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Biomedical subjects

J Garcia

Publications and source records attributed to J Garcia.

At least 37 records · Page 2Linked to original sources
PubMed2003

Comparison between a two-drug regimen with tacrolimus and steroids and a triple one with azathioprine in kidney transplantation: results of a European trial with 3-year follow up.

This study was designed to assess the efficacy and safety of two immunosuppressant regimens in kidney transplantation based on the administration of tacrolimus-one of them with tacrolimus, azathioprine, and corticosteroids (n=239) and the other with tacrolimus, and corticosteroids (n=236). After completing the initial 3-month study, the patients remaining in the study (197 and 195, respectively) were assessed for 3 years. The incidence of acute rejection (AR) episodes treated during this period was 28.8% with dual-drug therapy and 29.7% with triple-drug therapy. Late AR: episodes between 4 and 36 months were scarce (3.3% in dual and 4.2% in triple therapy). Chronic rejection incidence was 7.7% and 8.9%, respectively. The patients who experienced AR episodes during the first 3 months developed chronic rejection more frequently than those who did not suffer AR. Patient survival at 3 years was 95% vs 95.6%, and graft survival was 86.6% vs 86.5% (NS). Doses and blood levels of tacrolimus were similar in the two groups. Adverse effects were similar among both treatment groups. Median SCr was 123.8 micromol/L vs 114.9 micromol/L in patients who did experience AR: 145.9 micromol/L vs 132.6 micromol/L in those with early AR; and 194.5 micromol/L vs 152 micromol/L in those who presented with late AR. Need for de novo posttransplant insulin was 4.2% in the dual-drug group and 3.8% in the triple-drug cohort. These results demonstrate that, after 3 years of follow up, there were similar efficacy data among the dual- and triple-drug regimens. Thus, addition of azathioprine does not contribute any advantage in the middle term.

Acute Disease↗
PubMed2003

DRB1*1446 allele variations in the group-specific annealing sites of common amplification primers.

A cord blood unit from the Umbilical Cord Bank of Barcelona was initially typed by sequence-based typing (SBT) as DRB1* 0701. However, the subsequent confirmation by sequence-specific oligonucleotide probes (SSOP) revealed an unusual hybridization pattern that did not fit any of the known HLA-DRB1 alleles or allelic combinations. Molecular cloning and sequencing with primers located at introns 1 and 2 provided the definitive identification of a novel DRB1*1446 allele. It was similar to DRB1*1402 at exon 2 except for nucleotide substitutions at codons 10, 11 and 12 (from YST to LRK) that coincide with the 5'-end group specific site for the annealing of common amplification primers used by SBT and sequence-specific primers.

Alleles↗
PubMed2003

Plasmodium falciparum EBA-140 kDa protein peptides that bind to human red blood cells.

The erythrocyte-binding antigen 140 (EBA140) sequence was chemically synthesized in 61 20-mer sequential peptides covering the entire 3D7 protein strain, each of which was tested in erythrocyte-binding assays. Peptides 26135, 26144, 26147, 26160, 26170 and 26177 presented high erythrocyte-binding activity, with affinity constants ranging from 350 to 750 nM. Critical erythrocyte-binding residues were determined by competition-binding assays with glycine analogous peptides. Cross-linking assays with SDS-PAGE from high erythrocyte membrane protein binding peptides showed that all these peptides bound specifically to 25, 52 and 75 kDa erythrocyte membrane proteins. The nature of these receptor sites was studied in peptide-binding assays using enzyme-treated erythrocytes, showing that these protein receptors are susceptible to structural changes provoked by enzyme treatment (neuraminidase, trypsin or chymotrypsin). Inhibition invasion assays in 'in vitro' cultures showed that all specific high binding sequences were able to inhibit invasion by 11-69% at 200 microM concentration.

Amino Acid Sequence↗
PubMed2003

Extinction-colonization dynamics structure genetic variation of spotted sunfish (Lepomis punctatus) in the Florida Everglades.

The population genetics of aquatic animals in the Florida Everglades may be strongly influenced by extinction and colonization dynamics. We combined analyses of allozyme and microsatellite loci to test the hypothesis that two levels of population structure are present for spotted sunfish (Pisces: Centrarchidae: Lepomis punctatus) inhabiting the Everglades. We hypothesized that annual cycles of marsh dry-down increase local-scale genetic variation through a process of local extinction and colonization; we hypothesized that barriers to gene flow by levee/canal systems create a second, regional level of genetic variation. In 1996 and 1997, we sampled spotted sunfish from 11 Everglades sites that were distributed in three regions separated by levees. We documented patterns of genetic variation at 7 polymorphic allozyme loci and 5 polymorphic microsatellite loci. Most genetic variation was present among local populations, according to both types of genetic markers. Furthermore, samples from marsh sites were heterogeneous, while those from canals were not. These data supported our hypothesis that dry-down events and local population dynamics in the marsh have a significant effect on population genetic structure of spotted sunfish. We found no support for our hypothesis that water-management structures superimpose a second level of genetic structure on this species, possibly because canals obscure historical structure by facilitating gene flow or because the complete canal system has been in place for fewer than 20 generations of this species. Our data suggests a continent-island (canal-marsh) structure of populations with high gene flow among regions and recurrent mixing in marshes from canal and creek habitats.

Animals↗
PubMed2003

Argentinian plant extracts with relaxant effect on the smooth muscle of the corpus cavernosum of guinea pig.

Extracts of different polarity from Baccharis trimera, Haplopappus rigidus Huperzia saururus, Maytenus ilicifolia, Satureja parvifolia and Senecio eriophyton were tested for their relaxant activity on smooth muscle using L-phenylephrine precontracted strips of corpus cavernosum obtained from Guinea pigs. Highly significant and dose dependent results were obtained with the dichloromethane extracts of H. saururus (87% of relaxation at the dose of 10 mg/ml), S. parvifolia (95% of relaxation at 2.5 mg/ml) and S. eriophyton (94% of relaxation at 5 mg/ml). Similar effects were observed with the methanol extracts of H. saururus (88% of relaxation at 10 mg/ml) and S. parvifolia (84% of relaxation at 10 mg/ml). These results were comparable to those obtained with the dichloromethane and methanol extracts of the well known Mexican species Turnera diffusa. Moreover, the aqueous extract of H. rigidus and the aqueous and methanol extracts of S. eriophyton were highly effective in a dose dependent manner (more than 90% of relaxation at the dose of 10 mg/ml). Significant results, but with a lower overall relaxant activity (about 70% of relaxation at 10 mg/ml), could also be obtained with the aqueous extract of S. parvifolia and with the dichlormethane and methanol extracts of B. trimera and M. ilicifolia. The positive controls with Sildenafil citrate at doses ranging from 0.35 to 35 microg/ml yielded moderate effects (up to 46% of relaxation at 35 microg/ml). The effects observed in the present study seem to validate the folk medicinal use of the tested plants and open new ways in the search for natural products with vasodilatory effects.

Animals↗
PubMed2002

Chromatographic removal combined with heat, acid and chaotropic inactivation of four model viruses.

The virus removal of protein A affinity chromatography, inactivation capacity, acid pH and a combination of high temperature with a chaotropic agent was determined in this work. The model viruses studied were sendaivirus, human immunodeficency virus (HIV-IIIb), human poliovirus type-II, human herpesvirus I and canine parvovirus. The protein A affinity chromatography showed a maximum reduction factor of 8 logs in the case of viruses larger than 120 nm size, while for small viruses (18-30 nm) the maximum reduction factor was about 5 logs. Non viral inactivation was observed during the monoclonal antibody elution step. Low pH treatment showed a maximum inactivation factor of 7.1 logs for enveloped viruses. However, a weak inactivation factor (3.4 logs) was obtained for DNA nonenveloped viruses. The combination of high temperature with 3 M KSCN showed a high inactivation factor for all of the viruses studied. The total clearance factor was 23.1, 15.1, 13.6, 20.0 and 16.0 logs for sendaivirus, HIV-IIIb, human poliovirus type-II, human herpesvirus I and canine parvovirus, respectively.

Animals↗
PubMed2002

CD34+-enriched-CD19+-depleted autologous peripheral blood stem cell transplantation for chronic lymphoproliferative disorders: high purging efficiency but increased risk of severe infections.

OBJECTIVE: The main objective of this work was to decrease the incidence of relapse after autologous stem cell transplantation with a "double purging" procedure. METHODS: We used a "positive" (CD34) and "negative" (CD19) double selection method to improve the efficacy of "single purging" of hematopoietic harvests in poor-prognosis lymphoproliferative disorders. All patients included in the study had a positive molecular marker of their disease. Minimal residual disease (MRD) was studied by flow cytometry and PCR techniques during the purging procedure and after transplantation. RESULTS: Twenty-six patients fulfilled entry criteria. Median age of patients was 50 years (range: 33-66); 17 were male and 9 female. Thirteen (50%) of the patients mobilized an adequate number of CD34+ cells (>or=3 x 10(6)/kg) to proceed with the double-selection protocol. Twelve of the 13 harvests became PCR negative after purging. Ten patients were grafted with the selected products and all but one engrafted without delay. After a median follow-up of 30 months, 2 of 10 patients suffered a molecular relapse at 7 and 19 months respectively. The earlier relapse was observed in the patient who received a MRD+ product. Only one patient experienced a clinical relapse. Three patients died due to obliterans bronchiolitis, pneumococcal sepsis, and septic shock of unknown origin, respectively, and three others presented life-threatening infections. CONCLUSION: Therefore, CD34+/CD19+ positive/negative selection is an effective purging approach in patients with chronic lymphoproliferative disorders. This favorable effect is, however, counterbalanced by the high frequency of life-threatening infections.

Adult↗
PubMed2002

Molecular analysis of HLA-DRB1 polymorphism in north-east Spain.

The DRB1* polymorphism in 941 randomly selected individuals from the Umbilical Cord Blood Bank of Barcelona (92.75% of Spanish origin) was determined by sequence-based typing. The HLA profile was similar to that of other Mediterranean populations, with DRB1*0701 and *0301 being the most frequent alleles. This may be a consequence of the mixture of alleles as a result of migration from contiguous geographical areas.

Alleles↗
PubMed2002

British National Health Service's and women's costs of antenatal ultrasound screening and follow-up tests.

OBJECTIVE: To estimate resource use and costs associated with routine obstetric ultrasound and follow-up tests from both the British National Health Service and women's perspectives. METHODS: Women attending Liverpool Women's Hospital (UK) in 1998 and 1999 were involved in the study. Bottom-up and top-down costings of National Health Service resources using questionnaires and diaries to record staff time associated with procedures were performed. Questionnaires were used to assess women's costs of attending for antenatal ultrasound scans. RESULTS: Routine antenatal ultrasound scans at Liverpool Women's Hospital cost the National Health Service between 14 pounds sterling and 16 pounds sterling per scan. More detailed secondary scans and other follow-up procedures cost substantially more. Costs to women, their families and their employers were estimated at between 9 pounds sterling and 15 pounds sterling per scan, depending on assumptions about the opportunity costs of time when not in paid employment and costs to employers of women who were in paid employment. CONCLUSIONS: Accurate estimates of costs to the National Health Service associated with routine antenatal ultrasound scanning are substantially lower than that cited in much of the literature. Costs to women are very similar to National Health Service costs. Economic evaluations should attempt to include costs to users of the service, particularly when the burden of cost is likely to shift.

Adult↗
PubMed2002

Enzyme replacement therapy: from concept to clinical practice.

UNLABELLED: In the early 1960s, the first lysosomal storage disease was identified. Since then over 40 such diseases have been reported. The common feature is that enzyme deficiency leads to accumulation of undegraded macromolecules and lysosomal engorgement, resulting in organ dysfunction. Enzyme replacement therapy (ERT) is being developed for many of these disorders. The present paper summarizes the history of the development of ERT, with particular reference to the mucopolysaccharidoses, and specifically, to mucopolysaccharidosis type VII (MPS VII). The rarity of MPS VII has meant that ERT is not yet available for the small number of affected patients, although the study of MPS VII and murine models of the disease have played an important part in the development of treatment for related disorders, including Gaucher disease. CONCLUSION: Much progress has been made in our understanding of lysosomal storage diseases over the past 40 years. This has led to the development of effective ERT for some of the more common storage diseases, such as Fabry disease and Gaucher disease. Treatment is still awaited, however, for many of the other rare disorders in this area, such as MPS VII.

Animals↗
PubMed2001

WHO antenatal care randomised trial for the evaluation of a new model of routine antenatal care.

BACKGROUND: We undertook a multicentre randomised controlled trial that compared the standard model of antenatal care with a new model that emphasises actions known to be effective in improving maternal or neonatal outcomes and has fewer clinic visits. METHODS: Clinics in Argentina, Cuba, Saudi Arabia, and Thailand were randomly allocated to provide either the new model (27 clinics) or the standard model currently in use (26 clinics). All women presenting for antenatal care at these clinics over an average of 18 months were enrolled. Women enrolled in clinics offering the new model were classified on the basis of history of obstetric and clinical conditions. Those who did not require further specific assessment or treatment were offered the basic component of the new model, and those deemed at higher risk received the usual care for their conditions; however, all were included in the new-model group for the analyses, which were by intention to treat. The primary outcomes were low birthweight (<2500 g), pre-eclampsia/eclampsia, severe postpartum anaemia (<90 g/L haemoglobin), and treated urinary-tract infection. There was an assessment of quality of care and an economic evaluation. FINDINGS: Women attending clinics assigned the new model (n=12568) had a median of five visits compared with eight within the standard model (n=11958). More women in the new model than in the standard model were referred to higher levels of care (13.4% vs 7.3%), but rates of hospital admission, diagnosis, and length of stay were similar. The groups had similar rates of low birthweight (new model 7.68% vs standard model 7.14%; stratified rate difference 0.96 [95% CI -0.01 to 1.92]), postpartum anaemia (7.59% vs 8.67%; 0.32), and urinary-tract infection (5.95% vs 7.41%; -0.42 [-1.65 to 0.80]). For pre-eclampsia/eclampsia the rate was slightly higher in the new model (1.69% vs 1.38%; 0.21 [-0.25 to 0.67]). Adjustment by several confounding variables did not modify this pattern. There were negligible differences between groups for several secondary outcomes. Women and providers in both groups were, in general, satisfied with the care received, although some women assigned the new model expressed concern about the timing of visits. There was no cost increase, and in some settings the new model decreased cost. INTERPRETATIONS: Provision of routine antenatal care by the new model seems not to affect maternal and perinatal outcomes. It could be implemented without major resistance from women and providers and may reduce cost.

Adult↗
PubMed2001

An unusual C(2)-domain in the active-zone protein piccolo: implications for Ca(2+) regulation of neurotransmitter release.

Ca(2+) regulation of neurotransmitter release is thought to require multiple Ca(2+) sensors with distinct affinities. However, no low-affinity Ca(2+) sensor has been identified at the synapse. We now show that piccolo/aczonin, a recently described active-zone protein with C-terminal C(2)A- and C(2)B-domains, constitutes a presynaptic low-affinity Ca(2+) sensor. Ca(2+) binds to piccolo by virtue of its C(2)A-domain via an unusual mechanism that involves a large conformational change. The distinct Ca(2+)-binding properties of the piccolo C(2)A- domain are mediated by an evolutionarily conserved sequence at the bottom of the C(2)A-domain, which may fold back towards the Ca(2+)-binding sites on the top. Point mutations in this bottom sequence inactivate it, transforming low-affinity Ca(2+) binding (100-200 microM in the presence of phospholipids) into high-affinity Ca(2+) binding (12-14 microM). The unusual Ca(2+)-binding mode of the piccolo C(2)A-domain reveals that C(2)-domains are mechanistically more versatile than previously envisaged. The low Ca(2+) affinity of the piccolo C(2)A-domain suggests that piccolo could function in short-term synaptic plasticity when Ca(2+) concentrations accumulate during repetitive stimulation.

Amino Acid Sequence↗
PubMed2001

Double-channel excitation in the XAS spectra of divalent and trivalent iron complexes in water solution.

We present a detailed analysis of XAS spectra of divalent and trivalent iron complexes in water solutions. The interpretation of the spectra has been provided by multi-channel multiple scattering approach. On this basis, good agreement between experimental data and theoretical calculations has been obtained in both cases including two excitation channels in the final state.

Journal Article↗
PubMed2001

Cows' milk proteins cause similar Th1- and Th2-like immune response in diabetic and healthy children.

AIMS/HYPOTHESIS: Cows' milk proteins have been proposed to play a part in the pathogenesis of Type I (insulin-dependent) diabetes mellitus but both epidemiological and immunological studies have given conflicting results. Thus we aimed to study the immunological response to cows' milk proteins among diabetic and healthy children, focusing on the balance of Th1- and Th2-like lymphocytes. METHODS: Peripheral blood mononuclear cells from 30 Type I diabetic children (4 to 18 years old) were examined and compared with peripheral blood mononuclear cells from 18 healthy age-matched control children (7 to 15 years old). Expression of IFN-gamma and IL-4 mRNA were detected by realtime RT-PCR and as protein by ELISA after stimulation with BSA, the ABBOS-peptide (a. a. 152-169) and beta-lactoglobulin (betaLG) from cows' milk and ovalbumin from hens' egg. Phytohaemagglutinin and keyhole limpet haemocyanin were used as positive and negative controls, respectively. RESULTS: Bovine serum albumin caused a weak Th2-like response in Type I diabetic children, whereas BSA antibodies decreased with age only among healthy children. Otherwise, cows' milk proteins (BSA, ABBOS and betaLG) caused increased expression for IFN-gamma and IL-4 mRNA in diabetic and healthy children. BetaLG caused the strongest immunological response, which decreased with age only among diabetic children. However, ovalbumin from egg caused a similar activation of the immune system and the immune response was similar in both diabetic and healthy children. CONCLUSION/INTERPRETATION: Proteins from cows' milk caused an equal Th1- and Th2-like immune response in diabetic and healthy children. Thus, our results do not support the hypothesis that cows' milk antigens are important for the immune process associated with Type I diabetes.

Adolescent↗
PubMed2001

Diagnostic imaging of tumors of the hand and wrist.

Tumors of the hand and wrist most commonly result from dystrophic lesions and hamartomas. Neoplastic lesions are rare. Imaging modalities are required for their detection and accurate location, careful assessment of the internal structure and borders, evaluation of the relation with surrounding tendons, nerves, and vessels, and are also required for staging. A variety of imaging techniques, including standard radiographs, sonography, CT, and MRI, can be obtained. The aim of this article is to present paradigmatic images of a variety of expansible lesions of the hand and wrist and to describe and compare the diagnostic findings of different imaging techniques.

Bone Neoplasms↗
PubMed2001

Plasmodium falciparum: binding studies of peptide derived from the sporozoite surface protein 2 to Hep G2 cells.

Plasmodium falciparum sporozoite surface protein 2 (Pf SSP2), also called thrombospondin related anonymous protein (TRAP), is involved in the process of sporozoite invasion of hepatocytes. Pf SSP2/TRAP possesses two different adhesion domains sharing sequences and structural homology with von Willebrand factor A-domains and human repeat I thrombospondin (TSP). Pf SSP2/TRAP has also been implicated in sporozoite mobility and in mosquito salivary gland invasion processes. We tested 15-mer long synthetic peptides having five overlapping residues covering the complete protein Pf SSP2 sequence in binding assays to Hep G2 cells. In these 57 peptides, 21 high-activity binding peptides (HABPs) were identified; five were in the adhesion domains already described and 16 were in two regions toward the protein's carboxy and middle terminal part. Six HABPs showed conserved amino acid sequences: 3243 (21FLVNGRDVQNNIVDE35), 3279 (201FLVGCHPSDGKCNLY215), 3287 (241TASCGVWDEWSPCSV255), 3289 (251SPCSVTCGKGTRSRK265), 3327 (441ERKQSDPQSQDNNGNY455) and 3329 (451DNNGNRHVPNSEDREY465). The HABPs show saturable binding and dissociation constants between 140 and 900 nm with 40 000-855 000 binding sites per cell. The 3279 (201FLVGCHPSDGKCNLY215), 3323 (421NDKSDRYIPYSPLSP435) and 3331 (461SEDRETRPHGRNNENY475) HABPs have B epitopes in their sequences; these have previously been recognized by antibodies partially inhibiting hepatocyte invasion and development of the hepatic state. The 3287 (241TASCGVWDEWSPCSV255) and 3289 (251SPCSVTCGKGTRSRK265) HABPs share common sequences with the Pf SSP2/TRAP region II plus, which is present in a great number of adhesion proteins. Based on this information, six new peptides covering the high binding regions identified previously were synthesized and, using a competition assay, the amino acid involved in the binding were determined.

Amino Acid Sequence↗