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Biomedical subjects

S Ahlstedt

Publications and source records attributed to S Ahlstedt.

At least 37 records · Page 2Linked to original sources

Nasal symptoms and indices of nasal inflammation in flour-dust-exposed bakers.

OBJECTIVE: To analyze whether indices of nasal airway inflammation in bakers were related to nasal symptoms and exposure to airborne flour dust. METHODS: A cross-sectional study was performed in 12 currently flour-exposed bakers. They were examined by nasal lavage (NAL), visual inspection, a test of mucociliary clearance, and nasal peak expiratory flow (nasal PEF). NAL fluid was analyzed according to the inflammatory markers eosinophil cationic protein (ECP), indicating eosinophilic activity; myeloperoxidase (MPO), indicating active neutrophils; hyaluronic acid (HA) from active fibroblasts; tryptase, indicating activation of mast cells; and albumin, indicating plasma exudation. The bakers were also questioned about respiratory symptoms and working history. Their current and cumulative exposure to inhalable flour dust was estimated after exposure measurements and information about earlier work tasks. Office workers (n=16) without occupational exposure to dust or any other known nasal irritant or sensitizer served as controls. RESULTS: Personal inhalable dust measurements among the bakers working as dough makers or bread formers ranged from 1.0 to 3.8 mg/m3. Of the 12 bakers, 10 reported at least 1 nasal symptom (crusts, blockage, or a runny nose), a proportion significantly greater than that of the controls (P=0.009). Bakers with nasal symptoms had higher concentrations of markers of inflammation in their NALs as compared with nonsymptomatic bakers. The difference was significant for MPO (P=0.02) and HA (P=0.04) in relation to a runny nose. Tryptase was detected in only one NAL of the bakers. There was a positive correlation between the cumulative dose of inhalable flour dust and concentrations of MPO and HA in NAL. Two bakers were sensitized to wheat; they had the highest NAL concentrations of inflammatory markers. CONCLUSIONS: Our results indicate that flour dust exposure in bakers at levels below the current occupational exposure limit causes nasal mucosal inflammation, which, in turn, is related to nasal symptoms. We propose that the inflammation may be nonallergic, characterized by activation of neutrophils and fibroblasts.

Adult↗

Antibody-dependent cell-mediated cytotoxicity to gliadin-coated cells with sera from children with coeliac disease.

Antibody-dependent cell-mediated cytotoxicity (ADCC) has been suggested as a contributing immunological mechanism in the disease process of coeliac disease. In the present study, sera from coeliac children were examined for their capacity to mediate ADCC against gliadin-coated target cells. The ADCC-mediating efficacy of sera were tested using monocytes from healthy adults as effector cells and gliadin-coated erythrocytes from the same donor as targets. Using monocytes as effector cells, sera from children with active coeliac disease (untreated or challenged), demonstrated significantly higher ADCC-mediating capacity than sera from healthy and disease references as well as children with treated coeliac disease. A positive correlation was found between the ADCC-mediating capacity and serum IgG as well as IgA anti-gliadin antibody levels. The results suggest that an antibody-dependent monocyte/macrophage-induced cytotoxic reaction might be involved in the disease process of coeliac disease.

Adult↗

Eosinophil cationic protein and histamine after intestinal challenge in patients with cow's milk intolerance.

BACKGROUND: Mast cells and eosinophils are key cells in the development of active symptoms in allergic diseases and other inflammatory conditions, and they mediate their action through the release of very potent granule constituents. METHODS: Five patients with milk-related gastrointestinal symptoms diagnosed by double-blind placebo-controlled milk challenges, but with negative responses to skin prick tests and RASTs with milk, and eight healthy control subjects were investigated. Repeated perfusion studies were performed with a two-balloon, six-channel tube by using milk, casein, and whey as antigens. Luminal eosinophil cationic protein, histamine, and albumin were measured by radioimmunoassay. RESULTS: Luminal cow's milk induced a pronounced increase in intestinal secretion of histamine and eosinophil cationic protein in patients, but not control subjects, during the first 20 minutes after challenge (histamine from 123 +/- 12 to 543 +/- 175 ng/cm, hr; eosinophil cationic protein from 80 +/- 23 to 686 +/- 262 ng/cm, hr). Albumin, as a marker of plasma leakage, was also significantly increased. CONCLUSION: These data indicate that mast cells and eosinophils are effector cells not only in patients with allergic disease but also in patients intolerant to foods and lacking circulating antibodies. The underlying mechanisms may be a reaction mediated by locally appearing antibodies or an immunologic activation resembling that found in intestinal disorders such as celiac disease.

Adult↗

Induction of oral tolerance with effects on numbers of IgE-carrying mast cells and on bystander suppression in young rats.

The presence of IgE+ mast cells in the small intestine, bystander suppression of DTH and antibody responses to human serum albumin (HSA) were studied in young rats, made tolerant to ovalbumin (OA) by feeding an OA-containing diet for 1-4 weeks starting from weaning, and in sensitized control rats. One week after finishing the OA diet, both groups of rats were immunized with a mixture of OA and HSA in Freund's complete adjuvant (FCA) at one site on the back. The animals were then colonized for 5 days with a genetically manipulated Escherichia coli producing OA. Immunohistochemical staining of the small intestine of the rats fed the OA diet for 4 weeks showed significantly fewer IgE+ mast cells in the lamina propria, a lower level of MHC class antigen was found in the epithelial cells and in the lamina propria, and the villus crypt depth was also significantly less in tolerant compared with sensitized rats (P = 0.003, 0.007, 0.003, respectively). Sensitized rats showed a mild diarrhoea during the colonization in contrast to tolerant rats. All rats fed OA showed a significantly reduced IgE anti-OA antibody and DTH response to OA before colonization compared with the sensitized rats. Bystander suppression of IgG and IgE anti-HSA antibody responses was also seen, but only in the rats fed OA for either 1 or 4 weeks. Rats fed the OA-containing diet for 1, 3, or 4 weeks showed bystander suppression of the DTH response to HSA. After colonization with E. coli producing OA, rats tolerant to OA after either 1 or 4 weeks on an OA diet maintained tolerance to OA and bystander suppression HSA. These results suggest that oral tolerance to OA down-regulates signs of local inflammatory response by IgE, IgG antibody and T cell responses to OA, but also provides bystander suppression to an unrelated antigen, HSA.

Administration, Oral↗

Effects of luminal antigen on intestinal albumin and hyaluronan permeability and ion transport in atopic patients.

BACKGROUND: Increased luminal transport of proteins and fluid is part of the inflammatory reaction in inflammatory disease of the bowel and of the airways in allergic diseases and asthma. The objective of this study was to determine intestinal appearance rates of albumin and hyaluronan in vivo in atopic patients allergic to birch, as well as changes in net jejunal transport of monovalent ions and water induced by the antigen. METHODS: Secretion studies were performed with the use of a segmental jejunal perfusion system with a small two-balloon, six-channel tube. The intestinal mucosa was challenged with birch allergen in patients allergic to birch and in matched control subjects (n = 12 in both groups). RESULTS: In patients, but not in control subjects, the luminal antigen induced a net increase in albumin of 2689 +/- 567 micrograms/cm/hr and in hyaluronan of 2609 +/- 737 ng/cm/hr (p < 0.01 vs control subjects in both cases). Furthermore, basal net absorption of Cl- ions, Na+ ions, and water was converted to a net secretion after antigen challenge. CONCLUSION: Exposure to antigen normally acting on the respiratory tract induced increased permeability of the gastrointestinal mucosa. This would suggest less organ specificity and more general allergic recognition shared by several immunocompetent tissues in the body, probably mediated by circulating IgE antibodies.

Adult↗

Different expression of IL-2 receptor alpha-chain on a lamina propria T cell population and goblet cells in rats orally tolerized or sensitized to ovalbumin (OA) after colonization with an OA-producing Escherichia coli.

The aim of this study was to compare the local gut immune response in sensitized and orally tolerized experimental animals. The development of IgE/IgG antibodies and the DTH to OA was studied in rats made orally tolerant to OA and compared with sensitized control rats after colonization with an Escherichia coli genetically engineered to produce OA. At 3 weeks of age, pups were weaned onto a standard diet without OA or an OA-containing diet for 4 weeks and then switched to a standard diet without OA. Both groups of rats were parenterally immunized with a mixture of OA and human serum albumin (HSA) in Freund's complete adjuvant when they were 8 weeks old. After DTH measurement 2 weeks later, all rats were colonized with an E. coli producing OA for 5 days. The local immune response in the small intestine was assessed, using immunohistochemistry, as the expression of MHC class II molecules and IL-2 receptor (IL-2R) alpha-chain. The OA-tolerant rats showed the classical signs of oral tolerance, with a reduced IgE and IgG antibody and DTH response to OA before colonization. The difference between the two groups in the anti-OA antibody response became even more pronounced after colonization with the E. coli that produce OA. Rats orally tolerant to OA maintained a normal villus architecture after colonization, with a normal expression of MHC class II molecules similar to non-treated adult rats, but with a significantly higher (P = 0.004) expression of IL-2R alpha-chain on T cells in the lamina propria of the villus core compared with sensitized control rats. The tolerant rats showed a very weak staining with the anti-IL-2R alpha-chain-specific antibody on a few goblet cells in only one out of seven rats. In the sensitized control rats, a marked local immune response was seen with an intense staining with a monoclonal anti-IL-2R alpha-chain-specific antibody on goblet cells in five out of seven rats (P = 0.019) and also an increased expression of MHC class II molecules in the epithelial cells and cells in the lamina propria of all rats. Rats orally tolerant to OA maintained a normal villus architecture after colonization, but with a significantly higher (P = 0.004) expression of IL-2R alpha-chain on T cells in the lamina propria of the villus core compared with sensitized control rats. The novel finding that goblet cells express IL-2R alpha-chain and the striking difference in expression of the receptor and the numbers of goblet cells between tolerant and sensitized rats may suggest a direct T cell regulation of the goblet cells. A possibility that oral tolerance might be maintained by the activated T cells expressing IL-2R alpha-chain in the lamina propria of the villus core is also discussed.

Administration, Oral↗

Increased levels of hyaluronan and albumin after intestinal challenge in adult patients with cow's milk intolerance.

BACKGROUND: The mechanisms for adverse reactions to foods in the gastrointestinal tract are poorly understood. Presently, only limited possibilities are available for identification of adverse immunological reactions to different foods. OBJECTIVE: The intestinal inflammatory reactions in adult patients with a history of milk-related gastrointestinal symptoms were studied after intestinal challenges by a jejunal perfusion technique and compared with the reactions in a control group. METHODS: Five skin-prick test and radioallergosorbent test negative and lactose tolerant patients with a history of milk-related gastrointestinal symptoms, verified by double-blind placebo-controlled challenge, and eight healthy controls were investigated. Perfusions were performed allowing analyses of a well-defined 'closed' jejunal segment. Milk perfusions were performed in patients and controls after an overnight fast. Ten millilitres of milk were administered to the segment at 3 mL/min. The jejunal fluid levels of hyaluronan (hyaluronic acid) and albumin were measured. RESULTS: In the five patients the milk challenges induced as a mean fivefold increased levels of hyaluronan compared with prestimulation values, whereas no such increases were seen in the control subjects. Albumin, as a marker of plasma leakage, was also increased in the patients but not in the control subjects. CONCLUSION: The underlying mechanisms for locally increased levels of hyaluronan and also albumin in the intestinal lumen may be secretion of lymph rich in hyaluronan and reflect the mucosal oedema. This capacity of the intestinal mucosa to react with lymph leakage towards a locally infused allergen may be a possible way to delineate gastrointestinal reactions in food-related disorders.

Adult↗

Double blind, placebo controlled food reactions do not correlate to IgE allergy in the diagnosis of staple food related gastrointestinal symptoms.

BACKGROUND: The mechanisms for adverse reactions to foods in the gastrointestinal tract are poorly understood. There is conflicting evidence in the literature on the role for IgE mediated allergy in gastrointestinal reactions to staple foods. AIM: The aim was therefore to study the role of IgE mediated allergy in a group of patients with a history of gastrointestinal symptoms related to staple foods (cows' milk, hens' egg, wheat and rye flour) verified in double blind placebo controlled challenges (DBPCFC). PATIENTS: Fifteen patients with DBPCFC, identified by screening of 96 consecutive patients referred to our allergy clinic for investigation of suspected gastrointestinal symptoms due to staple foods. METHODS: The screening included diaries as well as elimination diets and open and blinded food challenges. The frequency of atopy were compared between the double blind positive and double blind negative patients. RESULTS: The positive DBPCFC in the 15 patients included eight patients with milk intolerance, four with wheat flour, two with egg, and one with rye flour. There was no indications of an allergic pathogenesis in all 15 patients with positive DBPCFC, as the skin prick test and radioallergosorbent test were negative for the relevant allergens. The frequency of atopy was four of 21 (19%) in the double blind negative group and three of 15 (20%) in the double blind positive group. CONCLUSION: In adult patients with staple food induced gastrointestinal symptoms, objectively verified by DBPCFC, there were no indications of IgE mediated allergy to the relevant foods suggesting other mechanisms in adults than in children. Future studies may include measures of local events in the shock organs in relation to food intake, for instance utilising inflammatory markers in jejunal fluids.

Adolescent↗

Bronchial brush biopsies for studies of epithelial inflammation in stable asthma and nonobstructive chronic bronchitis.

Recently, bronchial brush biopsy (BBB) has been introduced as a complimentary method to bronchial forceps biopsy for the study of bronchial epithelial cells. We wanted to determine whether epithelial inflammatory cells in bronchial brush biopsies can reflect mucosal inflammation assessed indirectly by levels of cellular activation markers in bronchial lavage fluid. We studied 15 healthy controls, 11 asthmatics with regular steroid inhalation therapy, 13 asthmatics without steroids, and 10 smokers with nonobstructive chronic bronchitis. Differential counts of epithelial and inflammatory cells were made from the BBB material. Bronchial lavage levels of eosinophil cationic protein (ECP), myeloperoxidase (MPO), tryptase, hyaluronan and interleukin-8 (IL-8) were measured as indirect markers for inflammatory cell activation. We found an increased percentage of eosinophil granulocytes in the BBB from the steroid-untreated asthmatic patients (1.16%) in comparison to the other groups (0.11%, 0.09% and 0.02%, respectively; p<0.01). In the steroid-untreated asthmatic patients, the percentage of eosinophils correlated with ECP in bronchial lavage fluid (r=0.73; p<0.01), indicating that the BBB method can reflect the degree of eosinophilic activation. A negative correlation was found for the percentage of eosinophils in BBB with levels of provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (PC20) for the asthmatic patients in the study (r= -0.67; p<0.003). The bronchial brush biopsy method appears to give information on the changes present in superficial bronchial epithelium in inflammatory airways disease. These changes appear to relate to the degree of inflammatory activity and disease severity in asthma.

Administration, Inhalation↗

Survey of gastrointestinal reactions to foods in adults in relation to atopy, presence of mucus in the stools, swelling of joints and arthralgia in patients with gastrointestinal reactions to foods.

BACKGROUND: Food intolerance in adults is mostly associated with vague symptoms and not clearly related to atopy and food allergy. A combination of different pathogenetic mechanisms may be responsible for the symptoms. OBJECTIVE: The aim of this study was to describe patients with a history of food-related gastrointestinal symptoms in relation to the presence of mucus in the stools, joint swelling and arthralgia and to determine whether or not there is an association between the presence of these parameters, atopic disease and the presence of immune complexes in serum. METHODS: Fifty-eight patients consecutively referred to our clinic with food-related gastrointestinal symptoms were investigated. RESULTS: Thirty-five patients (60%) had mucus in their stools, 24 patients (41%) complained about joint swelling and 41 patients (71%) had arthralgia. There were no correlations between these parameters and atopy according to Phadiatope test or skin prick test (SPT). No correlations were found between the occurrence of mucus in the stools, arthralgia and joint swelling. There were significantly higher levels of circulating immune complexes in patients with a history of arthralgia compared with patients with no such history (P < 0.03) and the number of individuals with the presence of such immune complexes was higher among the patients with arthralgia than among the patients without. In general the patients did not relate the exposure to certain foods to symptoms like joint swelling, arthralgia and presence of mucus in the stools. However, there were significant positive correlations between food-related gastrointestinal symptoms in the following instances: chocolate-induced gastrointestinal symptoms and mucus in the stools (P = 0.006), vegetable-induced gastrointestinal symptoms and mucus in the stools (P = 0.002) and meat-induced gastrointestinal symptoms and mucus in the stools (P = 0.003). In a group of individuals without food-related symptoms investigated separately, a very low frequency of mucus in the stools, joint swelling and arthralgia was seen (none, two and three individuals of the 20 subjects, respectively). Of 41 patients with immediate onset of gastrointestinal symptoms, 20 were atopic according to Phadiatope and SPT. Of 11 patients with late onset of symptoms 10 were negative in Phadiatope and SPT (P < 0.05). The most frequently involved foods were fruits, vegetables, milk, fish and meat. CONCLUSION: The results suggest the involvement of different inflammatogenic mechanisms in food-related gastrointestinal symptoms.

Adolescent↗

Update in allergy testing in childhood asthma: how do you know whether you are successfully controlling the patient's inflammation?

The levels of serum eosinophil cationic protein (ECP) in asthmatic patients have been shown to be increased in acute and undertreated asthma as a result of inflammation. ECP is released during in vitro clotting of peripheral blood. The exposure of the atopic individual to an offending allergen stimulates the activation of the blood eosinophils and their release of ECP into serum. Serum ECP levels reflect avoidance of the allergen, and successful treatment of asthma inflammation with corticosteroids cause a reduction of the inflammation in the lung. When individual patients with asthma are followed, the level of serum ECP can be used (1) as an early indicator of the degree of inflammation, (2) for monitoring the efficacy of corticosteroid therapy, and (3) for possible noncompliance with treatment.

Anti-Inflammatory Agents↗

ADCC-mediating capacity in children with cow's milk protein intolerance in relation to IgG subclass profile of serum antibodies to beta-lactoglobulin.

In a previous study sera from children with cow's milk protein intolerance (CMPI) exhibiting gastrointestinal symptoms were found to efficiently induce antibody-dependent cell-mediated cytotoxicity (ADCC) to beta-lactoglobulin-coated cells. In contrast, sera from children with coeliac disease showed a low ADCC-mediating capacity, despite high levels of IgG anti-beta-lactoglobulin antibodies. The study described here was undertaken to evaluate whether differences in IgG subclass profile of anti-beta-lactoglobulin antibodies could explain the observed variations in the ADCC-mediating capacity. Forty-eight sera from the following groups of children were investigated: CMPI with predominantly gastrointestinal symptoms, CMPI with skin symptoms of immediate-onset, children with untreated coeliac disease and healthy references. Absorption experiments indicated that primarily IgG1 antibodies were responsible for the ADCC-mediating capacity of the sera. Accordingly, the ADCC reactivity of individual sera correlated with their IgG1 antibody levels. Sera from CMPI children with gastrointestinal symptoms, most of which had a high ADCC reactivity, also demonstrated a distinctive subclass pattern of their anti-beta-lactoglobulin antibodies with higher relative proportions of IgG1 (ratios: IgG1/IgG, IgG1/IgG3 and IgG1/IgG4) than those from the other diagnostic groups. Using logistic regression analysis, the diagnostic potential of ADCC as well as of different IgG subclass variables for the recognition of gastrointestinal symptoms caused by CMPI was evaluated. The ADCC reactivity of sera was found to be the best predictor in this model.

Antibody-Dependent Cell Cytotoxicity↗

Bronchial inflammation in chronic bronchitis assessed by measurement of cell products in bronchial lavage fluid.

BACKGROUND: Bronchial inflammation in chronic bronchitis has not been characterised as well as in asthma. The present study was undertaken to assess whether a characteristic pattern of bronchial inflammatory markers could be found in patients with chronic bronchitis. METHODS: Bronchoscopy with bronchial lavage was performed in 42 patients with chronic bronchitis and in 13 healthy controls. Twenty three of the patients had non-obstructive chronic bronchitis and 19 had chronic bronchitis and chronic obstructive pulmonary disease (COPD). Eighteen of the patients with bronchitis had recurrent infective exacerbations and 24 did not. Intrabronchial bacterial cultures were taken with a protected specimen brush. RESULTS: Increased activity of neutrophils, fibroblasts, and eosinophils was found in the patients with chronic bronchitis as assessed by the levels of myeloperoxidase (MPO) and interleukin-8 (IL-8), hyaluronan, and eosinophil cationic protein (ECP), respectively. The levels of tryptase did not differ from the controls. High correlations were found between the levels of MPO and IL-8, as well as ECP and IL-8. No differences were found between the patients with COPD and those with non-obstructive chronic bronchitis. CONCLUSIONS: Recruitment and activation of both neutrophils and eosinophils seem to be a characteristic of chronic bronchitis. This activation is associated with IL-8. The patients with intrabronchial cultures of Streptococcus pneumoniae had the highest individual levels of MPO, ECP, and IL-8 of all subjects in the study, indicating that colonisation with S pneumoniae could promote bronchial inflammation.

Adult↗

Eosinophil cationic protein and tidal flow volume loops in children 0-2 years of age.

Many children with recurrent wheezing in early childhood develop asthma. Objective parameters to describe different groups of wheezers are limited, but tidal flow volume (TFV) response to inhaled salbutamol has demonstrated differences between children with and without asthma. Also, eosinophil cationic protein (ECP) has been associated with declining lung function in older children. We therefore investigated whether lung function and serum ECP (s-ECP) could differentiate between groups of wheezy young children. TFV loops were measured in 79 awake children (mean age 14 months). Minimum two wheezy episodes (mean 3.2) or minimum 4 weeks persistent wheeze were reported in 41 children (cases), whereas the 38 controls had no history of wheeze. Airways responsiveness (change in ratio of time until peak expiratory flow to total expiratory time (tPEF/tE) after inhaled nebulized salbutamol) was measured in 26 cases and 24 controls. Serum ECP and serum myeloperoxidase (s-MPO) were measured in all children. Cases had significantly lower mean tPEF/tE (0.21) than controls (0.33), and higher mean s-ECP (21.9 micrograms.L-1) than controls (14.0 micrograms.L-1). Serum ECP (but not s-MPO) correlated significantly with the percentage change in tPEF/tE from baseline (r = 0.7), but not with initial tPEF/tE. Serum ECP increased significantly with increasing immunoglobulin E (IgE), airways responsiveness and eosinophil count, but decreased with increasing age. TFV responsiveness to salbutamol and s-ECP levels correlate strongly, both probably reflecting airways inflammation, and may possibly be valuable prognostic tools in recurrent wheezy infants and toddlers.

Albuterol↗

Bystander suppression of the immune response to human serum albumin in rats fed ovalbumin.

Bystander suppression of delayed-type hypersensitivity (DTH) and the antibody response to human serum albumin (HSA) were studied in young normal rats and in young rats made partially tolerant to ovalbumin (OVA) by feeding an OVA-containing diet for 4 weeks from weaning. At 2 months of age, the animals were intracutaneously immunized with a mixture of OVA and HSA in Freund's complete adjuvant (FCA) at one site of the back, or separately at two different sites on the back. All rats made orally tolerant to OVA showed a significantly reduced IgE and IgG anti-OVA antibody production and DTH response to OVA, compared to the controls. OVA-fed rats subsequently immunized with a mixture of OVA + HSA had significantly lower IgE and DTH responses to HSA than the controls. When rats were immunized with OVA and HSA at two different sites, however, there was no difference in the response to HSA between the OVA-fed rats and the control rats, which rules out the possibility of shared epitopes between the antigens. Ear-challenge with the mixture of OVA + HSA gave a significantly lower DTH reaction in the tolerant rats immunized with a mixture of the antigens, compared to the control rats. However, suppression of the DTH reaction was not seen when tolerant and control rats were immunized with HSA alone and challenged with the mixture of OVA + HSA in one ear. These results present evidence that young rats orally tolerant to one antigen show a suppressed T-cell and antibody response to an unrelated antigen, provided that the two antigens are given in a mixture during the inductive phase. There was no evidence for bystander suppression of the T-cell response at the effector site.

Animals↗