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Biomedical subjects

P I Gaarder

Publications and source records attributed to P I Gaarder.

At least 19 recordsLinked to original sources
PubMed2003

The relationships between dehydroepiandrosterone sulphate (DHEAS), the intensity of Schistosoma mansoni infection and parasite-specific antibody responses. A cross-sectional study in residents of endemic communities in north-east Ethiopia.

There are speculations that the puberty-related hormone dehydroepiandrosterone sulphate (DHEAS) might influence the intensity of infection and immune responses during Schistosoma infections. We studied the relationships between DHEAS, intensity of Schistosoma mansoni infection and humoral immune responses in 135 residents of Ethiopia. Serum levels of eight antibody isotypes against worm and egg antigens were determined by ELISA. DHEAS was measured with an immunoluminometric assay. There was a significant negative correlation between serum levels of DHEAS and intensity of S. mansoni infection. A significant increase in serum levels of DHEAS in the age group 15-19 years was accompanied by a progressive decline in the intensity of infection. Peak level of DHEAS coincided with the lowest intensity of infection in the age group 20-29 years. Multiple regression analysis showed that DHEAS alone had a significant (p<0.0001) negative effect when the effect of age was removed. Age also had a significant (p<0.0001) negative effect on the intensity of infection, after removing the effect of DHEAS. The two predictive variables accounted for 34.4% of the decline in the intensity of infection. Age accounted for 24.9%, whereas DHEAS accounted for 15.2% when the effect of each of the variables was removed. DHEAS had significant negative effects on AWA-specific IgG (p=0.02) and IgG1 (p=0.018) and SEA-specific IgG1 (p=0.009), after adjusting for the effect of age.

Adolescent↗
PubMed2002

Differences in prevalence, intensity of infection and parasite-specific antibody levels do not predict different age-infection profiles.

Acquired immunity is believed to influence the age-infection profile of Schistosoma infections. We compared antibody responses against Schistosoma mansoni adult worm antigen (AWA) and soluble egg antigen (SEA) in 164 residents of two communities with different levels of infection. IgG, IgA, IgM, IgE, and IgG subclass 1 to 4 antibodies were determined by ELISA. Seventy-five of the subjects were from Harbu, an area with a prevalence of 39% and an intensity of infection of 116 eggs per gram of stool (EPG), whereas 89 subjects were from Bati, with a prevalence of 66% and intensity of infection of 256 EPG. In both communities the prevalence and the intensity of infection were highest in the age group 10-14 years, although both were significantly higher in Bati than in Harbu. Mean levels of AWA-specific IgA, IgM, IgG, IgG1 and IgG2, and of SEA-specific IgG, IgM, IgG2 and IgG3 were significantly higher in Bati than in Harbu. However, mean levels of IgE against worm and egg antigens were significantly higher in Harbu than in Bati. Significant differences were detected in the levels of IgA, IgE, IgG, IgM, IgG1 and IgG2 against AWA, and in IgE, IgM, IgG2 and IgG3 against SEA according to the place of residence. The levels of anti-AWA IgG, IgG1 and IgG2 and anti-SEA IgG, IgG1 and IgG4 were significantly associated with the intensity of infection. Anti-AWA IgM levels were associated with age, whereas sex and age had interacting effects on the levels of AWA-specific IgG1 and SEA-specific IgG and IgM. Antibody responses exhibited different age-related patterns in the two communities. This may indicate that differences in history of exposure influence the evolution of immune responses. However, the study did not support the view that differences in antibody levels between communities subject to different levels of infection result in a systematic deviation in age-infection profile (the "peak shift").

Adolescent↗
PubMed2001

Fine particles of widely different composition have an adjuvant effect on the production of allergen-specific antibodies.

Diesel exhaust particles (DEP) are reported to increase the specific IgE response to allergens, and results from our laboratory suggest that the particle core of DEP contribute to this adjuvant activity. The purpose of the present study was to explore further the adjuvant effect of particles per se, that is particles by themselves. NIH/Ola mice were given two intraperitoneal injections with ovalbumin (OVA; 10 microg) alone or OVA in combination with PSP, polytetrafluoroethylene (teflon), titanium dioxide (TiO(2)) or amorphous silica particles (2.8x10(10)-2.8x10(12)). Blood samples were drawn 7 days after the last injection, and serum levels of allergen-specific and total IgE and IgG2a were measured. All types of particles gave increased levels of allergen-specific IgE and IgG2a. Similar results were obtained after intranasal or intratracheal instillation with OVA plus PSP or silica. Our results indicate that fine particles of widely different composition may have an adjuvant effect on the production of allergen-specific antibodies.

Adjuvants, Immunologic↗
PubMed2001

IgE adjuvant effect caused by particles - immediate and delayed effects.

Diesel exhaust particles are reported to increase the specific IgE response to ovalbumin (OVA) and pollen. Evidence has been provided that the particle core contributes to this adjuvant activity. The purpose of our study was to investigate the effect of well-defined simple particles, polystyrene particles (PSP), on the production of allergen-specific IgE in a mouse model. The IgE adjuvant effect of PSP was investigated in experiments using intranasal (i.n.) instillation, intratracheal (i.t.) instillation or intraperitoneal (i.p.) injection. Delayed and cumulative adjuvant effects were investigated by giving mice i.p. injections with PSP 1-3 days, or on 4 consecutive days before OVA, respectively. The levels of allergen-specific and total IgE were measured. Irrespectively of immunisation route and protocol, OVA in combination with PSP elicited increased levels of both allergen-specific and total IgE when compared with OVA alone. Therefore, in the experimental model, particles were found to augment the specific IgE response to an allergen even when the allergen was introduced several days after the particles. These findings imply that individuals exposed to particulate air pollution at one point of time may develop an increased reaction towards allergens inhaled later that day or even several days after the particle exposure.

Adjuvants, Immunologic↗
PubMed2001

Exposure to pets and atopy-related diseases in the first 4 years of life.

BACKGROUND: It is still unclear how early-life exposure to pets is related to children's risk of developing atopy-related diseases. We estimated associations between early-life exposure to pets and atopy-related diseases at 0-4 years of life in a cohort of Norwegian children. METHODS: A population-based cohort of 2531 children born in Oslo, Norway, was followed from birth to the age of 4 years. Information on early-life exposure to pets, a number of possible confounders, and atopy-related diseases was mainly collected by questionnaire. RESULTS: In logistic regression analysis adjusting for potential confounders, the odds ratio for being exposed to pets in early life (reference category: not exposed) was, for bronchial obstruction at 0-2 years of life, 1.2 (95% confidence interval 0.9, 1.8); for asthma at the age of 4 years, 0.7 (0.5, 1.1); for allergic rhinitis at the age of 4 years, 0.6 (0.4, 1.0); and for atopic eczema at 0-6 months of life, 0.7 (0.5, 0.9). CONCLUSIONS: The results indicate that early-life exposure to pets or lifestyle factors associated with exposure to pets reduce the risk of developing atopy-related diseases in early childhood. However, these findings might also be explained by selection for keeping pets.

Animals↗
PubMed2001

Age- and sex-related differences in antibody responses against Schistosoma mansoni soluble egg antigen in a cohort of school children in Ethiopia.

Acquired immunity is believed to be the main factor in the age-related differences in prevalence and intensity of Schistosoma infections. We studied antibody responses against S. mansoni soluble egg antigen (SEA) by ELISA in children before treatment, 5 weeks and one year after treatment. After screening for S. mansoni infection, positive children were treated with praziquantel (40 mg per kg body weight). Infection rate was significantly higher in boys younger than 12 years than in girls in the same age group. Levels of all antibody isotypes, except IgG1 (before treatment) or IgA (one year after treatment), were higher in children older or equal to 12 years than in those younger. The difference between age groups was significant for IgE, IgM, IgG3 and IgG4 (before treatment) and IgE (one year after treatment). Similarly, all antibody isotypes, except IgE, before treatment were higher in boys than in girls. At 5 weeks after treatment, IgG, IgE and IgG1 showed an increasing tendency, whereas IgM and IgG3 tended to decrease. One year after treatment, significant decreases were observed in IgG, IgG1 and IgG4 and a significant increase in IgG2 levels. The study presents further evidence for the difference in acquired immunity between younger and older children, and between boys and girls. The study also suggests that praziquantel differentially affects antibody responses against S. mansoni SEA.

Adolescent↗
PubMed2000

The amino acid sequence of a monoclonal gamma 3-heavy chain from a patient with articular gamma-heavy chain deposition disease.

Abnormal deposition of proteins, including monoclonal immunoglobulin gamma-heavy chains, may cause tissue damage and organ dysfunction. We here report the amino acid sequence of the free gamma-heavy chains present in serum and urine of the first reported case (patient G. L.) of synovial heavy chain deposition disease. The protein was heavily deleted and consisted of the hinge, in addition to the CH2 and CH3 domains, in a dimeric form, thus lacking its variable domain as well as the CH1 domain. The sequence was consistent with the gamma 3 subclass (gamma 3GL). Gm typing revealed the gamma 3 allotypes G3m(b0) and G3m(b1) in accordance with the residues Pro123, Phe128, Thr171 and Phe268 in gamma 3GL. Furthermore, the gamma 3GL molecule was glycosylated at Asn in position 129. Finally, the gamma 3GL protein was shown to contain a typical binding site for the first complement component, C1q, namely the residues Glu150, Lys152 and Lys154, with the potential of binding and activating complement, causing tissue damage following deposition.

Amino Acid Sequence↗
PubMed2000

The adjuvant effect of particles-importance of genetic background and pre-sensitisation.

BACKGROUND: We have previously reported that simple and well-characterised particles, such as polystyrene particles (PSP), have an IgE adjuvant effect in mice. The purpose of this study was to explore the importance of genetic background concerning the adjuvant effect of PSP in different strains of mice. METHODS: Inbred NIH/Ola, BALB/c and C3H/HeJ mice were given two intraperitoneal injections with either PSP plus OVA or OVA alone, and then an intraperitoneal challenge with OVA alone. NIH/Ola mice were also pre-sensitised to develop a weak or strong IgE response to OVA, and then given an intraperitoneal challenge with PSP plus OVA or OVA alone. Serum levels of total and allergen-specific IgE and IgG2a were measured. RESULTS: PSP had a specific IgE and IgG2a adjuvant effect in NIH/Ola mice but not in C3H/HeJ and BALB/c mice. Weakly pre-sensitised NIH/Ola mice showed the same response pattern as the naive NIH/Ola mice. In contrast, strongly pre-sensitised mice showed an antibody response pattern similar to that of high-responder BALB/c mice. CONCLUSIONS: Our results indicate that the allergen responder status, either genetic or induced, is of importance for the adjuvant effect from particles. The IgE and IgG2a adjuvant effect may depend on the genetically determined susceptibility of an individual to be influenced by exposure to the adjuvant. Therefore, the allergy-enhancing effect from particle pollution may differ between individuals.

Adjuvants, Immunologic↗
PubMed2000

Renal and immunologic markers for chloralkali workers with low exposure to mercury vapor.

OBJECTIVES: The aim of this study was to investigate renal function and immunologic markers among chloralkali workers with long-term low exposure to mercury vapor. METHODS: Forty-seven currently exposed workers were compared with reference workers matched for age in a cross-sectional design. RESULTS: The mean urinary mercury concentration was 5.9 (range 1.1-16.8) nmol/mmol creatinine (Cr) for the exposed workers and 1.3 (range 0.2-5.0) nmol/mmol Cr for the referents. The chloralkali workers had been exposed for an average of 13.3 (range 2.8-34.5) years. The activity of N-acetyl-beta-D-glucosaminidase in urine (U-NAG) was higher in the exposed workers (mean 0.18 U/mmol Cr versus 0.14 U/mmol Cr, P=0.02). Associations between current urinary mercury, cumulative urinary mercury, and cumulative urinary mercury per year (intensity) and U-NAG, autoantibodies to myeloperoxidase (anti-MPO) and proteinase 3 in serum, respectively, were observed. The activity of U-NAG and anti-MPO was increased in the workers with the highest exposure, as assessed by their mean intensity of exposure. The highest activity of U-NAG was observed in the exposed workers with the lower concentrations of selenium in whole blood. CONCLUSIONS: The study indicates an effect of exposure on the kidney proximale tubule cells, possibly modified by individual selenium status, and an effect mediated by neutrophil granulocytes.

Acetylglucosaminidase↗
PubMed1999

Interleukin-13 and human immunoglobulin E production in severe combined immunodeficiency mice transplanted with human peripheral blood lymphocytes.

As normal mice do not respond to interleukin-13 (IL-13), we have used mice with severe combined immunodeficiency transplanted with human peripheral blood lymphocytes (hu-PBL-SCID mice) as an in vivo model for studying human IL-13. PBL from three donors (two allergic and one non-allergic) were prestimulated with IL-13 in vitro and thereafter transplanted into SCID mice. As evidenced by flow cytometry, IL-13 in the in vitro cell cultures was physiologically active and suppressed CD14 expression, while it enhanced the expression of CD23 on human monocytes. In the in vivo experiments, SCID mice transplanted with cells from both allergic donors produced twice as high maximum levels of IgE when the cells were preincubated with IL-13 in vitro before transplantation, as compared with mice receiving cells that had not been preincubated with IL-13. Two succeeding intraperitoneal (i.p.) injections of IL-13 resulted in a further increase of maximum IgE levels. Using cells from the non-allergic donor, no enhancing effect of IL-13 was observed. Transplanted human cells from one allergic donor examined were shown to migrate to the spleen and lungs of the recipient mice, while cells from the non-allergic donor were found only in the peritoneal cavity. Altogether, our results indicate that IL-13 enhances human IgE production in vivo and suggest that lymphocytes in allergic individuals are hyper-reactive to this cytokine. Furthermore, the allergic status of the cell donor may affect migration and engraftment of cells transplanted into SCID mice.

Animals↗
PubMed1998

Airborne house dust elicits a local lymph node reaction and has an adjuvant effect on specific IgE production in the mouse.

Indoor suspended particulate matter (SPM) consists of many different types of particles, the vast majority of which are less than 2.5 microm in diameter. An important question is how these particles, being inhalable, contribute to asthma and respiratory symptoms. One possibility is that these particles have an adjuvant effect on the immune response and increase the IgE production, or cause a non-specific irritation in the airways, contributing to bronchial hyper-responsiveness. In this study, the adjuvant activity of indoor SPM on the response to the model allergen ovalbumin (OA) in BALB/c mice was investigated, using the popliteal lymph node (PLN) assay. The adjuvant activity on the local lymph node response was determined by measuring the PLN weight, cell numbers and cell proliferation, and the adjuvant activity on the IgE production by measuring the levels of serum IgE specific to OA. SPM was found to give a significant PLN response, both when injected alone and together with OA. SPM was also found to enhance the production of specific IgE to OA when injected together with OA, after reinjection with OA, compared with immunisation with OA alone.

Animals↗
PubMed1998

Human IgE production in hu-PBL-SCID mice injected with birch pollen and diesel exhaust particles.

Mice with severe combined immunodeficiency were transplanted with human peripheral blood lymphocytes (hu-PBL-SCID mice). The response to immunisation with birch pollen was used to study possible effects of diesel exhaust particles (DEP) and aluminium hydroxide (Al(OH)3) on human IgE production in this human in vivo model. The adjuvants were well tolerated, as determined by the number of human cells in the peritoneal cavity at the end of the experiments. Total and birch pollen-specific IgE was detected in 76 and 41% of the mice, respectively. In the present experiments where the mice were stimulated early with birch pollen, a doubling in percentage of hu-PBL-SCID mice with production of specific IgE was observed, as compared to later stimulation used in previous experiments. Although a tendency to higher total IgE levels was observed after treatment with DEP, no statistically significant adjuvant effect of DEP or Al(OH)3 could be demonstrated. Electron microscopy analysis after immunogold labelling showed that the major birch pollen allergen Bet v I was released from the pollen grains and adsorbed to the surface of the DEP. Early stimulation with allergen appears to be important for optimal production of specific IgE in the hu-PBL-SCID model. However, our results show that further improvements are needed in order to demonstrate the expected effects from adjuvants and environmental pollutants.

Allergens↗
PubMed1998

Airborne house dust particles and diesel exhaust particles as allergen carriers.

BACKGROUND: Indoor suspended particulate matter (SPM) consists of many different types of particles, the vast majority of which are less than 2.5 microm in diameter. The question arises how these particles may contribute to asthma and respiratory symptoms. One possibility is that airborne dust particles act as carriers of allergens into the airways, as several allergens have been found to be associated with inhalable airborne dust particles. OBJECTIVE: We studied the presence of three different allergens on the surface of SPM, i.e. Can f 1 (dog), Bet v 1 (birch pollen) and Der p 1 (house dust mite). We also examined the ability of diesel exhaust particulates (DEP) to attach these allergens and Fel d I (cat) in vitro. METHODS: SPM was collected on polycarbonate filters and an immunogold labelling technique was used to detect the allergens on the particles. The specimens were examined in the backscatter mode of a scanning electron microscope. The same technique was used to examine the binding of the allergens to DEP, after exposing DEP to either crude allergen extracts or partly purified allergens. RESULTS: Both Can f 1 and Bet v 1 allergens were detected on the surface of the soot particles in SPM mixtures, although to a lesser degree than previously found with Fel d 1. Der p 1 (house dust mite), however, did not show any significant binding to SPM particles. Furthermore, DEP had the ability to adsorb all four allergens in vitro, although to a varying extent. CONCLUSION: Soot particles in airborne house dust may act as carriers of several allergens in indoor air. Furthermore, DEP has the ability to bind all the four allergens investigated under aqueous conditions in vitro.

Air Pollutants↗
PubMed1998

Mite-allergen levels in Norwegian homes.

The scarce data published on mite sensitization and mite-allergen levels in Norway indicate that the mites may not be of the same importance in allergic disease in Norway as in countries such as the UK and the rest of Europe. The problem also involves the low allergen levels and small amounts of dust collected for allergen determination, and when the level is to be expressed as mg/g, the lower detection limit will often vary from sample to sample, giving within the same investigation results such as <0.2 microg/g, <0.5 microg/g, and even <2.0 microg/g. The use of allergen levels expressed instead per area (microg/m2) at least results in a uniform lower detection limit, making statistical analysis easier.

Animals↗
PubMed1998

Residential dampness problems and symptoms and signs of bronchial obstruction in young Norwegian children.

To assess the role of dampness problems and house dust mite exposure in the development of bronchial obstruction in early life, a cohort of 3,754 children born in Oslo during 1992 and 1993 was followed for 2 yr. Bronchial obstruction was defined as two or more episodes with symptoms and signs of obstruction or one lasting 1 mo or more. A matched case-control study was carried out in 251 cases of bronchial obstruction (response rate: 98%) and their 251 paired controls. Information on home dampness problem(s), house dust mite exposure, and potential confounders was collected during home visits and by questionnaires. Dampness problems were confirmed in the homes of 27% of the cases and 14% of the controls, while a concentration of Dermatophagoides pteronyssinus allergens > 2 microg/g dust was found in the beds of 11 (4.5%) cases and three (1.2%) controls. In conditional logistic regression analysis controlling for potential confounders, confirmed dampness problems increased the risk of bronchial obstruction (adjusted odds ratio: 3.8; 95% confidence interval: 2.0-7.2). Exposure to D. pteronyssinus allergens > 2 microg/g dust increased the risk of bronchial obstruction (adjusted odds ratio: 2.8; 95% confidence interval: 0.7-11.7). Residential dampness problems in Oslo dwellings seem to increase symptoms and signs of bronchial obstruction in young children, apparently without increasing their exposure to house dust mites.

Airway Obstruction↗
PubMed1997

Diesel exhaust particles and carbon black have adjuvant activity on the local lymph node response and systemic IgE production to ovalbumin.

The possible adjuvant effect of diesel exhaust particles (DEP) on the response to the model allergen ovalbumin (OA) was studied in BALB/c mice using the popliteal lymph node (PLN) assay. In addition to changes in PLN weight, cell numbers and cell proliferation, specific serum IgE anti-OA antibody levels were measured. OA inoculated together with DEP into one hind footpad gave a significantly augmented response (increase in weight, cell numbers and cell proliferation) in the draining popliteal lymph node as compared to DEP or OA alone. Also, the local lymph node response was of longer duration when DEP were given with the allergen. Experiments in thymus-deficient nu/nu mice indicated that the lymph node response observed in BALB/c mice was of a specific immunologic character and not an unspecific inflammatory reaction. The OA-specific IgE response was increased in mice receiving OA together with DEP as compared to the response in mice receiving OA without DEP. Carbon black (CB) was given with and without OA in some experiments, as a surrogate for the non-extractable core of DEP. CB was found to resemble DEP in its capacity to increase the local lymph node response and serum specific IgE response to OA, but CB appeared to be slightly less potent than DEP. Thus, both DEP and CB had a significant adjuvant effect on the local immune-mediated inflammatory response and on the systemic specific IgE response to allergen. The results indicate that the non-extractable particle core contributes substantially to the adjuvant activity of DEP.

Adjuvants, Immunologic↗
PubMed1997

Total and birch pollen-specific human IgE in mice with severe combined immunodeficiency transplanted with human peripheral blood lymphocytes: donor dependence, seasonal variation and in vivo half-life.

BACKGROUND: There is a need for animal in vivo models in the study of human allergy. The aim of the present experiments was to study production and catabolism of human IgE in mice with severe combined immunodeficiency transplanted with human peripheral blood lymphocytes (hu-PBL-SCID mice). METHODS: Groups of SCID mice were transplanted intraperitoneally with hu-PBL from the same three donors in five experiments. Subgroups of transplanted mice were immunized with birch pollen. Production of human total and birch pollen-specific IgE in the hu-PBL-SCID mice was analyzed over a 7-week period. RESULTS: Human IgE was detected in 93% of the hu-PBL-SCID mice, and the production showed reproducible donor-dependent kinetics. Production of birch pollen-specific human IgE, however, was seen only in mice transplanted with cells from birch pollen-allergic donors. A greater proportion of the mice produced specific IgE when the experiment was started in, or some months after a birch pollen season with high pollen counts. The half-lives of passively transferred human IgE were determined to be 24.0 and 23.4 h for total and birch pollen-specific IgE, respectively. CONCLUSIONS: This study demonstrates that human IgE production in hu-PBL-SCID mice is very reproducible when the same donor is used several times. Specific IgE production in recipient mice seems to require the use of cell donors with the actual specific allergy, and is most readily obtained during or after a period of donor allergen exposure. The short half-lives found indicate that hu-PBL-SCID mice have a high ongoing production of human IgE.

Allergens↗