Tampe, Björn

[["dc.bibliographiccitation.artnumber","208"],["dc.bibliographiccitation.journal","Frontiers in Medicine"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Korsten, Peter"],["dc.contributor.author","Müller, Gerhard A."],["dc.contributor.author","Rademacher, Jan-Gerd"],["dc.contributor.author","Zeisberg, Michael"],["dc.contributor.author","Tampe, Björn"],["dc.date.accessioned","2019-09-24T08:03:09Z"],["dc.date.available","2019-09-24T08:03:09Z"],["dc.date.issued","2019"],["dc.description.abstract","Raynaud's phenomenon (RP) is almost universally present in patients with Systemic Sclerosis (SSc). RP represents a generalized vasculopathy and potentially lead to digital ulcers (DU), which may be complicated by superinfection, tissue necrosis, and limb loss. We report the analysis of an extracorporeal procedure in a 36-year-old female patient with diffuse SSc with refractory RP and DU despite treatment with diltiazem, candesartan, sildenafil, and intravenous iloprost. We performed rheopheresis (RheoP), a variant of double-filtration plasmapheresis, as a potential new treatment option for refractory patients despite optimal medical therapy. We performed two RheoP per week every 4 weeks for a total of 3 months. Clinical improvement in DU healing occurred with no adverse events directly related to the treatment. While there was no reduction in the number of Raynaud attacks with RheoP, a significant reduction of the duration of attacks from a median of 15 (5–45, 95% CI 10–15) to 7 (3–30, 95% CI 6–10) minutes with an improvement of the Raynaud Condition Score (RCS) improved from 4 to 2. In conclusion, RheoP is a feasible and potentially beneficial treatment modality in patients with refractory RP and DU. We propose that RheoP should be investigated in a larger number of patients in a clinical trial setting."],["dc.identifier.doi","10.3389/fmed.2019.00208"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16392"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/62449"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2296-858X"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Rheopheresis for Digital Ulcers and Raynaud's Phenomenon in Systemic Sclerosis Refractory to Conventional Treatments"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e0284"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Critical Care Explorations"],["dc.bibliographiccitation.lastpage","5"],["dc.bibliographiccitation.volume","2"],["dc.contributor.author","Hofmann-Winkler, Heike"],["dc.contributor.author","Moerer, Onnen"],["dc.contributor.author","Alt-Epping, Sabine"],["dc.contributor.author","Bräuer, Anselm"],["dc.contributor.author","Büttner, Benedikt"],["dc.contributor.author","Müller, Martin"],["dc.contributor.author","Fricke, Torben"],["dc.contributor.author","Grundmann, Julian"],["dc.contributor.author","Harnisch, Lars-Olav"],["dc.contributor.author","Heise, Daniel"],["dc.contributor.author","Kernchen, Andrea"],["dc.contributor.author","Pressler, Meike"],["dc.contributor.author","Stephani, Caspar"],["dc.contributor.author","Tampe, Björn"],["dc.contributor.author","Kaul, Artur"],["dc.contributor.author","Gärtner, Sabine"],["dc.contributor.author","Kramer, Stefanie"],["dc.contributor.author","Pöhlmann, Stefan"],["dc.contributor.author","Winkler, Martin Sebastian"],["dc.date.accessioned","2020-11-27T11:23:20Z"],["dc.date.accessioned","2021-10-27T13:22:21Z"],["dc.date.available","2020-11-27T11:23:20Z"],["dc.date.available","2021-10-27T13:22:21Z"],["dc.date.issued","2020"],["dc.description.abstract","Objectives: Severe acute respiratory syndrome coronavirus 2 cell entry depends on angiotensin-converting enzyme 2 and transmembrane serine protease 2 and is blocked in cell culture by camostat mesylate, a clinically proven protease inhibitor. Whether camostat mesylate is able to lower disease burden in coronavirus disease 2019 sepsis is currently unknown. Design: Retrospective observational case series. Setting: Patient treated in ICU of University hospital Göttingen, Germany. Patients: Eleven critical ill coronavirus disease 2019 patients with organ failure were treated in ICU. Interventions: Compassionate use of camostat mesylate (six patients, camostat group) or hydroxychloroquine (five patients, hydroxychloroquine group). Measurements and Main Results: Clinical courses were assessed by Sepsis-related Organ Failure Assessment score at days 1, 3, and 8. Further, viral load, oxygenation, and inflammatory markers were determined. Sepsis-related Organ Failure Assessment score was comparable between camostat and hydroxychloroquine groups upon ICU admission. During observation, the Sepsis-related Organ Failure Assessment score decreased in the camostat group but remained elevated in the hydroxychloroquine group. The decline in disease severity in camostat mesylate treated patients was paralleled by a decline in inflammatory markers and improvement of oxygenation. Conclusions: The severity of coronavirus disease 2019 decreased upon camostat mesylate treatment within a period of 8 days and a similar effect was not observed in patients receiving hydroxychloroquine. Camostat mesylate thus warrants further evaluation within randomized clinical trials."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2020"],["dc.identifier.doi","10.1097/CCE.0000000000000284"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17663"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/92088"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.eissn","2639-8028"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Camostat Mesylate May Reduce Severity of Coronavirus Disease 2019 Sepsis: A First Observation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2682"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Journal of Clinical Medicine"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Hakroush, Samy"],["dc.contributor.author","Tampe, Désirée"],["dc.contributor.author","Korsten, Peter"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Tampe, Björn"],["dc.date.accessioned","2021-08-12T07:45:59Z"],["dc.date.available","2021-08-12T07:45:59Z"],["dc.date.issued","2021"],["dc.description.abstract","Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a small vessel vasculitis, most frequently presenting as microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA). Acute tubular injury with the presence of tubulitis was previously reported to be of prognostic value in ANCA glomerulonephritis (GN). In particular, distinct tubular injury lesions were associated with the deterioration of kidney function at AAV disease onset, as well as renal resistance to treatment, and higher risk of progression to composite outcome in patients with AAV. To expand our knowledge regarding distinct tubular lesions in AAV, we aimed to describe acute tubular injury patterns in association with glomerular lesions in ANCA GN by systematic histological scoring. Methods: A total number of 48 renal biopsies with confirmed renal involvement of AAV admitted to the University Medical Center Göttingen from 2015 to 2020 were retrospectively examined. By systematic scoring of tubular injury lesions, the association between clinical parameters, laboratory markers, and histopathological findings was explored. Results: We have shown that cellular casts in renal biopsies were frequently observed in the majority of cases with ANCA GN. Furthermore, we showed that tubular epithelial simplification with dilatation correlated with MPA and MPO subtypes, C3c hypocomplementemia, severe renal involvement, and uACR. Red blood cell (RBC) casts were associated with increased levels of C-reactive protein (CRP), leukocyturia, and hematuria. Finally, we found that hyaline casts were associated with an increased fraction of glomeruli with global glomerular sclerosis. Conclusions: Acute tubular injury patterns were correlated with active ANCA GN, whereas tubular injury lesions reflecting the later stages of kidney disease correlated with chronic glomerular lesions. These results suggest an interplay between different renal compartments."],["dc.description.abstract","Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a small vessel vasculitis, most frequently presenting as microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA). Acute tubular injury with the presence of tubulitis was previously reported to be of prognostic value in ANCA glomerulonephritis (GN). In particular, distinct tubular injury lesions were associated with the deterioration of kidney function at AAV disease onset, as well as renal resistance to treatment, and higher risk of progression to composite outcome in patients with AAV. To expand our knowledge regarding distinct tubular lesions in AAV, we aimed to describe acute tubular injury patterns in association with glomerular lesions in ANCA GN by systematic histological scoring. Methods: A total number of 48 renal biopsies with confirmed renal involvement of AAV admitted to the University Medical Center Göttingen from 2015 to 2020 were retrospectively examined. By systematic scoring of tubular injury lesions, the association between clinical parameters, laboratory markers, and histopathological findings was explored. Results: We have shown that cellular casts in renal biopsies were frequently observed in the majority of cases with ANCA GN. Furthermore, we showed that tubular epithelial simplification with dilatation correlated with MPA and MPO subtypes, C3c hypocomplementemia, severe renal involvement, and uACR. Red blood cell (RBC) casts were associated with increased levels of C-reactive protein (CRP), leukocyturia, and hematuria. Finally, we found that hyaline casts were associated with an increased fraction of glomeruli with global glomerular sclerosis. Conclusions: Acute tubular injury patterns were correlated with active ANCA GN, whereas tubular injury lesions reflecting the later stages of kidney disease correlated with chronic glomerular lesions. These results suggest an interplay between different renal compartments."],["dc.description.sponsorship","Georg-August-Universität Göttingen"],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft"],["dc.identifier.doi","10.3390/jcm10122682"],["dc.identifier.pii","jcm10122682"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/88590"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-448"],["dc.publisher","MDPI"],["dc.relation.eissn","2077-0383"],["dc.rights","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Systematic Scoring of Tubular Injury Patterns Reveals Interplay between Distinct Tubular and Glomerular Lesions in ANCA-Associated Glomerulonephritis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Pharmacology"],["dc.bibliographiccitation.volume","13"],["dc.contributor.affiliation","Plüß, Marlene; \r\n1\r\nDepartment of Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Tampe, Désirée; \r\n1\r\nDepartment of Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Schwörer, Harald; \r\n2\r\nDepartment of Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Bremer, Sebastian Christopher Benjamin; \r\n2\r\nDepartment of Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Tampe, Björn; \r\n1\r\nDepartment of Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.author","Plüß, Marlene"],["dc.contributor.author","Tampe, Désirée"],["dc.contributor.author","Schwörer, Harald"],["dc.contributor.author","Bremer, Sebastian Christopher Benjamin"],["dc.contributor.author","Tampe, Björn"],["dc.date.accessioned","2022-08-31T07:08:38Z"],["dc.date.available","2022-08-31T07:08:38Z"],["dc.date.issued","2022-08-17"],["dc.date.updated","2022-08-31T07:05:37Z"],["dc.description.abstract","Potassium para-aminobenzoate (POTABA) is used to treat Peyronie’s disease by decreasing fibrosis and plaque size progression. Among potential side effects, drug-induced liver injury (DILI) attributed to POTABA administration has been reported in a few cases and inferred to immune hypersensitivity. In the present case, we investigated clinical, biochemical, and serological features as well as searched for non-drug-related causes, and applied the updated Roussel Uclaf Causality Assessment Method (RUCAM) confirming a highly probable causality of POTABA-induced liver injury. Moreover, we here observed specific activated CD3+ T lymphocytes during the acute phase of liver injury by monitoring of human leukocyte antigen receptor (HLA-DR) expression. Furthermore, improvement of biochemical markers of liver injury after POTABA withdrawal was associated with a rapid decline of CD3+ HLA-DR+ immune cells. In contrast, CD14+ monocytes expressing HLA-DR remained stable during recovery from liver injury. These observations implicate a specific involvement of activated T lymphocytes in liver injury mediated by POTABA. Clinicians should be aware of POTABA-induced liver injury, and measurement of activated immune cells by assessment of HLA-DR could provide pathomechanistic insights enabling biomonitoring of recovery from DILI."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.doi","10.3389/fphar.2022.966910"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113317"],["dc.language.iso","en"],["dc.relation.eissn","1663-9812"],["dc.rights","CC BY 4.0"],["dc.rights.uri","http://creativecommons.org/licenses/by/4.0/"],["dc.title","Case report: Kinetics of human leukocyte antigen receptor HLA-DR during liver injury induced by potassium para-aminobenzoate as assessed for causality using the updated RUCAM"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Immunology"],["dc.bibliographiccitation.volume","12"],["dc.contributor.affiliation","Abusukhun, Murad; \r\n1\r\nDepartment of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany"],["dc.contributor.affiliation","Winkler, Martin S.; \r\n3\r\nDepartment of Anesthesiology, Emergency and Intensive Care Medicine, University of Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Pöhlmann, Stefan; \r\n4\r\nInfection Biology Unit, German Primate Center-Leibniz Institute for Primate Research, Göttingen, Germany"],["dc.contributor.affiliation","Moerer, Onnen; \r\n3\r\nDepartment of Anesthesiology, Emergency and Intensive Care Medicine, University of Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Meissner, Konrad; \r\n3\r\nDepartment of Anesthesiology, Emergency and Intensive Care Medicine, University of Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Tampe, Björn; \r\n6\r\nDepartment of Nephrology, University of Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Hofmann-Winkler, Heike; \r\n4\r\nInfection Biology Unit, German Primate Center-Leibniz Institute for Primate Research, Göttingen, Germany"],["dc.contributor.affiliation","Bauer, Michael; \r\n1\r\nDepartment of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany"],["dc.contributor.affiliation","Gräler, Markus H.; \r\n1\r\nDepartment of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany"],["dc.contributor.affiliation","Claus, Ralf A.; \r\n1\r\nDepartment of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany"],["dc.contributor.author","Abusukhun, Murad"],["dc.contributor.author","Winkler, Martin S."],["dc.contributor.author","Pöhlmann, Stefan"],["dc.contributor.author","Moerer, Onnen"],["dc.contributor.author","Meissner, Konrad"],["dc.contributor.author","Tampe, Björn"],["dc.contributor.author","Hofmann-Winkler, Heike"],["dc.contributor.author","Bauer, Michael"],["dc.contributor.author","Gräler, Markus H."],["dc.contributor.author","Claus, Ralf A."],["dc.date.accessioned","2022-02-01T10:31:39Z"],["dc.date.available","2022-02-01T10:31:39Z"],["dc.date.issued","2021"],["dc.date.updated","2022-02-09T13:20:12Z"],["dc.description.abstract","Effective treatment strategies for severe coronavirus disease (COVID-19) remain scarce. Hydrolysis of membrane-embedded, inert sphingomyelin by stress responsive sphingomyelinases is a hallmark of adaptive responses and cellular repair. As demonstrated in experimental and observational clinical studies, the transient and stress-triggered release of a sphingomyelinase, SMPD1, into circulation and subsequent ceramide generation provides a promising target for FDA-approved drugs. Here, we report the activation of sphingomyelinase-ceramide pathway in 23 intensive care patients with severe COVID-19. We observed an increase of circulating activity of sphingomyelinase with subsequent derangement of sphingolipids in serum lipoproteins and from red blood cells (RBC). Consistent with increased ceramide levels derived from the inert membrane constituent sphingomyelin, increased activity of acid sphingomyelinase (ASM) accurately distinguished the patient cohort undergoing intensive care from healthy controls. Positive correlational analyses with biomarkers of severe clinical phenotype support the concept of an essential pathophysiological role of ASM in the course of SARS-CoV-2 infection as well as of a promising role for functional inhibition with anti-inflammatory agents in SARS-CoV-2 infection as also proposed in independent observational studies. We conclude that large-sized multicenter, interventional trials are now needed to evaluate the potential benefit of functional inhibition of this sphingomyelinase in critically ill patients with COVID-19."],["dc.description.abstract","Effective treatment strategies for severe coronavirus disease (COVID-19) remain scarce. Hydrolysis of membrane-embedded, inert sphingomyelin by stress responsive sphingomyelinases is a hallmark of adaptive responses and cellular repair. As demonstrated in experimental and observational clinical studies, the transient and stress-triggered release of a sphingomyelinase, SMPD1, into circulation and subsequent ceramide generation provides a promising target for FDA-approved drugs. Here, we report the activation of sphingomyelinase-ceramide pathway in 23 intensive care patients with severe COVID-19. We observed an increase of circulating activity of sphingomyelinase with subsequent derangement of sphingolipids in serum lipoproteins and from red blood cells (RBC). Consistent with increased ceramide levels derived from the inert membrane constituent sphingomyelin, increased activity of acid sphingomyelinase (ASM) accurately distinguished the patient cohort undergoing intensive care from healthy controls. Positive correlational analyses with biomarkers of severe clinical phenotype support the concept of an essential pathophysiological role of ASM in the course of SARS-CoV-2 infection as well as of a promising role for functional inhibition with anti-inflammatory agents in SARS-CoV-2 infection as also proposed in independent observational studies. We conclude that large-sized multicenter, interventional trials are now needed to evaluate the potential benefit of functional inhibition of this sphingomyelinase in critically ill patients with COVID-19."],["dc.identifier.doi","10.3389/fimmu.2021.784989"],["dc.identifier.eissn","1664-3224"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/98916"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-517"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1664-3224"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Activation of Sphingomyelinase-Ceramide-Pathway in COVID-19 Purposes Its Inhibition for Therapeutic Strategies"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2014"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Cells"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Tampe, Désirée"],["dc.contributor.author","Schridde, Laura"],["dc.contributor.author","Korsten, Peter"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Zeisberg, Michael"],["dc.contributor.author","Hakroush, Samy"],["dc.contributor.author","Tampe, Björn"],["dc.date.accessioned","2021-10-01T09:58:23Z"],["dc.date.available","2021-10-01T09:58:23Z"],["dc.date.issued","2021"],["dc.description.abstract","Kidney fibrosis is a common manifestation and hallmark of a wide variety of chronic kidney disease (CKD) that appears in different morphological patterns, suggesting distinct pathogenic causes. Broad macroscopically visible scars are the sequelae of severe focal injury and complete parenchymal destruction, reflecting a wound healing response as a consequence of infarction. In the kidney, chronic glomerular injury leads to atrophy of the corresponding tubule, degeneration of this specific nephron, and finally interstitial fibrosis/tubular atrophy (IF/TA). Compared to this glomerulus-induced focal replacement scar, diffuse fibrosis independent of tubular atrophy appears to be a different pathogenic process. Kidney fibrosis appears to develop in a compartment-specific manner, but whether focal and diffuse fibrosis has distinct characteristics associated with other glomerular or tubulointerstitial lesions remains elusive. In the present study, we aimed to analyze renal fibrotic patterns related to renal lesions, which directly contribute to renal fibrogenesis, to unravel fibrotic patterns and manifestations upon damage to distinct renal compartments. Patterns of kidney fibrosis were analyzed in experimental models of CKD and various renal pathologies in correlation with histopathological and ultrastructural findings. After the induction of isolated crescentic glomerulonephritis (GN) in nephrotoxic serum-nephritis (NTN), chronic glomerular damage resulted in predominantly focal fibrosis adjacent to atrophic tubules. By contrast, using unilateral ureteral obstruction (UUO) as a model of primary injury to the tubulointerstitial compartment revealed diffuse fibrosis as the predominant pattern of chronic lesions. Finally, folic acid-induced nephropathy (FAN) as a model of primary tubular injury with consecutive tubular atrophy independent of chronic glomerular damage equally induced predominant focal IF/TA. By analyzing several renal pathologies, our data also suggest that focal and diffuse fibrosis appear to contribute as chronic lesions in the majority of human renal disease, mainly being present in antineutrophil cytoplasmic antibody (ANCA)-associated GN, lupus nephritis, and IgA nephropathy (IgAN). Focal IF/TA correlated with glomerular damage and irreversible injury to nephrons, whereas diffuse fibrosis in ANCA GN was associated explicitly with interstitial inflammation independent of glomerular damage and nephron loss. Ultrastructural analysis of focal IF/TA versus diffuse fibrosis revealed distinct matrix compositions, further supported by different collagen signatures in transcriptome datasets. With regard to long-term renal outcome, only the extent of focal IF/TA correlated with the development of end-stage kidney disease (ESKD) in ANCA GN. In contrast, diffuse kidney fibrosis did not associate with the long-term renal outcome. In conclusion, we here provide evidence that a focal pattern of kidney fibrosis seems to be associated with nephron loss and replacement scarring. In contrast, a diffuse pattern of kidney fibrosis appears to result from primary interstitial inflammation and injury."],["dc.description.abstract","Kidney fibrosis is a common manifestation and hallmark of a wide variety of chronic kidney disease (CKD) that appears in different morphological patterns, suggesting distinct pathogenic causes. Broad macroscopically visible scars are the sequelae of severe focal injury and complete parenchymal destruction, reflecting a wound healing response as a consequence of infarction. In the kidney, chronic glomerular injury leads to atrophy of the corresponding tubule, degeneration of this specific nephron, and finally interstitial fibrosis/tubular atrophy (IF/TA). Compared to this glomerulus-induced focal replacement scar, diffuse fibrosis independent of tubular atrophy appears to be a different pathogenic process. Kidney fibrosis appears to develop in a compartment-specific manner, but whether focal and diffuse fibrosis has distinct characteristics associated with other glomerular or tubulointerstitial lesions remains elusive. In the present study, we aimed to analyze renal fibrotic patterns related to renal lesions, which directly contribute to renal fibrogenesis, to unravel fibrotic patterns and manifestations upon damage to distinct renal compartments. Patterns of kidney fibrosis were analyzed in experimental models of CKD and various renal pathologies in correlation with histopathological and ultrastructural findings. After the induction of isolated crescentic glomerulonephritis (GN) in nephrotoxic serum-nephritis (NTN), chronic glomerular damage resulted in predominantly focal fibrosis adjacent to atrophic tubules. By contrast, using unilateral ureteral obstruction (UUO) as a model of primary injury to the tubulointerstitial compartment revealed diffuse fibrosis as the predominant pattern of chronic lesions. Finally, folic acid-induced nephropathy (FAN) as a model of primary tubular injury with consecutive tubular atrophy independent of chronic glomerular damage equally induced predominant focal IF/TA. By analyzing several renal pathologies, our data also suggest that focal and diffuse fibrosis appear to contribute as chronic lesions in the majority of human renal disease, mainly being present in antineutrophil cytoplasmic antibody (ANCA)-associated GN, lupus nephritis, and IgA nephropathy (IgAN). Focal IF/TA correlated with glomerular damage and irreversible injury to nephrons, whereas diffuse fibrosis in ANCA GN was associated explicitly with interstitial inflammation independent of glomerular damage and nephron loss. Ultrastructural analysis of focal IF/TA versus diffuse fibrosis revealed distinct matrix compositions, further supported by different collagen signatures in transcriptome datasets. With regard to long-term renal outcome, only the extent of focal IF/TA correlated with the development of end-stage kidney disease (ESKD) in ANCA GN. In contrast, diffuse kidney fibrosis did not associate with the long-term renal outcome. In conclusion, we here provide evidence that a focal pattern of kidney fibrosis seems to be associated with nephron loss and replacement scarring. In contrast, a diffuse pattern of kidney fibrosis appears to result from primary interstitial inflammation and injury."],["dc.description.sponsorship","Georg-August-Universität Göttingen"],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft"],["dc.identifier.doi","10.3390/cells10082014"],["dc.identifier.pii","cells10082014"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/90053"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-469"],["dc.publisher","MDPI"],["dc.relation.eissn","2073-4409"],["dc.rights","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Different Patterns of Kidney Fibrosis Are Indicative of Injury to Distinct Renal Compartments"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","3509"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.lastpage","15"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Xu, Xingbo"],["dc.contributor.author","Tan, Xiaoying"],["dc.contributor.author","Tampe, Björn"],["dc.contributor.author","Wilhelmi, Tim"],["dc.contributor.author","Hulshoff, Melanie S."],["dc.contributor.author","Saito, Shoji"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Kalluri, Raghu"],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Zeisberg, Elisabeth M."],["dc.contributor.author","Zeisberg, Michael"],["dc.date.accessioned","2019-02-27T12:52:18Z"],["dc.date.available","2019-02-27T12:52:18Z"],["dc.date.issued","2018"],["dc.description.abstract","While suppression of specific genes through aberrant promoter methylation contributes to different diseases including organ fibrosis, gene-specific reactivation technology is not yet available for therapy. TET enzymes catalyze hydroxymethylation of methylated DNA, reactivating gene expression. We here report generation of a high-fidelity CRISPR/Cas9-based gene-specific dioxygenase by fusing an endonuclease deactivated high-fidelity Cas9 (dHFCas9) to TET3 catalytic domain (TET3CD), targeted to specific genes by guiding RNAs (sgRNA). We demonstrate use of this technology in four different anti-fibrotic genes in different cell types in vitro, among them RASAL1 and Klotho, both hypermethylated in kidney fibrosis. Furthermore, in vivo lentiviral delivery of the Rasal1-targeted fusion protein to interstitial cells and of the Klotho-targeted fusion protein to tubular epithelial cells each results in specific gene reactivation and attenuation of fibrosis, providing gene-specific demethylating technology in a disease model."],["dc.identifier.doi","10.1038/s41467-018-05766-5"],["dc.identifier.pmid","30158531"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15605"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/57643"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/225"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C01: Epigenetische Kontrolle der Herzfibrose"],["dc.relation","SFB 1002 | D03: ENPP3-vermittelter Phosphat-Metabolismus bei der Herzfibrose"],["dc.relation.issn","2041-1723"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG E. Zeisberg (Kardiales Stroma)"],["dc.relation.workinggroup","RG M. Zeisberg (Renale Fibrogenese)"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","High-fidelity CRISPR/Cas9- based gene-specific hydroxymethylation rescues gene expression and attenuates renal fibrosis"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1231"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Journal of Clinical Medicine"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Hakroush, Samy"],["dc.contributor.author","Kluge, Ingmar Alexander"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Korsten, Peter"],["dc.contributor.author","Tampe, Désirée"],["dc.contributor.author","Tampe, Björn"],["dc.date.accessioned","2021-06-01T09:42:37Z"],["dc.date.available","2021-06-01T09:42:37Z"],["dc.date.issued","2021"],["dc.description.abstract","Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic vasculitis, most frequently presenting as microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA). Kidney involvement is a common and severe complication of ANCA AAV which is observed in a considerable subset of patients, mainly affecting glomeruli. However, tubulointerstitial lesions have also been described in ANCA glomerulonephritis (GN). Therefore, we aim to describe active and chronic tubulointerstitial lesions in ANCA GN subtypes by systematic scoring analogous to the Banff scoring system while also utilizing clinical and laboratory findings. Methods: A total of 49 kidney biopsies with ANCA GN were retrospectively included in a single-center cohort study between 2015–2020. Results: We report that MPO-ANCA GN is associated with more severe deterioration of kidney function independent of systemic markers of AAV disease activity, and is also associated with increased proteinuria in MPO-ANCA GN and a decreased fraction of normal glomeruli. Finally, MPO-ANCA GN showed distinct, active, and chronic tubulointerstitial lesions. Conclusion: New insights into the pathophysiology of both entities, as well as differences in the clinical presentation of MPO- versus PR3-ANCA GN, could potentially pave the way for more precise treatment regimens. Therefore, it is important to understand the differences in histopathological presentation, especially in yet underestimated active tubulointerstitial lesions of ANCA GN subtypes. This research could further improve our understanding of distinct pathophysiological mechanisms."],["dc.description.sponsorship","Georg-August-Universität Göttingen"],["dc.identifier.doi","10.3390/jcm10061231"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85302"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.publisher","MDPI"],["dc.relation.eissn","2077-0383"],["dc.rights","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Systematic Histological Scoring Reveals More Prominent Interstitial Inflammation in Myeloperoxidase-ANCA Compared to Proteinase 3-ANCA Glomerulonephritis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Oncology"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Hakroush, Samy"],["dc.contributor.author","Wulf, Svenja"],["dc.contributor.author","Gallwas, Julia"],["dc.contributor.author","Tampe, Björn"],["dc.date.accessioned","2022-01-11T14:06:15Z"],["dc.date.available","2022-01-11T14:06:15Z"],["dc.date.issued","2021"],["dc.description.abstract","Ado-trastuzumab emtansine (T-DM1) is an antibody–drug conjugate consisting of the monoclonal antibody trastuzumab linked to the maytansinoid DM1 with potential antineoplastic activity and is approved for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. An analysis of the US Food and Drug Administration (FDA) Adverse Event Reporting System identified 124/1,243 (10%) renal adverse events for trastuzumab. However, there are no published case reports describing kidney biopsy findings related to nephrotoxicity of either trastuzumab or T-DM1. We report kidney biopsy findings in a case of nephrotic range proteinuria due to collapsing focal segmental glomerulosclerosis (FSGS) and tubular injury after initiation of T-DM1 therapy. After systematic exclusion of other causes, it is likely that the observed collapsing FSGS was associated with the prior initiation of T-DM1 therapy. This is further supported by the clinical course with improvement of proteinuria and kidney function 3 weeks after discontinuation of T-DM1 therapy without further specific treatment. In summary, we provide the first report of kidney biopsy findings in a case of nephrotic range proteinuria after initiation of T-DM1 therapy due to collapsing FSGS. This issue is especially relevant since T-DM1 is widely used, and nephrologists have to be aware of this potentially rare but severe complication."],["dc.description.abstract","Ado-trastuzumab emtansine (T-DM1) is an antibody–drug conjugate consisting of the monoclonal antibody trastuzumab linked to the maytansinoid DM1 with potential antineoplastic activity and is approved for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. An analysis of the US Food and Drug Administration (FDA) Adverse Event Reporting System identified 124/1,243 (10%) renal adverse events for trastuzumab. However, there are no published case reports describing kidney biopsy findings related to nephrotoxicity of either trastuzumab or T-DM1. We report kidney biopsy findings in a case of nephrotic range proteinuria due to collapsing focal segmental glomerulosclerosis (FSGS) and tubular injury after initiation of T-DM1 therapy. After systematic exclusion of other causes, it is likely that the observed collapsing FSGS was associated with the prior initiation of T-DM1 therapy. This is further supported by the clinical course with improvement of proteinuria and kidney function 3 weeks after discontinuation of T-DM1 therapy without further specific treatment. In summary, we provide the first report of kidney biopsy findings in a case of nephrotic range proteinuria after initiation of T-DM1 therapy due to collapsing FSGS. This issue is especially relevant since T-DM1 is widely used, and nephrologists have to be aware of this potentially rare but severe complication."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2021"],["dc.identifier.doi","10.3389/fonc.2021.796223"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/97865"],["dc.notes.intern","DOI-Import GROB-507"],["dc.relation.eissn","2234-943X"],["dc.relation.orgunit","Klinik für Nephrologie und Rheumatologie"],["dc.rights","CC BY 4.0"],["dc.title","Case Report: Collapsing Focal Segmental Glomerulosclerosis After Initiation of Ado-Trastuzumab Emtansine Therapy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","1407"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Missbach-Guentner, Jeannine"],["dc.contributor.author","Pinkert-Leetsch, Diana"],["dc.contributor.author","Dullin, Christian"],["dc.contributor.author","Ufartes, Roser"],["dc.contributor.author","Hornung, Daniel"],["dc.contributor.author","Tampe, Bjoern"],["dc.contributor.author","Zeisberg, Michael"],["dc.contributor.author","Alves, Frauke"],["dc.date.accessioned","2019-07-09T11:45:05Z"],["dc.date.available","2019-07-09T11:45:05Z"],["dc.date.issued","2018"],["dc.description.abstract","The increasing number of patients with end stage chronic kidney disease not only calls for novel therapeutics but also for pioneering research using convincing preclinical disease models and innovative analytical techniques. The aim of this study was to introduce a virtual histology approach using micro computed tomography (µCT) for the entire murine kidney in order to close the gap between single slice planar histology and a 3D high resolution dataset. An ex vivo staining protocol based on phosphotungstic acid diffusion was adapted to enhance renal soft tissue x-ray attenuation. Subsequent CT scans allowed (i) the detection of the renal cortex, medulla and pelvis in greater detail, (ii) the analysis of morphological alterations, (iii) the quantification of the volume as well as the radio-opacity of these portions and (iv) the quantification of renal fibrotic remodeling based on altered radio-opacity using the unilateral ureteral obstruction model. Thus, virtual histology based on PTA contrast enhanced CT will in future help to refine the outcome of preclinical research on kidney associated murine disease models."],["dc.identifier.doi","10.1038/s41598-018-19773-5"],["dc.identifier.pmid","29362427"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15031"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59157"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2045-2322"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","3D virtual histology of murine kidneys -high resolution visualization of pathological alterations by micro computed tomography."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]