Tsunami generation potential of a strike-slip fault tip in the westernmost Mediterranean.

Tsunamis are triggered by sudden seafloor displacements, and usually originate from seismic activity at faults. Nevertheless, strike-slip faults are usually disregarded as major triggers, as they are thought to be capable of generating only moderate seafloor deformation; accordingly, the tsunamigenic potential of the vertical throw at the tips of strike-slip faults is not thought to be significant. We found the active dextral NW-SE Averroes Fault in the central Alboran Sea (westernmost Mediterranean) has a historical vertical throw of up to 5.4 m at its northwestern tip corresponding to an earthquake of Mw 7.0. We modelled the tsunamigenic potential of this seafloor deformation by Tsunami-HySEA software using the Coulomb 3.3 code. Waves propagating on two main branches reach highly populated sectors of the Iberian coast with maximum arrival heights of 6 m within 21 and 35 min, which is too quick for current early-warning systems to operate successfully. These findings suggest that the tsunamigenic potential of strike-slip faults is more important than previously thought, and should be taken into account for the re-evaluation of tsunami early-warning systems.

Neuromyelitis optica and multiple sclerosis in sisters.

INTRODUCTION: The association of neuromyelitis optica (NMO) and multiple sclerosis (MS) has been reported, but details of the cases were not described. We report two Venezuelan Caucasian sisters with human leukocyte antigen (HLA) typing. RESULTS: Patient 1 fulfilled McDonald, et al. criteria with HLA A*24; B*07,*15; DRB1*01,*16 (DR2 positive). Patient 2 fulfilled the NMO revised criteria of Wingerchuck, et al. with HLA A*02,*24; B*07,*40; DRB1*04,*08, similar to Canadian aboriginal NMO cases and the Yukpa population from Venezuela. CONCLUSION: These cases confirmed the coexistence of NMO and MS in sisters, and further studies are needed to understand the genetic linkage between these diseases.

Application of a chimeric synthetic peptide in the development of a serologic method for the diagnosis of hepatitis G virus infection.

New putative antigenic peptides corresponding to the N- and C-terminal of the E2 envelope protein of GBV-C/HGV were synthesized using solid-phase chemistry. The antigens were obtained in linear and chimeric forms with the main aim of improving the sensitivity of the enzyme immunoassays. Furthermore, CD and FTIR have been used in conjunction to characterize their conformational changes showing that the chimeric peptide presents a more ordered secondary structure than its parent peptides.

Immune reconstitution after allogeneic stem cell transplantation with reduced-intensity conditioning regimens.

Reduced-intensity conditioning (RIC) regimens have been increasingly used as an alternative to conventional myeloablative conditioning (MAC) regimens for elderly patients, for patients medically infirm to qualify for conventional allogeneic stem cell transplantation (SCT), and for disorders in which traditional MAC-SCT are associated with high rates of non-relapse mortality. One of the theoretical advantages of RIC-SCT is that it might lend to better immune reconstitution after transplantation due to less damage of the thymus, allowing regeneration of naive T cells derived from prethymic donor stem cells, and due to the proliferation of immunologically competent host T cells that survive the conditioning regimen. Although limited, studies comparing immune recovery following RIC and MAC-SCT have been insightful. One of the main difficulties of these studies is the current spectrum of RIC protocols, which vary considerably in myeloablative and immunosuppressive potential, resulting in apparently contradictory findings. In spite of this, most reports have shown significant quantitative and/or qualitative differences in T- and B-cell reconstitution after RIC-SCT in comparison with conventional SCT. This paper will review current knowledge of immune reconstitution following RIC-SCT.

Prognostic factors of radiographic progression in early rheumatoid arthritis: a two year prospective study after a structured therapeutic strategy using DMARDs and very low doses of glucocorticoids.

The objective of the study was to analyze the prognostic factors of radiographic progression in a series of patients with early rheumatoid arthritis (RA) after 2 years of therapy with a structured algorithm using disease-modifying antirheumatic drugs (DMARDs) and very low doses of oral glucocorticoids. One hundred and five patients (81% female) with early RA (disease duration <2 years) treated with the same therapeutic protocol using gold salts and methotrexate in a step-up strategy, together with methylprednisolone (4 mg/day), were followed up for 2 years. The outcome variable was radiographic progression after 2 years of DMARD therapy using the modified Larsen method. Clinical, biological, immunogenetic, and radiographic data were analyzed at study entry and after 1 and 2 years of follow-up. Radiographic progression (increase of four or more units in the Larsen score) was observed in 32% of patients after 2 years of follow-up. The percentage of erosive disease increased from 18.3% at baseline to 28.9% at 12 months and 44.6% at 24 months, in spite of a significant improvement in disease activity. New erosions appeared in 33% of patients after 2 years. Several baseline parameters were associated with radiographic progression in the univariate analysis: shared epitope (SE) homozygozity, HLA-DRB*04 alleles, female gender, hemoglobin, erythrocyte sedimentation rate, and anticyclic citrullinated peptide antibodies (anti-CCP). In the multivariate analysis, female gender [odds ratio (OR) 5.5, 95% confidence interval (CI): 1.1-28.2, p = 0.04], DRB1*04 alleles (OR 3.1, 95% CI 1.1-9, p = 0.03) and, marginally, anti-CCP antibodies (OR 3.6, 95% CI 0.9-14.5, p = 0.06), were associated with progression. Female patients with both DRB1*04 alleles and anti-CCP antibodies showed the highest scores in radiographic progression. The presence, but not the titer, of anti-CCP antibodies predicted progression. The positive predictive value of the multivariate model for progression was only 53.9% whereas the negative predictive value was 80.3%. In a series of early RA patients treated with a structured algorithm using DMARDs and very low doses of glucocorticoids, radiographic progression was observed in one third of patients after 2 years. Female gender, DRB1*04 alleles (rather than the SE), and the presence of anti-CCP antibodies at baseline (independently of the titer) were the most important predictors of progression. The utility of these parameters in clinical practice is limited by their relatively low positive predictive value.

Antigenicity of chimeric and cyclic synthetic peptides based on nonstructural proteins of GBV-C/HGV.

In this work, new putative epitopes located in nonstructural proteins of GBV-C/HGV were synthesized using solid-phase chemistry for their use in immunoassays. The antigens were obtained in linear, chimeric and cyclic forms with the main aim of improving the sensitivity of the enzyme immunoassays. Our results showed, on one hand, that the combination of different antigens seems to be necessary to ensure good sensitivity and more specificity and, on the other hand, that cyclic compounds show higher ability to recognize anti-GBV-C/HGV antibodies than its parent peptide. Furthermore, CD and FTIR have been used in conjunction to characterize the conformational changes therein with synthetic constructs that could explain their different antigenicity.

Clinical characteristics, beta-cell function, HLA class II and mutations in MODY genes in non-paediatric subjects with Type 1 diabetes without pancreatic autoantibodies.

OBJECTIVE: To study clinical characteristics, beta-cell function, HLA typing and mutations in the hepatocyte nuclear factor (HNF)-1alpha and HNF-4alpha genes in Type 1 diabetes mellitus (T1D) patients without pancreatic autoantibodies. DESIGN AND METHODS: Twenty patients without pancreatic autoantibodies (Ab neg) and 20 with autoantibodies (Ab pos), age/gender matched, were included (age 17-34 years). Islet cell, glutamic acid decarboxylase, tyrosine phosphatase and insulin autoantibodies, basal and stimulated C-peptide were measured. HLA-DRB1-DQA1-DQB1 typing and screening for mutations in the HNF-1alpha and HNF-4alpha genes were performed. RESULTS: No differences were found in clinical presentation, metabolic control and beta-cell function in the two groups (onset or after 12 months). DRB1*0301-DQA1*0501-DQB1*0201 was the most frequent haplotype in both groups but we found a higher proportion of protective T1D haplotypes and Asp(beta57) in the Ab neg group, but in all the cases in combination with susceptible T1D haplotypes. We found two previously reported polymorphisms (HNF-1alpha, Ala98Val; HNF-4alpha, Thr130Ile) in Ab neg and a new variant (Ser165Gly) in the HNF-4alpha gene in an Ab pos subject. Conclusions In a non-paediatric population with newly diagnosed T1D, the absence of islet antibodies does not imply clinical or metabolic differences when compared with those cases with islet antibodies. Despite a similar HLA-DR/DQ typing, the presence of protective alleles and molecular properties in a higher proportion in the Ab neg group suggests that these factors could modulate the presence or absence of islet antibodies. Variants in HNF-1alpha and HNF-4alpha are unlikely to be major contributors to the pathogenesis of diabetes in antibody-negative T1D.

Immunocytochemical evidence on the effects of glucocorticoids on type I collagen synthesis in human osteoblastic cells.

The effects of glucocorticoids on DNA synthesis and cellular function were assessed in cultures of human osteoblastic cells by using indirect immunoperoxidase staining with a type I antiprocollagen antibody and by measuring procollagen type I N and C propeptides (PINP, PICP) in the culture medium by radiometric methods. Likewise, we analyzed the correlation between intracellular immunostaining and procollagen propeptides released into the culture medium, as well as the correlation between PINP and PICP. Human osteoblasts were cultured with and without addition of dexamethasone (DEX) at two supraphysiological concentrations, 10(-6) M and 10(-7) M, for 24 and 48 h. Treatment with DEX at 10(-6) M was associated with a significant decrease in the percentage of cells showing intracellular type I procollagen immunoreactivity at 24 and 48 h ( P < 0.05). Similar effects were observed with 10(-7) M DEX. Dexamethasone 10(-6) M and 10(-7) M also induced significant decreases in PINP and PICP values after 24 and 48 h of treatment ( P < 0.05). The decrease in intracellular procollagen immunoreactivity and propeptide secretion was not associated with a reduction in DNA synthesis. A highly significant correlation was observed between the values of PINP and PICP in the culture medium as well as between the values of intracellular immunostaining and PINP and PICP ( P < 0.001). In conclusion, our results suggest that supraphysiological doses of glucocorticoids produce a direct inhibition on osteoblastic function through their effect on type I procollagen synthesis. Immunoperoxidase detection of type I intracellular procollagen as well as the quantification of PINP and PICP in the culture medium are reliable methods of assessing osteoblast function.

Prevalence and clinical significance of anti-cyclic citrullinated peptide and antikeratin antibodies in palindromic rheumatism. An abortive form of rheumatoid arthritis?

OBJECTIVE: To analyse the prevalence and clinical significance of anti-cyclic citrullinated peptide antibodies (anti-CCP) and antikeratin antibodies (AKA) in patients with palindromic rheumatism (PR). METHOD: Sixty-three patients with PR were included: 33 were defined as pure or persistent PR at the time of serum test measurement, and 30 as associated PR, defined as patients with past history of PR who had developed persistent arthritis at the time of serum test: [21 with rheumatoid arthritis (RA)]. Sixty patients with early RA, and 80 with seronegative spondyloarthropathy were included as control groups. Anti-CCP were determined by a standardized ELISA test and AKA by indirect immunofluorescence in rat oesophagus. Clinical characteristics of these pure PR patients were compared according to the presence or absence of anti-CCP antibodies. A follow-up study was also performed. RESULTS: Anti-CCP were detected in 18 out of 32 (56.3%) patients with pure PR and 10 out of 30 (33.3%) with associated PR (38.1% in RA-associated PR patients). AKA were detected in 12 patients out of 33, with pure PR (36.4%), and in 9 out of 30 with associated PR (30%) (33.3% in RA-associated PR patients). The prevalence of anti-CCP and AKA in the RA control group was 55% (not significantly different from the pure PR group) and 61.7% (with respect to pure PR patients, P=0.02), respectively. In the spondyloarthropathy group, the prevalence of anti-CCP and AKA was 2.5 and 3.8%, respectively (P<0.001 compared with pure PR patients). No significant clinical differences were observed between pure PR patients with and without CCP antibodies. CONCLUSIONS: Anti-CCP and, to a lesser extent, AKA, were found in a high proportion of patients with PR, suggesting that this syndrome is an abortive form of RA. The predictive value of these antibodies in PR, as markers of progression to an established RA, remains uncertain.

Radiological progression in early rheumatoid arthritis after DMARDS: a one-year follow-up study in a clinical setting.

OBJECTIVE: To analyse the frequency and prognostic factors of radiographic progression in a series of Spanish patients with early rheumatoid arthritis (RA) after 1 yr of treatment with disease-modifying anti-rheumatic drugs (DMARDs). METHODS: Sixty patients (47 females, 13 males) with RA with a disease duration shorter than 2 yr [mean (s.d.) duration 9.5+/-6.6 months] were treated with the same therapeutic protocol using gold salts as the first DMARD and methotrexate as a second option, and were followed up for 1 yr. Radiographic progression in the hands and feet (total radiographic Larsen score and the erosion joint count) was used as the outcome variable. Clinical, laboratory, immunogenetic and radiographic data were obtained at study entry. Disease activity and response to therapy were measured at 6 and 12 months. RESULTS: Erosive disease was found in 21.7% of patients at baseline and in 38.3% after 1 yr. Although a substantial reduction in disease activity was observed during the 1 yr follow-up [disease activity score (DAS28) 5.8+/-0.8 at entry and 3.9+/-1.3 at 12 months, P < 0.001], the Larsen score rose from 1.9+/-3.3 to 5.6+/-9.8 after 1 yr. In 26.6% of patients, a raised erosion joint count was observed after 1 yr. Radiographic progression in the total joint radiographic damage (increase in Larsen score of >or=2) was observed in 36.6%. In the multivariate analysis, baseline pain [visual analogue scale (VAS)] and the presence of two copies of the shared epitope were associated with radiographic progression in the erosion joint count. Disease duration before study entry, VAS pain and Larsen score at baseline were significant predictors of radiographic progression in total damage (Larsen score). Baseline radiographic damage had the highest positive predictive value for progression. CONCLUSIONS: Radiographic progression was observed in up to 36.6% of patients with early RA after 1 yr of DMARD therapy in spite of a significant reduction in disease activity. Baseline factors, such as VAS pain, disease duration until DMARD therapy, damage score at baseline and the presence of two copies of the shared epitope, were associated with radiographic progression.

Differences in secondary structure of HAV-synthetic peptides induced by the sequential order of T- and B-cell epitopes.

The present study was undertaken to examine the structural features of two peptide constructs designed on the basis of linear combination of B and T-cell epitopes in different orientations (BT and TB) that may be important to explain the differences in the elicited antihepatitis A virus immune response and in the interaction with biological model membranes. A CD study was carried out and the corresponding quantitative analysis of the experimental data was done using deconvolution computer programs. Moreover, fluorescence experiments were performed to analyze differences in the fluorescence emission spectra of both molecules. The main conformational difference by CD studies was obtained working in aqueous medium. Although the TB sequence adopted a preferably random coil structure, the BT peptide was best fitted with beta-type structures. These results are further supported by fluorescence studies. These findings have relevance for the design of synthetic immunopeptides.

Assessment of synthetic peptides for hepatitis A diagnosis using biosensor technology.

In the present work we demonstrate the application of a commercial biosensor instrument (BIACORE 1000, Biacore AB, Uppsala) for the detection of antibodies against the hepatitis A virus (HAV) in human serum samples using linear and branched synthetic peptides related to the VP3 capsid protein of HAV. We also studied the conformation of the synthetic peptides by circular dichroism (CD) in order to analyse the changes in secondary structure of the constructs that could influence their recognition by antibodies. Linear and dimeric VP3(110-121) multiple antigen peptides (MAP) were the most sensitive and appropriate for serological studies of serum from HAV infected patients using BIACORE. Immobilization of tetrameric MAPs via amine groups apparently failed to preserve the active conformation of the peptide epitope since it led to lower antibody binding compared to linear and dimeric peptides. The CD analysis showed that the tetrameric MAP constructs tend to adopt a beta-sheet structure due to intermolecular aggregation, which limits epitope accessibility. Our results demonstrate the value of biospecific interaction analysis technology using synthetic peptides for the diagnosis of acute hepatitis A.

Use of linear and multiple antigenic peptides in the immunodiagnosis of acute hepatitis A virus infection.

The reactivities of two panels of anti-HAV human sera from geographically distinct areas (Chile and Spain) to synthetic peptides from the VP1, VP2 and VP3 hepatitis A virus capsid proteins were examined by an enzyme-linked immunosorbent assay (ELISA) procedure. Two and four branched multiple antigenic peptides (MAPs) and palmitoylated peptides were compared with free synthetic sequences for the detection of IgM anti-HAV antibodies in the two panels of human sera. Our results showed that acute hepatitis A patient sera recognized preferentially homogeneous two branched MAPs and palmitic acid conjugated peptides. The palmitoyl-derived VP3(110-121) peptide and the corresponding dimeric MAP were the most sensitive and appropriate for serological studies of HAV-infected patients by ELISA, sensitivity and specificity being higher than 90% and 95%, respectively. These peptide-based tests open up new avenues in the development of peptide-based immunosorbent assays for the detection of acute HAV disease.

Association study of proposed candidate genes/regions in a population of Spanish asthmatics.

A number of genes/regions have recently been reported to be linked to asthma or its related phenotypes (i.e. atopy and bronchial hyperresponsiveness), by genetic linkage and allele-sharing methods. We have performed a case-control study comparing the allelic distribution of nine microsatellite markers and two genetic variants in a group of patients attended at emergency room departments because of an acute attack of asthma with respect to an external healthy population of controls. A total of 146 asthmatic subjects and 50 population controls from Barcelona, Spain, were genotyped for nine microsatellite markers from some asthma/atopy candidate genes/regions: the beta-subunit of the high-affinity IgE receptor (Fc epsilonRI-beta) located on chromosome 11; the 5q31-32 candidate region; the T-cell receptor genes, TCR-alpha on chromosome 14 and TCR-beta on chromosome 7. Two genetic variants of the beta-subunit of the high-affinity IgE receptor (Fc epsilonRI-beta) gene were also analyzed. None of the asthmatic or control individuals carried the Ile181Leu variant. There were no significant differences between asthmatic and control subjects neither for the polymorphic markers nor for the other variant of the beta-subunit of the high-affinity IgE receptor (Fc epsilonRI-beta) gene. No association could be observed in this sample of Spanish asthmatics with the genes/regions studied.

HLA class II haplotypes in primary sclerosing cholangitis patients from five European populations.

The association of primary sclerosing cholangitis (PSC) to HLA class II genes was studied by comparing patients from five different European populations. Deduced HLA-DRB1, DQA1, DQB1 haplotypes of 256 PSC patients from England, Italy, Norway, Spain and Sweden were compared to those observed in 764 ethnically-matched controls. Increased frequencies of the DRB1*03, DQA1*0501, DQB1*02 (RR=3.0, P<0.00001) and the DRB1*13, DQA1*0103, DQB1*0603 haplotypes (RR=2.4, P<0.0001) were observed in all five patient groups. A total of 16% of the PSC patients were homozygous for the DRB1*03, DQA1*0501, DQB1*02 haplotype compared to 1% of the controls (RR=20, P<0.0001). The DRB1*04, DQA1*03, DQB1*0302 haplotype was significantly reduced in frequency(RR=0.4, P<0.00001). Among Norwegian, Swedish and British patients that did not carry neither the DRB1*03, DQA1*0501, DQB1*02 nor the DRB1*13, DQA1*0103, DQB1*0603 haplotype, an increased frequency of the DRB1*15, DQA1*0102, DQB1*0602 haplotype was observed (RR=2.0, P<0.0001). Thus, PSC was found to be positively associated to three different HLA class II haplotypes (i.e. the DRB1*03, DQA1*0501, DQB1*02, the DRB1*15, DQA1*0102, DQB1*0602 and the DRB1*13, DQA1*0103, DQB1*0603 haplotypes) and negatively associated to one HLA class II haplotype (i.e. the DRB1*04, DQB1*0302 haplotype).

Effects of insulin administration in a group of high-risk, non-diabetic, first-degree relatives of Type 1 diabetic patients: an open pilot trial.

AIMS: To elucidate the effect of prophylactic insulin, in a treatment schedule previously demonstrated to achieve beta-cell rest, in a group of high-risk, non-diabetic first-degree relatives of Type 1 diabetic patients. METHODS: Ten high risk subjects for Type 1 diabetes mellitus (DM) (seven male/three female, aged 19.8+/-9.6 years) defined as: first-degree relatives of Type 1 DM patients, islet cell autoantibodies (ICA) > or =20 Juvenile Diabetes Foundation (JDF) units twice, first phase insulin response (FPIR) to glucose in an intravenous glucose tolerance test < or =10th percentile of a control group were included in an open pilot trial. Five were treated with subcutaneous insulin: 0.1 IU/kg body weight/day of neutral protamine hagedorn (NPH) insulin once a day. Five declined treatment and were used as controls. Control and treatment groups did not differ in terms of age, ICA, insulin autoantibodies (IAA), glutamic acid dehydrogenase (GAD) and FPIR. RESULTS: Three out of five subjects in both groups developed Type 1 DM during follow-up: after 21, and 32-57 months in the insulin-treated group and after 4, and 18-60 months in the untreated group. Three out of six subjects who developed overt diabetes had a FPIR below the 2nd percentile of the control value at the onset of the study. All subjects who developed diabetes were positive for antibodies to GAD and expressed the HLA-DR3 or DR4 alleles, whereas only one of the non-progressors had these parameters (P < 0.05). During follow-up, a decrease in ICA titres was observed in the group which received prophylactic insulin in contrast with the untreated group. GAD, as well as insulin secretory capacity, remained unchanged in both groups. CONCLUSION: The subcutaneous administration of insulin (0.1 IU/kg body weight/day of NPH insulin once a day) in our group of high-risk subjects for Type 1 DM produced only a minor effect in some immunological markers (ICA), without preventing the development of overt disease. The efficacy and safety of insulin used at either a different dose or by a different route, as well as its potential effect in the early phases of prediabetes, warrants further investigation.

Heritability of running economy: a study made on twin brothers.

Running economy (RE), defined as the steady-state of oxygen uptake (VO2) for a given running velocity, is a factor of sports performance the genetic component of which has seldom been reported to date. We studied this component using a heritability index (HI) in a group of 32 male twins, 8 monozygotic (MZ) and 8 dizygotic (DZ) pairs, all sportsmen with similar perinatal and environmental backgrounds. Zygocity was determined by the identity of erythrocytic antigenic, protein and enzymatic polymorphism, and human leucocyte antigen serologic types between co-twins. The subjects exercised twice on a treadmill, once until exhaustion and again at submaximal intensities. Pulmonary gas exchange was measured continuously using an automatic analyser system during both tests. Blood samples were obtained during the recovery period to determine lactate concentrations. No significant differences were observed between MZ and DZ, in respect of RE at any speed or in maximal VO2 relative to body mass. Nevertheless, significant HI (P < 0.05) was found in maximal lactate concentrations (HI=0.75) and in respiratory equivalent for oxygen at two speeds, 7 km x h(-1) HI=0.71) and 8 km x h(-1) (HI=0.79), differences which probably suggest that there are differences in RE. In conclusion, we did not detect a genetic component in RE or in maximal oxygen uptake, but a genetic component for markers of anaerobic metabolism was present.

Comparison between a lyse-and-then-wash method and a lyse-non-wash technique for the enumeration of CD34+ hematopoietic progenitor cells.

The flow cytometric enumeration of CD34+ hemopoietic precursor cells (HPC) present in samples used for transplantation of HPC has proven to be the most powerful single parameter for prediction of engraftment. At present, several different methodological approaches are used for the flow cytometric enumeration of CD34+ HPC. In the present study we have compared two of these methods as regards enumeration of CD34+ HPC and their CD34+/CD19- and CD34+/CD19+ subsets: a lyse-non-wash procedure based on the use of a recently commercialized red cell lysing solution (Quicklysis, Cytognos, Salamanca, Spain) and a lyse-and-then-wash method in which the Becton Dickinson (San Jose, CA) FACS Lysing Solution was used. For that purpose a total of 52 samples corresponding to 20 G-CSF mobilized peripheral blood (PB) samples and 21 PB-derived leucapheresis products from patients undergoing autologous PB stem cell harvest, together with 11 bone marrow (BM) samples from healthy volunteers were analyzed. Our results show that for each of the three types of samples analyzed the use of the lyse-and-then-wash method is associated with significantly lower numbers of both total CD34+ HPC (P < or = 0.003) and its major CD34+/CD19- subset (P < or = 0.01) while no significant changes are detected in the number of CD34+/CD19+ HPC in BM samples (P > 0.05). The use of an internal standard (reference beads) added just prior to data acquisition, showed that the differences between both methods are due to a selective loss of CD34+ HPC and its major CD34+/CD19- subset in BM (P=0.002 and P=0.003), PB (P < 0.0001 and P < 0.0001) and PB-derived leucapheresis products (P < 0.0001 and P=0.0001). Finally, addition of a centrifugation and washing step to a group of 11 leucapheresis samples lysed with Quicklysis showed that they did not significantly affect the overall number of total CD34+, CD34+/CD19- and CD34+/CD19+ HPC obtained. In line with these findings elimination of centrifugation and washing steps when FACS Lysing Solution was used to lyse mature red cells almost corrected for the selective loss of CD34+ HPC. In spite of these differences a significant degree of correlation (r > 0.83 in all cases) was found between both methods regarding the total number of CD34+, CD34+/CD19- and CD34+/CD19+ HPC present in the BM, PB and PB-derived leucapheresis samples analyzed in this study.

HLA class II genes in soybean epidemic asthma patients.

From 1981 to 1987, 26 outbreaks of asthma caused by the inhalation of soybean dust, affecting a total of 688 individuals, were detected in Barcelona, Spain. Because only a small proportion of asthmatic individuals living in Barcelona expressed the epidemic phenotype, it is hypothesized that a genetically determined human leukocyte antigen (HLA) Class II factor could have played a role in the susceptible individuals. Accordingly, we studied the distribution of both HLA-DR and HLA-DQ in soybean epidemic asthmatic patients. An analysis of the HLA-DR and HLA-DQ genes for genetic polymorphisms of the beta 1 chain was done with the polymerase chain reaction (PCR) in 78 soybean epidemic asthma patients, and the findings were compared with those for 67 nonepidemic asthmatic individuals and 168 individuals from the general population. An allelic disequilibrium could be established; the risk of epidemic asthma was particularly associated with the DRB1*13 gene (p value corrected for multiple comparisons < 0.02). The association observed for the DRB1*13 gene was stronger in individuals in the lowest tertile for total IgE, with an estimated risk with a 95% confidence interval (CI), of 14.5 (1.6 to 130.8). The combination of two genes from among the DRB1*05-05, DRB1*05-06, and DRB1*06-06 genes was present in epidemic asthmatic subjects only. No association with an HLA-DQB1 allele could be observed. Genetic predisposition could contribute to the response of some asthmatic patients to exposure to soybean dust, having led to their being affected during the epidemics of asthma in Barcelona.

Could the A2A11 human leucocyte antigen locus correlate with maximal aerobic power?

1. The power of the aerobic metabolic pathway correlates well with successful physical performance in endurance sports events. The ability to alter the pathway through training presents well-known limitations, and consequently a good genetic endowment is essential to participate in elite sporting activities. 2. In 32 subjects (16 healthy pairs of male twin sportsmen, 8 monozygotic and 8 dizygotic) zygosity was determined by means of the genetic analysis of human leucocyte antigen (HLA) system specificities at class I and II loci and other genetic variants. The subjects performed a progressive exercise test on a treadmill to ascertain the maximal oxygen uptake (VO2max), measured by an automatic breath-by-breath analyser. We have considered the relationship between the A, B and C loci of the HLA system and VO2max. 3. We found a high correlation between the presence of both HLA A2 and A11 and VO2max. In the A2A11 group (n = 6) we found a VO2max (mean +/- SD) equal to 71 +/- 4 ml min-1 kg-1. The group without this pair of alleles (n = 26) showed a much lower aerobic power (58 +/- 5 ml min-1 kg-1). Differences between the two groups were found to be largely significant (P < 0.001). It is noteworthy that in two pairs of dizygotic twins, the higher VO2max value corresponded to the twin with the A2A11 allele. 4. The very marked concordance between the presence of the A2A11 locus of the HLA system and the VO2max could be of great interest for the identification of outstanding performers.