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Biomedical subjects

L A Hanson

Publications and source records attributed to L A Hanson.

At least 19 recordsLinked to original sources

Expression of idiotypic antibodies-1 and -2 and breastfeeding in relation to antibody levels against Haemophilus influenzae type B in children.

The aim of the study was to determine the concentrations of serum antibodies against Haemophilus influenzae type b in preschool children in relation to the distribution of idiotypic antibodies 1 and 2 (Id-1 and Id-2) and the exposure to breastfeeding in infancy. Sera were obtained from 74 control children recruited in an earlier case-control study before the introduction of general Hib vaccination. Duration of breastfeeding was monitored, and prevalence of noninvasive infections was registered. Concentrations of IgG1 and IgG2 anti-Hib, as well as of total Id-1 and Id-2, were determined in ELISA. The expression of Id-1 antibodies increased with age in contrast to the Id-2 antibodies that were found only in children up to 24 months of age. Expression of Id-1 antibodies was positively correlated with higher anti-Hib levels of both the IgG1 and IgG2 isotype. Children expressing Id-2 antibodies showed higher IgG2 anti-Hib concentrations than those who did not have Id-2 (P = 0.001). The concentrations of neither Id-1 nor Id-2 antibodies were related to the duration of breastfeeding. Duration of breastfeeding was related to increased anti-Hib IgG2 in healthy children above 18 months of age. These study shows that the expression of idiotype-1 and idiotype-2 antibodies was associated with higher IgG2 anti-Hib concentration and that breastfeeding could enhance the anti-Hib IgG2 production in children.

Antibodies, Bacterial↗

Perinatal essential fatty acid deficiency influences body weight and bone parameters in adult male rats.

Fetal and postnatal nutrition have long-term effects on the risk for development of diseases late in life in humans and animals. The aim of the present study was to investigate the effect of dietary deficiency of essential fatty acids (EFA) in the perinatal period on later body weight and bone mass. During late gestation and throughout lactation, rats were fed a control or an EFA-deficient (EFAD) diet. At 3 weeks of age the offspring were weaned onto an ordinary chow and followed until adult age. The mean body weight of adult rats receiving the EFAD diet during the perinatal period was significantly increased from 12 weeks of age compared to the controls (P<0.05). Analysis by peripheral quantitative computerized tomography (pQCT) at 44 weeks of age showed that the trabecular volumetric bone mineral density (BMD) of the femur was significantly decreased (P<0.05) but the cortical bone mineral content, cortical area, and cortical thickness were increased (P<0.05) in the EFAD group of rats. The length of the femur was not affected. In conclusion, neonatal EFA deficiency was in adult rats associated with increased body weight and significant changes in both cortical and trabecular bone. The results indicate that regulatory mechanisms related to bone mass seemed to be programmed by EFA in the perinatal period. The nature of this modulation needs to be identified.

Animal Feed↗

Antibody response to the Haemophilus influenzae type b-tetanus toxoid conjugate vaccine in healthy and infection-prone individuals with IgG3 subclass deficiency.

Searching for a possible explanation for the phenotypic heterogeneity in IgG3 deficiency, we studied the antibody response to a polysaccharide and a protein antigen in IgG3-deficient (IgG3d) adults after vaccination with Haemophilus influenzae type b capsular polysaccharide (Hib CP) conjugated to tetanus toxoid. Distribution of isotypes, idiotypes, clonotypes, and Gm allotypes were compared. All the vaccinated individuals, irrespective of the level of IgG3 and proneness to infections, developed protective levels of anti-Hib CP. Significantly lower prevaccination levels of IgG2 (p < 0.05) and IgG4 anti-Hib CP (p < 0.04 and p < 0.03) were noted among the infection-prone compared to the healthy IgG3d individuals and/or controls. Seventy percent of the IgG3d patients and none of the controls had the low responding Gm(ga-n/ga-n) genotype, while the majority of the controls had the alternative Gm(bfn/bfn) genotype. The conjugate ACT-HIB vaccine efficiently overcomes the IgG3 subclass deficiency state and the genetic predisposition for lower responsiveness, providing protection against Hib and tetanus infections. The proneness to infection in some IgG3d individuals may relate to their low prevaccination antibody levels.

Enzyme-Linked Immunosorbent Assay↗

Dietary n-6:n-3 fatty acid ratio in the perinatal period affects bone parameters in adult female rats.

PUFA and their metabolites are important regulators of bone formation and resorption. The effect of PUFA on bone growth may be especially striking during the perinatal period. The aim of the present study was to investigate the effect of diets with different n-6:n-3 fatty acid (FA) ratios during the perinatal period on bone parameters in the adult offspring. During late gestation and throughout lactation, rat dams were fed an isoenergetic diet containing 70 g linseed oil (n-3 diet), soyabean oil (n-6+n-3 diet) or sunflower-seed oil (n-6 diet) per kg with n-6:n-3 FA ratios of 0.4, 9 and 216, respectively. The offspring were weaned onto an ordinary chow and followed until 30 weeks of age. Bone parameters were analysed using peripheral quantitative computerised tomography and dual-energy X-ray absorptiometry. Femur length and cortical cross-sectional bone area and bone mineral content were significantly higher in the n-6+n-3 group than in the other groups. Cortical bone thickness in the n-6+n-3 group was increased compared with the n-3 group, but most cortical bone parameters did not differ between the n-3 and n-6 groups. The results suggest that regulatory mechanisms were influenced by the n-6:n-3 FA ratio early in life and not compensated for by the introduction of an ordinary diet after weaning.

Animals↗

Feeding patterns, diarrhoeal illness and linear growth in 0-24-month-old children.

The aim was to study the impact of simple healthcare interventions in 0-24-month-old children living in rural communities outside Lahore, Pakistan. Newborns belonging to four birth cohorts were followed monthly from 0-24 months of age living in rural communities. Three cohorts were from the same village: Cohort A (1984-1987), n = 485; Cohort B (1990-1992), n = 544; and Cohort C (1995-1997), n = 518. A fourth, Cohort D, was from neighbouring villages (1995-1997), n = 444. Findings from Cohort A formed the basis of a healthcare programme, including promotion of optimal breastfeeding practices, advice on oral rehydration therapy, and continued feeding during diarrhoea. The outcome measures studied were time of initiation of breastfeeding, feeding of prelacteals, exclusive breastfeeding, diarrhoeal illnesses, and postnatal linear growth. The median time of initiation of breastfeeding decreased from 47 to 3 h and exclusive breastfeeding increased from 5 per cent in Cohort A to more than 80 per cent in the subsequent cohorts, at 1 month of age. No prelacteals were given to 34 per cent of newborns in later cohorts compared with 100 per cent in Cohort A. Diarrhoeal illnesses during the first 6 months had reduced significantly. Postnatal linear growth improved by about 3 cm in the later cohorts. Appropriate changes in breastfeeding practices through integrated and focused healthcare, especially antenatally, can reduce diarrhoeal illnesses, and sustain and improve linear growth in young children.

Breast Feeding↗

Aberrant IgG2 antibody response to Neisseria meningitidis polysaccharide A after vaccination in frequently infected compared to healthy IgA-deficient individuals.

In search for a possible explanation of the phenotypic heterogeneity in selective immunoglobulin (Ig)A deficiency, we studied the IgG2 antibody response to meningococcal polysaccharide A (PSA) in IgA-deficient (IgAd) individuals after vaccination with meningococcal A + C polysaccharide vaccine. Two groups of IgAd individuals, one frequently infected and one clinically apparently healthy, as well as healthy controls, were studied. In response to meningococcal A + C polysaccharide vaccine, a significant titre increase of specific IgG2 anti-PSA was found in 71% of the control individuals, in 50% of the healthy and in 42% of the infection-prone IgAd individuals. The specific IgG2 response against meningococcal PSA was significantly lower in the infection-prone IgAd individuals compared to the controls (P < 0.05). Among the IgAd individuals who responded with a significant IgG2 antibody increase, the IgG2 antibody response was significantly lower in the infection-prone than in the healthy IgAd individuals (P < 0.05). Thus, a limited capacity to mount a specific IgG2 response may suggest a more profound antibody maturation defect in infection-prone IgAd patients compared to healthy IgAd individuals.

Adult↗

Haplotypes of the interleukin-4 receptor alpha chain gene associate with susceptibility to and severity of atopic asthma.

BACKGROUND: Development of asthma is likely to depend on a complex interaction between environmental and genetic factors. Several groups have suggested the gene of the IL-4 receptor alpha chain (IL4R) as a candidate gene for the development of asthma, although association with single polymorphisms has shown contradicting results. OBJECTIVE: We chose to analyse IL4R gene haplotypes and assess their possible relevance in susceptibility to asthma and to certain clinical phenotypes. METHODS: IL4R gene haplotypes were analysed, based on the three markers C-3223T, Q551R and I50V, using the expectation-maximization algorithm, in 170 atopic asthma patients and 350 controls, all adult Swedish Caucasians. RESULTS: Our data showed significantly higher levels of soluble IL-4R (sIL-4R) in asthma patients compared with controls (P<0.0001). Furthermore, we showed a significant association between the IL4R haplotype containing the alleles T-3223, V50 and R551 (TVR) of the IL4R gene, and susceptibility to atopic asthma, with a frequency of 6.5% in the patients compared with 1% in the controls (P<0.0005). A subgroup of patients with heterozygous or homozygous state for the T-3223, V50 and R551 alleles, also had lower levels of sIL-4R in their circulation compared with patients with homozygous state in the C-3223, I50 and Q551 alleles (P<0.05) and showed less severe asthma according to lung function test (P<0.05). Analysis of single markers showed the T-3223 IL4R allele to associate with lower serum levels of sIL-4 receptor (P<0.0001) and patients carrying the T allele also had more symptoms of active asthma (wheezing, P<0.01; coughing, P<0.05 and breathing difficulties, P<0.01). CONCLUSION: Our data suggest that asthmatic patients with low levels of sIL-4 receptor may represent a genetically distinct subgroup of atopic asthma. TVR haplotype analyses confirm the importance of IL4R as a candidate gene for susceptibility to asthma. This finding may have implications for the understanding of the pathogenesis of asthma and possibly for the development of more specific therapies.

Adolescent↗

The ratio of n-6 to n-3 fatty acids in maternal diet influences the induction of neonatal immunological tolerance to ovalbumin.

Prevalence of allergy is increasing in many countries and might be related to changed environmental factors, such as dietary fatty acids (FA). The present study investigates whether dietary ratio of n-6 to n-3 FA influences the induction of immunological tolerance to ovalbumin (OA) in neonatal rats. During late gestation and throughout lactation Sprague-Dawley rats were fed a diet containing 7% linseed oil (n-3 diet), sunflower oil (n-6 diet) or soybean oil (n-6/n-3 diet). At 10-16 days of age the rat offspring were subsequently exposed, or not, to OA via the milk. The offspring were weaned onto the same diets as the mothers and immunized with OA and the bystander antigen human serum albumin (HSA). In the offspring on the n-3 diet exposure to OA via the milk resulted in lower delayed type hypersensitivity reaction (DTH) and antibody responses against both OA and HSA, compared to those in the offspring not exposed to OA, indicating the induction of oral tolerance. In the offspring on the n-6 diet, the exposure to OA led to depressed specific immune responses against only OA, not HSA. In the offspring on the n-6/n-3 diet oral exposure to OA did not influence immune responses against OA, or HSA. The results indicate that the dietary ratio of n-6/n-3 FA is important for the induction of neonatal oral tolerance. Thus nonoptimal feeding may have effects on the development of immunological tolerance to dietary antigen ingested by the mother. The ratio of n-6/n-3 FA in the diet may be considered in the context of increased prevalence of allergy.

Animals↗

Protective effects of breastfeeding against urinary tract infection.

UNLABELLED: Protective factors in human milk act on mucosal membranes in the upper and lower respiratory tract and in the gastrointestinal tract. The way in which breastfeeding may reduce the risk of infections in a more remote site such as the urinary tract will be elucidated. CONCLUSION: The protective effect of breastfeeding on the urinary tract illustrates the complexity of the immune defence mechanisms responsible for such an action.

Breast Feeding↗

Induction of anti-secretory factor in human milk may prevent mastitis.

AIM: The aim of the study was to try to induce anti-secretory factor (AF) in human milk and possibly prevent mastitis. METHODS: Forty mothers who had normal deliveries and healthy full-term infants were randomly divided into two groups, 3-7 days postpartum. The experimental group received a food inducing AF. The control group received the same type of food, without AF-inducing properties. Milk was tested for AF after the mothers had eaten the cereals for 4-5 wk. AF was determined by intravenous injection of milk samples into rats measuring their capacity to prevent secretion into a gut loop of the rat injected with cholera toxin. RESULTS: The median levels of AF differed between the experimental (n = 12) and control groups (n = 16): 1.1 (0.7-1.25) units vs 0.1 (0.0-0.25) units, Z = -4.492, p < 0.0001 (11 mothers dropped out and one milk sample is missing from one of the control mothers). The frequency of mastitis in the experimental compared with the control group was reduced (p = 0.0086, permutation test). The median AF levels in mothers with or without mastitis differed; 0.0 (0.0-0.1) vs 0.5 (0.2-1.1), Z = -2.399, p = 0.017. CONCLUSION: We suggest a specially treated cereal induces AF in human milk and protects against clinically manifested mastitis.

Adult↗

Association of -1087 IL10 and -308 TNFA gene polymorphisms with serological markers of coeliac disease.

Coeliac disease (CD) is known to have a strong genetic background. We analyzed the association between serological markers of CD and the -1087 IL10 and -308 TNFA gene polymorphisms in Swedish patients. A higher frequency of the TNF2 allele was present in the patients compared with the controls (p < 0.0001). The frequency of the AA genotype of the IL10 gene in the patients was unexpectedly higher in comparison with the controls (p < 0.05). The levels of IgA anti-endomysium and antitissue transglutaminase antibodies were associated with IL10 but not with TNFA genotype. The patients with the AA or GG -1087 IL10 genotypes had significantly lower levels of antibodies in comparison with those with the AG genotype (p < 0.05 to p < 0.0005). However, when divided according to potential level of IL-10 production, the group of potentially high IL-10 producers among the CD patients demonstrated significantly lower levels of antitissue transglutaminase antibodies compared to potentially low IL-10 producers (p = 0.01). Our results show a relationship between the levels of IgA antibodies involved in CD with the IL10 genotypes. This suggests a possible involvement of IL-10 in the development of the disease.

Alleles↗

Breastfeeding and allergic disease: a multidisciplinary review of the literature (1966-2001) on the mode of early feeding in infancy and its impact on later atopic manifestations.

BACKGROUND: Strategies to prevent children from developing allergy have been elaborated on the basis of state-of-the-art reviews of the scientific literature regarding pets and allergies, building dampness and health, and building ventilation and health. A similar multidisciplinary review of infant feeding mode in relation to allergy has not been published previously. Here, the objective is to review the scientific literature regarding the impact of early feeding (breast milk and/or cow's milk and/or formula) on development of atopic disease. The work was performed by a multidisciplinary group of Scandinavian researchers. METHODS: The search in the literature identified 4323 articles that contained at least one of the exposure and health effect terms. A total of 4191 articles were excluded mainly because they did not contain information on both exposure and health effects. Consequently, 132 studies have been scrutinized by this review group. RESULTS: Of the 132 studies selected, 56 were regarded as conclusive. Several factors contributed to the exclusions. The studies considered conclusive by the review group were categorized according to population and study design. CONCLUSIONS: The review group concluded that breastfeeding seems to protect from the development of atopic disease. The effect appears even stronger in children with atopic heredity. If breast milk is unavailable or insufficient, extensively hydrolysed formulas are preferable to unhydrolysed or partially hydrolysed formulas in terms of the risk of some atopic manifestations.

Animals↗

Avidity progression of dietary antibodies in healthy and coeliac children.

In most individuals minute amounts of food proteins pass undegraded across the intestinal mucosa and trigger antibody formation. Children with coeliac disease have enhanced antibody production against gliadin as well as other dietary antigens, e.g. beta-lactoglobulin, in cow's milk. Antibody avidity, i.e. the binding strength between antibody and antigen, often increases during antibody responses and may be related to the biological effectiveness of antibodies. The aim of the present study was to determine the avidity of serum IgG antibodies against beta-lactoglobulin and gliadin in healthy children during early childhood and compare these avidities to those found in children with coeliac disease. The average antibody avidity was analysed using a thiocyanate elution assay, whereas the antibody activity of the corresponding sera was assayed by ELISA. The avidity of serum IgG antibodies against beta-lactoglobulin as well as gliadin increased with age in healthy children, even in the face of falling antibody titres to the same antigens. Children with untreated coeliac disease had IgG anti-beta-lactoglobulin antibodies of significantly higher avidity than healthy children of the same age, and the same trend was observed for IgG antigliadin antibodies. The present data suggest that the avidities of antibodies against dietary antigens increase progressively during early childhood, and that this process seems to be accelerated during active coeliac disease.

Aging↗

Anti-inflammatory activities of human lactoferrin in acute dextran sulphate-induced colitis in mice.

In this study, we investigated the anti-inflammatory effects of orally administered human lactoferrin (hLF) and two peptides, based on the bactericidal region of hLF (HLD1 and HLD2), on the course of experimental colitis. Acute colitis was induced in C57Bl/6 mice by giving 5% dextran sulphate (DX) in the drinking water. The mice were killed after 2 or 7 days of DX exposure. The animals were given hLF or the peptides orally twice a day (2 mg/dose/mouse) during the DX exposure. In the control animals, the hLF or the peptides were replaced by bovine serum albumin or water. The appearance of occult blood in the faeces and macroscopic rectal bleeding were significantly delayed and partly reduced in the hLF-treated animals compared with the control animals. The shortening of the colon, a pathological effect of DX exposure, was significantly less pronounced in the hLF-treated group compared with the control group. Also, the interleukin-1beta (IL-1beta) levels in the blood were significantly diminished in this group after 2 days of DX exposure. A significantly lower crypt score was observed in the distal part of the colon in the hLF-treated group compared with the control group. Also, significantly reduced numbers of CD4 cells, F4/80-positive macrophages and tumour necrosis factor-alpha-producing cells were detected by immunohistochemistry in the distal colon of the hLF-treated animals compared with the control animals after 7 days of DX exposure. A reduction was also observed concerning the IL-10-producing cells in the middle colonic submucosa. The HLD1 and HLD2 treatment, which was carried out for 2 days, only gave results almost identical to those of hLF, concerning clinical parameters after the 2 days of DX exposure. An even stronger effect was observed for HLD2, regarding decreased occult blood in the faeces and colon length. Our results show that perorally given hLF mediates anti-inflammatory effects on the DX-induced acute colitis, and further suggest that the bactericidal region of the hLF molecule may be involved in these activities.

Administration, Oral↗

Loss of ileal IgA+ plasma cells and of CD4+ lymphocytes in ileal Peyer's patches of vitamin A deficient rats.

Child mortality in diarrhoeal disease is increased significantly by vitamin A deficiency in poor countries. The pathological mechanisms are not known in detail. However, in this paper we report that vitamin A-deficient Wistar rats had much reduced IgA+ plasma cells in the ileal lamina propria (eightfold reduction from 470 cells/mm(2), P = 0.009), as well as a prominent reduction of CD4+ cells in the parafollicular regions of ileal Peyer's patches (reduction from 7200 to 105 cells/mm(2), P = 0.009). IL-2Ralpha-chain (CD25) positive lymphocytes in the ileal Peyer's patches were also reduced significantly in vitamin A deficiency (from 1400 to 300 cells/mm(2), P = 0.009). The density of CD8 cells tended to be increased relative to the control animals (from 5100 to 6000 cells/mm(2), not statistically significant). In conclusion, the marked decrease of lamina propria IgA+ plasma cells may be one cause of the high diarrhoeal mortality in vitamin A deficiency. This, in turn, appears to be related to reduced numbers of activated or regulatory CD4+ T cells in Peyer's patches.

Animals↗

An established immune response against ovalbumin is suppressed by a transferable serum factor produced after ovalbumin feeding: a role of CD25+ regulatory cells.

We have previously demonstrated that rats fed ovalbumin (OVA) develop a tolerogenic activity in serum, which upon transfer induces tolerance to OVA and suppression of the immune response to a bystander antigen. Here, we have extended these studies and analysed if the tolerogenic activity in serum could suppress an established immune response in the recipients. Rats were immunized with OVA, 4 and 1 week prior to the transfer of serum from either OVA-fed or control animals. Rats that received serum from OVA-fed donors had significantly lower delayed-type hypersensitivity (DTH) reaction against OVA 1 week after the serum transfer compared with the controls, and the levels of immunoglobulin (IgG) anti-OVA antibodies were significantly lower 2 and 4 weeks after serum transfer. Monomeric OVA in amounts corresponding to the OVA transferred with serum did not induce the reduction of DTH response or IgG anti-OVA antibody levels. In vitro, the proliferation of OVA-stimulated spleen cells, taken from recipients of tolerogenic serum, was significantly lower compared with spleen cells from the controls. The in vitro suppression seemed to be mediated by a population of CD25+ cells, because the removal of such cells from OVA-stimulated spleen cell suspensions resulted in increased proliferation in cultures from rats receiving tolerogenic serum. Our results showed that the tolerogenic serum factor can suppress an established immune response in recipient animals, possibly through induction of regulatory CD25+ cells. Whether this capacity might be used to influence chronic inflammatory conditions needs to be investigated.

Animals↗

Ketanserin attenuates the behavioural effects of corticosterone: implications for 5-HT(2A) receptor regulation.

The effects of chronic corticosterone treatment on sexual behaviour and wet-dog shakes were investigated in both female and male rats. The serotonergic type 2A (5-HT(2A)) receptor antagonist ketanserin was administered to test the hypothesis that the behavioural effects of corticosterone were mediated by increased 5-HT(2A) receptor activity. Rats were randomly assigned to one of four chronic treatment groups: control, ketanserin alone, corticosterone alone, or ketanserin and corticosterone. Ketanserin attenuated the corticosterone-induced changes in both sexual behaviour and wet-dog shakes. Ketanserin alone had no effect on these behaviours. Results suggest that increased 5-HT(2A) receptor activity mediates the effects of corticosterone on sexual behaviour and wet-dog shakes.

Animals↗