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Biomedical subjects

J Campos

Publications and source records attributed to J Campos.

At least 19 recordsLinked to original sources
PubMed2003

Beneficial effects of HLA class II incompatibility in living donor liver transplantation.

OBJECTIVE: To analyze the impact of HLA matching in both patient and graft evolution after LDLT. MATERIAL AND METHODS: Twenty recipients underwent LDLT with follow-up of 3 to 30 months. HLA typing was performed on all donor-recipient pairs; class I antigens were typed using serological methods and class II loci (DRB1 and DQB1) using low-resolution molecular typing. Recipient sera were cross-matched with donor lymphocytes. Antigen mismatches were analyzed for each locus individually, for each class as a whole and for HLA class I immunogenic triplets according to HLA Matchmaker software. RESULTS: Eighteen of 20 donor-recipient pairs were HLA haploidentical. All but one of the recipients had a negative cross-match before transplantation. While there was not a statistically significant correlation between HLA class I mismatches and the incidence of acute rejection episodes, HLA class II matching in DRB1 and DQB1 loci appeared to be associated with a higher incidence of acute rejection episodes after LDLT. Both host-versus-graft (HvG) and graft-versus-host (GvH) HLA class II compatibilities correlated with rejection episodes, especially for the GvH direction. CONCLUSIONS: HLA class II matching for DRB1 and DQB1 loci appears to be associated with a higher incidence of acute rejection episodes after LDLT. In this study, mismatches in class I HLA antigens are not related to an higher incidence of acute rejection episodes nor other complications after LDLT. Further studies are needed to unveil the role of HLA matching in LDLT.

Adolescent↗
PubMed2003

QSAR-derived choline kinase inhibitors: how rational can antiproliferative drug design be?

This review presents an overview of Choline Kinase (ChoK) inhibitors with antiproliferative activity. The consideration of ChoK as a novel target for the development of new anticancer drugs is justified. The synthesis of several derivatives based on structural modifications of hemicholinium-3 (HC-3) is not accompanied by potentiation of the neurological toxicity of HC-3. The increment of both ChoK inhibitory and antiproliferative activities was successfully obtained by the two following changes: a) substitution of the oxazonium moiety of HC-3 by several aromatic heterocycles, and b) using the 1,2-ethylene(bisbenzyl) moiety instead of the 4,4'-biphenyl fragment. In an attempt to understand the ChoK inhibitory activity, a quantitative structure-activity relationship was developed. The QSAR equations have described the forces involved in quantitative terms. The electron characteristic of the substituent at position 4 of the heterocycle and the lipophilic character of the whole molecule were found to significantly affect the antitumour activity in compounds 17-95. Trispyridinium compounds 91-95 are more potent than the bispyridinium ones 87-89 as ChoK inhibitors. Nevertheless, 91-95 are less active than 87-89 as antiproliferative agents because the latter show better lipophilicities to cross the cytosolic membranes. Inhibition of the growth of human tumours in nude mice has been demonstrated: Antitumour activity of compound 64 against human HT-29 produced a decrease of up to 70% in the size of the tumour in nude mice. These results indicate that ChoK can be used as a general target for anticancer drug design against Ras-dependent tumourigenesis.

Animals↗
PubMed2002

Antibiotic resistance in 1962 invasive isolates of Escherichia coli in 27 Spanish hospitals participating in the European Antimicrobial Resistance Surveillance System (2001).

In Europe, antimicrobial resistance of invasive pathogens has been monitored since 1998 by the European Antimicrobial Resistance Surveillance System (EARSS). The goal of this study is to analyse the susceptibility data of invasive Escherichia coli collected by 27 Spanish laboratories in 2001. Each laboratory identified strains and tested their susceptibility using its own methods. To assess the comparability of susceptibility test results, a quality assurance exercise was performed. We report data from 1962 invasive isolates of E. coli: 1959 from blood and three from cerebrospinal fluid, corresponding to the same number of patients. Resistance to ampicillin, co-trimoxazole, ciprofloxacin and gentamicin was found in 58.46%, 32.91%, 17.19% and 6.39% of isolates, respectively. Extended-spectrum beta-lactamase (ESBL) production was detected in 30 strains (1.55%). Ciprofloxacin resistance was higher in isolates from men and in-patients than in those from women and out-patients (P < 0.001). Resistance to ampicillin and co-trimoxazole was more widespread in children than in adults: 70.37% versus 57.87% (P = 0.01) and 41.84% versus 32.53% (P = 0.05). Non-significant differences in resistance to fluoroquinolones were observed between isolates from children (11.1%) and adults (17.54%), despite the fact that fluoroquinolones are not administered to children. Significantly, resistance to non-beta-lactam antibiotics (co-trimoxazole, ciprofloxacin and gentamicin) was more prevalent in ampicillin-resistant strains and ESBL-producing strains than in ampicillin-susceptible strains and non-ESBL-producing strains. Multidrug resistance was present in 13.92% of isolates; the most prevalent phenotype was resistance to ampicillin, co-trimoxazole and ciprofloxacin, which was detected in 59.36% of multiresistant strains and in 8.22% of strains overall.

Adult↗
PubMed2001

Patellar tendon-lateral femoral condyle friction syndrome: MR imaging in 42 patients.

OBJECTIVE: To demonstrate the MR imaging findings that occur between the posterior inferolateral patellar tendon and the lateral femoral condyle in patients with chronic anterior and or lateral knee pain. PATIENTS AND DESIGN: A retrospective review of the MR images in 42 patients who presented with chronic anterior or lateral knee pain was performed by two musculoskeletal radiologists. In 15 patients, post-contrast images were available. RESULTS: Sagittal and axial imaging planes best demonstrated the patellar tendon and its relationship with the lateral femoral condyle. In 40 patients, there was obliteration of the fat planes and abnormal signal intensity in the lateral soft tissues of the inferior patellofemoral joint. Enhancement after administration of gadolinium was noted in all cases in which contrast was administered. Eighteen patients showed cystic changes in the soft tissues adjacent to the lateral femoral condyle in addition to fat plane obliteration. In two patients, only cystic changes were noted in the lateral soft tissues. Abnormal patellar alignment was noted in 37 patients. Patellar tendon pathology was seen in nine patients. CONCLUSION: In evaluating anterior knee symptoms, MR imaging allows identification of changes that may be related to patellar tendon-lateral femoral condyle friction syndrome and that should be distinguished from other causes of anterior or lateral knee pain.

Adolescent↗
PubMed2001

Functional recovery of skilled forelimb use in rats obliged to use the impaired limb after grafting of the frontal cortex lesion with homotopic fetal cortex.

The long-term effect of transplanting embryonic frontal cortex into a unilateral frontal cortex lesion has been studied in adult rats. Before surgery, activity in an open field, muscular strength of both forelimbs, and performance in a paw-reaching-for-food task were scored in 26 rats. In 21 animals a unilateral cortex lesion was then made in the forelimb motor area of the hemisphere contralateral to the preferred paw in the paw-reaching-for-food task, while the other 5 animals were sham-operated. On retesting, the lesion animals changed the preferred paw. A solid homotopic transplant of embryonic tissue (embryonic day 17) was then placed in the lesion cavity in 11 of the lesion rats. Three months later neither lesion alone nor lesion plus transplantation affected open field behavior and muscular strength, but the lesion permanently affected performance in the paw-reaching-for-food task, as shown by a change of preferred paw and a functional deficit in the paw contralateral to the lesion. Transplantation ameliorated the deficits caused by the lesion, but this was only evident when animals were forced to reach with the paw contralateral to the lesion plus transplant. The behavioral results were independent of the size of the lesion and graft. Connections between graft and host tissue were studied by means of the fluorescent tracer 1,1'-dioctadecyl-3,3,3'3'-tetramethylindocarbocyanine perchlorate (DiI). A dense array of labeled fibers was found in the host cortex adjacent to the transplant. The results suggest that functional recovery depends on grafting but is only evident when the animal is obliged to use the affected limb.

Animals↗
PubMed2001

LUMO energy of model compounds of bispyridinium compounds as an index for the inhibition of choline kinase.

Eleven derivatives of 1,1'-[1,2-ethylenebis(benzene-1,4-diylmethylene)]bis(4-pyridinium) dibromides bearing various groups at C-4 of the pyridinium moiety were synthesized and examined for their inhibition of choline kinase (ChoK) and antiproliferative activities. The C-4 substituents include electron-releasing, neutral or electron-withdrawing groups. A one-parameter regression equation has been derived which satisfactorily describes the ex vivo inhibitory potency of ChoK of the title compounds. The electronic effect plays a critical function in the ex vivo inhibition of ChoK although the role of electrostatic interactions could be altered due to a solvation process of both ChoK and ligands.

Choline Kinase↗
PubMed2001

Differential interleukin-8 response of intestinal epithelial cell line to reactogenic and nonreactogenic candidate vaccine strains of Vibrio cholerae.

In this study, we analyzed whether attachment of Vibrio cholerae vaccine strains to human intestinal epithelial cells can induce an interleukin-8 (IL-8) response. The IL-8 transcripts were detected by PCR amplification of reverse-transcribed mRNA, and the gene product secretion was measured by an enzyme-linked immunosorbent assay. Infection of monolayers of the undifferentiated HT29-18N2 cell line with reactogenic (JBK70 and 81) and nonreactogenic (CVD103HgR and 638) vaccine strains of V. cholerae resulted in markedly higher IL-8 expression by epithelial cells exposed to reactogenic strains than by cells exposed to the nonreactogenic strains. Additionally, epithelial cells produced IL-8 transcripts following stimulation with cholera vaccine strains in a concentration-dependent manner. These results represent a new insight into the inflammatory component of reactogenicity and could be used as a predictive marker of vaccine reactogenicity prior to human testing.

Bacterial Adhesion↗
PubMed2001

[Larval susceptibility to chemical insecticides of two Aedes aegypti populations].

OBJECTIVE: Insect susceptibility has been one of the most important aspects to be monitored in public health programs for vector control. The purpose of the study is to assess the susceptibility to chemical insecticides of Aedes aegypti larvae in both areas under vector control and no vector control. METHODS: World Health Organization standard bioassays for diagnostic concentration and multiple concentrations were performed in mosquito larvae collected in an area under no vector control (Campinas, SP) and an area under vector chemical control (Campo Grande, MS), in Brazil. RESULTS: Potential resistance to a diagnostic concentration of temephos (DC=0.04 ppm) was registered for an Ae. aegypti larval population collected in Campinas. Multiple concentration tests confirmed the larvae resistance, with 24.5% of them surviving at the 0.0125 ppm concentration. Bioassays with the organophosphate fenitrothion (DC=0.08 ppm) and pyrethroid cypermethrin (DC=0.01 ppm) in the same population revealed their susceptibility to these agents. Bioassays carried out in an Ae. aegypti larval population collected in Campo Grande showed their susceptibility to temephos (DC=0.04 ppm) and cypermethrin (DC=0.01 ppm). LC50 and LC95 for cypermethrin (CE25), cyfluthrin (CE5), betacyfluthrin (SC1.25) and propoxur (CE20) were determined for Ae. aegypti. Using the Rockefeller standard strain values, ratios of resistance were estimated: 2.9, 2.2, 2.4 and 1.3 for LC50 and 3.5, 2.6, 3.9 and 1.3 for LC95, respectively. CONCLUSION: The findings reinforce the need for routinely monitoring pesticide efficacy as a very important step in vector control management programs.

Aedes↗
PubMed2001

Chromosomal comparisons among and within populations of Simulium (Chirostilbia) pertinax (Diptera, Simuliidae).

Chromosomal studies were carried on six larval populations of Simulium (Chirostilbia) pertinax from different locations in Brazil. Larvae were collected in the states of Paraná, Rio Grande do Sul, Rio de Janeiro and São Paulo. Polytene chromosome map comparisons within and among populations showed no differences in banding pattern, except for some limited polymorphism (secondary NOR and four band polymorphisms). There were no chromosomal variations associated with the resistance or susceptibility of the larvae to temephos. The chromosomal homosequentiality found among the six populations suggests that S. pertinax may be a monomorphic species.

Animals↗
PubMed2001

An integrated simulator for surgery of the petrous bone.

This paper describes work being undertaken as part of the IERAPSI (Integrated Environment for the Rehearsal and Panning of Surgical Intervention) project. The project is focussing on surgery for the petrous bone, and brings together a consortium of European clinicians and technology providers working in this field. The paper presents the results of a comprehensive user task analysis that has been carried out in the first phase of the IERAPSI project, and details the current status of development of a pre operative planning environment and a physically-based surgical simulator.

Cochlear Implantation↗
PubMed2000

QSAR of 1,1'-(1,2-ethylenebisbenzyl)bis(4-substitutedpyridinium) dibromides as choline kinase inhibitors: a different approach for antiproliferative drug design.

Ten new structures of a series of the title compounds were synthesized and screened for their activity to inhibit choline kinase under ex vivo conditions. Their inhibitory potency correlates with the 13C chemical shifts (in CD3OD) of the methylene group bearing the positively charged nitrogen. The inhibitory effect on proliferation against the HT-29 cell line is strongly dependent on its ability to inhibit the production of phosphorylcholine.

Cell Division↗
PubMed2000

Modulation of myogenic differentiation in a human rhabdomyosarcoma cell line by a new derivative of 5-fluorouracil (QF-3602).

The in vitro study of mechanisms involved in drug-induced maturation has made it possible to use differentiation-based therapy in clinical practice. The goal of this new therapy is the development of specific agents to induce cancer cells to stop proliferating and express characteristics of normal cells. Recently, by structural modifications of 5-fluorouracil (5-FU), we synthesized a new pyrimidine acyclonucleoside-like compound, 1-¿[3-(3-chloro-2-hydroxypropoxy)-1-methoxy]propyl¿-5-fluorouracil (QF-3602), which showed in rhabdomyosarcoma cells a low toxicity and time-dependent growth inhibition. In this work, we compared the degree of myogenic differentiation of RD rhabdomyosarcoma (RMS) cells after treatment with QF-3602 and 5-FU. Scanning and transmission electron microscopy (SEM and TEM) and immunocytochemical analyses showed that QF-3602 induced the appearance of myofilaments along the myotube-like giant RD cells, an increase in fibronectin and a decrease in vimentin expression. In contrast, only minor changes were observed with 5-FU. Moreover, polymerase chain reaction (PCR) analyses showed that QF-3602 did not induce overexpression of the mdr 1 gene, a resistance mechanism that frequently appears in classical cytotoxic therapy in these tumors. Compounds obtained by structural modifications of 5-FU may be useful in differentiation therapy as a new approach to the treatment of RMS.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Construction and characterization of a nonproliferative El Tor cholera vaccine candidate derived from strain 638.

In recent clinical assays, our cholera vaccine candidate strain, Vibrio cholerae 638 El Tor Ogawa, was well tolerated and immunogenic in Cuban volunteers. In this work we describe the construction of 638T, a thymidine auxotrophic version of improved environmental biosafety. In so doing, the thyA gene from V. cholerae was cloned, sequenced, mutated in vitro, and used to replace the wild-type allele. Except for its dependence on thymidine for growth in minimal medium, 638T is essentially indistinguishable from 638 in the rate of growth and morphology in complete medium. The two strains showed equivalent phenotypes with regard to motility, expression of the celA marker, colonization capacity in the infant mouse cholera model, and immunogenicity in the adult rabbit cholera model. However, the ability of this new strain to survive environmental starvation was limited with respect to that of 638. Taken together, these results suggest that this live, attenuated, but nonproliferative strain is a new, promising cholera vaccine candidate.

Amino Acid Sequence↗
PubMed2000

Glutaryl-CoA dehydrogenase deficiency in Spain: evidence of two groups of patients, genetically, and biochemically distinct.

Glutaryl-CoA dehydrogenase (GCDH) deficiency causes glutaric aciduria type I (GA I), an inborn error of metabolism that is characterized clinically by dystonia and dyskinesia and pathologically by neural degeneration of the caudate and putamen. Studies of metabolite excretion allowed us to categorize 43 GA I Spanish patients into two groups: group 1 (26 patients), those presenting with high excretion of both glutarate and 3-hydroxyglutarate, and group 2 (17 patients), those who might not be detected by routine urine organic acid analysis because glutarate might be normal and 3-hydroxyglutarate only slightly higher than controls. Single-strand conformation polymorphism (SSCP) screening and sequence analysis of the 11 exons and the corresponding intron boundaries of the GCDH gene allowed us to identify 13 novel and 10 previously described mutations. The most frequent mutations in group 1 were A293T and R402W with an allele frequency of 30% and 28%, respectively. These two mutations were also found in group 2, but always in heterozygosity, in particular in combination with mutations V400M or R227P. Interestingly, mutations V400M and R227P were only found in group 2, and at least one of these mutations was found in 11 of 15 unrelated alleles, accounting together for 53% of the mutant alleles in group 2. Therefore, it seems clear that two genetically and biochemically distinct groups of patients exist. The severity of the clinical phenotype seems to be closely linked to the development of encephalopathic crises rather than to residual enzyme activity or genotype. Comparison of GCDH protein with other acyl-CoA dehydrogenases (whose x-ray crystal structure has been determined) reveals that most of the mutations identified in GCDH protein seem to affect folding and tetramerization, as has been described for a number of mutations affecting mitochondrial beta-oxidation acyl-CoA dehydrogenases.

Alleles↗