PubMed Health⌕ Search

Biomedical subjects

K Gustafsson

Publications and source records attributed to K Gustafsson.

At least 73 records · Page 4Linked to original sources
PubMed1994

Serologic survey for Toxoplasma gondii infection in the brown hare (Lepus europaeus P.) in Sweden.

Serum samples from 176 brown hares (Lepus europaeus P.) shot in three areas of south and central Sweden during 1984 and 1985 were analyzed for antibodies to the protozoan parasite Toxoplasma gondii using several serological assays. No toxoplasma antibodies were detected in any of the sera, either by direct agglutination test or by ELISA, and selected sera were also negative in the IFAT and the Sabin Feldman dye test. Based on the high incidence of acute fatal toxoplasmosis in hares in Scandinavia, we propose that the brown hare is exceptionally susceptible to primary T. gondii infection.

Agglutination Tests↗
PubMed1994

Dose-response effects of boiled carrots and effects of carrots in lactic acid in mixed meals on glycaemic response and satiety.

OBJECTIVE: To evaluate the effect of dosage on the metabolic response to vegetables added to a mixed lunch meal, and to relate the amounts to the tripartite plate model. Carrots were chosen as an example, and the carrots were blanched, frozen and boiled to include possible effects of processing and cooking. The effects of carrots steeped in lactic acid, as produced at fermentation, were also studied. DESIGN: The test meals with carrots, and the control meal without vegetables, were balanced regarding energy (2000 kJ) and digestible carbohydrates (60 g) and similar in fat (17 g) and protein (16-19 g) content. The carrot portions of 100, 200 and 300 g contained 2.9, 5.8 and 8.7 g dietary fibre respectively. The meals were served in the morning after an overnight fast and in random order. Blood samples for the analysis of blood glucose, plasma insulin and C-peptide were collected and satiety was graded until 210 min postprandially. SETTING: The study was performed at the research laboratory, Dalby Health Sciences Centre (primary care). SUBJECTS: The 10 healthy, male volunteers, around 40 years of age, were recruited at random from the district's population list. None dropped out. RESULTS: The larger the carrot portion the lower were the glucose and insulin/C-peptide responses and the higher the satiety scores. The minimum amount causing significant effects was 200 g. According to the plate model, 200 g of boiled carrots was the most that could be included on half the plate. Addition of lactic acid to 200 g carrots augmented the effects on satiety scores and hormonal response. CONCLUSIONS: The addition of generous amounts of vegetables to a mixed meal improves the metabolic response.

Adult↗
PubMed1993

Extensive allelic polymorphism in the CDR2-like region of the miniature swine CD4 molecule.

MHC class II polymorphism is well documented whereas only minimal polymorphism has been reported for the CD4 molecule with which it interacts. We report on the structural basis of an allelic polymorphism of the CD4 molecule in miniature swine. Eleven of 13 nucleotide differences between the 2 alleles cause amino acid replacements. A majority of these replacements are clustered in a region protruding as a loop structure, termed Ig CDR2-like, from the surface of the amino terminal domain. This part of the human CD4 appears to comprise the binding site for the human immunodeficiency virus gp120 protein. The loop structure has also been implicated in the binding of CD4 to MHC class II, but this is currently a matter of some controversy. Our previous results have indicated that the porcine CD4 polymorphism, that we now show is situated in this loop, does not significantly affect the binding to class II. However, because the polymorphism appears to have been selected for and is situated in a very exposed part of the molecule, it is likely to be of functional significance.

Alleles↗
PubMed1993

Effects of different vegetables in mixed meals on glucose homeostasis and satiety.

Different vegetables--carrots, peas, Brussels sprouts and spinach--were added to a typical Swedish lunch test meal in portions of 96-164 g. The test and the control meals without vegetables were balanced with respect to digestible carbohydrates (59.7 g) and energy (2000 kJ, 475 kcal), and as far as possible also concerning protein and fat. The added vegetables contained 4.4 g dietary fibre. The meals were prepared by microwave heating and served in the morning after an overnight fast to 10 healthy, male volunteers. Postprandial blood glucose, plasma insulin and C-peptide levels were measured at regular intervals until 210 min. The satiety was graded on a simple scale of 1-10. The meal with spinach elicited significantly lower insulin and C-peptide responses than the control meal, but no significant differences in glucose response or satiety were observed. The other vegetables tested showed no significant effects either on glucose and hormonal responses or on satiety.

Adult↗
PubMed1992

Structure and expression of class II alpha genes in miniature swine.

Two overlapping genomic clones corresponding to the swine DRA class II gene were isolated and characterized. Restriction mapping and partial sequence data of the exon-containing fragments allowed identification and orientation of the five exons encoding the alpha chain. Two full length cDNA clones corresponding to the transcribed DRA gene from two different haplotypes of the swine MHC were sequenced. Nucleotide sequence alignments revealed that the two swine DRA cDNA were very similar and closely related to the human DRA equivalent. An additional glycosylation site, compared with those of human DRA, was found in the second external domain of the protein. Northern analyses showed that porcine DRA and DQA genes were the only two class II alpha genes expressed in the spleen, despite the presence of DPA and DZA genes in the genome. In addition to transfected cells expressing homologous pairs of alpha and beta chains from SLA-DR, stable transfectants expressing nonhomologous pairs of alpha and beta chains from DR and DQ loci were obtained, suggesting that such associations may contribute to the functional heterogeneity of class II products.

Animals↗
PubMed1992

Exon encoding the antigen-binding site of MHC class II beta-chains is divided into two subregions with different evolutionary histories.

The evolution of the Ag-binding site of polymorphic class II molecules was investigated by comparing the pattern of silent and replacement substitutions in the first domain exon of DQB and DRB alleles in two distantly related mammalian species, man and cattle. We show that the first domain can be subdivided into two regions, corresponding to the beta-strand and alpha-helical regions, with distinct evolutionary histories. The data for the alpha-helical region are in conflict with the standard phylogeny of mammalian class II genes. In this region, there is only weak locus divergence at the protein level and the frequency of silent substitutions is extremely low between nonorthologous genes (i.e., DQB-DRB) within species. We propose that the major underlying cause for the observed sequence similarity in the alpha-helical region is due to a selective constraint restricting the sequence divergence at the protein level. This selective constraint may be related to the interaction between different isotypic forms of polymorphic class II beta-chains and a common ligand. The extremely low frequencies of silent substitutions between nonorthologous genes within species are most likely due to the transfer of sequence information between loci by the occurrence of gene conversion-like events in the particular gene segment.

Animals↗
PubMed1992

Homologous collagen-induced arthritis in rats and mice are associated with structurally different major histocompatibility complex DQ-like molecules.

Collagen-induced arthritis (CIA) in rats, induced with homologous type II collagen (CII), is a genetically more restricted disease and has better resemblance to rheumatoid arthritis by its chronic disease course, than CIA induced with heterologous CII. The DA strain is highly susceptible to CIA induced with homologous CII, while the Lewis strain is resistant. (DAxLew)F1 is susceptible and backcrossing to Lewis reveals a close, but not complete, association of both arthritis and CII responsiveness to the RT1a haplotype. Analyses of congenic strains on DA and Lewis backgrounds suggest that expression of a major histocompatibility complex class II Ba molecule, encoded from the RT1Ba locus, is associated with arthritis susceptibility and CII responsiveness. The second exons coding for the first domains of the alpha and beta chains of both the RT1a and RT1l haplotypes were sequenced and the deduced amino acid sequences compared with the corresponding molecule associated with susceptibility to CIA in the mouse (H-2 Aq). The sequences of the respective alleles revealed no obvious structural homology explaining the extensive similarities in the development of chronic autoimmune arthritis. Instead, this finding implies that different trimolecular constituents (i.e. class II, T cell receptor, and CII peptides) may yield an antigen presentation event that is able to trigger a similar autoaggressiveness in the two rodent species.

Amino Acid Sequence↗
PubMed1992

Gene duplications and sequence polymorphism of bovine class II DQB genes.

The genetic diversity of bovine class II DQB genes was investigated by polymerase chain reaction amplification and DNA sequencing. The first domain exon was amplified from genomic DNA samples representing 14 class II haplotypes, defined by restriction fragment length polymorphism (RFLP) analysis. The presence of a polymorphism in the copy number of DQB genes was confirmed since two DQB sequences were isolated from certain haplotypes. Four subtypes of bovine DQB genes were found. DQB1 is the major type and was found in almost all haplotypes. DQB2 is very similar to DQB1 but was found only in the duplicated haplotypes DQ9 to 12. DQB3 and DQB4 are two quite divergent genes only present in certain duplicated haplotypes. The bovine DQB complexity thus resembles that in the human DRB region. Bovine DQB genes were found to be highly polymorphic as ten DQB1 alleles and four DQB2 alleles were identified. The observed sequence polymorphism correlated well with previously defined DQB RFLPs. Bovine and human DQB alleles show striking similarities at the amino acid level. In contrast, the frequency of silent substitutions is much higher in comparisons of DQB alleles between species than within species ruling out the possibility that any of the contemporary DQB alleles have been maintained since the divergence of humans and cattle. The frequency of silent substitutions between DQB alleles was markedly lower in cattle than in humans, in agreement with a previous comparison of human and bovine DRB alleles.

Alleles↗
PubMed1991

Expression of a swine class II gene in murine bone marrow hematopoietic cells by retroviral-mediated gene transfer.

As a first step in assessing the efficacy of a gene transfer approach to the induction of transplantation tolerance in our miniature swine model, double-copy retroviral vectors engineered to express a drug-resistance marker (neomycin) and a swine class II DRB cDNA were constructed. Infectious particles containing these vectors were produced at a titer of greater than 1 x 10(6) G418-resistant colony-forming units/ml using both ecotropic and amphotropic packaging cell lines. Flow cytometric analysis of DRA-transfected murine fibroblasts subsequently transduced with virus-containing supernatants demonstrated that the transferred sequences were sufficient to produce DR surface expression. Cocultivation of murine bone marrow with high-titer producer lines leads to the transduction of 40% of granulocyte/macrophage colony-forming units (CFU-GM) as determined by the frequency of colony formation under G418 selection. After nearly 5 weeks in long-term bone marrow culture, virus-exposed marrow still contained G418-resistant CFU-GM at a frequency of 25%. In addition, virtually all of the transduced and selected colonies contained DRB-specific transcripts. These results suggest that a significant proportion of very primitive myelopoietic precursor cells can be transduced with the DRB recombinant vector and that vector sequences are expressed in the differentiated progeny of these cells.

Animals↗
PubMed1991

Concerted evolution in a segment of the first domain exon of polymorphic MHC class II beta loci.

Genetic exchange of sequence information between members of a gene family, generally denoted gene conversion, causes a phenomenon called "concerted evolution" meaning that non-allelic genes do not evolve independently. The possible significance of this phenomenon in the evolution of major histocompatibility complex (MHC) class II genes has been investigated in the present study. The results of a phylogenetic analysis of human, mouse, bovine, and chicken class II sequences were consistent with the occurrence of gene conversion between polymorphic class II beta genes (i.e. DPB, DQB, and DRB) but not between these genes and the monomorphic DOB gene or between class II alpha genes. Gene conversion between polymorphic beta genes appears to be restricted to a gene segment between approximately nucleotide positions 94-286 in the first domain exon. Due to this genetic exchange, there is a greater interlocus similarity both at the DNA and protein level in this region than in the rest of the sequence. The region encodes a functionally important part of the class II molecule including more than half of the beta-chain residues of the antigen binding site and the residues in the alpha helix assumed to form contact with the T-cell receptor. The observed similarity in the alpha-helical region of class II beta molecules may be functionally significant for the utilization of the T-cell repertoire for antigen recognition in the immune system.

Animals↗
PubMed1991

Evolution of MHC polymorphism: extensive sharing of polymorphic sequence motifs between human and bovine DRB alleles.

The evolution of MHC polymorphism has been studied by comparing the amino acid and nucleotide sequences of 14 bovine and 32 human DRB alleles. The comparison revealed an extensive sharing of polymorphic sequence motifs in the two species. Almost identical sets of residues were found at several highly polymorphic amino acid positions in the putative antigen recognition site. Consequently, certain bovine alleles were found to be more similar to certain human alleles than to other bovine alleles. In contrast, the frequencies of silent nucleotide substitutions were found to be much higher in comparisons between species than within species implying that none of the human or bovine DRB alleles originated before the divergence of these distantly related species. The results suggest that the observed similarity in DRB polymorphism is due to convergent evolution and possibly the sharing of short ancestral sequence motifs. However, the relative role of the latter mechanism is difficult to assess due to the biased base composition in the first domain exon of polymorphic class II beta genes. The frequency of silent substitutions between DRB alleles was markedly lower in cattle than in man suggesting that the DRB diversity has evolved more rapidly in the former species.

Alleles↗
PubMed1991

Cloning and sequence analysis of 14 DRB alleles of the bovine major histocompatibility complex by using the polymerase chain reaction.

The genetic diversity in the first domain exon of a bovine class II DRB gene was investigated by PCR amplification and DNA sequencing. Genomic DNA samples representing 14 different class II haplotypes, defined by RFLP analysis, were used. The analysis revealed an extensive polymorphism and 14 alleles at a single locus, designated DRB3, were identified. Multiple amino acid substitutions were found in all pairwise comparisons of alleles; 5 to 21 substitutions in the 83 positions compared. The genetic diversity at the amino acid level found in cattle matches the one previously found in the DRB1 locus in man. The significantly higher frequency of replacement substitutions compared with the frequency of silent substitutions provides strong evidence that there is selection for genetic diversity in the bovine DRB3 first domain exon. A comparison of the DRB polymorphism in man and cattle reveals a striking similarity as regards the location of polymorphic positions in the DRB molecule and the degree of polymorphism at polymorphic positions. The majority of polymorphic positions in both species are found in the proposed antigen recognition site of the class II molecule. In addition, there are eight positions which are polymorphic in both species but have not been assigned to the antigen recognition site. The possible functional significance of the polymorphism of these latter positions is discussed.

Alleles↗
PubMed1991

The structure of human MHC class II genes.

The class II molecules of the human major histocompatibility complex bind intracellularly processed peptides and present them to T-helper cells. They therefore have a critical role in the initiation of the immune response. A salient feature of the class II molecules is their polymorphism. It has been shown that some autoimmune diseases are associated with certain class II alleles. This article reviews the basic structural features of class II molecules, and the genes encoding them as well as mechanisms governing the development of their extraordinary polymorphism.

Autoimmune Diseases↗