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Biomedical subjects

A S Kemp

Publications and source records attributed to A S Kemp.

At least 37 records · Page 2Linked to original sources

Proliferation and production of interferon-gamma (IFN-gamma) and IL-4 in response to Staphylococcus aureus and staphylococcal superantigen in childhood atopic dermatitis.

We have examined the cell-mediated immunity (CMI) to Staphylococcus aureus (S. aureus) and Staphylococcal enterotoxin B (SEB) in peripheral blood mononuclear cells (PBMC) from children with atopic dermatitis (AD) and from non-atopic child controls by measurement of proliferative responses and production of the cytokines IFN-gamma and IL-4. PBMC from children with AD showed significantly higher proliferative responses to both S. aureus (P < 0.01) and SEB (P < 0.05). Despite this enhanced proliferation, production of IFN-gamma in response to S. aureus (P < 0.001) and SEB (P < 0.01) from these PBMC was significantly diminished. In contrast, PBMC from children with AD were significantly more likely to produce IL-4 in response to S. aureus (P < 0.01). These findings demonstrate in vitro heightened CMI to S. aureus in children with AD, and implicate S. aureus as a potent inflammatory stimulant. Impaired IFN-gamma production to S. aureus in vivo may result in failure to eradicate S. aureus from skin. The organism's persistence on skin would contribute to inflammation by causing continued T cell activation and release of pro-inflammatory mediators.

Cell Division↗

Atopic eczema: its impact on the family and financial cost.

OBJECTIVE: To evaluate the impact of childhood atopic eczema on families and assess the personal financial cost of its management. DESIGN: Cross sectional survey. SETTING: Paediatric dermatology and paediatric diabetology outpatient clinics. PATIENTS: Parents of 48 randomly selected children with atopic eczema and 46 with insulin dependent diabetes mellitus. MAIN OUTCOME MEASURES: The impact on family score, the reported cost of relevant medical treatments, medical consultations, relevant hospitalisation, and income loss. RESULTS: Families of children with moderate or severe atopic eczema had a significantly higher impact on family score than families of diabetic children. A conservative estimate of the annual personal financial cost of managing mild, moderate, and severe eczema was Aus$330, 818, and 1255, respectively. The financial cost to the community for the management of atopic eczema in the study groups was greater. The personal financial cost of managing eczema was greater than for asthma. CONCLUSION: Childhood atopic eczema has a profound impact on the social, personal, emotional, and financial perspectives of families.

Adolescent↗

New perspectives on inflammation in atopic dermatitis.

Recent information implicates the stimulation of T cells by Staphylococcus aureus antigens and exotoxins as a likely factor in provoking the inflammatory response in atopic dermatitis. S. aureus secrets exotoxins called superantigens, which stimulate a large proportion of T cells. In addition, protein A, a component of the cell wall of S. aureus, is a potent B cell mitogen. This understanding provides a rationale for attempting to reduce the staphylococcal skin colonization of patients with severe atopic dermatitis and correlates with the clinical observation in a number of situations of marked improvement in atopic dermatitis following antibiotic treatment.

Adult↗

Interleukin-4 and interferon-gamma production in atopic and non-atopic children with asthma.

Previous studies have demonstrated increased production of interleukin-4 (IL-4) and reduced production of interferon (IFN)-gamma in stimulated peripheral blood mononuclear cell cultures from children and adults with atopic dermatitis, however, it is unclear whether such an imbalance of cytokine production relates to other childhood atopic diseases such as asthma, and in particular to the presence of the atopic state per se. The production of IL-4 and IFN gamma in phytohaemagglutin- (PHA)-stimulated peripheral blood mononuclear cell (PBMC) cultures from atopic and non-atopic children with moderately severe chronic persistent asthma, and a group of age-matched non-atopic controls who did not have asthma was examined. Atopic children with asthma produced significantly more IL-4 and less IFN gamma than non-atopic children with asthma and non-atopic controls who did not have asthma. There was no significant difference in IL-4 or IFN gamma production between non-atopic children with asthma and controls. These findings demonstrate that an imbalance of IL-4 and IFN gamma production is present in atopic asthma as previously documented in atopic dermatitis, therefore suggesting that it is a feature of the atopic state per se.

Asthma↗

Ontogeny of IL4 production.

There is evidence to suggest that the production of some cytokines in childhood is different to that in adults. The production of IL4 in PHA-stimulated PBMC cultures was examined in healthy neonates, children and adults to determine the ontogeny of IL4 production throughout childhood. In vitro IL4 production was found to be significantly reduced in neonates and children under 10 years of age as compared to adults, and to increase progressively with age. The mechanisms leading to reduced IL4 production in neonates were shown to be different to those in children, with a defect in signal transduction demonstrated for lymphocytes from neonates but not children < 10 years. The presence of an inhibitory factor in cord blood plasma was also noted. These age-dependent variations in IL4 production and response to stimulation with PMA/Ca may reflect differences in naive and memory T cell populations.

Adolescent↗

Reduced interferon-gamma secretion in neonates and subsequent atopy.

Low interferon-gamma (IFN-gamma) secretion has been found in individuals with active atopic disease. Whether this is a cause or result of the disease process is uncertain. Cord blood IFN-gamma secretion was examined in 35 neonates who were then prospectively followed up for 1 year for the development of atopic disease. Infants who developed either symptoms of atopic disease or a positive IgE-mediated skin prick test at 12 months of age produced significantly less IFN-gamma at birth compared with those who did not (p = 0.005). This reduced secretion of IFN-gamma at birth indicates that the defect in interferon secretion is a primary component of the atopic state rather than an effect of the disease process.

Breast Feeding↗

Cow milk allergy within the spectrum of atopic disorders.

In order to examine the relationship between cow milk allergy (CMA) and atopic disorders in childhood, a consecutive group of 42 infants with IgE mediated CMA was followed for at least 2 years. The incidence of sensitization to common food and inhalant antigens and the development of eczema, asthma, and food allergies was examined for the cohort and compared between patients whose CMA remitted and those with persistent disease. In this cohort the prevalence of eczema was 57%, asthma 69%, egg allergy 67%, peanut allergy 55%, and 83% of infants demonstrated positive skin-prick tests to three or more allergens. At the end of the study CMA had remitted in 13 patients (median age 44 months) whereas in 29 patients it persisted (median age 44 months). Although there was no significant difference in the incidence of eczema or asthma during the study between these two patient groups, the incidence of allergy to egg and peanut butter was significantly greater for children with persistent CMA. Consistent with our hypothesis that children with persistent CMA have a more severe dysregulation of IgE synthesis than those whose disease remits, patients with persistent CMA had a significantly higher incidence of and level of skin sensitivity to inhalant and other dietary allergens. Sensitization to the inhalant allergens Dermatophagoides pteronyssinus, cat dander and rye grass was frequently seen in early infancy and increased during the study period. Thus, children with IgE mediated CMA frequently generate IgE responses to multiple dietary and inhalant allergens in infancy and early childhood and develop immediate hypersensitivity to other foods as well as clinical eczema, and asthma.

Allergens↗

Reduced interferon-gamma (IFN-gamma) secretion with increased IFN-gamma mRNA expression in atopic dermatitis: evidence for a post-transcriptional defect.

Reduced secretion of IFN-gamma in atopic individuals has been implicated in the pathogenesis of disease, though the mechanisms leading to this reduced secretion have not been elucidated. As production of IFN-gamma has been shown to be predominantly regulated by its rate of transcription, expression of IFN-gamma mRNA was examined in atopic children and in age-matched, non-atopic controls by polymerase chain reaction (PCR)-assisted mRNA amplification. Children with atopic dermatitis were found to have constitutive expression of IFN-gamma mRNA in freshly isolated peripheral blood mononuclear cells (PBMC) and in unstimulated PBMC cultures which increased further following stimulation with phorbol myristate acetate (PMA)/Ca in vitro. In contrast, expression of IFN-gamma mRNA in controls was only detected in stimulated cultures, as has been demonstrated previously for normal adults. These findings demonstrate that circulating T cells from atopic children have been activated in vivo, and suggest that T cell activation is a significant component of the inflammatory process in atopic dermatitis. Although expression of IFN-gamma mRNA was increased in the atopic children, secretion was confirmed to be significantly lower than in controls, indicating that the defect(s) underlying reduced IFN-gamma secretion in these individuals lie post-transcriptionally.

Base Sequence↗

Spontaneous expression of IL-4 mRNA in lymphocytes from children with atopic dermatitis.

Normal lymphocytes do not generally produce or secrete lymphokines in the resting or unstimulated state and only express or release cytokines following activation. Recently, the spontaneous production of intracellular interferon-gamma (IFN-gamma) and spontaneous secretion of IL-6 has been documented in patients with atopic dermatitis. These findings indicated that lymphocytes had been previously activated in vivo. Such in vivo activation may also be associated with spontaneous production of IL-4. As measurement of IL-4 secretion by immunoassay is complicated by poor sensitivity, and only provides information on the net amount of cytokine present after secretion, adsorption, consumption and degradation have occurred, IL-4 mRNA expression in peripheral blood lymphocytes from children with atopic dermatitis and controls was examined by polymerase chain reaction (PCR)-assisted mRNA amplification. Spontaneous expression of IL-4 mRNA was detected in four of eight patients with severe atopic dermatitis. Following stimulation in vitro, seven of eight atopic patients demonstrated detectable IL-4 mRNA. In comparison, no spontaneous expression of IL-4 mRNA was found in controls, and only six of 10 controls expressed IL-4 mRNA in stimulated cultures. The spontaneous expression of IL-4 mRNA in unstimulated cultures from children with atopic dermatitis supports the possibility that previous in vivo activation has occurred, and suggests that IL-4 production is increased in vivo in atopic dermatitis. This in vivo activation together with the constitutive expression of IL-4 mRNA are likely to contribute to the spontaneous in vitro production of IgE in atopic patients.

Base Sequence↗

Features of transient hypogammaglobulinaemia in infants screened for immunological abnormalities.

The incidence of transient hypogammaglobulinaemia of infancy (THI) detected in a major paediatric centre over a 10 year period was examined. A total of 2468 subjects less than 2 years of age had an IgG measurement taken between July 1979 and March 1990. Subjects with known immunodeficiencies were excluded. Fifteen patients were classified as having THI with an initial IgG level less than the fifth centile followed by a second measurement within the normal range. A further 24 patients were identified as having possible THI with a single low IgG concentration. There were 60,174 live births each year in Victoria in the years 1979-88. This gives an incidence of proved THI of 23 per 10(6) births, and including proved and probable THI an incidence of 61 per 10(6) live births. Of those patients with proved THI 12/15 had symptoms of either atopic disease or food allergy/intolerance and three had gastrointestinal symptoms without any evidence of atopic disease. At presentation 12/15 (80%) were IgA deficient and 9/15 had IgM concentrations less than the 20th centile for age. It is suggested that in view of the preponderance of atopic and food intolerant patients that subclinical protein loss from the bowel due to allergic inflammation may be a contributing factor to the development of THI in some patients.

Agammaglobulinemia↗

Delayed umbilical cord separation in alloimmune neutropenia.

Delayed umbilical cord separation in association with neonatal alloimmune neutropenia is reported. Delayed umbilical cord separation has been described in association with defects in neutrophil function. The present case indicates that deficiency in neutrophil number should also be considered as a cause of delayed cord separation.

Female↗

Growth hormone deficiency and combined immunodeficiency.

The first description of an association of isolated growth hormone deficiency (IGHD) and combined immunodeficiency is presented. The findings suggest that IGHD should be considered as a cause of short stature in children with combined immunodeficiency before attributing growth retardation to infection.

Child, Preschool↗