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Biomedical subjects

E Ulvestad

Publications and source records attributed to E Ulvestad.

At least 55 records · Page 3Linked to original sources
PubMed1999

Reliability and sensitivity of diagnostic tests for primary Sjögren's syndrome.

OBJECTIVE: To investigate whether diagnostic tests for primary Sjögren's syndrome (pSS) are reproducible when repeated after one year (reliability). To evaluate whether the sensitivity of the diagnostic tests increases with repeated testing. METHODS: A structured interview investigating the subjective sensation of dry eyes and dry mouth, and the diagnostic tests Schirmer I, unstimulated whole saliva collection (UWSC), serological tests for antinuclear antibodies (ANA), for anti-Ro/SSA and anti-La/SSB antibodies as well as Waaler's test for rheumatoid factor, were performed twice with a one year interval in 66 patients with pSS. Reliability was given as the percentage of positive tests remaining positive at the second examination, while sensitivity was given as the percentage of patients with positive tests. RESULTS: Highest reliability was obtained for the sensation of dry mouth (98.2%) and sensation of dry eyes (96.4%), and anti-SSA/SSB antibodies (93.3%). Lowest reliability was obtained for rheumatoid factor at cutoff titer 1:32 (70.6%) and positive Schirmer I in one eye (77.4%). The reliability for ANA was 80% at cutoff titer 1:32, and increased to 93.3% at cutoff titer 1:128. UWSC had a reliability of 84.2%. The pooled sensitivity for all the tests increased significantly (p < 0.05) compared to the examination, which had the lowest sensitivity. CONCLUSION: The diagnostic tests for pSS are generally highly reliable when performed twice with a one year interval. The gain in sensitivity by repeating the tests is limited, being most marked for Schirmer I.

Adult↗
PubMed1998

[Large granular lymphocytic leukemia].

Large granular lymphocyte leukaemia (LGL leukaemia) is a rare, chronic lymphoproliferative bone marrow disease which can be considered a subtype of chronic T-cell lymphocytic leukaemia (T-CLL). We describe three patients with large granular lymphocyte leukaemia. They all suffered from chronic disease with neutropenia and relative lymphocytosis. An expansion of mature lymphocytes with the CD3+, CD8+, CD57+ immunophenotype was demonstrated in all three patients. Two patients had a history of recurring infections. Serological findings compatible with rheumatic disease were present in all three patients, and two suffered from rheumatoid arthritis. We have made a brief survey of this disease, which is characterized by relative or absolute lymphocytosis, neutropenia, and an increased risk of infection. Rheumatoid arthritis and other associated autoimmune manifestations occur frequently. Large granular lymphocyte leukaemia should be considered a possible diagnosis in patients with chronic neutropenia and relative lymphocytosis, in particular if rheumatic manifestations are also present. Flow cytometric immunophenotyping is a sensitive method in diagnosing this disease.

Aged↗
PubMed1998

T-lymphocyte functions in acute leukaemia patients with severe chemotherapy-induced cytopenia: characterization of clonogenic T-cell proliferation.

Intensive chemotherapy for acute leukaemia is followed by a period of severe chemotherapy-induced leukopenia. We used a limiting dilution assay to investigate whether remaining CD4+ and CD8+ T lymphocytes derived from such leukopenic patients could be activated and undergo clonogenic proliferation. The activation signal in our model was accessory cells (irradiated normal peripheral blood mononuclear cells) + phytohaemagglutinin (PHA) + interleukin-2 (IL-2). During severe leukopenia a majority of circulating lymphocytes were CD4+ T cells. Clonogenic proliferating T lymphocytes were detected for all patients. Higher frequencies of clonogenic cells were detected in the CD8+ subset as compared to the CD4+ subset. However, for both subsets frequencies of proliferating cells were decreased compared with healthy individuals. The CD4+ and CD8+ lymphocytes were also capable of proliferation in response to alloactivation, and accessory cells mainly containing acute myelogenous leukaemia blast were efficient as accessory cells for activation. For the CD4+ cells, increased proliferation was detected in the presence of acute myelogenous leukaemia (AML) blasts compared with normal accessory cells. Based on our results we conclude that: (1) although acute leukaemia patients with therapy-induced leukopenia have both a quantitative and a qualitative T-cell defect, (2) the remaining T-cell population includes a subset capable of clonogenic proliferation. However, (3) proliferation of the clonogenic CD4+ cells can be modulated by AML blasts.

Adult↗
PubMed1998

Effects of acute myelogenous leukemia blasts on platelet release of soluble P-selectin and platelet-derived growth factor.

Complex interactions occur between platelets and normal as well as leukemic myeloid cells. In vitro co-culture of platelets and acute myelogenous leukemia (AML) blasts with allogeneic platelets enhances blast proliferation and constitutive cytokine secretion. In the present study the effects of AML blasts on the platelet release of soluble mediators are characterized. Normal platelets released soluble (s) P-selectin and platelet-derived growth factor (PDGF), both when cultured alone and in the presence of AML blasts, and for certain patients the presence of AML blasts increased the platelet release of these mediators. Addition of exogenous interleukin (IL) 10 to platelet-AML blast cultures further increased platelet release of PDGF and sP-selectin. For certain patients decreased AML blast cytokine secretion was observed when PDGF-specific antibodies were added to cultures with blasts plus platelets, these results indicate that platelet release of PDGF is a molecular mechanism for the enhancement of AML blast cytokine secretion. We conclude that complex functional alterations are induced both in AML blasts and normal allogeneic platelets during in vitro co-culture of leukemia cells and platelets.

Journal Article↗
PubMed1998

Concentrations of cytokines in plasma of patients with large burns: their relation to time after injury, burn size, inflammatory variables, infection, and outcome.

OBJECTIVE: To monitor longitudinally the concentrations of cytokines in the plasma of patients with severe burns. DESIGN: Prospective open study. SETTING: Burns unit, university hospital, Norway. SUBJECTS: 27 patients (5 women and 22 men, mean age 37 (range 13-82) years). INTERVENTIONS: Measurement of plasma concentrations of interleukin-1beta(IL-1beta), interleukin-1 receptor antagonist (IL-1ra), interferon-7(IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) were measured by enzyme linked immunosorbent assays (ELISA). MAIN OUTCOME MEASURES: Changes in concentrations, and correlation with morbidity and mortality. RESULTS: The concentration of IL-1beta and IL-1ra were increased in all patients and highest at the time of admission. Initially there was little or no circulating IFN-gamma, but this increased from day 5-10 in all patients. Only 8/15 patients had transient increases in circulating TNF-alpha. Concentrations of IL-1ra correlated with total burn surface area (TBSA) and area of third degree burn, as well as with plasma concentrations of C - reactive protein (CRP). Concentrations of IL-1beta and IL-1ra were higher in patients who developed infective complications than in those who did not (interleukin-8 (IL-8) has previously been shown to follow this pattern as well). Patients who survived had significantly higher IL-1beta concentrations than those who died (13(1) compared with 3 (1) pg/ml, p = 0.005) CONCLUSION: There are significant time-dependent changes in plasma concentrations of IL-1beta, IL-1ra, IFN-gamma and TNF-alpha after serious burns. IL-1ra concentrations may be influenced by size of the burn and the acute phase response; IL-1beta, IL-1ra and IL-8 may have a role in the host's response to infection; and IL-1beta may influence outcome.

Adolescent↗
PubMed1998

Paradoxical haemolysis in a patient with cold agglutinin disease.

A patient with classical cold agglutinin disease initially experienced haemolytic episodes during cold exposure. However, with advancing disease cold-induced haemolysis ceased and was substituted with a haemolytic disposition at elevated body temperatures. To investigate this paradoxical development of disease manifestations, we performed a clinical and immunological study. Our results indicate that the patient's complement system became exhausted during the later phase of his disease, probably due to continual consumption of complement components. Initially, the patient had slightly decreased C4 concentrations and moderately reduced total haemolytic activity (CH50). Later C4 fell to undetectable levels and CH50 declined to zero. The increased haemolytic activity experienced during febrile episodes is probably due to a cold agglutinin with a high thermal amplitude, combined with enhanced synthesis of complement molecules during the acute phase response. Although C4 concentrations never increased to detectable levels during infections or inflammations an acute phase reaction was determined each time, as evidenced by increased concentrations of CRP. By reconstituting the patient's serum with active complement from donor serum or plasma, increased haemolytic activity was observed. These results indicate that some patients with cold agglutinin disease may experience deleterious haemolytic consequences if transfused with plasma-containing blood products.

Aged↗
PubMed1997

Interleukin 4 responses in acute leukaemia patients with severe chemotherapy-induced leucopenia.

T lymphocyte functions in acute leukaemia patients with severe chemotherapy-induced leucopenia were investigated using 3 different approaches: (i) analysis of serum concentrations of the T cell cytokine interleukin 4 (IL4) demonstrated that serum IL4 levels increased during complicating bacterial infections. However, this response was modulated by a concomitant increase in serum levels of the potential IL4 antagonist soluble IL4 receptor alpha chain (sIL4R alpha). (ii) Even during leucopenia a subset of T lymphocytes derived from leucopenic patients expressed the activation markers CD25 (IL2 receptor), CD71 (transferrin receptor) and HLA-DR. (iii) Subsets of circulating CD4+ and CD8+ T lymphocytes could undergo clonogenic proliferation in vitro, and a majority of these clones secreted IL4. CD4+ clones showed higher IL4 levels than CD8+ clones. Our results indicate that T lymphocytes can be activated and contribute to cytokine responses in acute leukaemia patients with severe chemotherapy-induced cytopenia.

Adolescent↗
PubMed1997

Suppressive effect on lymphoproliferation in vitro by soluble annexin II released from isolated placental membranes.

PROBLEM: Syncytiotrophoblast microvillous plasma membranes (StMPM) are potent suppressors of lymphoproliferation in vitro. We have previously shown that soluble annexin II (AII) is present at higher levels in retroplacental serum (RPS) than in peripheral serum, and that soluble AII has an immunosuppressive effect. The aims of this study were to determine whether AII can be released from StMPM and whether soluble AII from StMPM exerts any immunosuppressive effect. METHOD OF STUDY: Isolated StMPM were incubated in growth medium for 18 hr and supernatants were prepared by ultracentrifugation. Soluble AII was detected by immunoblotting. StMPM, StMPM supernatant, and affinity-purified AII were analysed in a lymphoproliferation assay for immunomodulating activity. RESULTS: AII heavy chain and its p11 light chain were detected both in StMPM supernatant and in RPS after removal of StMPM particles by ultracentrifugation. StMPM, StMPM supernatant, and purified AII suppressed lymphoproliferation in a dose-dependent manner. Absorption of AII from StMPM supernatant reduced the suppressive activity. The suppressive effect of StMPM supernatant and purified AII was completely reversed by heating at 100 degrees C for 30 min or by adding recombinant interleukin-2 at 100 units/ml. Although StMPM and affinity-purified AII suppressed the proliferation of lymphocytes from all donors tested, StMPM supernatant suppressed the proliferation of lymphocytes from 12 of 23 donors. Six of eight female non-suppressed donors were multiparae, whereas five of five female suppressed donors were nulliparae. CONCLUSIONS: Annexin II is released by isolated placental membranes in vitro and is present in RPS, indicating in vivo release of AII at the fetomaternal interface, probably as AII heterotetramer. AII has immunosuppressive activity and may be important in fetal allograft survival.

Annexin A2↗
PubMed1997

Chronic cold agglutinin disease of the "idiopathic" type is a premalignant or low-grade malignant lymphoproliferative disease.

We investigated the clinical, pathological, and immunological features of "idiopathic" cold agglutinin disease (CAD) in a population-based study. Fourteen patients were studied, giving a prevalence of about 14 per million with a mean age of 75 years. Haemolysis was present in all cases, but only eight patients had clinical symptoms of peripheral haemagglutination. Serum electrophoresis, immunofixation, morphological bone marrow evaluation, and flow cytometric immunophenotyping were used to detect any monoclonal lymphoproliferative disorder. Flow cytometry seemed to be a sensitive way to demonstrate a clonal B-cell proliferation. Some evidence of clonality was found in 13 patients, and a clonal lymphoproliferative disease was documented by flow cytometry or biopsy in 10 out of 11 patients. We conclude that CAD is a symptom-producing monoclonal lymphoproliferative disorder in nearly all patients.

Adult↗
PubMed1997

Inhibition of phytohaemagglutinin-induced lymphoproliferation by soluble annexin II in sera from patients with renal cell carcinoma.

Annexin II (AII) is a member of a family of glycoproteins which bind negatively charged phospholipids in a calcium-dependent manner. Annexins are membrane-associated proteins, expressed both in normal and malignant cells, but have also been detected as soluble molecules in serum and other body fluids. Because of their adhesive properties, it has been suggested that annexins play a role in the metastatic process. An ELISA was established for quantification of soluble AII. Within-run variation was 5.2-10.4% and run-to-run variation 12.4-15.6%. Soluble AII was detected in all sera studies. A strongly positive serum was arbitrarily given the value 100 AII units and used as reference serum. The mean level in sera from 20 normal blood donors was 49 (SE 5.6) AII units. Sera from peripheral blood of five patients with renal cell carcinoma and sera from blood obtained from the renal vein of the same patients contained 47 (SE 20) and 83 (SE 28) AII units, respectively. In two patients, AII levels were increased in renal vein serum as compared with peripheral blood serum. Interestingly, in both cases, and in none of the three remaining cases, phytohaemagglutinin-stimulated lymphoproliferation was suppressed by renal vein serum as compared with peripheral blood serum. Affinity absorption of AII from the renal vein sera with increased AII levels strongly reduced their immunosuppressive activity. Addition of affinity-purified AII to cell cultures suppressed lymphoproliferation. These data show that the level of AII is markedly increased in renal vein sera from some patients with renal cell carcinoma, suggesting that AII may be locally released in vivo. The study also demonstrates an immunosuppressive effect of soluble AII in vitro. We speculate that soluble AII released by the tumour has immunosuppressive properties. This study identifies soluble AII as a novel immunosuppressive factor in sera from patients with renal cell carcinoma. A further study including a larger number of patients is currently in progress, in order to investigate the pathological significance of this finding.

Annexin A2↗
PubMed1996

[Leakage of cerebrospinal fluid. Diagnosis and treatment].

Leakage of cerebrospinal fluid may occur after fracture of the skull base or after surgery on the skull base, nose, or paranasal sinuses. Further causes of cerebrospinal fluid leakage are tumours and malformations. It may also occur spontaneously. We describe four case reports illustrating diagnostic and surgical problems. Cerebrospinal fluid oto- and rhinorrhoea should be suspected in cases of recurring purulent meningitis. Immunologic demonstration of beta(2)-transferrin in secretions from the nose and ear is a diagnostic sign of cerebrospinal fluid or perilymph. Digital subtraction cisternography, CT cisternography, and flow-sensitive magnetic resonance imaging are sensitive methods for localising dural leakage. Frontal craniotomy has been the traditional surgical approach. The recent involvement of transnasal endoscopic sinus surgery and microsurgery has made it possible to treat cerebrospinal fluid oto- and rhinorrhoea with a high degree of success and less operative morbidity.

Adolescent↗
PubMed1996

IL-10 production by adult human derived microglial cells.

Microglia, a population of central nervous system (CNS) macrophages, have been demonstrated to support immune accessory and effector functions in the CNS. Numerous studies support the role of microglia in CNS development and pathology, where activation of microglia is consistently noted. The current study investigated microglial immune functions under basal and activation conditions and assessed the ability of interleukin-10 (IL-10), added exogenously or produced by microglia, to down-regulate microglial functions. This report demonstrates that microglia from the adult human brain produce IL-10 following interferon-gamma/lipopolysaccharide activation. Functionally, recombinant human IL-10 down-regulated basal HLA-DR expression by microglia and inhibited, in a dose-dependent response, the ability of microglia to stimulate CD4+ T-cells in antigen presentation assays. These data, together with recent observations of the inhibition of experimental allergic encephalomyelitis (EAE) following IL-10 administration and reduced CNS infection by Listeria monocytogenes after anti-IL-10 treatment, suggest that IL-10 production by microglia may have important immune-regulatory functions in CNS disease and disease models.

Adult↗
PubMed1995

Increased levels of circulating interleukin-8 in patients with large burns: relation to burn size and sepsis.

Large burns are followed by significant trauma-induced immunomodulation, and activated neutrophils can be demonstrated in the circulation of burn patients shortly after injury. Interleukin-8 (IL-8) is a recently described molecule with neutrophil activating properties and in the present study we have measured the concentration of this cytokine in plasma from 27 patients with large burns during hospitalization using an enzyme linked immunosorbent assay (ELISA). The mean patient plasma concentration of IL-8 at admission was about 60 times higher than that of healthy controls. Furthermore, patients with total body surface area burn of more than 40% had significantly higher IL-8 concentrations in plasma than patients with smaller burns. For patients without serious infectious complications, the IL-8 concentration fell gradually after injury, whereas in patients with complicating sepsis a second peak of IL-8 was demonstrated. Thus, the increased IL-8 concentrations seem to be related to burn size and to have a role in the pathophysiology of sepsis in patients with large burns. The large amounts of circulating IL-8 following thermal injury may contribute to the strong and sustained activation of neutrophils reported earlier in patients with large burns.

Adolescent↗
PubMed1995

The influence of tumour necrosis factor-alpha, interleukin-1 beta and interferon-gamma on the expression and function of the complement regulatory protein CD59 on the human colonic adenocarcinoma cell line HT29.

CD59 is a 18-25 kDa glycoprotein which, by inhibiting the formation of the membrane attack complex, protects homologous cells from complement mediated damage. We have described recently the expression and complement regulatory function of CD59 on colonic adenocarcinoma cells both in vivo and in vitro. In this study we have examined the influence of cytokines on the expression and complement regulatory function of CD59 on the colonic adenocarcinoma cell line HT29. CD59 expression on the HT29 cells was up-regulated after stimulation by mononuclear cells activated by mixed lymphocyte reaction and by culture supernatants from activated mononuclear cells. Similarly, a dose-dependent increase in CD59 expression was observed after stimulation with both tumour necrosis factor-alpha and interleukin-1 beta. A dose-dependent increase in the level of CD59 expression was also seen using low concentrations of interferon-gamma (IFN-gamma), while CD59 expression on cells cultured with high IFN-gamma concentrations was comparable to non-stimulated cells. Cytokine treated cells were more resistant to lysis by homologous complement than non-stimulated cells, and the increase in CD59 expression was shown to be partially responsible for this. The present data strengthen the role of CD59 as a possible participant in tumour escape.

Adenocarcinoma↗
PubMed1995

Antigen presentation by human fetal astrocytes with the cooperative effect of microglia or the microglial-derived cytokine IL-1.

Antigen presentation by endogenous glial cells is postulated to regulate reactivity of immune cells that gain entry into the CNS. We have previously observed, using a mixed lymphocyte reaction (MLR) system, that adult human-derived microglia can function as antigen-presenting cells (APC) for immediately ex vivo CD4+ T cells in a primary MLR (1 degree MLR) whereas astrocytes could not. We have now found that fetal human astrocytes can support CD4+ T cell proliferation in the presence of exogenous human recombinant (r) IL-2, and that astrocytes can support the continued proliferation of CD4+ T cells previously sensitized to sister astrocyte cultures in a secondary MLR. Additionally, adult human microglia, seeded into the nonpriming astrocyte: CD4+ T cell cocultures at non-T cell-stimulatory concentrations of 1000-5000 microglial cells per well, could reverse the inability of astrocytes to present antigen in the primary MLR. To examine the cellular basis for the inability of human astrocytes to function as APCs in the primary MLR, astrocyte- and microglial-enriched populations were established from human embryonic and adult brain, respectively, and analyzed for their ability to synthesize cytokines potentially relevant as accessory signals in the MLR. Microglia had transcript as determined by the reverse transcriptase-polymerase chain reaction (RT-PCR) and protein as determined by bioassay for IL-1 alpha, IL-6, and TNF alpha. Human fetal astrocytes had transcript for IL-6 but not for IL-1 alpha or TNF alpha under basal culture conditions and following IFN gamma stimulation. The addition of human rIL-1 from 1-50 U/ml could reverse the inability of astrocytes to present antigen in the primary MLR. These studies demonstrate that although in vitro highly enriched cultures of astrocytes absent of microglia cannot present antigen to immediately ex vivo blood-derived CD4+ T cells in the MLR, in situ, with the cooperative help of microglia-derived cytokines or accessory surface molecules, astrocytes may function as central nervous system APCs.

Adult↗
PubMed1994

Activation of adult human derived microglia by myelin phagocytosis in vitro.

The present study was designed to determine the extent to which cultured glial cells phagocytose normal central nervous system (CNS) myelin and CNS myelin opsonized with serum or purified antibody against myelin basic protein (MBP). Glial cells studied were mixed cultures (consisting of astrocytes, microglia, and oligodendrocytes) and enriched microglia established from adult human brain specimens and enriched astrocytes from fetal human brain. A human monocytic cell line, THP-1, was included as a control. Uptake of 125I-labelled myelin was followed over a 24 hr time period. An assay of oxidative burst (30 min) and cytokine bioassays measuring IL-1, IL-6, and tumor necrosis factor (TNF) production (6-48 hr) were used to investigate short- and long-term activation of phagocytosing cells. Maximum myelin uptake by phagocytosing glial cells occurred within 12-24 hr following myelin incubation. Opsonization of myelin prior to the phagocytosis assay resulted in greater myelin uptake by mixed glial cell cultures, microglia, and THP-1 cells over that of nontreated myelin. The magnitude of myelin phagocytosis by astrocytes was considerably lower than microglia and THP-1, and was not affected by myelin opsonization. Within 30 min of myelin phagocytosis, microglia and THP-1 cells underwent oxidative burst; opsonization of myelin by purified anti-MBP IgG and heat-inactivated serum enhanced the microglial oxidative burst activity. Production of IL-1, TNF, and most markedly IL-6 by microglia was increased following 12-24 hr of myelin ingestion. Our data demonstrate that myelin phagocytosis by adult human-derived microglia occurs in vitro, is augmented when myelin is opsonized, and results in the activation of microglia as assessed by oxidative burst and cytokine production.

Adult↗
PubMed1994

A dot-immunobinding assay for the demonstration of soluble Fc gamma receptors.

We have developed a sensitive dot-immunobinding assay to demonstrate and characterize the functional activity of soluble Fc gamma receptors (FcR). Samples containing soluble FcR were immobilized on a nitrocellulose membrane. Immune complexes of horseradish peroxidase and rabbit IgG antibodies to horseradish peroxidase (HRP) were allowed to react with nitrocellulose-bound FcR, and the immune complexes were visualized by HRP developer. The intensity of the grey dots reflected the amount of immune complex bound. Binding of immune complexes to placental extract containing soluble FcR was inhibited completely by IgG and Fc fragments, but not by F(ab')2 fragments, IgA and IgM. The method was used to characterize the subclass specificity of solubilized placental FcR. Human Fc fragments, and intact IgG1 and IgG3 proteins inhibited the binding whereas preparations of F(ab')2, IgG2 and IgG4 did not. In conclusion, the dot-immunobinding assay described is a rapid and simple method for the demonstration and characterization of functionally active soluble FcR.

Antigen-Antibody Complex↗