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Biomedical subjects

R López

Publications and source records attributed to R López.

At least 109 records · Page 6Linked to original sources
PubMed1999

Autologous stem cell transplantation in advanced follicular lymphoma. A single center experience.

BACKGROUND AND OBJECTIVE: The use of intensive therapy supported by autologous stem cell transplantation (ASCT) is being investigated as treatment for poor-prognosis follicular lymphomas (FL). A single-center experience is herein reported. DESIGN AND METHODS: From September 1990 to October 1997, 30 consecutive patients (pts) with advanced FL received transplants, 8 of bone marrow and 22 of peripheral blood. Thirteen harvests were purged by an immunomagnetic method using anti-B antibodies. Twenty-seven patients received salvage chemotherapy (CT) before ASCT with the objective of reaching this procedure in the best possible response. The disease status at ASCT was: 1(st) CR in 7 pts, > or =2(nd) CR in 6 pts, PR in 10 pts, untreated relapse in 2 pts and chemoresistant disease in 5 pts. RESULTS: There was only one transplant-related death (one month after ASTC). With a median follow-up of 19 (1-89) months, 27 pts are alive, 8 pts have relapsed/progressed at a median time of 11 (6-22) months after ASCT. The estimated 2-year PFS and OS are 57% (95% CI, 34-81%) and 83% (95% CI, 64-100%). When comparing the progression-free interval (PFI) before salvage CT and ASCT and the PFI after ASCT, of 17 evaluable pts, 10 had a PFI after ASCT longer than the previous interval, and 5 additional pts remain in CR/PR with a follow-up that has not yet reached the duration of pre-transplant response. By contrast, 2 pts had a short post-transplant response. INTERPRETATION AND CONCLUSIONS: High-dose therapy followed by ASCT obtains a high rate of responses, frequently longer than any previous PFI. Additional follow-up is necessary to determine whether there is any "plateau" in response duration and to define what proportion of pts may be cured with ASCT in this setting.

Adolescent↗
PubMed1999

Salvage chemotherapy with IAPVP-16 for advanced refractory or relapsed follicular lymphomas.

BACKGROUND AND OBJECTIVE: Patients with follicular lymphoma (FL) who do not respond to first-line chemotherapy or those who relapse after obtaining a remission have a poor outcome with standard treatment. In an effort to obtain a high rate of responses we designed an intensive brief duration salvage chemotherapy regimen. DESIGN AND METHODS: Forty-four consecutive patients with advanced follicular lymphoma were treated. Nine had primary refractory disease, 13 had achieved a partial remission, 16 were in untreated relapse or progression and six were in chemosensitive relapse. The IAPVP-16 regimen consists in ifosfamide 5 g/m(2) iv on day 1, etoposide 100 mg/m(2) iv on days 1-3, Ara-C 1.2 g/m(2)/12 hours iv on days 1-2 and methylprednisolone, 80 mg/m(2) iv on days 1-5. Granulocyte colony-stimulating factor was used from day 6 in 68 of 114 courses. RESULTS: Eighteen patients (41%) achieved a complete remission and 17 (39%) a partial remission, for an overall response rate of 80%. There were no treatment-related deaths. All treatment courses were followed by severe neutropenia, and 66% also by severe thrombocytopenia, but there were no serious hemorrhagic events. Neutropenic fever occurred in 56% of the courses with only four severe infections. Non-hematologic toxicity was modest. Twenty-eight patients proceeded to a stem cell transplantation. After a median follow-up of 25 months (range 4-95), the median progression-free survival and overall survival are 32 and 58 months, respectively. The median PFS was 33 months for responders and 11 months for non-responders (p=0.05), while the median OS has not been reached in responders and is 23 months in non-responders (p=0.0005). INTERPRETATION AND CONCLUSIONS: . The IAPVP-16 regimen is an effective and well tolerated treatment for advanced FL, allowing most eligible patients to proceed with significant tumor reduction to high-dose therapy and SCT.

Adult↗
PubMed1999

Construction of a new Streptococcus pneumoniae-Escherichia coli shuttle vector based on the replicon of an indigenous pneumococcal cryptic plasmid.

The nucleotide sequence of a cryptic plasmid (pRMG1) isolated from a type 1 Streptococcus pneumoniae has been determined and two recombinant plasmids, pRMGE1 and pRMGE2, bearing the pRMG1 replicon have been constructed. pRMGE2 is a shuttle vector for Escherichia coli and S. pneumoniae. The important characteristics of this cloning vector are: a size of 5.5 kb including a 1.4 kb fragment of pRMG1 (containing a double-stranded replication origin and an open reading frame encoding a putative replication initiation protein), a multicloning site, two antibiotic resistance markers for selection of plasmid containing cells, and blue-white colony screening in E. coli for identification of insert-containing plasmids.

Base Sequence↗
PubMed1999

Functional organization of the gene cluster involved in the synthesis of the pneumococcal capsule.

Streptococcus pneumoniae is a major human pathogen and its capsular polysaccharide has been shown to be the main virulence factor. The molecular organization of the genes governing the formation of this capsule was not studied until the 1990s. The capsular clusters (cap) of eight of the 90 known pneumococcal types have now been studied. The cap operon, located between the dexB and aliA genes, is arranged as a central region comprising the genes coding for the specific-type polysaccharide, flanked by open reading frames that are mostly common to all of the serotypes. The biochemical functions of 24 genes required for capsular polysaccharide biosynthesis have been elucidated but the precise role of the flanking regions in capsular formation is unknown. The natural genetic transformation characteristic of pneumococci, the arrangement of the cap locus and the abundance of transposable elements at this locus favor the genetic variability of the capsule in this microorganism. These well-documented observations together with the finding that some genes located outside the cap cluster may also participate in capsule formation increase the complexity of pneumococcal infection control.

Bacterial Capsules↗
PubMed1999

[Application of advanced oxidant systems in the treatment of residual waters in the petroleum industry (Fenton system)].

Typical contaminants from the oil industry were treated with the Fenton system (H2O2/Fe2+) under normal conditions of pressure and temperature. The treated contaminants, in harzadous concentrations, were the following: m-cresol, 2-chlorophenol, and methyl-tertbutyl -ether (MTBE). Additionally, waters contaminated with reformulated gasoline were also treated and the degradation of MTBE and volatile aromatics (benzene, toluene, ethylbenzene and xylene) was followed. The system efficiency, in the contaminated water treatment of two different samples were also tested. One of the samples came from oil production operations and the other from a petrochemical plants complex. In all cases an advanced mineralization of the contaminants was observed in relatively short periods of time. The rate constants, at room temperature, for degradation of m-cresol, 2-chlorophenol and MTBE were measured.

Ferrous Compounds↗
PubMed1998

Characterization of the galU gene of Streptococcus pneumoniae encoding a uridine diphosphoglucose pyrophosphorylase: a gene essential for capsular polysaccharide biosynthesis.

The galU gene of Streptococcus pneumoniae has been cloned and sequenced. Escherichia coli cells harboring the recombinant plasmid pMMG2 (galU) overproduced a protein that has been shown to correspond to a uridine 5'-triphosphate:glucose-1-phosphate uridylyltransferase (uridine diphosphoglucose [UDP-Glc] pyrophosphorylase) responsible for the synthesis of UDP-Glc, a key compound in the biosynthesis of polysaccharides. A gene very similar to the S. pneumoniae galU has been found in a partial nucleotide sequence of the Streptococcus pyogenes genome. Knockout galU mutants of type 1 pneumococci are unable to synthesize a detectable capsule. An identical result was found in type 3 S. pneumoniae cells in spite of the fact that these bacteria contain a type-specific gene (cap3C) that also encodes a UDP-Glc pyrophosphorylase. Since eukaryotic UDP-Glc pyrophosphorylases appear to be completely unrelated to their prokaryotic counterparts, we postulate that GalU may be an appropriate target for the search of new drugs to control the pathogenicity of bacteria like pneumococcus and S. pyogenes.

Amino Acid Sequence↗
PubMed1998

Molecular structure of the gene cluster responsible for the synthesis of the polysaccharide capsule of Streptococcus pneumoniae type 33F.

The organization and nucleotide sequence of the capsular gene cluster involved in the biosynthesis of the type 33F capsular polysaccharide of Streptococcus pneumoniae have been determined. The complete type 33F operon (cap33f) is composed of 14 potential open reading frames where the last ten genes are group-specific. Putative functions have been assigned to several gene products by sequence comparison with the proteins included in the databases. A functional promoter located immediately upstream from the first gene of the cap33f gene cluster has been demonstrated. A 20 kb DNA fragment containing the cap33f genes and the operon promoter was sufficient to transform a S. pneumoniae type 3 unencapsulated mutant to the type 33F capsule.

Bacterial Capsules↗
PubMed1998

Molecular characterization of PcpA: a novel choline-binding protein of Streptococcus pneumoniae.

The gene pcpA that encodes a novel pneumococcal choline-binding protein has been cloned and characterized. Northern blot analysis revealed that pcpA is expressed during the exponential phase of growth of pneumococci as a monocistronic transcript of about 2.3 kb. The transcription start site has been located 132 bp upstream of the start codon and the proposed -35 and -10 boxes that are highly similar to those of the typical sigma 70 promoters from Escherichia coli. This gene encodes a putative 79 kDa protein that contains a typical C-terminal choline-binding domain (ChBD). The ChBD of PcpA is built up by 11 identical motifs of 20 amino acids plus a tail of 19 amino acids, which represents the longest ChBD that has been characterized so far. Interestingly, two tandem arrays of five characteristic amphipathic leucine reach repeats (LRRs) of 22-26 amino acids in length have been found in the N-terminal region of PcpA. Since LRRs have been proposed to be involved in protein-protein and protein-lipid interactions our findings suggests a role for PcpA in pneumococcal adhesion.

Amino Acid Sequence↗
PubMed1998

[Epidemiologic situation of tuberculosis under the influence of HIV in the health area of Ibiza and Formentera (1987-1993)].

OBJECTIVES: To analyse the epidemiology of Tuberculosis and determine the characteristics of patients infected by HIV vs those not infected. DESIGN: A descriptive-retrospective study. SETTING: Ibiza and Formentera Health Area. PATIENTS: 268 patients over 16 diagnosed with TB between 7/1/1987 and 12/31/1993. MEASUREMENTS AND MAIN RESULTS: The highest accumulated annual incidence was detected in 1989 (82.4/100,000 inhabitants), but had decreased considerably by 1993 (42.8/100,000). The proportion of HIV+ cases increased to 37.0% of the total in 1993. 75% of the total were male and 57.5% between 20 and 39 (x = 38.1; SD = 15.4). 63.1% had pulmonary TB, 60.8% producing bacilli, 19.8% were HIV+, of which 47.2% were intravenous drug users and 20.8% homosexuals. There was a 75.4% cure rate, 4.9% who left treatment and 16.1% lost during follow-up. CONCLUSIONS: During the study period a progressive increase in the proportion of cases with HIV infection was observed. Control and follow-up of Tuberculosis was more difficult in these patients.

AIDS-Related Opportunistic Infections↗
PubMed1998

Evidence for horizontal transfer from Streptococcus to Escherichia coli of the kfiD gene encoding the K5-specific UDP-glucose dehydrogenase.

Capsular polysaccharides are important virulence factors both in Gram-positive and Gram-negative bacteria. A similar cluster organization of the genes involved in the synthesis of bacterial exopolysaccharides has been postulated in both cases, suggesting that these clusters evolved by module assembly. Horizontal gene transfer has been postulated to explain the polymorphism found in these cellular polymers. The cap1 K and cap3A genes coding for the pneumococcal type 1 and type 3 UDP-glucose dehydrogenases, respectively, have been compared with other UDP-sugar dehydrogenases. We have observed that the evolutionary distance between Cap1K and Cap3A is approximately equal to that found between Cap1K (or Cap3A) and other UDP-GlcDH of families evolutionarily distant like KfiD, the dehydrogenase from Escherichia coli K5. On the basis of comparisons of G + C content, patterns of synonymous and nonsynonymous substitutions, dinucleotide frequencies, and codon usage bias, we conclude that the kfiD gene has been introduced into E. coli from an exogenous source, probably from a streptococcal species.

Bacterial Capsules↗
PubMed1998

Endogenous cholecystokinin enhances postprandial gastroesophageal reflux in humans through extrasphincteric receptors.

BACKGROUND & AIMS: Exogenous cholecystokinin (CCK) decreases lower esophageal sphincter (LES) pressure and increases transient LES relaxations (TLESRs) in humans. The aims of this study were to determine whether endogenous CCK increases gastroesophageal reflux in humans and whether this is a direct effect on the LES. METHODS: Esophageal pH, LES pressure, and gallbladder volume were measured in 8 healthy volunteers after ingestion of a 181-kcal meal alone or adding 12 g cholestyramine to increase endogenous CCK release. In 7 additional volunteers, the effect of cholestyramine was studied during intravenous perfusion of saline or the CCK-A receptor antagonist loxiglumide. In circular LES strips from 9 transplant donors, we measured the effect of CCK-8 (10(-11) to 3 x 10(-8) mol/L) on basal tension and on electrical field-induced relaxation. RESULTS: Cholestyramine increased gallbladder emptying, reflux episodes, TLESRs, and time of esophageal pH of <4. Loxiglumide inhibited postprandial gallbladder emptying, reflux episodes, TLESRs, and time of pH of <4 and prevented the decrease in LES pressure induced by cholestyramine. In vitro, CCK-8 contracted LES strips through a tetrodotoxin-insensitive pathway but did not modify electrical field-induced LES relaxations. CONCLUSIONS: Endogenous CCK enhances postprandial gastroesophageal reflux in humans by increasing the rate of TLESRs and reduces postprandial LES pressure. These actions seem mediated by extrasphincteric CCK-A receptors that override a direct contractile effect of CCK on the LES muscle.

Adult↗
PubMed1998

Levels of IgM and IgA circulating immune complexes in dogs with leishmaniasis.

The concentrations of IgM and IgA circulating immune complexes (CIC) were determined in 82 dogs with naturally acquired leishmania infection and in a control group of 25 healthy dogs. The mean serum IgM and IgA CIC concentration in infected dogs were significantly (IgM; P < 0.004; IgA; P < 0.000) higher than in the control group. An increase in IgM and IgA CIC concentration was found in 47.6 and 95.1%, respectively, of the leishmania-infected dogs. The serum IgM and IgA CIC concentrations in infected dogs showing hypercreatininaemia were not statistically higher than those of sick dogs with normal creatininaemia. When hypercreatininaemia (> or = 1.30 mg/dl) was used as an indicator for CIC disease, the positive predictive value obtained with 0.368 for IgM CIC and 0.894 for IgA CIC, indicating that renal function impairment was associated with the high serum IgM and IgA CIC concentrations in 36.8 and 89.4%, respectively, of the infected dogs.

Animals↗
PubMed1998

Use of allopurinol for maintenance of remission in dogs with leishmaniasis.

Current treatments for infected dogs with leishmaniasis do not always provide long-term control of the disease and clinical relapses are common. In this study, the usefulness of long-term allopurinol administration in the maintenance of clinical remission in canine leishmaniasis was evaluated. Fifteen dogs with natural leishmania infection were subjected to an initial treatment based on the simultaneous administration of meglumine antimoniate (100 mg/kg/day) and allopurinol (30 mg/kg/day). Once clinical remission was achieved, a maintenance treatment with allopurinol (20 mg/kg/day) administered for one week a month was instituted. Results were compared with those of a retrospective control group comprising 15 infected dogs which only followed the induction treatment. Relapses occurred in 86 per cent of control dogs within 14 months of discontinuing treatment. In contrast, those dogs on intermittent oral allopurinol administration were successfully maintained in clinical remission for a follow-up period of 10 to 44 months. In this latter group, specific antibody titres decreased or were unchanged, no side effects directly attributable to allopurinol were seen and treatment was well accepted by the owners. It is concluded that long-term intermittent administration of allopurinol is an effective way of maintaining clinical remission in dogs with leishmaniasis.

Allopurinol↗
PubMed1998

Functional analysis of the two-gene lysis system of the pneumococcal phage Cp-1 in homologous and heterologous host cells.

The two lysis genes cph1 and cpl1 of the Streptococcus pneumoniae bacteriophage Cp-1 coding for holin and lysozyme, respectively, have been cloned and expressed in Escherichia coli. Synthesis of the Cph1 holin resulted in bacterial cell death but not lysis. The cph1 gene was able to complement a lambda Sam mutation in the nonsuppressing E. coli HB101 strain to produce phage progeny, suggesting that the holins encoded by both phage genes have analogous functions and that the pneumococcal holin induces a nonspecific lesion in the cytoplasmic membrane. Concomitant expression of both holin and lysin of Cp-1 in E. coli resulted in cell lysis, apparently due to the ability of the Cpl1 lysozyme to hydrolyze the peptidoglycan layer of this bacterium. The functional analysis of the cph1 and cpl1 genes cloned in a pneumococcal mutant with a complete deletion of the lytA gene, which codes for the S. pneumoniae main autolysin, provided the first direct evidence that, in this gram-positive-bacterium system, the Cpl1 endolysin is released to its murein substrate through the activity of the Cph1 holin. Demonstration of holin function was achieved by proving the release of pneumolysin to the periplasmic fraction, which strongly suggested that the holin produces a lesion in the pneumococcal membrane.

Amino Acid Sequence↗