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Biomedical subjects

G Möller

Publications and source records attributed to G Möller.

At least 55 records · Page 3Linked to original sources
PubMed1996

CD8+ cells are the main producers of IL10 and IFN gamma after superantigen stimulation.

Purified CD8+ T cells were recently shown to produce TH1 as well as TH2 types of cytokines upon restimulation, indicating an important role for these cells in regulation of immune responses. However, it is not known if the CD8+ cells would contribute to cytokine production in the presence of cytokine secreting CD4+ cells. In the present study the authors have investigated the proportion of cytokine-producing CD4+ and CD8+ cells in the spleen after in vitro or in vivo stimulation. They found that stimulation of spleen cells with the superantigen Staphylococcal Enterotoxin B (SEB) in the presence of IL4 promoted production of IL10 and IFN gamma predominately by CD8+ cells. In contrast, the production of IL4 was almost exclusively confined to the CD4+ subset. When priming with SEB in vivo before subsequent restimulation in vitro, a protocol previously shown to induce anergy, up to 80% of the IL10 and IFN gamma positive cell expressed the CD8 marker. Taken together, these results emphasize the important role of cytokine-producing CD8+ cells and indicate that CD4+ and CD8+ T cells may, in a given situation, produce distinct cytokines.

Animals↗
PubMed1996

Unresponsiveness of CD4+ T cells from a non-responder strain to HgCl2 is not due to CD8(+)-mediated immunosuppression: an analysis of the very early activation antigen CD69.

Injections of HgCl2 lead to autoimmune manifestations in genetically predisposed rats and mice. In this study, the authors examined the responsiveness of T subsets from different mouse strains to HgCl2 by tracing their expression of the very early activation antigen CD69. The authors found increased expression of the CD69 antigen on CD4+ T cells from the responder A.SW and BALB/c mice, but not on CD4+ T cells from the non-responder DBA/2 mice, indicating an activation of T helper cells in the responder strains. However, the CD69 antigen was induced on CD8+ T cells from all strains irrespective whether they were susceptible or resistant to mercury-induced autoimmunity. Since CD8+ T cells have been described as mediating immunosuppression and as being responsible for the resistance to autoimmune induction by mercury, the authors tested whether CD8+ T cells inhibited the activation of CD4+ T cells by HgCl2 in the non-responder strains. However, there was no evidence for a suppressive role of CD8+ T cells from the DBA/2 mice in the response to HgCl2. The findings indicate that T helper cells play a central role in the immunological effects of HgCl2 and unresponsiveness of T helper cells in the nonresponder strains is not due to CD8(+)-mediated immunosuppression.

Animals↗
PubMed1996

In vitro effects of HgCl2 on murine lymphocytes. II. Selective activation of T cells expressing certain V beta TCR.

In vivo administration of HgCl2 causes autoimmune manifestations in susceptible rats and mice. We have previously shown that mercury is a unique molecule that can primarily activate murine T lymphocytes to transformation and proliferation in vitro. To test whether a specific TCR repertoire predisposes the autoimmune development induced by HgCl2 and our hypothesis that mercury may function as a superantigen, we examined the TCR V beta repertoire in HgCl2-stimulated T cells from the responder BALB/c or SJL mice and the non-responder DBA/2 mice. We found a selective activation of T cells bearing a certain set of TCR B beta chains in response to HgCl2, e.g. V beta 6, V beta 8, V beta 10 and V beta 14 in the BALB/c strain. Moreover, depletion of V beta 8+ T cells, a family predominantly expanded in the BALB/c strain upon HgCl2 stimulation, profoundly inhibited the response to HgCl2 in this strain. An alternative selection of V beta segments, involving V beta 6, V beta 7 and V beta 14, was observed in the SJL strain in which the V beta 8 family is genetically deleted. Mechanism(s) whereby mercury modulates the immune system under a stringent genetic control and a possible therapeutic regime against mercury-induced autoimmune disease by administration of antibody specific to the TCR V beta region are discussed.

Animals↗
PubMed1996

A pilot study of rehabilitation at home after stroke: a health-economic appraisal.

This study aimed at describing the health-economic implications and organisational issues of rehabilitation at home in south-west Stockholm of 15 acute stroke patients, mean age 68.2, male:female ratio 9:6, independent in feeding and continent one week after their stroke. Average patient satisfaction with different dimensions of care was 92%. Perceived dysfunction, by means of the Sickness Impact Profile, 3 months after stroke was highest for Recreation-and-Pastime, Home Management and Ambulation. Between 3-12 months after stroke, functional improvement was particularly seen in Home Management, Recreation-and-Pastime and Emotional Behaviour. Three fourths of the patients received help with different ADL tasks from a family caregiver and 1/5 from home service assistants. According to the scores for subjective health of the spouses and time used to help the patient, the burden that the programme put on the patient's family was modest, temporary and in accordance with preferences reported by the elderly in Sweden. The mean duration of hospital stay for patients under rehabilitation at home was 14 days and for a selected comparison group with similar ADL-grade, 27 days. The mean number of therapy sessions at home was 11. Each home visit took 3.2 hours, 60% of which were direct patient time. In the selected comparison group, 1/3 was referred to other departments for rehabilitation and care, and 40% had contacts with day-care and paramedical professionals after discharge from the hospital. During the first year after stroke, the average, direct, per capita cost for rehabilitation at home amounted to SEK 127,730 divided between hospital care (50%), followed by contribution by family caregivers (18%), rehabilitation at home (10%), out-patient visits to physicians and nurses (8.8%), home-help service (7%), auxiliary equipment (2%), medication (1.5%), home adaptation (1%) and transportation service (0.3%). This organisational model of home-based rehabilitation of stroke patients constitutes a feasible, possibly less expensive alternative and complement to current rehabilitation in hospital and primary care, which could be further developed and evaluated.

Aged↗
PubMed1995

In vitro effects of HgCl2 on murine lymphocytes. I. Preferable activation of CD4+ T cells in a responder strain.

Mercury-induced autoimmune disorders have been demonstrated in rats and mice injected with HgCl2. We have studied the ability of HgCl2 to activate murine lymphocytes in vitro and found that it induced increased DNA synthesis, which peaked at days 4 to 6. Other metal ions, such as Mg2+ and Zn2+, had no or much less effect. Consistent with the in vivo studies, there were strain differences, and the most significant increase in thymidine uptake was induced in A.SW and BALB/c spleen cells. Both T lymphocytes and adherent cells were required for activation, and anti-CD4 Ab completely abrogated HgCl2-induced proliferation, suggesting the involvement of T helper cells. Cell phenotype analysis demonstrated that HgCl2 induced both proliferation and transformation of CD4+ and CD8+ T cells from BALB/c mice (responder strain). In contrast, only CD8+ T cells from the nonresponder DBA/2 mice were transformed. These findings indicate that helper T cells play a crucial role for the immunologic effects caused by HgCl2 and determine the ability of different mouse strains to respond to HgCl2.

Animals↗
PubMed1995

Subcutaneous immunoglobulin replacement in patients with primary antibody deficiencies: safety and costs.

Immunoglobulins (IgG) as replacement therapy in primary antibody deficiencies can be given as intramuscular injections, or as intravenous or subcutaneous infusions. Our aims were to obtain information on the frequency of adverse systemic reactions during subcutaneous therapy, the occurrence and intensity of tissue reactions at the infusion sites, and serum IgG changes. Furthermore, we compared costs between the different replacement regimes. Our study included 165 patients (69 women, 96 men, aged 13-76 years) with primary hypogammaglobulinaemia or IgG-subclass deficiencies. Data were compiled from questionnaires filled in by the patients and from their medical records. 33,168 subcutaneous infusions (27,030 in home therapy) had been given. 106 (of which 16 were at home) adverse systemic reactions (100 mild, 6 moderate) were recorded in 28 patients (17%). No severe or anaphylactoid reactions occurred. Despite large immunoglobulin volumes given during 434 patient years (28,480 infusions), no signs have been found that indicate the transmission of hepatitis virus. Transient tissue reactions occurred at the infusion sites but were not troublesome to most patients and we found significant increases in mean serum IgG. The use of subcutaneous instead of intravenous infusions at home would reduce the yearly cost per patient for the health-care sector by US $10,100 in Sweden alone. We conclude that subcutaneous administration of IgG is a safe and convenient method of providing immunoglobulins. We were able to reach serum IgG concentrations similar to those by the intravenous therapy and we found that the method could also be used successfully in patients with previous severe or anaphylactoid reactions to intramuscular injections.

Adolescent↗
PubMed1995

A comparison of the patient-borne costs of therapy with gamma globulin given at the hospital or at home.

The major aim of this study was to estimate and compare the patient-borne costs of lifelong subcutaneous gamma globulin therapy at the hospital and at home. Thirty patients were included and the data were collected with a questionnaire. The introduction of self-therapy at home reduced the total yearly costs by approximately 50% and the out-of-pocket expenses for the patients by 85%.

Adolescent↗
PubMed1994

Anti-IgM-Ficoll conjugates activate B cells from CBA but not CBA/N mice.

We have compared the stimulating effects of an anti-IgM-Ficoll conjugate on B cells from the two mouse strains CBA and CBA/N. CBA/N mice have a recessive defect on their X chromosome which make them unable to respond to T1-2 antigens and B cells from these mice are supposed to be in an immature state. We found that the anti-IgM-Ficoll conjugate stimulated B cells of the CBA strain to proliferate even without the addition of interleukins, but was not able to stimulate B cells from the CBA/N strain. To rule out that the unresponsiveness of CBA/N mice to anti-IgM-Ficoll was due to the immaturity of their B cells, we cultured B cells from both strains in the presence of an anti-IgM-Sepharose conjugate. This conjugate stimulated B cells from both mouse strains to proliferate in the presence of IL-4. These results agree with the hypothesis that the T1-2 antigen Ficoll is able to deliver activating signals to B cells and therefore cannot be considered as an inert carrier.

Animals↗
PubMed1994

Selective inability of LPS-activated B lymphocytes to produce antibodies against autologous and allogeneic MHC class I antigens.

Lipopolysaccharide (LPS)-activated B lymphocytes have been found to produce autoantibodies of a variety of specificities. We found that LPS-induced autoantibodies did not include antibodies against self H-2 class I antigens, suggesting a selective tolerance induction against some, but not other, autoantigens. However, LPS-activated B lymphocytes not only failed to produce antibodies against autologous H-2 class I antigens, but also against allogeneic H-2 class I antigens, suggesting a selective regulation of B cells to synthesize antibodies directed against autologous and allogeneic major histocompatibility complex antigens.

Animals↗
PubMed1994

Synthetic substrate analogues for UDP-GlcNAc: Man alpha 1-6R beta(1-2)-N-acetylglucosaminyltransferase II. Substrate specificity and inhibitors for the enzyme.

UDP-GlcNAc:Man alpha 1-6R beta(1-2)-N-acetylglucosaminyltransferase II (GlcNAc-T II; EC 2.4.1.143) is a key enzyme in the synthesis of complex N-glycans. We have tested a series of synthetic analogues of the substrate Man"'alpha 1-6(GlcNAc"beta 1-2Man'alpha 1-3)Man beta-O-octyl as substrates and inhibitors for rat liver GlcNAc-T II. The enzyme attaches N-acetylglucosamine in beta 1-2 linkage to the 2"'-OH of the Man"'alpha 1-6 residue. The 2"'-deoxy analogue is a competitive inhibitor (Ki = 0.13 mM). The 2"'-O-methyl compound does not bind to the enzyme presumably due to steric hindrance. The 3"'-, 4"'- and 6"'-OH groups are not essential for binding or catalysis since the 3"'-, 4"'- and 6"'-deoxy and -O-methyl derivatives are all good substrates. Increasing the size of the substituent at the 3"'-position to pentyl and substituted pentyl groups causes competitive inhibition (Ki = 1.0-2.5 mM). We have taken advantage of this effect to synthesize two potentially irreversible GlcNAc-T II inhibitors containing a photolabile 3"'-O-(4,4-azo)pentyl group and a 3"'-O-(5-iodoacetamido)pentyl group respectively. The data indicate that none of the hydroxyls of the Man"'alpha 1-6 residue are essential for binding although the 2"'- and 3"'-OH face the catalytic site of the enzyme. The 4-OH group of the Man beta-O-octyl residue is not essential for binding or catalysis since the 4-deoxy derivative is a good substrate; the 4-O-methyl derivative does not bind.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Lipopolysaccharide-stimulated events in B cell activation.

High concentrations of thymus-independent (TI) antigens are capable of inducing polyclonal B cell activation by their intrinsic mitogenic properties, irrespective of the specificity of the Ig receptors. Due to a genetic defect on the 4th chromosome, B cells from C3H/HeJ mice do not respond to lipopolysaccharide (LPS). In order to define at which step the mutation affects the signalling pathway, we compared B cells from C3H/HeJ and CBA mice with regard to changes of three events, namely cell size, and MHC class I and II antigen expression after LPS stimulation. We found that cell size and expression of MHC antigens increase in B cells from CBA mice after LPS stimulation, whereas B cells from C3H/HeJ mice do not respond at all. This suggests that the defect in C3H/HeJ mice interferes with early events in the signalling pathway, either due to the absence of a LPS receptor on B cell surface or the lack of an initial component necessary for effective signal transmission subsequent to LPS receptor binding. Our results also have shown that stimulation of anti-Ig antibodies and LPS differ in some signalling events and have different final effects on B cells, which suggests that they may function differently via distinct signalling pathways.

Animals↗
PubMed1994

Interleukin-4 induces in vitro migration in naive B cells through direct mechanisms.

Interleukin-4 (IL-4) mediated locomotor responses by murine B cells in vitro were examined in this paper. The IL-4 induced migration was found to act directly on purified, splenic B cells, without involvement of secondary mediators. It appeared that only a subpopulation of B cells was able to respond in migration assays. Flowcytometric analysis showed that the migrating cells had the characteristics of naive B cells: I-Alo, J11dhi, IgDhi. They also displayed high expression of the adhesion molecule L-selectin and made predominantly IgM antibodies. This is contrary to what has previously been observed regarding motile responses to chemotactic factors by T cells, which mostly affect memory or activated T cells. However, this is in accordance with other studies indicating that IL-4 is a cytokine that exerts its effect mainly on resting B cells.

Animals↗
PubMed1994

Chemical dehydration for rapid paraffin embedding.

We describe chemical dehydration with 2,2-dimethoxypropane (DMP) for rapid paraffin embedding using a mixture of DMP and mineral oil followed by mineral oil as clearing intermediates. This method is useful for classical histological techniques as well as for histochemistry and immunocytochemistry.

Desiccation↗
PubMed1994

A comparison of the resolution provided by different imaging systems and display media in surgery.

In microsurgery and in endoscopy in particular, the resolution provided by different imaging systems and display media is often a subject of discussion. Starting with the concept of contrast transfer, the terms pixel, pixel availability, and pixel acceptance are then introduced here. These parameters are determined for the applications relevant in practice for endoscopes, surgical microscopes, and the associated display media (eye, 35 mm film, video camera, and monitor). A comparison between pixel availability and pixel acceptance also allows a comparison between the different display media and the determination of the limiting factor in the image reproduction chain.

Endoscopes↗
PubMed1994

Interleukin-10 inhibits motility in murine and human B lymphocytes.

We here report the finding that the anti-inflammatory cytokine interleukin-10 (IL-10) inhibits motility of B lymphocytes. B cells were induced to display motile morphology and active migration by IL-4. IL-10 inhibited locomotor responses to IL-4, when B cells of both murine and human origin were used. The inhibitory effect of IL-10 was reversible, since washing of B cells preincubated in IL-10 restored the ability to respond to IL-4. Time-course experiments showed that IL-10 did not have to be present from the very onset of culture, but could be added as late as 5 hr after initiation. In addition, murine B cells stimulated with lipopolysaccharide (LPS) showed motile morphology, as well as cellular aggregation and proliferation. All these parameters were suppressed by IL-10. However, viability of B cells was not adversely affected by IL-10. Exposure to IL-10 did not result in any changes in the surface expression of molecules involved in adhesion, such as CD2, CD11a/CD18, CD44, CD54 or L-selectin, on B lymphocytes.

Animals↗
PubMed1993

Manipulation of the superantigen-induced lymphokine response. Selective induction of interleukin-10 or interferon-gamma synthesis in small resting CD4+ T cells.

The production of several lymphokines by freshly isolated CD4+ T cells has been analyzed at the single-cell level, after stimulation with staphylococcal enterotoxin B (SEB). High frequencies of cells producing interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) were induced, but very low frequencies of CD4+ T cells produced IL-4, IL-5 or IL-10 in response to SEB. Exogenously added IL-4 markedly altered the lymphokine profile induced during primary SEB stimulation. IFN-gamma production was reduced, while a high fraction of cells contained IL-10 and IL-4 after activation in the presence of IL-4. We further demonstrate that IL-4 and IL-10 or IFN-gamma production was selectively induced in resting, high-density CD4+ T cells during primary stimulation, by SEB + IL-4 or SEB. Under conditions where both IL-10 and IFN-gamma were produced, most cells contained only one of the two lymphokines.

Animals↗
PubMed1993

The effect of T cell-derived cytokines on B cell motility in vitro.

We have investigated the ability of interleukin-1 (IL-1), IL-2, IL-3, IL-4, IL-5, IL-6, and interferon-gamma (IFN-gamma) to induce motility in murine, splenic B lymphocytes. Two parameters of cellular locomotion were studied, namely acquisition of motile morphology (polarization) and in vitro migration through polycarbonate filters. Of the tested cytokines, only IL-4 gave a strong motile response among B cells. At the optimal concentration of 3 ng/ml, IL-4 induced polarization in 10-20% of the B cells within 30 min and in up to 40% after overnight exposure. The same amount IL-4 present in a microchemotaxis chamber stimulated migration through polycarbonate filters after overnight incubation in up to 15% of the input B cells. IFN-gamma could also induce some degree of polarization and migration, but only after 19 hr of exposure and to a much lesser extent than IL-4.

Animals↗