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Johannes Ring

Publications and source records attributed to Johannes Ring.

At least 19 recordsLinked to original sources
PubMed2005

Allergen-specific IgE measured by a continuous random-access immunoanalyzer: interassay comparison and agreement with skin testing.

BACKGROUND: Our aims were to evaluate the performance of a fully automated system for measuring circulating allergen-specific IgE (sIgE) against an established in vitro assay and to assess the system's diagnostic accuracy against objective clinical criteria for identifying sensitization to specific allergens. METHODS: Using both the IMMULITE 2000 Allergy system (IML) and an assay based on the widely used ImmunoCAP technology (CAP), we measured sIgE in serum samples from 169 persons with suspected allergies to airborne or insect venom allergens. Skin testing outcome served as the clinical comparison method. RESULTS: Interassay classification agreement between the IML and CAP, relative to the usual allergen-specific IgE cutoff of 0.35 kIU/L, ranged from 76% (yellow jacket venom) to 95% (orchard grass); agreement was 88.3% for all 9 allergens combined (766 results). The 90 discordant results, when resolved by skin testing, showed better agreement with the IML (72%) than with the CAP (28%). Compared with skin testing, for each of the 9 allergens studied, the area under the ROC curve was at least as large for the IML as for the CAP, reflecting in part the more extensive working range of the IML (0.10-100 kIU/L vs 0.35-100 kIU/L for CAP). CONCLUSION: Laboratory testing for sIgE can be performed on a fully automated, random-access system with an extended working range and with diagnostic accuracy for representative allergens equivalent to or better than that of the semiautomated CAP technology.

Allergens↗
PubMed2005

Recombinant adeno-associated virus type 2-mediated gene transfer into human keratinocytes is influenced by both the ubiquitin/proteasome pathway and epidermal growth factor receptor tyrosine kinase.

Efficient gene delivery into keratinocytes is a prerequisite for successful skin gene therapy. Vectors based on recombinant adeno-associated virus type 2 (rAAV-2) offer several promising features that make them attractive for cutaneous applications. However, highly efficient gene delivery may be hampered by different cellular factors, including lack of viral receptors, impairment of cytoplasmic trafficking or limitations in viral second-strand synthesis. This study was undertaken to find factors that influence rAAV-2-mediated in vitro gene transfer into human keratinocytes and, consequently, ways to optimize gene delivery. Transduction experiments using rAAV-2 vectors expressing green fluorescent protein (GFP) demonstrated that impaired cellular trafficking of vector particles and high levels of autophosphorylation at epidermal growth factor receptor tyrosine kinase (EGF-R TK) have a negative influence on gene transfer into keratinocytes. Treatment of keratinocytes with proteasome inhibitor MG132 resulted in a transient augmentation of GFP expression in up to 37% of cells. Treatment with EGF-R TK inhibitors (quinazoline type) enhanced transgene expression in 10-14.5% of the cells. Gene expression was stable for more than 10 weeks and persisted until proliferative senescence occurred. This stable gene expression allows speculation that keratinocyte stem cells have initially been transduced. These findings might have relevance for the use of rAAV-2 vectors in skin gene therapy: transient enhancement of rAAV-2 transduction with proteasome inhibitors might be useful for genetic promotion of wound healing or skin-directed vaccination. Treatment with quinazolines may increase rAAV-2 transduction of keratinocyte stem cells, which is important for gene therapy approaches to inherited diseases.

Cysteine Proteinase Inhibitors↗
PubMed2005

Pollen-associated phytoprostanes inhibit dendritic cell interleukin-12 production and augment T helper type 2 cell polarization.

Pollen grains induce allergies in susceptible individuals by release of allergens upon contact with mucosal membranes of the upper respiratory tract. We recently demonstrated that pollen not only function as allergen carriers but also as rich sources of bioactive lipids that attract cells involved in allergic inflammation such as neutrophils and eosinophils. Here we demonstrate that soluble factors from birch (Betula alba L.) pollen activate human dendritic cells (DCs) as documented by phenotypical and functional maturation and altered cytokine production. Betula alba L. aqueous pollen extracts (Bet.-APE) selectively inhibited interleukin (IL)-12 p70 production of lipopolysaccharide (LPS)- or CD40L-activated DC, whereas IL-6, IL-10, and TNFalpha remained unchanged. Presence of Bet.-APE during DC activation resulted in DC with increased T helper type 2 (Th2) cell and reduced Th1 cell polarizing capacity. Chemical analysis of Bet.-APE revealed the presence of phytoprostanes (dinor isoprostanes) with prostaglandin E(1)-, F(1)-, A(1)-, or B(1)-ring systems of which only E(1)-phytoprostanes dose dependently inhibited the LPS-induced IL-12 p70 release and augmented the Th2 cell polarizing capacity of DC. These results suggest that pollen-derived E(1)-phytoprostanes not only resemble endogenous prostaglandin E(2) structurally but also functionally in that they act as regulators that modulate human DC function in a fashion that favors Th2 cell polarization.

Betula↗
PubMed2005

Subepidermal cleft formation as a diagnostic marker for cutaneous malignant melanoma.

Cleft formation has been postulated as a clue to the histopathological diagnosis of malignant melanoma (MM). The frequency and reliability of clefts as a diagnostic criterion remain to be determined. We reviewed 503 cases of histologically proven MM searching for clefting between the epidermal layer and underlying MM. Cleft was defined as a separation of at least 0.3 mm in length. Conspicuous cleft formation was present in 120 (24%) of 503 MMs. The presence of clefts was not associated with age or sex of the patients, but showed a slight predilection for the back, a slightly higher prevalence in superficial spreading type of MM and for tumors with a Breslow thickness between 1 and 2 mm. Morphologically, clefts could be separated in 3 different types: linear (37.5%), single-nest (10.9%), and multi-nest (51.6%). In comparison, among 939 benign melanocytic lesions including 100 Spitz or Reed nevi, only 9 exhibited clefts longer than 0.3 mm (< 1%). One was an atypical compound nevus; all others were Spitz nevi, with the majority exhibiting an arched morphology above 1 or 2 large round nests. The relative frequency of cleft formation allowed a highly significant differentiation between MM and benign melanocytic lesions. Clefts are a reliable diagnostic criterion in favor of MM.

Biomarkers↗
PubMed2005

Association of NOD1 polymorphisms with atopic eczema and related phenotypes.

BACKGROUND: Interactions with microbial pathogens are crucial for the maturation of the immune system. The nucleotide-binding oligomerization domain protein 1 (NOD1) is a cytosolic receptor sensing a muropeptide found mostly in gram-negative bacterial peptidoglycans. NOD1 is located on chromosome 7p14-p15, a region that has been linked with atopy. Recently, polymorphisms of the closely related NOD2 have been associated with atopy-related traits. OBJECTIVES: Within a large population-based cohort of German adults (n = 1417), a case-control population for atopic eczema (n = 454), and a large cohort of parent-offspring trios for atopic eczema (189 trios), we evaluated 11 NOD1 polymorphisms for associations with atopic phenotypes. Methods Subjects were phenotyped by standardized questionnaires and interviews, skin examination, and serum IgE measurements. Genotyping was performed by using matrix-assisted laser desorption ionization-time of flight mass spectrometry. RESULTS: Analyses revealed significant association of one NOD1 haplotype with atopic eczema in the population-based cohort ( P = .004) and the case-control population ( P = .003). Another NOD1 haplotype was associated with decreased total IgE ( P = .008). In addition, significant associations with total serum IgE levels were observed for polymorphisms rs2907748 ( P = .006), rs2907749 ( P = .012), and rs2075822 ( P = .018). These polymorphisms were significantly associated with atopic eczema and asthma in the family-based association analyses ( P = .001-.043). Seven polymorphisms showed significant transmission distortion for total IgE levels ( P values < .0001-.029). CONCLUSION: These data indicate that genetic variants within NOD1 are important determinants of atopy susceptibility.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Atopy patch test--reproducibility and elicitation of itch in different application sites.

We evaluated the reproducibility of atopy patch test reactions and the quality and quantity of itch in 16 patients with atopic eczema and a history of a positive atopy patch test reaction, comparing three different application sites. The allergen was re-applied simultaneously on both forearms and the back. Intensity and quality of pruritus were evaluated using a visual analogue scale and the Eppendorf itch questionnaire, respectively. The atopy patch test reaction was highly reproducible, occurring in 15/16 (94%) patients. Pruritus was reported by 14/16 (88%) patients. There was no significant difference in either the intensity or quality of itch between the two forearms and the back (p>0.05). The mean peak visual analogue scale itch score was comparable across all three test sites (range 28.3-31.9). Regarding quantification of test reactions, a positive reaction was more frequent on the back (94% versus 69% on the arms) and the peak atopy patch test score was higher on the back compared with the arms (right forearm, p=0.0018 and left forearm, p=0.0683). Allergens should preferably be applied on the back for the atopy patch test. However, the atopy patch test can induce atopic itch irrespective of the application site.

Adolescent↗
PubMed2005

Seasonality in symptom severity influenced by temperature or grass pollen: results of a panel study in children with eczema.

Although seasonal variations are well known in many patients with eczema, no systematic population-based panel study evaluating seasonality and quantifying the influence of factors like climate and pollen on symptom variations has been conducted so far. Thirty-nine children with eczema, who had been identified in 1996 in a cross-sectional study on 1673 6-y-olds in Augsburg (Germany), participated in the study. Between March and September 1999, they daily recorded itch, extent, and possibly triggering factors on quantitative scales. Daily temperature, humidity, radiation, and pollen concentration were measured. Mixed linear models, taking the time series structure and confounding into account, were used for analysis. Seasonal patterns were significantly different between children: twenty-one had symptoms mainly in winter. They were affected by changes in outdoor temperature: itch was reduced by 22% (95% confidence interval (CI): 16%-27%) and extent by 65% (CI: 54%-72%) per 15 degrees C temperature increase. Eighteen children exhibited more symptoms in summer and especially during days with high grass-pollen exposure when itch was 16% higher (CI: 8%-24%) and extent 19% (CI: 2%-39%). This effect was stronger for children sensitized against pollen. Consideration of the individual type of eczema may help to arrange appropriate preventive and therapeutic measures.

Allergens↗
PubMed2005

Various members of the Toll-like receptor family contribute to the innate immune response of human epidermal keratinocytes.

Toll-like receptors (TLRs) are important pattern recognition molecules that activate the nuclear factor (NF)-kappaB pathway leading to the production of antimicrobial immune mediators. As keratinocytes represent the first barrier against exogenous pathogens in human skin, we investigated their complete functional TLR1-10 expression profile. First, reverse transcription-polymerase chain reaction (PCR) analysis revealed a very similar pattern of TLR mRNA expression when comparing freshly isolated human epidermis and cultured primary human keratinocytes. Thus, further experiments were carried out with primary keratinocytes in comparison with the spontaneously immortalized human keratinocyte cell line HaCaT. The quantitative expression of TLR1-10 mRNA in real-time PCR of primary human keratinocytes and HaCaT cells was analysed. Both cell types constitutively expressed TLR2, TLR3, TLR5, and to a lesser extent TLR10. TLR4 was only found in HaCaT cells, TLR1 to a higher degree in primary keratinocytes. In line with this, LPS induced mRNA expression of CD14 and TLR4 only in HaCaT cells. After stimulation with various TLR ligands, the NF-kappaB-activated chemokine interleukin-8 (IL-8) was measured. In primary keratinocytes and HaCaT cells the TLR3 ligand poly (I:C) was the most potent stimulator of IL-8 secretion. The TLR ligands peptidoglycan, Pam3Cys and flagellin which bind to TLR2, TLR1/TLR2 heterodimer, and TLR5, respectively, also induced IL-8 secretion, whereas no IL-8 was induced by LPS, R-848, loxoribine and cytosine guanine dinucleotide-containing oligodeoxynucleotide. A corresponding pattern was found in the RelA NF-kappaB translocation assay after ligand stimulation of primary keratinocytes. These studies provide substantial evidence for a functional TLR expression and signalling profile of normal human keratinocytes contributing to the antimicrobial defence barrier of human skin.

Biological Transport↗
PubMed2005

Pediatric tinea capitis: recognition and management.

Tinea capitis (ringworm of the head) is the most common dermatophytosis of childhood with an increasing incidence worldwide. If suspected clinically, further diagnostic procedures, including direct microscopy and culture, should be performed. Other scalp alterations, such as seborrheic dermatitis, atopic eczema, psoriasis, alopecia areata, folliculitis, and pseudopelade, may mimic ringworm of the head and must be identified. A proven fungal infection of scalp skin and hairs warrants immediate initiation of systemic treatment. At present, only oral griseofulvin is approved for therapy of scalp ringworm in children by health authorities. However, the advent of several newer antifungal agents such as itraconazole, fluconazole, and terbinafine has broadened the therapeutic armamentarium in recent years. These agents offer shorter treatment intervals, and their adverse effects and drug interaction profiles appear to be well within acceptable limits. In patients with tinea capitis, systemic therapy at weight-dependent dosages for an appropriate amount of time in conjunction with topical supportive measures will help to prevent disfiguring hair loss, permanent formation of scar tissue, spread of fungal organisms to other cutaneous regions, and infection of other persons.

Antifungal Agents↗
PubMed2004

Mouse models of atopic eczema critically evaluated.

Atopic eczema (AE) is a chronic relapsing inflammatory skin disorder with increasing prevalence in Western societies. Even though we have made considerable progress in understanding the cellular and molecular nature of cutaneous inflammation, the precise pathomechanisms of AE still remain elusive. Experimental animal models are indispensable tools to study the pathogenic mechanisms and to test novel therapeutic approaches in vivo. For AE a considerable number of mouse models have been proposed and have been used to study specific aspects of the disease, such as genetics, skin barrier defects, immune deviations, bacteria-host interactions or the role of cytokines or chemokines in the inflammatory process. While some models closely resemble human AE, others appear to reflect only specific aspects of the disease. Here we review the currently available mouse models of AE in light of the novel World Allergy Organization classification of eczematous skin diseases and evaluate them according to their clinical, histopathological and immunological findings. The pathogenetic analogies between mice and men will be discussed.

Animals↗
PubMed2004

Development and evaluation of a skin organ model for the analysis of radiation effects.

BACKGROUND AND PURPOSE: The reaction of tissues to ionizing radiation involves alterations in cell-cell and cell-matrix interactions mediated by cellular adhesion molecules. The aim of this study was to develop and evaluate an artificial skin organ model for the analysis of radiation effects. MATERIAL AND METHODS: A human co-culture system consisting of the spontaneously immortalized keratinocyte cell line HaCaT and primary HDFa fibroblasts embedded into a collagen sponge was established. This skin organ model has been characterized and evaluated for its suitability for radiobiological investigations. For that purpose, expression of beta(1)-integrin following irradiation was compared in the skin organ model and in HaCaT monolayer cells (FACScan and immunohistochemistry). Furthermore, the influence of ionizing radiation on DNA fragmentation was investigated in the skin organ model (TUNEL assay). RESULTS: The novel skin organ model showed characteristics of human skin as demonstrated by cytokeratin and Ki-67 immunoreactivity and by electron microscopy. A single dose of 5 Gy X-irradiation induced an upregulation of beta(1)-integrin expression both in the skin organ model and in HaCaT cells. Following irradiation, beta(1)-integrin immunoreactivity was intensified in the upper layers of the epidermis equivalent whereas it was almost absent in the deeper layers. Additionally, irradiation of the skin organ model also caused a marked increase of DNA fragmentation. CONCLUSION: These results demonstrate that the novel skin organ model is suitable to investigate cellular radiation effects under three-dimensional conditions. This allows to investigate radiation effects which cannot be demonstrated in monolayer cell cultures.

Cell Line, Transformed↗
PubMed2004

Lessons from atopy patch testing in atopic dermatitis.

The exposure of atopic eczema (AE) patients to their relevant protein allergens (eg, from house dust mite, cat dander, grass pollen, or food allergens) can trigger an exacerbation or maintain the disease. Diagnostic procedures are needed to specify allergen avoidance recommendations for the individual patient. Skin prick tests and specific serum IgE tests might be helpful in pointing out potential trigger factors, but relevance needs to be confirmed (eg, with food provocation tests). The atopy patch test (APT) involves the epicutaneous application of intact protein allergens in a diagnostic patch test setting with an evaluation of the induced eczematous skin lesions after 24 to 72 hours. The APT targets the cellular component of AE and helps round out the AE test spectrum. As a number of apparently minor test modifications greatly influence the sensitivity, specificity, and reproducibility of the APT, the European Task Force on Atopic Dermatitis (ETFAD) has developed a standardized APT technique. It consists of purified allergen preparations in petrolatum, applied in 12-mm diameter Finn chambers mounted on Scanpor tape to non-irritated, non-abraded, or tape-stripped skin of the upper back. The APT is read at 48 and 72 hours according to the test criteria and reading key of the ETFAD for appearance of erythema, and number and distribution pattern of the papules. In contrast with skin prick tests, the APT might even detect a relevant sensitization in the absence of specific IgE. Many studies have been undertaken to objectify the sensitivity and specificity of the APT to show its diagnostic use in clinical practice.

Advisory Committees↗
PubMed2004

Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003.

The nomenclature proposed in the October 2003 report of the Nomenclature Review Committee of the World Allergy Organization is an update of the European Academy of Allergology and Clinical Immunology Revised Nomenclature for Allergy Position Statement published in 2001. The nomenclature can be used independently of target organ or patient age group and is based on the mechanisms that initiate and mediate allergic reactions. It is assumed that as knowledge about basic causes and mechanisms improves, the nomenclature will need further review.

Advisory Committees↗
PubMed2004

Chemotaxis and activation of human peripheral blood eosinophils induced by pollen-associated lipid mediators.

BACKGROUND: Eosinophil accumulation at sites of allergic inflammation is largely regulated by chemokines and lipid mediators released by a variety of cells of the local microenvironment. Recent studies have shown that pollen grains, apart from their function as allergen carriers, are a rich exogenous source of eicosanoid-like lipid mediators that are rapidly released on contact with the aqueous phase and thus may contribute to the generation of local inflammatory responses. OBJECTIVE: Here we analyze the biological activity of pollen-associated lipid mediators (PALMs) on peripheral human blood eosinophils. METHODS: Human eosinophils were coincubated with pollen grains and analyzed by electron microscopy. The lipid mediator composition of aqueous pollen extracts (APEs) was analyzed by HPLC. Human eosinophils were exposed to APEs or lipid fractions from pollen. Effects on eosinophils were tested by transwell migration and surface expression of CD11b. RESULTS: In vitro experiments showed adhesion of eosinophils to Phleum pratense pollen. In chemotaxis assays eosinophils displayed significant directed migration to APEs. HPLC analysis of APEs from Phleum pratense and Betula alba pollen demonstrated the occurrence of linoleic and alpha-linolenic acid as well as their monohydroxylated derivatives. Moreover, total lipid extracts from pollen and RP-HPLC fractions containing monohydroxylated derivatives of linoleic and alpha-linolenic acid induced similar migratory responses, although to a lesser degree than APEs. In addition, APEs and lipid extracts induced up-regulation of CD11b surface expression and secretion of eosinophil cationic protein. APE-induced chemotaxis was blocked by the leukotriene B(4) receptor antagonist LY293111, suggesting that PALMs may serve as ligands for LTB(4) receptors. CONCLUSION: Pollen grains release lipid mediators that recruit and activate eosinophils in vitro. Similar mechanisms may be effective under natural exposure conditions, in which PALMs may play a role in the recruitment of eosinophils to the site of allergic inflammation.

Benzoates↗