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Ludwig Wagner
Department of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, A1090 Vienna, Austria

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Journal article
Published: 07 July 2021 in COVID
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A novel beta coronavirus that emerged in late December 2019 triggered a global pandemic. Diagnostic methods for rapid identification of infected individuals were established in new biotechnological approaches. Vaccine production and application to individuals and measurement of SARS-CoV-2 antibodies also began. Serum samples from 240 health care workers were collected at three-month intervals over nine months. Indirect SARS-CoV-2 nucleocapsid IgG ELISA tests were used to identify humoral immune responses. All seropositive individuals and those with borderline ELISA values were tested with a specifically generated multipanel nucleocapsid fragment immunoblot. Of the 240 individuals, 24 showed seroconversion in ELISA after experiencing COVID-19. All of them showed a positive reaction against the full-length nucleocapsid protein in the immunoblot. The highest reactivity was seen either against fragment N(100–300) or in a minority against the posterior part N(200–419). In general, the staining pattern of COVID-19 patients showed four phenotypes. In contrast, three individuals classified as borderline by ELISA reacted exclusively with fragments N(1–220) and N(100–300) containing the octamer amino acid sequence FYYLGTGP, which is identical in human coronaviruses sharing this sequence with SARS-CoV-2. These represent a unique and thus fifth phenotype. This work suggests the existence of distinct phenotypic patterns of IgG production towards N-protein subdomains.

ACS Style

Sahra Pajenda; Sebastian Kapps; Thomas Reiter; Raimundo Freire; Veronique Smits; Ludwig Wagner; Daniela Gerges; Wolfgang Winnicki; Gere Sunder-Plassmann; Alice Schmidt. Antibody Response against the SARS-CoV-2 Nucleocapsid Protein and Its Subdomains—Identification of Pre-Immunization Status by Human Coronaviruses with Multipanel Nucleocapsid Fragment Immunoblotting. COVID 2021, 1, 105 -114.

AMA Style

Sahra Pajenda, Sebastian Kapps, Thomas Reiter, Raimundo Freire, Veronique Smits, Ludwig Wagner, Daniela Gerges, Wolfgang Winnicki, Gere Sunder-Plassmann, Alice Schmidt. Antibody Response against the SARS-CoV-2 Nucleocapsid Protein and Its Subdomains—Identification of Pre-Immunization Status by Human Coronaviruses with Multipanel Nucleocapsid Fragment Immunoblotting. COVID. 2021; 1 (1):105-114.

Chicago/Turabian Style

Sahra Pajenda; Sebastian Kapps; Thomas Reiter; Raimundo Freire; Veronique Smits; Ludwig Wagner; Daniela Gerges; Wolfgang Winnicki; Gere Sunder-Plassmann; Alice Schmidt. 2021. "Antibody Response against the SARS-CoV-2 Nucleocapsid Protein and Its Subdomains—Identification of Pre-Immunization Status by Human Coronaviruses with Multipanel Nucleocapsid Fragment Immunoblotting." COVID 1, no. 1: 105-114.

Other
Published: 26 July 2020
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BackgroundChronic kidney disease patients show a high mortality in case of a SARS-CoV-2 infection. Thus, to be informed on Nephrology personnel’s sero-status might be crucial for patient protection. However, limited information exists about the presence of SARS-CoV-2 antibodies in asymptomatic individuals.MethodsWe examined the seroprevalence of SARS-CoV-2 IgG and IgM antibodies among health care workers of a tertiary care kidney center during the peak phase of the Covid-19 crisis in Austria using an orthogonal test strategy and a total of 12 commercial nucleocapsid protein or spike glycoprotein based assays as well as Western blotting and a neutralization assay.ResultsAt baseline 60 of 235 study participants (25.5%, 95% CI: 20.4-31.5) were judged to be borderline positive or positive for IgM or IgG using a high sensitivity/low specificity threshold in one test system. Follow-up analysis after about two weeks revealed IgG positivity in 12 (5.1%, 95% CI: 2.9-8.8) and IgM positivity in six (2.6%, 95% CI: 1.1-5.6) in at least one assay. 2.1% (95% CI: 0.8-5.0) of health care workers showed IgG nucleocapsid antibodies in at least two assays. By contrast, positive controls with proven Covid-19 showed antibody positivity among almost all test systems. Moreover, serum samples obtained from health care workers did not show SARS-CoV-2 neutralizing capacity, in contrast to positive controls.ConclusionsUsing a broad spectrum of antibody tests the present study revealed inconsistent results for SARS-CoV-2 seroprevalence among asymptomatic individuals, while this was not the case among Covid-19 patients.Trial registration numberCONEC, ClinicalTrials.gov number NCT04347694

ACS Style

Thomas Reiter; Sahra Pajenda; Ludwig Wagner; Martina Gaggl; Johanna Atamaniuk; Barbara Holzer; Irene Zimpernik; Daniela Gerges; Katharina Mayer; Christof Aigner; Robert Strassl; Sonja Jansen-Skoupy; Manuela Födinger; Gere Sunder-Plassmann; Alice Schmidt. Covid-19 serology in nephrology health care workers. 2020, 1 .

AMA Style

Thomas Reiter, Sahra Pajenda, Ludwig Wagner, Martina Gaggl, Johanna Atamaniuk, Barbara Holzer, Irene Zimpernik, Daniela Gerges, Katharina Mayer, Christof Aigner, Robert Strassl, Sonja Jansen-Skoupy, Manuela Födinger, Gere Sunder-Plassmann, Alice Schmidt. Covid-19 serology in nephrology health care workers. . 2020; ():1.

Chicago/Turabian Style

Thomas Reiter; Sahra Pajenda; Ludwig Wagner; Martina Gaggl; Johanna Atamaniuk; Barbara Holzer; Irene Zimpernik; Daniela Gerges; Katharina Mayer; Christof Aigner; Robert Strassl; Sonja Jansen-Skoupy; Manuela Födinger; Gere Sunder-Plassmann; Alice Schmidt. 2020. "Covid-19 serology in nephrology health care workers." , no. : 1.

Journal article
Published: 06 April 2020 in BMC Nephrology
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In the past urine was considered sterile. Through the introduction of next generation sequencing, it has become clear that a urinary microbiome exists. Acute kidney injury (AKI) represents a major threat to kidney transplant recipients. Remarkable changes in the urinary metabolome occur during AKI, which may influence the urinary microbiome. To our knowledge, this is the first study that examines the urinary microbiome in renal transplant recipients (RTX) and non-transplant recipients (nRTX) at time of AKI. In this cross-sectional pilot-study the urinary microbiome of 21 RTX and 9 nRTX with AKI was examined. Clean catch morning urine samples were obtained from all patients on the first day of AKI diagnosis. AKI was defined according to KDIGO guidelines. Urinary microbiota and the urinary metabolome during AKI were assessed in one patient. 16S rRNA sequencing was performed. Sequences were processed using UPARSE-pipeline for operational taxonomic units (OTU) and taxon finding. We successfully extracted and sequenced bacterial DNA from 100% of the urine samples. All 30 patients revealed at least 106,138 reads. 319 OTU and 211 different genera were identified. The microbiotic diversity richness in the RTX group was no different from the nRTX group. Eighteen genera were solely present in nRTX and 7 in RTX. The urinary microbiome at time of AKI showed different bacterial genera in RTX compared to nRTX. The nRTX group exhibited no different diversity to the RTX group. Irrespective of the status of a previous renal transplantation, the urinary microbiome comprised > 210 different genera. An intraindividual change in microbiota diversity and richness was observed in one study patient during recovery from AKI.

ACS Style

Daniela Gerges-Knafl; Peter Pichler; Alexander Zimprich; Christoph Hotzy; Wolfgang Barousch; Rita M. Lang; Elisabeth Lobmeyr; Sabina Baumgartner-Parzer; Ludwig Wagner; Wolfgang Winnicki. The urinary microbiome shows different bacterial genera in renal transplant recipients and non-transplant patients at time of acute kidney injury – a pilot study. BMC Nephrology 2020, 21, 1 -10.

AMA Style

Daniela Gerges-Knafl, Peter Pichler, Alexander Zimprich, Christoph Hotzy, Wolfgang Barousch, Rita M. Lang, Elisabeth Lobmeyr, Sabina Baumgartner-Parzer, Ludwig Wagner, Wolfgang Winnicki. The urinary microbiome shows different bacterial genera in renal transplant recipients and non-transplant patients at time of acute kidney injury – a pilot study. BMC Nephrology. 2020; 21 (1):1-10.

Chicago/Turabian Style

Daniela Gerges-Knafl; Peter Pichler; Alexander Zimprich; Christoph Hotzy; Wolfgang Barousch; Rita M. Lang; Elisabeth Lobmeyr; Sabina Baumgartner-Parzer; Ludwig Wagner; Wolfgang Winnicki. 2020. "The urinary microbiome shows different bacterial genera in renal transplant recipients and non-transplant patients at time of acute kidney injury – a pilot study." BMC Nephrology 21, no. 1: 1-10.

Journal article
Published: 02 October 2019 in PeerJ
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Monoclonal overproduction of kappa and/or lambda light chains might result in renal light chain deposition disease. Light chain associated cast nephropathy and renal AL-amyloidosis represent two further pathologies going along with monoclonal gammopathy of renal significance and multiple myeloma. While cast nephropathy often manifests with acute kidney injury, AL-amyloidosis is rather accompanied with chronic kidney disease. Urine samples were collected from 17 patients with multiple myeloma or monoclonal gammopathy. The urine sediment was stained for cast morphology by H/E and light chain immunofluorescence. Following micro-selection of casts under microscope, proteomic analysis of casts was performed by mass spectrometry. Sucrose gradient sedimentation was employed and light chain architecture examined by immunoblotting. Uromodulin was measured by ELISA in sucrose gradient fractions. Urinary casts were observed of about 30 µm in diameter by H/E staining and under immunofluorescence microscopy. Casts with a diameter of 20 µm were observed as a novel variant. Proteome analysis showed that in addition to the expected light chain variants produced by the malignant clone of plasma cells, also histones such as H2B and cathepsin B were contained. Uromodulin was not detectable in urinary casts of all patients. All eleven patients with lambda light chains showed predominant dimerized light chains in the urine immunoblot. Six patients with kappa light chains presented with predominantly monomeric forms of light chains in the immunoblot. The densitometric evaluated ratio of lambda dimers vs. monomers was significantly higher (2.12 ± 0.75) when compared with the ratio of kappa dimers vs. monomers (0.64 ± 0.47), p = 0.00001. Aggregates of light chains separated in part into denser sucrose fractions. This work on urinary casts and light chains demonstrates that hyaline tubular casts represent a complex formation of protein-protein aggregates with histones and cathepsin B identified as novel cast components. Apart from the proteomic composition of the casts, also the formation of the light chains and aggregates is of relevance. Dimerized light chains, which are typical for lambda paraproteins, might be less dialyzable than monomeric forms and may therefore identify patients less responsive to high cut-off dialysis.

ACS Style

Thomas Reiter; Daniela Knafl; Hermine Agis; Karl Mechtler; Ludwig Wagner; Wolfgang Winnicki. Structural analysis of urinary light chains and proteomic analysis of hyaline tubular casts in light chain associated kidney disorders. PeerJ 2019, 7, e7819 .

AMA Style

Thomas Reiter, Daniela Knafl, Hermine Agis, Karl Mechtler, Ludwig Wagner, Wolfgang Winnicki. Structural analysis of urinary light chains and proteomic analysis of hyaline tubular casts in light chain associated kidney disorders. PeerJ. 2019; 7 ():e7819.

Chicago/Turabian Style

Thomas Reiter; Daniela Knafl; Hermine Agis; Karl Mechtler; Ludwig Wagner; Wolfgang Winnicki. 2019. "Structural analysis of urinary light chains and proteomic analysis of hyaline tubular casts in light chain associated kidney disorders." PeerJ 7, no. : e7819.

Journal article
Published: 09 July 2019 in BMC Nephrology
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Acute kidney injury represents a major threat to the transplanted kidney. Nevertheless, these kidneys have the potential to fully recover. Tubular regeneration following acute kidney injury is driven by the regenerative potential of tubular cells originating from a tubular stem cell pool. We investigated urinary sediments of acute kidney injury transplanted patients and compared it to those of non-transplanted patients. Thereby we discovered tubular cell agglomerates, which have not been described in vivo. We hypothesized that these so-called nephrospheres were associated with recovery from acute kidney injury. Urine sediment of 45 kidney-transplanted and 19 non-transplanted individuals was investigated. Nephrospheres were isolated and stained for several molecular markers including aquaporin 1 (AQP1) and calcium sensing receptor (CASR). Nephrospheres were cultured to examine their growth behavior in vitro. In addition, quantitative PCR for CASR, AQP1, and podocin (NPHS2) was performed. Nephrospheres were excreted in the urine of 17 kidney-transplant recipients 7 days after onset of acute kidney injury and were detectable over several days until kidney function was recovered to baseline creatinine levels. None were found in the urine of non-transplanted individuals. Nephrospheres were either AQP1+/CASR+ or AQP1−/CASR+ and could be cultured for 27 days. Mitotic cells could still be visualized after 17 days in culture. Quantitative PCR detected AQP1 in both kidney-transplanted and non-transplanted individuals during the phase of creatinine decline. As a limitation qPCR was only performed for the entire urinary sediment. Nephrospheres are three dimensional tubular cell agglomerates which appeared in urine of kidney transplant recipients recovering from acute kidney injury. Appearance of nephrospheres in urine was independent of the duration after kidney transplantation. Nephrospheres proliferated in cell culture and kept expressing kidney specific marker. Presence of nephrospheres in urine showed a specificity of 100% and a sensitivity of 60.71% for recovery.

ACS Style

Daniela Knafl; Wolfgang Winnicki; Peter Mazal; Ludwig Wagner. Urinary nephrospheres indicate recovery from acute kidney injury in renal allograft recipients – a pilot study. BMC Nephrology 2019, 20, 1 -10.

AMA Style

Daniela Knafl, Wolfgang Winnicki, Peter Mazal, Ludwig Wagner. Urinary nephrospheres indicate recovery from acute kidney injury in renal allograft recipients – a pilot study. BMC Nephrology. 2019; 20 (1):1-10.

Chicago/Turabian Style

Daniela Knafl; Wolfgang Winnicki; Peter Mazal; Ludwig Wagner. 2019. "Urinary nephrospheres indicate recovery from acute kidney injury in renal allograft recipients – a pilot study." BMC Nephrology 20, no. 1: 1-10.

Journal article
Published: 01 May 2018 in Nephrology Dialysis Transplantation
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INTRODUCTION AND AIMS: Tubular regeneration following acute kidney injury (AKI) undergoes a complex but already well-investigated course in rodent models. Tubular progenitor cells involved in this process have been identified by a specific marker profile. These are mostly localized at the proximal tubule and were shown to have the potential to proliferate.

ACS Style

Daniela Knafl; Wolfgang Winnicki; Christian Gerges; Peter Mazal; Ludwig Wagner. FP239NEPHROSPHERE-LIKE STRUCTURES IN URINE OF ALLOTRANSPLANT RECIPIENTS FOLLOWING ACUTE KIDNEY INJURY. Nephrology Dialysis Transplantation 2018, 33, i109 -i109.

AMA Style

Daniela Knafl, Wolfgang Winnicki, Christian Gerges, Peter Mazal, Ludwig Wagner. FP239NEPHROSPHERE-LIKE STRUCTURES IN URINE OF ALLOTRANSPLANT RECIPIENTS FOLLOWING ACUTE KIDNEY INJURY. Nephrology Dialysis Transplantation. 2018; 33 (suppl_1):i109-i109.

Chicago/Turabian Style

Daniela Knafl; Wolfgang Winnicki; Christian Gerges; Peter Mazal; Ludwig Wagner. 2018. "FP239NEPHROSPHERE-LIKE STRUCTURES IN URINE OF ALLOTRANSPLANT RECIPIENTS FOLLOWING ACUTE KIDNEY INJURY." Nephrology Dialysis Transplantation 33, no. suppl_1: i109-i109.

Research article
Published: 16 November 2017 in PLOS ONE
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Acute kidney injury (AKI) is frequently observed in serious infections, following nephrotoxic medication, surgery and trauma. Here we tested whether the detection of two recently identified biomarkers for AKI, Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) and Insulin-Like Growth Factor Binding Protein 7 (IGFBP7), depends on the expression of these proteins in cells of the urinary sediment. We collected urine samples of 33 kidney transplant recipients and 14 non-transplanted patients who all had AKI (stages 1–3 according to KDIGO), and measured [IGFBP7]x[TIMP-2] using the NephroCheck® Astute1 40 ™ meter. Concomitantly, we analyzed IGFBP7 and TIMP-2 mRNA expression by quantitative polymerase chain reaction (qPCR) from urinary sediment of the same patients, and correlated the results with [IGFBP7]x[TIMP-2] (protein), by linear regression analysis. We also determined the association between [IGFBP7]x[TIMP-2] and estimated glomerular filtration rate (eGFR), and between IGFBP7 and TIMP-2 mRNA expression and markers of inflammation. Light microscopy and confocal immunofluorescence served to illustrate changes in the urinary sediment over the time course of renal function improvement. Of the 47 analyzed AKI patients, 14 presented with ascending urinary tract infection. Serum creatinine (sCr), blood urea nitrogen (BUN) and eGFR in all patients were 3.9±2.28 mg/dL, 47.59±23.1 mg/dL and 22.88±16.0 mL/min/1.73m2, respectively, on average ±standard deviation. [IGFBP7]x[TIMP-2] was 2.33±9.95 (ng/ml)2/1000, and did not associate with IGFBP7 and TIMP-2 gene expression (r = -0.0220, p = 0.4216; respectively r = 0.0972, p = 0.1909). [IGFBP7]x[TIMP-2] did not associate with eGFR; IGFBP7 and TIMP-2 mRNA expression. Improvement of renal function went along with disappearance of casts, decrease in aquaporin1 positive renal epithelial cells and leukocytes from the urinary sediment. The gene expression pattern of IGFBP7 and TIMP-2 from urinary sediment, which contains desquamated renal tubular epithelial cells, did not correlate with [IGFBP7]x[TIMP-2] protein, indicating that IGFBP7 and TIMP-2 measured in the NephroCheck® test originated predominantly from intact but stressed cells of the kidney itself.

ACS Style

Daniela Knafl; Markus Muller; Sahra Pajenda; Zeynep Genc; Manfred Hecking; Ludwig Wagner. The urine biomarker panel [IGFBP7]x[TIMP-2] (NephroCheck® parameter) does not correlate with IGFBP7 and TIMP-2 gene expression in urinary sediment. PLOS ONE 2017, 12, e0188316 .

AMA Style

Daniela Knafl, Markus Muller, Sahra Pajenda, Zeynep Genc, Manfred Hecking, Ludwig Wagner. The urine biomarker panel [IGFBP7]x[TIMP-2] (NephroCheck® parameter) does not correlate with IGFBP7 and TIMP-2 gene expression in urinary sediment. PLOS ONE. 2017; 12 (11):e0188316.

Chicago/Turabian Style

Daniela Knafl; Markus Muller; Sahra Pajenda; Zeynep Genc; Manfred Hecking; Ludwig Wagner. 2017. "The urine biomarker panel [IGFBP7]x[TIMP-2] (NephroCheck® parameter) does not correlate with IGFBP7 and TIMP-2 gene expression in urinary sediment." PLOS ONE 12, no. 11: e0188316.

Journal article
Published: 01 May 2017 in Nephrology Dialysis Transplantation
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ACS Style

Daniela Knafl; Sahra Pajenda; Zeybep Genc; Manfed Hecking; Ludwig Wagner. SP251TIMP2 AND IGFBP7 IN URINE. Nephrology Dialysis Transplantation 2017, 32, 1 .

AMA Style

Daniela Knafl, Sahra Pajenda, Zeybep Genc, Manfed Hecking, Ludwig Wagner. SP251TIMP2 AND IGFBP7 IN URINE. Nephrology Dialysis Transplantation. 2017; 32 (suppl_3):1.

Chicago/Turabian Style

Daniela Knafl; Sahra Pajenda; Zeybep Genc; Manfed Hecking; Ludwig Wagner. 2017. "SP251TIMP2 AND IGFBP7 IN URINE." Nephrology Dialysis Transplantation 32, no. suppl_3: 1.

Journal article
Published: 31 March 2016 in Journal of Nephropathology
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Background: Acute kidney injury (AKI) is a life threatening condition. Despite intensive care treatment the occurrence cannot be predicted as very little indicators exist for direct measurement when tubular epithelial cell injury takes place. We therefore searched for novel peptide indicators expressed at intracellular level at the proximal kidney tubule for its appearance in urine samples. Objectives: Establishing a test for urinary C20orf116 protein measurement. Patients and Methods: Generation of immunoreagents against C20orf116 also named DDRGK1. These were used to measure its presence in urine collected at 8-24 hours interval in a prospective study from 99 ICU patients at 4-6 time points. These patients received therapy because of serious infection and were categorized into 4 groups. Results: 1) Ten tested highly for C20orf116 undergoing AKI graded Failure or Loss (3210 ± 4268 ng/mL) according to RIFLE criteria, all requiring renal replacement therapy (RRT) out of them 9 died. 2) Six patients with pre-existing kidney disease developed AKI and required RRT but had much lower C20orf116 levels of (33 ± 19), two of them died. 3) In contrast, out of 11 patients undergoing AKI grade Risk or Injury, four tested positive for C20orf116 but to much lower extent (66 ± 43) who recovered fully. 4) Out of 72 patients 25 tested positive (18 ± 12 ng/mL) not fulfilling criteria of AKI but with serum creatinine (sCr) rises of 1.2-1.4 (n = 52). Healthy donors (n = 48) showed no detectable C20orf116 at any time point. Conclusions:C20orf116 excretion was detectable more than 24 hours before sCr rise could be measured; high level seemed to indicate severity of organ failure.

ACS Style

Dashurie Neziri; Sahra Pajenda; Rebecca Amuge; Aysegul Ilhan; Marlene Wewalka; Gregor Hoermann; Christian Zauner; Ludwig Wagner. DDRGK1 in urine indicative of tubular cell injury in intensive care patients with serious infections. Journal of Nephropathology 2016, 5, 65 -71.

AMA Style

Dashurie Neziri, Sahra Pajenda, Rebecca Amuge, Aysegul Ilhan, Marlene Wewalka, Gregor Hoermann, Christian Zauner, Ludwig Wagner. DDRGK1 in urine indicative of tubular cell injury in intensive care patients with serious infections. Journal of Nephropathology. 2016; 5 (2):65-71.

Chicago/Turabian Style

Dashurie Neziri; Sahra Pajenda; Rebecca Amuge; Aysegul Ilhan; Marlene Wewalka; Gregor Hoermann; Christian Zauner; Ludwig Wagner. 2016. "DDRGK1 in urine indicative of tubular cell injury in intensive care patients with serious infections." Journal of Nephropathology 5, no. 2: 65-71.

Case reports
Published: 09 December 2015 in BMC Nephrology
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Acute kidney injury is frequently observed at the intensive care unit, after surgery, and after toxic drug administration. A rise in serum creatinine and a fall in urine output are consequences of much earlier injury to the most sensitive part of tubular cells located at the proximal tubule. The aim of the present study was to investigate the course of two cell-cycle arrest urinary biomarkers compared to serum creatinine in four clinical settings: ischemic reperfusion injury, cardiac failure, severe acute kidney injury, and chemotherapy-induced kidney injury. A recently developed bedside test known as NephroCheck measures two urinary parameters: insulin-like growth factor binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinase-2 (TIMP-2). The test is based on a sandwich immunoassay technique. The final test output, labeled AKIRisk, is shown as a numeric result. This report revealed that [IGFBP7] · [TIMP-2] in urine rise rapidly prior to any change in serum creatinine. A unique feature of all four clinical settings is that a rapid decline predicts the recovery of kidney function. Besides, a subclinical kidney injury might be detected by the test. This bedside test detects biomarkers of renal injury. A rapid decline in AKIRisk was associated with the restoration of kidney function, whereas a prolonged high AKIRisk score was associated with end-stage renal disease. However, the dynamics seem to differ, depending on the cause and the extent of injury. Further studies will be needed to clarify the issue.

ACS Style

Sahra Pajenda; Aysegül Ilhan-Mutlu; Matthias Preusser; Sebastian Roka; Wilfred Druml; Ludwig Wagner. NephroCheck data compared to serum creatinine in various clinical settings. BMC Nephrology 2015, 16, 1 -7.

AMA Style

Sahra Pajenda, Aysegül Ilhan-Mutlu, Matthias Preusser, Sebastian Roka, Wilfred Druml, Ludwig Wagner. NephroCheck data compared to serum creatinine in various clinical settings. BMC Nephrology. 2015; 16 (1):1-7.

Chicago/Turabian Style

Sahra Pajenda; Aysegül Ilhan-Mutlu; Matthias Preusser; Sebastian Roka; Wilfred Druml; Ludwig Wagner. 2015. "NephroCheck data compared to serum creatinine in various clinical settings." BMC Nephrology 16, no. 1: 1-7.

Journal article
Published: 28 July 2015 in Endocrine-Related Cancer
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The Hedgehog (Hh) pathway is an important regulator of early tissue patterning and stem cell propagation. It was found to be aberrantly activated in numerous types of human cancer and might be relevant in cancer stem cells. The identification of adult stem cells in the pituitary raised the question if tumor-initiating cells and Hh signaling are involved in pituitary adenoma formation. The present study aimed at the evaluation of Hh signaling in relation to stem cell and cell cycle markers in 30 human pituitary adenomas and in cultured murine adenoma cells. Therefore, expression levels of components of the Hh pathway, stem cell marker SOX2, cell cycle regulator tumor-protein 53 (TP53), proliferation marker Ki67 (MKI67) and superoxide dismutase 1 (SOD1) were evaluated in 30 human pituitary adenomas in comparison to control tissue. Modulation of cell function and target gene expression by the inhibition and activation of the Hh pathway were studied in murine adenoma cells. We show that transcription factor glioma-associated oncogene 1 (GLI1) is overexpressed in 87% of all pituitary adenomas. The expression of GLI1 significantly correlated with that of SOX2, TP53, MKI67 and SOD1. Inhibition of GLI1 resulted in the downregulation of the above genes and severe cell death in mouse adenoma cells. On the other hand, activation of the Hh pathway increased cell viability and target gene expression. In conclusion, our findings point toward an alternative, ligand-independent Hh pathway activation with GLI1 playing a major role in the cell survival of pituitary adenoma cells.

ACS Style

Katharina Lampichler; Patricio Ferrer; Greisa Vila; Mirjam I Lutz; Florian Wolf; Engelbert Knosp; Ludwig Wagner; Anton Luger; Sabina M. Baumgartner-Parzer. The role of proto-oncogene GLI1 in pituitary adenoma formation and cell survival regulation. Endocrine-Related Cancer 2015, 22, 793 -803.

AMA Style

Katharina Lampichler, Patricio Ferrer, Greisa Vila, Mirjam I Lutz, Florian Wolf, Engelbert Knosp, Ludwig Wagner, Anton Luger, Sabina M. Baumgartner-Parzer. The role of proto-oncogene GLI1 in pituitary adenoma formation and cell survival regulation. Endocrine-Related Cancer. 2015; 22 (5):793-803.

Chicago/Turabian Style

Katharina Lampichler; Patricio Ferrer; Greisa Vila; Mirjam I Lutz; Florian Wolf; Engelbert Knosp; Ludwig Wagner; Anton Luger; Sabina M. Baumgartner-Parzer. 2015. "The role of proto-oncogene GLI1 in pituitary adenoma formation and cell survival regulation." Endocrine-Related Cancer 22, no. 5: 793-803.

Journal article
Published: 01 April 2013 in Endocrine Abstracts
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ACS Style

Katharina Lampichler; Patricio Ferrer; Greisa Vila; Anton Luger; Engelbert Knosp; Ludwig Wagner; Sabina Baumgartner-Parzer. The role of GLI1 in pituitary tumor formation and pituitary cell survival. Endocrine Abstracts 2013, 1 .

AMA Style

Katharina Lampichler, Patricio Ferrer, Greisa Vila, Anton Luger, Engelbert Knosp, Ludwig Wagner, Sabina Baumgartner-Parzer. The role of GLI1 in pituitary tumor formation and pituitary cell survival. Endocrine Abstracts. 2013; ():1.

Chicago/Turabian Style

Katharina Lampichler; Patricio Ferrer; Greisa Vila; Anton Luger; Engelbert Knosp; Ludwig Wagner; Sabina Baumgartner-Parzer. 2013. "The role of GLI1 in pituitary tumor formation and pituitary cell survival." Endocrine Abstracts , no. : 1.

Clinical trial
Published: 01 January 2013 in Critical Care
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Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI. We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection. Moderate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P 0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method. Two novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI. ClinicalTrials.gov number NCT01209169.

ACS Style

Kianoush Kashani; Ali Al-Khafaji; Thomas Ardiles; Antonio Artigas; Sean M Bagshaw; Max Bell; Azra Bihorac; Robert Birkhahn; Cynthia M Cely; Lakhmir S Chawla; Danielle L Davison; Thorsten Feldkamp; Lui G Forni; Michelle Ng Gong; Kyle J Gunnerson; Michael Haase; James Hackett; Patrick M Honore; Eric Aj Hoste; Olivier Joannes-Boyau; Michael Joannidis; Patrick Kim; Jay L Koyner; Daniel T Laskowitz; Matthew E Lissauer; Gernot Marx; Peter A McCullough; Scott Mullaney; Marlies Ostermann; Thomas Rimmelé; Nathan I Shapiro; Andrew D Shaw; Jing Shi; Amy M Sprague; Jean-Louis Vincent; Christophe Vinsonneau; Ludwig Wagner; Michael G Walker; R Gentry Wilkerson; Kai Zacharowski; John A Kellum. Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Critical Care 2013, 17, R25 -R25.

AMA Style

Kianoush Kashani, Ali Al-Khafaji, Thomas Ardiles, Antonio Artigas, Sean M Bagshaw, Max Bell, Azra Bihorac, Robert Birkhahn, Cynthia M Cely, Lakhmir S Chawla, Danielle L Davison, Thorsten Feldkamp, Lui G Forni, Michelle Ng Gong, Kyle J Gunnerson, Michael Haase, James Hackett, Patrick M Honore, Eric Aj Hoste, Olivier Joannes-Boyau, Michael Joannidis, Patrick Kim, Jay L Koyner, Daniel T Laskowitz, Matthew E Lissauer, Gernot Marx, Peter A McCullough, Scott Mullaney, Marlies Ostermann, Thomas Rimmelé, Nathan I Shapiro, Andrew D Shaw, Jing Shi, Amy M Sprague, Jean-Louis Vincent, Christophe Vinsonneau, Ludwig Wagner, Michael G Walker, R Gentry Wilkerson, Kai Zacharowski, John A Kellum. Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Critical Care. 2013; 17 (1):R25-R25.

Chicago/Turabian Style

Kianoush Kashani; Ali Al-Khafaji; Thomas Ardiles; Antonio Artigas; Sean M Bagshaw; Max Bell; Azra Bihorac; Robert Birkhahn; Cynthia M Cely; Lakhmir S Chawla; Danielle L Davison; Thorsten Feldkamp; Lui G Forni; Michelle Ng Gong; Kyle J Gunnerson; Michael Haase; James Hackett; Patrick M Honore; Eric Aj Hoste; Olivier Joannes-Boyau; Michael Joannidis; Patrick Kim; Jay L Koyner; Daniel T Laskowitz; Matthew E Lissauer; Gernot Marx; Peter A McCullough; Scott Mullaney; Marlies Ostermann; Thomas Rimmelé; Nathan I Shapiro; Andrew D Shaw; Jing Shi; Amy M Sprague; Jean-Louis Vincent; Christophe Vinsonneau; Ludwig Wagner; Michael G Walker; R Gentry Wilkerson; Kai Zacharowski; John A Kellum. 2013. "Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury." Critical Care 17, no. 1: R25-R25.

Comparative study
Published: 30 June 2012 in Gender Medicine
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There is evidence that diabetic polyneuropathy (PNP) is associated with reduced bone mineral density (BMD) in type 1 diabetes but little is known about the impact of diabetic PNP on bone metabolism in type 2 diabetes. The aim of this study was to evaluate differences in bone metabolism by measuring markers of bone turnover and BMD in men and postmenopausal women with type 2 diabetes and diabetic PNP compared with those without PNP. Gender differences were analyzed for both groups of patients. One hundred twenty patients with type 2 diabetes, 68 without PNP (43 men, 25 women, mean age 62 [8] years) and 52 with PNP (28 men, 24 women, mean age 64 [8] years) were studied. Clinical parameters with bone turnover biomarkers such as osteocalcin, bone alkaline phosphatase, procollagen type 1 amino-terminal propeptide, and carboxy-terminal telopeptide of type 1 collagen were measured in all patients. Dual energy x-ray absorptiometry to evaluate BMD was performed in a subgroup of patients. After controlling for age, body mass index, duration of diabetes, smoking, glycosylated hemoglobin, homeostasis model assessment index for insulin resistance, serum C-reactive protein, creatinine, calcium, gamma-glutamyltransferase, parathyroid and sex hormones levels, presence of micro/macrovascular complications, statin- as well as diabetes-related therapies, levels of carboxy-terminal telopeptide of type 1 collagen and procollagen type 1 amino-terminal propeptide were significantly higher among patients with PNP when compared with patients without PNP (P = 0.01 and P = 0.03, respectively). Differences in bone biomarkers were more pronounced among men with diabetes. BMD did not differ significantly between patients with and without PNP, independent of gender. Male patients with PNP exhibit a higher rate of bone turnover than men without PNP. High rate of bone turnover increases the susceptibility for developing osteoporosis. Prevention of diabetic PNP might also reduce the incidence of osteoporosis and fractures in patients with type 2 diabetes.

ACS Style

Sazan Rasul; Aysegul Ilhan; Ludwig Wagner; Anton Luger; Alexandra Kautzky-Willer. Diabetic Polyneuropathy Relates to Bone Metabolism and Markers of Bone Turnover in Elderly Patients With Type 2 Diabetes: Greater Effects in Male Patients. Gender Medicine 2012, 9, 187 -196.

AMA Style

Sazan Rasul, Aysegul Ilhan, Ludwig Wagner, Anton Luger, Alexandra Kautzky-Willer. Diabetic Polyneuropathy Relates to Bone Metabolism and Markers of Bone Turnover in Elderly Patients With Type 2 Diabetes: Greater Effects in Male Patients. Gender Medicine. 2012; 9 (3):187-196.

Chicago/Turabian Style

Sazan Rasul; Aysegul Ilhan; Ludwig Wagner; Anton Luger; Alexandra Kautzky-Willer. 2012. "Diabetic Polyneuropathy Relates to Bone Metabolism and Markers of Bone Turnover in Elderly Patients With Type 2 Diabetes: Greater Effects in Male Patients." Gender Medicine 9, no. 3: 187-196.

Journal article
Published: 01 January 2012 in Frontiers in Molecular Neuroscience
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Secretagogin is a calcium-binding protein highly expressed in neuroendocrine cells. It has been shown to be involved in insulin secretion from pancreatic beta cells and is a strong candidate as a biomarker for endocrine tumours, stroke and eventually psychiatric conditions. Secretagogin has been hypothesized to exert a neuroprotective role in neurodegenerative diseases like Alzheimer’s disease. The expression pattern of Secretagogin is not conserved from rodents to humans. We used brain tissue and primary neuronal cell cultures from rat to further characterize this calcium binding protein in rodents and to perform a few functional assays in vitro. Immunohistochemistry on rat brain slices revealed a high density of secretagogin-positive cells in distinct brain regions. Secretagogin was found in the cytosol or associated with subcellular compartments. We tested primary neuronal cultures for their suitability as model systems to further investigate functional properties of Secretagogin in a cellular background that is close to the conditions in native neuronal tissue. These cultures can easily be manipulated by treatment with biological agents and by transfection with heterologous constructs. We show that, like in pancreatic beta cells and insulinoma cell lines also in neurons the expression level of Secretagogin is dependent on extracellular insulin and glucose. Further, we show also for rat brain neuronal tissue, that Secretagogin interacts with the microtubule-associated protein Tau and that this interaction is dependent on Ca2+. Future studies should aim to study in further detail the molecular properties and function of Secretagogin in individual neuronal cell types, in particular the subcellular localization and trafficking of this protein and a possible active secretion by neurons.

ACS Style

Magdalena Emaj; Ivan Milenkovic; Jan Bauer; Tord Eberggard; Martina Eveit; Aysegül Eilhan-Mutlu; Ludwig Ewagner; Verena Eva Tretter. Novel Insights into the Distribution and Functional Aspects of the Calcium Binding Protein Secretagogin from Studies on Rat Brain and Primary Neuronal Cell Culture. Frontiers in Molecular Neuroscience 2012, 5, 84 .

AMA Style

Magdalena Emaj, Ivan Milenkovic, Jan Bauer, Tord Eberggard, Martina Eveit, Aysegül Eilhan-Mutlu, Ludwig Ewagner, Verena Eva Tretter. Novel Insights into the Distribution and Functional Aspects of the Calcium Binding Protein Secretagogin from Studies on Rat Brain and Primary Neuronal Cell Culture. Frontiers in Molecular Neuroscience. 2012; 5 ():84.

Chicago/Turabian Style

Magdalena Emaj; Ivan Milenkovic; Jan Bauer; Tord Eberggard; Martina Eveit; Aysegül Eilhan-Mutlu; Ludwig Ewagner; Verena Eva Tretter. 2012. "Novel Insights into the Distribution and Functional Aspects of the Calcium Binding Protein Secretagogin from Studies on Rat Brain and Primary Neuronal Cell Culture." Frontiers in Molecular Neuroscience 5, no. : 84.

Journal article
Published: 01 January 2012 in Molecular Pain
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Background: Secretagogin (Scgn), a member of the EF-hand calcium-binding protein (CaBP) superfamily, has recently been found in subsets of developing and adult neurons. Here, we have analyzed the expression of Scgn in dorsal root ganglia (DRGs) and trigeminal ganglia (TGs), and in spinal cord of mouse at the mRNA and protein levels, and in comparison to the well-known CaBPs, calbindin D-28k, parvalbumin and calretinin. Rat DRGs, TGs and spinal cord, as well as human DRGs and spinal cord were used to reveal phylogenetic variations. Results: We found Scgn mRNA expressed in mouse and human DRGs and in mouse ventral spinal cord. Our immunohistochemical data showed a complementary distribution of Scgn and the three CaBPs in mouse DRG neurons and spinal cord. Scgn was expressed in ∼7% of all mouse DRG neuron profiles, mainly small ones and almost exclusively co-localized with calcitonin gene-related peptide (CGRP). This co-localization was also seen in human, but not in rat DRGs. Scgn could be detected in the mouse sciatic nerve and accumulated proximal to its constriction. In mouse spinal cord, Scgn-positive neuronal cell bodies and fibers were found in gray matter, especially in the dorsal horn, with particularly high concentrations of fibers in the superficial laminae, as well as in cell bodies in inner lamina II and in some other laminae. A dense Scgn-positive fiber network and some small cell bodies were also found in the superficial dorsal horn of humans. In the ventral horn, a small number of neurons were Scgn-positive in mouse but not rat, confirming mRNA distribution. Both in mouse and rat, a subset of TG neurons contained Scgn. Dorsal rhizotomy strongly reduced Scgn fiber staining in the dorsal horn. Peripheral axotomy did not clearly affect Scgn expression in DRGs, dorsal horn or ventral horn neurons in mouse. Conclusions: Scgn is a CaBP expressed in a subpopulation of nociceptive DRG neurons and their processes in the dorsal horn of mouse, human and rat, the former two co-expressing CGRP, as well as in dorsal horn neurons in all three species. Functional implications of these findings include the cellular refinement of sensory information, in particular during the processing of pain.

ACS Style

Tie-Jun Sten Shi; Qiong Xiang; Ming-Dong Zhang; Giuseppe Tortoriello; Henrik Hammarberg; Jan Mulder; Kaj Fried; Ludwig Wagner; Anna Josephson; Mathias Uhlén; Tibor Harkany; Tomas Hökfelt. Secretagogin is Expressed in Sensory CGRP Neurons and in Spinal Cord of Mouse and Complements other Calcium-Binding Proteins, with a Note on Rat and Human. Molecular Pain 2012, 8, 80 -80.

AMA Style

Tie-Jun Sten Shi, Qiong Xiang, Ming-Dong Zhang, Giuseppe Tortoriello, Henrik Hammarberg, Jan Mulder, Kaj Fried, Ludwig Wagner, Anna Josephson, Mathias Uhlén, Tibor Harkany, Tomas Hökfelt. Secretagogin is Expressed in Sensory CGRP Neurons and in Spinal Cord of Mouse and Complements other Calcium-Binding Proteins, with a Note on Rat and Human. Molecular Pain. 2012; 8 ():80-80.

Chicago/Turabian Style

Tie-Jun Sten Shi; Qiong Xiang; Ming-Dong Zhang; Giuseppe Tortoriello; Henrik Hammarberg; Jan Mulder; Kaj Fried; Ludwig Wagner; Anna Josephson; Mathias Uhlén; Tibor Harkany; Tomas Hökfelt. 2012. "Secretagogin is Expressed in Sensory CGRP Neurons and in Spinal Cord of Mouse and Complements other Calcium-Binding Proteins, with a Note on Rat and Human." Molecular Pain 8, no. : 80-80.

Journal article
Published: 01 May 2011 in Human Pathology
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Renal cell carcinomas are divided into several subgroups according to their histopathologic characteristics. The outcome, therapy responses, and the applicability of molecular-targeted therapies depend on the tumor classification and on the tumor stage. Recent advances within the biomarker research facilitated the exact classification of the molecular character of the renal tumor. For example, the calcium-binding proteins parvalbumin and S-100A1 are characteristically expressed in renal cell carcinoma subgroups. This led us to investigate the expression of the novel calcium-binding protein secretagogin in renal cell carcinomas. Tissue microarray cylinders including 94 clear-cell renal cell carcinomas, 61 non-clear-cell renal cell carcinomas (37 papillary renal cell and 24 chromophobe carcinomas), and 30 oncocytomas were analyzed by immunohistochemistry. This showed remarkable secretagogin expression in 37% of the clear-cell renal cell carcinomas. Non-clear-cell renal cell carcinomas and oncocytomas were completely negative. Consequently performed immunoblotting analyses confirmed this expression profile. Because publicly available data direct toward a formation of a hierarchical cluster of secretagogin overexpressing clear-cell renal cell carcinomas, we conducted a clinical follow-up of the patients with clear-cell renal cell carcinoma. This revealed significantly more metastasis within the secretagogin-positive clear-cell renal cell carcinoma subgroup (49% versus 28%; P < .05). In conclusion, we report on detection of the novel calcium-binding protein secretagogin within a subgroup of clear-cell renal cell carcinomas. The increased metastasis rates within the secretagogin-positive subgroup of clear-cell renal cell carcinomas direct toward a clinical impact of our findings.

ACS Style

Aysegul Ilhan; Dashurie Neziri; Magdalena Maj; Peter R. Mazal; Martin Susani; Wolfgang Base; Wolfgang Gärtner; Ludwig Wagner. Expression of secretagogin in clear-cell renal cell carcinomas is associated with a high metastasis rate. Human Pathology 2011, 42, 641 -648.

AMA Style

Aysegul Ilhan, Dashurie Neziri, Magdalena Maj, Peter R. Mazal, Martin Susani, Wolfgang Base, Wolfgang Gärtner, Ludwig Wagner. Expression of secretagogin in clear-cell renal cell carcinomas is associated with a high metastasis rate. Human Pathology. 2011; 42 (5):641-648.

Chicago/Turabian Style

Aysegul Ilhan; Dashurie Neziri; Magdalena Maj; Peter R. Mazal; Martin Susani; Wolfgang Base; Wolfgang Gärtner; Ludwig Wagner. 2011. "Expression of secretagogin in clear-cell renal cell carcinomas is associated with a high metastasis rate." Human Pathology 42, no. 5: 641-648.

Journal article
Published: 01 January 2011 in World Journal of Diabetes
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Frequent concomitant manifestation of type 2 diabetes mellitus (T2DM) and Alzheimers disease (AD) has been recently demonstrated by epidemiological studies. This might be due to functional similarities between β-cells and neurons, such as secretion on demand of highly specific molecules in a tightly controlled fashion. An additional similarity represents the age-related alteration of hyperphosphorylated tau in AD patients. Similarly, alterations have been identified in β-cells of T2DM patients. The islet amyloid polypeptide has been associated with β-cell apoptosis. As a consequence of increasing age, the accumulation of highly modified proteins together with decreased regenerative potential might lead to increasing rates of apoptosis. Moreover, reduction of β-cell replication capabilities results in reduction of β-cell mass in mammals, simultaneously with impaired glucose tolerance. The new challenge is to learn much more about age-related protein modifications. This can lead to new treatment strategies for reducing the incidence of T2DM and AD

ACS Style

Magdalena Maj; Aysegul Ilhan; Dashurie Neziri; Wolfgang Gärtner; Tord Berggård; Johannes Attems; Wolfgang Base; Ludwig Wagner.. Age related changes in pancreatic beta cells: A putative extra-cerebral site of Alzheimer’s pathology. World Journal of Diabetes 2011, 2, 49 -53.

AMA Style

Magdalena Maj, Aysegul Ilhan, Dashurie Neziri, Wolfgang Gärtner, Tord Berggård, Johannes Attems, Wolfgang Base, Ludwig Wagner.. Age related changes in pancreatic beta cells: A putative extra-cerebral site of Alzheimer’s pathology. World Journal of Diabetes. 2011; 2 (4):49-53.

Chicago/Turabian Style

Magdalena Maj; Aysegul Ilhan; Dashurie Neziri; Wolfgang Gärtner; Tord Berggård; Johannes Attems; Wolfgang Base; Ludwig Wagner.. 2011. "Age related changes in pancreatic beta cells: A putative extra-cerebral site of Alzheimer’s pathology." World Journal of Diabetes 2, no. 4: 49-53.

Journals
Published: 01 January 2011 in Molecular BioSystems
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Secretagogin is a hexa EF-hand Ca2+-binding protein expressed in neuroendocrine, pancreatic endocrine and retinal cells. The protein has been noted for its expression in specific neuronal subtypes in the support of hierarchical organizing principles in the mammalian brain. Secretagogin has previously been found to interact with SNAP25 involved in Ca2+-induced exocytosis. Here, the cellular interaction network of secretagogin has been expanded with nine proteins: SNAP-23, DOC2alpha, ARFGAP2, rootletin, KIF5B, β-tubulin, DDAH-2, ATP-synthase and myeloid leukemia factor 2, based on screening of a high content protein array and validation and quantification of binding with surface plasmon resonance and GST pulldown assays. All targets have association rate constants in the range 104–106 M−1s−1, dissociation rate constants in the range 10−3–10−5s−1 and equilibrium dissociation constants in the 100 pM to 10 nM range. The novel target SNAP23 is an essential component of the high affinity receptor for the general membrane fusion machinery and an important regulator of transport vesicle docking and fusion. Complementary roles in vesicle trafficking are known for ARFGAP2 and DOC2alpha in regulating fusion of vesicles to membranes, kinesin 5B and tubulin for transport of vesicles in the cell, while rootletin builds up the rootlet believed to function as a scaffold for vesicles. The identification of a discrete network of interacting proteins that mediate secretion and vesicle trafficking suggests a regulatory role for secretagogin in these processes.

ACS Style

Mikael C. Bauer; David J. O'connell; Magdalena Maj; Ludwig Wagner; Dolores J. Cahill; Sara Linse. Identification of a high-affinity network of secretagogin-binding proteins involved in vesicle secretion. Molecular BioSystems 2011, 7, 2196 -2204.

AMA Style

Mikael C. Bauer, David J. O'connell, Magdalena Maj, Ludwig Wagner, Dolores J. Cahill, Sara Linse. Identification of a high-affinity network of secretagogin-binding proteins involved in vesicle secretion. Molecular BioSystems. 2011; 7 (7):2196-2204.

Chicago/Turabian Style

Mikael C. Bauer; David J. O'connell; Magdalena Maj; Ludwig Wagner; Dolores J. Cahill; Sara Linse. 2011. "Identification of a high-affinity network of secretagogin-binding proteins involved in vesicle secretion." Molecular BioSystems 7, no. 7: 2196-2204.

Journal article
Published: 01 January 2011 in Cardiovascular Diabetology
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Type 2 diabetes is associated with increased levels of Angiopoietin-2 (Ang-2) and soluble Tie-2 (sTie-2), but its impact on vascular disease is still unknown. This study aimed to further explore the associations of Ang-2 and sTie-2 with metabolic control and diabetic complications. In a cross-sectional designed study, levels of Ang-2 and sTie-2 as well as their relationships to cardiometabolic parameters were determined in 80 type 2 diabetic subjects (age 65 ± 7 years, female 47.4%). After controlling for age and BMI, Ang-2 levels were associated with levels of sTie-2, diastolic blood pressure, plasma insulin, homeostasis model assessment of insulin resistance (HOMA-IR), creatinine, glomerular filtration rate (GFR), and gamma-glutamyl transferase (GGT) (all p < 0.02). Presence of diabetic macrovascular complications, polyneuropathy and insulin therapy were associated with higher Ang-2 levels (p < 0.05). Conversely, sTie-2 levels were associated with glycated hemoglobin (HbA1c), fasting plasma glucose and insulin, HOMA-IR, triglyceride, and liver function parameters (all p < 0.03). Multiple linear regression analysis showed that Ang-2 remained significantly associated only with levels of GGT (p < 0.04), whereas sTie-2 remained significantly associated with HbA(1c), insulin levels, and HOMA-IR (p < 0.03). No differences in Ang-2 and sTie-2 levels were observed with regard to gender of participants. Ang-2 is independently associated with levels of GGT while sTie-2 is independently associated with levels of HbA(1c), plasma insulin and HOMA-IR in type 2 diabetic subjects. Therefore we suggest that the associations of Ang-2 and sTie-2 with type 2 diabetes are based on different patho-physiological mechanisms.

ACS Style

Sazan Rasul; Marie Helene Reiter; Aysegul Ilhan; Katharina Lampichler; Ludwig Wagner; Alexandra Kautzky-Willer. Circulating angiopoietin-2 and soluble Tie-2 in type 2 diabetes mellitus: a cross-sectional study. Cardiovascular Diabetology 2011, 10, 55 -55.

AMA Style

Sazan Rasul, Marie Helene Reiter, Aysegul Ilhan, Katharina Lampichler, Ludwig Wagner, Alexandra Kautzky-Willer. Circulating angiopoietin-2 and soluble Tie-2 in type 2 diabetes mellitus: a cross-sectional study. Cardiovascular Diabetology. 2011; 10 (1):55-55.

Chicago/Turabian Style

Sazan Rasul; Marie Helene Reiter; Aysegul Ilhan; Katharina Lampichler; Ludwig Wagner; Alexandra Kautzky-Willer. 2011. "Circulating angiopoietin-2 and soluble Tie-2 in type 2 diabetes mellitus: a cross-sectional study." Cardiovascular Diabetology 10, no. 1: 55-55.