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Biomedical subjects

M B Hansen

Publications and source records attributed to M B Hansen.

At least 55 records · Page 3Linked to original sources
PubMed1997

Decreased plasma levels of factor II + VII + X correlate with increased levels of soluble cytokine receptors in patients with malaria and meningococcal infections.

The levels of coagulation factors II + VII + X and of blood platelets (thrombocytes) as well as of cytokines and soluble cytokine receptors were studied in the patients with malaria or meningococcal infections. The coagulation factors were decreased particularly in the meningococcal patients, while thrombocytes were lowest in the Plasmodium falciparum malaria patients. There was no correlation between factors II + VII + X and thrombocytes, but plasma levels of coagulation factors II + VII + X were found to correlate inversely with levels of soluble interleukin-2 receptor (sIL-2R) and soluble tumour necrosis factor-I (sTNF-RI) in patients with malaria and meningococcal infections. Elevated sIL-2R and sTNF-RI levels and decreased coagulation factors reverted to normal within 3-5 days after initiation of therapy in P. falciparum patients followed consecutively. Estimation of coagulation factors may be used to monitor the course of these common and potentially life-threatening infections.

Acute Disease↗
PubMed1996

Biomolecular regulation of the IgE immune response III. Cytokine profiles in atopic dermatitis, inhalant allergy and non-allergic donors.

Cytokines-in particular interleukin 4 (IL-4), IL-5 and interferon gamma (IFN-gamma)-regulate both IgE synthesis and eosinophil activation in atopic diseases. To elucidate whether distinct profiles of cytokine production were related to serum level of IgE and eosinophilia, the spontaneous and inducible in vitro cytokine secretion from peripheral blood mononuclear cells (PBMC) was investigated. PBMC were isolated and cultured from three groups of donors: (1) patients with atopic dermatitis (AD) and high levels of serum IgE (> 5000 IU/ml, n = 11), (2) patients with diagnosed inhalant allergy (IA) and serum IgE in the range of 200-2000 IU/ml (n = 10), and (3) non-allergic individuals (NA) with serum IgE below 100 IU/ml (n = 10). The production of cytokines was determined in cultures after 24 h [IL-1 alpha, IL-4, IL-5, IL-6, tumour necrosis factor alpha (TNF-alpha), and TNF-beta] or 72 h (IL-2, IFN-gamma). The spontaneous production of IL-1 alpha was increased in the AD group compared to NA (P = 0.002), whereas for unstimulated cultures no other cytokine differed between patient groups. To identify conditions for optimal cytokine production, various combinations of phytohaemagglutinin (PHA), calcium ionophore (ION), and phorbol ester (PMA) were tested as stimuli. The combination ION + PMA induced the highest levels of IL-2, IL-4, IL-5, IFN-gamma and TNF-alpha, whereas maximal production of IL-6 and TNF-beta were induced by PHA and PHA + PMA, respectively. The AD group demonstrated a significantly lower production of TNF-alpha and IFN-gamma compared with the two other groups, and IL-4 and IL-5 production increased in the IA group. The results suggest that in spite of the common features, i.e. raised serum IgE and eosinophilia, in IA and AD patients, the underlying aberrations in the cytokine network is different.

Cytokines↗
PubMed1996

Age and segmental differences in 5-hydroxytryptamine-induced hypersecretion in the pig small intestine.

5-Hydroxytryptamine is a mediator in cholera toxin-induced hypersecretion in the small intestine. Our hypothesis is that the hypersecretion induced by 5-hydroxytryptamine in the small intestine decreases with increasing age and in an aboral direction in the small intestine. In vivo, measuring accumulated fluid in ligated loops, the apparent maximal efficacy of the 5-hydroxytryptamine-induced jejunal secretion in pig neonates was 4.8 +/- 1.1 mg x mg(-1) dry loop x 45 min(-1). The apparent maximal efficacy decreased by 23% and 63% in young and adult pigs, respectively, compared with neonates. In vitro, measuring changes in short-circuit current in Ussing chambers, the apparent maximal efficacy was 66.7 +/- 4.8 micronA x cm(-2) in neonates and was reduced by 30% and 57% in young and adult pigs, respectively. Young pigs were used in the segmental study. The apparent maximal efficacy in vivo was 3.7 +/- 0.5 mg x mg(-1) dry loop and decreased by 22% and 56% in the mid and distal small intestine, respectively. By contrast, in vitro the apparent maximal efficacy was elevated by 56% to 72.0 +/- 5.0 micronA x cm(-2) in the distal compared with the proximal part. In conclusion, the secretory response to 5-hydroxytryptamine in pig small intestine decreases with increasing age and in the aboral direction according to in vivo results. We suggest that the decrease in sensitivity to 5-hydroxytryptamine can explain a part of the reduced secretory response to cholera toxin with age and in the aboral direction of the small intestine.

Aging↗
PubMed1996

Differential interleukin-6 (IL-6) responses of three established myeloma cell lines in the presence of soluble human IL-6 receptors.

We investigated the possible influence of recombinant (r) sIL-6R on the growth of three IL-6 non-responsive or weakly IL-6 responsive long-term myeloma cell lines. The three cell lines chosen for the study (U266, L363 and Fravel) all expressed gp130 but differed in their expression of IL-6R and IL-6. mRNA analysis by northern blot and reverse transcriptase polymerase reaction showed that the cell line U266 was the only one that expressed IL-6 mRNA. Only U266 and L363 expressed IL-6R mRNA. 125I-rIL-6 binding studies and FACS analysis, using biotinylated IL-6 and antibodies directed against the IL-6R and gp130, showed corresponding results on the protein level. Addition of rsIL-6R resulted in induction of IL-6 responsiveness in L363 cells, whereas the 3H-thymidine incorporation of the cell lines U266 and Fravel was unaffected by rsIL-6R addition. In conclusion, the IL-6 unresponsive growth of several long-term myeloma cell lines in vitro can in some, but not all cases, be due to a deficiency in exogenous sIL-6R.

Antigens, CD↗
PubMed1996

Anti-interleukin-6 autoantibodies in plasma are associated with an increased frequency of infections and increased mortality of patients with alcoholic cirrhosis.

Altered cytokine metabolism has been implicated in the pathogenesis of alcoholic liver disease. Recently, autoantibodies to cytokines have been proposed to act as modifiers of cytokine functions. In this study plasma levels of anti-interleukin-1 alpha (IL-1 alpha autoantibodies and anti-IL-6 autoantibodies were determined by RIAs in 96 patients with alcoholic cirrhosis and in 16 healthy individuals. After 19 months (median) the prognostic significance of the cytokine autoantibodies was investigated using univariate analysis (Log-rank test) and multivariate regression analysis (Cox model). The seroprevalences of anti-IL-1 alpha autoantibodies and anti-IL-6 autoantibodies (42 and 18%, respectively) in the patients were not different from healthy individuals and did not relate to severity of liver disease. The presence of anti-IL-1 alpha autoantibodies was of no prognostic significance. Independent of severity of liver disease, patients with anti-IL-6 autoantibodies in plasma had a higher risk of acquiring infections and higher risk of death (P < 0.02) compared to patients without anti-IL-6 autoantibodies. The authors concluded that anti-IL-6 autoantibodies are associated with increased mortality when present in the plasma of patients with alcoholic cirrhosis, which is probably secondary to recurrent infections, but not to underlying severity of liver disease.

Adult↗
PubMed1996

Effect of 5-HT2 and 5-HT3 receptor antagonists on cholera toxin-induced fluid hypersecretion in the pig jejunum.

5-Hydroxytryptamine is a mediator in cholera toxin-induced hypersecretion in the small intestine. The aim of this study was to determine the effect of the 5-hydroxytryptamine receptor antagonists ketanserin, granisetron, ondansetron and tropisetron on cholera toxin-induced hypersecretion in the pig jejunum. Hypersecretion was induced by cholera toxin in ligated jejunal loops. The antagonists were administered subcutaneously at a dose of 100 micrograms/kg. Furthermore, the effect of intraluminally instilled ondansetron was studied. None of the antagonists altered basal absorption or caused fluid hypersecretion. Cholera toxin caused a dose-dependent electrolyte and fluid hypersecretion. The apparent maximal effect, 6.8 +/- 0.4 mg fluid x mg dry loop-1, was reduced by ondansetron, granisetron and tropisetron by about 40%, 30%, and 20%, respectively, whereas ketanserin had no effect. Intraluminal ondansetron reduced the effect of cholera toxin by about 50%. These results demonstrate that 5-hydroxytryptamine3 antagonists administered subcutaneously reduce the cholera toxin-induced hypersecretion in the pig jejunum. Finally, the results support species differences with respect to the antagonistic effect of the tested drugs in cholera toxin-induced hypersecretion.

Analysis of Variance↗
PubMed1996

The effect of alpha-trinositol on cholera toxin-induced hypersecretion and morphological changes in pig jejunum.

alpha-Trinositol (D-myo-inositol 1,2,6-trisphosphate, PP56) is a novel antiinflammatory drug. This study elucidates the effect of intravenous alpha-trinositol on basal and acute fluid transport and morphological changes following cholera toxin administration in pig jejunum in vivo. Using isolated jejunal tied-off loops, the fluid hypersecretory (accumulation) effect of different doses of cholera toxin was studied in pigs treated intravenously with saline added different doses (0, 4, 8, 16 and 32 mg x kg-1 x hr-1) of alpha-trinositol. Levels of alpha-trinositol, as well as stereomicroscopical, light microscopical and scanning electron microscopical morphological studies were performed. Cholera toxin evoked a dose-dependent fluid hypersecretion. Treatment with alpha-trinositol caused a dose-dependent inhibition of the cholera toxin-induced fluid hypersecretion and did not affect basal fluid absorption. The 16 mg x kg-1 x hr-1 alpha-trinositol dose gave a maximal inhibition of 36%. Morphological studies showed only minor changes following 6 hr of exposure to 20 micrograms x loop-1 cholera toxin. These changes consisted of dilation of the villus capillaries, an increase of apical membrane blebbing and a reduction of the intercellular space. Treatment with 16 mg x kg-1 x hr-1 alpha-trinositol alone did not induce any morphological changes, and did not alter the morphological changes induced by cholera toxin, which caused fluid hypersecretion and only minor acute morphological changes. In conclusion, alpha-trinositol treatment reduced cholera toxin-induced fluid hypersecretion without altering basal fluid absorption, basal morphology, or cholera toxin-induced morphological changes in pig jejunum in vivo.

Animals↗
PubMed1996

Experimental studies of intestinal ion and water transport.

A major advance in transport physiology was H. H. Ussing's development of the voltage-clamp method, and later the Koefoed-Johnsen-Ussing model for Na+ transport. In the same decade, J. C. Skou identified the Na(+)-K(+)-ATPase, which maintains the Na+ and K+ gradients that drive most epithelial transport processes. With this foundation, Danish scientists have pursued the mechanism of ion transport and the resulting solute-linked water flow. Recent contributions have been on isosmotic transport, suggesting solute recycling, and KCl-water cotransport in the basolateral epithelial cell membrane. Efficient small intestinal nutrient absorption is dependent on coupling to the Na+ gradient. Cotransport of Na+ and glucose is quantitatively the most important absorptive mechanism in the small intestine, as illustrated by the success of oral rehydration solutions in diarrhoea. The majority of amino acids are likewise transported by Na+ dependent carriers, but recent experiments have identified a concomitant Cl- dependency for some. Regulation of intestinal secretion, both under normal digestive processes, and in response to enterotoxins, has turned out to be very complex. It involves local and central neuronal regulation through an array of neurotransmitters and local actions of gastrointestinal hormones. Major effectors are the submucosal neurons and the main transmitters serotonin, vasoactive intestinal peptide, acetylcholine, substance P, and neurotensin. Development of antisecretagogues is impeded by the existence of several receptor subtypes and significant species differences. The Na+ and water-conserving properties of the large intestine have been shown to be regulated by adrenocortical hormones, with aldosterone as a potent stimulator of colonic Na+ absorption. A major colonic function is the symbiosis with the anaerobic bacterial population. The fermentation of carbohydrate to short-chain fatty acids, which can be absorbed, supplements small intestinal digestive function.

Animals↗
PubMed1996

Autoantibodies to IL-1 alpha in sera from umbilical cords, children, and adults, and from patients with juvenile chronic arthritis.

Antibodies against interleukin-1 alpha (aAb-IL-1 alpha) have previously been demonstrated in sera of healthy adults and in patients with inflammatory diseases. In the present investigation the occurrence of aAb-IL-1 alpha was examined by second antibody precipitation technique in sera from umbilical cords (n = 11), children (n = 45), and adults (n = 20), as well as in 51 patients with juvenile chronic arthritis (JCA) of pauciarticular (n = 34), polyarticular (n = 8), or systemic onset type (n = 9). RESULTS. The frequency of positive sera was significantly lower in children than in cord blood and adults as were the levels of aAb-IL-1 alpha (p < 0.0001). In the non-neonatal group of individuals the levels of aAb-IL-1 alpha correlated positively with age (r = 0.394, p = 0.0015). The frequency of sera positive for aAb-IL-1 alpha was higher in the JCA patients, as were the levels (p < 0.005), and correlated positively with disease activity as evaluated by joint score and visual analogue score.

Adult↗
PubMed1995

Influence of interleukin-6 (IL-6) autoantibodies on IL-6 binding to cellular receptors.

Neutralizing autoantibodies to interleukin-6 (aAb-IL-6) have been reported in healthy individuals, in patients with autoimmune diseases, and in pharmaceutically prepared pooled IgG (IVIg). We investigated the ability of aAb-IL-6 derived from IVIg to interfere with IL-6 binding to the undifferentiated monocytic cell line U-937. High-affinity aAb-IL-6, primarily of the IgG1 subclass, constituted approximately 1:10(6) of the total IgG in IVIg preparations. IL-6 binding to cellular receptors was strongly inhibited by one class of aAb-IL-6. These antibodies recognized epitope(s) on IL-6 essential for the binding of IL-6 to the alpha subunit of the IL-6 receptor (IL-6R). Another class of aAb-IL-6 recognized epitope(s) on IL-6, which is not essential for the binding to IL-6R but nevertheless important for the formation of high-affinity cellular IL-6 binding. These antibodies presumably interfered with the association of IL-6 receptor beta chains (gp130) with IL-6/IL-6R complexes, implicating that small IL-6/aAb-IL-6 immune complexes bound saturably (low affinity/high capacity) to cellular IL-6 receptors. There was no detectable binding of IL-6 through aAb-IL-6 and Fc receptors on U-937, and IVIg had no direct IL-6 receptor antagonizing activity. Dissociation kinetics of IL-6/aAb-IL-6 complexes at 37 degrees C revealed that IL-6 was liberated from 75% of the aAb-IL-6 with a half-time (t/2) approximately 4 h but bound almost irreversibly to the remaining aAb-IL-6 (t/2 > 20 h). Cellular IL-6 uptake and degradation was suppressed by aAb-IL-6. Taken together, the data suggest that loss of immunologic tolerance against IL-6 might be a novel physiological mechanism by which IL-6 activities are effectively attenuated. Finally, binding of IL-6 in complex with IgG1 aAb-IL-6 on cells expressing IL-6 receptors implicates that such cells could be targets of antibody-dependent immunological reactions, including cytotoxic reactions.

Animals↗
PubMed1995

Cytokines and autoantibodies to cytokines.

Cytokines are essential components of our defense and repair systems but also potentially harmful mediators of infectious and immunoinflammatory reactions. Clinically important cytokines function systemically as pleiotropic hormones with overlapping effects on many cell types. All engage in a complex network of agonists and antagonists. Some immunoglobulin G (IgG) antibodies have been found to be potent and specific regulators of cytokines. These antibodies bind interleukin (IL-1)alpha, IL-6, IL-10, leukemia inhibitory factor (LIF), and interferon (IFN)-alpha/beta with exceptional force. They neutralize their corresponding cytokines ex vivo and perhaps in vivo, although they may also function as cytokine carriers. The biological role of autoantibodies to cytokines is not yet understood, but they may provide a level of regulation not appreciated at present. Inappropriate production/function of such antibodies could be pathogenetically involved in immunoinflammatory and other diseases. Cytokine antibodies may also contribute to the anti-inflammatory effects of human IgG therapy.

Adjuvants, Immunologic↗
PubMed1995

Interleukin-4 and interferon-gamma production by Leishmania stimulated peripheral blood mononuclear cells from nonexposed individuals.

Interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) production by Leishmania reactive peripheral blood mononuclear cells (PBMC) from non-exposed individuals was investigated. IFN-gamma was measured in culture supernatants after antigen stimulation. For the measurement of IL-4, antigen stimulated cells were pulsed with PMA and ionomycin before IL-4 release was measured. L. donovani and L. major antigens induced IL-4 production (105-1748 pg/ml) in 13 and seven cultures, and IFN-gamma production (1.7 - > 66 IU/ml) in 14 and 11 of 20 cultures, respectively. IL-4 production rose steeply after 6 days of antigen stimulation suggesting a response due to antigen recognition. Both IL-4 and IFN-gamma production was abrogated by depletion of CD2+ or CD4+ but not CD8+ cells. CD2+ or CD4+ but not CD8+ enriched cultures produced cytokines as unseparated PBMC. Thus, in non-exposed individuals circulating Leishmania reactive CD4+ T cells could be demonstrated. The cells from different individuals showed different patterns of IFN-gamma and/or IL-4 production upon antigenic stimulation. In experimental leishmaniasis the early balance between IFN-gamma and IL-4 is important for the clinical outcome. Our findings call for studies of the importance of cytokine production by cross-reactive T cells for the outcome of L. donovani infections in humans and show that the method for IL-4 detection is useful for this purpose.

Animals↗
PubMed1995

Tropisetron and octreotide reduce serotonin-induced fluid hypersecretion in pig jejunum.

In vitro data suggest that the serotonin receptor subtype 4 (5-HT4) mediate part of the serotonin (5-HT)-induced intestinal secretion. This study elucidates the involvement of the intestinal 5-HT4 receptor subtype and the anti-diarrhoeal therapeutic potentials of tropisetron and octreotide in 5-HT-induced intestinal hypersecretion in vivo. The effects of intraluminal 5-HT, 5-methoxytryptamine, and tropisetron (ICS 205-930), and subcutaneous octreotide (SMS 201-995) on fluid hypersecretion (accumulation) was studied in tied-off loops in pig jejunum. 5-HT, 5-methoxytryptamine (5-HT4 agonist), and tropisetron (5-HT3/5-HT4 antagonist) all induced a dose-dependent hypersecretion. Low doses of tropisetron reduced, while high doses of tropisetron enhanced the 5-HT and 5-methoxytryptamine responses. Taking into account the hypersecretory effect by itself, tropisetron seemed to completely block the hypersecretory effects of 5-HT and 5-methoxytryptamine. Finally, octreotide reduced the hypersecretory effect of 5-HT, maximally by 30%. These results suggest the involvement of the intestinal 5-HT4 receptor subtype in 5-HT-induced hypersecretion in pig jejunum in vivo. Furthermore, this study demonstrates a potential therapeutic value for octreotide in 5-HT-related diarrhoeagenic disorders in the pig.

Animals↗
PubMed1995

Bacterial colonization of the larynx and trachea in healthy children.

Fifty healthy children were included in the study; tracheal and laryngeal aspirations were performed after oral endotracheal intubation during minor surgery. The aspirates were evaluated and examined in the same way as aspirates from children suspected of pneumonia; 31 samples were accepted for the final analysis. After culturing, specimens from 30 children exhibited growth of potential pathogenic bacteria either from the larynx, the trachea or both. Prior to culture, bacteria were seen by microscopy in 24 samples from 30 children. These results indicate that the majority of healthy children carry potential pathogenic bacteria, not only in the larynx but also to a certain extent in the trachea. We conclude that aspirates from the larynx and the trachea are of limited value in the diagnosis of bacterial pneumonia in children.

Adolescent↗
PubMed1995

Biomolecular regulation of the IgE immune response. II. In vitro IgE synthesis and spontaneous production of cytokines.

Distinct subtypes of T-helper cells have been incriminated as sources of a common regulatory mechanism behind IgE synthesis and eosinophil activation in IgE-mediated diseases. To investigate whether IgE-producing cells are in fact stimulated in vivo or have an increased susceptibility to certain stimuli, the in vitro IgE synthesis was compared for different patient groups. Peripheral blood mononuclear cells (PBMC) were isolated from three groups of donors: (1) patients with atopic dermatitis and high levels of serum IgE (> 5000 IU/ml, n = 11); (2) patients with diagnosed inhalant allergy and serum IgE in the range of 200-2,000 IU/ml (n = 10), and (3) nonallergic donors with serum IgE below 100 IU/ml (n = 10). PBMC were tested for the spontaneous and IL-4-induced IgE synthesis in 11-day cultures during which adhering cells were removed on day 2 by transferring the suspended cells and the medium to new wells. The three groups differed markedly in their capacity to synthesize IgE. The atopic dermatitis group demonstrated high spontaneous IgE synthesis (median 11.8 ng/ml), which was doubled (24.3 ng/ml, p < 0.05) by stimulation by IL-4. The two other groups had low spontaneous synthesis (0.7 and 0.3 ng/ml) but this increased (1.7 and 0.7 ng/ml, p < 0.01) upon IL-4 stimulation. The spontaneous production of IFN-gamma in the cultures did not differ between the groups, but upon stimulation with phorbol myristate acetate, the atopic dermatitis group demonstrated significantly lower IFN-gamma levels compared to the two other groups. The IL-4 production in the cultures were generally below the detection limit (100 pg/ml), and whereas plasma levels of 1-2 ng/ml of soluble IL-4 receptor could be detected in all donors, no differences could be detected between the groups. These data suggest that reduced ability in atopic dermatitis of mounting an IFN-gamma response may account for the high levels of plasma IgE and IgE synthesis found in these patients.

Adult↗