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Biomedical subjects

S Sjölander

Publications and source records attributed to S Sjölander.

10 recordsLinked to original sources

Intranasal immunisation with influenza-ISCOM induces strong mucosal as well as systemic antibody and cytotoxic T-lymphocyte responses.

Intranasal administration of vaccines is preferred for induction of mucosal immune responses. In this study, mice were immunised intranasally and subcutaneously with influenza-immuno stimulating complexes (influenza-ISCOM). The intranasal dose was 15-times the subcutaneous dose. All mice dosed with influenza-ISCOMs survived challenge with live virus and comparable serum antibody and splenic cytotoxic T-lymphocyte responses were detected in both groups. Induction of mucosal IgA was significantly higher with intranasal immunisation and was comparable to responses induced with the heat labile enterotoxin of Escherichia coli as adjuvant. These findings demonstrate that intranasal administration of high dose influenza-ISCOM results in potent systemic and mucosal immune responses.

Adjuvants, Immunologic↗

Questionnaire versus direct technical measurements in assessing postures and movements of the head, upper back, arms and hands.

OBJECTIVES: This study compares questionnaire-assessed exposure data on work postures and movements with direct technical measurements. METHODS: Inclinometers and goniometers were used to make full workday measurements of 41 office workers and 41 cleaners, stratified for such factors as musculoskeletal complaints. The subjects answered a questionnaire on work postures of the head, back, and upper arms and repeated movements of the arms and hands (3-point scales). The questionnaire had been developed on the basis of a previously validated one. For assessing worktasks and their durations, the subjects kept a 2-week worktask diary. Job exposure was individually calculated by time-weighting the task exposure measurements according to the diary. RESULTS: The agreement between the self-assessed and measured postures and movements was low (kappa = 0.06 for the mean within the occupational groups and kappa = 0.27 for the whole group). Cleaners had a higher measured workload than office workers giving the same questionnaire response. Moreover, the subjects with neck-shoulder complaints rated their exposure to movements as higher than those without complaints but with the same measured mechanical exposure. In addition, these subjects also showed a general tendency to rate their postural exposure as higher. The women rated their exposure higher than the men did. CONCLUSIONS: The questionnaire-assessed exposure data had low validity. For the various response categories the measured exposure depended on occupation. Furthermore, there was a differential misclassification due to musculoskeletal complaints and gender. Thus it seems difficult to construct valid questionnaires on mechanical exposure for establishing generic exposure-response relations in epidemiologic studies, especially cross-sectional ones. Direct technical measurements may be preferable.

Adult↗

On the evolution of reality--some biological prerequisites and evolutionary stages.

The discussion of the evolutionary origins of consciousness has largely been concentrated to the human mind, and it is only in recent years that a comparative ethological view has come into play. Even here, a tendency has been to look mainly at the primates. There is a vast literature that discusses the differences between human consciousness and cognition, compared with that of the other primates, but much less attention has been given to the fact that evolutionary gaps-fulgurations, emergencies, new systems-have occurred at many stages in the evolution of cognition. More especially, the complexity of rather simple cognitive systems in lower animals has been underestimated, as well as the necessary prerequisites for a cognition worthy of the name to exist. Of particular interest in the discussion has been the views from evolutionary epistemology and radical constructivism, since they support the ethologically founded view that mind representations do not depict reality, but are adaptations for a successful way of behaving in the physical world, that reality in this sense is in the mind, that there are many realities, varying for different species-rich or poor in complexity-but all of them basically of the same nature. Even such human achievements as mathematics or logic may thus be seen as specific cognitive adaptions in our species, not as independent aspects of the physical world.

Animals↗

N-linked glycans in the CD4-binding domain of human immunodeficiency virus type 1 envelope glycoprotein gp160 are essential for the in vivo priming of T cells recognizing an epitope located in their vicinity.

Deglycosylation of viral glycoproteins has been suggested to influence the number of available T cell determinants and to increase T cell recognition of antigens. In this study, we have investigated whether T cell responses to the HIV-1 envelope glycoprotein gp160 were influenced by deletion of three N-glycans of the protein. Wild type (wt) and a mutated form of gp160 (gp160A123) lacking the three N-glycans in the C-terminal CD4-binding region efficiently induced antigen-specific T cell responses in mice of the H-2b, H-2d, and H-2k haplotypes. Further, T cells primed by either wt gp160 or gp160A123 were stimulated in vitro to a similar extent by the homologous and heterologous protein, indicating that deletion of the glycans did not affect the overall immunogenicity and antigenicity of gp160A123. Wild-type gp160 and gp160A123 induced comparable T cell responses to those of epitopes which with respect to the secondary structure of gp160 were distant from the deleted glycans. However, in mice of the H-2b haplotype, wt gp160 primed T cells which responded in vitro to a peptide containing one of the deleted N-glycosylation sites (Asn448), whereas T cells induced by gp160A123 were unable to recognize this peptide. Thus, deletion of the glycans abrogated the in vivo priming of T cells recognizing an epitope in close proximity to the deletion sites. Furthermore, enzymatically deglycosylated gp160 failed to induce a T cell response to this epitope. These results indicate that the in vivo generation of certain T cell determinants from glycoproteins is dependent on the glycosylation of the protein.

Amino Acid Sequence↗

Induction of homologous virus neutralizing antibodies in guinea-pigs immunized with two human immunodeficiency virus type 1 glycoprotein gp120-iscom preparations. A comparison with other adjuvant systems.

The immunogenicity in guinea-pigs of the human immunodeficiency virus type 1 envelope glycoprotein gp120 in immune stimulating complex (iscom) was compared to that of gp120 adjuvanted with QuilA-matrix (iscom without attached antigen), aluminium hydroxide (alum) and the Ribi adjuvant system. Gp120 was either incorporated into iscoms by covalent conjugation (iscom(c)) or by acid treatment of gp120 (iscom(a) and both these preparations induced high ELISA antibody titres to gp120. Virus neutralizing (VN) antibodies were most frequently induced by gp120 in iscom(c), iscom(a) or in alum and correlated to high titres to the V3-region of gp120. Further, antibodies induced by gp120-iscom(c) most efficiently inhibited binding of a VN monoclonal antibody GP13 to the CD4 binding region of gp120 whereas gp120-iscom(a) induced the highest mean titre of antibodies blocking the binding of [125I]gp120 to CD4. These results suggest that the gp120-iscom preparations efficiently induced high levels of gp120 specific antibodies and that the adjuvant formulation of gp120 affect the specificity and functional properties of elicited antibodies.

Adjuvants, Immunologic↗

Influence of N-linked glycans in V4-V5 region of human immunodeficiency virus type 1 glycoprotein gp160 on induction of a virus-neutralizing humoral response.

One of the functions of N-linked glycans of viral glycoproteins is protecting otherwise accessible neutralization epitopes of the viral envelope from neutralizing antibodies. The aim of the present study was to explore the possibility to obtain a more broadly neutralizing immune response by immunizing guinea pigs with gp160 depleted of three N-linked glycans in the CD4-binding domain by site-directed mutagenesis. Mutant and wild type gp160 were formulated into immunostimulating complexes and injected s.c. into guinea pigs. Both preparations induced high serum antibody response to native gp120 and V3 peptides. Both preparations also induced antibodies that bound equally well to the V3 loop or the CD4-binding region, as determined by a competitive enzyme-linked immunosorbent assay (ELISA). The sera from animals, immunized with mutated glycoprotein, did not neutralize nonrelated HIV strains better than did sera from animals, immunized with wild type glycoprotein. Instead, a pattern of preferred homologous neutralization was observed, i.e., sera from animals, immunized with mutant gp160, neutralized mutant virus better than wild type virus, and vice versa. These data indicated that elimination of the three N-linked glycans from gp160 resulted in an altered local antigenic conformation but did not uncover hidden neutralization epitopes, broadening the immune response.

AIDS Vaccines↗

Integrated fluid handling system for biomolecular interaction analysis.

An integrated fluid handling system used for multichannel biomolecular interaction analysis is described. Reactions between biological molecules are monitored in real time by measuring changes in the angular position where surface plasmon resonance occurs at a biospecific active surface. The adsorption efficiency of the analyte onto the biospecific active surface is up to approximately 3%, due to the low channel height, 50 microns, in the flow cell. When a large part of the total biospecific active surface for surface plasmon resonance probing (approximately 0.15 mm2) is used, the sensitivity is high. Sample sizes in the order of 1-50 microL can be injected. The sample zone dispersion is minimized by the low dead volume in the system (approximately 0.4 microL) accomplished by using integrated sample loops and thin conduits. An asset of this integration is the low reagent consumption. The sensor chip with the biospecific active surface is reusable and easily exchanged. Experimental results obtained with a theophylline monoclonal antibody as the analyte are compared with a theoretical model. The standard deviation for the repeatability is approximately 5% typically with 50 microL of 250 pM analyte, and the assay time is 10 min. The detection limit is approximately 10 pg of the analyte on the probed spot of the surface. Possible improvements of the sensitivity and detection limit are discussed.

Antibodies, Monoclonal↗

Singing birds, playing cats, and babbling babies: why do they do It?

Rarely, animals do what they do because they are aware of the function of the behaviour or its outcome. Instead, they will very often perform behaviour out of context, spontaneously, as play. The impression (strengthened by introspection in the human species) is that they do it because they get some kind of internal reward. Nevertheless, such seemingly meaningless behaviour may have an ultimate function to adjust behavioural programs to the body, to practice, to perfect the execution of the behaviour. If the proximate reason for doing what the animal does may be to attain a pleasurable state, the ultimate, evolutionary reason may still be that increased practice will give some gain in fitness. If one presupposes internal rewarding and punishing systems as intervening factors, it becomes much simpler to explain why birds sing, kittens play or babies babble without any outer reward and out of any functional context, more than needed from a strictly functional view, spontaneously and just for the fun of it.

Animal Communication↗