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M Schlaak

Publications and source records attributed to M Schlaak.

At least 19 recordsLinked to original sources
PubMed2005

[Reactions of the skin to solar radiation].

When spending time out of doors in summer, certain rules of behavior need to be observed. Environmental factors such as, for example, water, the beach and the midday sun all have a major influence on the UV radiation burden to which people may be subjected. In addition, the sun's rays can interact with certain medications, alcohol and drugs, as also cosmetics, and trigger pathological skin reactions. A permanently sun-damaged skin is not only very difficult to treat, but is also frequently associated with malignant changes. Moderate exposure to the sun after prior gradual acclimatization is to be recommended. Patients with increased photosensitivity require special photoprotective agents.

Basal Cell Carcinoma↗
PubMed2003

Bronchoalveolar and serological parameters reflecting the severity of sarcoidosis.

The aim of the present study was to determine which bronchoalveolar lavage fluid (BALF) and serological parameters reflect the severity of newly diagnosed pulmonary sarcoidosis. Seventy-four previously untreated sarcoid patients were categorised into three groups: 10 patients with Löfgren's syndrome, 51 patients with stable disease and 13 patients with progressing disease requiring systemic steroid treatment. Total BALF cell count, percentage of alveolar lymphocytes and lymphocyte CD4/ CD8 ratio were not associated with severity of disease. Interestingly, a significant increase in percentages of BALF neutrophils (5.2 +/- 1.1%) and eosinophils (1.7 +/- 0.6%) was observed in sarcoid patients with progressing disease. Elevated percentages of these two cell types were the only BALF parameters associated with a more frequent necessity for systemic steroid therapy. This association between an elevated percentage of BALF neutrophils and the necessity for steroid treatment was observed in advanced as well as early sarcoidosis (radiological types I and II). Serum levels of soluble interleukin-2 receptor and neopterin were significantly elevated in progressing disease compared to stable disease or Löfgren's syndrome. The present results demonstrate that increased percentages of neutrophils (>3.0%) and eosinophils (>1%) in bronchoalveolar lavage fluid from newly diagnosed pulmonary sarcoidosis is associated with a significantly higher risk of necessity for steroid therapy and may be helpful markers of progressive disease. Furthermore, of the serological parameters investigated, only serum levels of soluble interleukin-2 receptor and neopterin were associated with disease severity.

Adult↗
PubMed2002

Pattern of NOS2 and NOS3 mRNA expression in human A549 cells and primary cultured AEC II.

The human alveolar type II epithelium-like cell line A549 expresses nitric oxide synthase type 2 (NOS2), but not NOS3, and produces nitric oxide (NO) upon appropriate stimulation. However, relatively little is known regarding the NOS2 and NOS3 expression of type II human alveolar epithelial cells (AEC II) in primary culture. We detected NOS3 mRNA in freshly isolated AEC II and after 24 h of culture. NOS3 mRNA levels were much higher in AEC II cultured for 24 h with or without interferon-gamma, interleukin-1beta, and tumor necrosis factor-alpha, compared with freshly isolated cells. Cytokine stimulation did not change the NOS3 mRNA expression level in AEC II compared with unstimulated cells. NOS3 protein expression was verified by Western blot, and measuring nitrate/nitrite revealed that the protein is active. In contrast, neither NOS2 mRNA nor protein could be detected in freshly isolated, unstimulated or cytokine-stimulated human AEC II in 24- or 72-h primary cultures, whereas A549 cells expressed NOS2 message and protein upon stimulation with proinflammatory cytokines. In situ hybridization confirmed that AEC II express NOS3, but not NOS2 mRNA in vivo. These data demonstrate that there are significant differences between primary AEC II and A549 cells in NOS mRNA expression pattern.

Adenocarcinoma↗
PubMed2002

Anti-Chlamydophila immunoglobulin prevalence in sarcoidosis and usual interstitial pneumoniae.

Sarcoidosis and usual interstitial pneumoniae (UIP) are diseases of unknown aetiology affecting the lower respiratory tract. Although there are a number of studies investigating the causal role of these disorders, no micro-organism could be identified as the causal agent. The high incidence of Chlamydophila pneumoniae infections associated with lung injury encouraged the present investigations to screen patients with sarcoidosis and with UIP for their Chlamydophila-specific immune response. Thirty-nine patients with sarcoidosis, 26 patients with UIP and 34 controls were tested for the prevalence of Chlamydophila-specific antibodies in bronchoalveolar lavage fluids (BALF) and sera. Samples were tested for the presence of antibodies in a genus-specific test for Chlamydophila-lipopolysaccharide (LPS) and in a species-specific test for C. pneumoniae. This study revealed a significantly higher prevalence of Chlamydophila LPS-specific immunoglobulin (Ig)-G in the BALF of sarcoidosis patients (36.8%) compared to controls (8.8%) and patients with UIP (12.0%). Similar findings were observed in sera. The prevalence of C. pneumoniae-specific antibodies in BALF was significantly higher in sarcoidosis patients for IgG and IgA (IgG: 74.4%; IgA: 46.2%) and in UIP for IgG (IgG: 50.0%; IgA: 11.5%) compared to controls (IgG: 14.7%; IgA: 14.7%). The elevated prevalence of Chlamydophila-specific antibodies in sarcoidosis patients might implicate Chlamydophila as a causal agent. However, considering the high prevalence of Chlamydophila antibodies in the healthy population, the data presented might reflect Chlamydophila co-infections in pre-injured lungs seen in these patients.

Adult↗
PubMed2002

Human alveolar epithelial cells induce nitric oxide synthase-2 expression in alveolar macrophages.

It was hypothesized that cell-to-cell interaction between human alveolar macrophages (AM) and alveolar epithelium, might be an important factor leading to nitric oxide synthase-2 (NOS2) messenger ribonucleic acid (mRNA) and protein expression by constituent cells of the alveolar wall and/or AM. NOS2 mRNA and the protein expression patterns of human AM and alveolar epithelial cells type II (AEC-II) isolated from normal parts of lung resections of patients with pulmonary malignancies were determined. In addition, NOS2 mRNA expression in human AM co-cultured with autologous AEC-II in the presence of pro-inflammatory cytokines interleukin (IL)-1beta, tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma or lipopolysaccharide (LPS) was investigated. The effect of human surfactant protein-A (SP-A) on IFN-gamma-mediated NOS2 mRNA expression in human AM was also studied. Neither NOS2 mRNA nor protein could be detected in freshly isolated, unstimulated or cytokine-stimulated AEC-II. In contrast, freshly isolated AM from bronchoalveolar lavage or lung tissue samples expressed immunoreactivity for NOS2 protein, but no NOS2 mRNA could be detected by reverse transcriptase polymerase chain reaction. All stimuli tested failed to induce NOS2 mRNA expression in human AM in vitro. Only AM-AEC-II co-culture in the presence of IFN-gamma led to NOS2 mRNA and protein expression. In situ hybridization of NOS2 mRNA on lung tissue explants and immunohistochemical staining of cytospin preparations of AM-AEC-II co-cultures demonstrated that NOS2 is expressed in AM but not in AEC-II. This co-culture effect could not be reproduced by substitution of AEC-II with SP-A. These data give evidence of a regulatory network controlling human nitric oxide synthase-2 expression in the lower respiratory tract.

Blotting, Western↗
PubMed2001

Results from a genome-wide search for predisposing genes in sarcoidosis.

Sarcoidosis is a systemic disease of granulomatous inflammation and unknown etiology. An inherited predisposition is involved, and many candidate susceptibility genes have been tested in association studies. We have applied the more general strategy of genome-wide microsatellite linkage analysis to identify chromosomal regions that contribute to the risk of sarcoidosis. On the basis of 225 microsatellite markers tested in 63 families with affected siblings (138 patients) and multipoint nonparametric linkage (NPL) analysis, we found the most prominent peak (six adjacent markers including D6S1666; NPL score = 2.99; p = 0.001) at the major histocompatibility complex (MHC). Six minor peaks (p < 0.05) were found on chromosomes 1 (D1S1665 ), 3 (D3S1766 ), 7 (D7S821 and D7S3070), 9 (D9S934), and the X chromosome (DXS6789). A subset of nine families with more than two affected siblings (30 patients) contributed little to the peak at the MHC (D6S1666; NPL score = 0.79; p = 0.21). Our results point to locus heterogeneity of susceptibility to sarcoidosis, with a major effect of the MHC.

Adult↗
PubMed2001

Gene polymorphisms of immunoregulatory cytokines and angiotensin-converting enzyme in Wegener's granulomatosis.

Wegener's granulomatosis is a granulomatous and vasculitic disease of unknown origin. Gene polymorphisms are known to affect phenotypes of numerous diseases. Polymorphisms within the angiotensin-converting enzyme (ACE), transforming growth factor-beta1 (TGF-beta1), and interleukin-10 (IL-10) genes are suspected to modify the course of granulomatous disorders. We examined whether the genotype frequencies of the named polymorphisms differ in Wegener's granulomatosis from those in healthy controls. Thirty-nine patients with Wegener's granulomatosis were genotyped for the deletion/insertion polymorphism in intron 16 of the ACE gene, a biallelic polymorphism in codon 25 of the TGF-beta1 gene and a biallelic polymorphism at position -1082 of the IL-10 gene and compared with healthy blood donors. For the ACE polymorphism no significant differences were detected neither in the allele frequencies nor in the genotype frequencies. For TGF-beta1 a trend to genotype CG was found. The most interesting result was the observed, significant shift to genotype AA of the IL-10 polymorphism in Wegener's granulomatosis. IL-10 and TGF-beta1, immunoregulatory cytokines capable of down-regulating T helper cell type 1 response, showed a significant shift or a trend, respectively towards genotypes associated with reduced cytokine release, leading to the hypothesis that different immunoregulatory cytokine patterns dependent on gene polymorphisms might be involved in the pathogenesis of Wegener's granulomatosis.

Adult↗
PubMed2001

Differential mediator release from basophils of allergic and non-allergic asthmatic patients after stimulation with anti-IgE and C5a.

The differentiation between allergic and non-allergic asthma is a common and important challenge for the clinician. Until now, no in vitro diagnostic characteristics have been described to distinguish between these types. To examine the diagnostic value of a basophil stimulation test, we compared anti-IgE- and C5a-induced mediator release from peripheral blood leucocytes in different types of bronchial asthma. Peripheral blood leucocytes (PBL) from 10 aspirin-sensitive asthmatics (ASA), 12 non-allergic asthmatics without aspirin intolerance (NAA), seven allergic asthmatics (AA), and nine healthy controls were prepared by dextran sedimentation. After priming with interleukin-3 (IL-3) PBL were stimulated with anti-IgE and C5a, and the release of histamine (HR) and sulfidoleukotrienes (LTR) in the supernatant was compared. Additionally, purified leucocyte fractions were studied to determine the cellular source of mediator release. Upon stimulation with anti-IgE LTR was slightly, but not significantly, lower in ASA and NAA compared to AA and controls. In contrast, C5a-triggered LTR was significantly higher in ASA (14.4 +/- 12.88 pg/105 cells) and NAA (22.9 +/- 22.61 pg/105 cells) than in AA (9.6 +/- 3.29 pg/105 cells) and controls (7.5 +/- 7.19 pg/105 cells) (P < 0.05). This difference between ASA and NAA vs. AA and controls was even more pronounced when determining the quotient C5a-/anti-IgE-induced LTR (P < 0.001). At an optimal cut-off point of 1.0, calculated by relative operating characteristics (ROC) analysis, the positive predictive value for a donor to belong to ASA or NAA was 0.94. No significant differences could be found in HR between the asthmatic patient groups and healthy controls in either condition. As cellular source of LTR and HR the basophil could be determined. Determination of anti-IgE- and C5a-induced LTR from basophils allows us to discriminate between allergic and non-allergic asthmatic patients. For diagnostic purposes the quotient C5a-/anti-IgE-induced LTR is more significant than considering a single parameter. ASA cannot be distinguished from NAA.

Adolescent↗
PubMed2001

Discontinuous IgE-binding epitopes contain multiple continuous epitope regions: results of an epitope mapping on recombinant Hol l 5, a major allergen from velvet grass pollen.

The knowledge of IgE-binding epitopes on allergen molecules is important for better understanding allergen-antibody interactions and, thus, for developing new strategies for immunotherapy. Our purpose was to more precisely define the number and structure of IgE-binding epitopes of a paradigmatic major grass pollen allergen. We performed an IgE-binding epitope mapping of rHol l 5, a group V pollen allergen of velvet grass (Holcus lanatus), with overlapping fragments (length between 15 and 186 amino acids), which were expressed in E. coli as MBP fusion proteins. Using sera of 65 grass pollen allergic patients, the fragments were analysed by immunoblotting for IgE reactivity. Specificity of antibody binding was confirmed by competitive blot inhibition assays. At least four different continuous IgE-binding epitopes were identified on small fragments (about 30 amino acids), and at least five different discontinuous IgE-binding epitopes on larger fragments, which were destroyed by further fragmentation. The fragments were differentially recognized by individual patients' sera. By investigating IgE-binding to one of the small fragments in more detail, we found further epitope regions on this fragment. It was noteworthy that IgE reactivity to small fragments was weak compared to large fragments or to the complete molecule. Competitive blot inhibition experiments showed that binding of IgE antibodies to the small fragments was specific but with lower avidity than to the complete rHol l 5. rHol l 5 harbours multiple discontinuous as well as continuous IgE-binding epitopes spread over the whole molecule, which were individually recognized by IgE antibodies from different patients. Low avidity of IgE antibodies to small fragments suggests that the continuous epitope regions do not represent the complete epitope and are most probably parts of discontinuous epitopes.

Allergens↗
PubMed2001

Angiotensin-converting enzyme (ACE) gene polymorphisms and familial occurrence of sarcoidosis.

OBJECTIVES: The aim of this study was to test for genetic linkage and association between polymorphisms of the angiotensin-converting enzyme (ACE) gene and familial occurrence of sarcoidosis. DESIGN, SETTING AND SUBJECTS: German families with more than one member suffering from sarcoidosis were contacted and a DNA bank was established. Sixty-two families (140 patients, 77 females and 63 males, and 104 unaffected relatives) were genotyped for the ACE gene insertion/deletion (I/D) polymorphism and for two flanking variable sites (ACE A-5466C and ACE 4656(CT)2/3). As controls, 100 DNAs from unrelated resident Caucasians (50 females, 50 males) were analysed. ACE allele and genotype frequencies were determined, and parametric linkage and affected sib pair analyses and transmission disequilibrium tests were performed. RESULTS: There was a striking over-representation of the ACE I/D genotype DD in patients with sarcoidosis and their families as compared with controls of the study and well founded genotype frequencies from the literature. The same was evident for the accompanying genotypes CC and 2,2 of the flanking polymorphisms. Linkage between the segregation of ACE alleles and the disorder within families was clearly excluded for simple models of inheritance. However, there was a suggestive but not significant (P = 0.06) excess of allele sharing amongst affected siblings. There was no transmission disequilibrium for any ACE allele or haplotype. CONCLUSIONS: ACE is involved in the pathogenesis of sarcoidosis, but the ACE polymorphisms are not an inherited main cause of the disease. They are more likely to modify the development of the disorder, and the ACE I/D genotype DD might be a promoter to clinical manifestation.

Adult↗
PubMed2001

A glycoprotein from Schistosoma mansoni eggs binds non-antigen-specific immunoglobulin E and releases interleukin-4 from human basophils.

We have recently shown that soluble extracts from Schistosoma mansoni eggs (SmEA) triggered basophils from nonsensitized donors to rapidly release interleukin (IL)-4. Assuming that this mechanism might play a role in vivo in biasing the immune response towards a Th2 phenotype, we determined basic properties of the IL-4-inducing activity contained in SmEA. Sensitivity to pepsin digestion indicated protein nature. Binding to and specific elution from Concanavalin A-sepharose suggested that this protein contains mannose residues, thus being a glycoprotein. The IL-4-inducing activity was stable for 30 min at room temperature towards shifting the pH between 3 and 10. When incubated at 100 degrees C, it was stable at pH 3, but less stable at neutral and alkaline pH. Electroelution from an SDS-PAGE gel indicated an apparent molecular weight of the IL-4-inducing activity between 31 and 66 kDa. Although binding to purified human immunoglobulin E (IgE) and activating basophils IgE-dependently, SmEA appears to activate basophils in a non-antigen-specific way, since the cells were purified from noninfected donors. Because the IL-4-inducing activity was found to be released from eggs, it could be an important factor in the environment of the eggs skewing the immune response towards the Th2 phenotype.

Animals↗
PubMed2001

[Corrected normal values for serum ACE by genotyping the deletion-/insertion-polymorphism of the ACE gene].

BACKGROUND: In sarcoidosis, serum ACE is widely recognised as a marker of disease activity. Since 1990 a deletion-/insertion polymorphism of the ACE gene is known and a correlation between the genotypes of this polymorphism and serum ACE levels has been observed. Homzygotes for the deletion allele (DD) have the highest levels and homozygotes for the insertion allele (II) the lowest. Heterozygote (DI) persons show intermediate levels. The extent of this influence varies in populations of different ethnic origin. In a large cohort of healthy individuals from North of Germany, genotype-based normal ranges for serum ACE were determined for the population of Germany for the first time. METHODS: In 262 healthy individuals the genotype of the ACE D/I gene polymorphism was determined from genomic DNA by a PCR method. In addition, in serum samples of all these individuals ACE level was measured with a kinetic test. RESULTS: The genotype DD was found in 29.4 % of the individuals examined, the genotype DI in 49.6 % and the genotype II in 21.0 %, respectively. These results are similar to those found in previous investigations in other populations of Central European origin. The mean serum ACE levels (95 % confidence interval) in individuals with the genotypes DD, DI and II are 59.8 U/l (31.8 - 87.8), 47.7 U/l (18.6 - 76.8) and 32.2 U/l (13.7 - 50.7), respectively. Without taking the genotype into account, the average value is 48.0 U/l (15.0 - 80.9). Differences between all genotype groups are highly significant (p < 0.0001). CONCLUSIONS: In sarcoidosis patients, the determination of this ACE gene polymorphism once in the course of the disease allows a better interpretation of the serum ACE levels measured.

Acetylcholinesterase↗
PubMed2001

Interleukin-12 as successful adjuvant in tuberculosis treatment.

Interleukin-12 (IL-12) proved to be an effective and successful adjuvant to a standard antituberculotic medication in a patient suffering from progressive clinical tuberculosis (TB). IL-12 is a potent enhancer of interferon-gamma production which is necessary for killing intracellular bacteria like mycobacteria. This patient's TB was progressive, although sensitivity to first-line antituberculotics was proven and medication was given as directly observed therapy over more than 8 months. The 3-month adjuvant therapy with IL-12 significantly and convincingly improved results. It is believed that this case, the first in the literature to describe adjuvant interleukin-12 therapy in tuberculosis, strongly encourages the study of adjuvant interleukin-12 therapy on a more systematic basis.

AIDS-Related Opportunistic Infections↗
PubMed2001

Analysis of gene polymorphisms in interleukin-10 and transforming growth factor-beta 1 in sarcoidosis.

BACKGROUND AND AIM OF WORK: Interleukin-10 (IL-10) and transforming growth factor-beta 1 (TGF-beta 1) are anti-inflammatory cytokines that play important roles in the immunoregulatory processes of numerous granulomatous diseases. In sarcoidosis polymorphisms (PMs) within these cytokine genes are suspected of modifing the course of the disorder. Therefore, we were interested in whether the genotype frequencies for a PM at position -1082 of the IL-10 or in codon 25 of the TGF-beta 1 gene differ in sarcoidosis or its distinct phenotypes in comparison with healthy individuals. METHODS: In 51 sarcoidosis patients and 72 healthy blood donors, genotyping for the named PMs was performed by PCR methodology and restriction enzyme digestion. Patients were retrospectively classified according to their course of disease, namely spontaneous remission, regressive under therapy, or chronic-progressive. RESULTS: For TGF-beta 1 PM the genotype frequencies ranged between 81.8-90.5, 9.6-13.9 and 0-5.3 percent for genotype GG, CG and CC respectively. For IL-10 PM the values ranged between 17.7-23.2, 54.4-68.4 and 21.1-26.4 percent for AA, AG and GG. Statistical comparisons of the allele and genotype frequencies between the clinical defined sarcoidosis groups and the healthy blood donors revealed no significant differences.

Adult↗
PubMed2000

Analysis of differentially regulated mRNAs in peripheral blood monocytes of berylliosis patients after in vitro stimulation.

In berylliosis and other granulomatous diseases the macrophage is regarded as effector cell in granuloma formation. However, little is known about granuloma-associated regulation of genes in these cells. Differential display reverse transcription polymerase chain reaction (DDRT-PCR) is an attractive method for detection of differentially expressed genes. Since DDRT-PCR requires a comparably low quantity of RNA, its application to rare and limited amounts of clinical samples is convenient. In the present study we applied DDRT-PCR in a multiple and complex comparison of expressed sequence tags induced in response to various granuloma-associated and control stimuli. Since we are interested in granuloma-restricted changes, we tested peripheral blood monocytes from berylliosis patients by DDRT-PCR stimulated with up to nine different stimuli, including BeSO4, the causal agent of berylliosis. Comparison of a total of 1663 sequence tags in four berylliosis patients revealed a mean of 32.5-37.4% differentially regulated sequence tags in peripheral blood monocytes of berylliosis patients, caused by stimuli including beryllium or Mycobacterium tuberculosis and control stimuli such as Latex or Zymosan. In 7.7-28.0% of the analyzed sequence tags we detected a differential regulation restricted to the presence of granuloma-associated stimuli BeSO4, HgS, LiCO3, NiSO4, lipopolysaccharide, and/or heat killed M. tuberculosis; 1.4-12.3% were induced by more than one granuloma-associated stimulus. Alterations associated with BeSO4 and one of the named stimuli were detected in 1.4-4.5%. An exclusive association with BeSO4 was found in 2.6-5.7% of the analyzed sequence tags.

Adult↗
PubMed2000

Accessory function and costimulatory molecule expression of alveolar macrophages in patients with pulmonary tuberculosis.

An effective immune response against M. tuberculosis requires a coordinated interaction of alveolar macrophages (AM) and lymphocytes. Secondary signals, such as accessory function (AF) of antigen presenting cells and interaction of costimulatory molecules are also important for T cell activation. In the present study we determined the AF and the expression of CD11a, CD54, CD58, CD80, CD86 and HLA-DR costimulatory molecules by AMs lavaged from patients with pulmonary tuberculosis and controls. We hypothesized that alterations in AF and costimulatory molecule expression may influence the presentation of tuberculosis. Therefore these parameters were also correlated with the radiographic extension of the disease. AMs of patients with tuberculosis exhibited an increased AF and a significantly increased expression of co-stimulatory molecules compared with controls. Furthermore, we observed that the expression of CD54 (ICAM-1) decreased with the course of the disease. We conclude that the infection by M. tuberculosis results in an increased AF of AMs and the activity of AMs remains uninfluenced by the extension of the disease. Clear-cut changes of patterns of costimulatory molecule expression by AMs could not be observed with the progression of tuberculosis.

Antigens, CD↗
PubMed2000

Low in vitro production of interferon-gamma and tumor necrosis factor-alpha in HIV-seronegative patients with pulmonary disease caused by nontuberculous mycobacteria.

We studied 32 HIV-seronegative patients with pulmonary disease caused by nontuberculous mycobacteria (NTM). Immunologic studies included lymphocyte subset analysis by flow cytometry, measurement of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) production following in vitro stimulation of diluted whole blood (DWB) and peripheral blood mononuclear cells (PBMC) by phytohemagglutinin (PHA), anti-CD3 as well as purified protein derivative of tuberculin (PPD), and in four cases with different amounts of the very mycobacterium, which caused disease in these patients. Data were compared to those of 30 HIV-seronegative patients with disease by Mycobacterium tuberculosis (MTb). Following alpha-CD3-stimulation of PBMC, NTM patients showed lower IFN-gamma (P < 0.00005) and lower TNF-alpha (P < 0.02). For a subgroup of tuberculin skin test-positive NTM patients we found significantly lower PPD-induced IFN-gamma releases in cultured DWB (P < 0.0002) and PBMC (P < 0.0004) compared to MTb patients. Data for PPD-induced TNF-alpha release for this subgroup were also significant (P < 0.001 and P < 0.05, respectively). The four NTM patients with poor PPD-induced IFN-gamma response hardly showed increased cytokine production on stimulation with their specific mycobacterium. The lower production capacity of IFN-gamma and TNF-alpha of NTM patients compared to the MTb patients points to an immunologic imbalance forming the basis for their increased susceptibility to pulmonary infections by nontuberculous mycobacteria.

Adult↗