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O Olerup

Publications and source records attributed to O Olerup.

106 records · Page 6Linked to original sources
PubMed1990

[HLA and associated diseases--progress in molecular biology].

HLA genes and their products are of central importance for the development of autoimmune diseases. HLA antigens influence the immune repertoire of T cells and therefore all immune responses are HLA dependent. Research in molecular genetics have helped to identify both HLA genes and specific T cell clones involved in autoimmune reactions, which create possibilities of immune intervention.

Antigen-Presenting Cells↗
PubMed1989

T and B cell responses of Plasmodium falciparum malaria-immune individuals to synthetic peptides corresponding to sequences in different regions of the P. falciparum antigen Pf155/RESA.

The C-terminal (3') amino acid repeat region of the Plasmodium falciparum Ag Pf155/RESA, a vaccine candidate, contains immunodominant T and B cell epitopes. In order to identify additional T cell epitopes in the molecule, synthetic peptides corresponding to the centrally (5') located repeat region, as well as to four nonrepeated regions, were synthesized. T cells from 46 P. falciparum-primed individuals living in a holoendemic area of The Gambia where malaria transmission is seasonal were tested for their responsiveness to the peptides by thymidine incorporation and IFN-gamma release. There was a considerable variation in the response to different peptides. Proliferation and IFN-gamma release were not correlated in individual donors, underlining the importance of measuring both activities when screening donor populations for total T cell responsiveness to a given Ag. Whereas 72% of the donors responded with proliferation and/or IFN-gamma release to the intact protein the mean % responders to the peptides was 40%. The most frequent responses (up to 60%) were induced with peptides from the 3'- and 5'-repeat region of the protein. Analysis of some closely related sequences in the 3'-repeat region indicated that they contained at least two epitopes that were either distinct or cross-reacting in different donors, suggesting difference in the genetic control of these responses. When the same peptides were investigated for reactivity with antibodies, the best T cell inducing sequences also displayed the best antibody reactivities. However, in individual donors, T and B cell responses were not correlated. T cell responses were shown to persist after a period with no P. falciparum transmission, whereas antibody concentrations tended to decrease, suggesting differences in the requirements of boosting at the T and B cell levels, respectively.

Amino Acid Sequence↗
PubMed1989

Primarily chronic progressive and relapsing/remitting multiple sclerosis: two immunogenetically distinct disease entities.

HLA class II gene polymorphism was investigated in 100 patients with clinically definite multiple sclerosis (MS) by restriction fragment length polymorphism analysis of Taq I-digested DNA using DRB, DQA, and DQB cDNA probes. Twenty-six patients had primarily chronic progressive MS and 74 had relapsing/remitting MS. The latter group included patients with a secondary progressive evolution of symptoms. Both clinical forms of MS were found to be associated with the DRw15,DQw6 haplotype. In addition, primarily chronic progressive MS was positively associated with the DQB1 restriction fragment pattern seen in DR4,DQw8, DR7,DQw9, and DRw8, DQw4 haplotypes, as well as negatively associated with the Taq I DQB1 allelic pattern corresponding to the serological specificity DQw7. Relapsing/remitting MS was positively associated with the DQB1 allelic pattern observed in the DRw17,DQw2 haplotype. These three DQB1 alleles are in strong negative linkage disequilibria with DRw15. The two susceptibility markers of each clinical form of MS act additively in determining the genetic susceptibility, as the relative risks for individuals carrying both markers roughly equal the sum of respective risks. Different alleles of the DQB1 locus defined by restriction fragment length polymorphisms contribute to susceptibility and resistance to primarily chronic progressive MS as well as to susceptibility to relapsing/remitting MS. The observed immunogenetic heterogeneity between the different clinical forms of MS favors the hypothesis that primarily chronic progressive MS and relapsing/remitting MS are two distinct disease entities.

Alleles↗
PubMed1989

Individuals with HLA-DR blank alleles display well-known DR-DQ RFLPs.

We have characterized HLA-DRB, -DQA, and -DQB gene polymorphism in a large number of serologically DR blank haplotypes with the restriction enzymes Taq I, Bam HI, and Pvu II, with the aim of finding new RFLPs in the Caucasian population. Locus-specific RFLPs were combined for a definition of Taq I DR-DQ haplotypes. All observed DNA haplotypes could be found in a control group of 100 individuals, but with a different distribution. Serologically less well-defined specificities were over-represented in the blank group, in particular the DRw13-associated Taq I DR-DQ haplotype T-13.3. We conclude that the majority of DR blank haplotypes are probably closely related or identical to previously defined DR alleles. The extent of DR polymorphism in the Caucasian population seems to be well mapped, considering the extremely small proportion of rare Taq I DR-DQ haplotypes and lack of new patterns in this study.

Alleles↗
PubMed1988

Allergic contact dermatitis to nickel is associated with a Taq I HLA-DQA allelic restriction fragment.

RFLP analysis of the HLA class II genes DRA, DQA, and DQB was performed in 33 patients with allergic contact eczema to nickel. A significant association with a Taq I HLA-DQA allelic restriction fragment was found. Twenty-two of 33 patients compared to 31 of 100 healthy controls had a 4.5-kb DQA fragment (corrected P value less than 0.05, relative risk 4.5, and etiologic fraction 0.52). In order to study whether the magnitude of the response in a lymphocyte proliferative assay to nickel sulfate was controlled by HLA class II genes or not, the patients were divided into low, intermediate, and high responders. No significant differences were found in the distribution of Taq I HLA class II allelic patterns between the groups.

DNA Probes, HLA↗
PubMed1988

T cell reactivity of defined peptides from a major Plasmodium falciparum vaccine candidate: the Pf155/RESA antigen.

Several immunodominant B-cell epitopes of the P. falciparum antigen blood stage Pf155/RESA, a major vaccine candidate antigen, are located in the molecular regions containing amino acid repeats. We started to map Pf155/RESA for T cell reactive epitopes. For this purpose, short synthetic peptides corresponding to the 3'- and 5' repeat regions of the molecule as well as to non-repeated sequences outside these regions were prepared. T cells from P. falciparum primed donors from two highly endemic areas of Africa were tested for their responsiveness to the peptides by thymidine incorporation and/or interferon gamma (IFN-gamma) release. There was a considerable variation in the response to the different peptides. However, the strongest and most frequent responses were seen with a few peptides from the 3'- and 5'-repeat regions. Thus, the immunodominant B cell epitope regions of Pf155/RESA, contain several T cell epitopes. Since the repeat regions are known to be conserved in different P. falciparum strains, the T cell epitopes reported here may be suitable constituents of a P. falciparum subunit vaccine.

Animals↗
PubMed1985

Neuropeptide Y may mediate effects of sympathetic nerve stimulations on colonic motility and blood flow in the cat.

The present study investigated sympathetic mechanisms involved in the regulation of colonic motility and blood flow in the cat. Infusion of neuropeptide Y (NPY) close i.a. produced an inhibition of colonic motility and a vasoconstriction of long duration but no post-infusion vasodilatation. In contrast to NPY, porcine pancreatic polypeptide did not evoke any vascular or motility response. On a molar basis, NPY was 25 times more potent than noradrenaline in producing 50% reduction of the colonic blood flow. These vascular and motility effects of NPY were resistant to guanethidine, phentolamine, phenoxybenzamine and propranolol. Thus, the action of NPY on vascular and colonic smooth muscle did not seem to be mediated via adrenergic receptors. Noradrenaline administered close i.a. produced inhibition of colonic motility, and vasoconstriction followed by a rapid vasodilatation. These effects were completely blocked by combined alpha- and beta-adrenoceptor blockade. Electrical stimulation of the splanchnic and lumbar colonic nerves produced an overall inhibition of colonic motility, and vasoconstriction of the proximal and distal colon, respectively, with a rapid post-stimulatory vasodilatation. After combined alpha- and beta-adrenoceptor blockade the inhibitory effect of the nerve stimulations on colonic motility partly remained together with a marked vasoconstriction, which was most pronounced upon lumbar colonic nerve stimulation. All vascular effects of sympathetic nerve stimulation were eradicated by guanethidine, which also abolished the inhibitory motility response to splanchnic nerve stimulation. However, lumbar colonic nerve stimulation elicited a colonic contraction, possibly due to stimulation of afferent C-fibres. The present findings indicate the existence of a sympathetic nonadrenergic neuronal mechanism mediating vasoconstriction and inhibition of colonic motility in the cat. Thus, NPY may be released from noradrenergic neurons to act on colonic smooth muscle and vessels.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

Human leucocyte antigen (HLA) and malaria morbidity in a Gambian community.

Human leucocyte antigen (HLA) class I and class II typing was performed on 177 children in a rural area of The Gambia who were followed for 2 years in a longitudinal study of malaria morbidity. A comparison was made between those who experienced an episode of clinical malaria in one or both years and those who showed no evidence of infection in either year. No convincing association was found between morbidity and class I phenotype. An overall association of morbidity with the distribution of class II haplotypes was seen, but association with individual DR-DQ haplotypes were not conclusive.

Animals↗
PubMedDate not supplied

No human leukocyte antigen-A, -B or -DR association in Swedish patients with hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a cicatrizing, inflammatory and recurrent disease restricted to inverse skin, such as that of the axilla and groin of younger adults. In a previous study, using serological tissue-typing techniques, no significant increases in the human leukocyte antigen (HLA)-A and -B specificities were found in patients with HS. The aim of this study was to determine the frequencies of HLA-A, -B and, for the first time, HLA-DR alleles, using genomic tissue-typing methods in patients with HS. Forty-two unrelated Swedish patients with HS were included and compared with 250 controls. According to clinical staging adopted from Hurley all of the patients had stage II HS, i.e. recurrent abscesses with tract formation and cicatrization and single or multiple widely separated lesions. No association with HLA-A, -B or -DRB1 alleles was found in patients with HS. Genetic factors associated with the HLA class I or II regions do not appear to contribute significantly to the possible genetic susceptibility of HS.

Adult↗