An unusual case of ventricular fibrillation.
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Acromegaly↗
Biomedical subjects
T K Hansen
Publications and source records attributed to T K Hansen.
Hormonal regulation of mannan-binding lectin synthesis in hepatocytes.
Activation of the complement system via the plasma protein mannan-binding lectin (MBL) provides a first line of defence against infections. The plasma level of MBL is, in part, determined genetically, but may also be influenced by different hormones in vivo. Here we study the hormonal regulation of MBL synthesis from the human hepatocyte cell line HuH-7. Cells were exposed to medium with growth hormone (GH), hydrocortisone, insulin-like growth factor (IGF)-1, insulin, interleukin (IL)-6 or thyroid hormones (T3 or T4). After 3 days the concentration of MBL in the culture supernatants was determined and the amount of mRNA for MBL was measured, relative to mRNA for beta2 microglobulin. GH, IL-6, T3 and T4 significantly increased MBL synthesis in a dose-dependent manner, while hydrocortisone, insulin and IGF-1 had no effect. T3 caused a fourfold increase at 1 nM of T3 (P < 0.001) and at 100 nM of T3 the production was increased more than eightfold. The effect of T4 was less potent, reaching an eightfold increase at 1 microM of T4 (P < 0.001). GH augmented the production of MBL threefold at a concentration of 100 ng/ml (P = 0.018) with no further effect up to 10 microg/ml, whereas IL-6 caused only a very weak increase in MBL production. MBL mRNA levels were stable during the first 24 h of T3 stimulation but increased significantly between 24 and 48 h. The results suggest that MBL synthesis in humans may be increased by thyroid hormone and GH, whereas it does not exhibit a classical IL-6-dependent response.
C-Reactive Protein↗
Modulation of chemokine gene expression in CD133+ cord blood-derived human mast cells by cyclosporin A and dexamethasone.
We have recently developed a protocol for generating huge numbers of mature and functional mast cells from in vitro differentiated umbilical cord blood cells. Using CD133 as a positive selection marker to isolate haematopoietic progenitors we routinely expand the number of recovered cells at least 150-fold, which vastly exceeds the yields of conventional protocols using CD34+ cells as a source of progenitors. Taking advantage of the large quantities of in vitro differentiated mast cells, here we assess at the levels of transcription and translation the kinetics of chemokine gene induction following receptor mediated mast cell activation or following pharmacological activation of specific signal transduction cascades that become activated upon classical FcepsilonRI receptor crosslinking. We demonstrate that chemokine genes encoding IL-8, MCP-1, MIP-1alpha, and MIP-1beta are induced with different kinetics and with different amplitudes in a receptor activation dependent manner, and that these events can be mimicked using pharmacological agents which activate distinct signal transduction pathways. These findings were corroborated by adding immunomodulators such as cyclosporin A and dexamethasone prior to mast cell activation. Finally, we demonstrate that the same modulators added after mast cell activation can differentially quench ongoing chemokine gene induction. Thus, considering the vast yields of mast cells, our protocol is valuable not only for studying regulation of gene expression in mast cells in general, but also as an experimental tool to develop better and more balanced treatments of mast cell related disorders.
AC133 Antigen↗
Mannose-binding lectin (MBL) and vascular complications in diabetes.
The complement system has evolved over time as an effective part of the immune system, acting effectively in frontline combat against invading microorganisms. Unfortunately, any war might involve "collateral damage", and emerging data indicate that activation of the complement system may cause damage to innocent bystander cells and tissues in some situations. This may apply to complement activation and inflammation as it occurs following myocardial ischemia and reperfusion, which is know to aggravate the subsequent myocardial injury; and it has recently been proposed that complement activation may be an important factor in the development of diabetic renal complications. Mannose-binding lectin (MBL, also known as mannan-binding lectin) is a plasma protein that activates the complement cascade after binding to carbohydrate structures. Circulating MBL levels vary widely from person to person, which is mainly due to frequently occurring polymorphisms within the encoding gene on chromosome 10. One may speculate that these genetically determined differences in MBL levels and hence in complement activation may play a role in existing familial clustering in both cardiovascular disease and diabetes-related vascular complications. The present review will focus on the function of MBL and the complement system, and on recent data indicating an association between MBL status and diabetic micro- and macrovascular complications.
Animals↗
The clinical relevance of sensitization to pollen-related fruits and vegetables in unselected pollen-sensitized adults.
BACKGROUND: Previous studies have described cross-reactivity between fresh fruits, vegetables and pollen. However, no data demonstrates the clinical relevance of sensitization to pollen-related fruits and vegetables in unselected pollen-sensitized adults with and without symptoms in the pollen season. OBJECTIVE: The aim of this study was to estimate the clinical relevance of sensitization to pollen-related fruits and vegetables in unselected pollen-sensitized adults and to examine the diagnostic value of skin-prick test (SPT), histamine release and specific IgE compared with the outcome of oral challenge. METHODS: In total, 936 unselected adults (female : male 479 : 457, median age 33.7 years) were examined for pollen sensitization and clinical cross-reactivity with pollen-related fruits and vegetables by questionnaire, SPT, histamine release, specific IgE and oral challenge. RESULTS: The prevalence of pollen sensitization was 23.8% (n = 223). The probability of a clinical reaction to pollen-related foods in the respective pollen-sensitized groups was: 24% (birch), 4% (grass), 10% (mugwort), 35% (birch + grass), 8% (grass + mugwort) and 52% (birch + grass + mugwort). The odds ratio of a clinical reaction to pollen-related fruits and vegetables in symptomatic pollen-sensitized adults was as high as four times (birch + grass) the odds ratio of a clinical reaction in asymptomatic pollen-sensitized adults. CONCLUSION: This study not only demonstrates a high prevalence of clinical reactions to fruits and vegetables in pollen-sensitized adults, but also a discrepancy between the prevalence of sensitization to fruits and vegetables and the clinical relevance in different pollen-sensitized groups with symptoms in the pollen season as a significant factor.
Adult↗
The prevalence of food hypersensitivity in an unselected population of children and adults.
A rising prevalence of food hypersensitivity (FHS) and severe allergic reactions to food has been reported the last decade. To estimate the prevalence of FHS to the most common allergenic foods in an unselected population of children and adults. We investigated a cohort of 111 children <3 yr of age, 486 children 3 yr of age, 301 children older than 3 yr of age and 936 adults by questionnaire, skin prick test, histamine release test and specific immunoglobulin E followed by oral challenge to the most common allergenic foods. In total, 698 cases of possible FHS were recorded in 304 (16.6%) participants. The prevalence of FHS confirmed by oral challenge was 2.3% in the children 3 yr of age, 1% in children older than 3 yr of age and 3.2% in adults. The most common allergenic foods were hen's egg affecting 1.6% of the children 3 yr of age and peanut in 0.4% of the adults. Of the adults, 0.2% was allergic to codfish and 0.3% to shrimp, whereas no challenges with codfish and shrimp were positive in the children. The prevalence of clinical reactions to pollen-related foods in pollen-sensitized adults was estimated to 32%. This study demonstrates the prevalence of FHS confirmed by oral challenge to the most common allergenic foods in an unselected population of children and adults.
Adolescent↗
Effects of GH replacement therapy in adults on serum levels of leptin and ghrelin: the role of lipolysis.
OBJECTIVE: The regulation and function of systemic ghrelin levels appear to be associated with food intake and energy balance rather than GH. Since GH, in turn, acutely induces lipolysis and insulin resistance in skeletal muscle, we aimed to study the isolated and combined effects of GH, free fatty acids (FFAs) and insulin sensitivity on circulating ghrelin levels in human subjects. DESIGN: Seven GH-deficient patients (aged 37 +/- 4 years (mean +/- s.e.)) were studied on four occasions in a 2 x 2 factorial design with and without GH substitution and with and without administration of acipimox, which lowers FFA levels by inhibition of the hormone-sensitive lipase, in the basal state and during a hyperinsulinemic euglycemic clamp. RESULTS: Serum FFA levels decreased with acipimox administration irrespective of GH status. The GH-induced reduction in insulin sensitivity was countered by acipimox. Fasting ghrelin levels decreased insignificantly during GH administration alone, but were reduced by 33% during co-administration of GH and acipimox (Aci) (in ng/l): 860 +/- 120 (-GH - Aci), 711 +/- 130 (-GH + Aci), 806 +/- 130 (+GH - Aci), 574 +/- 129 (+GH + Aci), P < 0.01. The clamp was associated with a further, moderate lowering of ghrelin. GH and acipimox induced a reciprocal 25% increase in serum leptin levels (microg/l): 11.2 +/- 4.4 (-GH - Aci), 11.7 +/- 4.4 (-GH + Aci), 11.5 +/- 4.4 (+GH - Aci), 13.9 +/- 4.2 (+GH + Aci), P = 0.005. CONCLUSION: Our data suggest that antilipolysis via suppression of the hormone-sensitive lipase in combination with GH administration is associated with significant and reciprocal changes in ghrelin and leptin.
Adult↗
Increased levels of mannan-binding lectin in type 1 diabetic patients with incipient and overt nephropathy.
AIMS/HYPOTHESIS: Diabetic nephropathy is associated with insulin resistance, and low-grade inflammation and activation of the complement system may contribute to this cascade. Mannan-binding lectin (MBL) activates the complement system, and elevated MBL concentrations have been observed in normoalbuminuric type 1 diabetic patients. The aim of this study was to assess whether MBL is associated with diabetic nephropathy in type 1 diabetes, and whether there is an association between MBL and low-grade inflammatory markers or insulin resistance. METHODS: A total of 191 type 1 diabetic patients from the Finnish Diabetic Nephropathy Study were divided into three groups based upon their AER. Patients with normal AER (n=67) did not take antihypertensive medication, while patients with microalbuminuria (n=62) or macroalbuminuria (n=62) were all treated with an ACE inhibitor. As a measure of insulin sensitivity we used estimated glucose disposal rate. MBL was measured by an immunofluorometric assay, C-reactive protein by a radioimmunoassay and IL-6 by high-sensitivity enzyme immunoassay. RESULTS: Patients with normal AER (median [interquartile range]: 1,154 microg/l [180-2,202 microg/l]) had lower levels of MBL than patients with microalbuminuria (1,713 microg/l [724-2,760 microg/l]; p=0.029) or macroalbuminuria (1,648 microg/l [568-3,394 microg/l]; p=0.019). There was a significant correlation between MBL and estimated glucose disposal rate, but not between MBL and C-reactive protein or IL-6 levels in univariate analysis. However, in a multiple regression analysis, HbA1c was the single variable independently associated with MBL (beta+/-SEM: 0.26+/-0.08; p=0.003). CONCLUSIONS/INTERPRETATION: MBL concentrations are increased in type 1 diabetic patients with diabetic nephropathy. MBL was not associated with low-grade inflammatory markers.
Adult↗
An inter-laboratory evaluation of selective media for the detection and enumeration of yeasts from blue-veined cheese.
Five countries representative of laboratories 1-5 evaluated 11 different selective media, designed to suppress mould and bacterial growth and support yeasts growth, for the recovery of yeast populations from blue veined cheeses. In addition, qualitative results were also incorporated. The yeast enumeration values were subjected to statistical analysis using analysis of variance (ANOVA) and the Tukey-Kramer multiple comparison test. With the exception of Laboratory 3, none of the other laboratories was successful in recovering yeasts on all the media. Six of the media proved inadequate for the enumeration of yeasts in the mould invested environment and were therefore omitted from statistical analysis. No significant differences in quantitative data obtained on Rose-Bengal Chloramphenicol Agar (RBCA), Dichloran Rose-Bengal Chloramphenicol Agar (DRBC), Dichloran 18% Glycerol Agar (DG18), and Malt extract agar supplemented with NaCl and oxytetracycline (MES) were detected by four of the collaborating laboratories whereas one laboratory found RBCA to be superior for yeast enumeration. DG18 and Malt Extract Agar with Biphenyl (MEB), however, were ranked superior based on qualitative results compared to the other media, attributed to distinctive individual yeast colonies and mould inhibition. RBCA, DRBC, DG18, and MES on the other hand, all proved to be adequate in supporting yeast colony development for quantitative analysis in samples obtained from blue veined cheeses.
Agar↗
Cross-reactivity to eel, eelpout and ocean pout in codfish-allergic patients.
Fish allergy is one of the most common food allergies in both children and adults and patients with allergic reactions to one fish species have in many cases been given the advice to avoid all fish, without further evaluation. The possible common reactivity between different fish species is not well studied. Because of this and a possible exploitation of fish species hitherto not much used in the Scandinavian diet ocean pout, eelpout and eel were evaluated. We examined the serological and biological cross-reactivity of these species in double-blind challenged-confirmed codfish-allergic patients using CAP, Maxisorp-radio allergosorbent test (RAST) inhibition, western blot, skin prick test (SPT) and histamine release (HR). All 18 codfish allergic patients had specific IgE to ocean pout, eelpout and eel determined by Maxisorp-RAST. All four fish species could induce basophil HR using blood from 16 of 18 patients and all patients tested reacted in SPT. This study demonstrates that patients with a verified clinical allergy to codfish in a high frequency express biological cross-reactivity to other fish species. By RAST inhibition this common reactivity was shown to be a true cross-reactivity.
Adolescent↗
Absorption and systemic availability of two synthetic growth hormone secretogogues and transport of glucose by the proximal small intestine of anestrus dogs after administering estradiol.
Pharmacokinetics for one growth hormone secretogogue (NNC 26-0722), but not for another (NN703), differ between dogs in estrus or anestrus. We examined if the differences could be mimicked by administering estradiol during anestrus and if there was a relationship with rates of small intestine absorption. Pharmacokinetics for oral doses of NN703 (1.0-1.6 mg kg(-1)) did not differ among dogs in estrus, anestrus, or anestrus and given estradiol for 1 week (days 1, 3, and 6; 40 micro g kg(-1)), whereas plasma concentrations of NNC 26-0722 increased from undetectable in untreated, anestrus dogs to several hundred nanograms per milliliter in dogs given estradiol, with maximal concentrations measured 5 min after oral dosage. Estradiol treatment increased small intestinal absorption of NNC 26-0722 by 100% (P<0.05), but did not increase absorption of NN703, and caused a 64% increase in carrier-mediated glucose transport at 50 mmol l(-1) (P<0.05) due to increased densities of transporters. These findings indicate estrus and estradiol enhance absorptive functions of the dog proximal small intestine and can affect pharmacokinetics for some orally administered drugs.
Administration, Oral↗
Exercise, hormones, and body temperature. regulation and action of GH during exercise.
UNLABELLED: That physical exercise stimulates pituitary GH secretion has been known for forty years, but the underlying mechanisms as well as the physiological significance remain elusive. We have previously shown that the concomitant increase in core temperature is essential for the exercise-induced GH release, inasmuch as exercise performed at 4 C results in a suppression of GH secretion, whereas passive heating constitutes a potent stimulus for GH release. Moreover, studies in normal subjects show that GH stimulates sweat production and evaporative heat loss during heat exposure with and without exercise, whereas GH-deficiency is associated with reduced sweat secretion and increased heat storage during similar conditions. The neurotransmitters involved in GH secretion during exercise remain uncertain; we therefore investigated the putative role of ghrelin, which is a gut-derived endogenous ligand for the GHS receptor. We measured circulating ghrelin levels before during and after submaximal aerobic exercise in healthy subjects and GH-deficient patients. The circulating ghrelin levels were unchanged during and after exercise in all subjects. Growth hormone stimulates lipolysis and lipid oxidation during basal and fasting conditions and we recently investigated whether GH also regulates substrate metabolism during exercise. The design involved GH-deficient patients studied during exercise with and without GH administration as compared to untreated healthy subjects. Growth hormone predominantly stimulated the turnover of free fatty acids in the recovery phase after exercise. CONCLUSIONS: 1) the increase in GH release during exercise is associated with the concomitant increase in body temperature, 2) GH stimulates sweat secretion and heat evaporation during exercise, which seems to be of distinct physiological significance, 3) ghrelin is not involved in exercise-induced GH release, 4) the impact of GH on substrate metabolism during exercise includes increased FFA turnover.
Body Temperature↗
Circulating ghrelin concentrations are reduced in healthy offspring of Type 2 diabetic subjects, and are increased in women independent of a family history of Type 2 diabetes.
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Diabetes Mellitus, Type 2↗
Assessment of the potential allergenicity of ice structuring protein type III HPLC 12 using the FAO/WHO 2001 decision tree for novel foods.
The introduction of novel proteins into foods carries a risk of eliciting allergic reactions in individuals sensitive to the introduced protein. Therefore, decision trees for evaluation of the risk have been developed, the latest being proposed by WHO/FAO early in 2001. Proteins developed using modern biotechnology and derived from fish are being considered for use in food and other applications, and since allergy to fish is well established, a potential risk from such proteins to susceptible human beings exists. The overall aim of the study was to investigate the potential allergenicity of an Ice Structuring Protein (ISP) originating from an arctic fish (the ocean pout, Macrozoarces americanus) using the newly developed decision tree proposed by FAO/WHO. The methods used were those proposed by FAO/WHO including amino acid sequence analysis for sequence similarity to known allergens, methods for assessing degradability under standardised conditions, assays for detection of specific IgE against the protein (Maxisorb RAST) and histamine release from human basophils. In the present paper we describe the serum screening phase of the study and discuss the overall application of the decision tree to the assessment of the potential allergenicity of ISP Type III. In an accompanying paper [Food Chem. Toxicol. 40 (2002) 965], we detail the specific methodology used for the sequence analysis and assessment of resistance to pepsin-catalysed proteolysis of this protein. The ISP showed no sequence similarity to known allergens nor was it stable to proteolytic degradation using standardised methods. Using sera from 20 patients with a well-documented clinical history of fish allergy, positive in skin prick tests to ocean pout, eel pout and eel were used, positive IgE-binding in vitro to extracts of the same fish was confirmed. The sera also elicited histamine release in vitro in the presence of the same extracts. The ISP was negative in all cases in the same experiments. Using the proposed decision tree, we demonstrated the safety of the ISP to patients already sensitised to fish, as well as to individuals potentially susceptible to producing IgE responses to proteins. Furthermore, the practicability of the new decision tree was confirmed.
Adolescent↗
Oral administration of the growth hormone secretagogue NN703 in adult patients with growth hormone deficiency.
OBJECTIVE: Little is known of the usefulness of GH secretagogues (GHSs) in GH-deficient (GHD) adults. The objective of this study was to determine the number of responders to treatment with NN703 in GHD adults. DESIGN: A multicentre, randomized, double-blind, and placebo-controlled study. PATIENTS: Ninety-seven GHD adults were included. MEASUREMENTS: The GH response before and after 1 week of oral treatment with NN703 (n = 83) or placebo (n = 14) was determined. The first and last dose of NN703 was 3 mg/kg, whereas the dose of NN703 was 1.5 mg/kg/day during the 6 days between the first and last doses. Furthermore, all 97 patients received 1 micro g/kg GH-releasing hormone (GHRH) 3 weeks after the last dose of NN703. RESULTS: Serum GH peak and area under curve (AUC) values after the first NN703 administration were greater than those after placebo administration (P < 0.05). However, after correction for the lower body mass index (BMI) in the NN703 group, this difference lost statistical significance. After 1 week of therapy, GH peak and AUC values were similar following the final doses of NN703 and placebo. Serum peak and AUC values of other anterior pituitary hormones were similar between the NN703 and placebo groups both after the first and last administration of study drug. Nine of the 83 patients (11%) responded with a serum peak GH concentration >or= 5 micro g/l after the first and/or last NN703 administration, whereas no patient responded after placebo administration. Serum IGF-I was unaffected by 1-week NN703 treatment, whereas serum IGFBP-3 was increased (P < 0.05 vs. placebo) also after correction for BMI. Mean serum peak GH concentration after GHRH administration was 2.1 micro g/l (+/-0.3, SEM), which was higher than that after the first NN703 administration (1.32 +/- 0.3, P < 0.05). CONCLUSION: NN703 administration was generally well tolerated. Eleven per cent of the GHD adult patients responded with a peak GH response >or= 5 micro g/l after the first and/or last administration of oral NN703. Although a majority of GHD adults will not respond to NN703, the present results suggest that oral NN703 treatment could be useful in some adult patients with moderately severe GHD. These patients may be identified by a test dose of GHS.
Administration, Oral↗
Growth hormone and mannan-binding lectin: emerging evidence for hormonal regulation of humoral innate immunity.
An increasing number of studies in animals and humans indicate that growth hormone (GH) and insulin-like growth factor-I (IGF-I) modulate immune function. It was recently reported that, surprisingly, GH therapy increased the mortality in critically ill patients. The excessive mortality was almost entirely due to septic shock or multi-organ failure, which could suggest that a GH-induced modulation of immune function was involved. Mannan-binding lectin (MBL) is a plasma protein that plays an important role in innate immunity through activation of the complement cascade and inflammation following binding to carbohydrate structures. The serum concentration of MBL is subject to large between-subjects differences, which primarily are caused by genetic factors. However, mounting evidence supports a significant influence from growth hormone on MBL levels. In the present review, we focus on the function of MBL, on the influence of growth hormone on MBL levels, and on the possible clinical consequences of this new link between the endocrine and the immune system.
Acute-Phase Reaction↗
Circulating levels of ghrelin and GLP-1 are inversely related during glucose ingestion.
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Adult↗
Feast or famine - are GLP-1 and ghrelin secretion intertwined?
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Appetite↗