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Biomedical subjects

M Halonen

Publications and source records attributed to M Halonen.

At least 37 records · Page 2Linked to original sources
PubMed1999

Breast-feeding, maternal IgE, and total serum IgE in childhood.

BACKGROUND: There is controversy regarding the relationship of the effect of breast-feeding on markers of allergy such as total serum IgE in childhood. OBJECTIVE: This study, using longitudinal data, tested the hypothesis that the relation of breast-feeding to IgE in childhood differs depending on maternal total IgE level. METHODS: Total serum IgE was assessed with the paper radioimmunosorbent test at 4 ages in nonselected children enrolled at birth into the prospective Tucson Children's Respiratory Study. Children were classified as never breast-fed, breast-fed less than 4 months, or breast-fed 4 months or longer, on the basis of physician report or questionnaires completed by parents by the time the child was 18 months old. A longitudinal random effects model was used to test for group differences and temporal trends in IgE for children classified with reference to maternal IgE (high tertile vs all others) and breast-feeding history. A total of 664 children with 1457 observations were included. RESULTS: Among children whose mothers were in the 2 lower tertiles of IgE, breast-feeding was associated with lower total serum IgE at age 6 years (24.2 vs 44.3 IU/mL for never breast-fed children; P <.02); similar trends existed at age 11 years. In contrast, for children whose mothers were in the highest tertile of IgE, breast-feeding of 4 months or longer was associated with higher IgE levels in the child compared with those never breast-fed or breast-fed less than 4 months (97.0 vs 38.9 IU/mL; P <. 005). These cross-sectional analyses were confirmed with the longitudinal random effects model, which also showed no effect of confounders. Paternal IgE showed no similar relation with child IgE. CONCLUSION: Breast-feeding appears to have paradoxic relations with IgE in childhood, depending on maternal IgE level. These findings may help explain the contradictory results found in other investigations of the relation of breast-feeding to allergic symptoms and markers.

Breast Feeding↗
PubMed1999

Perinatal events in the development of asthma.

Many potential factors are likely involved in the pathogenesis of asthma. These include prenatal, peripartum, and postnatal influences. Prenatally, genetic endowment, maternal smoking, in utero allergen sensitization, and alterations in maternal immune function, especially at the placental level, may increase the risk for asthma and atopy. In the peripartum period, suspected factors include obstetric practices (eg, the use of prostaglandins, hormones, and other agents) and prematurity. Postnatally passive smoke exposure, neonatal or early childhood infections and breast-feeding are under increasing scrutiny as to their possible role in the development of asthma. Despite the volumes of work already reported, much more is left to be done to sort out the complex interrelationships of these and other as yet unsuspected influences on the development of asthma.

Allergens↗
PubMed1999

Association of radiologically ascertained pneumonia before age 3 yr with asthmalike symptoms and pulmonary function during childhood: a prospective study.

Epidemiologic evidence suggests an association between reports of pneumonia in early life and the subsequent development of diminished lung function. However, no studies are available in which the diagnosis of pneumonia was based on radiologic evidence. Lower respiratory illnesses with or without a radiologically confirmed diagnosis of pneumonia were assessed in a study of 888 children enrolled at birth. Pulmonary function tests, markers of atopy, asthma diagnosis, and prevalence of respiratory symptoms were assessed at different ages between birth and 11 yr. Incidence of pneumonia during the first 3 yr of life was 7.4%. Respiratory syncytial virus was the most frequent agent identified both in children with pneumonia and in those with lower respiratory tract illness (LRI) without pneumonia (36.4% versus 35.6%, respectively). Children with a diagnosis of pneumonia were more likely to have physician-diagnosed asthma and current wheezing at ages 6 and 11 yr than were those who had no LRIs. When compared with children without LRIs, those with a diagnosis of pneumonia had lower levels of maximal flows at FRC at mean age of 2 mo (albeit not significantly) and at age 6 yr, and lower levels of FEV1 and FEF25-75 at age 11 yr. These deficits were independent of known confounders, including wheezing at the time of study, and were partly and significantly reversed after administration of a bronchodilator. We conclude that children with radiologically confirmed pneumonia have diminished airway function that is probably present shortly after birth. These deficits are at least in part due to alterations in the regulation of airway muscle tone.

Aging↗
PubMed1999

Two subphenotypes of childhood asthma that differ in maternal and paternal influences on asthma risk.

Asthma is a phenotypically heterogeneous disease. Two subgroups are defined here based initially on skin test reactivity to the allergen Alternaria at age 6 from among a large population of children born and raised in the Southwestern desert environment of Tucson, Arizona. When compared with asthma among Alternaria-positive subjects, asthma among Alternaria-negative subjects was associated with lower levels of total serum IgE, no relation to local aeroallergen skin tests, a younger age at diagnosis, greater remittance by age 11, and more frequent wheezing lower respiratory illnesses (LRIs) in the first year of life. Despite the difference in total serum IgE, however, IgE concentrations were significantly higher in each asthma group compared with its respective control group. Asthma in each parent contributed approximately equivalent risk for Alternaria-positive asthma in the child. However, neither parental skin test sensitization nor total serum IgE levels provided risk for asthma in the child. Inheritance patterns for Alternaria-negative asthma revealed a contribution from maternal but not paternal asthma. Thus, dividing asthma in children at age 6 into Alternaria-positive and Alternaria-negative groups identifies subphenotypes that are further distinguished by differences in phenotypic markers and parental influences.

Alternaria↗
PubMed1999

Familial aggregation and segregation analysis of eosinophil levels.

The number of circulating eosinophils is associated with the risk of asthma in population samples. Therefore, eosinophil levels may be an intermediate phenotype for asthma amenable to genetic analysis. We examined familial aggregation of the number of eosinophils x 10(6) L(-1) and the percentage of eosinophils based on a 300 count differential in 644 Hispanic and non-Hispanic white families, with 2, 097 subjects, enrolled in the Tucson Children's Respiratory Study. Both measures were adjusted for age, season and year at the time blood was drawn, sex, and ethnicity. Segregation analysis was conducted in the 458 non-Hispanic white families, as there were no significant familial correlations in the Hispanic families, and there was significant heterogeneity by ethnic group. Familial correlations (rho) in the non-Hispanic white families were as follows: mother-father, 0.05; mother-child, 0.18 (p < 0.001); father-child, 0.07; sibling-sibling, 0.31 (p < 0.001). Without covariates analyses indicated a polygenic/multifactorial mode of inheritance. After adjusting for current and past asthma an oligogenic mode of inheritance was suggested, plus additional residual familial components that were mainly maternally mediated. This study supports the notion of multiple, relatively common genes interacting to determine genetic susceptibility to asthma. Holberg CJ, Halonen M, Wright AL, Martinez FD. Familial aggregation and segregation analysis of eosinophil levels.

Adult↗
PubMed1999

A Polymorphism* in the 5' flanking region of the CD14 gene is associated with circulating soluble CD14 levels and with total serum immunoglobulin E.

Total serum immunoglobulin (Ig)E levels are genetically regulated, but the mechanism of inheritance is not well understood. Cytokines produced by T-helper (Th)1 and Th2 lymphocytes control IgE synthesis. Bacterial antigens may favor the development of Th1 cells from naive CD4-positive T cells through a CD14-dependent pathway. CD14 is constitutively expressed on the surface of monocytes and macrophages, and is also present in serum in a soluble form (sCD14). The CD14 gene maps to chromosome 5q31.1, a candidate region for loci regulating total serum IgE. We hypothesized that genetic variants in the CD14 gene could influence Th-cell differentiation and thus total serum IgE. We identified a C-to-T transition at base pair -159 from the major transcription start site (CD14/-159). Among 481 children recruited from a general population sample, frequency of allele C was 51.4%. TT homozygotes had significantly higher sCD14 levels than did carriers of both the CC and CT genotypes (P = 0.01). TT homozygotes also had significantly lower levels of IgE than did carriers of the other two genotypes, but differences were significant only among children who were skin test-positive to local aeroallergens (P = 0.004). There was no association between CD14/-159 and either interleukin (IL)-4 or interferon (IFN)-gamma responses by peripheral blood mononuclear cells. However, IFN-gamma and IL-4 responses were positively and negatively correlated, respectively, with serum sCD14 levels. We conclude that CD14/-159 plays a significant role in regulating serum sCD14 levels and total serum IgE levels.

Base Sequence↗
PubMed1998

Differential immune responses to acute lower respiratory illness in early life and subsequent development of persistent wheezing and asthma.

BACKGROUND: Recent epidemiologic evidence suggests that 2 wheezing syndromes coexist in early life: transient wheezing, limited to early childhood, and persistent wheezing, which starts in early childhood and persists beyond that age. OBJECTIVE: Whether the nature of the immune response occurring during acute lower respiratory illnesses (LRIs) in infancy differs between these 2 groups of wheezers has yet to be determined. METHODS: We compared total serum IgE levels and peripheral blood eosinophil counts obtained during the acute phase of the first LRI with those obtained during the convalescent phase or with well-baby samples in persistent (n = 49) and transient early wheezers (n = 88), as well as in children who had only nonwheezing LRIs (n = 43) during the first 3 years of life. RESULTS: Total serum IgE levels were significantly higher (P =.008) during the acute phase compared with the convalescent phase of the LRI in persistent wheezers, a response not observed in transient early wheezers (P =.7). Peripheral blood eosinophil counts were significantly reduced during the acute phase of the LRI (P =.009) in transient early wheezers, a response not observed among persistent wheezers (P =.7). Acute responses in children who had nonwheezing LRIs only were similar to those seen in transient early wheezers. CONCLUSION: Alterations in acute immune response to viral infection may be detected at the time of the first wheezing episode in subjects who will go on to have persistent wheezing symptoms.

Acute Disease↗
PubMed1998

Occupationally Oriented Medical Rehabilitation and Hairdressers' Work Techniques--A one-and-a-half-year follow-up.

This study examined changes in work techniques and musculoskeletal symptoms after occupationally oriented medical rehabilitation arranged for 21 hairdressers who were experiencing neck-shoulder or back pain but were still able to work. OWAS (Ovako Working Posture Analysing System) analyses of working postures and questionnaire data were obtained at the beginning of the courses and one and a half years later. The participants worked with their back bent and twisted or their arms at or over shoulder level more seldom (p <.0001) at the end of the follow-up than at the beginning of the rehabilitation. Subjective work-related physical and mental strain had decreased by 45.4% (p <.001) and 27.1% (p <.05), respectively, and subjective neck and back pain by 40.0% (p <.01) and 45.3% (p <.01), respectively. This study suggests that occupationally oriented medical rehabilitation can have significant and long-lasting effects on the rehabilitee's work techniques and subjective well-being.

Journal Article↗
PubMed1998

Platelet-activating factor induction of activator protein-1 signaling in bronchial epithelial cells.

Platelet-activating factor (PAF) has been implicated in the pathogenesis of allergic and inflammatory events in the airway. In the present study, we sought to determine if PAF receptors are present on human bronchial epithelial cells and whether PAF binding to these receptors leads to activation of activator protein-1 (AP-1)-mediated transcription. Radioligand binding studies demonstrated specific binding sites for the PAF antagonist [3H]WEB 2086 (3-[4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f]-[1,2,4]triazolo[4,3- a][1,4]diazepine-2-yl]-1-(4-morpholinyl)-1-propanone) on primary bronchial epithelial cells with an equilibrium dissociation constant (Kd) = 9.8 nM and maximal density of binding sites (Bmax) = 42.4 fmol/mg of protein. The expression of PAF receptors in these cells was further confirmed by reverse transcriptase-polymerase chain reaction, which revealed amplification products derived from PAF receptor mRNA corresponding to transcripts 1 and 2. In the bronchial epithelial cell line BEAS-2B transfected with an expression plasmid for the human PAF receptor, PAF stimulation increased AP-1 DNA binding activity as determined by electrophoretic mobility shift assays. The Fos and Jun family proteins were identified as components of the DNA-protein complexes by anti-peptide antibodies in gel supershift assays. Additionally, PAF significantly induced AP-1 mediated transcription which was dependent on the expression of PAF receptors. The PAF antagonist WEB 2086 blocked the PAF effect but not that induced by 12-O-tetradecanoyl phorbol-13-acetate, indicating the specificity of the PAF response. These results indicate that activation of airway epithelial cells through stimulation of PAF receptors includes up-regulation of the nuclear transcription factor AP-1 and AP-1 transcriptional activity.

Bronchi↗
PubMed1998

Antenatal interventions in childhood asthma.

The occurrence of asthma in most young children is likely to result from altered or disrupted immune maturation. The persistence of Th2-like lymphocyte responses to common allergens rather than the extinction of immune response (immune tolerance) or the deflection of response to a Th1 pattern (immune deviation) may underlie the development of asthma and the atopic phenotype. It is likely that this failure of normal immune maturation begins early in life, and that both genetic predisposition and environmental factors operating at critical times act jointly to cause it. There is clear evidence that the development of immune response capability begins in utero, and that maternal allergic and other exposures can affect this process before birth. While there is some evidence that the onset of atopy or atopic symptoms can be ameliorated or delayed in early life by reducing maternal prenatal allergen exposure (either food or inhaled allergens), there is currently no convincing evidence that prenatal maternal allergen avoidance will diminish asthma incidence in children. There are similarly no data available to evaluate if dietary antioxidants, postulated but unproven to have a protective role on airway reactivity and asthma incidence and severity in adults, have any protective role in utero. In contrast, maternal smoking during pregnancy has been shown in several studies to be associated with reductions in pulmonary function measures (flows at low lung volumes) in both infants and older children that are consistent with abnormalities seen in asthmatics. This finding, coupled with the clear association of postnatal environmental tobacco smoke exposure with increased wheezing and asthma risk in children, make maternal smoking cessation the prenatal intervention most likely to be effective in reducing asthma risk in children.

Adult↗
PubMed1997

Evidence for platelet-activating factor receptor subtypes on human polymorphonuclear leukocyte membranes.

Platelet-activating factor (PAF) is a potent phospholipid mediator that acts through specific cell surface receptors. The existence of PAF receptor subtypes has been suggested by functional and radioligand binding studies in a variety of cells and tissues. This report addresses this issue more directly and demonstrates differences between specific PAF receptors in human polymorphonuclear leukocytes (PMNs) and COS-7 cells transfected with the cloned human PAF receptor gene. The presence of more than one receptor in human PMNs is supported by three different studies. First, the Kd from the saturation isotherms for the binding of [3H]WEB 2086 on PMNs was 7-fold larger (Kd = 29.2 nM) than the kinetic Kd (4.2 nM). Second, the pseudo-Hill slope determined from the saturation experiments with PMNs was significantly lower than unity (0.69 +/- 0.05 SEM), and the saturation Kd values for transfected COS-7 (Kd = 9.6 nM) and PMN membranes were significantly different. These results contrasted with those for the transfected COS-7 cells, which showed a Kd from the saturation isotherms similar to that of the kinetic Kd (3.2 nM) and a pseudo-Hill slope that was not different from 1.0. Third, when the radiolabeled ligand [3H]WEB 2086 was increased in concentration from 10 to 50 nM in inhibition experiments with the human PMN membranes, the Ki increased, indicative of binding mainly to receptors with lower affinity. These results suggest that PAF receptor subtypes exist in human PMNs based on distinct radioligand binding characteristics from the human cloned PAF receptor.

Animals↗
PubMed1997

Alternaria as a major allergen for asthma in children raised in a desert environment.

The relationships of asthma and allergic rhinitis with individual immediate skin test responses were examined for preferential associations and for changes with age in children raised in a semiarid environment. Prevalence of physician-diagnosed asthma was 9.8% at age 6 (n = 948) and 15.5% at age 11 (n = 895). Immediate skin test responses to Bermuda grass were the most prevalent among children with allergic rhinitis and control subjects, whereas responses to the mold, Altenaria alternata, were the most prevalent among asthmatics. Skin test responses for crude house dust, Dermatophagoides farinae, and cat had low prevalences in all groups. By logistic regression, Alternaria was the only allergen independently associated with increased risk for asthma at both ages 6 and 11. Allergic rhinitis showed independent association with sensitization to Bermuda grass and mulberry tree pollen at age 11 but did not show an independent relation to any single allergen at age 6. Logistic regression further revealed that persistent asthma (diagnosed before age 6) was independently associated with Alternaria skin tests at both ages 6 and 11, whereas new asthma (diagnosed after age 6) was associated with Alternaria skin tests at age 6 but not at age 11. We conclude that Alternaria is the major allergen associated with the development of asthma in children raised in a semiarid environment and that skin test responses at age 6 are more closely linked to asthma than those at age 11.

Allergens↗
PubMed1996

Serum levels of the soluble low affinity receptor for IgE and soluble interleukin-2 receptor in childhood, and their relation to age, gender, atopy and allergic disease.

Identifying immune factors associated with the development of atopy can enhance our understanding of the in vivo mechanisms involved and may have utility in paradigms designed to prevent disease. Two candidates suggested for such roles are the soluble low affinity receptor for IgE (sCD23) and the soluble interleukin-2 receptor (sCD25). To assess serum levels of these factors blood samples were collected at birth and at age 6 in a large nonselected population from Tucson, AZ. Log mean sCD23 and sCD25 levels decreased from birth to age 6, (for sCD23 0.60 ffi 0.26pg/l, n = 340 and 0.53 + 0.28pg/l, n = 333 and for sCD25 1.95 i 0.14pM, n = 304 and 1.86 ffi 0.20pM, n = 327, for the two ages respectively. Anglo children had lower sCD23 levels at birth compared to Hispanic children (p < 0.01); no effect of gender was observed. Skin test reactivity at age 6 was directly related to sCD25 levels at age 6 (p = 0.007) and even levels at birth showed a similar trend (p = 0.06). These relations were distinct from any relation to total serum IgE. No relation was observed with sCD23 levels for either skin test reactivity or serum IgE. The prevalences of asthma, rhinitis and eczema by age 6 were unrelated to sCD25 or sCD23 levels. The results indicate that soluble CD23 and CD25 have higher levels at birth than later in childhood and that the development of skin test reactivity may be associated with regulatory mechanisms involving sCD25, whereas sCD23 was not similarly implicated.

Age Factors↗
PubMed1996

Regional mapping of the human platelet-activating factor receptor gene (PTAFR) to 1p35-->p34.3 by fluorescence in situ hybridization.

The human platelet-activating factor cell-surface receptor (PTAFR) is a G protein-coupled receptor thought to contribute to many atopic and inflammatory diseases and, perhaps, to the growth of some neoplasms. Exploring the possibility that the PTAFR might be involved in the genetic predisposition to any disease requires knowledge of its chromosomal localization. In this paper we have used a 20-kb human genomic fragment containing the coding sequence of the cloned PTAFR to determine the regional chromosomal localization of the gene. Using fluorescence in situ hybridization, the localization of the human PTAFR gene was mapped to 1p35-->p34.3.

Chromosome Mapping↗
PubMed1996

Recurrent cough in childhood and its relation to asthma.

Risk factors for recurrent cough (RC) in childhood, and its relation to asthma were investigated as part of the prospective, longitudinal Tucson Children's Respiratory Study. RC, defined as > or = 2 episodes of cough without a cold in the past year, was assessed by questionnaire in 987 children at age 6. Children having RC without wheeze (n = 154) did not differ from children with neither symptom (n = 610) in serum IgE levels, skin test response, size-corrected forced expiratory flow, or percentage of decline following cold air challenge. In contrast, children with both RC and wheeze (n = 116) had significantly more respiratory illness, more atopy, lower flow at end-tidal expiration (V'maxFRC), and greater declines in lung function following cold air challenge than children with neither symptom. Current parental smoking was a risk for RC without wheeze, whereas male gender, maternal allergy, wheezing lower respiratory tract illness (LRI) in early life, and high IgE were significant risks for RC with wheeze, compared with children having neither symptom. RC early in life resolved in the majority of children, between ages 2-3 yr and age 6, and between age 6 and age 11. High IgE and positive skin prick test were associated with persistence of RC to age 6 among children who wheezed, and markers of allergy were associated with persistence of RC between 6 and 11 yr. These findings suggest that recurrent cough in the absence of wheeze differs in important respects from classic asthma, and using the same label to refer to these distinct syndromes may obscure their diverse pathophysiologies.

Asthma↗
PubMed1996

Segregation analysis of physician-diagnosed asthma in Hispanic and non-Hispanic white families. A recessive component?

The inheritance of asthma, evident from its high family concordance, is not well understood. To investigate whether asthma may be inherited through a major gene with two alleles, segregation analyses were conducted in 3,369 individuals from 906 nuclear families enrolled, without selection, in a longitudinal study of respiratory health in Tucson, Arizona. Physician-diagnosed asthma and its age of onset were ascertained for each family member when children were at a mean age of 7 yr. Age of asthma diagnosis was allowed for in analyses, and the impact of the covariate total serum IgE level on age of onset was examined. Segregation analyses were conducted with and without residual family effects, with and without the covariate IgE. The hypothesis of a single two-allele locus for asthma was rejected. However, depending on the method of assessment of the residual familial effects, either a polygenic/multifactorial mode of inheritance alone, or an oligogenic model with some evidence of a recessive component present in the population with the high frequency of 0.67, were compatible with the data. Results were unchanged with the addition of the covariate IgE.

Adult↗