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Biomedical subjects

F Moreno

Publications and source records attributed to F Moreno.

At least 163 records · Page 9Linked to original sources

Methicillin-resistant Staphylococcus aureus as a community organism.

An increase in methicillin-resistant Staphylococcus aureus (MRSA) infections prompted a study of MRSA during a 21-month period in a 600-bed university hospital in southern Texas. MRSA cases were classified as community, nosocomial, or transfer cases. A case-control study of risk factors for community MRSA compared with community methicillin-susceptible S. aureus (MSSA) was performed. Pulsed field gel electrophoresis (PFGE) of whole cell DNA typing was used as a marker of strain identity for 31 consecutive isolates collected during the last 8 months of the study. During the 21 months there were 170 patients with MRSA infection or colonization, an incidence of 0.2 per 1,000 patient-days. Ninety-nine (58%) of 170 isolates were from community cases; the community to nosocomial case ratio was 2:1. No significant risk factors differentiated patients with community MRSA compared with community MSSA. Most community MRSA isolates studied (15 [68%] of 22) had distinct PFGE patterns, as did many nosocomial MRSA isolates (4 [44%] of 9). MRSA isolates were commonly present on admission to the hospital, and multiple MRSA strains were demonstrated among both community and hospital isolates.

Adult↗

Splicing mutations of the polycystic kidney disease 1 (PKD1) gene induced by intronic deletion.

Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disease which frequently results in renal failure. The major ADPKD gene, polycystic kidney disease 1 (PKD1), has recently been identified. In an attempt to understand better the aetiology of this disorder we have searched for mutations in the PKD1 gene. Analysis of three regions in the 3' part of the gene has revealed two mutations that occur by a novel mechanism. Both mutations are deletions (of 18 or 20 bp) within the same 75 bp intron and although these deletions do not disrupt the splice donor or acceptor sites at the boundary of the intron, they nevertheless result in aberrant splicing. Two different transcripts are produced in each case; one includes the deleted intron while the other has a 66 bp deletion due to activation of a cryptic 5' splice site. No normal product is generated from the deleted gene. Aberrant splicing probably occurs because the deleted intron is too small for spliceosome assembly using the authentic splice sites; this mechanism has previously only been described from in vitro studies of vertebrate genes. A 9 bp direct repeat has been identified within the intron, which probably facilitated deletion by promoting misalignment of sequence. The possible phenotypic implications of producing more than one aberrant PKD1 transcript in these cases are discussed.

Adult↗

The clinical and molecular epidemiology of bacteremias at a university hospital caused by pneumococci not susceptible to penicillin.

To determine the epidemiology of bacteremias due to pneumococci not susceptible to penicillin (PNSP) at a university hospital, active microbiologic surveillance of bacteremias due to PNSP was done for 28 months. Controls were bacteremias caused by penicillin-susceptible pneumococci. Antimicrobial susceptibilities for alternative antibiotics were determined. Pulsed-field gel electrophoresis (PFGE) and serotyping were used as markers of strain identity. Of 113 pneumococcal isolates, 14 (13%) were intermediate or resistant to penicillin (MIC > or = 0.1 microgram/mL). Twelve PNSP were resistant to other drugs: chloramphenicol (5), tetracycline (6), trimethoprim-sulfamethoxazole (5), cefotaxime (1), and erythromycin (1). Independently significant risk factors associated with PNSP bacteremia were sepsis and prior treatment with beta-lactam antibiotics. PFGE revealed 10 distinguishable patterns among 12 isolates available for typing. In general, PFGE typing correlated with serotyping. It also distinguished some isolates of the same serotype. PFGE typing and serotyping suggest that the frequency of PNSP in the San Antonio, Texas, area is not due to dissemination of a single clonal strain.

Adolescent↗

sbmC, a stationary-phase induced SOS Escherichia coli gene, whose product protects cells from the DNA replication inhibitor microcin B17.

Microcin B17 (MccB17) is a ribosomally synthesized peptide antibiotic of 43 amino acids that induces double-strand breaking of DNA in a DNA gyrase-dependent reaction. As a consequence, the SOS regulon is induced and massive DNA degradation occurs. In this work we have characterized an Escherichia coli gene, sbmC, that in high copy number determines high cell resistance to MccB17. sbmC encodes a cytoplasmic polypeptide of 157 amino acids (M(r), 18,095) that has been visualized in SDS-polyacrylamide gels. The gene is located at min 44 of the E. coli genetic map, close to the sbcB gene. sbmC expression is induced by DNA-damaging agents and, also, by the entry of cells into the stationary growth phase. A G-->T transversion at the fifth nucleotide of the quasicanonical LexA-box preceding the gene makes recA cells 16-fold more resistant to exogenous MccB17. The gene product, SbmC, also blocks MccB17 export from producing cells. Altogether, our results suggest that SbmC recognizes and sequesters MccB17 in a reversible way.

Bacterial Proteins↗

Spectroscopic analysis of the binding of amylobarbitone, secbutobarbitone, pentobarbitone, phenobarbitone and quinalbarbitone to human serum albumin.

The binding of five barbiturates: amylobarbitone, secbutobarbitone, pentobarbitone, phenobarbitone and quinalbarbitone to human serum albumin (HSA) was studied by difference spectroscopy and spectrofluorimetric titrations. There were no changes in the HSA spectral properties. Our result suggest that there are two classes of binding sites on HSA for these barbiturates. A detailed investigation of the effect of their binding to HSA by deconvoluted spectra, suggests that the interaction of barbiturate-HSA takes place principally on the subdomain IIIA of HSA.

Barbiturates↗

Structure and organization of plasmid genes required to produce the translation inhibitor microcin C7.

The translation inhibitor microcin C7 (MccC7) is a linear heptapeptide whose N terminus has been replaced by an N-formyl group and whose C terminus has been replaced by the phosphodiester of 5'-adenylic acid and n-aminopropanol (J. I. Guijarro, J. E. González-Pastor, F. Baleux, J. L. San Millán, M. A. Castilla, M. Rico, F. Moreno, and M. Delepierre, J. Biol. Chem. 270:23520-23532, 1995). MccC7 production and immunity determinants lie on a 6.2-kb region of the Escherichia coli plasmid pMccC7. This region was entirely sequenced. It contains six open reading frames, which were shown to be true genes by different complementary approaches. Five genes, mccABCDE, which are transcribed in the same direction, are required to produce mature extracellular microcin. The sixth gene, mccF, adjacent to mccE, is transcribed in the opposite direction and encodes specific self-immunity. Genes mccA to -E constitute an operon transcribed from a promoter (mccp) located upstream of mccA. mccA is 21 nucleotides long and encodes the unmodified heptapeptide (J. E. González-Pastor, J. L. San Millán, and F. Moreno, Nature [London] 369:281, 1994). A comparison of predicted gene polypeptide products with those included in databases shows that an 81-amino-acid stretch of MccB is strikingly homologous to fragments of the same length of proteins ThiF and ChlN from E. coli, HesA from Anabaena sp. strain PCC7120, and UBA1, the ubiquitin-activating enzyme from different eukaryotic species. MccC displays several hydrophobic domains, suggesting a transmembrane location. The carboxyl end of MccE displays 41.2% identity with RimL, a protein required to acetylate the ribosome protein L12 from E. coli. In the absence of the other mcc genes, mccA impairs the growth of host cells, suggesting that unmodified MccA has antibiotic activity. A model for MccC7 biosynthesis, export, and immunity is proposed.

Amino Acid Sequence↗

Reversibility of tachycardia-induced cardiomyopathy after radiofrequency ablation of incessant supraventricular tachycardia in infants.

Tachycardia-induced cardiomyopathy developed in a 3 month old infant with permanent junctional reciprocating tachycardia, which was incessant despite medical treatment. The patient underwent transcatheter radiofrequency ablation. There were no complications and 8 months after the procedure the patient was symptom free without medication.

Cardiomyopathies↗

Studies of the specificities of IgE antibodies found in sera from subjects with allergic reactions to penicillins.

Penicillins are immunogenic when administered to humans and in some instances they can also be allergenic, inducing specific IgE antibodies. Whilst the major haptenic group, the penicilloyl, is well characterised, less is known about the relative importance of the different parts of the structure for antibody binding and how this can influence the specificity of patients response. In order to investigate this further, sera from subjects who had suffered an IgE-mediated reaction to penicillins were studied using the radioallergosorbent test (RAST) and RAST inhibition. The assays employed reagents related to the penicillins causing the reaction. Using 173 sera, positive RAST results were only found with reagents based on benzyl penicillin (BP) and amoxicillin (AX). Fifty-three positive sera were selected for further studies and categorized into three groups: (A) sera only RAST positive to AX, (B) sera only positive to BP and (C) sera positive to both penicillins. RAST inhibition studies were then carried out using monomeric penicilloyl conjugates and compounds representing parts of the penicilloyl structures of BP and AX. For all three groups, monomeric penicilloyl conjugates were the most efficient inhibitors but there were differences for the other compounds. Group A sera were also inhibited by the side chain amoxicillin, whereas group B sera were poorly inhibited by all other inhibitors. Group C sera showed two patterns of inhibition, both consistent with their more cross-reactive profile.

Amoxicillin↗

Isolation of microsatellites from the spinal muscular atrophy (SMA) candidate region on chromosome 5q and linkage analysis in Spanish SMA families.

A locus responsible for autosomal recessive spinal muscular atrophy (SMA) on chromosome 5q11.2-q13.3 has been mapped to a critical interval delimited by markers D5S435 and D5S557. By a modification of the Vectorette-(GT)n method, we have isolated three polymorphic CA repeats from two YACs of the SMA region. Two of them (D5S1417 and D5S1416) map within the SMA critical region, and the other (D5S1415) is centromeric to D5S435. Linkage analysis in Spanish SMA families with eleven markers showed that in our families the disease is linked to this region and confirmed that the novel markers are tightly linked to the SMA locus. The most likely order of markers was 5cen-(D5S63/D5S1356)-(D5S125/D5S465)- (D5S435/D5S1417/D5S1416/D5S557)-D5S610- D5S112-D5S127-5qter, with odds against alternative orders > 1,000:1. Genetic distances are in agreement with those previously published. However, the recombination fraction between D5S610 and D5S112 is remarkably greater than expected from the physical distance, suggesting a hot spot for recombination in this region. Our results from haplotype and multipoint analyses show that the SMA locus must lie between D5S465 and D5S112, and lend further support to the current location of the SMA locus.

Base Sequence↗

Study of the interaction between xylazine and bovine serum albumin by fluorescence quenching measurements.

The binding of xylazine to bovine werum albumin (BSA) was studied by fluoresence quenching, as a function of temperature. The experimental data could be fitted to both the Stern-Volmer equation and the Stern-Volmer equation modified by Lehrer. The temperature dependence of the Stern-Volmer constant, Ksv suggests that the mechanism of the quenching process is mainly dynamic in origin. The thermodynamic parameters were estimated based on such temperature dependence. The positive values found for the enthalpy and entropy changes seem to indicate that the hydrophobic contribution is the predominant intermolecular force stabilizing the xylazine-BSA complex. Fluorescence quenching was also used to calculate the binding constants by the Scatchard procedure. The values of these constants are of the same order of magnitude as the Stern-Volmer constants. These results, together with the spectral changes in the fluorescence emission spectra of BSA induced by xylazine, suggest that the interaction may take place in subdomains IIA and IIIA since these subdomains have been proposed to bind drugs and other hydrophobic materials.

Animals↗

Refining the localization of the PKD2 locus on chromosome 4q by linkage analysis in Spanish families with autosomal dominant polycystic kidney disease type 2.

Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disorder. At least two distinct forms of ADPKD are now well defined. In approximately 86% of affected European families, a gene defect localized to 16p13.3 was responsible for ADPKD, while a second locus has been recently localized to 4q13-q23 as candidate for the disease in the remaining families. We present confirmation of linkage to microsatellite markers on chromosome 4q in eight Spanish families with ADPKD, in which the disease was not linked to 16p13.3. By linkage analysis with marker D4S423, a maximum lod score of 9.03 at a recombination fraction of .00 was obtained. Multipoint linkage analysis, as well as a study of recombinant haplotypes, placed the PKD2 locus between D4S1542 and D4S1563, thereby defining a genetic interval of approximately 1 cM. The refined map will serve as a genetic framework for additional genetic and physical mapping of the region and will improve the accuracy of presymptomatic diagnosis of PKD2.

Adult↗

Genetic analysis of Cuban autosomal dominant polycystic kidney disease kindreds using RFLPs and microsatellite polymorphisms linked to the PKD1 locus.

We report on linkage analysis and haplotype characterization in 12 Cuban families with autosomal dominant polycystic kidney disease (ADPK) using PKD1-linked markers. They included both standard restriction fragment length polymorphisms (26.6., BLu24, and pGGG1) as well as microsatellite polymorphisms (CW2, 16AC2.5, and SM6). All of the examined families were fully informative for genetic diagnosis and no evidence of unlinked families was found. Analysis of two recombination events places PKD1 distal to the marker BLu24 and reduces the size of the region likely to contain the disease gene by approximately 300 kb. The allele frequencies of each marker were similar in the ADPKD and normal populations.

Alleles↗

An old antibiotic for a new multiple-resistant Enterococcus faecium?

Enterococci have become an important cause of nosocomial infections and may demonstrate high-level resistance to multiple antibiotics. We present the case of a 68-year-old man with a history of small cell lung cancer, who developed bacteremia due to a strain of Enterococcus faecium. The isolate was resistant to multiple antibiotics including vancomycin, ampicillin, aminoglycosides, quinolones, and macrolides. The patient was successfully treated with doxycycline and removal of an infected central venous catheter.

Aged↗

Use of the signal-averaged electrocardiogram for predicting inducible ventricular tachycardia in patients with unexplained syncope: relation to clinical variables in a multivariate analysis.

OBJECTIVES: The purpose of this study was to determine the predictors of electrically induced ventricular tachycardia in a large sample of patients with unexplained syncope and to examine the value of the signal-averaged electrocardiogram (ECG) in those patient subsets with varying pretest probability of ventricular tachycardia. BACKGROUND: In patients with unexplained syncope, electrophysiologic study can provide important diagnostic information, such as inducibility of ventricular tachycardia. The signal-averaged ECG can predict inducible ventricular tachycardia, but its utility has not been prospectively studied in a large group of patients with unexplained syncope. METHODS: At six hospitals, 189 consecutive patients with unexplained syncope underwent signal-averaged ECG and electrophysiologic studies. RESULTS: Ventricular tachycardia was induced in 28 patients (15%). Univariate predictors of ventricular tachycardia included history of previous myocardial infarction, reduced left ventricular ejection fraction and abnormal signal-averaged ECG results. The signal-averaged ECG was the most sensitive test but had poor specificity. By multivariate analysis, the signal-averaged ECG and history of previous myocardial infarction were independently predictive. The risk of ventricular tachycardia increased 17-fold in patients with a previous myocardial infarction who also had an abnormal signal-averaged ECG. In patients with no history of previous myocardial infarction, no additional testing was useful in identifying those at risk for inducible ventricular tachycardia. CONCLUSIONS: The signal-averaged ECG was the most sensitive noninvasive test available to predict sustained ventricular tachycardia at electrophysiologic study but was false positive in many patients. A history of previous myocardial infarction followed by the signal-averaged ECG was the most efficient screening process for predicting electrically induced ventricular tachycardia.

Adult↗

Mycobacterium kansasii pericarditis in patients with AIDS.

Pericardial effusion has been reported to occur in up to 38% of patients with AIDS. Many different etiologies for pericarditis have been described. In some instances, such infections have caused severe hemodynamic complications and life-threatening conditions. Mycobacterium kansasii is known to cause pulmonary and disseminated infections in immunocompromised patients, including those with AIDS; however, to the best of our knowledge, pericarditis due to an infection with this organism has not been described. We report the first three cases of M. kansasii pericarditis in patients with AIDS.

Acquired Immunodeficiency Syndrome↗