Biomedical subjects
Publications and source records attributed to K Gustafsson.
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cDNA for a beta-chain of HLA-DR antigens was cloned and the partial nucleotide sequence was determined. The data suggest that the beta-chain consists of approximately 230 amino acids, of which about 200 are exposed on the cell surface. The beta-chain appears to be composed of two exposed disulphide-containing domains. The arrangement of the disulphide loops suggests that the beta-chain is similar in structure to the HLA-A, B, C antigen subunits and the immunoglobulin chains. For the beta-chain domain closest to the membrane this similarity was verified at the level of primary structure. The partial amino acid sequence of the NH2-terminal domain did not display any apparent homology to HLA-A, B, C antigens and immunoglobulins. However, the similarity established here between the two types of major histocompatibility antigen subunits and the immunoglobulin chains suggests a common ancestral origin for at least some regions of these molecules.
The lipoprotein lipase activity in adipose tissue of Sprague-Dawley rats 1, 4, 9 and 15 months of age, was investigated. The study revealed that a significant inverse relationship exists between serum triglyceride level and lipoprotein lipase activity in epididymal fat pad. Thus, the lipoprotein lipase activity in 1 and 15 months old rats are on the average 5.3 and 1.1 nkat/g wet weight, respectively, simultaneously as serum triglyceride level increase from 0.74 mmol/l to 3.51 mmol/l, respectively. It is suggested that impaired removal of very low density lipoproteins is one possible explanation of the enhanced levels of this lipoproteins in the old rat. The lipase activity investigated had the characteristic properties of lipoprotein lipase, i.e. it was activated by the addition of serum, inhibited by high ionic strength and varied with the nutritional state. However, it could not be exclude that monoacylglycerol lipase present in epididymal fat pad also decreased with age. The possible connection between the age-related reduction of lipoprotein lipase activity in epididymal fat pad and the age-related gomerulonephritis found in these rats is discussed.
The lipid composition of the serum lipoproteins of Sprague-Dawley rats with varying degrees of hyperlipidemia was investigated. The concentrations of all the lipoproteins were increased with increasing hyperlipidemia. The elevation was found to be more pronounced for very low density VLDL) and low density (LDL) than for high density lipoproteins (HDL). A linear relationship exists between triglyceride and cholesterol contents of VLDL fractions independent of the VLDL level. Eighty to ninety per cent of serum triglycerides are located in the VLDL fraction. Linear relationships were found between the levels of serum triglycerides or VLDL triglycerides and the levels of LDL and HDL cholesterol, respectively. Furthermore, linear relationships exist between total cholesterol content in serum and cholesterol concentration in VLDL, LDL and HDL, respectively. Thus, lipoprotein levels may be estimated by measuring serum cholesterol or triglyceride concentrations. Disk electrophoresis and ultracentrifugation revealed that the LDL fraction (d. 1.006 - 1.063) could be divided into two fractions, which both increase with age. The spontaneous hyperlipoproteinemia of the old rats make these animals suitable as a model for evaluation of drugs against human hyperlipoproteinemia.
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Activity in computer-monitored running wheels, behavior in open-field tests, body temperature measured by rectal probe, and vocalization were examined in rats after a single injection of 2.5 g/kg ethanol or saline. A reduction in running-wheel activity occurred during intoxication, followed by a significant increase in running 20-24 hr after the injection. Also 24 hr after ethanol, among rats kept in normal cages, there was an increase in body temperature and vocalization and a decrease in ambulation in a dark, quiet open field. Each of these 3 aftereffects was reduced or abolished in the rats with access to a running wheel. The results confirm and extend previous findings of aftereffects of acute intoxication in rats with a time course similar to hangover in humans.
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Class II antigens of the major histocompatibility complex (MHC) consist of a family of closely related cell surface-expressed glycoproteins. These antigens, which are genetically polymorphic, control important aspects of the immune response. At least three types of human class II antigens, namely, DR, DC and SB (refs 2-4), have been identified. All class II antigens are heterodimers composed of one alpha- and one beta-chain. The genes for both types of subunits are encompassed within the MHC. The general features of the DC and DR antigens have recently been elucidated. Much less is known, however, about the SB molecules. Here we describe the isolation of a cDNA clone as well as a genomic clone encoding a beta-chain whose amino acid sequence is compatible with the partial amino-terminal sequence of SB beta-chains.
The ability of interferons to modulate the antigenic phenotype of tumor cells may involve alterations in the transcription, translation, membrane expression and shedding of Major Histocompatibility Complex (MHC) and Tumor Associated Antigens (TAAs). In the present study we have investigated possible mechanisms by which recombinant human interferons, IFN-alpha, -beta and -gamma, alter the antigenic profile of long- and short-term human melanoma cultures. IFN-alpha and -beta induced similar changes in the synthesis, expression and shedding of two TAAs, a HMW-MAA and a Cyt-MAA, in the established melanoma cell line Colo 38, whereas IFN-gamma exerted a differential effect on these melanoma associated antigens. Moreover, IFN-gamma was relatively more effective than IFN-alpha or -beta in upregulating the synthesis, expression and shedding of class I MHC antigens. At the same time a dramatic differential effect of the interferons was observed with class II MHC antigens. IFN-alpha or -beta induced a modest increase in the synthesis and expression of these antigens, whereas IFN-gamma was greater than 3-fold more active in inducing the synthesis and expression of DR/DP antigens and greater than 4- and greater than 10-fold more effective in increasing the synthesis and expression, respectively, of DQ antigens. Analysis of the levels of cytoplasmic mRNA for the DR-alpha and DQ-beta genes indicated no significant difference between IFN-alpha, beta or -gamma treated cells suggesting that IFN-gamma enhancement of the synthesis of DR and DQ antigens may occur at a posttranscriptional level. In the case of a newly established human melanoma cell line (MG-3) IFN-gamma enhanced the synthesis but not the expression of DR antigens and did not alter either the synthesis or expression of DQ antigens. Our studies indicate that the effects of interferons on the antigenic phenotype of melanoma cells will vary depending on the type of interferon employed, the antigen monitored and the target cell studied. In addition, it is also apparent that some of the biosynthetic steps involved in regulating the synthesis, expression and shedding of antigens may be coordinately regulated in some melanoma cells, whereas these processes may be under independent control in other melanoma populations.