspepsia, nausea, vomiting, and gastrointestinal bleeding that may be melena or hematemesis. Most of the time patients are asymptomatic and the lesions are discovered as an incidental finding. When bleeding occurs, and it may be severe in certain situations, the patient may develop signs of anemia, such as dyspnea, fatigue, and even high-output cardiac failure. The authors present a patient who was evaluated for melena and who was found to have a duodenal polyp that proved to be a Brunner's gland adenoma on pathology.

Adenoma↗

Dissociation of the signalling and antiviral properties of SDF-1-derived small peptides.

BACKGROUND: The chemokine receptor CXCR4 (a receptor for the Cys-X-Cys class of chemokines) is a CD4-associated coreceptor for T-cell-tropic strains of human immunodeficiency virus 1 (HIV-1) and represents a target for antiviral therapy. Infection by T-tropic HIV-1 can be blocked by stromal-cell-derived factor-1 (SDF-1), the natural ligand of CXCR4. The broad variety of cells expressing CXCR4 and the perturbations observed in mice deficient for SDF-1 suggest that antiviral compounds antagonizing the signalling activity of CXCR4 might have severe side effects in vivo. Compounds that interfere selectively with HIV entry and not with SDF-1 signalling would therefore be useful. RESULTS: A series of peptides, each of 13 residues, spanning the whole SDF-1alpha sequence were tested for their ability to block HIV-1 infection. The antiviral and signalling properties of SDF-1 were retained by a peptide corresponding to its amino terminus. Removal of the first two residues resulted in an antiviral antagonist of the SDF-1-CXCR4 signalling pathway. We prepared 234 single-substitution analogues and identified one antiviral analogue that had drastically reduced agonistic or antagonistic properties. The antiviral peptides competed with the monoclonal antibody 12G5 for CXCR4 binding. Their antiviral activity seems to be due to receptor occupancy rather than induction of receptor endocytosis. CONCLUSIONS: The amino terminus of the SDF-1 chemokine is sufficient for signal transduction via CXCR4 and for inhibition of HIV-1 entry, but these activities could be dissociated in a peptide analogue. This peptide represents a lead molecule for the design of low molecular weight antiviral drugs.

Amino Acid Sequence↗

Emergence of Streptococcus pyogenes strains resistant to erythromycin in Gipuzkoa, Spain.

The aim of this study was to determine the evolution of resistance to macrolides and other antibiotics in strains of Streptococcus pyogenes isolated in the province of Gipuzkoa, Spain. During the period 1984-1996, all 2561 strains of Streptococcus pyogenes studied showed full susceptibility to penicillin. Until 1990, only 1.2% of Streptococcus pyogenes isolates were resistant to erythromycin. Since then, resistance to erythromycin increased every year until 1995, when 34.8% (87/250) of Streptococcus pyogenes strains were found to be resistant. In 1996 the rate of resistance to erythromycin was 17.8% (75/422). During the study period, 96.1% (246/256) of the Streptococcus pyogenes isolates resistant to erythromycin were susceptible to clindamycin. Of the remaining erythromycin-resistant Streptococcus pyogenes strains, resistance to clindamycin was constitutive in seven strains and inducible in three. When investigated by the polymerase chain reaction (PCR), all Streptococcus pyogenes strains resistant to erythromycin and susceptible to clindamycin showed the 1.4 kb fragment of the mefA gene, recently described as the novel macrolide-efflux-resistance determinant. The most frequent T-agglutination patterns among Streptococcus pyogenes resistant to erythromycin were T4 and T8,25. The emergence and rapid spread of erythromycin-resistant Streptococcus pyogenes in Gipuzkoa and its relationship to the presence of the mefA gene are described.

Agglutination↗

Regression and its mechanisms after laser in situ keratomileusis in moderate and high myopia.

OBJECTIVE: The purpose of the study was to evaluate the degree and mechanism of regression after laser in situ keratomileusis (LASIK) on moderate to highly myopic eyes during the first postoperative year. DESIGN: A prospective, single-center, clinical trial. PARTICIPANTS: A total of 52 eyes of 38 patients were entered in the study; 47 eyes had complete data available at each postoperative visit. INTERVENTION: The intervention was LASIK using the microkeratome to create an 8.5- to 9.0-mm diameter, 130- to 160-micron-thick flap. A spherical midstromal multizone ablation (inner zone, 4.5 mm; outer zone, 5.5-6.0) was then performed using the Summit OmniMed excimer laser (Summit Technology, Inc, Waltham, MA). The mean preoperative refraction was -14.02 diopters (D). Retreatment for undercorrection and regression was performed between postoperative months 3 and 6 on 13 eyes. MAIN OUTCOME MEASURES: Manifest spherical equivalent, mean central corneal power, and central corneal thickness were the parameters measured. RESULTS: At 3 months, follow-up data were available on 47 eyes. The mean refractive regression was -1.07 D (7.6%) from the first week to the third month. During the first postoperative year, the mean regression of manifest spherical equivalent (MSE), increase in corneal power, and increase in corneal thickness were symmetric in magnitude and time course for the 34 eyes that did not require retreatment (-0.96 D, +1.03 D, and 15 microns, respectively). CONCLUSION: Early regression of refractive effect after LASIK appears to be a consequence of an increase in corneal thickness associated with central corneal steepening. No evidence of progressive corneal ectasia was observed during the first year of follow-up. Longer follow-up is required to confirm these trends.

Adult↗

High seroprevalence of Coxiella burnetii infection in Eastern Cantabria (Spain).

BACKGROUND: Coxiella burnetii is the causative agent of Q fever, a worldwide zoonosis which shows a wide diversity of clinical manifestations. The objective of this seroepidemiological study was to estimate the prevalence of antibodies to C. burnetii in a representative population of the Eastern area of the Cantabrian Community (Northern Spain). METHODS: A cross-sectional study was conducted in 595 subjects from Eastern Cantabria. Four different zones (one urban and three rural zones) were defined according to the geographical characteristics of the area and the economic activities of the population. The population sample for this study was collected between December 1994 and March 1995, and was stratified by age, sex and municipality of residence. IgG and IgM antibodies against C. burnetii were assayed by an indirect immunofluorescence technique. RESULTS: The prevalence of anti-phase II Coxiella IgG (titre > or = 1:16) was 48.6% (95% confidence interval: 44.6-52.6%), with 81.3% havinga titre of > or = 1:64. The prevalence of IgG increased with age, ranging from 12.0% in people < 15 years to 70.3% in those > 65 years (P < 0.001). The antibody detection rate was higher in males (53.6%) than in females (43.3%) (P < 0.01). The prevalence of anti-phase II Coxiella IgG was less among subjects living in the urban zone (32.8%) than in those living in the other three rural zones: the two situated on the coast (54.0% and 54.9% respectively) and the inner mountainous zone (82.3%) (P < 0.001). CONCLUSIONS: The prevalence of C. burnetii infection observed in this study is one of the highest reported in Europe. The eastern area of Cantabria is a hyperendemic area for Q fever.

Adolescent↗

Erythromycin resistance of Streptococcus pyogenes in Madrid.

BACKGROUND: Erythromycin is considered to be an adequate alternative to penicillin for patients who are allergic to penicillin. Erythromycin-resistant Streptococcus pyogenes strains have been reported in some parts of the world. METHOD: The in vitro activity of erythromycin and other antimicrobial agents was determined in a total of 1310 clinical Streptococcus pyogenes isolates collected in the city of Madrid from January, 1993, through December, 1996. RESULTS: All strains showed susceptibility to penicillin, rifampin, vancomycin and chloramphenicol. Tetracycline resistance was 8.5%. In 36 of the strains (2.7%) MIC was 4 microg/ml for ofloxacin. Clindamycin resistance was observed in only 18 strains (1.4%); this resistance was constitutive in 15 and inducible in 3 strains. Resistance to erythromycin was observed in 14.3% of the strains, showing an increase during the study period (2.0% in 1993 vs. 22.4% in 1996; chi square for linear trend 68.8, P < 0,0001); >90% of them showed the novel resistance phenotype described by Seppälä et al. and 32 of 32 of these strains showed by PCR the 1.4-kb fragment of the mefA gene recently described as the novel macrolide efflux resistance determinant. The erythromycin-resistant strains were isolated more often in pediatric patients (144 of 872) than in adults (44 of 438) (chi square 9.9, P = 0.0016). CONCLUSION: The study emphasizes the need to screen for resistance to macrolides in S. pyogenes and indicates that resistance to erythromycin in S. pyogenes has increased significantly in Madrid.

Adolescent↗

Distribution of HLA class II alleles among Spanish patients with pemphigus vulgaris.

Twenty-six unrelated Spanish Caucasian individuals affected by pemphigus vulgaris (PV) were HLA typed and frequencies compared with those of 200 ethnically matched healthy controls. Twenty-three out of 26 patients were HLA-DR4. The frequency of HLA-DR14 was also increased (31%; controls: 4%). Of the 23 patients positive for HLA-DR4, 21 carried the DRB1*0402 allele. Therefore, the frequency of HLA-DRB1*0402 among patients was 81% (4% in controls; P=4.7x10(-27), OR=100.8). Interestingly, HLA-DR13, a frequent HLA-DR specificity in the Spanish general population (27%), was absent among the PV patients (P=0.009; Pc=0.1; OR=0.05). Taking together these data, we can conclude that, in the Spanish population, PV is preferentially and strongly associated with HLA-DRB1*0402, whereas DRB1*13 seems to confer a protective effect in our population.

Alleles↗