Biomedical subjects

N Novak

Publications and source records attributed to N Novak.

At least 19 recordsLinked to original sources

PubMed2006

The pathophysiology of atopic eczema.

Atopic eczema (AE) represents a pruritic chronic inflammatory skin disease with a complex background, triggered by genetic and environmental factors. Different dendritic cells subtypes, such as Langerhans cells, inflammatory dendritic epidermal cells and plasmacytoid dendritic cells, play a key role in AE and impact on the mechanisms underlying AE, such as the recruitment of inflammatory cells, T-cell priming, and cytokine and chemokine release. In addition, allergens in combination with bacterial and viral stimuli influence the course and severity of AE. In this review, we highlight the recent progress made in the pathophysiology of AE focusing on the latest research results published in this field.

Antigen-Presenting Cells↗

PubMed2006

Comparative analysis of nasal and oral mucosa dendritic cells.

BACKGROUND: Mucosal dendritic cells (DC) play a crucial role in tolerance induction as seen in mucosal immunotherapy of atopic diseases. Nevertheless little is known about the phenotypical differences of oral and nasal mucosal DC (nmDC). Recently, we could show that oral mucosal myeloid CD1a(+) DC (omDC) differ from their skin counterparts especially by the expression of high affinity receptor for immunoglobulin E (IgE; FcepsilonRI). However, expression pattern of FcepsilonRI and phenotypical characteristics of CD1a(+) nmDC have not been elucidated in detailed yet. METHODS: We performed detailed phenotypical comparison of nmDC and omDC of atopic and nonatopic individuals. RESULTS: As reported for omDC, FcepsilonRI on nmDC of atopic donors was elevated and mostly occupied by IgE while FcepsilonRI was present only in low amounts on nmDC of nonatopic donors. Nevertheless, the highest FcepsilonRI expression has been observed on omDC. Furthermore, significant amounts of costimulatory molecules CD40, CD80 and CD86 could be detected on nmDC that expressed more CD80 compared with omDC. Moreover, nmDC displayed less major histocompatability complex (MHC) class I and II molecules than omDC. In addition, nmDC expressed more C-type lectins CD205, CD206 as well as myeloid marker CD11b while omDC displayed increased expression of CD207 and lipopolysaccharide (LPS) receptor CD14. CONCLUSION: Together these data imply that nmDC phenotypical differ from omDC which might result in diverse functional properties and might be of relevance for selecting routes for immunotherapy of atopic diseases. Moreover these data provide a basis for further studies investigating immunological mechanisms underlying mucosal immunotherapy.

Adult↗

PubMed2006

Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL Consensus Report.

There are remarkable differences in the diagnostic and therapeutic management of atopic dermatitis practiced by dermatologists and pediatricians in different countries. Therefore, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams who were given the task of finding a consensus to serve as a guideline for clinical practice in Europe as well as in North America. The consensus report is part of the PRACTALL initiative, which is endorsed by both academies.

Adult↗

PubMed2006

Different expression of adhesion molecules and tetraspanins of monocytes of patients with atopic eczema.

BACKGROUND: Atopic eczema (AE) and psoriasis vulgaris (Pso) represent the most frequent chronic inflammatory skin diseases, which have a high number of characteristics in common but differ in their clinical picture and immunological background. A shared feature of both AE and Pso is a high recruitment of distinct proinflammatory cells from the blood into the skin at the initiation of the disease. A multistep adhesion cascade via different adhesion receptors consisting of 'tethering' and 'rolling' mediated by selectins, alpha-integrins and beta-integrins and the 'arrest' of the cells is initiated during this process. AIMS OF THE STUDY: To evaluate the expression of adhesion molecules and tetraspanins of monocytes of patients with AE and Pso in comparison with healthy controls. METHODS: We analysed the expression of adhesion molecules and tetraspanins on monocytes freshly isolated from the peripheral blood of patients with AE (n = 40) and Pso (n = 65) during exacerbation of their disease in comparison with healthy, non-atopic controls (n = 50). RESULTS: A high number of similarities between monocytes of patients with AE and patients with Pso, and disease-related differences in the expression of CD62L, CD62P, CD11a, CD11b, CD11c, CD49b, CD49d, CD49e and CD18 and the tetraspanins CD9, CD53, CD63 and CD151, which were elevated on monocytes of patients with AE could be observed. CONCLUSION: A distinct expression pattern of adhesion molecules and tetraspanins on monocytes of patients with AE and Pso might influence the recruitment process of inflammatory precursor cells and facilitate new approaches for therapeutic strategies aimed at interrupting the very earliest steps of the fateful recruitment process.

Adolescent↗

PubMed2005

Recent highlights in the pathophysiology of atopic eczema.

Atopic eczema (AE) belongs to the group of atopic diseases that have become increasingly prevalent over the last decades. The pathophysiology of AE has long remained enigmatic, but much scientific effort has been invested in elucidating the genetic background and the immunological mechanisms underlying AE, leading to a better understanding of this complex disease and to new therapeutic strategies. This review provides an update on the scientific progress that has been achieved in clarifying the pathophysiological mechanisms of AE.

Dermatitis, Atopic↗

PubMed2005

Association of CARD15 polymorphisms with atopy-related traits in a population-based cohort of Caucasian adults.

BACKGROUND: Influences of microbial pathogens are crucial for the maturation of the immune system. Caspase-recruitment domain containing protein 15 (CARD15) is a cytosolic receptor involved in bacterial recognition by antigen-presenting cells. CARD15 polymorphisms have been associated with Crohn's disease. Recently, associations with atopic phenotypes have been reported in children. OBJECTIVE: Within a large population of German adults (n=1875), we evaluated eight CARD15 polymorphisms for associations with atopic phenotypes. METHODS: Subjects were phenotyped by standardized questionnaires and interviews as well as total and allergen-specific IgE measurements. Genotyping was performed using matrix-assisted laser desorption ionization--time of flight mass spectrometry. Haplotypes were estimated using the SAS/Genetics module. RESULTS: Subjects with a T allele at rs1077861 had a decreased risk of developing asthma (odds ratio OR=0.648, P=0.013), whereas the presence of an A allele at rs3135500 was significantly associated with an increased risk (OR=1.374, P=0.023). In addition, a CARD15 haplotype revealed to be protective against the development of asthma (OR=0.326, P=0.003). Subjects with an A allele at position rs5743266 or a T allele at rs2066842 had a significantly decreased risk of developing allergic rhinoconjunctivitis with ORs of 0.820 (P=0.049) and 0.801 (P=0.025). Polymorphism rs2066845 showed a significant association with increased total serum IgE (OR=2.155, P=0.006). CONCLUSION: Genetic variants of CARD15 that might result in inappropriate immunomodulation are not only associated with autoimmune diseases but also with atopic disorders.

Alleles↗

PubMed2005

The mode of topical immunomodulators in the immunological network of atopic dermatitis.

For a long time, therapeutic strategies of atopic dermatitis (AD) have been dominated by the application of local or systemic steroids or other immunosuppressive agents, which have been limited by their potential for unwanted local or systemic side effects. Recently, the use of a new generation of topical nonsteroidal, immunomodulatory drugs has revolutionized the therapeutic options of this often recalcitrant allergic-inflammatory skin disease. Research work has focused on the identification of the exact mode of action and the immune specificities of the so-called 'topical immunomodulators' (TIMs) such as tacrolimus and pimecrolimus in AD. In addition to the previous findings about the mode of action of TIMs on T cells, other target cells of TIMs such as keratinocytes, mast cells, eosinophils and dendritic cells have been identified recently as potential therapeutic targets. In this overview, we provide a research update about the anti-inflammatory and anti-allergic properties of TIMs on effector cells of AD that may be involved in the complex pathophysiology of AD.

Acute Disease↗

PubMed2005

Dancing with the enemy: the interplay of herpes simplex virus with dendritic cells.

Summary Herpes simplex virus (HSV) represents a smart pathogen, which displays both lytic and latent modes of interaction with its natural human host. In order to be optimally equipped for immune evasion and to reply to any attacks of the host during reactivation, HSV has developed a multitude of cleverly devised defence strategies. Dendritic cells (DC) as antigen-presenting cells located at the border zones of the body and the environment have been shown to play a crucial role as one of the first cells interacting with HSV beside epithelial cells, on one hand, and as important controllers of the viral spreading on the other hand. Here, we provide a research update about the interaction of HSV with DC and summarize the latest proceedings in this field.

Antigens, CD↗

PubMed2005

In search for predictive factors for atopy in human cord blood.

Since early prevention is regarded as an important corner stone in the management of atopic diseases, the identification of reliable markers detecting individuals at risk are of major interest. Therefore, many efforts have been made to unravel reliable predictors for atopy which might identify children at risk and allow the initiation of preventive strategies at an early stage. In the past, much scientific energy has been forced in particular on the development of as noninvasive methods as possible to reach this goal. It is obvious that the identification of markers for atopy at the earliest time of life - namely immediately after birth - represents one of the most attractive attempts. In consequence various studies have been initiated to address this issue investigating markers for atopy in cord blood. Most of them have been geared to our current knowledge about cellular and soluble factors which are dysregulated in adolescent atopic individuals. Although the findings of these studies will improve our knowledge about the initial evolution of atopy, several parameters evaluated did not show any association or have led to almost conflicting results. In order to provide an up-date about the current developments in this field, recent research findings on predictive factors for atopy in cord blood are summarized in the following synopsis.

Antigen-Presenting Cells↗

PubMed2004

The role of antigen presenting cells at distinct anatomic sites: they accelerate and they slow down allergies.

It has been repeatedly demonstrated that allergic reactions are driven by the continuous flow of antigen uptake and presentation processes, which are perpetuated mainly by dendritic cells (DC). The ability of allergens to cause allergic inflammation is contingent upon the presence of an immunological milieu and microenvironment that either privileges Th2 responses or prohibits these reactions by the induction of contraregulatory anti-inflammatory activities of the immune system. In the light of recent developments it appears that DC have to manage two opposing tasks: on the one hand they can favor pro-inflammatory reactions and actively induce a T-cell response, yet on the other hand they serve an important function as 'silencers' in the immune system by sending out anti-inflammatory, tolerance inducing signals. This unique capacity of DC has opened several exciting possibilities for a role of DC in both - accelerating and slowing down allergic reactions. It is therefore a challenge to understand in which way DC subtypes located at distinct anatomic sites with frequent allergen exposure, such as the skin, the nasal mucosa, the respiratory tree or the mucosa of the intestinal tract can have an impact on mechanisms involved in tolerance induction or effective immunity.

Allergens↗

PubMed2004

Successful treatment of acrodermatitis continua suppurativa with topical tacrolimus 0.1% ointment.

Acrodermatitis continua suppurativa of Hallopeau (ACS) is a rare pustular variant of psoriasis in which numerous treatment modalities have been used without any consistent long-term effect. We report for the first time two patients with ACS which was successfully treated with topical tacrolimus 0.1% ointment. Our observations raise hopes that this new treatment strategy for ACS may constitute a novel effective therapeutic option for this recalcitrant condition.

Acrodermatitis↗

PubMed2003

New treatment modalities for granuloma faciale.

Granuloma faciale (GF) is a rare, chronic skin disorder in which numerous treatment modalities have been used without any consistent long-term effect. We report three cases of GF, two of which were successfully treated with the Laserscope potassium-titanyl-phosphate 532-nm laser within 2 weeks and one with topical tacrolimus ointment 0.1%. Our observations suggest that these new treatment modalities for GF, which we report here for the first time, can provide effective and non-invasive treatment for this disease.

Aged↗

PubMed2003

The central role of FcepsilonRI in allergy.

The high-affinity receptor for immunoglobulin E (IgE), FcepsilonRI, plays a central role in the initiation and control of atopic allergic inflammation. On mast cells and basophils, the function of the receptor is well known and constitutes cellular degranulation and the release of various mediators. FcepsilonRI on antigen-presenting cells (APCs), however, does not lead to degranulation of preformed granula, but has different functions: signal transduction pathways like the activation of NF-kappaB are initiated to induce inflammatory cytokine gene expression. In addition, FcepsilonRI on APCs acts as an allergen-focusing structure and can efficiently amplify allergen presentation in an IgE-dependent manner. Recently, we and others have gained new insight into the regulation and function of FcepsilonRI on APCs, which has shed new light on the modulating effects of the immune system in atopic inflammation.

Animals↗

PubMed2002

Characterization of monocyte subtypes in the allergic form of atopic eczema/dermatitis syndrome.

BACKGROUND: Monocyte (Mo) subsets exhibiting distinct phenotypic and functional properties identified in peripheral blood are assumed to be under the control of soluble factors from their surrounding micromilieu. Atopic eczema/dermatitis syndrome (AEDS) is accompanied by humoral and cellular alterations among which an increased expression of the high-affinity receptor for IgE (Fc epsilon RI) on antigen presenting cells, like Mo, could be found. Therefore we analyzed the assembly of circulating Mo populations and their Fc epsilon RI surface expression during the course of AEDS. METHODS: Blood samples were taken from AEDS patients before and after topical treatment as well as from psoriasis patients and healthy control donors. Detailed analysis of Mo subsets was done by flow cytometry. Meticulous clinical scoring included quantification of the surface damage using the eczema area and severity index (EASI score) as well as evaluation of the serum level of thymus- and activation-regulated chemokine (TARC); this was done before and after 2 weeks of topical treatment with tacrolimus ointment 0.1%. RESULTS: During the exacerbation phase of AEDS, patients harboured a different assembly of Mo subtypes from normal nonatopic individuals and patients with psoriasis with a significant increased population of CD14(+)CD64(-) CD16(+) Mo. Clinical improvement led to a significant decrease of this subpopulation in favor of CD14(+)CD64(+)CD16(-) Mo, leading to a composition of Mo subsets similar to the state found in healthy donors. Interestingly, Fc epsilon RI expression was confined to the CD14(+)CD64(+)CD16(-) Mo subpopulation and the percentage of this Fc epsilon RI(+) Mo subset increased significantly in the peripheral blood after topical treatment. CONCLUSION: Our data provide for the first time clear evidence that fluctuations of Mo subsets in AEDS might reflect qualitatively and quantitatively distinct contributions of Mo subsets to the development of AEDS.

Adult↗

PubMed2002

Enhanced expression and activity of protein-tyrosine kinases establishes a functional signaling pathway only in FcepsilonRIhigh Langerhans cells from atopic individuals.

The trimeric high-affinity IgE receptor (FcepsilonRI) on human epidermal Langerhans cells mediates IgE-dependent antigen uptake and subsequent antigen focusing. Its expression is upregulated on Langerhans cells (FcepsilonRIhigh Langerhans cells) and inflammatory dendritic epidermal cells (FcepsilonRIhigh inflammatory dendritic epidermal cells) in the skin of patients with atopic dermatitis. In the absence of the amplifying beta-chain in these cells, FcepsilonRI signaling (indicated by calcium mobilization and activation of the transcription factor nuclear factor-kappaB) is only detectable in FcepsilonRIhigh Langerhans cells from atopics, but not FcepsilonRIlow Langerhans cells from nonatopics. Therefore we investigated protein-tyrosine kinases putatively involved in FcepsilonRI signaling in Langerhans cells and asked whether differences in their expression and FcepsilonRI-induced activity could explain the dichotomic responses observed in atopic vs nonatopic individuals. First, we found the src protein-tyrosine kinases p53/56lyn, p59fyn, p56/59hck, p55c-fgr, and p60c-src to be expressed in Langerhans cells from all donors. In addition, whereas p56lck was lacking, p72syk and the negative regulatory p50csk were detected. Upon terminal maturation of Langerhans cells in vitro, no significant change of the protein- tyrosine kinase expression profile except downregulation of p56/59hck was observed. In contrast, significant upregulation of all protein-tyrosine kinase expressed except p50csk was detected in FcepsilonRIhigh Langerhans cells, but not in FcepsilonRIhigh inflammatory dendritic epidermal cells. Finally, the important protein-tyrosine kinases substrate phospholipase C-gamma1, which is also essential for downstream calcium mobilization, was only phosphorylated upon FcepsilonRI triggering in FcepsilonRIhigh Langerhans cells from atopics, but not in FcepsilonRIlow Langerhans cells from nonatopics. Therefore, upregulation of FcepsilonRI and protein-tyrosine kinase expression as well as subsequent protein-tyrosine kinase activity may explain, at least in part, that an efficient signaling pathway in terms of calcium mobilization is restricted to FcepsilonRIhigh Langerhans cells from atopic individuals. Key words:

Cell Line↗

PubMed2002

Metabolic syndrome X--high risk factor for acute myocardial infarction and its complications.

Metabolic Syndrome X is a clinical entity which comprises the following factors: diabetes mellitus, arterial hypertension, high levels of triglyceride and/or low levels of HDL cholesterol, central obesity and microalbuminuria (by WHO criteria). The first goal of this study was to determine the frequency of the Metabolic Syndrome X (MSX) in patients with acute myocardial infarction compared with the general population. The second goal of the study was to examine the frequency of heart failure and reinfarction rate in the patients with myocardial infarction, with and without MSX. Furthermore, the relationship between gender and MSX was analyzed. A total of 101 patients with acute myocardial infarction took part in randomized trial (32 women and 69 men). MSX and all of its components were diagnosed according to WHO criteria. To determine statistical significance of our results, we used chi2 test and t-test for independent samples. From 101 patient 48 had MSX (47.52%), while in the general population incidence of MSX is 3-4%. The reinfarction and the heart failure rate were significantly higher in the group of patients with MSX (p = 0.0067 and p = 0.0217, respectively). To conclude, the results of the present study confirm that MSX is a high risk factor for myocardial infarction and its complications.

Adult↗

PubMed2001

Engagement of Fc epsilon RI on human monocytes induces the production of IL-10 and prevents their differentiation in dendritic cells.

The local cytokine environment and the presence of stimulatory signals determine whether circulating monocytes will finally acquire characteristics of dendritic cells (DCs) or macrophages. Because FcepsilonRI expressed on professional APCs, e.g., monocytes and DCs, has been suggested to play a key role in the pathophysiology of atopic diseases, we evaluated the effect of receptor ligation on the generation of monocyte-derived DCs (MoDCs). Aggregation of FcepsilonRI at the initiation of the IL-4-GM-CSF-driven differentiation resulted in the emergence of macrophage-like cells with a strong expression of the mannose receptor and a low level of CD1a and the DC-specific markers CD83 and the actin-bundling protein (p55). These cells sustained the ability to take up FITC-labeled Escherichia coli by phagocytosis and were significantly less efficient in stimulating purified allogeneic T cells. In addition, receptor ligation of FcepsilonRI at the beginning of the culture prevented the generation of MoDCs, mainly due to a dramatic increase in the IL-10 production. These results suggest that FcepsilonRI aggregation prevents the generation of CD1a(+) MoDCs and imply a novel pivotal function of this receptor in modulating the differentiation of monocytes.

Cell Differentiation↗

PubMed2001

IgE receptors.

IgE receptors are implicated as important components of the immunological pathway in allergic and inflammatory diseases. Recent investigations have begun to unravel the structure, signal transduction and function of IgE receptors from different cell types in rodent and human systems. Studies of the mechanisms involved might provide opportunities for therapeutic intervention strategies in the treatment of allergic and hypersensitivity reactions.

Animals↗