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Biomedical subjects

M G Ercilla

Publications and source records attributed to M G Ercilla.

At least 19 recordsLinked to original sources
PubMed2006

Relevance of MICA antibodies in acute humoral rejection in renal transplant patients.

The presence of MICA antibodies was examined in eleven patients diagnosed with AHR. MICA typing was performed in both recipients and donors. Sera were collected sequentially: pre-transplant, at the AHR episode and at follow-up. Sera from 30 patients with functioning graft were also analysed. A stable MICA()008 transfected cell line was used as target to identify MICA antibodies. MICA antibodies were not detected pre-transplant nor post-transplant in patients receiving a compatible graft. MICA antibodies were detected post-transplant AHR in patients receiving an incompatible graft. The persistence of MICA antibodies was associated with chronic graft dysfunction in 3 of 4 patients in this series; although it was not always associated with the graft loss in treated AHR. None of the 30 patients in the control group with long-term functioning grafts showed antibodies to MICA()008. This report provides some insights of the relevance of MICA antibodies in AHR.

Acute Disease↗
PubMed2006

The prevalence of HFE C282Y gene mutation is increased in Spanish patients with porphyria cutanea tarda without hepatitis C virus infection.

OBJECTIVES: To investigate the role of C282Y and H63D mutations, and hepatitis C virus (HCV) infection in the pathogenesis of porphyria cutanea tarda (PCT). DESIGN: Prospective case-control study. SETTING: A large clinical and research institute for the study and treatment of cutaneous diseases in Barcelona, Spain. PATIENTS: Ninety-nine consecutive patients with PCT and one hundred and twenty-six control patients (76 healthy subjects and 50 patients chronically infected with HCV), were recruited. MAIN OUTCOME MEASURES: The frequency of the C282Y and H63D mutations in patients with PCT vs. controls and the relationship of these mutations with HCV infection, and iron status, as judged by serum iron, liver iron and ferritin levels. RESULTS: C282Y mutation was significantly increased in PCT patients. This mutation was more frequent among non-HCV-infected patients. Increased ferritin levels and hepatic iron overload were also observed in PCT patients with heterozygous C282Y state. H63D mutation was only significantly increased among PCT patients with chronic hepatitis C infection. No significant iron overload was observed in patients with H63D mutation. CONCLUSIONS: This study confirms the high frequency of C282Y mutation in patients with PCT and its relationship with iron overload. The C282Y mutation has a relevant role in Spanish patients with PCT not associated with HCV chronic infection. On the other hand, the prevalence of the H63D mutation seems not to be increased in patients with PCT. The possibility of an association between HCV infection and H63D mutation in inducing PCT can be hypothesized.

Adult↗
PubMed2004

Description of a novel HLA-DRB1 allele found in a candidate for bone marrow transplantation.

We report the identification of a new DRB1* allele in a Spanish Caucasoid family during a search for a histocompatible bone marrow donor. This novel allele, designated as DRB1*1145, differs from DRB1*1123 in one nucleotide at position 199 in exon 2 (A replacing T), leading to one amino acid change from phenylalanine (Phe) to isoleucine (Ile) at codon 67. The propositus's father had identical class II alleles but showed a minor mismatch at locus B (B*4403 by B*4402) and a C-locus mismatch (Cw*1502 by Cw*0501). We discuss the criteria of selecting a non-related bone marrow donor with a minor mismatch on the DRB1* allele or the related father having a minor mismatch at B locus and a C-locus mismatch.

Alleles↗
PubMed2001

Identification of a new HLA-DRB1 allele (DRB1*0318) in three members of a Caucasian Spanish family.

This communication reports the identification of a new allele HLA-DRB1*03 in three members of a Caucasian Spanish family. The new allele has been officially named HLA-DRB1*0318 by the World Health Organization Nomenclature Committee. The exon 2 sequence of this new allele is identical to that of DRB1*03011 except for the first nucleotide of codon 45. The nucleotide change (C replacing G) leads to the amino acid substitution of glycine to arginine (GGG-->CGG) at position 45. This position of the beta1 domain shows very little polymorphism among DRB1* alleles (nucleotide changes at this position have only been reported for DRB1*1436 and DRB1*0105) and locates in the vicinity of the highly polymorphic position 47, which is a constituent of the groove's pocket interacting with the amino acid position 7 of the antigen peptide. The familial study showed that the new allele was maternally transmitted into the HLA-A*3002, -B*1801, -Cw*0501, -DRB1*0318, -DRB3*0202, -DQB1*0201 haplotype. Interestingly, the two siblings of the family, which were HLA identical and suffered of insulin-dependent diabetes mellitus (IDDM), were carriers of the two HLA haplotypes (DRB1*03/DQB1*0201 and DRB1*04/DQB1*0302) reported as susceptibility markers to IDDM in Caucasians.

Alleles↗
PubMed1996

Genotyping hepatitis C virus isolates from Spain, Brazil, China, and Macau by a simplified PCR method.

An improved and simplified method of genotyping was developed for classifying hepatitis C virus (HCV) isolates into the five common genotypes, i.e., I/1a, II/1b, III/2a, IV/2b, and V/3a, by PCR with genotype-specific primers deduced from the core gene. Sense and antisense primers, specific for each of the five common genotypes, were designed by comparison of 319 core gene sequences from HCV isolates of various genotypes from genetic groups 1 to 9. In the first round of PCR, a sequence of 433 bp representing nucleotides 319 to 751 was amplified with universal primers. The second round of PCR was performed with respective sense and antisense primers in two separate reactions, one for the amplification of genotypes I/1a and II/1b and the other for the amplification of genotypes III/2a, IV/2b, and V/3a. The specificity of genotyping was confirmed with a panel of 191 serum samples containing HCV isolates whose core gene sequences were known: 110 serum samples infected with HCV of the five common genotypes and 81 serum samples infected with HCV of other genotypes. The use of sense and antisense primers for genotype II/1b (primers 389 and 492) abolished the cross-reaction of the antisense primer for genotype II/1b (primer 133) with some HCV isolates of genotype I/1a found by our original method. The new method was used for genotyping 130 HCV isolates from Spain, 53 from Brazil, 106 from China, and 30 from Macau. A total of 329 bp of the NS5b region (nucleotides 8279 to 8607) of five isolates from Spain and five isolates from Macau which could not be classified as any of the five common HCV genotypes or genotype 2c were sequenced, and the sequences were compared with those of HCV isolates of known genotypes; two isolates from Spain were deduced to be of genotype 4d and one was deduced to be of genotype 1d, while the remaining two isolates from Spain had novel genotypes in genetic group 2; however, all five isolates from Macau were of genotype 6a.

Brazil↗
PubMed1995

Persistent hepatitis C viremia after acute self-limiting posttransfusion hepatitis C.

Persistent viremia after clinical or subclinical hepatitis C virus (HCV) infection is believed to occur in patients with chronic hepatitis C, but little is known about the duration of HCV replication in patients with acute hepatitis who have recovered or the relation of HCV viremia with the kinetics of antibodies to HCV (anti-HCV). We tested HCV-RNA and anti-HCV in serial serum samples from 41 patients with posttransfusion non-A, non-B hepatitis, followed for an average of 6 years after transfusion. Serum HCV-RNA was measured by nested polymerase chain reaction, which used primers from the 5' untranslated region of the HCV genome. Anti-HCV were tested with first- and second-generation enzyme-linked immunosorbent assays (ELISA 1 and ELISA 2), and with a second-generation recombinant immunoblot assay. Of the 41 patients, 10 recovered and 31 progressed to chronic liver disease. HCV-RNA was detected in serum before or simultaneously with the onset of hepatitis in all cases, and lasted between 2 and 6 weeks in 5 of the 10 patients who recovered, whereas it persisted for the entire follow-up period in every case with chronic hepatitis and in the remaining 5 patients with self-limiting hepatitis. Anti-HCV were detected with ELISA 2 in the first serum sample, with raised serum transaminases in 57% of patients, but in only 6% with ELISA 1. In the sample obtained 1 month after the onset of hepatitis, anti-HCV were detected with ELISA 2 in 94% of patients, but in 34% with the ELISA 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Is hepatitis C virus infection a trigger of porphyria cutanea tarda?

The causes of liver disease, ranging from fatty changes to cirrhosis and hepatocellular carcinoma, in porphyria cutanea tarda (PCT) remain unclear. We tested 100 consecutive PCT patients for antibodies to hepatitis C virus (HCV) by enzyme-linked immunosorbent assay and a recombinant immunoblot assay. 75 (79%) patients with sporadic PCT but none of 5 with familial PCT were positive. HCV RNA was found in serum of all 18 anti-HCV-positive patients tested. There were no significant differences in the prevalence of anti-HCV between treated and untreated patients or between those with and without various HCV risk factors. The frequency of anti-HCV increased with the severity of liver histology. These findings implicate HCV in the aetiology of PCT-associated liver disease.

Enzyme-Linked Immunosorbent Assay↗
PubMed1992

[Familial study for the early diagnosis of insulin-dependent diabetes mellitus].

BACKGROUND: Diabetes is more frequently found than expected in families of first grade with children with diabetes type I. METHODS: With the aim of identifying the potential candidates prone to develop diabetes type I, genetic and metabolic analysis was carried out on the members of 11 families with a diabetic type I child. They were distributed into three groups: 11 diabetic patients (IDDM); 22 progenitors and 13 unaffected siblings. The HLA haplotype was determined, the spectrum of autoantibodies and the intravenous glucose tolerance test (IVTT) were performed. RESULTS: In two progenitors postprandial glycemia values corresponding to intolerance to carbon hydrates were obtained. Moreover, in one the IVTT was found to be low in the normal values. Of a total of 12 non diabetic descendents studied, 4 shared identical HLA haplotypes as the diabetic, 5 were haploidentical and 3 unidentical. The DR 3 antigen was detected in 90% of the diabetics; in 68% of the progenitor group and in 50% of the non diabetic descendents. Sixty-two percent of the children inherited the DR 4 antigen of the father (p less than 0.05), while 37% do so from the mother. Of the siblings with a haplotype identical to that of the diabetic, 2 were also ICA positive; asymptomatic at the moment of the study but in one the diabetes type I became manifest after 2 years of evolution. CONCLUSIONS: Subjects at high risk of becoming type I diabetics may be identified at a preclinical phase by means of HLA typing and the detection of immunologic and metabolic markers associated with the disease.

Adolescent↗
PubMed1991

Incidence of non-A, non-B hepatitis after screening blood donors for antibodies to hepatitis C virus and surrogate markers.

OBJECTIVE: To compare the effect of screening blood donors for antibodies to hepatitis C virus (anti-HCV) on the incidence of non-A, non-B hepatitis in recipients with that of screening blood donors for antibodies to hepatitis B core antigen (anti-HBc) and elevated alanine aminotransferase levels. DESIGN: Cohort analysis of serum samples from donors and recipients. Recipients were followed for 12 months to determine the occurrence of non-A, non-B hepatitis. SETTING: The blood-transmitted viruses unit and the liver unit of a university teaching hospital. SUBJECTS: A total of 250 patients who had open heart surgery and their 3142 blood donors. MEASUREMENTS: Donor sera were tested for anti-HCV by enzyme-linked immunosorbent assay (ELISA) and, in the event of a positive result, by recombinant immunoblot assay (RIBA). Antibodies to anti-HBc and serum alanine aminotransferase (ALT) levels were also measured. Measurements of anti-HCV and ALT activity in recipients were done before transfusion and at regular intervals during follow-up. MAIN RESULTS: Of the 250 transfusion recipients, 40 developed non-A, non-B hepatitis. Of the 3142 donors, 70 were positive for anti-HCV by ELISA, 440 were positive for anti-HBc, and 177 had alanine aminotransferase levels between 0.67 and 1.33 mukat/L. The sensitivity (87%), specificity (89%), positive predictive value (59%), and negative predictive value (97%) of blood-donor screening were higher for anti-HCV than for anti-HBc (82%, 36%, 21%, and 91%, respectively) and 70%, 29%, and 91%, respectively). The expected number of donors excluded because of the presence of anti-HCV was considerably smaller than that of donors with positive results for surrogate markers of hepatitis. CONCLUSION: Screening blood donors for the presence of anti-HCV is more accurate than screening for surrogate markers (anti-HBc and ALT) and protects more effectively against post-transfusion non-A, non-B hepatitis.

Alanine Transaminase↗
PubMed1991

Sequence analysis of the putative structural genes of hepatitis C virus from Japanese and European origin.

cDNA fragments encoding the putative structural genes of the hepatitis C genome were isolated from a plasma pool of Japanese non-A, non-B hepatitis patients and from sera of individual Spanish patients. From the Japanese plasma pool a series of E1 clones was obtained that showed 88-98% homology among each other, both at the nucleotide and amino acid level. Compared to the sequences published by the Chiron Corporation and Takeuchi et al., the amino acid homology was 75-79% and 91-94%, respectively. Analysis of the core and E2/NS1 genes showed a high conservation of the core sequence and a high sequence variation in the 5' end of the E2/NS1 gene. The E1 gene of one Spanish isolate showed greater homology to the Chiron than to the Japanese sequence. Another Spanish isolate was more homologous to the Japanese sequence indicating that both hepatitis C genotypes are present in Europe. Analysis of the E1 gene of an isolate derived from a single patient with a 5-year interval revealed nine nucleotide and five amino acid changes.

Amino Acid Sequence↗
PubMed1990

Hepatitis C virus infection in patients with nonalcoholic chronic liver disease.

STUDY OBJECTIVE: To determine the prevalence and meaning of antibodies to the hepatitis C virus (HCV) in patients with nonalcoholic chronic liver diseases. DESIGN: Cross-sectional study. SETTING: The liver unit of a referral-based university hospital. PATIENTS: Three hundred and forty-six consecutive patients, including 137 with cryptogenic chronic liver disease, 156 with chronic hepatitis B, 47 with primary biliary cirrhosis, and 8 with persistently abnormal aminotransferase serum levels and normal liver histology. Among patients with cryptogenic liver disease, 41 received blood transfusions before discovery of liver disease and 18 had circulating nonorgan-specific autoantibodies. For comparison, 1495 apparently healthy volunteer blood donors were included in the study. LABORATORY INVESTIGATIONS: The presence of anti-HCV antibodies (anti-HCV) was determined by a recently developed enzyme-linked immunoassay. MEASUREMENTS AND MAIN RESULTS: In patients with cryptogenic liver disease, the prevalence of anti-HCV was 82% (95% CI, 76% to 89%), being higher (P = 0.02) in patients with histories of blood transfusion than in those with unknown sources of exposure. Antibodies to HCV were not detected in patients with antinuclear antibodies at high titer. Among patients with chronic hepatitis B, anti-HCV were found in 11% (CI, 5% to 18%) of those with hepatitis B virus (HBV)-associated DNA in serum and in 29% (CI, 17% to 43%) of those with undetectable HBV replication (P less than 0.05). The prevalence of anti-HCV in blood donors was 1.2% (CI, 1.1% to 1.3%). CONCLUSIONS: Our results indicate that HCV infection probably plays an important etiologic role in cryptogenic liver disease and, in some patients, in chronic hepatitis B. Determining whether anti-HCV are present appears to be useful for differentiating viral from autoimmune chronic liver diseases.

Adolescent↗
PubMed1989

[Susceptibility to chronic HLA-system-associated lymphocytic thyroiditis. Its relationship with insulin-dependent diabetes mellitus].

The genetic association between HLA-system and chronic lymphocytic thyroiditis (CLT) related or not to type I diabetes mellitus (IDDM), have been analysed in three groups of children: 16 with CLT, 9 with CLT and IDDM, 11 with IDDM and 200 normal controls. The DQw1 antigen (75% vs 55%) was found associated with CLT, furthermore the observed increase of DR1 and DR2 antigens (37% respectively) is secondary to the linkage disequilibrium that exists between them and DQw1. DR3 antigen (60%) was found significantly increased (p less than 0.001) in CLT patients compared with the control group (24%). In diabetic patients, DR3 and DR4 were found in 85% and 63% respectively (p less than 0.001). The DR3 associated haplotype in CLT patients was different from the diabetic one's. All the diabetics, but one, were DR3-B18 haplotype carriers, but this association was only found in 25% CLT patients. The titre of thyroid microsomal antibodies (MCHA) was more frequent in the patients with DQw1 antigen (MCHA DQw1+ : 1/1072; DQw1- : 1/606). The CLT predisposition in childhood may be influenced by genes located within the HLA-region probably more than one, different from the genes related to IDDM. One of this genes closed to the HLA-DQ region, will be involved in the production of autoantibodies.

Adolescent↗
PubMed1989

[Use of FMC macromolecular medium for determination of the erythrocyte ABO group using microtiter plates].

Several blood group determination techniques have been developed in recent years which provide easy handling, fine reproducibility and similar or even higher sensitivity than the procedures commonly employed, aimed to be used in the automation of blood bank work. A microtitration plate technique for ABO determination on red cells is presented in this report. A macromolecular medium, comprised of a mixture of the polymers Ficoll 400 and carboxymethyl cellulose (FMC) is used ad coadjuvant for the reaction. This medium increases by 15- the score units and by 4-fold (or more) the intensity of haemagglutination (titration) in typing the ABO antigenicity of red cell A, B, O and AB groups.

ABO Blood-Group System↗