Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    facet.materialart.
    Unknown
    German Medical Science GMS Publishing House; Düsseldorf
    In:  Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2014); 20141028-20141031; Berlin; DOCPO19-262 /20141013/
    Publication Date: 2014-10-14
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Abstract: 8-demethyl-8-aminoriboflavin-5`-phosphate (AFP) synthase (RosB) catalyzes the key reaction of roseoflavin biosynthesis by forming AFP from riboflavin-5`-phosphate (RP) and glutamate via the reaction intermediates 8-demethyl-8-formylriboflavin-5`-phosphate (OHC-RP) and 8-demethyl-8-carboxylriboflavin-5`-phosphate (HO2C-RP). To understand this challenging reaction in which a methyl substituent of an aromatic ring is replaced by and amine we structurally characterized RosB in complex with OHC-RP (2.0 Angström) and in complex with AFP (1.7 Angström). RosB is composed of four flavodoxin-like subunits which have been upgraded with specific extensions and a unique C-terminal arm. It appears that RosB has evolved from an electron- or hydride-transferring flavoprotein to a sophisticated multi-step enzyme which uses RP as a substrate (and not as a cofactor). Structure-based active site analysis was complemented by mutational and isotope-based mass-spectrometric data to propose an enzymatic mechanism on an atomic ground. As most pronounced feature we found an anion hole adjacent to the C8 methyl of RP that stabilizes a hydroxylate for C8 methyl deprotonation and a peroxide anion generated during O2 attack and also fixes glutamate required for the final transamination reaction.
    Type of Publication: Journal article published
    PubMed ID: 27981706
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    facet.materialart.
    Unknown
    German Medical Science GMS Publishing House; Düsseldorf
    In:  Jahrestagung der Gesellschaft für Medizinische Ausbildung (GMA); 20180919-20180922; Wien; DOCP21.1 /20180919/
    Publication Date: 2018-09-20
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    facet.materialart.
    Unknown
    German Medical Science GMS Publishing House; Düsseldorf
    In:  Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2013); 20131022-20131025; Berlin; DOCGR11-1390 /20131023/
    Publication Date: 2013-10-24
    Keywords: Radiokarpalgelenk ; Hand ; Biomechanik ; Kinetik ; Prothetik ; ddc: 610
    Language: German
    Type: conferenceObject
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Keywords: RECEPTOR ; CELLS ; EXPRESSION ; proliferation ; CELL ; Germany ; human ; DISEASE ; DISEASES ; POPULATION ; GENE-EXPRESSION ; TIME ; PATIENT ; INJURIES ; LIGAND ; MESANGIAL CELLS ; NEPHRITIS ; RESPONSES ; kidney ; MARKER ; renal ; T cell ; T cells ; T-CELL ; T-CELLS ; antibodies ; antibody ; FORM ; TARGET ; NO ; immunohistochemistry ; DIFFERENCE ; NUMBER ; MARKERS ; LYMPHOCYTES ; MIGRATION ; LIGANDS ; RECRUITMENT ; T-LYMPHOCYTES ; T lymphocyte ; TARGETS ; glomerulonephritis ; NEPHROPATHY ; RECEPTORS ; DIFFERENTIAL EXPRESSION ; chemokine ; T lymphocytes ; INJURY ; PROGNOSTIC MARKERS ; targeting ; CHEMOKINE RECEPTOR ; ABSENCE ; COMPARTMENTS ; PATTERN ; CCR5 ; TRANSPLANT REJECTION ; CD3 ; REAL-TIME ; mRNA ; GLOMERULAR-DISEASES ; RENAL BIOPSIES ; CHEMOKINE RECEPTORS ; CHEMOKINE RECEPTOR CXCR3 ; chemokines ; HUMAN KIDNEY-DISEASES ; INDUCIBLE PROTEIN-10 ; lupus ; LYMPHOCYTE-FIBROBLAST INTERACTIONS ; MESANGIAL CELL ; PROLIFERATIVE GLOMERULONEPHRITIS
    Abstract: Chemokines play pivotal roles in the recruitment of inflammatory cells into the kidney. The chemokine receptors CXCR3 and CCR5 are expressed on activated T lymphocytes, and expression of CXCR3 by mesangial cells has been suggested. Detailed description of CXCR3 expression might form a rational basis for use as a diagnostic marker and for therapeutic CXCR3 targeting in human glomerulonephritis. We studied the expression of CXCR3 in renal biopsies by immunohistochemistry (n = 45), and real time RTPCR (n = 78). Biopsies were from patients with IgA nephropathy, lupus nephritis, and membranoproliferative glomerulonephritis. Furthermore, cultured human mesangial cells (HMC) were studied for CXCR3 expression, and for functional responses to the ligands CXCL10/IP-10 and CXCL9/Mig. CXCR3-positive cells were rarely found in glomerular tufts, but formed a major part of the tubulointerstitial infiltrates. Consistently, CXCR3 mRNA expression was too low to be quantified in glomerular compartments, and was not detectable in HMC. The published staining for CXCR3 of mesangial cells could be traced to cross-reactivity of an antibody for CXCR3 with a potentially related chemokine receptor as revealed by FACS analysis. Despite an absence of CXCR3 expression, mesangial cells reacted to CXCR3 ligands by proliferation and migration, which was blocked by pertussis toxin but not by an anti-CXCR3 antibody. These results indicate that HMC do not express the classical CXCR3, but may potentially express a related receptor with shared ligand specificity. By immunohistochemistry the number of CXCR3-positive cells, mainly interstitial T cells, correlated with renal function, proteinuria, and percentage of globally sclerosed glomeruli. A significant morphological and numerical correlation between CD3, CXCR3, and CCR5-positive cells indicated a CXCR3/CCR5 double-positive T cell population. No apparent difference in the CXCR3 expression pattern was found between disease entities. CXCR3 expression was localized to interstitial T cells, and these cells correlated strongly with important prognostic markers. Therefore interstitial CXCR3, as well as CCR5-positive T cells might play an important role during progressive loss of renal function, and are potential therapeutic targets in human glomerular diseases
    Type of Publication: Journal article published
    PubMed ID: 14742268
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Keywords: Germany ; THERAPY ; DIAGNOSIS ; DISEASE ; HISTORY ; PATIENT ; INFECTION ; PATHOGENESIS ; FAILURE ; SERUM ; acute interstitial nephritis ; corticosteroids ; VARIETIES ; ANTIBIOTIC-THERAPY ; acute anuric renal failure ; drug-induced acute interstitial nephritis ; exanthema ; KAWASAKI DISEASE
    Abstract: A 15-year-old girl with a history of Kawasaki disease was admitted to Our nephrological department due to acute renal failure. Despite antibiotic therapy because of fever and the symptoms of a pharyngitis in the last few days, the girl showed persisting fever and developed arthralgias, an exanthema and a rising serum creatinine as well as anuria. A wide variety of differential diagnoses has to be thought of because of the history of the Kawasaki disease (symptoms like fever, pharyingitis, exanthema and arthralgia), i.e. hemolytic-uremic syndrome, vasculitis, ascending infection, postinfection glomerulonephritis. In consideration of etiologically unclear "rapidly progressive renal failure" with anuria and thrombocytopenia an immediate renal biopsy was done and revealed a severe drug induced acute interstitial nephritis. Due to this diagnosis we treated the patient with corticosteroids. Within 4 weeks serum creatinine declined to 1.8 mg/dl but did not normalize
    Type of Publication: Journal article published
    PubMed ID: 16724658
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Keywords: GENE-EXPRESSION ; ESCHERICHIA-COLI ; GLUTATHIONE-REDUCTASE ; FUNCTIONAL-CHARACTERIZATION ; GRAM-POSITIVE BACTERIA ; HUMAN FAD SYNTHETASE ; FLAVIN MONONUCLEOTIDE RIBOSWITCH ; STREPTOMYCES-DAVAWENSIS ; ANTIBIOTIC ROSEOFLAVIN ; ADENINE-DINUCLEOTIDE
    Abstract: Antimetabolites are molecules, which are structurally similar to molecules needed to carry out primary metabolic reactions.The inhibitory activity of an antimetabolite depends on its successful competition with the natural substrate, ligand, modulator or cofactorof a given biomolecule. Antimetabolites are indispensable as molecular tools in order to understand biological processes. Beyond that,antimetabolites have a large variety of applications in the pharmaceutical and food industries. The identification of the structural riboflavin(vitamin B2) analog roseoflavin in Streptomyces davawensis demonstrates that anti-vitamins/cofactor analogs may serve as lead structuresfor the development of novel antibiotics. The latter is supported by the recent finding that roseoflavin had a profound inhibiting effecton the growth and infectivity of the human bacterial pathogen Listeria monocytogenes at very low concentrations. Roseoflavin isstudied in our laboratory as a model compound. We investigate the biosynthesis, the possible large-scale production, the metabolization,the mechanism of action and the resistance mechanism of the producer organism in order to pave the way for the structured analysis ofother vitamin analogs yet to be discovered. These compounds hopefully will help to replenish the arsenal of antimicrobials urgentlyneeded to fight multiresistant bacterial pathogens.
    Type of Publication: Journal article published
    PubMed ID: 23116394
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    Abstract: The bacteria Streptomyces davawensis and Streptomyces cinnabarinus produce roseoflavin, the only known natural riboflavin (vitamin B2 ) analogue with antibiotic activity. Roseoflavin can be considered a natural antimetabolite and has been postulated to be biosynthesized from riboflavin via the key intermediate 8-demethyl-8-aminoriboflavin (AF). The required site-specific substitution of one of the methyl groups on the dimethylbenzene ring of riboflavin by an amino group (to give AF) is challenging. The pathway from riboflavin to AF has remained elusive, and the corresponding enzyme/s was/were unknown. Herein, we show by systematic gene deletion, heterologous gene expression, and biochemical studies that the enzyme specified by the gene BN159_7989 from S. davawensis is able to carry out a whole set of chemical reactions starting from riboflavin-5'-phosphate to give the final product 8-demethyl-8-aminoriboflavin-5'-phosphate (AFP).
    Type of Publication: Journal article published
    PubMed ID: 27062037
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    Abstract: Mammals synthesize, cell-type specifically, the diastereomeric hexosylceramides, beta-galactosylceramide (GalCer) and beta-glucosylceramide (GlcCer), which are involved in several diseases, such as sphingolipidosis, diabetes, chronic kidney diseases, or cancer. In contrast, Bacteroides fragilis, a member of the human gut microbiome, and the marine sponge, Agelas mauritianus, produce alpha-GalCer, one of the most potent stimulators for invariant natural killer T cells. To dissect the contribution of these individual stereoisomers to pathologies, we established a novel hydrophilic interaction chromatography-based LC-MS2 method and separated (R 〉 1.5) corresponding diastereomers from each other, independent of their lipid anchors. Testing various bacterial and mammalian samples, we could separate, identify (including the lipid anchor composition), and quantify endogenous beta-GlcCer, beta-GalCer, and alpha-GalCer isomers without additional derivatization steps. Thereby, we show a selective decrease of beta-GlcCers versus beta-GalCers in cell-specific models of GlcCer synthase-deficiency and an increase of specific beta-GlcCers due to loss of beta-glucoceramidase 2 activity. Vice versa, beta-GalCer increased specifically when cerebroside sulfotransferase (Gal3st1) was deleted. We further confirm beta-GalCer as substrate of globotriaosylceramide synthase for galabiaosylceramide synthesis and identify additional members of the human gut microbiome to contain immunogenic alpha-GalCers. Finally, this method is shown to separate corresponding hexosylsphingosine standards, promoting its applicability in further investigations.
    Type of Publication: Journal article published
    PubMed ID: 28373486
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    Abstract: OBJECTIVE: To evaluate myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 (TLR4) expression in relation to clinical features of epithelial ovarian cancer, histologic subtypes, and overall survival. PATIENTS AND METHODS: We conducted centralized immunohistochemical staining, semi-quantitative scoring, and survival analysis in 5263 patients participating in the Ovarian Tumor Tissue Analysis consortium. Patients were diagnosed between January 1, 1978, and December 31, 2014, including 2865 high-grade serous ovarian carcinomas (HGSOCs), with more than 12,000 person-years of follow-up time. Tissue microarrays were stained for MyD88 and TLR4, and staining intensity was classified using a 2-tiered system for each marker (weak vs strong). RESULTS: Expression of MyD88 and TLR4 was similar in all histotypes except clear cell ovarian cancer, which showed reduced expression compared with other histotypes (P〈.001 for both). In HGSOC, strong MyD88 expression was modestly associated with shortened overall survival (hazard ratio [HR], 1.13; 95% CI, 1.01-1.26; P=.04) but was also associated with advanced stage (P〈.001). The expression of TLR4 was not associated with survival. In low-grade serous ovarian cancer (LGSOC), strong expression of both MyD88 and TLR4 was associated with favorable survival (HR [95% CI], 0.49 [0.29-0.84] and 0.44 [0.21-0.89], respectively; P=.009 and P=.02, respectively). CONCLUSION: Results are consistent with an association between strong MyD88 staining and advanced stage and poorer survival in HGSOC and demonstrate correlation between strong MyD88 and TLR4 staining and improved survival in LGSOC, highlighting the biological differences between the 2 serous histotypes.
    Type of Publication: Journal article published
    PubMed ID: 29502561
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...