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Biomedical subjects

J L Martínez

Publications and source records attributed to J L Martínez.

At least 19 recordsLinked to original sources

Pressure induced effects on the Fermi surface of superconducting 2H-NbSe2.

The pressure dependence of the critical temperature T(c) and upper critical field H(c2)(T) has been measured up to 19 GPa in the layered superconducting material 2H-NbSe2. T(c)(P) has a maximum at 10.5 GPa, well above the pressure for the suppression of the charge density wave (CDW) order. Using an effective two-band model to fit H(c2)(T), we obtain the pressure dependence of the anisotropy in the electron-phonon coupling and Fermi velocities, which reveals the peculiar interplay between CDW order, Fermi surface complexity, and superconductivity in this system.

Journal Article↗

Crystal and magnetic structure of the double perovskite Sr2CoUO6: a neutron diffraction study.

Sr2CoUO6 double perovskite has been prepared as a polycrystalline powder by solid-state reaction, in air. This material has been studied by X-ray, neutron powder diffraction (NPD) and magnetic measurements. At room temperature, the crystal structure is monoclinic, space group P2(1)/n, Z= 2, with a= 5.7916(2), b= 5.8034(2), c= 8.1790(3) A, beta= 90.1455(6)degrees. The perovskite lattice consists of a completely ordered array of CoO6 and UO6 octahedra, which exhibit an average tilting angle phi= 11.4 degrees. Magnetic and neutron diffraction measurements indicate an antiferromagnetic ordering below TN = 10 K. The low-temperature magnetic structure was determined by NPD, selected among the possible magnetic solutions compatible with the P2(1)/n space group, according with the group theory representation. The propagation vector is k= 0. A canted antiferromagnetic structure is observed below TN = 10 K, which remains stable down to 3 K, with an ordered magnetic moment of 2.44(7)mu(B) for Co2+ cations. The magnetic moment calculated from the Curie-Weiss law at high temperatures (5.22 mu(B)/f.u.) indicates that the orbital contribution is unquenched at high temperatures, which is consistent with high-spin Co2+((4)T(1g) ground state) in a quasi-regular octahedral environment. Magnetic and structural features are consistent with an electronic configuration Co2+[3d(7)]-U6+[Rn].

Journal Article↗

[A study of clinical response to antibiotic treatment in subjects with chronic bacterial prostatitis].

A study was carried out on the clinical response to antibiotics in 105 patients with chronic bacterial prostatitis. Two groups of patients were compared in a retrospective study. The results of rectal examination, ultrasound scan, microbiological analysis, and response to different antibiotic therapy regimens were compared. There was a high incidence of perineal-testicular pain and sexual potency reduction; prostate congestion and pain on rectal examination were frequently reported. All the patients had positive microbial cultures, with Gram-negative microorganisms being predominantly isolated. Following the administration of different antibiotic therapy regimens, symptoms either disappeared or diminished, irrespective of whether positive cultures remained. A poorer clinical response was observed in patients with positive prostate ultrasound and rectal examination, and with isolated Gram-negative bacilli. No differences were observed between either group in clinical response to different antimicrobial regimens.

Adult↗

Finding universal correlations between cationic disorder and low field magnetoresistance in FeMo double perovskite series.

We search for general patterns that explain the low field magnetoresistance at low temperatures in the system A(2-x)A'xFeMoO6. The observed linear dependence of the low field magnetoresistance with the saturation magnetization for the series is related to the antisite disorder at the Fe and Mo sites. This is explained in terms of a spin dependent crossing of intragranular barriers originated from the presence of antiferromagnetic SrFeO3 patches that naturally develop when antisite disorder occurs in the double perovskite. The presence of a moderate level of antisite disorder is at the very root of low field magnetoresistance although effects such as disorder distribution, connectivity, or morphology add their contribution.

Journal Article↗

Time course of serum hepatitis C virus-RNA during chronic hepatitis C treatment accurately predicts the type of response.

AIM: To establish the value of alanine aminotransferase normalization and hepatitis C virus-RNA clearance as predictors of sustained virological response in naïve and relapser chronic hepatitis C patients on mono or combination therapy. METHODS: A total of 282 hepatitis C patients were studied: 98 naïves on interferon, and 64 naïves and 75 relapsers on interferon plus oral ribavirin; 45 patients were excluded. Drugs were administered at standard doses for 12 months. Alanine aminotransferase and hepatitis C virus-RNA were determined at baseline and at weeks 4, 12, 24, 48, and at 72 and 96 weeks after completion of therapy. RESULTS: The rate of sustained response was greater (P < 0.05) in naïves and relapsers on combination therapy (33% and 48%, respectively) than in naïves on interferon alone (16%). Hepatitis C virus-RNA significantly decreased from baseline by week 4 in naïves on interferon and relapsers on combination therapy and by week 12 in naïves on combination therapy. Alanine aminotransferase levels paralleled viremic load in naïves on interferon, yet in patients on combination therapy, alanine aminotransferase normalized independently of the virological response. During treatment, the main factor associated with sustained response was hepatitis C virus-RNA clearance by week 4 in naïves on interferon and relapsers on combination therapy, and by week 24 in naïves on combination therapy. CONCLUSION: Clearance of viraemia constitutes the best predictor of a sustained response to therapy, but needs to be measured at patient-specific times.

Adult↗

Frequency and determinants of microalbuminuria in mild hypertension: a primary-care-based study.

OBJECTIVE: To evaluate the frequency of microalbuminuria and its relationship with several risk factors and left ventricular mass in a population of mildly hypertensive subjects attended in a primary-care setting. DESIGN: Cross-sectional study. SETTING: Eight primary-care centres. PATIENTS: Two hundred and twenty-three non-diabetic patients recently diagnosed with mild hypertension were included in the study. None of them had clinical evidence of target-organ damage or had received prior antihypertensive treatment. INTERVENTIONS: Subjects included in the study underwent clinical interview, measurement of blood pressure (BP) on three visits, blood analysis, measurement of albumin by immunonephelometry in three overnight urine collections, 24 h BP monitoring and M-mode and Doppler echocardiography. MAIN OUTCOME MEASURES: Tobacco habit, clinic BP, body mass index, serum lipids and uric acid, glycaemia, urinary albumin excretion (UAE), ambulatory BP and left ventricular mass index. RESULTS: The frequency of microalbuminuria was 7.2%. Microalbuminuric patients were more likely to be men and to be characterized by higher ambulatory BP, body mass index and uric acid levels. Regression analysis demonstrated that male sex and 24 h systolic BP were determinants of UAE. Patients with white-coat hypertension showed lower UAE than did subjects with sustained hypertension. Although a certain relationship between UAE and left ventricular mass index was found, these variables were not significantly correlated. CONCLUSIONS: A low proportion of mildly hypertensive patients attended in a primary care setting are microalbuminuric. In this population, UAE is an expression of BP values over 24 h and correlates with several risk factors.

Adult↗

Prognostic value of tumoral ploidy in a series of spanish patients with acute lymphoblastic leukemia.

The prognostic value of tumoral ploidy and its relation with nonrandom chromosome alterations were analyzed in 89 cases of acute lymphoblastic leukemia. Ploidy is associated with the number of nonrandom chromosome alterations and survival. The pseudodiploid and hypodiploid groups had a high incidence of nonrandom alterations and poor survival while the diploid and high hyperdiploid groups had a lower incidence of nonrandom alterations and longer survivals. The patients in the low hyperdiploid group with random alterations received the same treatment as the diploid and high hyperdiploid groups but had poor survivals. Our analysis confirms that ploidy is a very important prognostic factor and suggests that patients with low hyperdiploidy should receive intensive therapies similar to those of patients in the groups with a high number of nonrandom alterations.

Adolescent↗

Cloning and characterization of SmeDEF, a novel multidrug efflux pump from Stenotrophomonas maltophilia.

Stenotrophomonas maltophilia is a nosocomial bacterial pathogen intrinsically resistant to several antibiotics. The mechanisms involved in this intrinsic multiresistance phenotype are poorly understood. A library of chromosomal DNA from a spontaneous multidrug-resistant S. maltophilia D457R mutant (A. Alonso and J. L. Martinez, Antimicrob. Agents Chemother. 41:1140-1142, 1997) was screened for complementation of erythromycin susceptibility on an antibiotic-hypersusceptible Escherichia coli DeltaacrAB strain. Cloning and further analysis revealed that a 6-kbp region constituting a transcriptional unit was capable of complementing the antibiotic-susceptible phenotype of an E. coli DeltaacrAB strain. We identified three open reading frames, smeD, smeE and smeF, which code for members of the membrane fusion protein, resistance nodulation division, and outer membrane factor families, respectively. Drug susceptibility assays indicated that the SmeDEF system cloned in E. coli mediates resistance to a wide range of antibiotics. Ethidium bromide and norfloxacin accumulation experiments in the presence and in the absence of carbonyl cyanide m-chlorophenylhydrazone showed that this system constitutes a drug efflux pump dependent on the membrane proton motive force. The presence of high levels of smeDEF mRNA in the multiresistant D457R mutant was consistent with the high levels of SmeF (formerly Omp54) observed in the same strain. In contrast, transcription levels of smeDEF in the D457 strain were tiny, which correlates with the low levels of SmeF observed for this strain. Also, for both the D457 and D457R strains, we observed growth phase-dependent regulation in which the highest level of transcription corresponded to early exponential phase, with transcription decreasing throughout the growth curve to undetectable levels at 24 h.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Biological cost of AmpC production for Salmonella enterica serotype Typhimurium.

Chromosomally mediated AmpC-type beta-lactamases are frequently found among Enterobacteriaceae. Hyperproduction of AmpC beta-lactamase results in high-level resistance to beta-lactam antibiotics. One striking feature of Salmonella is the absence of the structural ampC gene, encoding AmpC beta-lactamase, in contrast with other members in the Enterobacteriaceae family, such as Escherichia, Citrobacter, or Enterobacter. The horizontal acquisition of ampC genes is one of the causes of the increased resistance to extended-spectrum cephalosporins and beta-lactamase inhibitors among gram-negative rods. Nevertheless, despite the high number of beta-lactam-resistant Salmonella isolates so far described, only two strains expressing resistance to cephalosporin and beta-lactamase inhibitors which is mediated by AmpC-type enzymes have been found. In this work, data are provided which support the possibility that the maintenance and expression of the ampC gene may represent an unbearable cost for Salmonella in terms of reduction of some of its lifestyle attributes, such as growth rate and invasiveness. The deleterious AmpC burden can be eliminated by decreasing the production of AmpC when both the regulatory gene, ampR, and ampC are present in Salmonella. Thus, it is suggested that the two genes have to be acquired together by Salmonella, leading to an inducible beta-lactam resistance phenotype. AmpC synthesis did not produce major variations in the peptidoglycan composition of Salmonella.

Animals↗

Stenotrophomonas maltophilia D457R contains a cluster of genes from gram-positive bacteria involved in antibiotic and heavy metal resistance.

A cluster of genes involved in antibiotic and heavy metal resistance has been characterized from a clinical isolate of the gram-negative bacterium Stenotrophomonas maltophilia. These genes include a macrolide phosphotransferase (mphBM) and a cadmium efflux determinant (cadA), together with the gene cadC coding for its transcriptional regulator. The cadC cadA region is flanked by a truncated IS257 sequence and a region coding for a bin3 invertase. Despite their presence in a gram-negative bacterium, these genetic elements share a common gram-positive origin. The possible origin of these determinants as a remnant composite transposon as well as the role of gene transfer between gram-positive and gram-negative bacteria for the acquisition of antibiotic resistance determinants in chronic, mixed infections is discussed.

Anti-Bacterial Agents↗

Aminoglycoside resistance mediated by the bifunctional enzyme 6'-N-aminoglycoside acetyltransferase-2"-O-aminoglycoside phosphotransferase.

The expression of the bifunctional aminoglycoside inactivating enzyme 6'-N-aminoglycoside acetyltransferase-2"-O-aminoglycoside phosphotransferase is the most important mechanism of high-level aminoglycoside resistance in Staphylococcus and Enterococcus. The enzyme is unique because it presents two different aminoglycoside-modifying activities located in different regions of the molecule. The gene aac(6')-aph(2") which encodes the synthesis of the enzyme is present in Tn4100-like transposons which are inserted both in R plasmids and the chromosomes of aminoglycoside-resistant isolates. The genetic structure of aac(6')-aph(2")-containing isolates indicates that their origin is not clonal, but plasmid conjugation together with multiple insertion events are in the basis of the rapid spread of aminoglycoside resistance among Gram-positive bacteria. There is not any prevalent genetic linkage of aac(6')-aph(2") with other antibiotic-resistance determinant. However, most methicillin resistant Staphylococcus strains present also high-level aminoglycoside resistance as the consequence of constant antibiotic pressure. This situation could change in the next future with the reported reemergence of gentamicin-susceptible MRSA isolates. Recent data show that inhibitors of eukaryotic protein kinases inhibit as well the aminoglycoside phosphotransferase activity. This effect indicates a common structure for these two families of proteins and opens the possibility for a meaningful survey of inhibitors of 6'-N-aminoglycoside acetyltransferase-2"-O-aminoglycoside phosphotransferase useful in clinical practice.

Acetyltransferases↗

Environmental and clinical isolates of Pseudomonas aeruginosa show pathogenic and biodegradative properties irrespective of their origin.

Virulence properties of pathogenic bacteria, as well as resistance to antibiotics, are thought to arise through a specialization process favoured by the strong selection pressure imposed in clinical treatments. Nevertheless, in the case of opportunistic pathogens, it is unclear whether strains can be classified into virulent and non-virulent isolates. Clones of the opportunistic pathogen Pseudomonas aeruginosa do not seem to be associated to a particular biovar or pathovar, which suggests that virulence characteristics in opportunistic pathogens may already be present in environmental (non-clinical) isolates. We have explored this possibility, studying environmental isolates (mainly from oil-contaminated soils) and clinical isolates (from bacteraemia and cystic fibrosis patients) of P. aeruginosa. All environmental strains were found to actively efflux quinolones, which are synthetic antibiotics not expected to be present in the environment. These strains contained multidrug resistance determinants, were capable of invading epithelial cells and presented genes from the quorum-sensing and type III secretion systems. Some of them expressed either haemolytic or proteolytic activities or both, characteristics considered to be typical of virulent strains. All the strains tested, of clinical or environmental origin, could use alkanes (oil hydrocarbons) as a carbon source. Our results suggest that clinical and non-clinical P. aeruginosa strains might be functionally equivalent in several traits relevant for their virulence or environmental properties. Selection of clinically relevant traits, such as antibiotic resistance or cellular invasiveness, in opportunistic pathogens present in soil ecosystems is discussed.

Animals↗

Emergence of multidrug-resistant mutants is increased under antibiotic selective pressure in Pseudomonas aeruginosa.

Pseudomonas aeruginosa is one of the most important opportunistic pathogens involved in nosocomial infections, cystic fibrosis patients included. Hospital isolates frequently present multidrug-resistance (MDR) phenotypes as the consequence of constant antibiotic selective pressure. The kinetics of emergence of P. aeruginosa MDR mutants under antibiotic selective pressure indicated that long-term incubation in the presence of the bacteriostatic antibiotic tetracycline increases the mutation rate per cell per day of P. aeruginosa PAO1 by several orders of magnitude. The tetracycline-resistant mutants obtained were stable, showed decreased susceptibility to antibiotics belonging to different structural families, and contained an outer-membrane protein not present in the wild-type P. aeruginosa strain PAO1. These data are consistent with the hypothesis that incubation in the presence of tetracycline favours the emergence of MDR mutants in P. aeruginosa. The results are relevant for understanding the rapid emergence of antibiotic-resistant mutants among bacterial populations during infections. Their relationship to other models of increased mutagenesis under stress is discussed with respect to the adaptive mutation phenomenon.

Anti-Bacterial Agents↗

[Inhibition of pump and permeability mechanisms].

The presence of multidrug efflux-pump systems in bacteria showing resistance to various drugs is increasingly reported in the literature. These systems are inducible by compounds such as salicylate and can thus be involved in situations of phenotypic resistance at the point of the infection which would otherwise be barely detectable under standard laboratory testing conditions. On the other hand, mutants which overproduce efflux-pumps and show increased levels of antibiotic resistance are easily selectable. It has been shown that inactivation of efflux-pump determinants produces an increased susceptibility to different antibiotics as well as prevents the emergence of mutants with a high-level antibiotic resistance to drugs such as quinolones. The search for efflux-pump inhibitors to be used in combination with other currently used antibiotics is therefore an important task for the renewal of the antibacterial therapeutic armamentarium. No efflux-pump inhibitors are commercially available as yet. However, several companies are in the process of working on their development. In this review, we discuss four possible targets that could be useful in the screening of inhibitors of efflux-pump systems in bacteria.

Bacteria↗

Ultrastructure of fish cells involved in cellular defences against Saprolegnia infections: evidence of non-leucocytic nature.

Fish cells attached to hyphae were observed in brown trout Salmo trutta L. infected with Saprolegnia parasitica. Earlier studies with light microscopy indicated that these cells were lymphocytes and neutrophils and that they were involved in the defence mechanisms against Saprolegnia infections. However, using electron microscopy, we found these attached cells did not show leucocytic characteristics, but instead shared some ultrastructural features with filament-containing cells. The pressure of a dense mass of cytoplasmic filaments precludes the leucocytic nature of these cells. How these cells could be involved in cellular defences against fungi is discussed.

Animals↗

[Angina caused by subclavian-coronary steal in patients revascularized with internal mammary artery].

After coronary bypass surgery in the left internal mammary artery, occlusive atherosclerosis in the proximal subclavian artery can produce reverse flow in the mammary artery and myocardial ischemia (coronary-subclavian steal syndrome). This is a rare cause of recurrent myocardial ischemia. We present two patients with postoperative complete obstruction in the proximal subclavian artery and inverse flow in the mammary artery producing severe ischemia in the left anterior descending artery territory. Both patients were treated with subclavian-subclavian bypass, which in one patient was ineffective in producing an adequate anterograde flow in the left internal mammary artery. We review clinical management, diagnostic methods and therapeutic options used in the coronary-subclavian steal syndrome.

Aged↗