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Biomedical subjects

L Contu

Publications and source records attributed to L Contu.

At least 55 records · Page 3Linked to original sources
PubMed1994

Successful unrelated bone marrow transplantation in beta-thalassaemia.

A 16-year-old Sardinian girl affected by homozygous beta-thalassaemia was submitted to allogeneic BMT using an HLA-identical, MLC-negative, unrelated donor. The donor and the patient were homozygous for the entire extended haplotype A30, Cw5, B18, F130, DRB1*0301, DRB3*0202, DQA1*0501, DQB1*0201 and heterozygous for DPB1*0301/DPB1*0202. The conditioning regimen consisted of 14 mg/kg busulphan and 160 mg/kg cyclophosphamide. Engraftment was achieved 14 days from BMT and the haematological reconstitution was complete without any signs of acute or chronic GVHD. Seven months after the transplant the patient was in excellent general condition. The hypothesis is advanced that when two HLA extended haplotypes are shared by donors and recipients, particularly in homozygosity, this is a very favourable immunogenetic condition in unrelated BMT.

Adolescent↗
PubMed1993

Association of the HLA-A2, CW2, B27, S31, DR2 haplotype with ankylosing spondylitis. A possible role of non-B27 factors in the disease.

With the aim of searching for HLA haplotypes and non-B27 allele frequency variations in Sardinian AS patients, HLA-A, B, Cw, DR, DQ and Bf, C4A and C4B typing and haplotype assignment was carried out in the families of 25 AS patients and in 44 healthy individuals, all B27 heterozygotes. In the AS patients a significant increase of the A2, Cw2, B27, DR2, DQ1 haplotype was found. This depends only partially on the linkage disequilibrium existing in the Sardinian population between B27 and the other alleles of this haplotype, and rather seems to be due to a primary association of Cw2 and DR2 alleles with AS. Preliminary data seem to show that this haplotype bears the S31 complotype and the DRB1*1601 allele both in the AS patients and in the healthy controls. The pathogenetic implications of these findings are discussed.

Adult↗
PubMed1993

Allogeneic bone marrow transplantation combined with multiple anti-HIV-1 treatment in a case of AIDS.

A 25-year-old woman with AIDS was submitted to HLA-identical allogeneic BMT after cytoablation with busulphan and cyclophosphamide and combined anti-HIV-1 therapy with zidovudine, IFN-alpha 2 and anti-HIV-1-specific T cell clones. Marrow engraftment occurred after 18 days and tests for HIV-1 were negative after 30 days but the hematologic reconstitution of the patient was poor. A second BM infusion from the same donor was ineffective and treatment with GM-CSF only induced a transient increase of the blood cell count, suggesting iatrogenic damage to the BM microenvironment. The development of ARDS led to the death of the patient 10 months after transplantation. Post-mortem investigation did not reveal any active infections and PCR on autopsy tissues was negative for HIV-1.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Pyridoxol L,2-pyrrolidon-5 carboxylate prevents active fibroplasia in CCl4-treated rats.

In the present study we evaluated the protective activity of pyridoxol L,2-pyrrolidon-5 carboxylate (metadoxine) against CCl4 intoxication in rats, especially in relation to liver fibrosis. After 6 consecutive weeks of CCl4 treatment, the animals developed liver fibrosis and inflammation as revealed by histological analysis which also included semiquantitative scoring of these features. In addition the serum levels of the immunoreactive prolyl hydroxylase (SIRPH), an enzyme involved in the hydroxylation of the procollagen molecule, were significantly higher (44.2 +/- 16.3 micrograms/ml; P less than 0.005) in this group of animals than in controls (26.1 +/- 8.06). On the contrary, animals treated with CCl4 + metadoxine (200 mg/kg i.p.) had less severe liver fibrosis and normal SIRPH levels (21.5 +/- 14.6). These data suggest that metadoxine may be an effective pharmacological tool for preventing the progression of liver disease in rats exposed to CCl4 to cirrhosis.

Animals↗
PubMed1992

Study of HLA segregation in 479 thalassemic families.

479 families, each with a proband affected by homozygous beta-thalassemia, were typed for HLA. 224 families with a total of 1020 members were typed for the HLA-A, B, C, DR and DQ loci and 255 families with 1046 family members, were typed for the HLA-A, B, and C loci. Altogether, 896 A, B, C, DR and DQ haplotypes and 1020 A, B and C haplotypes were defined. At the same time, 120 healthy unrelated individuals from the same population were typed and used as controls. The analysis of the results was carried out at antigen, allele, haplotype, genotype and sex ratio level with the aim of looking on the one hand, for the existence of heterogeneity between the probands, the unrelated individuals and the healthy siblings and, on the other, for the existence of any distortion whatsoever of the HLA segregation in either the probands or in the healthy siblings in respect of the expected values according to the Mendelian equilibrium. No significant differences were evident between the probands and the controls by the tests carried out at different levels of the HLA system. This leads us to exclude the existence of an association between beta-thalassemia and HLA in the population studied. Moreover, the analysis of the transmission of the alleles, the haplotypes, the genotypes and the sex-ratio by parents to both affected and to healthy children did not show any clear evidence of segregation distortion in respect of the theoretical values.

Alleles↗
PubMed1992

A high frequency of the A30, B18, DR3, DRw52, DQw2 extended haplotype in Sardinian celiac disease patients: further evidence that disease susceptibility is conferred by DQ A1*0501, B1*0201.

This study characterizes by serological and molecular methods the HLA class I and class II alleles in a group of celiac disease children, their parents and a control group of Sardinian descent. We found the DR3-DQw2 haplotype in all patients which was, in almost all cases (84%), associated with the HLA-A30, B18, DR3, DRw52, DQw2 extended haplotype named "Sardinian haplotype" because of its frequency (12-15%) in this Caucasian population. This is the first time that this DQw2-linked haplotype has been reported with such a high frequency in CD. However, no different distribution of "Sardinian haplotype" was found comparing CD patients with 91 haplotyped DQw2-positive controls. This finding indicates that the DQw2 antigen in Sardinians is almost always associated with the A30, B18, DR3, DRw52, DQw2 extended haplotype. The DQA1 and DQB1 second exon sequence analysis of the B18,DR3 and B8,DR3 haplotypes showed the DQA1*0501 and DQB1*0201 alleles which shared the already published sequences. DPB1 subtyping showed the DPB1*0301 allele more frequently (p less than 0.005) in CD patients but this difference was no longer significant when patients and controls, both heterozygous for the DR3-DQw2 haplotype, were compared. We suggest that the divergent HLA extended haplotypes and DP allele associated with CD, described in different Caucasian populations, can be explained by the particular DQw2 linkage disequilibrium in each population.

Adult↗
PubMed1992

HLA structure of the Sardinian population: a haplotype study of 551 families.

A study on the HLA structure of the Sardinian population was carried out on 551 healthy unrelated families representing all of the island districts. Altogether 2202 HLA-A, B, Cw, DR individual haplotypes and 853 different haplotypes were determined. Cavalli-Sforza and Edwards' genetic distance index for the total of 62 tested alleles showed a modest heterogeneity between one district and another (0.09-0.16). The genetic distance between Sardinians and the rest of the Italian population was 0.23 (0.22-0.26) and progressively increased in comparisons with caucasoids (0.26), negroids (0.34) and mongoloids (0.41). Sixty-three two-locus haplotypes with a high positive linkage disequilibrium were observed in our family sample. The percentages of two-locus haplotypes in LD shared with other populations turned out to be 45% with caucasoids, 20% with negroids and 10% with mongoloids. The distribution of the A, B, Cw, DR haplotypes is shown with 673 of them represented only once or twice, and 10 (1.2%) 14-322 times each. Of the latter, 8 are extended haplotypes, 6 of which characterize the Sardinian population. The analysis of our data suggests that the present-day Sardinian population is the result of a superposition of different populations, mainly consisting of caucasoids on a pre-caucasoid paleo-Mediterranean substratum.

Adult↗
PubMed1991

A new HLA-DR2 extended haplotype is involved in insulin-dependent diabetes mellitus susceptibility.

To ascertain why HLA-DR2 seems to confer only a moderate resistance to insulin-dependent diabetes mellitus (IDDM) in the high-incidence population of Sardinia, Italy, 32 families having one individual affected with IDDM (the proband) and 31 families without IDDM history were randomly selected from the same geographical area and serologically and molecularly HLA typed. The 64 haplotypes of the probands were then compared with the 122 haplotypes determined in the parents from the control families. Two haplotypes were found to have the highest percentage in the general population (12.3% and 7.3%, respectively). The first is the already described "Sardinian" extended haplotype A30, Cw5, B18, 3F130, DR3, DRw52, DQw2 (39.0% in IDDM patients). The second is an extended haplotype that has not been identified before (A2, Cw7, B17, 3F31, DR2, DQw1), and, due to the DR2 allele, we expected it to be decreased in IDDM. However, a stratified analysis performed by removing the DR3 and DR4 haplotypes showed that the frequency of this haplotype is significantly increased in IDDM patients. A peculiar feature of this haplotype is its DQw1 allele, which is DQB1*0502 and has serine in position 57 of the DQ beta chain. The absence of an aspartic acid in this position seems to confer susceptibility to IDDM and not resistance. The fact that DQB1*0502 was present in 75% of the Sardinian DR2 haplotypes may explain why, in Sardinia, DR2 is not providing the commonly recognized resistance to IDDM.

Autoimmune Diseases↗
PubMed1989

The "Sardinian" HLA-A30,B18,DR3,DQw2 haplotype constantly lacks the 21-OHA and C4B genes. Is it an ancestral haplotype without duplication?

The C4 and 21-OH loci of the class III HLA have been studied by specific DNA probes and the restriction enzyme Taq 1 in 24 unrelated Sardinian individuals selected from completely HLA-typed families. All 24 individuals had the HLA extended haplotype A30,Cw5,B18, BfF1,DR3,DRw52,DQw2, named "Sardinian" in the present paper because of its frequency of 15% in the Sardinian population. Eighteen of these were homozygous for the entire haplotype, and six were heterozygous at the A locus and blank (or homozygous) at all the other loci. In all completely homozygous cells and in four heterozygous cells at the A locus, the restriction fragments of the 21-OHA (3.2 kb) and C4B (5.8 kb or 5.4 kb) genes were absent, and the fragments of the C4A (7.0 kb) and 21-OHB (3.7 kb) genes were present. It is suggested that the "Sardinian" haplotype is an ancestral haplotype without duplication of the C4 and 21-OH genes, practically always identical in its structure, also in unrelated individuals. The diversity of this haplotype in the class III region (about 30 kb less) may be at least partially responsible for its misalignment with most haplotypes, which have duplicated C4 and 21-OH genes, and therefore also for its decreased probability to recombine. This can help explain its high stability and frequency in the Sardinian population. The same conclusion can be suggested for the Caucasian extended haplotype A1,B8,DR3 that always seems to lack the C4A and 21-OHA genes.

Blotting, Southern↗