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Biomedical subjects

J A Woodfolk

Publications and source records attributed to J A Woodfolk.

At least 19 recordsLinked to original sources
PubMed2006

Cytokines as a therapeutic target for allergic diseases: a complex picture.

Production of IgE antibodies promotes the development of allergic disorders such as asthma, rhinitis and atopic eczema. Though Th2 cytokines play a pivotal role in the allergic inflammatory cascade, therapeutic strategies which target these factors have not been curative in clinical trials. In humans, the allergic phenotype encompasses a broad spectrum of diverse clinical entities, which are dictated by genetics as well as the nature of the allergen and the time in life at which allergen is encountered. The disparate findings in animal and human systems highlight the complexity of cytokine-mediated events in allergic responses in man. Different allergic phenotypes cannot be distinguished strictly on the basis of Th1 and Th2 cytokines. These observations coupled with an emerging role for regulatory T cells in modulation of the allergic response warrant re-examination of the cytokine network in allergic disease. This article highlights the challenges of dissecting the role of individual cytokines in the development of allergic responses and manifestation of allergic symptoms. Regulatory T cells have been implicated in modulation of the activity of allergen-specific Th1 and Th2 effector cells and immune outcome; however, the characteristics of these regulatory T cells remain largely undefined. The effects of existing and emerging therapies which target Th1, Th2 and regulatory cytokines on established allergic responses are examined in the context of this new paradigm. Taken together, existing data suggest that a multi-faceted approach, which is tailored to each patient, will be required in order to attain clinical benefit.

Animals↗
PubMed2005

Asthma and indoor air: contrasts in the dose response to cat and dust-mite.

UNLABELLED: The role of the indoor environment in asthma is of major concern because (i) the disease has become more severe; (ii) we spend>or=90% of our lives indoors and (iii) a large proportion of asthmatic children and young adults are allergic to allergens found indoors. Recent evidence that children raised in a home with animals, i.e. indoor cat or dog, are less likely to become allergic has provided a great opportunity to understand the mechanisms controlling the prevalence of allergic disease. In addition the results pose a challenge to many of the hypotheses about reasons for the increase in asthma. The evidence that children or adults who make a modified TH2 response i.e. immunoglobulin (Ig)G and IgG4 ab without IgE, are not at increased risk of asthma strongly supports the role of IgE in asthma. Equally the results may give insight into a form of tolerance that could be a target for protecting patients against allergic disease. PRACTICAL IMPLICATIONS: Evidence for the immune response to cat allergen shows that the alternative response to an allergy, TH2 response, is a controlled or modified form of the response not a Th1 response. Furthermore, avoiding cats in the home in most communities would not decrease the prevalence of sensitization to cats because there is cat allergen distributed in schools, other public buildings, and homes without a cat.

Air Pollution, Indoor↗
PubMed2003

Quantitative measurement of airborne allergens from dust mites, dogs, and cats using an ion-charging device.

BACKGROUND: Increasing evidence suggests that children raised with an animal(s) in the house have a decreased risk of becoming sensitized. However, it is not clear whether this phenomenon is related to airborne exposure. OBJECTIVE: To estimate airborne exposure to animal dander and dust mite allergens using a device that can sample large volumes of air silently. METHODS: The device, which uses an ion-charging technique to move air and to collect particles, was run at 1.7 m3/min for 24 h in 44 homes with and without animals. The allergen collected was measured by ELISA for Fel d 1, Can f 1, Der p 1, and Der f 1. RESULTS: Airborne Fel d 1 was present in all homes with a cat (n=27). The quantities measured, i.e. 0.5-20 microg in 24 h, represent 0.01-0.3 microg Fel d 1 inhaled/day at normal breathing rates (20 L/h). Values for houses without a cat were 0.01-0.05 microg inhaled/day. Airborne Fel d 1 correlated significantly with floor Fel d 1 (r=0.58, P<0.001). Results for Can f 1 were similar in houses with a dog, but this allergen was only detected airborne in two houses without a dog. Neither Der p 1 nor Der f 1 (i.e. <0.01 microg) was detected, which represents < or =1 ng inhaled/day during normal domestic activity. During disturbance airborne mite was detected with both the ion-charging device and a filter run in parallel. For cat and mite allergens there was a close correlation between the two techniques (r=0.84, P<0.001). CONCLUSION: Exposure to cat or dog allergen airborne in homes with an animal can be up to 100 times higher than exposure to mite allergen. The results are in keeping with a model where immunological tolerance to animal dander allergens results from high exposure.

Air Pollutants↗
PubMed2001

Diversity of the human allergen-specific T cell repertoire associated with distinct skin test reactions: delayed-type hypersensitivity-associated major epitopes induce Th1- and Th2-dominated responses.

Distinct immune responses in humans to the Trichophyton rubrum Ag, Tri r 2, are associated with different patterns of T cell epitope recognition based on in vitro proliferation to peptides derived from this 29-kDa protein. Specifically, the amino-terminal immunodominant epitope, peptide 5 (P5), stimulates strong T cell proliferative responses in subjects with delayed (DTH), but not immediate (IH) hypersensitivity skin tests. Evidence of a role for cytokines or changes in epitope recognition over time was examined in responses to Trichophyton using primary PBMC cultures established from seven IH and seven DTH subjects. Responses stimulated by Tri r 2 were dominated by the Th1 cytokine IFN-gamma (IFN-gamma:IL-5 > or = 4:1) in five DTH subjects, even in the presence of Th2-dominated responses (IFN-gamma:IL-5 < or = 3:1) to a subset of major epitopes. Paradoxically, P5 induced IL-5 and IL-10 production in DTH, but not IH subjects (p = 0.003 (IL-5), p = 0.024 (IL-10)), with no significant difference in IFN-gamma levels between the two groups. In cultures from IH responders, no IL-5 was measurable after stimulation with P6 and P7 (as well as P5); this region of the molecule was shown previously to stimulate markedly reduced T cell proliferation in these individuals. Repeat proliferation assays confirmed no change in the pattern of peptide recognition after > or =20 mo in IH or DTH subjects. We conclude that T cell repertoires associated with distinct immune responses to Tri r 2 can be distinguished based on Th2 cytokine induction by DTH-associated major epitopes localizing to the amino-terminal region of the molecule.

Adult↗
PubMed2000

Distinct human T cell repertoires mediate immediate and delayed-type hypersensitivity to the Trichophyton antigen, Tri r 2.

The 29-kDa subtilase homologue, Tri r 2, derived from the dermatophyte fungus Trichophyton rubrum, exhibits unique immunologic characteristics in its ability to elicit immediate (IH) and delayed-type (DTH) hypersensitivity skin tests in different individuals. Thus, Tri r 2 provides a model for comparing the T cell repertoire in subjects with distinct immune responses to a single Ag. Recombinant Tri r 2 produced as a GST fusion protein in Escherichia coli stimulated strong in vitro lymphoproliferative responses in 10 IH and 10 DTH responders. Patterns of T cell epitope recognition were compared between skin test groups using 28 overlapping peptides (each in 12 replicate wells) derived from Tri r 2 to stimulate T lymphocyte proliferation in vitro. Peptide 5 (P5; aa 41-60) induced the strongest response in DTH subjects and showed the largest difference between DTH and IH responders in proliferation (mean standardized index, 2.22 and 0.82, respectively; p = 0.0047) and number of positive wells (81 vs 12). Responses to P5 were associated with diverse HLA haplotypes. These results showed that P5 contains an immunodominant epitope specifically associated with DTH and that this peptide is recognized in a permissive manner. Cross-validated linear discriminant analysis using T cell proliferative responses to two regions of Tri r 2 (aa 51-90 and 231-270) gave a 95% predictive accuracy for classification of subjects into IH or DTH groups. We conclude that different immune responses to Trichophyton are mediated by distinct T cell repertoires between individuals with IH and DTH reactions to Tri r 2.

Adult↗
PubMed2000

The role of intervention in established allergy: avoidance of indoor allergens in the treatment of chronic allergic disease.

Avoidance of exposure to indoor allergens is an important element in the treatment of allergic disease. The results of several studies provide strong evidence in support of a role for allergen avoidance; however, strategies that optimize allergen reduction in houses have not been determined. Complex issues regarding the efficacy of physical and chemical measures that target house dust mite, pet, and cockroach allergens in the home are discussed. The greatest challenge is to educate allergic patients so that they can play an important role in controlling their own disease.

Air Pollution, Indoor↗
PubMed1999

Assessment of vacuum cleaners and vacuum cleaner bags recommended for allergic subjects.

BACKGROUND: High-quality vacuum cleaners and vacuum cleaner bags are often recommended to allergic patients as a means of reducing indoor allergen exposure. A number of vacuum cleaners on the market today claim to capture 99.9% of particles 0.3 microm or larger entering the vacuum cleaner, and many vacuum cleaner bags are now being sold as microfiltration bags. OBJECTIVE: The purpose of this study was to compare the allergen-trapping abilities of vacuum cleaners and to use a new technique for testing vacuum cleaner bags that are recommended for allergic patients. METHODS: Vacuum cleaners were tested in an 18-m(3) laboratory room permeated with dust containing high levels of cat allergen by using techniques previously described. Air was sampled with parallel filters in conjunction with a particle counter. The filters were assayed by ELISA for cat allergen (Fel d 1). Vacuum cleaner bags were tested by using a modified dust trap to pull sieved house dust containing a known amount of Fel d 1 across the material used for the bag. Allergen passing through the bag was trapped on a filter covering the exit of the trap and analyzed for Fel d 1. RESULTS: In general, vacuum cleaners designed for allergic patients leaked lower amounts of allergen (<0.5-4.04 ng/m(3)) than that found in our previous studies (<0.5-100 ng/m(3)). Single-layer vacuum cleaner bags performed poorly (1250-2640 ng recovered) compared with most of the 2- and 3-layer microfiltration bags (0.53-2450 ng recovered). The range of allergen recovered from the 2-layer bags (0.93-2450 ng recovered) highlighted the variability found between manufacturers. CONCLUSION: The results suggest that although allergen leakage has been reduced, there is still room for improvement. A method of testing allergen leakage by using Fel d 1 should be applied to vacuum cleaners and bags recommended for allergic patients.

Air Pollution↗
PubMed1999

Treatment of late-onset asthma with fluconazole.

BACKGROUND: Although the etiology of intrinsic or late-onset asthma is generally not known, some cases are associated with overt dermatophyte infection and immediate hypersensitivity to proteins derived from fungi of the genus Trichophyton. OBJECTIVE: We sought to test the efficacy of oral antifungal treatment for Trichophyton-induced asthma by using fluconazole in a placebo-controlled trial. METHODS: Eleven patients with severe or moderately severe asthma were randomized to treatment with fluconazole 100 mg daily or placebo for 5 months (phase 1); during the following 5 months, all patients received active drug (phase 2). Subjects were evaluated by skin tests, bronchial provocation tests, and measurement of serum antibodies to Trichophyton species antigens. Clinical response was monitored by changes in peak flow values measured during a 2-week period at the end of each phase and by changes in bronchial sensitivity, symptoms, and steroid requirements. RESULTS: At the end of the first 5 months of active treatment, there was a highly significant decrease in bronchial sensitivity to Trichophyton (P =.012) and in oral steroid requirement (P =.01). At the end of phase 2, mean peak expiratory flow rates increased in 9 of 11 patients. An improvement in symptoms, peak flow, and steroid use was maintained up to 36 months after starting fluconazole in patients who continued to receive treatment. CONCLUSION: The results show that fluconazole can be useful in the treatment of patients with severe or moderately severe asthma who have dermatophytosis. These findings are consistent with the argument that proteins derived from fungi on the skin and nails can contribute to allergic disease.

Adult↗
PubMed1998

Trichophyton antigens associated with IgE antibodies and delayed type hypersensitivity. Sequence homology to two families of serine proteinases.

The dermatophyte fungus Trichophyton exhibits unique immunologic properties by its ability to cause both immediate and delayed type hypersensitivity. An 83-kDa Trichophyton tonsurans allergen (Tri t 4) was previously shown to elicit distinct T lymphocyte cytokine profiles in vitro. The homologous protein, Tri r 4, was cloned from a Trichophyton rubrum cDNA library, and the recombinant protein was expressed in Pichia pastoris. This 726-amino acid protein contained an arrangement of catalytic triad residues characteristic of the prolyl oligopeptidase family of serine proteinases (Ser-Asp-His). In addition, a novel Trichophyton allergen, encoding 412 amino acids, was identified by its human IgE antibody-binding activity. Sequence similarity searches showed that this allergen, designated Tri r 2, contained all of the conserved residues characteristic of the class D subtilase subfamily (41-58% overall sequence identity). Forty-two percent of subjects with immediate hypersensitivity skin test reactions to a Trichophyton extract exhibited IgE antibody binding to a recombinant glutathione S-transferase fusion protein containing the carboxyl-terminal 289 amino acids of Tri r 2. Furthermore, this antigen was capable of inducing delayed type hypersensitivity skin test reactions. Our results define two distinct antigens derived from the dermatophyte Trichophyton that serve as targets for diverse immune responses in humans.

Allergens↗
PubMed1997

Evaluation of different techniques for washing cats: quantitation of allergen removed from the cat and the effect on airborne Fel d 1.

BACKGROUND AND OBJECTIVE: The purpose of this study was to examine the quantity and distribution of the major cat allergen, Fel d 1, on cats and to evaluate the efficacy of washing, both in removing allergen from the cat and reducing airborne allergen levels. METHODS: Airborne samples were collected on four glass fiber filters in a 30 m3 room, before and 3 hours after serial washing of eight cats (45-minute sampling at 18 L/min for each filter). Aliquots of hair and bath water were also collected and assayed for Fel d 1 content. RESULTS: Extracting cat hair with tap water or pet shampoo for 3 minutes removed mean levels of 191 and 245 microg of Fel d 1 per gram of hair, respectively; the quantity of allergen on samples of cat hair ranged from 1 microg/gm to more than 1770 microg/gm. The highest concentration of allergen was found on hair from the neck. Estimates of the total Fel d 1 on the cat, based on shaving the whole cat, ranged from 3 to 142 mg (mean = 67 mg). Washing cats reduced airborne allergen 3 hours later. Washing three cats at weekly intervals for 5 weeks in a veterinarian's office produced a mean decrease of 44% in airborne Fel d 1 (n = 15, p < 0.02). Washing three cats by immersion for 3 minutes at weekly intervals for a 1-month period produced a mean decrease in airborne allergen of 79% (n = 12, p < 0.001). However, after repeated washing, the airborne levels before the next wash were not consistently decreased. The quantity of Fel d 1 removed by immersion varied from 1 to 35 mg. CONCLUSION: Cats carry large quantities of Fel d 1, only a small proportion of which (approximately 0.002%/hr) becomes airborne. Washing cats by immersion will remove significant allergen from the cat and can reduce the quantity of Fel d 1 becoming airborne. However, the decrease is not maintained at 1 week.

Air Pollutants↗