Biomedical subjects
Publications and source records attributed to F García-Sánchez.
A novel A*6836 allele was completely characterized by sequence-based typing (SBT) in a cord blood sample from an Ecuadorian donor. A*6836 discloses six clustered amino acid residue changes at the alpha-1 domain, codons 76-83, regarding its closer A*680102 allele. Therefore, A*6836 would be a new human leukocyte antigen (HLA)-A molecule showing a Bw4-epitope.
The effects of shading in combination with salinity treatments were studied in citrus trees on two rootstocks with contrasting salt tolerance to determine if shading could reduce the negative effects of salinity stress. Well-nourished 2-year-old 'Valencia' orange trees grafted on Cleopatra mandarin (Cleo, relatively salt tolerant) or Carrizo citrange (Carr, relatively salt sensitive), were grown either under a 50% shade cloth or left unshaded in full sunlight. Half the trees received no salinity treatment and half were salinized with 50 mM Cl- during two 9 week salinity periods in the spring and autumn interrupted by an 11 week rainy period. The shade treatment reduced midday leaf temperature and leaf-to-air vapour pressure deficit regardless of salinity treatments. In non-salinized trees, shade increased midday CO2 assimilation rate (A(CO2)) and stomatal conductance, but had no effect on leaf transpiration (E(lf)). Shade also increased leaf chlorophyll and photosynthetic water use efficiency (A(CO2)/E(lf)) in leaves on both rootstocks and increased total plant dry weight in Cleo. The salinity treatment reduced leaf growth and leaf gas exchange parameters. Shade decreased Cl- concentrations in leaves of salinized Carr trees, but had no effect on leaf or root Cl- of trees on Cleo. There were no significant differences in leaf gas exchange parameters of shaded and unshaded salinized plants but the growth reduction from salinity stress was actually greater for shaded than for unshaded trees. Shaded trees on both rootstocks had higher leaf Na+ than unshaded trees after the first salinity period, and this shade-induced elevated leaf Na+ persisted after the second salinity period in trees on Carr. Thus, shading did not alleviate the negative effects of salinity on growth and Na+ accumulation.
Differences between rootstocks, 'Cleopatra' mandarin and 'Carrizo' citrange, in soil-plant water relations and the influence of these factors on vigor, crop yield, fruit quality and mineral nutrition were evaluated in field-grown Clemenules mandarin trees irrigated at 100% of potential seasonal evaporation (ET(c)) (control treatment), or irrigated at 100% ET(c), except during Phases I and III of fruit growth and post-harvest when no irrigation was applied (deficit irrigation (DI) treatment), for 3 years. Differences between rootstocks in plant-soil water relations were the primary cause of differences among trees in vegetative development and fruit yield. After 3 years of DI treatment, trees on 'Cleopatra' showed more efficient soil water extraction than trees on 'Carrizo', and maintained a higher plant water status, a higher gas exchange rate during periods of water stress and achieved faster recovery in gas exchange following irrigation after water stress. The DI treatment reduced vegetative development more in trees on 'Carrizo' than in trees on 'Cleopatra'. Cumulative fruit yield decreased more in DI trees on 'Carrizo' (40%) than on 'Cleopatra' (27%). The yield component most affected by DI in 'Cleopatra' was the number of fruit, whereas in 'Carrizo' it depended on the severity of water stress reached in each phase (severe water stress in Phase I affected mainly the number of fruit, whereas it affected fruit size the most in Phase III). In the third year of DI treatment, water-use efficiency decreased sharply in trees on 'Carrizo' (70%) compared to trees on 'Cleopatra' (30%). Thus, trees on 'Cleopatra' were able to tolerate moderate water stress, whereas trees on 'Carrizo' were more sensitive to changes in soil water content.
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The new human leukocyte antigen (HLA)-C allele Cw*0742 was identified by sequence-based typing in a Caucasian bone marrow donor. HLA-Cw*0742 differs from Cw*070201 by a single nucleotide position at codon 113 (TAT --> TTT), giving rise to an amino acid substitution from Tyr to Phe.
Four new HLA classical class I alleles in the three loci are described in Caucasian individuals. A*3012 was first suspected by an abnormal serologic pattern that would be explained by the single amino acid substitution at the A30-specific Ser17. B*270505 differs from B*270502 in a silent substitution at an up to now constant position in the B locus. B*3541 encodes for a new Cys at position 118 that has not been encountered in neither human nor primate alleles. Cw*0716 seems to be originated by a large-scale interallelic recombination event between Cw*0701/*0706/*0718 and Cw*020202, giving rise to a new antigen-binding cleft conformation.
Data organization has become a strategic target for biologists due to the increasing volume of genomic data available for them. For this purpose, we need a complete knowledge model for representing biological system. In this paper, we deal with both processes for the creation and integration of shareable, reusable domain models within biology, which is a critical issue. In particular, this work introduces a new cooperative development approach for biology ontologies. This approach is based on the integration of the ontologies supplied by different human experts. Two experiments in biological domains are presented and their results discussed.
Two novel human leukocyte antigen (HLA) class II alleles for DRB3 and DQB1 genes detected in Caucasoid Spanish individuals are described: DRB3*0218 and DQB1*030202. Both alleles have been found during routine high-resolution typing by sequencing. DRB3*0218 shows a novel DRB3 gene polymorphic position, located at amino acid residue 58, alanine to glutamic acid. This residue is shared by several DRB1 alleles, including all described DRB1*11 subtypes. DQB1*030202 differs from DQB1*030201 by a point mutation at position 319 (T to C). This nucleotide change generates a new codon at amino acid position 75 that is not shared by any other DQB1 allele.
The hyperferritinemia-cataract syndrome, inherited as a Mendelian dominant trait, is due to mutations in the 5' non-coding region of the ferritin light chain gene that modifies the shape of the IRE (iron responsive element) region, which loses its normal function of regulating the synthesis of ferritin light chains. Excess of light chains results in complexes that accumulate into the lens giving rise to early cataracts. We present a Spanish family with seven affected members through three generations. A genetic study reveals a substitution of a single base (C-->T) at position 33 in the IRE sequence in the index case and in one affected brother, whereas a non-affected sister shows the normal sequence. The hyperferritinemia-cataract syndrome was identified in 1995 and is still poorly understood. Clinicians should suspect it when treating any subject with early cataracts, even more if they are familial, or in patients with very high levels of ferritinemia without evidence of iron overload. There are no known consequences of the syndrome other than cataracts, and its proper diagnosis carries a favorable prognosis and eliminates the risk of unnecessary phlebotomies.
Large volume leukapheresis (LVL) has been proposed as a simplified single-apheresis approach to collect the target number of CD34(+) cells. We retrospectively analyzed results of LVL in cytokine-mobilized patients weighing less than 20 kg to evaluate adverse events and variables affecting the yield. The only major adverse event recorded was transient and reversible systolic hypotension (three episodes). All the other adverse events were mild and did not require treatment. In multivariate analysis leukocyte count (P=0.001) and younger age (P=0.009) affected the CD34(+) cell number in the peripheral blood before apheresis. The number of CD34(+) cells before the apheresis was the only variable affecting CD34(+) cell yield in multivariate analysis (P=0.0001). In all, 77% of patients achieved the target CD34(+) cell dose of 2 x 10(6)/kg in their first apheresis. Recruitment was seen in 72% of the procedures, and this was related to the total blood volume processed (P=0.0005).
Patients that receive a T-cell depleted (TCD) hematopoietic stem cell transplantation (SCT) show higher risk of graft failure/rejection and of disease relapse than those that receive unmanipulated grafts. The purpose of the present investigation was to analyze the usefulness of chimaerism quantification in bone marrow (BM), peripheral blood (PB), and leukocyte lineages such as T lymphocytes (CD3+,both CD4+ and CD8+), B lymphocytes (CD19+) and myeloid cells (CD15+), for the early detection of graft failure/rejection episodes and disease relapse after TCD-PBSCT. Two of the ten (2/10) patients included in the study showed stable complete chimaerism (CC). The other 8/10 patients showed decreasing mixed chimaerism (MC) and 7 of them had either graft failure (n = 1)/rejection (n = 3) or disease relapse (n = 3). In two patients relapsed from chronic myeloid leukemia, MC was observed in BM and PB, with higher percentages of autologous cells in BM, as well as in leukocyte lineages, with higher percentages of recipient cells in the myeloid lineage than in lymphocytes. Combined analysis of chimaerism and minimal residual disease allowed early diagnosis of relapse and successful rescue therapy with donor leukocyte infusions (DLI), before the onset of hematological relapse. Chimaerism analysis allowed early diagnosis of incipient graft rejection in 3 patients. These patients showed MC both in BM and PB, with greater percentages of recipient cells in PB. Analysis of leukocyte lineages showed higher percentages of autologous cells in T lymphocytes (mainly CD8+) than in B or myeloid cells. Two of these patients were successfully treated with DLI and recovered normal PB counts and BM cellularity, as well as CC. The graft versus recipient hemopoiesis effect harbored by the donor immunocompetent cells infused seems useful forthe treatment of graft rejection, provided that an early diagnosis is made.
Two new HLA class I alleles have been recognised by molecular-based typing. B*3805 was initially identified by polymerase chain reaction using sequence-specific primers (PCR-SSP) and afterwards confirmed by sequencing based typing (SBT) studies in a Spanish Caucasian blood cord unit. A unique nucleotide change throughout exons 2, 3 and 4, leading to the amino acid replacement Ser11Ala, differentiates B*3801 and *3805. This position behaves as a dimorphic residue in HLA-B and -C loci, and seems to be structurally unrelated to peptide and TcR recognition. Cw*0408 was first detected by SBT in two African American bone marrow donors in combination with its most structurally related allele, Cw*04011. The single amino acid change found between Cw*04011 and Cw*0408 was Thr163Leu, a residue involved in pocket A of the peptide-binding cleft. This new allele could be the result of a gene conversion event between Cw*04011 and any of the Cw*03 alleles.
The development of molecular techniques for HLA typing has allowed the identification of genes previously assigned as serologic blank alleles. Lack or poor cell surface expression has been found for molecules coded by HLA-A, -B, -DRB4, -DRB5, and -DPB1 genes. In this report we describe the first HLA-C gene encoding for a null cell surface molecule. HLA-Cw*0409 N shows a point deletion at position 1095 within exon 7. This mutation provokes a codon reading shift, generating a new translation stop codon 97 bp downstream to that described in alleles normally expressed. This new stop codon location implies the presence of 32 extra amino acid residues in the cytoplasmic domain. Transfection experiments suggest that elongation of the cytoplasmic domain in Cw*0409 N would be the cause of cell surface expression failure, although Cw*0409 N heavy chain is able to create stable complexes with beta2-microglobulin. HLA-C fragment length analysis in a small selected group of samples with B44-Cblk haplotypic associations allowed us to identify two additional subjects showing both a serologic silent Cw*04 allele and a point base deletion at the 3' end of the HLA-C gene. This finding indicates that the allele frequency of Cw*0409 N within serologic C blank alleles would be appreciable, although basically restricted to the (A23)-Cw*0409 N-B*4403-DR7-DQ2 haplotype.
In children, the optimal mobilization schedule for harvesting peripheral blood progenitor cells (PBPC) is an issue of continuous research. We have studied a schedule based on high and daily divided doses of G-CSF (12 microg/kg body weight twice daily) for 4 days for PBPC priming. Toxicity related to G-CSF was observed in 13 patients (23%), mainly mild bone pain and myalgia. The median CD34(+)cell number collected was 4.4 (0.4-35 x 10(6)/kg body weight), with 46 patients achieving 2 x 10(6)/kg body weight (83.6%) after a single large volume leukapheresis. In conclusion, this mobilization schedule allows safe and efficient collection of the minimum target CD34(+) cell dose in most pediatric patients by only one procedure.
On the basis of the susceptibility of normal myelomonocytic cells to adenoviral vectors, we have studied the possibility of selectively transducing myelomonocytic murine leukemic cells (WEHI-3B) with regular (Reg-Ad) and genetically modified (RGD-Ad) adenoviral vectors. An 8-h incubation of WEHI-3B cells with 100 pfu of Reg-Ad vectors/cell resulted in the whole population becoming positive for transgene expression. Under identical conditions of infection, 20-30% of mouse bone marrow (BM) cells were positive for the transgene. When RGD-Ad vectors were used, a brief exposure (10 min) of WEHI-3B cells to 150 pfu of the virus/cell was enough for 100% of the leukemia cells to become positive for the marker transgene (EGFP). Under these conditions, only 15-20% of BM cells and of primitive hematopoietic progenitors (Lin(-)Sca-1(+) cells) became EGFP(+), indicating an improved selectivity of the vectors for the leukemic cells. The incubation of WEHI-3B but not normal BM cells with soluble fiber protein (FP) inhibited the infection with Reg-Ad. The use of the RGD-Ad bypassed the FP-CAR interaction required for the transduction of WEHI-3B cells with Reg-Ad, suggesting that the abrogation of this requirement accounts for the improved infectivity of these leukemic cells and for the selectivity of RGD-Ad in targeting WEHI-3B leukemia cells.
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Celiac disease is an immunological disease provoked by some cereal proteins in HLA-DQ-mediated susceptible individuals. The role of intestine infiltrating alphabeta T cells in the pathogenesis of the disease has been functionally established. In the present report, we have studied the repertoire of TCRBV genes, spectratype distribution, and CDR3 sequences of intestinal T cell populations isolated from three CD patients at diagnosis and two normal control biopsies. Oligoclonal TCRBV usage was observed both in CD and control samples. However, a much more restricted TCRBV usage was evident in normal mucosa. The use of BV gene families was linked to no dominant rearrangements in CD, while apparent oligoclonal patterns were found in normal biopsies. Only 3 out of 73 sequenced transcripts derived from preponderant TCRBV genes in the three celiac samples were obtained twice. In contrast, only 13 different rearrangements were found out of 32 analyzed in control samples. In spite of the polyclonal behavior of T cells in CD mucosa, some conserved motifs in the CDR3 region were noticed among rearrangements derived from different TCRBV genes and patients. The lack of expanded T cell clones in the damaged tissue could be explained in terms of antigen diversity or by non-specific immunological responses in the symptomatic phase of the disease.