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Biomedical subjects

M B Hansen

Publications and source records attributed to M B Hansen.

At least 91 records · Page 5Linked to original sources
PubMed1994

Failure of tropisetron to inhibit jejunal water and electrolyte secretion induced by 5-hydroxytryptamine in healthy volunteers.

The effects of the 5-hydroxytryptamine (5-HT3) receptor antagonist, ICS 205-930 (tropisetron), on basal and 5-HT induced jejunal secretion of water and electrolytes were examined using a double blind, randomised crossover design. In seven healthy volunteers steady state perfusions of the proximal jejunum were performed twice with the Loc-I-Gut tube after 5+5 mg ICS 205-930 or placebo capsules were given. After equilibration for 60 minutes and completion of a 120 minute basal period 5-HT (10 micrograms/kg x min intravenously) was infused for 120 minutes. Net water absorption (mean (SEM)) in the basal period was 0.55 (0.84) ml/cm x h and 0.74 (0.72) ml/cm x h after placebo and ICS 205-930, respectively (p > 0.05). Infusion of 5-HT caused significant net secretion of water after placebo (2.05 (0.58) ml/cm x h; p < 0.02) as well as ICS 205-930 (2.60 (0.89) ml/cm x h; p < 0.05). As ICS 205-930 excerted no effects on either basal or 5-HT induced water and electrolyte transport in the intact human jejunum the compound is probably not efficacious as an anti-secretory drug in patients with 5-HT induced diarrhoea.

Adult↗
PubMed1994

ICS 205-930 reduces 5-methoxytryptamine-induced short-circuit current in stripped pig jejunum.

The effect of ICS 205-930 on serotonin (5-hydroxytryptamine, 5-HT) and 5-methoxytryptamine (5-MeOT) induced short-circuit current (SCC) was studied in muscle-stripped pig jejunum in vitro. The selective 5-HT4 receptor agonist 5-MeOT and 5-HT both induced a concentration-dependent increase in SCC. The maximal efficacy of 5-HT was twice that of 5-MeOT. ICS 205-930 (Tropisetron) induced a small increase in SCC. Furthermore, ICS 205-930 reduced the 5-MeOT but not the 5-HT induced increase in SCC, except at the 100 microM ICS 205-930 concentration. Pretreatment with bumetanide reduced 5-HT, 5-MeOT, and ICS 205-930 induced peak increases in SCC by 64, 75, and 58%, respectively. Pretreatment with atropine reduced 5-HT, 5-MeOT, and ICS 205-930 induced peak increases in SCC by 38, 75, and 58%, respectively. Pretreatment with hexamethonium reduced 5-HT, 5-MeOT, and ICS 205-930 induced peak increases in SCC by 33, 50, and 36%, respectively. Pretreatment with tetrodotoxin reduced the peak increase in SCC elicited by 5-MeOT and ICS 205-930 by 41 and 50%, respectively. This study demonstrates involvement of a ICS 205-930, hexamethonium, atropine, bumetanide, and tetrodotoxin sensitive receptor in 5-MeOT induced SCC in muscle-stripped pig jejunum in vitro. These data suggest involvement of a neuronal 5-HT4 receptor subtype and acetylcholine in 5-HT elicited SCC and chloride secretion in the pig jejunum.

5-Methoxytryptamine↗
PubMed1994

Ketanserin and granisetron reduce cholera toxin-induced hypersecretion in pig jejunum.

BACKGROUND: Serotonin antagonists have been proven antisecretory in cholera toxin (CT)-induced hypersecretion in the small intestine of rodents. The pig small intestine is a good model for the human small intestine with regard to physiologic and pharmacologic processes. METHODS: The antisecretory effect of intraluminally administered methysergide, renzapride, ketanserin, granisetron, and tropisetron on CT-induced hypersecretion was tested in isolated pig jejunal loops in vivo. RESULTS: Methysergide, ketanserin, and granisetron reduced the hypersecretory effect of CT maximally by 25%, 80%, and 50%, respectively. Tropisetron enhanced whereas renzapride did not alter the CT response. Combination of ketanserin and granisetron gave a maximal inhibitory effect of about 85%. Surprisingly, renzapride, granisetron, and tropisetron each induced hypersecretion. Taking into account the hypersecretory effect of the antagonists, they all reduced this CT-elicited hypersecretion. CONCLUSIONS: Results suggest involvement of the 5-hydroxytryptamine-2 and 5-hydroxytryptamine-3 receptor subtypes as mediators in CT-induced hypersecretion in pig jejunum, and antidiarrheal therapeutic potentials of ketanserin and granisetron.

Animals↗
PubMed1994

Effect of indomethacin, renzapride, methysergide, ketanserin, granisetron and citalopram on serotonin-induced fluid accumulation in pig jejunum.

The purpose of this study was to elucidate the intestinal serotonin (5-HT) receptor subtypes involved in fluid transport in the pig jejunum in vivo. The fluid accumulating effect of intraluminally administered 5-HT, renzapride, methysergide, ketanserin, granisetron, citalopram and intravenous indomethacin, was tested in tied-off loops in vivo. 5-HT caused a dose-dependent fluid accumulation, which was reduced by indomethacin by about 30%. Renzapride, methysergide, ketanserin, granisetron and citalopram all caused fluid accumulation. Taking into account these fluid accumulating effects, renzapride, methysergide, ketanserin and granisetron reduced the fluid accumulating effect of 5-HT, giving a maximal reduction of 70, 46, 76, and 80%, respectively. These data suggest the existence of intestinal 5-HT receptor subtypes involved in fluid transport in the pig jejunum. The antagonistic effects of indomethacin, ketanserin and granisetron, suggest the involvement of prostaglandins, as well as the 5-HT2 and the 5-HT3 receptor subtypes in the fluid accumulating response of 5-HT.

Animals↗
PubMed1994

Chronic fatigue syndrome--a controlled cross sectional study.

OBJECTIVE: To look for signs of immunodeficiencies and/or longstanding infections underlying chronic fatigue syndrome (CFS). METHODS: Twenty-one patients fulfilling the Centers for Disease Control criteria for CFS were compared to 21 age and sex matched controls. A number of viral antibodies as well as the following tests evaluating the immune system were studied: autoantibody profile, cell surface markers on isolated blood mononuclear cells, cytokine production, lymphocyte proliferative responses, natural killer cell activity and quantitation of immunoglobulin secreting cells. RESULTS: Production in vitro of the predominantly T cell derived cytokines interleukin 2 and interferon gamma was significantly higher in patients with CFS compared to the control group. Furthermore, the serum concentrations of IgA and IgE were lower in patients with CFS; however, this difference was caused by a larger number with values of IgA and IgE above the upper limit of the normal range among the controls than among the patients with CFS. All other variables were similar in the 2 groups. CONCLUSION: A pathogenically significant imbalance of the immune system in patients with CFS cannot be excluded. However, evidence of a causal link between abnormal immunity and CFS was not obtained.

Adolescent↗
PubMed1993

Cytokines in sputum and serum from patients with cystic fibrosis and chronic Pseudomonas aeruginosa infection as markers of destructive inflammation in the lungs.

The presence of interleukin (IL)-1 receptor antagonist (IRAP) in plasma and sputum from patients with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa lung infection was investigated together with IL-1 alpha, IL-1 beta, IL-6, and tumor necrosis factor-alpha (TNF) in a cross-sectional study. All cytokines were assayed by ELISAs. High concentrations of IRAP, IL-1 alpha, IL-1 beta, IL-6, and TNF in sputum samples and low or nondetectable levels of circulating cytokines were frequently found. Increased concentrations of plasma IRAP are positively correlated with decreasing pulmonary function. In a longitudinal study of serum IRAP, a higher level of IRAP was detected in a group of patients with poor pulmonary function compared to a group with good pulmonary function.

Adolescent↗
PubMed1993

Involvement of eicosanoids and inositol 1,4,5-trisphosphate in serotonin-induced secretion in rat ileum in vivo.

1. The possible involvement of eicosanoids, cyclic adenosine monophosphate (c-AMP), and inositol 1,4,5-trisphosphate (IP3) in serotonin-(5-hydroxytryptamine-) induced secretion in rat ileum in vivo was studied. 2. Serotonin caused a significant increase in mean IP3 levels. Indomethacin reduced serotonin-induced secretion of water by 28%. Thus, IP3 and eicosanoids appear to be intracellular mediators of serotonin-induced secretion in rat ileum. 3. Serotonin, BRL 24924, and cisapride all inhibited theophylline-induced increases in c-AMP concentrations in rat ileal segments. Neither BRL 24924 nor cisapride caused any change in IP3 levels. 4. These data suggest that a 5-HT2 receptor dependent on IP3 and eicosanoids is involved in mediating in serotonin-induced secretion in rat small intestine.

Animals↗
PubMed1993

High-affinity IgG autoantibodies to IL-6 in sera of normal individuals are competitive inhibitors of IL-6 in vitro.

Nano- to picomolar concentrations of high affinity IgG antibody to interleukin 6 (IL-6ab) were detected in sera of 71 of 467 normal Danish blood donors (15%). IL-6 bound to the Fab fragments of IL-6ab, and the antibody specifically and competitively interfered with enzyme-linked immunosorbent assays for human IL-6. Only IL-6ab-positive sera interfered with these ELISAs. A statistically positive correlation was found between total IL-6 binding and specific IL-6 binding to serum (P < 0.0001), suggesting that IL-6ab dominates as IL-6 binding factors in normal human serum. The IL-6ab also inhibited binding of IL-6 to receptors on the human U-937 macrophage-like cell line, the human U-266 myeloma cell line and the mouse hybridoma cell line B13.29, clone B9 (B9 cells). IL-6-induced proliferation of the B9 cells was competitively inhibited by IL-6ab. We conclude that sera of normal individuals may contain appreciable levels of autoantibodies to IL-6. These IgG autoantibodies may be physiologically and pathophysiologically important because they are potent inhibitors of IL-6 in vitro.

Antigen-Antibody Reactions↗
PubMed1993

Specific binding of interleukin 1 (IL-1) beta and IL-1 receptor antagonist (IL-1ra) to human serum. High-affinity binding of IL-1ra to soluble IL-1 receptor type I.

Molecules that bind recombinant interleukin 1 (rIL-1) beta and rIL-1 receptor antagonist (rIL-1ra) with high affinity were detected in sera of healthy individuals. rIL-1 beta bound with dissociation constants in the nanomolar range, and the serum binding capacity was 40-50 ng/ml. rIL-1ra bound with 30 times higher affinity, and the serum binding capacity was 0.7-1 ng/ml. Rabbit antibodies against the recombinant-derived extracellular part of human IL-1 receptor type I (rsIL-1RI) selectively inhibited the binding of 125I-rIL-1ra to the serum factor(s). Almost 70% of the high-affinity IL-1ra-binding capacity was recovered after immunosorption with these antibodies. Binding of 125I-rIL-1ra to rsIL-1RI was blocked by rIL-1 alpha and by rIL-1 beta. In contrast, the purified rIL-1ra-binding factor (IL-1raBF) failed to bind rIL-1 alpha and rIL-1 beta. Gel filtration chromatography indicated a 1:1 binding of rIL-1 beta and rIL-1ra to their respective serum factors. The apparent molecular size of both serum factors was 70-80 kDa. Using SDS-PAGE and autoradiography, IL-1raBF had a molecular size of 60 kDa. We conclude that IL-1raBF, a serum factor which selectively and with high affinity binds IL-1ra (Kd = 70 pM), is related to or identical with a soluble form of IL-1RI. If upregulated during disease, IL-1raBF may constitute yet another level of natural regulation of IL-1 bioactivities.

Antibodies↗
PubMed1993

Effects of an acute bolus growth hormone infusion on the human immune system.

This study was performed to examine the in vivo effects of a bolus of recombinant human growth hormone (r-hGH) on the human immune system. In a double blind placebo controlled cross over study, healthy volunteers were given 2 IU r-hGH as an intravenous infusion. r-hGH did not influence the subpopulations of blood mononuclear cells (BMNC), natural killer cell activity, in vitro proliferative responses or production of interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-6, IL-8, tumor necrosis factor alpha (TNF alpha), TNF beta or interferon gamma in supernatants from BMNC stimulated with either lipopolysaccharide or phytohemagglutinin. However, two h after infusion a significant neutrocytosis occurred. It is concluded that a bolus infusion of r-hGH to healthy volunteers exerts only minor effects on the human immune system.

Adult↗
PubMed1993

Tumour necrosis factor and interleukin-6 production induced by components associated with merozoite proteins of Plasmodium falciparum.

P. falciparum merozoite antigens, merozoite surface protein-1 (MSP-1) and rhoptry associated protein-1 (RAP-1), were shown to be liberated into the supernatant of in vitro parasite cultures and to be included in the endotoxin-like exoantigen complex, previously designated Ag7. Material affinity purified from culture supernatants, using immobilized monoclonal antibodies specific for RAP-1 or MSP-1, stimulated normal human mononuclear cells to produce TNF and IL-6 in vitro. However, stimulation of TNF was absent, and that of IL-6 was reduced, when the antigens were purified from detergent extracts of infected erythrocytes. These results indicate that the RAP-1 and MSP-1 proteins themselves do not stimulate the production of TNF. Instead, other components associating with these exoantigens may be responsible for the TNF production. Mouse antisera blocking TNF production stimulated by P. yoelii exoantigens also blocked TNF production stimulated by material affinity purified from P. falciparum culture supernatants using RAP-1 specific monoclonal antibody, indicating the conserved structure of the TNF inducing component.

Animals↗
PubMed1993

Effect of methylprednisolone on the cytokine response in patients undergoing lung surgery.

Tumour necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha) and IL-6, when released in excess, have been suggested to be important host mediators of the immunoinflammatory response to injury and infections. Corticosteroids suppress this response in vitro. This study was undertaken to investigate if a single dose of methylprednisolone (MP) could modify the cytokine response in patients undergoing lung surgery. Twenty-one patients with lung cancer were allocated randomly to treatment with MP 30 mg/kg i.v. (MP group) or isotonic saline (control group). Patients were anaesthetized with a balanced anaesthesia combined with thoracic epidural anaesthesia. MP or saline was administered immediately before induction of anaesthesia. The cytokines in plasma were measured by ELISA, and blood samples were collected preoperatively, at the end of surgery, 4 h later, and 1 and 5 days postoperatively. All patients had detectable IL-6 in plasma. Compared to preoperative values, plasma IL-6 levels in the MP group increased from 114 pg/ml (12-350 pg/ml) (mean, range) to peak value 146 pg/ml (15-580 pg/ml) on the first postoperative day. In the control group, IL-6 levels increased from 99 pg/ml (17-350 pg/ml) preoperatively to 125 pg/ml (10-300 pg/ml) on the first postoperative day. The increases were not significant. TNF alpha was detectable in only two patients, one from each group. Low levels of IL-1 alpha were demonstrated in three patients in the MP group and in four patients in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Leishmania donovani-reactive Th1- and Th2-like T-cell clones from individuals who have recovered from visceral leishmaniasis.

Infections in humans by Leishmania donovani parasites can result in a fatal disease, visceral leishmaniasis (VL), or in a self-limiting asymptomatic infection. In murine models of the infection employing Leishmania major, the course of the disease can be directed into a VL-like syndrome by interleukin-4 (IL-4)-producing Th2 cells, or cure may result by Th1 cells secreting gamma interferon (IFN-gamma). The present study examined the potential of human T cells to generate Th1 or Th2 responses to L. donovani. The profiles of IFN-gamma, IL-4, and lymphotoxin secretion after antigen stimulation were analyzed in a panel of L. donovani-reactive CD4+ human T-cell clones generated from individuals who had recovered from VL after antimonial treatment. Two of the T-cell clones produced large amounts of IL-4 without production of IFN-gamma, seven clones produced both IFN-gamma and IL-4, and eight produced only IFN-gamma. This is the first report of a Th1- and Th2-type response in human leishmaniasis. These results suggest that in analogy with murine models, there is a dichotomy in the human T-cell response to L. donovani infections. Preferential activation of IL-4-producing Th2-like cells may be involved in the exacerbation of human VL, whereas activation of IFN-gamma-producing Th1 cells may protect the host from severe disease. Identification of leishmanial antigens activating one or the other type of T cells will be important in the development of vaccines against leishmaniasis.

Animals↗
PubMed1993

Elevated plasma interleukin 6: a biochemical marker of human preterm labour.

Maternal peripheral venous plasma interleukin 6 (IL-6) concentrations were determined during human pregnancy and labour at term and preterm. During preterm labour, IL-6 concentrations were significantly elevated (p < 0.02) compared to gestationally matched, non-labouring controls (53.7 +/- 15.7 pg/ml, n = 17, and 15.4 +/- 6.4 pg/ml, n = 23, respectively). IL-6 concentrations did not vary significantly during normal pregnancy and labour at term. These data support a role for IL-6 in the pathogenesis of human preterm labour, are evidence for the contention that preterm labour is mechanistically distinct at a biochemical level from normal labour at term and identify maternal peripheral venous plasma IL-6 as a biochemical marker of this condition.

Biomarkers↗
PubMed1993

Binding of cytokines to pharmaceutically prepared human immunoglobulin.

Pharmaceutically prepared IgG, pooled from sera of over 2,000 normal individuals, contained both monomeric and dimeric IgG. Each type of IgG bound 125I-labeled interleukin (IL)-1 alpha, IL-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha. Increased binding to IgG was observed if 125I-IL-1 beta was denatured by heating to 39 degrees C. However, the binding of both nondenatured and denatured 125I-IL-1 beta was not inhibited by unlabeled IL-1 beta. In contrast, binding of 125I-IL-1 alpha, 125I-IL-6, and 125I-TNF alpha was inhibited by the corresponding unlabeled cytokine. Papain-digestion of IgG abolished binding of 125I-TNF alpha but failed to influence the displaceable binding of 125I-IL-1 alpha and 125I-IL-6. 125I-TNF alpha was a mixture of trimeric and monomeric forms, the latter being the predominant form at lower concentrations. The apparent saturability of 125I-TNF alpha was explained by a higher nonspecific binding of monomeric than of trimeric 125I-TNF alpha to IgG. The amounts of cytokine antibodies in IgG preparations would contribute approximately 2 micrograms anti-IL-1 alpha IgG and 1 microgram anti-IL-6 IgG per kg body wt during high dose immune globulin therapy. In conclusion, pharmaceutical preparations of human IgG contain specific and neutralizing, high affinity antibodies against IL-1 alpha and IL-6, but not against TNF alpha or IL-1 beta. There are significant methodological pitfalls that hamper detection of IgG autoantibodies against cytokines.

Animals↗
PubMed1993

Cytokines in plasma and ultrafiltrate during continuous arteriovenous haemofiltration.

Cytokines are considered to be important mediators in the pathophysiology of sepsis and septic shock. We investigated if continuous arteriovenous haemofiltration (CAVH) could be used to remove excessive amounts of the cytokines tumour necrosis factor-alpha (TNF alpha), interleukin (IL)-1 alpha and IL-6 from peripheral blood in critically ill patients. Nine septic patients with renal failure were treated with CAVH. Ultrafiltrate and plasma were tested for cytokines by ELISA. All patients had detectable TNF alpha and IL-6 plasma levels, ranging from 10-750 pg/ml and 50-4,575 pg/ml, respectively. TNF alpha was removed by the ultrafiltrate with concentrations ranging from 10-1,000 pg/ml. The TNF alpha levels were significantly higher in the ultrafiltrate samples than in the corresponding plasma samples (P < 0.003). IL-6 was undetectable in the ultrafiltrate from five of the patients despite concomitant high plasma levels. IL-1 alpha was detectable in both plasma and ultrafiltrate in four patients. All patients developed multi-organ failure and septic shock and seven died. It is concluded that TNF alpha and IL-1 alpha but not IL-6 can be removed by CAVH in patients with sepsis.

Acute Kidney Injury↗
PubMed1992

Measurement of antigen-dependent interleukin-4 production by human peripheral blood mononuclear cells. Introduction of an amplification step using ionomycin and phorbol myristate acetate.

The study of T cell responses in parasitic disease and allergy in humans has been limited by difficulties in the measurement of interleukin-4 (IL-4) in supernatants from antigen-stimulated peripheral blood mononuclear cells (PBMC). To obtain measurable amounts of IL-4 in vitro, we have added an amplification step to the antigen-specific response. Human PBMC were stimulated by tetanus toxoid (TT) or tuberculin (PPD) for 6 days and then pulsed with ionomycin and phorbol myristate acetate (PMA) for 24 h. TT-stimulated cells from nine revaccinated donors but not from seven unvaccinated donors and four that had only received childhood vaccinations against tetanus produced high levels of IL-4 (median (range) 1500 (300-3800), 316 (0-1600), and 270 (100-410) pg/ml, respectively, as measured by an enzyme linked immunosorbent assay, P = 0.005). PPD did not increase IL-4 production above the background level, although the majority of PPD-stimulated PBMC proliferated and produced interferon-gamma (IFN-gamma) in cultures without ionomycin and PMA. TT-induced IL-4 production correlated positively with proliferation. Culture supernatants did not interfere with IL-4 immunoreactivity and failed to affect ionomycin and PMA induced IL-4 production. The findings suggest that proliferating antigen-specific T cells were the source of IL-4 in these experiments. The method should prove useful for comparing the IL-4 producing ability of antigen-specific T cells from different individuals.

Antigens↗