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Biomedical subjects

B Schlüter

Publications and source records attributed to B Schlüter.

At least 19 recordsLinked to original sources
PubMed2006

Clinical and immunological characteristics of patients with Sjögren's syndrome in relation to alpha-fodrin antibodies.

OBJECTIVES: To analyse the prevalence of alpha-fodrin antibodies in patients with primary (pSS) and secondary Sjögren's syndrome (sSS) and the relation to clinical, serological and immunological features. METHODS: Serum IgA and IgG antibodies to the 120 kDa alpha-fodrin were determined by ELISA technique in 62 pSS patients and 28 sSS patients. Results were correlated with clinical symptoms and laboratory findings as well as with the HLA-DR genotype. Additionally, antibody concentrations were correlated with the numbers of peripheral blood mononuclear cells (PBMCs) secreting interleukin (IL)-6, IL-10, interferon-gamma (INF)-gamma, and tumour necrosis factor-alpha determined by ELISPOT analysis. Lymphocytes and monocytes were examined flow-cytometrically for the expression of activation markers. Healthy age- and sex-matched volunteers served as controls. RESULTS: The sensitivity of IgA and IgG alpha-fodrin antibodies was 35 and 31%, respectively, in pSS patients. In sSS patients, the sensitivity was 29 and 21%, respectively. In pSS patients with IgG antibodies, recurrent parotid swelling was significantly more prevalent. Also the number of INF-gamma secreting PBMCs and the percentage of CD4/CD71+ lymphocytes as well as CD14/HLA-DR+ monocytes were significantly increased in this group compared with alpha-fodrin-negative patients or with controls. Interestingly, these patients also had a shorter disease duration. No association of alpha-fodrin antibodies with the HLA-DR genotype was found. CONCLUSION: Due to the low prevalence, serum antibodies to alpha-fodrin turned out to be of limited diagnostic value in our study. However, our data suggest that IgG antibodies to alpha-fodrin are indicative of clinical and immunological activity in pSS especially in patients with shorter disease duration and may thus serve as a marker of disease activity.

Adult↗
PubMed2004

Interleukin 10 promoter microsatellite polymorphisms are associated with response to long term treatment with etanercept in patients with rheumatoid arthritis.

OBJECTIVES: To analyse the association of interleukin 10 (IL10) promoter polymorphisms, which have been shown to be related to IL10 secretion capacity, with the response to long term treatment with etanercept in patients with rheumatoid arthritis (RA). METHODS: Fifty patients with active RA were treated for up to 4 years (median 39 months, range 3-52) with stable doses of etanercept as monotherapy. Treatment response was assessed as defined by the EULAR criteria in an intention to treat analysis, with the last observation carried forward. IL10 promoter microsatellite polymorphisms IL10.R and IL10.G were genotyped by fragment length analysis in patients and 189 healthy controls matched for ethnicity, age, and sex. Haplotypes were reconstructed using a method based on bayesian, coalescent theory with the PHASE software. RESULTS: IL10 microsatellite polymorphisms were not associated with susceptibility to RA. When patients with good treatment response (n = 25) were compared with patients with moderate (n = 17) or no response (n = 8), a significantly different distribution of the prevailing alleles R2, R3 and G9, G13, respectively, became evident. Good treatment response was associated with carriage of the R3 allele or R3-G9 haplotype, whereas the allele G13 and the haplotype R2-G13 predominated in patients with moderate or no response. CONCLUSION: Genotyping of the IL10 promoter microsatellites may be useful in predicting the clinical response to etanercept in patients with RA. The high prevalence of the presumptive IL10 low producer allele R3 in patients with a favourable response suggests that IL10 promotes disease activity in RA under the specific condition of tumour necrosis factor antagonism.

Adult↗
PubMed2004

Interleukin-10 promoter microsatellite polymorphisms in systemic lupus erythematosus: association with the anti-Sm immune response.

OBJECTIVES: Overproduction of interleukin-10 (IL-10) is a pivotal feature in the pathophysiology of systemic lupus erythematosus (SLE). In vitro IL-10 secretion has previously been related to haplotypes of the IL-10 promoter microsatellite polymorphisms IL10.R and IL10.G. Published data concerning the association of IL10.G alleles with susceptibility to SLE are inconsistent in different ethnic populations. We analysed the association of IL-10 promoter microsatellite polymorphisms with disease susceptibility and manifestations in German Caucasian patients with SLE. METHODS: Two hundred and ten (210) SLE patients fulfilling the 1997 revised ACR criteria and 158 ethnically, age- and sex-matched healthy controls were genotyped for the IL-10 promoter microsatellite polymorphisms by fragment length analysis. Haplotypes were reconstructed using a Bayesian coalescent theory-based method with PHASE software. Allele and haplotype distributions were compared between patients and controls and between subgroups of patients with different clinical and immunopathological findings. RESULTS: In the study population no significant associations of individual IL10.R and G alleles or their haplotypes with susceptibility to SLE or major clinical manifestations were observed. By contrast, alleles G14 and G15 and haplotypes R2-G14 and R2-G15 were significantly over-represented in anti-Sm antibody-positive patients. CONCLUSIONS: The IL-10 promoter microsatellite polymorphisms and their haplotypes do not constitute a major risk factor for SLE in German Caucasians. However, the identification of genetic markers such as the IL-10 high-response haplotype R2-G14 predisposing for the production of anti-Sm antibodies may help to elucidate the conditions that lead to the development of SLE.

Adolescent↗
PubMed2004

Long-term treatment with etanercept significantly reduces the number of proinflammatory cytokine-secreting peripheral blood mononuclear cells in patients with rheumatoid arthritis.

OBJECTIVES: To determine the influence of etanercept treatment on the number of peripheral blood mononuclear cells (PBMC) secreting immunoregulatory key cytokines and the correlation of these cell counts with treatment response in patients with rheumatoid arthritis (RA). METHODS: Nineteen patients with RA were treated with etanercept as monotherapy. Frequencies of PBMC secreting cytokines were determined by ELISPOT analysis before and after 9 months of therapy and compared with values for healthy controls (HC). The clinical outcome was assessed as defined by the ACR criteria. RESULTS: Fifteen patients fulfilled the ACR20, seven patients the ACR50 and two patients the ACR70 criteria. Initially elevated numbers of tumour necrosis factor-alpha- and interleukin (IL)-1beta-secreting PBMC were reduced to HC levels, and normal or low numbers of IL-6- and interferon-gamma (IFN-gamma)-secreting PBMC were reduced below HC levels. The number of IL-10-secreting PBMC did not differ from that in HC and did not change significantly over time. The pretreatment IFN-gamma:IL-10 ratio correlated to reduction in the tender and swollen joint counts. CONCLUSIONS: Long-term treatment with etanercept in patients with RA significantly reduces the numbers of proinflammatory cytokine-secreting PBMC, while the number of IL-10-secreting cells is unaffected. Although the changes described did not affect the safety or efficacy of etanercept therapy, these alterations may account for the long-term systemic effects. The pretreatment IFN-gamma:IL-10 ratio may be of prognostic value in predicting the improvement in joint symptoms.

Adult↗
PubMed2004

[Restless legs syndrome in childhood].

The diagnostic criteria of restless legs syndrome were defined in 1995 by the International Restless Legs Syndrome Study Group (IRLSSG). In light of the latest scientific evidence and increasing clinical experience, the diagnostic criteria were revised in a consensus workshop. Participants of the workshop considered the development of new diagnostic criteria especially important for the following subgroups: (1) for children and (2) for the cognitively impaired elderly. The common characteristic of both groups lies in their difficulty in expressing subjective symptoms adequately. This considerably impedes the diagnosis of restless legs syndrome. In 2002, a proposal for diagnostic criteria of restless legs syndrome in childhood was formulated by members of the study groups "Movement Disorders and Sleep" and "Paediatrics" of the German Sleep Society. The proposal was partially incorporated into the diagnostic criteria for restless legs syndrome in childhood suggested by the IRLSSG. The current criteria are recommendations to enhance further research and must be validated by clinical studies. The following article gives an overview of published studies on restless legs syndrome in childhood, reviews the proposals for diagnostic criteria, and summarizes the peculiarities to be considered in diagnosing restless legs syndrome in children.

Adolescent↗
PubMed2004

Increased frequency of GM-CSF secreting PBMC in patients with active systemic lupus erythematosus can be reduced by immunoadsorption.

An objective was to determine the frequency of GM-CSF secreting peripheral blood mononuclear cells (PBMC) in patients with active systemic lupus erythematosus (SLE) and their relation to other cytokine secreting PBMC, activation markers on lymphocytes/monocytes, clinical manifestations and anti-dsDNA antibodies. A second objective was to further investigate the influence of immunoadsorption (IA) therapy on these parameters. The number of GM-CSF, interleukin-1beta (IL-1beta), IL-6, interferon-gamma (INF-gamma) or tumour necrosis factor-alpha (TNF-alpha) secreting PBMC was assessed by ELISPOT assay in 10 patients with active SLE. Further, the expression of activation markers on lymphocytes and monocytes was determined by flow cytometry. Three courses of IA were performed in the patients. Seventeen healthy, age- and sex-matched volunteers served as controls. GM-CSF secreting PBMC were significantly increased whereas INF-gamma secreting cells were decreased in SLE patients. The expression of CD71 (transferrin receptor) on CD4+ T-cells and of the costimulatory molecule CD86 on B-lymphocytes was significantly increased in SLE patients. GM-CSF secreting PBMC and CD4+/CD71+ T-cells correlated with anti-dsDNA antibody titres and decreased towards levels of controls during IA. Disease activity and anti-dsDNA autoantibody titres were significantly reduced after the treatment. Our results demonstrate significant alterations of cellular and humoral immunity in SLE patients. The impaired immunity can be modulated by IA. Thus IA may prove an immunomodulatory therapeutic option in addition to the mere depletion of anti-dsDNA autoantibodies.

Adult↗
PubMed2003

Interleukin 1beta and tumour necrosis factor alpha secreting cells are increased in the peripheral blood of patients with primary Sjögren's syndrome.

OBJECTIVE: To study systemic alterations of cytokine secreting peripheral blood mononuclear cells (PBMC) in primary Sjögren's syndrome (pSS) and their relation to common clinical and immunological manifestations of this disease. METHODS: PBMC spontaneously secreting tumour necrosis factor alpha (TNFalpha), interleukin 1beta (IL1beta), and interleukin 6 (IL6) were assessed by enzyme linked immunospot (ELISPOT) analysis in a cohort of 31 patients with pSS fulfilling the modified European classification criteria. Nineteen healthy volunteers served as controls. ELISPOT results were correlated with glandular and extraglandular manifestations and autoantibody titres-that is, rheumatoid factor (RF) isotypes, anti-Ro/SS-A, anti-La/SS-B as determined by an enzyme linked immunosorbent assay (ELISA) technique. RESULTS: The number of TNFalpha and IL1beta secreting cells was significantly higher in patients with pSS than in controls. No differences were detected in the number of IL6 secreting PBMC. Patients with recurrent parotid swelling (RPS) had a significantly increased number of IL1beta secreting PBMC. Moreover, the number of IL1beta secreting PBMC correlated with the disease duration (r(s)=0.479; p<0.01) and with the concentration of IgM RF (r(s)=0.63; p<0.01) and IgG RF (r(s)=0.42; p<0.05). Other autoantibodies did not correlate with cytokine secreting PBMC. CONCLUSION: The increased systemic secretion of IL1beta and TNFalpha in patients with pSS points to a pathogenic impact of these cytokines in this autoimmune disease. In particular the correlation of IL1beta secreting PBMC with RPS and RF production indicates that IL1beta is a crucial regulator in the development of local and systemic disease manifestations.

Adult↗
PubMed2003

The transforming growth factor-beta1 gene polymorphism (G915C) is not associated with systemic lupus erythematosus.

Lymphocyte production of transforming growth factor (TGF)-beta1 is decreased in systemic lupus erythematosus (SLE). The lack of this immunoregulatory cytokine may contribute to the characteristic T cell disregulation and aberrant B cell stimulation in SLE patients. The less common C allele of the TGFB1 polymorphism (G915C) is associated with a lower TGF-beta1 production capacity. We performed a population-based case-control study to analyse the impact of this polymorphism on disease susceptibility, on clinical SLE manifestations and autoantibody production. A total of 203 German Caucasian SLE patients (fulfilling the 1982 ACR disease duration 11.5 +/- 7.0 years) and 158 ethnically, age- and sex-matched healthy controls were genotyped with a mutagenically separated polymerase chain reaction. There were no significant differences in the genotype distribution and allele frequencies between patients (915 C = 0.08) and healthy controls (915 C = 0.10). Comparing subgroups of patients, we found no association of major disease manifestations or specific autoantibodies with TGFB1 genotypes or alleles. The TGFB1 polymorphism (G915C) neither significantly contributes to the disease susceptibility, nor predisposes to clinical and immunological manifestations typical of SLE. Further studies are needed to corroborate the pathogenic role of TGF-beta1 in SLE patients and to identify the precise genetic elements controlling its production.

Adult↗
PubMed2001

Lack of association between the -260 C-->T promoter polymorphism of the endotoxin receptor CD14 gene and the CD14 density of unstimulated human monocytes and soluble CD14 plasma levels.

OBJECTIVE: CD14 is a receptor for endotoxin and binds components of Gram-positive and Gram-negative bacteria. CD14-bearing monocytes respond to stimulation with the increased synthesis and release of cytokines. The recently described -260 C-->T promoter polymorphism of the CD14 gene has been found to be related to a risk of myocardial infarction. This study evaluated the role of this polymorphism in the expression of monocyte and soluble CD14. Moreover, the effect of the CD14 -260 genotypes for the ex vivo TNF-alpha response to endotoxin was analyzed in whole blood. PATIENTS AND PARTICIPANTS: Ninety-five healthy blood donors were studied. MEASUREMENTS AND RESULTS: CD14 -260 genotyping was performed by means of a real-time PCR with fluorescence labeled hybridization probes. CD14 expression on human monocytes (mCD14) was assessed by fluorescence-activated cell sorting analysis with anti-CD14 monoclonal antibodies. Plasma levels of soluble CD14 (sCD14) were measured by ELISA. The TNF-alpha synthesis was determined by chemiluminescence in whole blood after endotoxin stimulation. There were no differences in mCD14 density, sCD14 levels, or the tumor necrosis factor-alpha concentrations between individuals with the three different CD14 -260 genotypes CC, CT, and TT. CONCLUSIONS: The CD14 -260 polymorphism does not affect the CD14 expression of unstimulated circulating monocytes or soluble CD14 plasma levels.

Adult↗
PubMed2001

The human ABCG4 gene is regulated by oxysterols and retinoids in monocyte-derived macrophages.

Here we report the induction of gene expression of ABCG4, a member of the ABC transporter subfamily G, from human macrophages by oxysterols and retinoids, agonists of the nuclear receptors LXR and RXR. The cloned ABCG4 transcript has a size of 3.5 kb and contains an open reading frame which encodes a polypeptide of 646 amino acids. Structurally, the putative ABC transporter protein consists of a nucleotide binding fold followed by a cluster of six transmembrane-spanning domains and thus conforms to the group of half-size ABC transporters. Among the human ABC transporter subfamily G members the novel transporter shows highest protein sequence homology and identity to ABCG1 (84 and 72%, respectively). Analysis of the genomic organization demonstrates that the ABCG4 gene is composed of at least 14 exons which extend across a region of 12.6 kb in size on chromosome 11q23.3. Based on its structural features and an LXR/RXR-responsive regulation similar to the cellular lipid export protein ABCA1, we conclude that ABCG4 may be involved in macrophage lipid homeostasis.

ATP Binding Cassette Transporter, Subfamily G↗
PubMed2001

Interleukin-6 promoter polymorphism (--174 G/C) in Caucasian German patients with systemic lupus erythematosus.

BACKGROUND: A biallelic polymorphism (--174 G/C) within the interleukin-6 (IL-6) promoter reportedly has functional importance through the modulation of IL-6 expression in vitro and in vivo. METHODS: We performed a population-based case-control study to analyse the association of the --174 G/C polymorphism with disease susceptibility and clinical manifestations in 211 German patients with systemic lupus erythematosus (SLE). RESULTS: There were no significant differences in allelic and genotypic frequencies between patients and healthy controls. Comparing patients with various disease manifestations, we found an association of the --174 G allele with discoid skin lesions (Pc=0.034) and anti-histone antibodies (Pc=0.009). CONCLUSIONS: The IL-6 promoter polymorphism --174 G/C does not contribute significantly to disease susceptibility, but predisposes to distinct clinical and immunological features. A genetically determined high IL-6 response may have a pathogenic role under these conditions.

Adult↗
PubMed2001

Impact of FDG PET on patients with differentiated thyroid cancer who present with elevated thyroglobulin and negative 131I scan.

UNLABELLED: FDG PET is increasingly performed in patients with differentiated thyroid cancer who present with elevated human thyroglobulin (hTG) levels and negative 131I scan. The aim of this study was to evaluate the impact of FDG PET on treatment in these patients. METHODS: A total of 118 FDG PET studies were performed on 64 patients, and follow-up data were available for all patients. Whole-body images were acquired 1 h after intravenous injection of 370 MBq (10 mCi) FDG using a PET scanner with an axial field of view of 16.2 cm. Tumor-suspicious FDG PET studies were evaluated by histology, cytology, 131I uptake, CT or MRI, and follow-up of hTg levels. The therapeutic consequence was noted for each patient. Moreover, results of FDG PET were correlated with hTg levels. RESULTS: Forty-four patients had positive scans, which were proven to be true-positive in 34 patients, whereas 7 patients had false-positive findings. Two patients exhibited a secondary malignancy. One patient did not fit in any category, having true-positive, false-positive, and false-negative findings. On the other hand, 20 patients had negative scans. These were true-negative findings in 5 patients, whereas the remaining 15 patients had false-negative results. Accordingly, the positive predictive value of FDG PET was 83% (34/41), whereas the negative predictive value was 25% (5/20). Treatment was directly changed in 19 of 34 patients with true-positive PET studies: 18 patients had further surgery, and 4 patients were referred for external irradiation, 3 of them after incomplete removal of local recurrences. FDG PET showed widespread disease in 7 patients; thus, palliative treatment, rather than curative therapy, was initiated. True-positive FDG PET findings were correlated positively with increasing hTg levels (i.e., FDG PET was true-positive in 11%, 50%, and 93% of patients with hTg levels of <10, 10-20, and >100 microg/L, respectively). CONCLUSION: FDG PET is a valuable diagnostic tool in patients with differentiated thyroid cancer who present with increased hTg levels and negative 131I scans because it permits selection of patients for surgery, which may be curative. FDG PET is most promising at hTg levels of >10 microg/L.

Adult↗
PubMed2000

Simultaneous detection of ubiquinol-10, ubiquinone-10, and tocopherols in human plasma microsamples and macrosamples as a marker of oxidative damage in neonates and infants.

A HPLC-method was developed for the simultaneous detection of the lipophilic antioxidants ubiquinol-10, ubiquinone-10, alpha-tocopherol, and gamma-tocopherol in plasma macrosamples (100 microl) as well as microsamples (10 microl) using electrochemical detection with internal standardization (gamma-tocotrienol, ubiquinol-9, ubiquinone-9). The use of a mobile phase containing ammonium formate instead of lithium perchlorate as conductivity salt and the use of a PEEK column instead of a steel column improved the reproducibility of the method. The components were separated on a RP C18 column. The detection limits for all components were between 1 and 28 fmol. The within-day precision varied between 3 and 13% for all measured substances. The analytical recovery was between 93 and 109%. The plasma levels from 10 healthy donors were determined in microsamples and macrosamples taken by micropuncture or venous puncture, respectively. A good correlation of the antioxidant levels for both methods strengthened the reliability and the transferability of the results. The present method can be used to assess the role of these antioxidants in diseases associated with oxidative damage in childhood.

Antioxidants↗
PubMed1999

Rhythms and complexity of respiration during sleep in pre-term infants.

The aim of this study is to test rhythmic and complex properties of respiratory control in former ventilated, pre-term infants during quiet and active sleep. The children had a higher risk for sudden infant death due to bronchopulmonary dysplasia (BPD). Twelve infants suffering from BPD and 12 control infants, matched regarding their post-conceptional age, were examined polygraphically during quiet (QS) and active sleep (AS). The respiratory rate (RR), the ratio (LF/HF) between the low-frequency power (LF) and the high-frequency power (HF) of the spectra of the thoracic respiratory effort, and the frequency of the dominant peak within LF (LFF) and HF (HFF) were computed. The correlation dimension (D2) of the respiratory signal was calculated to determine the complexity of the respiratory control. The transcutaneous pO2 (tcpO2) and pCO2 and the oxygen saturation (sO2) were analysed. Infants with BPD had significantly higher RR and HFF during QS (median: BPD 48 breaths min-1; control 32 breaths min-1). tcpO2 and sO2 were significantly lower in the BPD group. No differences were found in LF/HF, LFF or D2 between groups, either in QS or in AS. D2 ranged between 1.8 and 3.8, showing significantly higher values during AS. LFF was found to be lower during active sleep (AS 0.04-0.05 Hz; QS about 0.06 Hz). We propose that in infants with BPD the lower lung compliance and the higher resistance, and possibly also the hypoxaemia, contribute to the acceleration of breathing. The behaviour of RR, spectral parameters and D2 indicates a specific, functional setting rather than a regulatory impairment in infants with BPD.

Bronchopulmonary Dysplasia↗
PubMed1999

Aspects of the antimicrobial efficacy of grapefruit seed extract and its relation to preservative substances contained.

The antimicrobial efficacy as well as the content of preservative agents of six commercially available grapefruit seed extracts were examined. Five of the six extracts showed a high growth inhibiting activity against the test germs Bacillus subtilis SBUG 14, Micrococcus flavus SBUG 16, Staphylococcus aureus SBUG 11, Serratia marcescens SBUG 9, Escherichia coli SBUG 17, Proteus mirabilis SBUG 47, and Candida maltosa SBUG 700. In all of the antimicrobial active grapefruit seed extracts, the preservative benzethonium chloride was detected by thin layer chromatography. Additionally, three extracts contained the preserving substances triclosan and methyl parabene. In only one of the grapefruit seed extracts tested no preservative agent was found. However, with this extract as well as with several self-made extracts from seed and juiceless pulp of grapefruits (Citrus paradisi) no antimicrobial activity could be detected (standard serial broth dilution assay, agar diffusion test). Thus, it is concluded that the potent as well as nearly universal antimicrobial activity being attributed to grapefruit seed extract is merely due to the synthetic preservative agents contained within. Natural products with antimicrobial activity do not appear to be present.

Anti-Bacterial Agents↗
PubMed1998

Histological verification of positive fluorine-18 fluorodeoxyglucose findings in patients with differentiated thyroid cancer.

Fluorine-18 fluorodeoxyglucose and positron emission tomography (FDG-PET) is a new imaging modality used in the follow-up of patients with differentiated thyroid cancer if the results of (131)I scintigraphy are negative in spite of an elevated thyroglobulin level. The aim of this retrospective analysis was to estimate the value of FDG-PET regarding the operability of patients with positive findings. From January 1994 to October 1997, we investigated 60 patients with differentiated thyroid carcinoma by FDG-PET. Thirteen patients were operated on after positive findings. Most of these lesions were suspected of having lymph-node involvement or local recurrences in the thyroid bed. One patient showed a solitary distant metastasis in the scapula. Thirteen of 16 operations in these 13 patients confirmed the suspected involvement of thyroid cancer. The false-positive findings were caused by inflamed lymph nodes in two cases and benign thymus tissue in one case. We conclude that PET is a useful diagnostic tool to guide early surgical therapy in patients with (131)I negative differentiated thyroid carcinoma.

Adenocarcinoma, Follicular↗
PubMed1997

Respiratory control in children with Prader-Willi syndrome.

UNLABELLED: Physiological parameters of infants and children with Prader-Willi syndrome were examined in order to clarify whether there were indicators of disturbed respiratory control mechanisms in the pre-obesity stage of the syndrome. From January 1993 to March 1995 in eight patients with Prader-Willi syndrome (five boys, three girls, aged 6 weeks-12.5 years), polysomnography was performed and compared with 28 children matched for gestational age, sex, birth weight and age at sleep study. The recordings included thoracic and abdominal breathing movements, nasal airflow, tcPO2, tcPCO2, oxygen saturation, EEG, EOG and ECG. Respiratory responses to hypercapnia during quiet sleep were obtained from five Prader-Willi patients and ten peers. The Prader-Willi group showed an increased number of apnoeas per hour of sleep, a decreased nadir of oxygen saturation, increased maximum of the instantaneous heart rate and decreased respiratory responses to hypercapnia during quiet sleep. CONCLUSION: These findings indicate a primary disturbance of central respiratory control in patients with Prader-Willi syndrome which may be worsened by the development of obesity.

Age of Onset↗