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Biomedical subjects

S Wegener

Publications and source records attributed to S Wegener.

At least 19 recordsLinked to original sources
PubMed2007

[From hedgehogs to men. Zoophilic dermatophytosis caused by Trichophyton erinacei in eight patients].

The hedgehog is an in Germany previously unrecognized source of human ringworm. Eight hedgehog caretakers from Göttingen and the surrounding area developed dermatophytosis caused by Trichophyton erinacei. Four patients who handled the animals without gloves developed lesions on the hands that were more in keeping with hand eczema, leading to a delay in diagnosis. The other caretakers who wore gloves presented with typical ringworm on the arms, the big toe, the back, the abdomen, and the thighs. Their typical clinical features led to an early diagnosis and treatment.

Adult↗
PubMed2006

Mutations of the tumor suppressor gene SOCS-1 in classical Hodgkin lymphoma are frequent and associated with nuclear phospho-STAT5 accumulation.

The suppressors of cytokine signaling (SOCS) are critically involved in the regulation of cellular proliferation, survival, and apoptosis via cytokine-induced JAK/STAT signaling. SOCS-1 silencing by aberrant DNA methylation contributes to oncogenesis in various B-cell neoplasias and carcinomas. Recently, we showed an alternative loss of SOCS-1 function due to deleterious SOCS-1 mutations in a major subset of primary mediastinal B-cell lymphoma (PMBL) and in the PMBL line MedB-1, and a biallelic SOCS-1 deletion in PMBL line Karpas1106P. For both cell lines our previous data demonstrated retarded JAK2 degradation and sustained phospho-JAK2 action leading to enhanced DNA binding of phospho-STAT5. Here, we analysed SOCS-1 in laser-microdissected Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL). We detected SOCS-1 mutations in HRS cells of eight of 19 cHL samples and in three of five Hodgkin lymphoma (HL)-derived cell lines by sequencing analysis. Moreover, we found a significant association between mutated SOCS-1 of isolated HRS cells and nuclear phospho-STAT5 accumulation in HRS cells of cHL tumor tissue (P < 0.01). Collectively, these findings support the concept that PMBL and cHL share many overlapping features, and that defective tumor suppressor gene SOCS-1 triggers an oncogenic pathway operative in both lymphomas.

Amino Acid Sequence↗
PubMed2001

Penicillin-resistant streptococcus pneumoniae: review of moxifloxacin activity.

Streptococcus pneumoniae is a significant pathogen of respiratory tract infections such as pneumonia, sinusitis, meningitis, and acute otitis media. Rising incidences of antimicrobial resistance among pneumococcal strains reported worldwide have led to research into and development of advanced antibacterials with improved gram-positive activity. Moxifloxacin, a new 8-methoxy quinolone, has been tested against a variety of S. pneumoniae strains, including penicillin-sensitive, intermediately resistant to penicillin, and penicillin-resistant strains. We review the preclinical data corroborated by the available clinical experience to demonstrate moxifloxacin's activity against S. pneumoniae strains, irrespective of penicillin susceptibility.

Animals↗
PubMed2001

A gene related to yeast HOS2 histone deacetylase affects extracellular depolymerase expression and virulence in a plant pathogenic fungus.

A gene, HDC1, related to the Saccharomyces cerevisiae histone deacetylase (HDAC) gene HOS2, was isolated from the filamentous fungus Cochliobolus carbonum, a pathogen of maize that makes the HDAC inhibitor HC-toxin. Engineered mutants of HDC1 had smaller and less septate conidia and exhibited an approximately 50% reduction in total HDAC activity. Mutants were strongly reduced in virulence as a result of reduced penetration efficiency. Growth of hdc1 mutants in vitro was normal on glucose, slightly decreased on sucrose, and reduced by 30 to 73% on other simple and complex carbohydrates. Extracellular depolymerase activities and expression of the corresponding genes were downregulated in hdc1 mutant strains. Except for altered conidial morphology, the phenotypes of hdc1 mutants were similar to those of C. carbonum strains mutated in ccSNF1 encoding a protein kinase necessary for expression of glucose-repressed genes. These results show that HDC1 has multiple functions in a filamentous fungus and is required for full virulence of C. carbonum on maize.

Amino Acid Sequence↗
PubMed2001

Sulfonylurea drugs do not influence initial stroke severity and in-hospital outcome in stroke patients with diabetes.

BACKGROUND AND PURPOSE: Sulfonylurea drugs inhibit ATP-dependent potassium channels and may increase mortality after myocardial infarction. Sulfonylurea drugs also inhibit ischemic preconditioning in experimental models of brain ischemia and in clinical studies in the human heart. METHODS: In the present study we examined the impact of sulfonylurea drugs on in-hospital mortality and the immediate neurological deficit of diabetic stroke patients. From a larger stroke data bank, we studied 146 diabetic patients with acute hemispheric ischemic stroke. Sixty patients were using sulfonylurea drugs. RESULTS: Major baseline characteristics such as age, blood pressure, admission glucose level, HbA(1c), distribution of cardiovascular risk factors, and presumed stroke etiology (Trial of Org 10172 in Acute Stroke Treatment [TOAST] criteria) were not different. Mortality (15% versus 14%; P=0.86) and initial stroke severity (Canadian Neurological Scale score, 7.4 versus 7.5; P=0.79) were not significantly different between patients with and without sulfonylurea drugs. Further end points such as Rankin Scale score, deteriorating stroke, duration of hospital stay, type of infarcts on CT/MRI, requirement of intensive care, and complications were not different. In a stepwise logistic regression model, sulfonylurea drugs were not independent predictors for increased mortality, deteriorating stroke, or stroke severity. CONCLUSIONS: In the present hospital-based study, sulfonylurea drugs in patients with diabetes and stroke are not associated with increased stroke severity, mortality, or a worse in-hospital outcome.

Aged↗
PubMed2000

RPD3-type histone deacetylases in maize embryos.

Posttranslational core histone acetylation is established and maintained by histone acetyltransferases and deacetylases. Both have been identified as important transcriptional regulators in various eukaryotic systems. In contrast to nonplant systems where only RPD3-related histone deacetylases (HD) have been characterized so far, maize embryos contain three unrelated families of deacetylases (HD1A, HD1B, and HD2). Purification, cDNA cloning, and immunological studies identified the two maize histone deacetylase HD1B forms as close homologues of the RPD3-type deacetylase HDAC1. Unlike the other maize deacetylases, HD1A and nucleolar HD2, HD1B copurified as a complex with a protein related to the retinoblastoma-associated protein, Rbap46. Two HD1B mRNA species could be detected on RNA blots, encoding proteins of 58 kDa (HD1B-I) and 51 kDa (HD1B-II). HD1B-I (zmRpd3) represents the major enzyme form as judged from RNA and immunoblots. Levels of expression of HD1B-I and -II mRNA differ during early embryo germination; HD1B-I mRNA and protein are present during the entire germination pathway, even in the quiescent embryo, whereas HD1B-II expression starts when meristematic cells enter S-phase of the cell cycle. In line with previous results, HD1B exists as soluble and chromatin-bound enzyme forms. In vivo treatment of meristematic tissue with the deacetylase inhibitor HC toxin does not affect the expression of the three maize histone deacetylases, whereas it causes downregulation of histone acetyltransferase B.

Amino Acid Sequence↗
PubMed2000

Alternative splicing in the regulatory region of the human phosphatases CDC25A and CDC25C.

CDC25 phosphatases play key roles in cell proliferation by activating cell cycle-specific cyclin-dependent kinases (CDKs). We identified four new splice variants in the amino-terminal regulatory region of human cdc25C and one in cdc25A. All variants except one retain an intact catalytic domain. Alternative splicing results in loss of phosphorylation sites for kinases like CDK and the calcium/calmodulin-dependent kinase II (CaMKII), which influence CDC25 activity and compartmental localization. In NT2 teratocarcinoma cells, induced for nerve cell differentiation, the smaller sized variant of cdc25C was upregulated. At the protein level both phosphorylation state and isoform distribution differed between cell lines and cell cycle phases.

Alternative Splicing↗
PubMed1997

Genomic sequence and mapping of a methyljasmonate-induced O-methyltransferase from barley (Hordeum vulgare L.).

We have isolated a genomic clone corresponding to a caffeic acid O-methyltransferase (COMT) from barley (Hordeum vulgare L.) using a cDNA for a previously described jasmonate-regulated mRNA showing homology to COMT. Primer extension was used to characterize the 5' end of the mRNA while the 3' end, intron/exon structure and other features of the sequence were deduced by comparison to the cDNA sequence and/or conserved motifs. The gene is mapped to chromosome five and is absent in the barley cultivar Morex. Southern and northern analyses suggest that no differences in genomic structure and jasmonate inducibility exist between the barley cultivar Salome (source of the cDNA clone) and Igri (source of the genomic clone). This genomic clone is thus suitable for promoter studies with respect to jasmonate induction.

Acetates↗
PubMed1997

[Inline filtration of erythrocyte concentrates with the Leucoflex LCR4 T/B system].

The in-line-filtration of red cell concentrates (RCC) is an effective method to reduce white-cell-induced reactions. SAG-M RCCs were prepared in quadruple top/bottom bag systems and filtered after storage at 4 degrees C (study: n = 12). The mean white blood cell (WBC) reduction was 99.9% with the number of residual WBCs at about 0.67 x 10(6) per unit and with a loss of Hb mass of 10.64%. No cell fragments of WBCs and monocytes were detected (MAIPA). After storage of 42 days, mean values of hemolysis level (0.64%) and ATP concentration (2.27 mumol/g Hb) were improved compared with unfiltered RCCs. Comparably good results of leukocyte depletion were achieved by preparation of about 3,000 in-line filtrated RCCs for clinical use, measured by routine quality control (n = 25). Our experience shows that the systems are easy to handle and to use. The Leucoflex LCR4 in-line T/B system (Maco Pharma) can be recommended in the clinical practice by virtue of the effective leukocyte elimination, particularly in those blood banks with platelet concentrate production from buffy coats beside the RCC in-line filtration.

Equipment Design↗
PubMed1996

Influence of anticoagulants on the level of soluble HLA class I and class II antigens measured in blood samples.

The existence of soluble forms of HLA class I and class II antigens in human serum is well established and altered concentrations of these serum proteins have been described to be associated with various diseases. Since soluble HLA antigens (sHLA) can be measured both in serum and plasma samples, we investigated whether anticoagulant treatment influences the determined levels of soluble HLA class I (sHLA-I) or soluble HLA-DR (sHLA-DR). Analyzing paired samples of serum and plasma of 40 healthy individuals we found significantly lower serum levels of sHLA-DR (0.31 +/- 0.15 ng/ml) compared to EDTA plasma levels (0.58 +/- 0.20 ng/ml). By contrast, serum levels of sHLA-I (0.89 +/- 0.74 micrograms/ml) were only slightly lower than EDTA plasma values (0.95 +/- 0.86 micrograms/ml), a situation similar to that of sIL-2R and sCD4 levels. Further experiments intended to clarify the reasons of the reduced sHLA-DR serum levels revealed that (i) the blood storage time before centrifugation did not influence the sHLA-DR level, (ii) treatment of serum with anticoagulant did not augment the measured sHLA-DR concentration, and (iii) the recovery of spiked sHLA-DR was significantly lower when added to native blood than to serum or anticoagulant-treated blood. These results suggest that sHLA-DR is partly removed by the process of blood clotting thus resulting in diminished sHLA-DR serum levels.

Anticoagulants↗
PubMed1996

A muscarinic acetylcholine receptor, present in the epithelial cell line from Chironomus tentans.

A muscarinic cholinergic receptor (mAchR) is present in the non-neuronal epithelial cell line from Chironomus tentans. Scatchard plot analysis (KD = 1.4 nM) using the non-selective antagonist quinuclidinylbenzilate (QNB), as well as kinetic data (KD = 1.7 nM), reveals one class of high affinity binding sites. About 2000 binding sites/cell are present. The receptor concentration (54.5 +/- 7.5 fmol/mg protein) is comparable to the values reported from insect brain. The receptor interacts only with muscarinic ligands; nicotinergic acetylcholine receptors are not present. Binding properties are not comparable to any of the muscarinic subtypes known from vertebrate tissues. The rank order of competition of radiolabelled QNB is: QNB > atropine > PrBCM > oxotremorine, pirenzepine > methoctramine. The competition curve obtained with carbamylcholine is shifted to higher ligand concentrations in the presence of Gpp(NH)p and to lower carbamylcholine concentrations by 1 mM NEM. With antibodies against muscarinic receptor from calf brain one band with a molecular weight of about 80 kDa is detected on Western blots. The moulting hormone 20-OH-ecdysone transiently increases the concentration of muscarinic receptor.

Animals↗
PubMed1994

Generation and characterization of a human monoclonal IgG antibody specific for HLA-B12.

We describe here the generation and characterization of a human monoclonal IgG antibody (UL/F14) specific for HLA-B12. The antibody is suitable for complement-dependent lysis on lymphoblastoid cell lines and stimulated peripheral blood mononuclear cells. UL/F14 competes for antigen binding with an HLA-B12 human monoclonal IgM antibody and with a specific alloantiserum. Protein chemistry shows that the monoclonal antibody UL/F14 can precipitate solubilized HLA-B12 molecules.

Antibodies, Monoclonal↗
PubMed1994

[HLA and association with illness].

Even though HLA associations meanwhile are known to be existent in more than 40 diseases, practical application of HLA typing for diagnostic and prognostic purposes is limited to only a few diseases (for instance HLA-B27 typing in ankylosing spondylitis). Still, new aspects were found for genetics, etiology as well as for pathogenesis of numerous diseases. Knowledge about the structure of HLA antigens and their biological function has led to a better understanding of the immunomechanisms. Using molecular biological techniques it was possible, in some diseases, to define those alleles and aminoacid sequences within the HLA molecule which are primarily responsible for the disease association. Thereby the topic of HLA and disease developed into a research field that is equally interesting for hemogeneticists, immunologists and clinicians and also has connections to the clinical praxis.

Autoimmune Diseases↗
PubMed1994

Quantitation of soluble HLA-DR antigens in human serum and other body fluids.

The existence of soluble forms of MHC class II molecules is well established. To quantify soluble HLA-DR antigens (sHLA-DR) in human serum and other body fluids, we developed an enzyme immunoassay using two non-overlapping HLA-DR-specific monoclonal antibodies (RoDR, BL-la/5) and an immunoaffinity chromatography-purified sHLA-DR standard. In serum of healthy individuals, sHLA-DR levels were found in the range between 0.6 and 3 ng/ml (median 0.85 ng/ml) whereas EDTA plasma samples showed concentrations about 20 times higher (median 21 ng/ml). In tears, saliva, sweat, urine, amniotic fluid, cerebrospinal fluid, and bronchoalveolar lavage, sHLA-DR could also be detected. No association was found between sHLA-DR serum levels and distinct HLA specificities. In the sera of patients with autoimmune diseases, slightly enhanced sHLA-DR values were found (juvenile rheumatoid arthritis: median 2.0 ng/ml, lupus erythematosus: 1.5 ng/ml, diabetes mellitus: 2.1 ng/ml).

Amniotic Fluid↗
PubMed1994

[Protein A immunoadsorption al a new apheresis procedure for elimination of HLA antibodies].

The protein A immunoadsorption allows to remove antibodies of the classes IgG, IgM and IgA in special quantities from the plasma. IgG subclasses 1, 2 and 4 will be removed for 100% and IgG of class 3 for nearly 80%. For this reason immunoadsorptions are a useful therapeutic method especially for immunological diseases with antibodies of IgG type. The successful use of immunoadsorption in the removal of HLA antibodies in patients with acute myeloic leukemia and patients after kidney allograft is reported.

Blood Transfusion↗
PubMed1993

The presequence of cytochrome c1 from potato mitochondria is encoded on four exons.

The structural organization of a nuclear gene encoding cytochrome c1 from potato was determined. The gene spans 5.1 kb and contains eight introns. All intron/exon junctions follow the GT/AG rule. Functional domains of the mature cytochrome c1 protein are located on separate exons. The presequence, which targets the cytochrome c1 precursor to the mitochondrion and to the correct intra-mitochondrial location, is encoded on the first four exons. The largest intron (2.8 kb) separates the information for mitochondrial targeting from the "intra-mitochondrial sorting domain" of the cytochrome c1 protein. In contrast to other organellar precursor proteins, there is no intron between the DNA sequence encoding the presequence and the mature protein. This may indicate that during evolution the genetic information for the prokaryotic cytochrome c1 was transferred to the nucleus together with the bacterial secretion signal which is structurally and functionally related to "intramitochondrial sorting domains".

Amino Acid Sequence↗
PubMed1992

[11th International Histocompatibility Workshop 1991: Personal data for the Multiple Sclerosis Study].

In our multiple sclerosis (MS) study as a part of the 11th IHWS we HLA-typed 6 MS families with 9 patients and defined the complement polymorphisms (BF, C2, C4) of these families. The aims of the study were the definition of the MS susceptibility gene and the investigation of the involvement of other factors in the etiopathogenesis of MS. The MS study of the IHWS demonstrated a strong association with HLA-DRw15 and -DWw6 in a Caucasian population. The heterozygous C2 deficiency in our family PD1 linked with the haplotype A25 B18 DR2 BFS C4A4 C4B2 confirmed by complement titration may express the participation of complement factors in the etiopathogenesis of MS resulting in immunogenetic heterogeneity of MS. Analysis of the 3 MS pairs of sisters shows the linkage of HLA with the assumed MS susceptibility gene. This could not be confirmed in the whole MS family study of the 11th IHWS.

Chromosome Mapping↗