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Biomedical subjects

L Andersson

Publications and source records attributed to L Andersson.

At least 289 records · Page 16Linked to original sources

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↗

Immobilized metal ion affinity chromatography of serum albumins.

The interaction of several serum albumins with chelated (iminodiacetate, IDA) and immobilized (agarose-IDA) metal ions, Co2+, Ni2+, Cu2+ and Zn2+, was studied. There was no retention of human, bovine, porcine, murine and avian albumins on IDA-Zn(II) and IDA-Co(II) columns. However, all albumins studied, i.e., those of: man, cow, pig, dog, rabbit, rat, mouse, chicken and pigeon were retained on IDA-Cu(II) columns, and all except dog albumin were retained also on IDA-Ni(II). The recognition of albumins by chelated and immobilized transition metals seems to be related to an affinity for the imidazole side chains. It is postulated that one to three imidazoles is involved in this interaction, under the employed experimental conditions (pH 7.0; 1 M sodium chloride). There is no evidence for any significant contribution of tryptophan or cysteine (Cys 34) residues to the chromatographic event. The retention of defatted albumin and albumin oligomers (human), on IDA-Cu(II) columns was not significantly different from that of non-defatted albumin or albumin monomer, respectively.

Animals↗

Substantial glucose leakage from liposomes on filters and upon molecular-sieve chromatography in determinations of reconstituted glucose-transport activity and liposome volumes.

Transport-protein activities are often determined by procedures that involve isolation of liposomes containing the transported radioactive solute. We determined the activity of the human red cell glucose transporter in liposomes and, by similar procedures, internal volumes of liposomes. For these purposes, we isolated freeze-thawed liposomes loaded with [14C]glucose, either by filtration on cellulose-nitrate and cellulose-acetate filters, or by chromatography on Sephadex. The interaction of liposomes with filters caused substantial leakage of [14C]glucose. About half of the internal [14C]glucose was released on the filters from glucose-transporter liposomes with inhibited transport. Chromatography at high flow rate provided higher and more accurate values than did the filtration procedure. Leakage corrections could be made by use of flow-cell scintillation elution profiles. The ratios between the corrected chromatographic volume values and the filtration values were 1.4-3.0 for liposomes without protein, 2.4-4.0 for glucose-transporter liposomes and 3.6-7.9 for liposomes with several human red cell integral membrane proteins. The D-glucose equilibrium exchange with glucose-transporter liposomes at 50 mM D-glucose was 2.0 nmol D-glucose per microgram transporter per second as determined by use of chromatography at high flow rate. The filtration procedure gave only 0.6 nmol.microgram-1.s-1 due to the [14C]glucose leakage. In our experiments, the chromatographic procedure thus proved superior.

Biological Transport↗

Increased erythroid potentiating activity/tissue inhibitor of metalloproteinases and jun/fos transcription factor complex characterize tumor promoter-induced megakaryoblastic differentiation of K562 leukemia cells.

Molecular cloning has revealed that erythroid potentiating activity (EPA) and tissue inhibitor of metalloproteinases (TIMP) represent two distinct activities of a single protein. We have studied the expression of the EPA/TIMP gene at the mRNA and protein levels during 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced megakaryoblastic differentiation of K562 human chronic myeloid leukemia cells. Northern hybridization analysis showed that the EPA/TIMP mRNA was increased within 3 hours of TPA-induction and reached maximal levels (about 50-fold induction) during the first day of treatment. The expression of mRNAs for two major metalloproteinases, collagenase-I and stromelysin, were activated in parallel in the differentiation-induced K562 cells. The increase of EPA/TIMP mRNA correlated with increased EPA/TIMP protein biosynthesis and secretion: the TPA-induced cells secreted substantially enhanced amounts of metabolically labeled proteins, of which EPA/TIMP represented up to 50% after the first day of treatment (over 100-fold induction). The induction of EPA/TIMP mRNA was associated with its increased transcription. EPA/TIMP induction required continuous protein synthesis, being completely inhibited by addition of the protein synthesis inhibitor cycloheximide simultaneously with TPA, but only partially inhibited in a time-dependent manner if cycloheximide was added after TPA. Unlike in other cells tested, the jun and c-fos transcription factor mRNAs showed a prolonged biphasic induction response in K562 cells during TPA treatment. This response was associated with enhanced activity of a transfected recombinant reporter plasmid containing binding sites for the jun/fos transcription factor complex (AP-1) similar to the TPA-responsive element (TRE) sequence we found in the EPA/TIMP gene promoter. We suggest that the induction of EPA/TIMP and several other genes specific for the differentiating K562 cells may be a consequence of the sustained activation of immediate early genes encoding transcription factors, such as jun and c-fos.

Cell Line↗

Structures on the I-A molecule predisposing for susceptibility to type II collagen-induced autoimmune arthritis.

The susceptibility to type II collagen (CII)-induced arthritis (CIA) in mice is profoundly influenced by major histocompatibility complex (MHC) class II genes in the H-2 region. Analyses of MHC-congenic strains on the B10 background show that only strains developing an anti-CII antibody response after immunization with autologous CII develop arthritis after induction with CII from various species. The susceptible haplotypes have been found to be H-2q, H-2r, H-2w3 and H-2w17. In addition, these haplotypes respond to different patterns of CII derived from various species suggesting that T cell receptors and CII peptides interact. In contrast, certain haplotypes closely related to H-2q, such as the H-2p and H-2w5 haplotypes, are resistant to induction of CIA and are nonresponders to CII. We have earlier shown that a critical structure on the I-A beta molecule determines the susceptibility differences between the p and q haplotypes. We have now determined the structure of exon 2 of the A beta as well as some of the A alpha genes of the remaining haplotypes in the p, q and r families. The sequences show similarities between the CIA-susceptible haplotypes in the A beta C-terminal part and the A alpha N-terminal part of the first domains forming a large part of the antigenic peptide-binding site. Among the wild mouse-derived haplotypes, the w5 haplotype showed an A beta sequence identical to that of the p haplotype consistent with its nonresponder nature to CII immunization. These findings suggest that (a) structures shared between different class II molecules are of importance for the susceptibility to disease in mouse strains and (b) most likely recognition of different CII peptides is important for development of disease.

Amino Acid Sequence↗

Some hygienic observations from the glass industry.

Metallic compounds and other agents used in the manufacturing of glass are probably responsible for the cancer risks observed for glassworkers, especially glassblowers. Few hygienic observations have been reported from the art glass industry. Three glassworks were therefore studied with regard to air concentrations of lead, arsenic, nickel and manganese. The hygienic conditions of the blow-pipes were investigated at these glassworks and another two with regard to inside deposits of slag containing lead, arsenic, manganese and nickel as possible transporters that cause oral exposure. Atomic absorption spectrophotometry was used for the analyses. Apart from lead, the metal concentrations in the air were around the detection limit. Glassworks producing heavy crystal glass usually had higher concentrations of lead in the air than the semi-crystal glassworks. Seven out of 12 samples from heavy crystal glassworks exceeded the Swedish threshold limit of 50 micrograms/m3, while only four out of 28 samples from the semi-crystal glassworks exceeded this limit. Regarding metals in the slag from inside the blow-pipes, the concentrations (geometrical means) of lead and nickel were higher in the heavy crystal glassworks (6.9 micrograms lead/mg slag, and 5.0 micrograms nickel/mg slag versus 0.7 micrograms lead/mg slag and 0.6 micrograms nickel/mg slag in semi-crystal glassworks, respectively). The concentration of arsenic was similarly low in the pipes from all the glassworks (approximately 0.30 micrograms/mg slag) and the concentration of manganese was only slightly higher in heavy crystal glassworks (5.4 micrograms/mg slag versus 3.6 micrograms/mg slag in semi-crystal glassworks).

Air Pollutants, Occupational↗

Glucose transporters are abundant in cells with "occluding" junctions at the blood-eye barriers.

We studied the distribution of the "erythroid/brain" glucose transporter protein in the human and rat eye by immunocytochemistry with monoclonal and polyclonal antibodies to the C terminus of the human erythrocyte glucose transporter. We found intense immunocytochemical staining in the endothelium of microvessels of the retina, optic nerve, and iris but not in microvessels of the choroid, ciliary body, sclera, and other retro-orbital tissues. In addition, we found marked immunocytochemical staining of retinal pigment epithelium, ciliary body epithelium, and posterior epithelium of the iris. The common feature of all those endothelial and epithelial cells that stained intensely for the glucose transporter is the presence of "occluding" intercellular junctions, which constitute the anatomical bases of the blood-eye barriers. We propose that a high density of the glucose transporter is a biochemical concomitant of epithelial and endothelial cells with barrier characteristics, at least in tissues that have a high metabolic requirement for glucose.

Animals↗

Dichotic listening, forced attention, and brain asymmetry in righthanded and lefthanded children.

Righthanded and lefthanded 7-year-old children (both boys and girls) were compared for dichotic listening performance under free report and forced attention conditions. Previous findings from our laboratory have shown that, while adults reverse the right ear advantage (REA) during the forced-left condition, children do not. Since the finding in children was unexpected, the first aim of the present study was to replicate our previous results. A second aim was to include lefthanded children with the hypothesis that they should more easily revert to a LEA, because of less homogeneous lateralization. The results essentially replicated our previous findings, during all three recall conditions. No sex differences were observed, and both handedness groups showed the same overall response pattern.

Attention↗

The relationship between bovine major histocompatibility complex class II polymorphism and disease studied by use of bull breeding values.

The predictive value of class II DQ and DYA polymorphisms of the bovine major histocompatibility (MHC) complex (BoLA) for the incidence of disease in dairy cattle was estimated in a sample of 196 progeny-tested AI bulls of the Swedish Red and White breed. The BoLA DQ and DYA types of the bulls were determined by analysing restriction fragment length polymorphisms (RFLPs). Breeding values of bulls for clinical mastitis, all diseases including clinical mastitis and diseases other than clinical mastitis were used as measures of disease resistance or susceptibility. The relationship between MHC polymorphism and bull breeding values for disease resistance was evaluated statistically by linear regression analysis. A significant association between the haplotype DQ1A and susceptibility to clinical mastitis was revealed. No other DQ haplotype nor the DYA locus has a significant effect on any of the disease traits studied.

Animals↗

Restriction fragment length polymorphism of bovine lysozyme genes.

Genetic polymorphism of bovine lysozyme (LYZ) genes was investigated by analysing restriction fragment length polymorphism (RFLP). The analysis revealed three RFLP loci designated LYZ1, LYZ2 and LYZ2. Each system included two or three allelic variants. Evidence for close genetic linkage of the three loci was found. There was also a significant linkage disequilibrium among the three loci in a sample of about 200 breeding bulls from one breed. No statistically significant association was found between LYZ RFLPs and breeding values of bulls for disease or milk production traits.

Alleles↗

Avulsed human teeth replanted within 15 minutes--a long-term clinical follow-up study.

Twenty-one avulsed human permanent teeth replanted within 15 min after trauma were followed radiographically for an average of 5 years. Seven teeth did not show any root resorption during the observation period. In 8 teeth shallow resorption cavities were observed, but no signs of progression were observed with increased observation time. In 6 teeth some progressive root resorption was observed with increased observation time. The depth of root resorption cavities was assessed using a radiographic index, and the rate of root resorption was defined as the index change over time. The rate of root resorption was determined. It was concluded that teeth replanted within 15 min after the avulsion have a favourable long-term prognosis.

Adolescent↗

Beneficial effect of hepatic arterialization on hypogonadism in male rats with portacaval shunt.

The effect of portacaval shunt (PCS) with and without hepatic arterialization (HA) upon the liver morphology, hemodynamics, and in relation to testicular weight, histology, and plasma sex steroid levels has been investigated in male rats. PCS rats showed a significant decrease in hepatic blood flow, body and liver weights, together with signs of severe hypogonadism. In contrast, in HA rats the increment in liver blood flow was associated with higher body and liver weights. In spite of total portal blood shunting, a beneficial effect on testicular morphology and an increase in plasma testosterone level were observed. In respect to plasma estradiol levels the intergroup differences could not be evaluated due to large individual variations. This was probably caused by the presence of cross-reactive plasma component(s) masking the level of endogenous estrogen. It is concluded that portosystemic shunting is not of primary importance in the etiology of PCS-related hypogonadism in the male.

Animals↗

Narcissism and loneliness.

The research described here centers on how a narcissistic intrusion during early childhood may develop into narcissistic difficulties which manifest themselves, later in life, in feelings of loneliness. The results from a study of elderly women in Stockholm, Sweden, indicated that loneliness in old age is greater among an intruded group in comparison to those whose parental influence was not intrusive. The feelings of loneliness are even more severe if the mother was a housewife. There was also a relationship between social position and loneliness, but only for those women whose family orientation was not intrusive and whose mothers were housewives. The results encourage further study of the etiological contributions of parental influence during childhood on later experience of loneliness.

Aged↗

Attachment and detachment of human epidermal melanocytes.

Human epidermal melanocytes can leave their basal position following topical application of sodium lauryl sulphate. They thereby undergo changes which strongly indicate that the dense plates along their cytomembrane constitute a mechanism for attachment to the basal lamina. These detached melanocytes move rapidly to, or are transported to, more superficial levels of the living epidermis. They are probably not desquamated, but disintegrate within the stratum spinosum. It was remarkable that one melanocyte was found that broke the basal lamina, showing that melanocytes are capable of migrating, under certain conditions. A special fixation method which exposes the cytomembranes and allows the demarcation of cells and their finest cytomembrane protrusions was used to demonstrate that keratinocytes often bulge into the innermost spinous layer and become attached to the basal lamina only via more or less thin cytoplasmic protrusions. This is in contrast to the routine textbook description of a basal layer that consists of a strict single row of cuboid or columnar keratinocytes.

Administration, Cutaneous↗