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Biomedical subjects

M B Hansen

Publications and source records attributed to M B Hansen.

At least 73 records · Page 4Linked to original sources
PubMed1995

High avidity IFN-neutralizing antibodies in pharmaceutically prepared human IgG.

This paper demonstrates and characterizes naturally occurring antibodies to interferon (IFN) in human IgG preparations. In vitro neutralization of the antiviral effect of IFN alpha and IFN beta, but not IFN gamma, was observed in 12 of 15 normal IgG preparations. The neutralizing capacity was higher against rIFN alpha 2A and rIFN alpha 2C than against lymphoblastoid IFN alpha and IFN beta. Frühsommer meningoencephalitis hyperimmune IgG and hepatitis-B hyperimmune IgG showed potent neutralization, whereas anti-rhesus D-, anti-rabies-, and anti-tetanus IgG showed weak neutralization. Saturable binding of 125I-rIFN alpha 2A was demonstrated only in those IgG preparations found to neutralize the antiviral effect of IFN. Significant correlation between IFN binding and neutralization capacity was observed. The antibodies bound with Fab to rIFN alpha 2A with an avidity of approximately 30 pM; the majority was of the IgG1 subclass. Maximum binding capacity was 490 pg rIFN alpha 2A/mg IgG. Cross-binding of rIFN alpha 2C, lyIFN alpha N1 and IFN beta occurred with 10 and 100-200 times lower activities than that of rIFN alpha 2A. There was no cross-binding with rIFN gamma or rIL-6. IgG preparations containing anti-IFN antibodies blocked the binding of 125I-rIFN alpha 2A to A549 cells. In conclusion, pharmaceutically prepared human IgG preparations contain variable but significant levels of high-avidity IFN alpha and IFN beta neutralizing antibodies.

Antibodies, Monoclonal↗
PubMed1995

Cytokine autoantibodies in rheumatoid arthritis.

Sera from 42 patients with rheumatoid arthritis (RA) and 40 healthy controls (HC) were examined for cytokine autoantibodies (CK-aAb) by accurate and sensitive radioimmunoassays. The prevalences of detectable CK-aAb in RA (HC) were: aAb-IL-1 alpha = 36% (38%); aAb-IL-6 = 29% (13%), p = 0.06; aAb-IL-8 = 0% (0%); aAb-IFN alpha = 12% (3%), p = 0.11. The levels of the individual CK-aAb did not correlate, and there were no correlations between CK-aAb levels and clinical or laboratory variables. CK-aAb levels remained constant in 8 RA patients tested over a period of 6 months. With regard to alterations in aAb-IL-1 alpha levels, 4/11 HC were consistently positive over 18-36 months; 2/11 converted and became highly positive. The levels of aAb-IFN alpha and aAb-IL-6, but not aAb-IL-1 alpha, tended to be increased in RA patients; aAb-IL-8 were undetectable in both RA and HC.

Adult↗
PubMed1995

Tumour necrosis factor alpha in uncomplicated malaria in young adults.

The purpose of this study was: 1) to measure tumour necrosis factor alpha (TNF) in the plasma of Plasmodium falciparum infected subjects; and 2) to correlate the presence of TNF to symptomatology. Plasma from 77 malaria infected individuals (with malaria parasites) were assayed for TNF by ELISA. The mean age of the subjects under study was 16.36 +/- 0.80 (mean +/- SEM) years. Thirty-nine (51%) subjects had measurable plasma TNF. Taking symptomatology into account, 10 (59%) of the 17 asymptomatics and 29 (48%) of the 60 symptomatics had measurable plasma TNF. A risk ratio of 0.9 was obtained for the association between the detection of plasma TNF and the presence of symptoms. In plasma from 13 healthy controls no TNF was detected. The results suggest that if TNF plays a negative role in the pathogenesis of malaria, it must be in the presence of other predisposing factors.

Adolescent↗
PubMed1995

Interleukin-6 autoantibodies: possible biological and clinical significance.

The pleiotropic cytokines, interleukin (IL)-1 alpha, type I interferons and IL-6 also act on cells involved in antibody production. Somehow the immunologic tolerance to these cytokines is often spontaneously broken--even in healthy individuals. Thus, relatively high concentrations of high affinity IgG antibodies against IL-1 alpha and IL-6 frequently occur in the circulation of healthy adults. The autoantibodies specifically antagonize the respective cytokines in vitro. Thermodynamic estimations strongly suggest that autoimmunity can play a significant role in the regulation of certain cytokines. In the light of IL-6 autoantibodies the possible biological and clinical significance of cytokine autoimmunity is discussed.

Autoantibodies↗
PubMed1995

New aspects of the pathophysiology and treatment of secretory diarrhoea.

This review presents recent findings regarding the physiological and pathophysiological extra- and intracellular mechanisms of secretory diarrhoea. Putative interventions directed towards counteracting the mechanisms causing fluid loss, especially in relation to the enteric nervous system, intracellular mediators, and localization of fluid and electrolyte transport, are discussed. The enteric nervous system regulates the complex process of transmural fluid and electrolyte transport by controlling the function of the mucosa, the motility, and the microcirculation in both health and disease. Most of the processes, leading to secretory diarrhoea, involve activation of the enteric nervous system, with local release of neurotransmitters and other endogenous effectors, which induce chloride secretion. A new therapeutic approach is based on stimulation of absorption and inhibition of secretion by using receptor agonists and antagonists, and modulators of intracellular signal transduction. A physio-pharmacological review of serotonin and the antisecretory factor as modulators of intestinal fluid and electrolyte transport is given.

Diarrhea↗
PubMed1994

[Chronic fatigue syndrome--a controlled cross-sectional study].

Twenty-one patients fulfilling the Center for Disease Control criteria for chronic fatigue syndrome (CFS) were examined in a controlled study. Viral antibodies and tests evaluating the immune system were investigated in the patients and in a control group of 21 sex- and age-matched individuals. Production in vitro of the predominantly T-cell-derived cytokines interleukin-2 and interferon-gamma was significantly higher in patients with CFS compared the control group. Furthermore, the serum concentrations of IgA and IgE were significantly lower in patients with CFS; however, the values were within the normal reference range. All other variables were similar in the two groups. This study does not suggest a clearly disordered immune system or a chronic viral infection as a major pathogenetic factor in CFS. Longitudinal studies of immunological and virological parameters in CFS are warranted as are studies on patients that are severely handicapped.

Adolescent↗
PubMed1994

Stimulation of the B9 hybridoma cell line by soluble interleukin-6 receptors.

Interleukin-6 (IL-6) exerts its effects by binding to specific receptors on the cell surface. The IL-6 receptor consists of at least two components, a ligand binding 80 kDa low-affinity component (IL-6R) and a signal-transducing non-ligand binding 130 kDa component (gp130). The presence of soluble forms of these components has been described in both conditioned media and biological fluids. The soluble (s) IL-6R has been shown to enhance the IL-6 sensitivity of several both murine and human IL-6 sensitive cell types. A sensitive and commonly used method for measuring biological IL-6 activity is based on the IL-6 dependent proliferation of the murine hybridoma cell line B9. In this paper, we demonstrate that recombinant (r) human (h) sIL-6R enhances the sensitivity of B9 cells in a dose-dependent manner. The rhsIL-6R enhanced the binding of 125I-rhIL-6 to B9 cells. The rhsIL-6R induced stimulation of B9 proliferation was maximal at 100 ng/ml, even without addition of rhIL-6 and in the presence of anti-hIL-6 antibodies. This may be due to endogenous IL-6 production by the B9 cells, low levels of IL-6 in the fetal calf serum used, or perhaps an IL-6 independent effect by the rhsIL-6R. In conclusion, this and other reports point to the necessity of confirming measured biological activities through the use of neutralizing specific antibodies or parallel measurements in immunochemical assays.

Animals↗
PubMed1994

5-HT receptor subtypes involved in luminal serotonin-induced secretion in rat intestine in vivo.

The purpose of this study was to compare the 5-hydroxytryptamine (5-HT) receptor subtypes involved in secretion of water and electrolytes (sodium, potassium, and chloride) induced by luminally administered serotonin in rat jejunum and ileum in vivo. Ketanserin partially inhibited and ICS 205-930 totally inhibited serotonin-evoked secretion. Ketanserin induced mild basal secretion while ICS 205-930 alone reduced basal absorption. There were no differences in the effects of ketanserin or ICS 205-930 on serotonin-induced secretion by rat jejunum versus ileum. Neither N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophanamide nor methysergide altered the secretory effect of serotonin in rat ileum. The substituted benzamides, cisapride, and BRL 24924, and the 5-HT4 agonist, 5-methoxytryptamide, induced water and electrolyte secretion. While BRL 24924 did not alter the subsequent serotonin-induced secretory fluxes, cisapride slightly inhibited the induced secretion. These results suggest that (1) in both segments of the intestine, 5-HT2, 5-HT3, and/or 5-HT4 receptor subtypes are involved in the regulation of intestinal transport of water and electrolytes under basal conditions; (2) serotonin-induced water and electrolyte secretion is mediated by pathways involving 5-HT2, 5-HT3, and 5-HT4 receptor subtypes in both rat jejunum and ileum; (3) 5-HT1 receptors do not seem to be involved in the mediation of intestinal water and electrolyte transport; (4) these effects are similar to those described for systemically administered 5-HT.

5-Methoxytryptamine↗
PubMed1994

5-Hydroxytryptamine2 and 5-hydroxytryptamine3 receptors mediate serotonin-induced short-circuit current in pig jejunum.

The purpose of this study was to determine the effect of methysergide, ketanserin, granisetron, cisapride, and renzapride on serotonin (5-hydroxytryptamine-evoked short-circuit current in muscle and myenteric plexus-stripped pig jejunum using the Ussing chamber technique. Ketanserin, granisetron, cisapride, and renzapride all reduced the 5-hydroxytryptamine-induced increase in short-circuit current by about 50%. Combination of ketanserin and granisetron only reduced the 5-hydroxytryptamine-induced peak increase in short-circuit current by 25%. Cisapride caused a small concentration-dependent increase in short-circuit current. Atropine and hexamethonium both almost completely suppressed the cisapride-induced peak increase in short-circuit current. Atropine and hexamethonium both almost completely suppressed the cisapride-induced peak increase in short-circuit current. Ketanserin, granisetron, methysergide, and renzapride did not alter the basal short-circuit current. These results suggest that 5-hydroxytryptamine elicits an increase in short-circuit current by activating epithelial and submucosal 5-hydroxytryptamine2 and 5-hydroxytryptamine3 receptor subtypes. Furthermore, the short-circuit current-increasing effect of cisapride, is due to activation of at least muscarinic and nicotinic receptors.

Animals↗
PubMed1994

Increased plasma levels of soluble IL-2R are associated with severe Plasmodium falciparum malaria.

Plasma samples from children with mild and severe Plasmodium falciparum malaria and from children with unrelated diseases were collected to investigate whether the clinical outcome of infection was associated with plasma factors which reflected the activity of different cells of the immune system. Children with severe P. falciparum malaria had significantly higher plasma levels of soluble IL-2R than children with mild malaria. Plasma levels of IL-2R and levels of parasitaemia were significantly correlated. Neither parasitaemia nor plasma levels of tumour necrosis factor-alpha (TNF-alpha), IL-6, lymphotoxin (LT), interferon-gamma (IFN-gamma), IL-4, soluble IL-4R or soluble CD8 differed significantly between the two groups of children with malaria. High plasma levels of soluble CD8 were associated with failure of lymphocytes to produce IFN-gamma in vitro following stimulation with P. falciparum antigen. We conclude that soluble IL-2R is a useful marker of disease severity independently of the association with levels of parasitaemia, and that functional regulation of different lymphocyte subsets occurs during acute malaria episodes.

CD8 Antigens↗
PubMed1994

Sex- and age-dependency of IgG auto-antibodies against IL-1 alpha in healthy humans.

Naturally occurring anti-interleukin (IL)-1 alpha IgG antibodies (Ab-IL-1 alpha) were measured in sera of 466 healthy Danish blood donors. Ab-IL-1 alpha bound IL-1 alpha with exceptionally high affinity (Kd: 10(-11) M) and neutralized both cell-associated and extracellular IL-1 alpha but not IL-1 beta or IL-1 receptor antagonist. More than 80% of the saturable binding of rIL-1 alpha to serum was to Ab-IL-1 alpha, suggesting that these antibodies are the quantitatively most important IL-1 alpha-binding components in serum. Judged by second antibody precipitation assay, the prevalence of Ab-IL-1 alpha varied between 30% and 75% and correlated positively with age (P = 0.037). The binding capacity of serum also increased with age. Although men were more frequently positive than women (P < 0.001), there were no sex- or age-dependent alterations in the average affinities of the antibodies. Free IL-1 alpha-like molecules were generally not detected in these sera. However, acid treatment showed that 25% of Ab-IL-1 alpha-positive sera contained low amounts of IL-1 alpha-Ab-IL-1 alpha immune complexes. IgG4 represented the main IgG isotype, whereas IgG3 Ab-IL-1 alpha were undetectable. The relative amounts of IgG4 Ab-IL-1 alpha increased while IgG2-and IgG1 Ab-IL-1 alpha decreased in elderly individuals. The presence in normal individuals and the lack of affinity maturation with age suggest that Ab-IL-1 alpha may be regulatory natural auto-antibodies perhaps coded by germline genes.

Adolescent↗
PubMed1994

Serotonin-induced short-circuit current in pig jejunum.

This paper presents the effects of serotonin (5-HT) on short-circuit current (SCC), sodium and chloride fluxes, and prostaglandin E2 release in pig jejunum, using the Ussing-chamber technique. 5-HT elicited a dose-dependent increase in SCC, yielding an EC50 of 6 +/- 4 microM and EMAX of 77 +/- 8 microA.cm-2 using about 100 microM. Inhibited sodium absorption and stimulated chloride secretion carried part of the 5-HT-induced SCC. 5-HT caused a dose-independent PGE2 release, and indomethacin reduced the SCC-inducing effect of 5-HT by 40%. Octreotide, a long-lasting somatostatin analogue, also reduced 5-HT-induced SCC by about 40%, while tetrodotoxin (TTX) did not alter the effect of 5-HT. In conclusion, 5-HT causes a dose-dependent indomethacin and octreotide-sensitive, and TTX-insensitive increase in SCC, and a chloride secretion and inhibited sodium absorption and an increased release of PGE2 in pig jejunum in vitro.

Animals↗
PubMed1994

Serine-stretch protein (SERP) of Plasmodium falciparum corresponds to the exoantigen Ag2, a target of antibodies associated with protection against malaria.

A mixture of Plasmodium falciparum exoantigens inducing lymphocyte activation and cytokine production was shown to contain the malaria vaccine candidate, the serine-stretch protein. This protein was shown serologically to correspond to Ag2, an exoantigen recognized by antibodies linked with protection against malaria. The glycophorin-binding protein, the histidine-rich protein II, the S-antigen, the heat shock protein 70, the ring-infected erythrocyte surface antigen, and the apical membrane antigen-1 were also shown serologically to be present in the mixture of exoantigens.

Amino Acid Sequence↗
PubMed1994

Inhibition of bacterial motility with human antiflagellar monoclonal antibodies attenuates Pseudomonas aeruginosa-induced pneumonia in the immunocompetent rat.

Two human monoclonal antibodies, directed against the type a and type b flagellar proteins of Pseudomonas aeruginosa, inhibited bacterial motility in vitro specifically and in a concentration-dependent manner. In order to determine if this decreased bacterial motility was associated with a decreased pathogenicity, the ability of these human antiflagellar monoclonal antibodies to attenuate P. aeruginosa-induced pneumonia in the rat was assessed. Incubation of P. aeruginosa with a 1:1 mixture of the human antiflagellar monoclonal antibodies prior to pulmonary instillation significantly (P < 0.05) ameliorated the bacterium-induced decrease in arterial blood oxygen pressure, blunted the increase in respiratory rate, and markedly reduced the area of pulmonary inflammation. Similarly, intravenous administration of the human antiflagellar monoclonal antibodies 1 h after pulmonary instillation of the bacteria also reduced the in vivo pathogenicity of P. aeruginosa. Therefore, human antiflagellar monoclonal antibodies can decrease the in vitro motility of P. aeruginosa and can reduce its in vivo pathogenicity when administered either before or after bacterial challenge.

Animals↗