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Biomedical subjects

J A Warner

Publications and source records attributed to J A Warner.

At least 19 recordsLinked to original sources
PubMed2000

Prenatal origins of allergic disease.

The prevalence of asthma and related allergic disorders has increased considerably over the last 25 years. Because genetic stock has not changed, environmental factors must have influenced the phenotype. Infants who experience the development of allergy already have an altered immune response at birth. We have investigated the development of immune responses during gestation and the effect of maternal allergen exposure during pregnancy and infant exposure in the first month of life on the development of allergy and disease. There was higher specific peripheral blood mononuclear cell proliferation to house dust mite and birch pollen in the third trimester compared with the second trimester, with the first positive responses seen at 22 weeks gestation. Maternal exposure to birch pollen after 22 weeks resulted in higher infant peripheral blood mononuclear cell responses to birch pollen at birth. Infants born at term, with at least 1 atopic parent with asthma, who experienced the development of allergic symptoms and positive skin prick test by 1 year of age had raised proliferative responses to house dust mite at birth compared with those infants with no symptoms. In genetically predisposed individuals, antenatal factors including maternal and thereby fetal exposure to allergens and materno-placental-fetal immunologic interactions are active in determining whether an allergic predisposition is manifested as disease.

Antibody Formation↗
PubMed2000

Mechanical ventilation and high-efficiency vacuum cleaning: A combined strategy of mite and mite allergen reduction in the control of mite-sensitive asthma.

BACKGROUND: The relationship between exposure to house dust mite (HDM) allergens and prevalence of sensitization to these allergens in patients with asthma has been confirmed in many studies. Mite population growth is regulated by humidity. Reducing humidity and removing allergen by efficient vacuuming should control mite allergen and reduce symptoms. OBJECTIVE: We sought to investigate the effect of mechanical ventilation and high-efficiency vacuuming on HDM numbers and Der p 1 concentrations in the homes of mite-sensitive asthmatic subjects and to evaluate the effect of any reductions on symptoms. METHODS: The homes of 40 HDM-sensitive asthmatic subjects were randomized to receive (1) mechanical ventilation and a high-efficiency vacuum cleaner (HEVC); (2) mechanical ventilation alone; (3) an HEVC alone; and (4) no intervention. Homes and patients were monitored for 12 months. Change in absolute humidity, mite numbers, Der p 1 concentrations, lung function, bronchial hyperresponsiveness, and symptom scores were analyzed. RESULTS: Homes with mechanical ventilation achieved significantly lower humidity levels than those without (P <.001), with an associated reduction of mite numbers (P <.05) and Der p 1 concentrations (P <.001 ¿in nanograms per gram, P =.006 ¿in milligrams per square meter) in bedroom carpets and some other mite sources in the ventilated areas of the homes. The addition of a vacuum cleaner enhanced this effect. There was a trend for an improvement in histamine PC(20) (P =.085) in the patients whose homes were ventilated. CONCLUSION: The use of a mechanical ventilation system in suitable homes resulted in some reduction in numbers of HDM and Der p 1 concentrations. The addition of an HEVC slightly enhanced the effect but not sufficiently to see an improvement in symptoms.

Adolescent↗
PubMed2000

Putting priming into perspective - from cellular heterogeneity to cellular plasticity.

The concept of priming is widely used in cell biology and has come to mean the functional enhancement of a given cell by cytokines. 'Primed' cells have a number of other cellular alterations, although the relationship between functional and phenotypical diversity has not been established. Here, Claus Kroegel and colleagues discuss the dynamic nature of inflammatory-cell priming, which might be part of a broader means of comprehending cell function in disease.

Cell Adhesion Molecules↗
PubMed2000

Fetal and neonatal IL-13 production during pregnancy and at birth and subsequent development of atopic symptoms.

BACKGROUND: Cytokine production at the materno-fetal interface may influence the development of atopy-predisposing immune responses. Because IL-13 possesses IL-4-like activity and may regulate the immune responses observed in atopy, it may contribute to the expression of the atopic phenotype initiated during intrauterine life. OBJECTIVE: We sought to examine IL-13 expression by fetal and neonatal cells and the placenta. METHODS: The production of IL-13 by neonatal and fetal T cells was examined by culturing the cells in the presence or absence of PHA. Production of IL-13 at term was considered in the context of the later development of atopic disease in the child. IL-13 expression in the placenta was assessed by using immunohistochemistry. RESULTS: IL-13 immunoreactivity within the placenta was restricted to 16 to 27 weeks' gestation (6/6 positive vs 0/10 at >27 weeks' gestation). In contrast, spontaneous release of IL-13 by fetal mononuclear cells was first observed from 27 weeks' gestation but was undetectable after 37 weeks' gestation. PHA-stimulated mononuclear cells showed increased IL-13 levels in 80% of samples. Term babies (>37 weeks' gestation) with a parental history of atopy with atopic symptoms by 3 years of age produced significantly lower concentrations of PHA-induced IL-13 when compared with babies with no parental history of atopy (P =.034). CONCLUSION: Thus babies at risk of atopic disease in infancy display defective IL-13 production at birth. This may represent an inherent immaturity in the development of T cell-cytokine responses in babies at genetic risk for atopy or could be a consequence of downregulation of responses by other factors. Normal pregnancy, irrespective of atopic status, is associated with the production of appreciable quantities of IL-13 initially by the placenta and subsequently by the fetus. The regulation of this production and its consequences for the mother and fetus remains to be elaborated.

Female↗
PubMed1999

Primary sensitization in infants.

OBJECTIVE: It has become increasingly clear that the mechanisms by which an allergic immune response is generated are complex and may begin even before a baby is born. Genetic, environmental, nutritional, and immunologic factors acting during pregnancy all play a role in determining whether or not a baby is born with a propensity to develop allergic sensitization and subsequent allergic disease. The objective of the research described in this article is to determine whether manipulation of any or all of these could lead to prevention of disease. DATA SOURCES: The database used was Medline up to and including 1997. The Conference Proceedings of the XVth World Congress of Asthmology in Montpellier 1996 are quoted. Many of the research hypotheses are generated from work performed in our own laboratories. STUDY SELECTION: The criteria used to select studies for review centered around a necessity for the data to have been collected in very early life with, if possible, a follow-up period to determine disease progression, or for the data to have been collected during pregnancy to elucidate primary mechanisms. RESULTS: It has been shown that a fetus is able to mount a proliferative response to a common allergic trigger (beta-lactoglobulin, house dust mite, etc) as early as 22 weeks of pregnancy. Maternal exposure to allergens influences her own IgG production which modulates the allergen exposure of the fetus resulting in either primary sensitization of T cells or "tolerance" to the allergen. Atopic mothers create a more Th2-orientated environment for the developing fetus than non-atopic mothers. CONCLUSIONS: Manipulation of the maternal immune response during pregnancy, either by altering her environment or controlling her allergic reactions, may be a method of preventing the development of allergic disease in infants.

Allergens↗
PubMed1999

Can we predict which wheezy infants will continue to wheeze?

Early intervention strategies in infant wheezing will be dependent on the ability to predict persistence of disease. We undertook a prospective longitudinal study to determine which factors might be predictive for the persistence of wheeze. We examined a group of 107 children 3 to 36 mo of age with at least one atopic parent. Children were recruited within 12 wk of first wheeze. Factors assessed included: personal atopy (IgE > 1 SD above age-related normal and/or eczema and/or positive skin tests); parental atopy; number of siblings; age at first wheeze; sex; serum-soluble IL-2R; proliferation of peripheral blood mononuclear cells (PBMC) to beta-lactoglobulin and to D. pteronyssinus; production of IFN-gamma on stimulation of PBMC with beta-lactoglobulin and with D. pteronyssinus. A positive clinical outcome (child requiring prophylactic antiasthma treatment after 1 yr) was observed in 53 (49.5%) children. Predictor variables were assessed by univariate and multivariate logistic regression. Wheeze was more likely to be persistent in older, atopic children with biparental atopy. The model offering best prediction of persistent wheeze with least risk of including asymptomatic subjects was age at presentation + sIL-2R. Trials of early intervention strategies using a logistic regression equation based on this model for patient recruitment can now be designed.

Asthma↗
PubMed1999

Mexican-American male batterers on the MCMI-III.

This study examined personality characteristics of Mexican-American male batterers. 60 Mexican-American male batterers (M = 33.6 yr.) in the court system in South Texas took the MCMI-III and their MCMI-III scores were compared with the scores of a community sample of 45 Mexican-American individuals (M = 30.4 yr.). The batterers frequently scored higher than the nonbatterers on the Avoidant and Passive-Aggressive scales, while nonbatterers frequently scored higher on the Histrionic scale. The batterers scored significantly higher on 18 out of 24 MCMI-III scales, while nonbatterers scored significantly higher on two scales.

Adult↗
PubMed1999

Endorsements by Mexican-Americans of the Bem Sex-Role Inventory: cross-ethnic comparison.

Gender-related personality traits among Mexican-American men and women were examined. The sample consisted of 307 Mexican-Americans (150 women, 157 men) in a predominantly Mexican and Mexican-American community in South Texas. Mexican-American men scored significantly higher than the women on eight masculine items, whereas Mexican-American women scored higher than the men on four feminine items. A comparison between the scores of Mexican-Americans on the Bem Sex-Role Inventory with those of the original sample in the inventory's manual showed that the scores for the Masculinity and Femininity subscales for both Mexican-American men and women were not significantly different from those of the original sample. A significant difference, however, was found on some of the items of the inventory. Analysis also indicated that more Mexican-American men were categorized as Feminine and Androgynous than were non-Hispanic Euro-American males in the original sample. Among Mexican-American women there were more individuals classified as Masculine and Undifferentiated and a lower percentage as Feminine than among the original sample. Implications and recommendations based on the results are discussed.

Adult↗
PubMed1999

HLA class II genotype, HLA-DR B cell surface expression and allergen specific IgE production in atopic and non-atopic members of asthmatic family pedigrees.

HLA class II polymorphism is variably associated with sensitization to specific allergens, but few convincing HLA associations with asthma or the general state of atopy have been demonstrated. In this study we investigated HLA class II genotype associations with asthma, atopy and specific IgE (sIgE) production to six allergen extracts and six purified major allergens (Der p 1, Der p 2, Fel d 1, Can f 1, Alt a 1 and Phl p 5) in 176 individuals from 20 asthmatic family pedigrees. In selected individuals, cell surface HLA-DR peripheral B-cell expression was correlated with HLA-DRB1 genotype and atopic status. Results showed that HLA-DRB1*08 was negatively associated with asthma (2% vs 17%; Pc = 0.02; OR = 0.08) and atopy (0% vs 16%; Pc = 0.04; OR = 0.1), while DRB1*15 was positively associated with asthma (36% vs 13%; Pc = 0.02; OR = 3.6). Analysis of DRB1 sequences showed that only 29% of individuals with GAG TAC TCT ACG at codons 9-12 in one or both alleles were atopic, compared with 53% of individuals without this sequence (P = 0.002; OR = 0.36). DPA1*0201 was negatively associated with sIgE to both grass pollen mix and Phl p 5 (0% vs 23%; Pc = 0.02; OR = 0.14). A non-significant trend towards higher HLA-DR B-cell expression was seen in both non-atopic and DRB1*08 individuals. In conclusion, this single centre study has demonstrated a number of HLA class II genotype associations with asthma, atopy and sIgE to grass pollen mix and Phl p 5, including hitherto unreported DRB1*08, DRB1 codon 9-12 and DPA1*0201 associations. No significant associations between HLA-DR expression and DRB1 genotype or atopy were demonstrated, although a trend towards higher expression was seen in non-atopic individuals and individuals of DRB1*08 genotype.

Allergens↗
PubMed1998

The effect of tyrosine kinase inhibitors on IgE-mediated histamine release from human lung mast cells and basophils.

OBJECTIVE AND DESIGN: To investigate the role of tyrosine kinases (TK) in IgE-mediated signal transduction in human lung mast cells (HLMC) and basophils. MATERIALS: Peripheral blood basophils (n > or = 4) and human lung mast cells (n > or = 6). TREATMENT: Cells were preincubated with TK inhibitor for 15 min at 37 degrees C, before the addition of anti-IgE. METHODS: Histamine release (HR) was assayed using a fluorimetric technique. Results were compared using nonparametric statistics. RESULTS: Piceatannol and ST638 significantly (p < or = 0.05) inhibited anti-IgE induced HR from HLMCs and basophils whilst lavendustin C had no effect in either cell type. Herbimycin A also significantly (p < or = 0.05) inhibited anti-IgE induced HR from both cell types, an effect which was dose dependent but did require a 16 h preincubation with drug. CONCLUSIONS: In summary, HLMCs and basophils exhibit distinct inhibitory profiles in the presence of various inhibitors of TK.

Basophils↗
PubMed1998

Maternal programming in asthma and allergy.

There has been increasing interest in the possibility that the mother has an important role to play in influencing the development of fetal and infant immune responses to allergens during gestation. This finding, by several groups, of specific immune responses of infants at birth to individual trigger factors associated with an underlying immaturity of cytokine production, is intriguing in the light of the development of subsequent allergic disease. The interactions between mother, placenta and fetus are now forming a focus for ongoing research and may be a potential target for intervention aimed at preventing allergic asthma.

Allergens↗
PubMed1998

A childhood asthma death in a clinical trial: potential indicators of risk.

A 9 yr old girl with a history of eczema and asthma was admitted to our specialist asthma service and recruited into a trial designed to investigate systemic as well as therapeutic benefits of inhaled corticosteroids. Eight months after referral the patient died from an acute asthma attack. This childhood asthma death during an inhaled steroid trial has facilitated identification of risk factors. Despite good clinical response to inhaled corticosteroids, the patient was distinguishable from the other patients by: increased variability of the morning and evening peak flow rates; increased reactivity, though not sensitivity, to histamine; and an unprecedented rise in serum soluble interleukin-2 receptor levels immediately after commencing inhaled steroids. The immunological basis for corticosteroid resistance and immunohistochemical studies on postmortem specimens from asthma deaths suggest that T-cell activation markers may be indicators of the fatality prone asthmatic.

Administration, Inhalation↗
PubMed1997

Prenatal origins of asthma and allergy.

The prevalence of asthma and related allergic disorders has increased considerably over the last 25 years. Genetic stock has not changed, so environmental factors must have influenced the phenotype. Infants who develop allergy already have an altered immune response at birth. We have investigated the development of immune responses during gestation and the effect of maternal allergen exposure during pregnancy and infant exposure in the first month of life on the development of allergy and disease. There was higher specific peripheral blood mononuclear cell proliferation to house dust mite (P = 0.01) and birch pollen (P = 0.004) in the third trimester compared with the second trimester, with the first positive responses seen at 22 weeks gestation. Maternal exposure to birch pollen after 22 weeks resulted in higher (P = 0.005) infant peripheral blood mononuclear cell responses to birch pollen at birth. Infants born at term, with at least one atopic, asthmatic parent, who developed allergic symptoms and positive skin prick test by one year of age had raised proliferative responses to house dust mites at birth compared to those with no symptoms (P = 0.01). In genetically predisposed individuals, antenatal factors, including maternal and thereby fetal exposure to allergens and maternoplacental-fetal immunological interactions, are active in determining whether an allergic predisposition is manifested as disease.

Allergens↗
PubMed1997

The effect of co-induction with midazolam upon recovery from propofol infusion anaesthesia.

Forty-eight patients undergoing day-case anaesthesia were asked to complete pre- and postoperative tests of psychomotor function in order to study the influence of co-induction with midazolam in conjunction with propofol/alfentanil anaesthesia on postoperative psychomotor recovery. The study was placebo controlled and double blind with patients receiving either 0.03 mg.kg-1 of midazolam or saline 2 min before induction of anaesthesia with propofol and alfentanil. Patients who underwent co-induction with midazolam had significantly impaired concentration and rapidity of response but improved accuracy and vigilance when compared with those who received saline. The study confirmed that co-induction with a subanaesthetic dose of midazolam reduced the induction dose of propofol by up to 50%. We conclude that co-induction with midazolam reduces psychomotor recovery in the immediate postoperative phase following propofol infusion anaesthesia.

Adjuvants, Anesthesia↗
PubMed1997

Vesicular transport of Charcot-Leyden crystal protein in f-Met peptide-stimulated human basophils.

The ultrastructural localization of Charcot-Leyden crystal (CLC) protein during f-Met-peptide-induced degranulation of human basophils was analyzed at multiple times after stimulation. In this secretion model, piecemeal and anaphylactic degranulation occurred sequentially in stimulated cells and were followed by reconstitution of granule contents. This analysis showed that granule number and alteration and location of gold-labeled, formed CLCs changed over time. CLCs were extruded from granules and remained attached to plasma membranes early after stimulation. At later times, similar structures reappeared in granules in quantity. Smooth-membrane-bound vesicles, analyzed by number, by visible particle contents (or lack of contents) and by gold labeling for CLC protein, showed that empty vesicles increased at the earliest time sampled (0 time) and plunged thereafter in actively extruding and completely degranulated cells. Vesicles containing granule particles were elevated initially at 10 s and at later times. Gold-labeled CLC-protein-containing vesicles were of either empty or particle-filled varieties, and both types were involved with CLC protein transport out of cells at early times and into cells at later times as basophils recovered. Thus, vesicle transport of CLC protein is a mechanism for producing piecemeal degranulation and endocytotic recovery of released CLC protein from human basophils. This vesicular shuttle may be an effector mechanism for widespread piecemeal losses from granules in basophils in inflammatory sites in vivo in human disease.

Anaphylaxis↗