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Biomedical subjects

J A Warner

Publications and source records attributed to J A Warner.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Effect of a bed covering system in children with asthma and house dust mite hypersensitivity.

Allergen avoidance is regarded as an important approach to management of atopic asthma. The effect of Intervent bed covering systems on house dust mite (HDM) allergen exposure, asthma symptoms and markers of inflammation was investigated in 31 HDM sensitive asthmatic children. Dust concentrations of Dermatophagoides pteronyssinus allergen 1 (Der p 1) were monitored before and after covering the mattress, duvet and pillow with active and placebo covers for 3 months, in a single-blind, cross-over trial. Twice daily peak expiratory flow rate (PEFR), daily symptom scores and treatment schedule were recorded. Bronchial hyperresponsiveness was monitored by histamine challenge (provocative concentration of histamine causing a 20% fall in forced expiratory volume in one second (PC20)), and inflammation by measuring eosinophil cationic protein (ECP), eosinophil protein X (EPX), eosinophil peroxidase (EPO), and soluble interleukin-2 receptor (sIL-2R) in serum. There was a significant reduction in Der p 1 when the mattress, duvet and pillow were covered with the active bedding. There was no significant improvement in symptoms of asthma, PEFR, bronchodilator usage of PC20. Also, ECP, EPX, sIL-2R concentrations did not change for either treatment. EPO concentrations were significantly lower in the active compared to the placebo period. The active bed covers reduced retrievable Dermatophagoides pteronyssinus allergen 1 (Der p 1) from the bedding, with short term clinical benefit.

Adolescent↗

Localization of Charcot-Leyden crystal protein in individual morphological phenotypes of human basophils stimulated by f-Met peptide.

BACKGROUND: Human basophils undergo anaphylactic degranulation, characterized by extrusion of membrane-free granules, and piecemeal degranulation, characterized by progressive removal of granule contents in the absence of granule extrusion. F-Met peptide stimulates a degranulation continuum in human basophils that includes both forms of secretion. Charcot-Leyden crystal protein is stored in the granules of unstimulated human basophils. OBJECTIVE: The objective of this study was to determine the subcellular localization of the Charcot-Leyden crystal protein in individual morphological basophil phenotypes that are stimulated by f-Met peptide and are associated with secretion. METHODS: A post-embedding immunogold analysis was used to detect changes in the subcellular sites of Charcot-Leyden crystal protein in human basophils stimulated with f-Met peptide. Human basophils from normal donors were purified by countercurrent centrifugal elutriation and Percoll density gradients, stimulated to degranulate with 1 micron f-Met peptide (or incubated in buffer controls), and recovered for histamine assay, electron microscopy and immunogold labelling. Specificity controls included omission of the primary antibody and substitution of the primary antibody with non-immune normal rabbit IgG or with Charcot-Leyden crystal protein-Sepharose-absorbed primary antibody. RESULTS: The results showed new sites of labelling and different densities of labelling for Charcot-Leyden crystal protein in distinctive basophil phenotypes stimulated by f-Met peptide. New sites for Charcot-Leyden crystal protein included nucleus, cytoplasm, degranulation channel, degranulation channel membrane, plasma membrane, and a newly recognized granule population similar to primary granules in eosinophils. These new sites, as well as previously documented sites of Charcot-Leyden crystal protein (granules, intragranular Charcot-Leyden crystals, cytoplasmic vesicles) showed variable labelling when analysed by phenotype. Other sites (besides intragranular Charcot-Leyden crystals) of formed Charcot-Leyden crystals included cytoplasm, degranulation channel, extracellular space and, rarely, nucleus. Analysis of cytoplasmic vesicles, total granules and altered granules, and gold particles in subcellular compartments in seven identifiable phenotypes revealed that f-Met peptide stimulated human basophils to empty their granules by transporting Charcot-Leyden crystal protein in vesicles to the plasma membrane in the absence of granule extrusion in cells exhibiting piecemeal degranulation. In cells exhibiting anaphylactic degranulation, gold-labelled Charcot-Leyden crystals were extruded to the cells' exterior in concert with granule particles and concentric dense membranes contained within granules. Completely degranulated cells had a high density of plasma membrane gold label that was associated with numerous gold-laden endocytotic cytoplasmic vesicles. Basophils reconstituted their main granule population, within which Charcot-Leyden crystals resided, in part by endocytosis of previously released plasma membrane-bound Charcot-Leyden crystal protein. Completely recovered cells displayed decreased Charcot-Leyden crystal protein labelling of the plasma membrane and vesicle compartments, the presence of a highly labelled new granule subset that resembled Charcot-Leyden crystal protein-containing primary granules in eosinophils, and the highest density of granule and intragranular Charcot-Leyden crystal gold labelling of all phenotypes that developed after stimulation. CONCLUSION: Seven individual f-Met peptide-activated human basophil phenotypes labelled by an ultrastructural immunogold method to detect subcellular sites of Charcot-Leyden crystal protein showed changing distributions of this protein which document the capability of human basophils to undergo complex release and recovery reactions that may be pertinent to the functions of Charcot-Leyden crystal protein and the capabilit

Anaphylaxis↗

Immune responses during pregnancy and the development of allergic disease.

It is now established that allergen exposure in the first few months of life is important in the development of specific allergic sensitisation (1, 2). Furthermore, the immune response of infants born to families with a strong history of allergic disease is relatively immature at birth in comparison to infants with no family history of allergies, with reduced production of Interferon-gamma (IFN-gamma) (3-5) and lower levels of T cell activation and memory (6). It therefore seems logical that the interaction of these two factors must be important in the ontogeny of allergic disease.

Allergens↗

The eosinophil and its role in asthma.

1. The eosinophil is part of the host defence mechanism to parasitic infection, but is also a key cell in many inflammatory disorders. 2. Eosinophils synthesise a range of pro-inflammatory and cytotoxic mediators, such as basic proteins, hydrolytic enzymes, lipid mediators, cytokines, oxygen metabolites and neuropeptides. 3. Eosinophils are recruited to the lung during episodes of asthma. They migrate from the blood vessels into the tissue via a series of interactions between their surface adhesion molecules and endothelial cells or the extracellular matrix. 4. Activation and prolonged survival of eosinophils occurs upon exposure to mediators released from other tissue resident leukocytes, including eosinophils themselves, and from respiratory tract epithelial cells. Release of eosinophilic mediators causes tissue damage and persistent inflammation of the lung. 5. Currently the most effective therapy for asthma lies with anti-inflammatory drugs, of which the main choices are inhaled corticosteroids or cromolyn sodium and nedocromil sodium.

Animals↗

Fetal peripheral blood mononuclear cell proliferative responses to mitogenic and allergenic stimuli during gestation.

Blood samples were obtained from fetuses and premature babies (n = 51) (15-34 weeks gestation) to determine at what stage the fetal immune system was able to produce a positive proliferative response to common allergens. Peripheral blood mononuclear cells (PBMC) were stimulated with the mitogen, phytohaemagglutinin (PHA), and the allergens, house dust mite, cat fur, birch tree pollen, beta-lactoglobulin, ovalbumin and bee venom (mellitin). Results were expressed as ratios of stimulated to unstimulated 3H thymidine incorporation, and as percent positive responders. There was an increase in proliferation ratio which correlated with increasing gestational age for PHA (p < 0.0001), cat fur (p = 0.042), birch pollen (p = 0.022) and beta-lactoglobulin (p = 0.006). The point in gestation when cells from some individuals began responding to the allergens with a ratio of 2.0 was at approximately 22 weeks. PBMC proliferative response ratios were higher from samples from babies > 22 weeks gestation compared to < 22 weeks for the mitogen and all allergens, except mellitin. There was also a greater proportion of positive responders from samples > 22 weeks compared to < 22 weeks for the mitogen and all allergens, except mellitin. Maternal exposure to birch pollen, which has a discrete season, was assessed to determine whether exposure had occurred at 22 weeks gestation or beyond. Results showed a higher proliferative response in infant cells stimulated with birch pollen (p = 0.005) and higher proportion of positive responders (p = 0.01) in the group of babies whose mothers had been exposed to birch pollen beyond 22 weeks, compared to those whose mothers had not been so exposed. These results suggest that in utero fetal exposure to an allergen from around 22 weeks gestation may result in primary sensitisation to that allergen, leading to positive proliferative responses, at birth.

Adult↗