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Biomedical subjects

R de Pablo

Publications and source records attributed to R de Pablo.

At least 37 records · Page 2Linked to original sources
PubMed1996

Complete coding region of the new HLA-DQB1*0612 allele, obtained by RT-PCR.

A novel HLA-DQB1 allele was detected by oligotyping in the Bubi population of Equatorial Guinea. In order to characterize the new allelic variant, a RT-PCR method which permitted the cloning of its complete coding region was designed. With this method, we have determined the nucleotide sequence of the new DQB1*0612 allele, related to *0604 and *0609 but differing from them at polymorphic codon 70. A proposal for the improvement of the sequencing strategies of HLA class II alleles is made.

Alleles↗
PubMed1996

Molecular cloning of two new HLA-C alleles: Cw*1801 and Cw*0706.

Nucleotide sequence analysis of the HLA-C alleles of the GB92 cell line, heterozygous for B*8101 and B*4407, revealed the existence of two new allelic variants: Cw*1801 and Cw*0706. The former allele, initially detected as a PCR-SSP variant, displays a hybrid aspect, sharing sequence motifs with Cw*07 at exons 1 and 2, and with Cw*04 at distal exons. In serological assays, Cw*1801 is only recognized by some cross-reactive sera. Cw*0706 shows a primary structure closely related to previously known Cw7 alleles, but carries new sequence motifs at its 3'-end. Preliminary data indicate that Cw*1801 is associated to B*8101 and that Cw*0706, B*4407 could account for a part of the Cw7, B44 haplotypes observed in African populations.

Alleles↗
PubMed1995

Anchored PCR cloning of the novel HLA-Cw*0704 allele detected by PCR-SSP.

The novel HLA-Cw*0704 allele, previously detected as the PCR-SSP variant Cw7/8v, has been cloned and sequenced from the homozygous typing cell KRO3/4 after amplification by anchored PCR. The nucleotide sequence of Cw*0704 is closely related to those of other Cw*07 alleles, but carries specific changes in exon 3 consistent with its serological behavior-a short Cw7 cross-reactive with antibodies directed against HLA-Cw8. Some of the substitutions of Cw*0704 have not been previously described for HLA-C but are found in HLA-B alleles and in published C sequences of non-human primates. The new allele carries a novel polymorphism in its 5' untranslated region (5' ut) that could be shared by all Cw*07 alleles. By PCR-SSP, Cw*0704 is a relatively common allele in English Caucasoids at a frequency of 4.6%. It is most often observed on HLA-B44 haplotypes previously described as HLA-C "blank", although linkage disequilibria with other HLA-B specificities have been found.

Amino Acid Sequence↗
PubMed1995

A novel TaqI/DQA RFLP associated with HLA-DR9, DQ9 (DQA1*0302).

A new TaqI/DQA restriction fragment length polymorphism (RFLP) has been found in two Spanish Caucasoid individuals. The novel polymorphic fragment has a relative mobility of 4.2 kb and is associated with an HLA-A2,Cw*1401,B51,DR9,DR53,DQ9 haplotype. Nucleotide sequence analysis indicates that individuals showing this RFLP pattern do not carry a new DQA1 allele, but that (DQA1*0302) commonly observed in DR9,DQ9 haplotypes. The new RFLP seems to be a locally restricted marker of uncertain origin.

Alleles↗
PubMed1994

Molecular characterization of a novel, serologically detectable, HLA-C allele: Cw*1602.

Cw*1602, a novel HLA-C allele belonging to the newly assigned Cw*16 group, has been cloned and sequenced from a Spanish Caucasoid cell expressing a "Cw6.2" phenotype. Some of the polymorphic substitutions of the new allele, and linkage disequilibrium to B51, had been predicted on the basis of previously published studies. The primary structure of Cw*1602 is in agreement with its serologic reactivity and, in comparison with that of Cw*1601, underlines the dimorphism of HLA-C molecules at residues 77 and 80 of the alpha 1-domain alpha helix.

Alleles↗
PubMed1993

Molecular cloning and polymerase chain reaction-sequence-specific oligonucleotide detection of the allele encoding the novel allospecificity HLA-Cw6.2 (Cw*1502) in Spanish gypsies.

A proposed novel allospecificity, HLA-Cw6.2, has been reported to be commonly found (approximately 25%) in Spanish Gypsies. Full-length cDNAs of the allele (Cw*1502) coding for this antigen have been cloned in this study. A simple PCR-SSO method for its detection has been standardized and a correlation with the serologic Cw6.2 phenotype has been established. This specificity has been also detected in the homozygous typing cell RML. Although the primary structures of Cw*1502 and Cw*0601 are not closely related, they share specific motifs that may account for their serologic cross-reactivity. Two novel HLA-C alleles (Cw*12022 and Cw*0602) are also reported.

Alleles↗
PubMed1993

Time course of hemostatic abnormalities in sepsis and its relation to outcome.

OBJECTIVES: To investigate the time course and the relation to prognosis of coagulation and fibrinolytic abnormalities in patients with septic shock. PATIENTS AND METHODS: Forty-eight consecutive patients admitted to the medical ICU with the diagnosis of septic shock (diagnosed by defined criteria) were studied. Mortality was 25 of 48. Mean age was 57 +/- 7.3 years. Blood samples were obtained on days 1, 4, and 7 after hospital admission to measure tissue-type plasminogen activator antigen (t-PA), urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitor antigen (PAI-1), plasminogen, alpha 2-antiplasmin, fibrinogen, antithrombin III, protein C, protein S, thrombin-antithrombin complexes (TAT), D-dimer, and von Willebrand factor-related antigen (vWF:Ag). RESULTS: All patients showed marked abnormalities in both the coagulation and fibrinolytic systems. There were signs of coagulation activation and elevation of both activators and inhibitors of fibrinolysis. Nonsurvivors showed lower levels of protein C and antithrombin III and higher concentration of TAT than survivors. While both t-PA and PAI-1 concentrations were high in survivors and nonsurvivors, only survivors showed a progressive normalization of both parameters during the study period. Low plasminogen levels and plasminogen/alpha 2-antiplasmin ratio were found in both groups, presenting a trend toward normalization only in survivors. The differences reported were not apparent at the time of hospital admission. CONCLUSIONS: Septic shock is characterized by coagulation activation and fibrinolysis activation and inhibition. Nonsurvivors present a particular hemostatic profile characterized by a more marked activation of coagulation and a more intense inhibition of fibrinolysis. None of the abnormalities studied was significantly different between survivors and nonsurvivors at the time of hospital admission. In the presence of fibrin formation, nonsurvivors present a maintained imbalance in the fibrinolytic response determined by higher PAI-1 plasma concentration, probably contributing to their poor outcome.

Antithrombin III↗
PubMed1992

[The effects of prostacyclin on oxygen transport in adult respiratory distress syndrome].

BACKGROUND: Patients with the adult respiratory distress syndrome (ARDS) present a deficit of tissue oxygenation which may be unmasked if increases in oxygen uptake (VO2) are observed when increases in oxygen delivery (DO2) are induced. Prostacyclin is a drug to which microvasodilator effects have been attributed and it has been proposed as an efficient agent for increasing histic enhancement of oxygen. METHODS: An infusion of prostacyclin was administered to 13 patients diagnosed with ARDS at doses of 10, 20, and 30 ng/kg per minute monitored with a Swan-Gatz catheter. RESULTS: The values are expressed as the percentage median of the increase with p less than 0.05 being considered as statistically significant. Prostacyclin significantly increased DO2 (10, 18 and 15% at the different doses). The VO2 rose significantly only following the first dose (13%). There was a correlation between the increase of DO2 and that of VO2 following the administration of the first dose (r = 0.70, p = 0.017. An important systemic vasodilator and pulmonary effect was observed accompanied by increases in the pulmonary (20, 56 and 59%) and reductions of PaO2 (-33.5, -40 and -48%) which may have been due to inhibition of hypoxic vasoconstriction. CONCLUSIONS: Prostacyclin is efficient for unmasking a lack of oxygen in patients with adult respiratory distress syndrome. The deleterious effects of this drug on systemic hemodynamics and on gaseous interchange makes not only the monitorization of arterial pressure but also of the parameters of gaseous interchanges necessary in these patients.

Adult↗
PubMed1992

Characterization of an HLA-DR15 DQ5 haplotype found in the Spanish Caucasoid population.

HLA class II typing by RFLP and PCR-SSOP has been performed on HLA-DR2-positive individuals as a part of a study on MHC in a Spanish Caucasoid population. The results of this study reveal that HLA-DR15 (DRB1*1501 DRB5*0101) and DQ5 (DQA1*0102 DQB1*0501/0502) are not uncommonly associated in such a population. Family segregation has been assessed and allogeneic reactivity against some classic DR2 haplotypes has been tested; a stimulatory capability of DQ6 antigen in this situation is shown. It is suggested that the reported association is not uncommon in European Caucasoids as well as in other populations and it should be considered in matching for transplantation and in DR2-associated diseases.

Base Sequence↗
PubMed1992

Distribution of HLA antigens in Spanish Gypsies: a comparative study.

We have studied the HLA-class I and class II antigen distribution in a sample of 75 Spanish Gypsies and 74 Spanish non-Gypsies by serology, restriction fragment length polymorphism, and protein chain reaction and hybridization with allele-specific oligonucleotide probes. When both population samples are compared, we find that Gypsies have a statistically significantly higher frequency of A1, A11, B61, Cw6, DQ5 and haplotypes DR16 DQ5 Dw21 and DR14 DQ5 Dw9 DR52b. Frequency of A3, A29, B44, DR4, DQ2, DQ8 and haplotypes DR1 DQ5 and DR7 DQ2 DB17 DR53 are significantly lower in this ethnic group. The analysis of the serological data in the two populations demonstrates that Cw6 can be split into long Cw6 (Cw6.1) and short Cw6 (Cw6.2). Haplotype A1-Cw6-B61-DR14-DQ5 is the most characteristic in Gypsies, with a frequency of 13%. Estimation of the genetic distances shows that Spanish Gypsies are closer to Indian Caucasoid populations than to the Spanish non-Gypsy population. HLA data support the proposed historical origin of this ethnic group.

Alleles↗