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Biomedical subjects

J Ring

Publications and source records attributed to J Ring.

647 records · Page 36Linked to original sources

Biophysical characteristics of healthy skin and nonlesional skin in atopic dermatitis: short-term effects of ultraviolet A and B irradiation.

The present study was designed to evaluate basic differences in surface structure and viscoelastic properties of nonatopic versus atopic skin and facultative acute changes following ultraviolet irradiation. Therefore, biophysical measurements by means of profilometry and cutometry were carried out on sun-protected unaffected gluteal skin areas in both groups before and 24 h after single UVA and UVB irradiations. The results indicate that the clinically unaffected skin of patients with atopic eczema differs from normal skin in terms of increased roughness parameters, but not concerning depth of furrows or viscoelastic properties (viscosity and biological elasticity, cutometrically calculated). Single UVA irradiation with 50 J/cm(2) induced neither measurable changes in the skin's surface structure nor in its viscoelastic properties in both groups after 24 h. However, irradiation with a single erythemogenic dose of 1 MED UVB was followed by a short-term significant increase in the depths of furrows and decrease in biological elasticity in normal and atopic skin, accompanied by an increase in viscosity in normal skin.

Adult↗

Enu mouse mutagenesis: generation of mouse mutants with aberrant plasma IgE levels.

BACKGROUND: The ENU Mouse Mutagenesis Project aims at a large-scale, systematic production of mouse mutants using the alkylating agent ethyl-nitrosourea (ENU). Offspring of mutagenized mice are subjected to a multiparameter screen to detect alterations in various phenotypes with the ultimate goal of identifying novel genes relevant for the expression of the phenotype. Using this approach, we have analyzed plasma IgE concentrations to identify mouse mutants with aberrant plasma IgE levels. METHODS AND RESULTS: ENU-mutagenized male C3HeB/FeJ were mated to wild-type females to produce F1 offspring. F1 animals were analyzed for alterations in their plasma IgE concentrations that showed a dominant mode of inheritance, or bred further to screen for recessive phenotypes. Plasma IgE concentrations were determined by ELISA and a normal range for plasma IgE was established using C3HeB/FeJ wild-type animals. So far we have tested 6568 F1 animals. Repeated testing confirmed a stable aberrant IgE phenotype in 124 animals. To confirm the genetic basis of the observed phenotype, these mice were subjected to confirmation crossing. Currently we have established 9 independent mutant mouse lines (3 with high plasma IgE and 6 with plasma IgE below detection limit) that have been genetically confirmed and additional 24 variant mouse lines are currently undergoing confirmation testing. CONCLUSION: ENU mouse mutagenesis allowed us to generate and identify mouse mutants with aberrant plasma IgE levels, which may be used to characterize novel genes involved in IgE regulation and may serve as animal models for IgE-mediated diseases.

Alkylating Agents↗

Secretion of proinflammatory eicosanoid-like substances precedes allergen release from pollen grains in the initiation of allergic sensitization.

It is commonly believed that allergic sensitization starts when an allergen contacts the surface of an antigen-presenting cell in mucosal or skin epithelia. Most studies dealing with this aspect use allergen extracts as stimulus. Under natural exposure conditions, however, the bioavailability of allergen depends on allergen liberation from internal binding sites within the allergen carrier, e.g. pollen grains. In comparing total protein and major allergen release from timothy grass (Phleum pratense L.) pollen freshly collected on rural meadows or near high-traffic roads, there was a striking difference between the pollen, with higher allergen release rates from rural meadow pollen grains. Thus, allergen release does not explain the higher prevalence rates of atopic sensitization and disease observed in many epidemiological studies in children exposed to automobile exhaust. Therefore, other possible effectors from pollen grains were investigated. Pollen grains incubated in protein- free buffer were found to secrete significant amounts of eicosanoid-like substances, namely leukotriene (LT) B(4)-like and prostaglandin E(2)-like substances, in a pH-, time- and temperature-dependent fashion. The highest values of eicosanoid secretion were found in birch, grass and mugwort pollen, while pine (Pinus sylvestris L.) pollen showed only marginal eicosanoid-like secretion. Additionally, the release of these substances was significantly higher from pollen which had been collected near roads with heavy traffic, indicating a stronger proinflammatory activity of these pollen grains. In order to investigate the effects of air pollutants, native pollen grains were exposed in a dose- and time-dependent fashion in a fluidized bed reactor to traffic-related pollutants, e.g. volatile organic compounds (toluene, m-xylene), leading again to a significant increase in the secretion of LTB(4)-like immunoreactivity, in contrast to exposure with sulfur dioxide. This finding opens a new dimension of understanding of the early events in allergic sensitization, indicating that proinflammatory effects of the allergen carrier, e.g. the pollen grain itself, can lead to activation of the mucosal membrane. These findings might help to also explain the higher prevalence rates of pollen allergy in areas with high automobile exhaust emissions. Furthermore, the allergenic 'potency' of various allergens has to be redefined at the allergen carrier level with regard to different stages of allergen and mediator release prior to the contact with the host's immune system.

Air Pollution↗

New aspects of itch pathophysiology: component analysis of atopic itch using the 'Eppendorf Itch Questionnaire'.

Itch represents a leading symptom in dermatological practice with many psychophysiological aspects. Instruments for qualitative registration of these central nervous factors and evaluation of therapeutic measures are still missing. We analyzed in detail the subjective itch sensation in 108 patients with acute atopic eczema with a new questionnaire developed in analogy to the McGill pain questionnaire. The descriptors with the highest load in atopic itch and the most frequent reaction patterns in atopic eczema patients were identified. Itch intensity (mean VAS 62%) and eczema severity (SCORAD mean 41 points) showed a different frequency distribution pattern with a correlation of r = 0.33 (p < 0.05). Principal component analysis of the itch questionnaire data was performed and compared with the standardized SCORAD severity index for the patients with atopic eczema. Three main factors of atopic itch explained 58% of the total variance: (1) 'suffering' (correlation with SCORAD, r = 0.6); (2) 'phasic intensity' (correlation with SCORAD, r = 0.4), and (3) 'ecstatic' component (associated with certain active reaction patterns). In conclusion, the complete description of itch has to consider different factors, which may be described on a more general level by three main components. Two of these are correlated with objective criteria of disease activity.

Adolescent↗

Staphylococcal enterotoxin B affects in vitro IgE synthesis, interferon-gamma, interleukin-4 and interleukin-5 production in atopic eczema.

Peripheral blood mononuclear cells from patients with atopic eczema (AE) stimulated with the 'superantigen' Staphylococcus enterotoxin B (SEB) secreted significantly more interleukin (IL)-4 and IL-5 as well as IgE, and markedly less interferon-gamma than those from healthy controls. Our results support the assumption that SEB produced by S. aureus colonizing the skin of patients with AE may induce expansion of IL-4- and IL-5-producing Th2 clones, leading to increased IgE synthesis and eosinophil activation.

Antigens, Bacterial↗

Oral provocation test in the diagnosis of anaphylactoid reactions to 'mild' analgesic preparations.

'Mild' analgesic preparations (MAPs) are well known elicitors of anaphylactoid reactions (ARs). The identification of the causative agent is often difficult since reliable skin tests or in vitro methods are not available. In 128 patients (32 males, 96 females) with a history of ARs to MAPs containing only one single analgesic compound, placebo-controlled oral provocation tests (OPTs) were performed. Among 100 of them undergoing the OPT with the suspected drug, there was a concordance between the patient's history and the OPT in 44 patients. Concomitant ARs to other mild analgesics (without a history of previous incompatibility) were observed in 113 of 413 OPTs, but in almost all cases one or more alternative analgesics were tolerated in the OPT. Our results confirm that the OPT remains at present the most reliable diagnostic procedure alongside a comprehensive history in patients with ARs to MAPs. Because many of the patients showed concomitant ARs to unsuspicious analgesics OPTs should include a standard battery of different analgesics. The simple recommendation of one single preparation, such as acetaminophen, as a 'safe' substitute without an OPT is not recommended.

Administration, Oral↗

Air pollution and allergy: experimental studies on modulation of allergen release from pollen by air pollutants.

The fact that allergic diseases increase in prevalence is a generally accepted and worldwide phenomenon. The causes for this increase are not known: only hypothetical concepts exist. Epidemiological studies comparing Eastern and Western European populations have shown a striking difference in the prevalence of respiratory atopic diseases, which is lower in the East. At the same time, different patterns of air pollution have been described, namely 'classical' type I, characterized by SO2 and dust prevailing in the East, and 'modern' type II, characterized by organic compounds, fine particles and ozone, which is more prominent in the West. Type II was associated in multivariate regression analysis with increased prevalence of IgE-mediated allergy. Pollen grains collected from industrial regions with high polyaromatic hydrocarbon load in West Germany, but not in East Germany, were shown to be agglomerated with airborne particles. In vitro exposure of pollen to particles indicated morphological changes and increased allergen release from the pollen. In vitro exposure of pollen to gaseous pollutants (SO2 and NO2) under different conditions of humidity resulted in SO2-induced, but not NO2-induced reduction of allergen release from pollen. It is concluded that the bioavailability of grass pollen allergens may be modulated by air pollutants, supporting the concept of an interaction between pollen and pollutants in the atmosphere outside the organism which in turn may affect allergy-relevant phenomena.

Air Pollutants↗

The 'atopy patch test' in evaluating the role of aeroallergens in atopic eczema.

The atopy patch test (APT) is a procedure involving epicutaneous patch tests with allergens known to elicit IgE-mediated reactions and the evaluation of eczematous skin lesions. APT can be performed on normal uninvolved skin without artificial manipulations such as tape stripping or use of irritants. APT has been standardized regarding the use of vehicle and dose response relationships. In several studies, approximately two thirds of patients with atopic eczema (AE) showed positive APT reactions to aeroallergens, most frequently to house dust mite. Positive APT reactions were significantly more frequent in patients with a typical air-exposed eczematous distribution pattern. Using evaporimetry to study transepidermal water loss, allergen-induced disturbance of epidermal barrier functions was found to be significantly more pronounced on APT reactions compared to classical contact allergy patch test sites in the same individual. It has been shown that with APT eczematous skin lesions can be elicited by skin contact with aeroallergens, at least in a subgroup of patients with AE, and thereby, that IgE-mediated allergy does play a role in the etiopathophysiology of this disease. Future studies should help to bring this test into clinical routine in order to establish an equivalent for 'skin provocation' comparable to nasal and bronchial provocation tests in respiratory allergy.

Allergens↗

What makes a child allergic? Analysis of risk factors for allergic sensitization in preschool children from East and West Germany.

Earlier epidemiologic studies within Germany found a higher frequency of allergic sensitization in West Germany. The reasons for that and the role of environmental factors in the process of allergic sensitization are not fully understood. This study aimed to determine the prevalence of positive skin-prick test results 5 years after unification and to investigate risk factors for allergic sensitization in preschool children. A total of 1235 children (5-6 years) from two West and five East German locations were skin-prick tested after the compulsory school entrance examination. Six common aero- (birch, grass, mugwort pollen, cat, HDM, alternaria) and two food allergens (egg, milk) were used and additional information was obtained by questionnaire. Of the tested children 23.3% exhibited at least one positive reaction. The prevalence of sensitization to the single allergens was as follows: grass (14.4%), birch (6.6%), mugwort pollen (4.5%), cat (8.5%), HDM (5.5%), alternaria (4.9%), egg (2.8%), and milk (3.9%). In the crude analysis significantly more children were sensitized in the East German city Magdeburg (40.2%) compared to the West German control region Borken (23.5%) (OR 2.20, CI 1.47-3.29). Dampness and visible molds were reported in 8.8% of all households, but significantly more often for East German apartments (10.3% versus West Germany 1.9%, OR 5.85, CI 2.55-16.53). Dampness and molds were associated with a higher frequency of sensitizations (40.6% versus 27.6% in unaffected homes). After controlling for sex, parental atopy, SES, family size, and smoking during pregnancy, this association remained statistically significant (OR 1.93, CI 1.19-3.12). With regard to single allergens, dampness and visible molds were significantly associated with sensitization to HDM (OR 3.37, CI 1.63-6.96), cat (OR 3.19, CI 1.11-5.74), and mugwort pollen (OR 2.86, CI 1.29-6.35). In addition, family size was inversely and linearly associated with the frequency of sensitization (OR for four, three, and two-person households: 1.10 (0.74-1.63), 1.57 (1.06-2.42), 2.70 (1.39-5.24), respectively, when compared to family size of five or more). Neither parental predisposition for atopic diseases nor parental education level influenced the prick test reactivity. We conclude that in addition to genetic predisposition, environmental factors like indoor climate and probably infectious stimuli (family size) play an important role in the process of allergic sensitization in children.

Allergens↗

MIA as a reliable tumor marker in the serum of patients with malignant melanoma.

BACKGROUND: Reports published in 1996 concerning the protein MIA proposed it as a useful tumor marker for patients suffering from malignant melanoma. Therefore we systematically started to measure MIA levels in patients with malignant melanoma. It was and still is questionable whether MIA in the serum of melanoma patients is a reliable tumor marker in terms of course of disease, therapy-monitoring and prognostic value. Previous studies have already confirmed the specifity of MIA as a tumor marker for malignant melanoma. MATERIALS AND METHODS: Using an ELISA- System, we examined over 830 blood samples of 326 melanoma patients. The cut-off was determined at 9.8 ng/ml. RESULTS: 5.6% (n = 17) of melanoma patients at stage I/II (n = 302) showed increased MIA levels, whereas at stage III/IV (n = 5/n = 19) high levels were found in 60.0% and 89.5% respectively. Patients at stage III/IV with MIA levels below the cut-off turned out to be the ones after metastatic surgery, irradiation or chemotherapy. None of these patients developed further metastases during follow-up, just as patients at stage I/II without increased MIA levels. After a distinct rise of MIA levels, metastases could be detected at the same time or shortly after. On the other hand we saw decreasing levels after or during therapy. CONCLUSION: Our data showed that MIA is a suitable serum marker to detect metastases and to monitor course and therapy of disease. The prognostic value (increased MIA levels at stage I/II), however, requires further investigation.

Antigens, Tumor-Associated, Carbohydrate↗

[Contact urticaria with transition to protein contact dermatitis in a cook with atopic diathesis].

Protein contact dermatitis is a rare disease within the group of occupational dermatoses. However, it is of some importance to people in food handling occupations. Skin symptoms usually manifest as immediate-type reactions (type-I-reaction according to Coombs and Gell), but changes to type IV-reactions are known. This applies especially to people with atopic eczema who have contact to fish proteins. This can be derived from a case presented here and a few similar observations described in the literature.

Animals↗

Passive cutaneous anaphylaxis: improvement of quantitative analysis by radioactively labelled antigen.

Experiments were performed to improve the quantitative analysis of passive cutaneous anaphylaxis (PCA) by labelling the antigen with radioactive iodine. After intradermal injection of antibodies and intravenous administration of labelled antigen in rats a close correlation was found between the radioactivity measured in skin biopsies and the amount of antigen as well as the amount of antibodies. This direct dependence makes it possible to improve quantitatively the reading of PCA test results. A quantitative correlation was also found when radioactivity is measured over the skin by scanning procedures. Therefore it is not necessary to cut out skin biopsies. Thus the same test animal can be used several times, which minimizes biological variations.

Animals↗