Biomedical subjects

M B Hansen

Publications and source records attributed to M B Hansen.

At least 109 records · Page 6Linked to original sources

PubMed1992

[Changes in mental function after anesthesia and surgery].

Minor short-term depression of mental function is seen after anaesthesia and surgery. However, general anaesthesia does not seem to cause permanent damage or depress mental function beyond the first 2-4 postoperative days and no significant advantages of regional anaesthesia, as regards to cerebral function, are found after this period. Severe cases of long term mental deterioration after surgery and anaesthesia may be explained by other factors such as per- and postoperative complications. The risk of mental disturbance is increased in patients with psychiatric disease or presenile dementia and may be due to ongoing treatment with tricyclic antidepressant and neuroleptic drugs. Centrally acting cholinergic drugs, hypotension and hypoxia together with postoperative pain and sleep deprivation should be avoided.

Anesthesia, General↗

PubMed1992

[Magnetic resonance imaging (MRI) in central pontine myelinolysis].

Three cases of central pontine myelinolysis (CPM) including magnetic resonance (MRI), are presented and the literature describing the pathological physiological background for the appearance in MRI is reviewed. MRI is recommended as the method of choice in cases of suspected CPM.

Demyelinating Diseases↗

PubMed1992

Sulfone-aromatic ligands for thiophilic adsorption chromatography: purification of human and mouse immunoglobulins.

New thiophilic matrices and new procedures were used for the purification of immunoglobulins both from human serum and from hybridoma cell cultures containing fetal calf serum. A range of aromatic and heteroaromatic ligands containing hydroxyl or amino groups have been coupled to divinyl sulfone-activated agarose. The resulting affinity matrices have the general formula M-O-CH2-CH2-SO2-CH2-CH2-X-Y, where M is the agarose matrix, X is oxygen or nitrogen, and Y is an aromatic or heteroaromatic compound. Contrary to earlier expectations these matrices showed pronounced thiophilic binding patterns when tested for the selective binding of immunoglobulins from human serum. The binding is influenced by the structure of the aromatic part of the ligand, the ligand concentration, and the concentration and type of lyotropic salt. 2-Hydroxypyridine coupled to divinyl sulfone-activated agarose was used to purify murine monoclonal antibodies (IgG1 and IgM) from hybridoma cell cultures containing fetal calf serum. Compared to previous methods, significantly increased binding capacity (300-1500%) was obtained by using 1.0-1.2 M ammonium sulfate. Purity of the monoclonal antibody may be optimized for each individual clone by washing the column with either a low concentration of ammonium sulfate or polyethylene glycol before elution.

Animals↗

PubMed1992

1,25-Dihydroxyvitamin D3-mediated suppression of T lymphocyte functions and failure of T cell-activating cytokines to restore proliferation.

1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) has been shown to be a potent inhibitor of lymphocyte proliferation in vitro. The present study was undertaken to determine if this is caused by a direct effect on the lymphocytes, and to evaluate to what degree this suppression may be restored by the addition of cytokines. 1,25-(OH)2D3, > or = 10(-10) M, significantly inhibited the proliferation of pokeweed mitogen (PWM)-driven human peripheral blood mononuclear cells (MNC). Depletion of monocytes did not alter the response to 1,25-(OH)2D3. The antiproliferative effect was preceded by decreased production of interleukin (IL)-1 alpha and lymphotoxin (LT), both of which are crucially involved in T cell activation. However, the suppressive effect of 1,25-(OH)2D3, seen in MNC cultures stimulated with PWM alone, was of the same magnitude as the effect seen in MNC cultures stimulated with a combination of PWM and recombinant (r)IL-1 alpha, rIL-6, recombinant tumour necrosis factor (rTNF) alpha, rIL-2 or rLT, as well as PWM plus conditioned medium. Although pretreatment of monocytes for 2 h with 1,25-(OH)2D3 caused significant reduction in the release of IL-1 alpha and TNF alpha, reconstitution of monocyte-depleted cultures with similarly treated monocytes had no inhibitory effect on the proliferative response. In conclusion, even though it cannot be excluded that a low but critical number of monocytes are essential for the suppressive effect of 1,25-(OH)2D3-mediated inhibition of MNC proliferation, the inhibition is most likely the result of a direct effect on the lymphocytes and independent of monocytes and exogenously added cytokines.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Involvement of non-classical 5-HT receptor in serotonin and cisapride induced secretion in hen colon.

1. In hen colon 5-HT induces a tetrodotoxin-resistant, bumetanide-sensitive, chloride secretion, positively coupled with adenylate cyclase activity. 2. The 5-HT receptor mediating this response seems non-classical since it cannot be blocked by 5-HT1-like, 5-HT2 or 5-HT3 antagonists. 3. Effects are presented of new putative 5-HT agonists and antagonists on short circuit current and cord conductance in the hen colon, using the Ussing chamber technique. 4. The substituted benzamides, cisapride and BRL 24924, induced a dose-dependent short circuit currents but both with less potency than 5-HT. 5. Cisapride mediated this dose-dependent bumetanide sensitive response mainly by release of acetylcholine, since atropine reduced cisapride response by 70%. 6. Neither BRL 24924, 5-HTP-DP, ketanserin, ICS 205-930, prazosin, yohimbine, atropine nor piroxicam, covering the 5-HT1P, 5-HT2P, 5-HT2, 5-HT3, 5-HT4, adrenergic and muscarinic receptor types and the prostaglandin synthesis, altered 5-HT induced increases in short circuit current and cord conductance. 7. Results suggest (a) cisapride mediates it's response mainly by releasing acetylcholine, which then stimulates muscarinic receptors to release 5-HT. (b) Involvement of a non-classical 5-HT receptor subtype in 5-HT induced chloride secretion in hen colon.

Acetylcholine↗

PubMed1992

Effects of human anti-IL-1 alpha autoantibodies on receptor binding and biological activities of IL-1.

Immunoglobulin G (IgG) antibodies to interleukin 1 alpha (IL-1 alpha) are frequently found in the sera of healthy human individuals. The effects of these autoantibodies on receptor binding and biological activities of human IL-1 were tested. Using the murine T-lymphocyte line NOB-1, human thyrocytes and human foreskin fibroblasts, the antibodies competitively inhibited the biological activity of human recombinant IL-1 alpha (rIL-1 alpha). The degree of inhibition correlated with 125I-rIL-1 alpha binding to IgG in different immunoglobulin preparations and in individual sera. These antibodies also neutralized the IL-1 activity of isolated membrane fragments and lysates of human blood monocytes activated by lipopolysaccharide. In contrast, the supernatant IL-1 activity was not affected. Stronger inhibition of biological activity and cell binding of 125I-rIL-1 alpha was obtained with NOB-1 cells than with human thyrocytes. The antibodies failed to interfere with the biological activity of rIL-1 beta. It is concluded that IgG autoantibodies of IL-1 alpha in the sera of healthy humans selectively inhibit the biological activity of the soluble and membrane-associated forms of IL-1 alpha in vitro, and that the degree of biological inhibition afforded by these antibodies depends upon the target cell.

Animals↗

PubMed1992

Serum-induced suppression of interferon (IFN) activity. Lack of evidence for the presence of specific autoantibodies to IFN-alpha in normal human sera.

IgG antibodies binding to different IFN species have been described in sera of healthy and diseased individuals. Human serum immunoglobulins have also been shown to interfere with IFN bioactivity. To characterize these antibodies, human recombinant IFN-alpha 2A (rIFN-alpha) was radioiodinated, and ligand binding studies were performed in human sera as well as on the human cell line A-549 in the presence of human serum. 125I-rIFN-alpha bound to serum factors of healthy individuals. However, less than 3% of the binding was to IgG and the binding was non-saturable and therefore most likely non-specific. 125I-rIFN-alpha bound to receptors on A-549 cells, and the ligand-receptor complexes appeared to internalize. However, both cell binding and internalization of 125I-rIFN-alpha were independent of the presence of human serum. We conclude that normal human sera do not contain detectable autoantibodies to rIFN-alpha.

Animals↗

PubMed1992

Recognition of Leishmania antigens by T lymphocytes from nonexposed individuals.

Crude antigen preparations of Leishmania promastigote sonicates were found to induce in vitro proliferation and gamma interferon production in peripheral blood mononuclear cells (PBMC) from individuals without known exposure to the parasite. The proliferating cells were mainly CD2-positive T cells. The proliferative response was maximal after more than 6 days of incubation with the antigens in contrast to the proliferation induced by the mitogenic lectin phytohemagglutinin (PHA), which peaked after 3 to 5 days. Judged by limiting dilution analysis, the frequencies of antigen-reactive precursor cells were less than 1:10,000 and varied considerably between individuals. Depletion of CD45R0-positive (memory) cells from the PBMC abolished proliferative responses induced by Leishmania antigen and by tetanus toxoid. In cell populations depleted of CD45RA-positive (naive) cells, only a small reduction in response was observed. Cell populations depleted of either CD45R0-positive cells or CD45RA-positive cells both responded to PHA. We conclude that presumably unexposed individuals have a low number of Leishmania-reactive T cells in their circulatory systems. The Leishmania-reactive T cells in these individuals are most likely memory cells recognizing antigens present both in the Leishmania preparations and in the environment.

Adult↗

PubMed1991

Inhibitor of interleukin-1 alpha and interleukin-1 beta-induced T-cell activation in serum of patients with active Crohn's disease.

Interleukin-1 is a family of polypeptides with a wide spectrum of immunoinflammatory activities pertinent to Crohn's disease, including T-cell activation. Using specific enzyme-linked immunosorbent assays, only sera from two of 19 patients (11%) with active Crohn's disease contained interleukin-1 alpha and interleukin-1 beta activity. Using the thymocyte proliferation assay, sera from the same patients contained significantly increased inhibitory activity against interleukin-1 alpha (P = 0.025) and interleukin-1 beta-induced cell activation (P = 0.00005) as compared with controls. Changes in both interleukin-1 alpha (P = 0.020) and interleukin-1 beta (P = 0.012) inhibitor concentrations correlated significantly with changes in clinical disease activity. None of the patient sera contained IgG or IgM autoantibodies to IL-1 alpha, nor did they exert significant inhibitory activity against interleukin 1 beta in the fibroblast prostaglandin E2-induction assay. Taken together, these data provide evidence for the presence of one or several regulators of interleukin-1-induced T-cell activation in sera from patients with active Crohn's disease.

Adult↗

PubMed1991

Human anti-interleukin 1 alpha antibodies.

Autoantibodies to the cytokine interleukin (IL)-1 alpha are frequently found in sera of apparently healthy humans. We have developed a sensitive radioimmunoassay (RIA) and an indirect enzyme-linked immunosorbent assay (ELISA) for the detection of human serum antibodies to IL-1 alpha at concentrations below 10 pmol/l. The RIA is based on coprecipitation of 125I-labelled human recombinant IL-1 alpha (rIL-1 alpha) by rabbit antibodies to human immunoglobulins. The ELISA is based on recovery of added rIL-1 alpha to serum samples and takes advantage of the fact that free human autoantibodies to IL-1 alpha in a dose dependent manner reduce recovery of added rIL-1 alpha. The assays correlate exceedingly well (r = 0.99, P less than 0.001). Their inter- and intraassay coefficients of variation were less than 30% and less than 5% (RIA) and less than 20% and less than 10% (ELISA). Both assays were used to measure the presence of anti-IL-1 alpha antibodies in sera of patients with various autoimmune diseases. Autoantibodies to IL-1 alpha were detectable in up to 75% of these sera, but the frequencies and titers varied considerably between individuals with different diseases.

Autoantibodies↗

PubMed1991

Down-regulation of monocyte functions by treatment of healthy adults with 1 alpha,25 dihydroxyvitamin D3.

A number of in vitro studies suggest an immunoregulatory role of 1 alpha,25 Dihydroxyvitamin D3 (1,25-(OH)2D3). The hormone inhibits production of interleukin-2 and immunoglobulin, and it blocks lymphocyte proliferation. Diverse effects on monocyte functions have been reported. However, immunological effects of 1,25-(OH)2D3 have not been substantiated in vivo. Six healthy male volunteers, aged 28-45 yr, were treated orally with 1,25-(OH)2D3 (tabl. Rocaltrol), 1 microgram twice daily for 7 days. Blood and urine samples were collected before and 7 days after initiation of treatment. Blood mononuclear cells from individuals treated with 1,25-(OH)2D3 showed a significantly reduced production of both interleukin-1 alpha (45%) and tumor necrosis factor-alpha (58%) (both measured by ELISA). Interleukin-6, production, measured by the B9 cell assay, was reduced in five individuals (78%), and unchanged in one. There was no effect on the release of interleukin-1 beta. There was no measurable effect on interleukin-2, interferon gamma or immunoglobulin production, or on mitogen-induced proliferation of blood mononuclear cells. Serum-osteocalcin and urine excretion of calcium were increased to 131 and 173%, respectively. The serum-calcium and serum-phosphate levels were unchanged.

Administration, Oral↗

PubMed1991

Interleukin-1 receptors on human thyroid cells and on the rat thyroid cell line FRTL-5.

Cellular binding of interleukin-1 (IL-1) was tested on monolayers of human thyrocytes in secondary culture, on long-term cultures of human thyrocytes, and on the rat thyroid cell line FRTL-5. The human thyrocytes in secondary culture showed specific binding of human 125I-rIL-1 alpha. Scatchard plots of data obtained at 4 degrees C indicated the presence of a single population of receptors with a Kd of 30 to 170 pM and 2,000 to 6,000 receptors per cell. Incubation at room temperature resulted in internalization of the receptor-ligand complex. Parallel experiments were performed with the IL-1 receptor-positive murine T-cell lines EL-4 and NOB-1. The IL-1 receptors on these cells had Kd values one fifth to one tenth those on human thyroid cells in secondary culture. Both rIL-1 alpha and rIL-1 beta inhibited 125I-rIL-1 alpha binding to human thyrocytes and the murine T cells. In contrast to the cells in secondary culture, there was no specific binding of 125I-rIL-1 alpha to long-term cultivated human thyroid cells or to the FRTL-5 cells. We concluded that recently described differences in the response to IL-1 of different thyroid cell culture systems are most likely caused by differences in expression of IL-1 receptors.

Animals↗

PubMed1991

Anti-interleukin-6 antibodies in normal human serum.

High-avidity IgG antibodies to the cytokine interleukin-6 (IL-6) were found in sera of apparently healthy adult individuals. These antibodies specifically interfered with an ELISA (enzyme-linked immunosorbent assay) for IL-6 in which specific polyclonal rabbit antibodies to human recombinant IL-6 (rIL-6) were used. Furthermore, using precipitation of 125I-rIL-6 with rabbit antibodies to human immunoglobulins (Ig), the sera of 7 out of 68 Danish blood donors were found to contain specific antibodies in substantial amounts. Judged by ELISA interference, gel filtration of sera incubated with 125I-rIL-6 and second antibody precipitation of 125I-rIL-6, IgG seemed to be the dominant IL-6 binding protein in these normal sera. Using specific antibodies to human Ig light chains, it was found that the anti-IL-6 antibodies were of polyclonal origin. Moreover, there are at least two epitopes on the IL-6 molecule, because more than one IgG bound to some IL-6 molecules at the same time. The anti-IL-6 antibodies did not cross-react with a number of other human recombinant-derived and native cytokines. The antibodies recognized native as well as rIL-6, but preferentially monomeric IL-6.

Autoantibodies↗

PubMed1991

Elastolytic activity of human monocytes from synovial fluid and blood of patients with arthritis. Relations to levels of interleukin 6 and soluble interleukin 2 receptor.

Synovial fluid (SF) and blood from 24 patients with non-traumatic, sterile hydarthron were examined for monocyte elastolysis (MøE) and for levels of interleukin 6 (IL-6) and of soluble interleukin 2 receptor (sIL-2R). Six patients had osteoarthrosis (OA) and 18 patients had inflammatory hydarthron (IH), 10 of whom had rheumatoid arthritis (RA). Blood MøE was lower in OA than in IH, both measured as basal MøE activity and after in vitro stimulation with immune complexes and phorbol myristate acetate (PMA). SF MøE was higher than MøE in blood (p less than 0.01). This increase in SF MøE could be mimicked in vitro by prestimulation of blood Mø with low levels of IC. SF IL-6 and sIL-2R were also elevated (p less than 0.01). All three parameters correlated to the degree of joint inflammation evaluated by SF leucocyte level, complement activation, blood C Reactive Protein, and to the clinical evaluation of the joint. The increase in SF MøE, IL-6 and sIL-2R in patients with IH, points to a stimulation of Mø and lymphocytes in the joint.

Adult↗

PubMed1991

Effects of in vitro hyperthermia on the proliferative response of blood mononuclear cell subsets, and detection of interleukins 1 and 6, tumour necrosis factor-alpha and interferon-gamma.

The role of endogenously mediated fever and exogenous hyperthermia as modulators of immune functions remains poorly understood. It is known that fever is mediated by several cytokines, including interleukin-1 alpha and interleukin-1 beta (IL-1 alpha and IL-1 beta), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha) and the interferons. The present communication examines the effect of exogenous hyperthermia on the detection of these cytokines and shows the suppressive effect of elevated temperature (39 degrees) on the amount of IL-1 beta, IL-6 and IFN-gamma (P less than 0.001) but not on IL-1 alpha and TNF-alpha concentrations. It is suggested that a negative feedback mechanism exists between temperature and the production of some of the molecules involved in the mediation of fever. It is known that hyperthermia increases the proliferative response of lymphocytes. We found a twofold increase in [3H]thymidine incorporation at 39 degrees compared to 37 degrees. The distribution of cells expressing CD3, CD4, CD8, CD14, CD16, CD19 and CD25 markers was the same at 37 degrees and 39 degrees.

Antigens, CD↗

PubMed1990

A sensitive antiviral neutralization bioassay for measuring antibodies to interferons.

An improved bioassay for measuring neutralizing antibodies to interferons (IFN) is described. The assay is based upon an objective and precise quantification of the viral cytopathic effect. This effect is measured via the dehydrogenase-system in cells, and quantified spectrophotometrically. Virus-infected cells, in contrast to non-infected cells, possess low enzyme activity resulting in low OD signals. This fall in OD can be prevented by the addition of a small, but fixed amount of IFN before the addition of virus. Anti-IFN sera will neutralize the protective effect of IFN. This effect can be quantified by measurement of the reduction in the OD signals. Antibodies to recombinant IFN were found to cross-react with human leukocyte IFN although to a ten-fold lower degree. The assay requires no expensive reagents, it is performed in 96-well microtrays and the results can be measured in an ordinary ELISA scanner. The assay is highly reproducible, yielding inter- and intra-assay variability of less than 10%. The sensitivity is much higher than that reported previously for the CPE technique and that of ELISA techniques.

Animals↗

PubMed1990

Autoantibodies to crude human leucocyte interferon (IFN), native human IFN, recombinant human IFN-alpha 2b and human IFN-gamma in healthy blood donors.

Recently, naturally occurring antibodies to IFN-alpha were discovered in a few systemic lupus erythematosus (SLE) and cancer patients; however, in most patients monitored for anti-IFN antibodies before treatment, no antibodies were found. In an attempt to explain the 'IFN-blocking effect' that we observed in all serum samples we investigated 200 sera from healthy blood donors. We isolated the globulin fraction, and used rabbit anti-human IgG and IgM columns, protein A columns and T-gel affinity chromatography to isolate human IgG and IgM. All sample fractions were tested in a biological IFN neutralization assay by means of a sensitive MTT-assay. We found that normal human serum contained autoantibodies to crude human leucocyte IFN, native human fibroblast IFN, recombinant human leucocyte IFN-alpha 2b and recombinant human IFN-gamma, and that these naturally occurring antibodies were biologically active immunoglobulins of IgG and IgM type. These anti-IFN antibodies were also present in purified human normal immunoglobulin pools. We conclude that all humans have naturally occurring anti-interferon antibodies in their serum, and it is a tempting theory that human cytokines and lymphokines are, at least partly, regulated by immunoglobulins.

Adolescent↗

PubMed1990

A new sensitive bioassay for precise quantification of interferon activity as measured via the mitochondrial dehydrogenase function in cells (MTT-method).

A biological method for precise quantification of interferons has been developed. The method is based upon the dehydrogenase system of the intact target cells, which will normally convert an artificial substrate, MTT, into formazan (blue), which, in turn, can be measured spectrophotometrically. This conversion is greatly reduced by cytocidal viruses in a dose-dependent manner. The protection of target cells by interferon against challenge virus is reflected in a diminished reduction in the production of formazan, thus giving a very precise method for quantification of interferon. The lowest level of detection is around 0.10 international units. The intra- and inter-assay variability appear to be below 10%. The assay, which makes no use of expensive ingredients, is performed in 96-well micro-trays and read in an inexpensive ELISA-scanner.

Biological Assay↗