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Biomedical subjects

E Ulvestad

Publications and source records attributed to E Ulvestad.

83 records · Page 5Linked to original sources

Suppression of mitogen-induced lymphoproliferation by soluble IgG Fc receptors in retroplacental serum in normal human pregnancy.

A competitive ELISA was used to quantify soluble IgG Fc receptors (FcR) in retroplacental serum (RPS) and peripheral serum (PS) from 10 women after uncomplicated full-term deliveries. The RPS contained significantly higher amounts of soluble FcR than did PS from the same individuals. RPS suppressed phytohaemagglutinin-stimulated lymphoproliferation as compared with PS, and a positive correlation (r = 0.66) was found between the degree of suppression and the difference in soluble FcR level between RPS and PS. Absorption of sera with Sepharose 4B coupled with heat-aggregated IgG strongly reduced the immunosuppressive activity, whereas absorption with Sepharose coupled with IgG F(ab')2 fragments did not. When IgG-binding material was eluted from Sepharose beads and added to cell cultures, the immunosuppressive activity was restored. The data indicate that soluble FcR at physiological levels have immunosuppressive properties. FcR-mediated immunosuppression may be of importance for maintenance of local immunosuppression during pregnancy.

Female↗

Biology of adult human microglia in culture: comparisons with peripheral blood monocytes and astrocytes.

We have compared phenotypic and functional properties of surgically derived adult human microglia to autologous and allogenic peripheral blood-derived monocytes and to astrocytes derived from the same surgical resection. We found that microglia differed from peripheral blood monocytes with respect to adhesion properties and survival rates in vitro. Microglia, similar to resident macrophages in different tissues, expressed many but not all (CD4, Leu-M3, non-specific esterase) monocyte/macrophage associated markers tested, a pattern similar to that of terminally differentiated cells of this lineage. As with other human tissue macrophages, but in contrast to astrocytes, microglia did not undergo DNA synthesis in vitro, assessed using BrdU incorporation. Under basal culture conditions the majority of microglia of all morphologic subtypes (ameboid, bipolar, ramified) expressed MHC class II molecules; by flow cytometric analysis, mean fluorescence intensity of these cells was less than that of blood monocytes (relative to isotype control). In vitro MHC class II antigen expression on microglia, under basal and interferon gamma activating conditions, was greater than on astrocytes. Freshly derived T cells cultured with 1-10% autologous microglia plus Candida albicans underwent active proliferation, indicating the functional capacity of the microglia to serve as antigen-presenting cells.

Astrocytes↗

Myasthenia gravis muscle antibodies examined by ELISA: IgG and IgM antibodies characterize different patient subgroups.

Sera from 90 myasthenia gravis (MG) patients were examined for antibodies against skeletal muscle citric acid extract (CA) antigens by ELISA and indirect haemagglutination (IHA). 31% (ELISA) and 24% (IHA) of the sera were positive, and the results of the two tests were in good agreement. 18 of 28 patients positive in ELISA had IgG CA-antibodies, 10 had IgM and 3 IgA CA-antibodies. The patients with IgG antibodies had a high mean age of MG disease onset, and 9/14 thymectomized patients had a thymoma. Patients with IgM CA-antibodies had a much lower age of onset and 4/5 thymectomized patients had thymus hyperplasia. IgM antibody positive patients had a long disease duration, indicating that they produce IgM antibodies for an indefinite period of time without switching to IgG antibody production.

Adolescent↗

IgG Fc receptor heterogeneity in human peripheral nerves.

The presence of Fc-receptors for IgG, FcRI (CD64), FcRII (CD32) and FcRIII (CD16) in human peripheral nerves was studied by indirect immunofluorescence staining of cryostat sections with monoclonal antibodies (mabs). The mabs 32.2 against FcRI, IV.3 and C1KM5 against FcRII, B1D6 against a 40 kD FcR with low affinity for IgG, and Leu-11b and 3G8 against FcRIII stained a few scattered cells in the endoneurium, apparently monocytes/macrophages. In addition, B1D6 and Leu11b gave a membranous staining of Schwann cells, endothelial cells and perineurial cells. Axons and fibroblasts were not stained by any of the mabs. The FcR may be important in binding immune complexes, in phagocytosis, in the release of lymphokines as well as cytotoxic and inflammatory mediators and in local immunoregulation.

Antibodies, Monoclonal↗

Fc gamma receptor heterogeneity in the human placenta.

Fc receptors for IgG, FcRI (CD64), FcRII (CD32), and FcRIII (CD16) in human placenta were studied by indirect immunohistochemistry using avidin-biotin peroxidase complexes for the staining of cryostat sections. The MoAb 32.2 against FcRI stained cells in the loose connective tissue of the placental villi. The MoAb IV3 (FcRII) and C1KM5 (FcRII) also stained stromal cells and in addition stained the endothelium of the placental villi. The MoAb anti-Leu-11b against FcRIII and B1D6 against a 40-kDa FcR from placenta stained both stromal cells and endothelium as well as the fetal trophoblasts lining the villi. The MoAb 3G8 (FcRIII) also stained trophoblasts and stromal cells but did not stain the endothelium. The heterogeneity of FcR expression on human placenta is established. The function of the different receptors is still unclear.

Antibodies, Monoclonal↗

Purification of a functional 40 kD human placental Fc gamma-receptor using a monoclonal antibody.

F(ab')2-fragments of a mouse monoclonal antibody (B1D6) reacting with placental receptors for the Fc part of IgG (FcR) were used as affinity reagents for the purification of an antigen from placental extract (PE). The antigen agglutinated ovine erythrocytes (E) sensitized with rabbit antibodies (A) (EA), but not E or E sensitized with F(ab')2-fragments. It reduced the EA rosette-formation with mononuclear cells and the binding of soluble immune complexes to placental tissue. The antigen bound to aggregated IgG and Fc-fragments of IgG, but not to native IgG or F(ab')2-fragments of IgG. The data indicate that the purified antigen possesses FcR activity with low affinity for IgG. SDS-PAGE and Western blot showed one distinct band of approximately 40 kD. The electrophoretic mobility did not change after reduction and the band reacted with concanavalin A indicating that the FcR are single-chained glycoproteins.

Antibodies, Monoclonal↗

IgG Fc receptors in sera from patients with rheumatoid arthritis and systemic lupus erythematosus.

A murine monoclonal antibody to receptors for IgG (FcR) in human placenta was used in a competitive ELISA to demonstrate soluble FcR in human sera. Sera from 20 blood donors, 30 patients with systemic lupus erythematosus and 50 patients with rheumatoid arthritis were examined. Soluble FcR were demonstrated in all sera. However, significantly lower amounts of FcR were demonstrated in the patient groups as compared to blood donors. Whether this is due to increased consumption or reduced production has to be further investigated. The findings may be of significance in the pathogenesis of these diseases.

Arthritis, Rheumatoid↗

Bannwarth's syndrome: serum and CSF IgG antibodies against Borrelia burgdorferi examined by ELISA.

A newly identified spirochete, Borrelia burgdorferi, has recently been established as the causal agent of chronic meningoradiculitis (Bannwarth's syndrome, BS). An etiological diagnosis can be obtained by specific antibody determination. To detect intrathecally produced Borrelia antibodies, we examined paired serum and CSF samples from 10 BS patients and 41 controls. CSF/serum IgG specific antibody indices were calculated by relating the CSF/serum ratio of specific antibody activity to the CSF/serum ratio of total IgG and of albumin; 8/10 BS patients compared to 4/39 controls had elevated index values. In only one of the 4 positive controls could spirochetal infection be excluded. We conclude that determination of specific antibody indices is a reliable and sensitive diagnostic test for nervous system B. burgdorferi infection.

Antibodies, Bacterial↗

Cells encapsulated in alginate: a potential system for delivery of recombinant proteins to malignant brain tumours.

Growth and progression of malignant brain tumours occurs in a micromilieu consisting of both tumour and normal cells. Several proteins have been identified with the potential of interfering directly with tumour cells or with the neovascularisation process, thereby inhibiting tumour growth. A continuous delivery of such inhibitory proteins to the tumour microenvironment by genetically engineered cells could theoretically be of considerable therapeutic importance. In this study we have investigated the growth characteristics of cells encapsulated in alginate, which represents a potential delivery system for recombinant proteins that may have antitumour effects. Three different cell lines, NHI 3T3, 293 and BT4C were encapsulated in alginate, which is an immuno-isolating substance extracted from brown seaweed. The encapsulated cells were observed at specific intervals during a 4-month period after in vitro propagation and as transplants into the cortex of BD-IX rats. Morphological studies showed that encapsulated cells proliferated and formed spheroids within the alginate in the in vitro cultures and after implantation into the brain. Even after 4 months in vivo a substantial amount of living cells were observed within the alginate beads. A vigorous infiltration of mononuclear cells was observed in the brain bordering the alginate beads, one week after implantation. However, there was a gradual decrease of mononuclear cells at the border zone beyond the first week of implantation. The majority of inflammatory cells were reactive microglia and invading monocytes, as verified by immunohistochemistry. The data further shows that alginate encapsulated cells can be frozen in liquid N2 and will retain their viability and proliferative capacity.

3T3 Cells↗

Acute phase haemolysis in chronic cold agglutinin disease.

We previously described a paradoxical form of chronic cold agglutinin disease (CAD) in which haemolysis occurred during episodes of fever but only marginally during exposure to colds. In order to investigate the molecular basis for this response we performed a 12-month prospective study of a patient with CAD and paradoxical haemolysis. Blood samples were collected monthly during health, and daily following hospitalization owing to hip fracture. During health we observed decreased levels of C3, undetectable C4, a non-functional classical pathway and a normal alternative pathway. Increased concentrations of C1-INH/C1rs complexes indicated continuous formation of C1-antibody-antigen complexes. There was a low-grade temperature-dependent fluctuating haemolysis as evidenced from measurements of lactate dehydrogenase. Following the hip fracture, the haemolysis increased. Levels of interleukin (IL)-1beta, IL-6, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha increased as did C1-INH, C3, C4, CRP, and lactate dehydrogenase. The results support our hypothesis stating that paradoxical haemolysis in CAD is controlled by the availability of early classical pathway complement molecules and that haemolysis following acute phase responses occurs as a consequence of increased complement synthesis.

Acute Disease↗

Characterization of ribosomal P autoantibodies in relation to cell destruction and autoimmune disease.

Autoantibodies against the ribosomal P proteins are related to cell death and tissue destruction and are frequently exhibited in patients with systemic lupus erythematosus (SLE). In an attempt to explore the effect of tissue destruction on the induction of anti-P autoantibodies, we searched for anti-P autoantibodies by enzyme-linked immunosorbent assay in 201 antinuclear antibody (ANA)-positive individuals, in 10 patients with treated kidney SLE and in 45 acute leukaemia patients undergoing intensive chemotherapy. The autoantibody reactivity was further characterized using one- and two-dimensional immunoblot analysis and immunofluorescence. Anti-P were detected in 5.5% (11/201) of ANA-positive individuals, but not in kidney-affected SLE patients or in patients with leukaemia. Seven of 11 anti-P-positive patients had SLE (3/11), primary Sjögrens's syndrome (1/11) and other autoimmune diseases (3/11). A relation between disease activity and anti-P was suggested by follow-up examinations in one SLE patient, supported by the absence of anti-P autoantibodies in the 10 treated kidney SLE patients. Anti-P autoantibodies were detected by immunoblot in one patient with SLE indicating anti-P2 predominance and in the patient with Sjögrens's syndrome indicating anti-P1 predominance. Diverging humoral responses in these ANA- and anti-P-positive patients were further illustrated by immunofluorescence, elucidating varying nuclear reactivity and anti-P pattern. The observation of anti-P in individuals with active autoimmune disease, but not in patients with chemotherapy-induced cell damage, suggests that anti-P antibodies are part of a specific disease process, and not elicited as a response to cell destruction per se.

Adult↗