- Prof em. (Allergology) University of Bergen, Norwayedit
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Research Interests: Medicine, Humans, Female, Pubmed, Male, and 6 morePleural Diseases, Aged, Middle Aged, Pneumothorax, Pleural Effusion, and PLEURODESIS
Research Interests: Dermatology, Medicine, Allergy, Humans, Female, and 6 morePubmed, Hashish, Cannabis, Adult, Conjunctivitis, and Drug hypersensitivity
Horizontal isoelectric focusing (IEF) and two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (2-D SDS-PAGE) combined with electrophoretic transfer (ET) and immunoautoradiography (IAR) were used to characterize the... more
Horizontal isoelectric focusing (IEF) and two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (2-D SDS-PAGE) combined with electrophoretic transfer (ET) and immunoautoradiography (IAR) were used to characterize the crude alder (Alnus incana) pollen extract (AI crude) and fraction AI 34. IEF resolved AI crude and AI 34 into 34 and 39 distinct protein bands, respectively, when stained with Coomassie brilliant blue. The band patterns were similar and the majority of bands were located in the pH region 4.0-7.0. After ET and IAR, the distribution of antigenic reactivities was similar to that of the protein stain. Allergenic reactivity was detected in the pH region 4.6-5.2 only, where two bands at pH 4.9 demonstrated dominating IgE-binding properties. The 2-D reference maps of AI crude and AI 34 consisted of 40 and 45 protein spots, respectively. The autoradiogram of AI crude demonstrated 35 spots capable of binding rabbit IgG. The main IgE-binding zone was located at pH 4.6-5.2 and 20 kilodaltons with an area of weaker autoradiographic signals at pH 4.6-5.2 and 40 kilodaltons. ET from polyacrylamide gels to nitrocellulose (NC) membranes was quantitative and IAR gave significant radiostaining of spots containing 0.01 and 0.1 microgram of AI crude in the IgG and IgE systems, respectively. For the characterization of the alder pollen extract, horizontal 2-D SDS-PAGE combined with ET and IAR provided a powerful supplement to conventional crossed immuno- and radioimmunoelectrophoretic techniques (CIE/CRIE).
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Research Interests: Medicine, Norway, Humans, Anaphylaxis, Pubmed, and 4 moreAnesthesia, Registries, Anesthetics, and Drug hypersensitivity
The crude aqueous extracts of birch (Betula verrucosa) and hazel (Corylus avellana) pollen were characterized by horizontal isoelectric focusing (IEF) and one-dimensional and two-dimensional sodium dodecyl sulfate polyacrylamide gel... more
The crude aqueous extracts of birch (Betula verrucosa) and hazel (Corylus avellana) pollen were characterized by horizontal isoelectric focusing (IEF) and one-dimensional and two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (1-D and 2-D SDS/PAGE). Isoelectric focusing reference patterns obtained in pH 3.5 to 9.5 gradient gels contained 31 and 41 bands while the 2-D patterns consisted of 51 and 72 protein spots, respectively. Electrophoretic transfer to nitrocellulose membranes and subsequent 125I-immunoautoradiography demonstrated IgE binding in the region between pH 4.8 and 5.4 for both extracts. The main allergenic reactivities of this pH region were distributed by SDS/PAGE to the molecular weights of 29.5, 17, and 12.5 kilodaltons for birch and 15.5 and 12 kilodaltons for hazel. The high resolving power and the independence of rabbit antibodies were considered the major advantages of the described 2-D methodology as compared with conventional crossed immunoelectrophoretic and radioimmunoelectrophoretic techniques.
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A major allergen from birch pollen (Betula verrucosa) was isolated by a combination of gel permeation chromatography and preparative isoelectric focusing, and was found adequate for further immunological and chemical characterization. The... more
A major allergen from birch pollen (Betula verrucosa) was isolated by a combination of gel permeation chromatography and preparative isoelectric focusing, and was found adequate for further immunological and chemical characterization. The crude aqueous pollen extract was eluted in 6 UV-absorbance peaks from an Ultrogel AcA-54 column. The main allergenic components were detected in two peaks of molecular weights 29,000 (BV4) and 40,000 daltons, respectively. BV4 contained one quantitatively dominating antigen as assessed by crossed immunoelectrophoresis, and was selected for further purification by isoelectric focusing. Column isoelectric focusing of BV4 gave four protein fractions with pI values corresponding to 5.18, 5.42, 5.76, and 5.94. The pI 5.18 protein was quantitatively dominating. This protein inhibited the radio-allergosorbent test in 8 out of 10 sera from birch pollen-sensitive individuals. Using a serum pool, the inhibition curve of BV4 pI 5.18 was parallel to that of the crude extract and gave a similar maximum inhibition. This allergen was shown to be homogeneous as judged by a single, symmetrical precipitate in crossed immunoelectrophoresis, one band in high-volt electrophoresis and a sharp strip in thin-layer analytical electrofocusing. Amino acid analysis showed a high content of serine. The N-terminal analysis as well as the carbohydrate concentration were preliminarily reported and will be confirmed in future studies.
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The aqueous extract of alder (Alnus incana) pollen was found to consist of a protein mixture amounting to 3% of the dry pollen weight. Separation by gel permeation chromatography on an AcA-54 column resulted in 6 fractions designated... more
The aqueous extract of alder (Alnus incana) pollen was found to consist of a protein mixture amounting to 3% of the dry pollen weight. Separation by gel permeation chromatography on an AcA-54 column resulted in 6 fractions designated chronologically to their relative elution volumes (AI 1 to AI 6). The immunological reactivity of these fractions was demonstrated in both IgE and IgG test systems. Being both immunochemically and quantitatively dominant fraction AI 4 was selected for further purification by a semipreparative isoelectric focusing column. A well-resolved and apparently homogeneous component with a pI value of 4.78 was eluted from the IEF column. The homogeneity of this fraction was demonstrated by one sharp band in thin layer IEF, one single band in HVE, one distinct sharp peak in HPLC and a symmetrical precipitate in CIE. The molecular weight was estimated to 22,500 daltons. Fraction pI 4.78 was shown to be a major allergen of alder pollen, it elicited a 1.17 histamine wheal reaction in skin prick test at a concentration of 1 mg . ml-1 and showed a significantly high RAST inhibition in all of the reaginic sera used. Fraction pI 4.78 was found to be an adequate model allergen of alder pollen well suited for further immunochemical characterization.
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Anaphylactic reactions to neuromuscular blocking agents during general anesthesia constitute a major cause of concern and a great source of debate among anesthesiologists. The authors' recent investigations, taking the striking... more
Anaphylactic reactions to neuromuscular blocking agents during general anesthesia constitute a major cause of concern and a great source of debate among anesthesiologists. The authors' recent investigations, taking the striking differences of incidence between Norway and Sweden as the point of departure, have provided valuable insights into the pathogenetic mechanisms and the highly uneven geographical distribution of these rare, but dramatic and notoriously unpredictable, events. Eventually, a cough syrup containing pholcodine emerged as the most likely suspect. This new knowledge led to the withdrawal of the drug from the Norwegian market and to the examination of the role of pholcodine-containing drugs in other countries. The present article is a brief summary of the research behind this development.
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The immunological properties of the aqueous crude alder pollen extract (AI crude) and gel filtration fractions AI 3, AI 4 and AI 34 (pool of fractions AI 3 and AI 4) were examined by immuno- and radioimmuno-electrophoretic techniques,... more
The immunological properties of the aqueous crude alder pollen extract (AI crude) and gel filtration fractions AI 3, AI 4 and AI 34 (pool of fractions AI 3 and AI 4) were examined by immuno- and radioimmuno-electrophoretic techniques, RAST titration, RAST inhibition and skin prick tests (SPT). In CIE, the AI crude extract and AI 34 displayed reference precipitate patterns consisting of 27 and 24 visible Coomassie brilliant blue stained lines, respectively. The CRIE allergogram performed by incubation with 18 individual reaginic sera detected three IgE-binding antigens characterized by different IgE-binding properties. Antigen No. 7 (Ag 7) was demonstrated to be the major IgE antibody-binding antigen of alder pollen, while Ag 1 and Ag 11 were classified as intermediate allergens. The allergens of alder pollen were located in fractions AI 3 and AI 4 of the gel filtration chromatogram. Ag 7 was present in both fractions as demonstrated by FRIE with autoradiography (FRIEWA) on the gel filtration fractions and tandem-CRIE of AI 3 and AI 4. The CRIE allergogram, RAST, RAST inhibition and SPT demonstrated fraction AI 34 to be allergenically representative of the AI crude extract both qualitatively and quantitatively. Thus, fraction AI 34 was considered an optimal purified allergen extract of alder pollen, a suitable material for further biochemical characterization and trials on purification of the allergenic reactive antigens.
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Summary Anaphylaxis during general anaesthesia is a rare but dramatic event that has been increasingly reported during the last decades. Neuromuscular blocking agents (NMBAs) represent the most frequent causes, with suxamethonium (SUX) as... more
Summary Anaphylaxis during general anaesthesia is a rare but dramatic event that has been increasingly reported during the last decades. Neuromuscular blocking agents (NMBAs) represent the most frequent causes, with suxamethonium (SUX) as the prominent culprit drug. In most cases IgE-mediated mechanisms are involved, but since up to half the patients have not been previously exposed to anaesthetic drugs, other drugs or environmental chemicals sharing the quaternary ammonium ions (QAI) epitope with NMBAs are suspected of initiating IgE-sensitization. No gold standard for diagnosis exists, but most protocols include history, immunoassays for serum tryptase and IgE antibodies and skin and mediator release tests. The calculated frequency of reactions varies considerably between countries, from about 1 in 5 000 to 1 in 20 000 anaesthetics in high prevalence countries. NMBA related anaphylaxis is much more common in Norway than in Sweden, a discrepancy at least partly explained by differently exposed and sensitized populations as indicated in a recent publication. The effect of possible IgE sensitizers was studied by testing 84 different chemicals collected from Norwegian and Swedish homes, of which several inhibited IgE binding to SUX and/or morphine (MOR). However, no difference in exposure to the above chemicals was found, except for the use of cough mixtures containing pholcodine (PHO). These are purchased without precription (OTC) in Norway but are not available in Sweden. Further, the prevalence of IgE-sensitization to MOR, SUX and PHO in Bergen, Norway and Stockholm, Sweden was investigated. In Norway, 0.4 % of blood donors, 3.7 % of allergics and 38.5 % of NMBA anaphylactics were sensitized to SUX, as were 5.0, 10.0 and 66.7 % respectively to MOR. Among blood donors and allergics from Stockholm, no IgE antibodies to SUX or MOR were detected. IgE antibodies to PHO were present in 6.0 % of blood donors from Norway but in none from Sweden. Additionally, in a pilot study two Norwegian individuals IgE-sensitized to PHO, MOR and SUX responded with a dramatic increase in serum IgE antibodies to 60 and 105 times the levels before exposure after one single daily dose of PHO during one week. A PHO hypothesis is proposed, according to which the consumption of PHO- containing cough mixtures in Norway could offer one explanation both for the much higher prevalences of IgE-antibodies to PHO, MOR and SUX as well as NMBA induced anaphylaxis than in Sweden. PHO exposure could also be of relevance for the different prevalences of perianaesthetic anaphylaxis reported from other countries. However, further studies are needed.
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Background According to a recent press release, the European Medicines Agency (EMA) after conducting a review of the safety and effectiveness of pholcodine (PHO) – a morphine (MOR) analogue and possibly one of the strongest... more
Background According to a recent press release, the European Medicines Agency (EMA) after conducting a review of the safety and effectiveness of pholcodine (PHO) – a morphine (MOR) analogue and possibly one of the strongest IgE-sensitizing agents known – has decided to let patients in the European Union continue to be exposed through the unrestricted use of cough and cold medicines. As suggested by published information, summarized in this commentary, we advise this decision be revised.
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Research Interests: Immunology, Gastroenterology, Inflammation, Medicine, Food Allergy, and 15 moreHumans, Female, Digestion, Male, Immunoglobulin E, Irritable Bowel Syndrome, Intestinal permeability, Clinical Sciences, Aged, Middle Aged, Adult, Gastrointestinal Tract, Biological markers, General Population, and food hypersensitivity
1. Biro P, Seifert B, Pasch T. Complaints of sore throat after tracheal intubation: a prospective evaluation. Eur J Anaesthesiol 2005;22:307–11. 2. Macario A, Weinger M, Carney S, Kim A. Which clinical anesthesia outcomes are important to... more
1. Biro P, Seifert B, Pasch T. Complaints of sore throat after tracheal intubation: a prospective evaluation. Eur J Anaesthesiol 2005;22:307–11. 2. Macario A, Weinger M, Carney S, Kim A. Which clinical anesthesia outcomes are important to avoid? The perspective of patients. Anesth Analg 1999;89:652–8. 3. Chatterji S, Gupta NR, Mishra TR. Valvular glottic obstruction following extubation. Anaesthesia 1984;39:246–7. DOI: 10.1213/01.ane.0000253673.82633.22
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Research Interests: Nursing, Medicine, Norway, Humans, Female, and 13 moreImmunoglobulin E, Beauty Culture, Prevalence, Occupational, Questionnaires, Adult, Occupational Exposure, Public health systems and services research, Atopic Dermatitis, Prospective Study, Case Control Studies, Occupational and environmental medicine, and Respiratory Tract Diseases
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Owing to lack of objective measures, the diagnosis of food hypersensitivity may be difficult. The aim of this study was to investigate whether the intestinal response to direct provocation in patients with food hypersensitivity could be... more
Owing to lack of objective measures, the diagnosis of food hypersensitivity may be difficult. The aim of this study was to investigate whether the intestinal response to direct provocation in patients with food hypersensitivity could be recognized by ultrasound. Thirty-two patients with chronic abdominal complaints, self-attributed to food hypersensitivity/allergy were included in the study. Via a nasoduodenal tube, the duodenal mucosa was challenged with the suspected food item dissolved in 10 ml water or saline. Using external ultrasound, the sonographic features (wall thickness and diameter of the duodenal bulb and jejunum, peristalsis activity and luminal fluid) were recorded before and during one hour after challenge. Sonographic changes were observed after challenge in 14 (44%) of the 32 patients. A positive sonographic response (increased wall thickness, diameter, peristalsis and/or luminal fluid) was significantly related to a positive skin prick test (p = 0.008) and a positive double-blind placebo-controlled food challenge (p = 0.03). A significant correlation was found between provocation-induced symptoms and wall thickness of the duodenal bulb (r = 0.50, p = 0.004) or the jejunum (r = 0.42, p = 0.02). Intra- and interobserver variation of the tracing procedure showed low values. Responses of the proximal small intestines to direct provocation (swelling of the wall and exudation of fluid into the lumen) could be visualized by transabdominal ultrasound. This new provocation test could be helpful in the evaluation of patients with food hypersensitivity.
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Research Interests: Medicine, Probability, Humans, Digestive and Liver Diseases, Female, and 15 moreConstruct Validity, Male, Dyspepsia, Health Care Workers, Clinical Sciences, Aged, Prevalence, Middle Aged, Adult, Analysis of Variance, Prognosis, Indexation, General Population, Case Control Studies, and food hypersensitivity
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Visualization by autoradiography of specific IgE binding in crossed radioimmunoelectrophoresis (CRIE) and other 125I‐immunoautoradiography (IAR) techniques is done in two different ways; either by traditional direct autoradiography... more
Visualization by autoradiography of specific IgE binding in crossed radioimmunoelectrophoresis (CRIE) and other 125I‐immunoautoradiography (IAR) techniques is done in two different ways; either by traditional direct autoradiography (D‐ARG), where the film is exposed to the 125I‐anti‐lgE incubated sample at room temperature, or by indirect autoradiography (ID‐ARG), applying intensifying screen, low‐temperature exposure and, eventually, pre‐exposure. This study confirmed that D‐ARG provided the benefits of simplicity and better image resolution with the disadvantage of prolonged exposure periods. ID‐ARG reduced the exposures needed to produce film image densities of 0.01 and 0.1 A540 nm (i.e. autoradiographic sensitivity (ARσ) and autoradiographic speed (ARs)) to 1/l8 and 1/55 respectively of the corresponding exposures in D‐ARG. The lowest detection limits for 125I in 24 h were 1.2 cpm mm−2 with the indirect and 6.8cpm mm−2 with the direct systems investigated. The major drawbacks of ID‐ARG were inferior image resolution and higher background levels, especially when pre‐exposure was included.
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Research Interests: Mast Cells, Medicine, Humans, LaTeX, Anaphylaxis, and 15 moreFemale, Male, Immunoglobulin E, Medical Physiology, Morphine, Clinical Sciences, General Anesthesia, Adult, Biological markers, Quaternary Ammonium Compounds, Choline, Neurosciences, Drug hypersensitivity, succinylcholine, and General Anaesthesia
ABSTRACT
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The reports on fish parasite Anisakis simplex allergy have increased in countries with high fish consumption in the last decade. In Norway, a high consumption country, the prevalence of immunoglobulin E (IgE) sensitization to A. simplex... more
The reports on fish parasite Anisakis simplex allergy have increased in countries with high fish consumption in the last decade. In Norway, a high consumption country, the prevalence of immunoglobulin E (IgE) sensitization to A. simplex was still unknown. Thus, our objective was to investigate the sensitization prevalence in this country. At the Haukeland University Hospital, Bergen, Norway, two main groups of surplus serum samples were collected: one from newly recruited blood donors (BDO) and the other from the Allergy laboratory (ALL) after analysing IgE and IgE antibodies. The latter was divided into three series: one containing unsorted sera and two sorted by either Phadiatop®≥0.35 kUA/l or total IgE ≥1000 kU/l. The sera were analysed for total IgE and IgE antibodies against A. simplex, shrimp, house dust mite (HDM), cod and cross‐reactive carbohydrates (CCDs). The prevalence of IgE sensitization to A. simplex was 2.0%, 2.2% and 6.6% in BDO, the unsorted and Phadiatop® positive...
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Three major allergens from cod fish, egg white and tree pollen, were characterized by studies on their allergenic and antigenic structures. The major allergen of cod fish, Allergen M "parvalbumins pI 4.75", is composed... more
Three major allergens from cod fish, egg white and tree pollen, were characterized by studies on their allergenic and antigenic structures. The major allergen of cod fish, Allergen M "parvalbumins pI 4.75", is composed of 113 amino acid residues with a molecular weight of 12,328 daltons. It comprised three domains, AB, CD and EF, consisting of 3 helices interspaced by one loop. Each of the loops of the CD and EF domains each coordinates one Ca2+. The antigenicity and allergenicity of Allergen M was deduced from studying the modified protein and some particular synthetic peptides. Three sites were encompassing IgE binding epitopes namely peptides 33-44, 65-74 and 88-96. A novel peptide (49-64), of the CD-domain, was demonstrated to be allergenically/antigenically active and cross reactive with birch pollen allergen, which incidentally was used as a negative control. This site encompassed two repetitive sequences (D-E-D-K) and (D-E-L-K), suggested to be mutually critical for the specificity of antibody binding. This hypothesis was reconfirmed by SPPS of several analogous peptides of region 39-64. Furthermore, peptide 88-103 of the EF-domain was similarly synthesized; it functioned as a monovalent hapten, blocking and not eliciting allergic reaction. Moreover, peptide 13-32 of domain AB, the non-calcium binding domain, was thoroughly tested. The results of PK inhibition showed clear activity and the peptide was found to function at the level of a divalent determinant. Ovalbumin (OA) is the most dominant of five major allergens of egg white and universally used as model protein. OA allergenic epitopes were shown to be mainly determined by the primary structure and depend on certain peptide chain length. The N-terminal decapeptide (OA 1-10) was shown to react with reaginic IgE. Direct skin test on egg allergic patients, showed no activity and the site was therefore concluded to encompasses one single Ig binding haptenic epitope. Peptide OA 323-339, was demonstrated to be valuable in studies of T-cell recognition of protein antigens. Three analogous peptides of this region were prepared and clearly shown to be immunogenic in rabbits and to bind specific IgE from patients allergic to egg. OA 323-339 was concluded to encompass an allergenic and antigenic epitope which was recognized by human and rabbit B-lymphocytes. Eight peptides in the region 11-122 were similarly synthesized. A test battery was performed to study this region using rabbit polyclonal antibodies and human specific IgE. Some of these sites were involved in binding of particular Ig paratopes. Five immunogenic peptides from the major allergens of tree pollen extracts (segment 23-38), were synthesized. The selection of those peptides was setteled using two algorithms for providing the optimal hydrophobicity.(ABSTRACT TRUNCATED AT 400 WORDS)
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Research Interests: Dermatology, Medicine, Allergy, Humans, Female, and 5 moreHashish, Cannabis, Adult, Conjunctivitis, and Drug hypersensitivity
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Research Interests: Nursing, Medicine, Norway, Humans, Female, and 13 moreImmunoglobulin E, Beauty Culture, Prevalence, Occupational, Questionnaires, Adult, Occupational Exposure, Public health systems and services research, Atopic Dermatitis, Prospective Study, Case Control Studies, Occupational and environmental medicine, and Respiratory Tract Diseases
IgE-mediated anaphylaxis to neuromuscular blocking agents (NMBA), frequent in Norway, was proposed to be caused by exposure to pholcodine (PHO) carrying the allergenic quarternary ammonium ion epitope. Consequently, the PHO-containing... more
IgE-mediated anaphylaxis to neuromuscular blocking agents (NMBA), frequent in Norway, was proposed to be caused by exposure to pholcodine (PHO) carrying the allergenic quarternary ammonium ion epitope. Consequently, the PHO-containing drug was withdrawn from the market in March 2007. Describe the effects of withdrawal of PHO on IgE, IgE-antibodies and reported frequencies of anaphylaxis to NMBAs. Three hundred sera from supposedly allergic patients sampled yearly through 2006 to 2010 were analysed for IgE antibodies to PHO, suxamethonium (SUX) and morphine (MOR). Furthermore, IgE and preliminary reports from the Norwegian Network for Anaphylaxis under Anaesthesia (NARA) were monitored. PHO exposure was associated with IgE sensitization to PHO, MOR and SUX. However, after withdrawal, within 1 year, antibody prevalences to PHO and SUX fell significantly from 11.0% to 5.0% and from 3.7% to 0.7%, respectively. At 3 years, SUX had fallen to 0.3%, PHO to 2.7% and MOR to 1.3%. By 2 years, the prevalence of elevated IgE was significantly reduced. After 3 years, the incidence of reported suspected anaesthetic anaphylaxis fell significantly, both the total number, the reactions related to NMBAs and those with IgE antibodies to SUX. Withdrawing of PHO lowered significantly within 1-2 years levels of IgE and IgE antibodies to PHO, MOR and SUX, and, within 3 years, the frequency of NMBA suspected anaphylaxis. The results strengthen the PHO hypothesis considerably and equally the need to question the existence of cough depressants containing PHO.