Jenny Krause

University Medical Center Hamburg-Eppendorf

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Christian Casar

University Medical Center Hamburg-Eppendorf

Ansgar W. Lohse

Universität Hamburg

Henning Wege

Klinikum Esslingen

Samuel Huber

Universität Hamburg

Johann von Felden

Universität Hamburg

Harald Ittrich

University Medical Center Hamburg-Eppendorf

Christoph Schramm

University Medical Center Hamburg-Eppendorf

Kornelius Schulze

Universität Hamburg

Thorben W. Fründt

University Medical Center Hamburg-Eppendorf

Nicola Gagliani

Universität Hamburg

Cooperative Institutions

Universität Hamburg

238

University Medical Center Hamburg-Eppendorf

234

European Foundation for the Study of Chronic Liver Failure

Heidelberg University

University of Cologne

ERN GUARD-Heart

University Medical Center

Heinrich Heine University Düsseldorf

ERN RARE-LIVER

Martini-Klinik

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

The combination of EpCAM-positive circulating tumor cells and serum AFP/AFP-L3/DCP predicts outcome after curative resection of hepatocellular carcinoma

Journal of Hepatology (2020)

Johann von Felden Martin Schoenlein Berit Behrends Christian Casar Thorben Fruendt

10.1016/s0168-8278(20)31250-2

Cite

Citations (0)

Myeloperoxidase Mediates Postischemic Arrhythmogenic Ventricular Remodeling

Circulation Research (2017)

Martin Mollenhauer Kai Friedrichs Max Lange Jan Gesenberg Lisa Remane

Rationale: Ventricular arrhythmias remain the leading cause of death in patients suffering myocardial ischemia. Myeloperoxidase, a heme enzyme released by polymorphonuclear neutrophils, accumulates within ischemic myocardium and has been linked to adverse left ventricular remodeling. Objective: To reveal the role of myeloperoxidase for the development of ventricular arrhythmias. Methods and Results: In different murine models of myocardial ischemia, myeloperoxidase deficiency profoundly decreased vulnerability for ventricular tachycardia on programmed right ventricular and burst stimulation and spontaneously as assessed by ECG telemetry after isoproterenol injection. Experiments using CD11b/CD18 integrin–deficient (CD11b −/− ) mice and intravenous myeloperoxidase infusion revealed that neutrophil infiltration is a prerequisite for myocardial myeloperoxidase accumulation. Ventricles from myeloperoxidase-deficient (Mpo −/− ) mice showed less pronounced slowing and decreased heterogeneity of electric conduction in the peri-infarct zone than wild-type mice. Expression of the redox-sensitive gap junctional protein Cx43 (Connexin 43) was reduced in the peri-infarct area of wild-type compared with Mpo −/− mice. In isolated wild-type cardiomyocytes, Cx43 protein content decreased on myeloperoxidase/H 2 O 2 incubation. Mapping of induced pluripotent stem cell–derived cardiomyocyte networks and in vivo investigations linked Cx43 breakdown to myeloperoxidase-dependent activation of matrix metalloproteinase 7. Moreover, Mpo −/− mice showed decreased ventricular postischemic fibrosis reflecting reduced accumulation of myofibroblasts. Ex vivo, myeloperoxidase was demonstrated to induce fibroblast-to-myofibroblast transdifferentiation by activation of p38 mitogen-activated protein kinases resulting in upregulated collagen generation. In support of our experimental findings, baseline myeloperoxidase plasma levels were independently associated with a history of ventricular arrhythmias, sudden cardiac death, or implantable cardioverter–defibrillator implantation in a cohort of 2622 stable patients with an ejection fraction >35% undergoing elective diagnostic cardiac evaluation. Conclusions: Myeloperoxidase emerges as a crucial mediator of postischemic myocardial remodeling and may evolve as a novel pharmacological target for secondary disease prevention after myocardial ischemia.

10.1161/circresaha.117.310870

Cite

Citations (67)

Cancer-Associated Fibroblasts Induce Proliferation and Therapeutic Resistance to Everolimus in Neuroendocrine Tumors through STAT3 Activation

Neuroendocrinology (2022)

Tania Amin Fabrice Viol Jenny Krause Martina Fahl Corinna Eggers

Cancer-associated fibroblasts (CAF) have been identified as relevant contributors to cancer progression and drug resistance in many tumors. Although neuroendocrine tumors (NET) are often associated with a strong stromal reaction, no study has addressed whether CAF are involved in progression and therapeutic resistance in NET. The aim of this study was to characterize the role of CAF in NET.We established primary CAF cultures derived from NET liver metastases to study the effect on NET cell lines NT-3 and BON. Immunohistochemistry was performed on tissue sections of primary and metastatic NET tissue.Immunohistochemistry identified CAF dispersed in between tumor cells and within fibrotic bands separating tumor cell clusters in NET. Stimulating NET cells with CAF decreased expression of SSTR2 and chromogranin A and induced expression of CXCR4. CAF induced a 2.3-fold increase in proliferation and completely reversed the response to everolimus in NT-3 cells. We identified STAT3 as the main signaling pathway induced by CAF. STAT3 targeting by small interfering RNA knockdown and inhibitors prevented CAF-induced proliferation and restored everolimus responsiveness. STAT3 activation in NET tissue was associated with decreased chromogranin A expression, increased Ki-67 index, and decreased 5-year overall and progression-free survival. CAF directly influence proliferation and therapeutic response in NET cells.Identifying STAT3 as the contributing pathway of this so far neglected tumor-stroma interaction has the potential to become a new therapeutic target to halt tumor growth and to restore therapeutic responsiveness in NET.

Chromogranin A

Everolimus

Tumor progression

10.1159/000528539

Cite

Citations (15)

NKp44/HLA-DP-dependent regulation of CD8 effector T cells by NK cells

Cell Reports (2024)

Benedetta Padoan Christian Casar Jenny Krause Christoph Schultheiß Martin E. Baumdick

Although natural killer (NK) cells are recognized for their modulation of immune responses, the mechanisms by which human NK cells mediate immune regulation are unclear. Here, we report that expression of human leukocyte antigen (HLA)-DP, a ligand for the activating NK cell receptor NKp44, is significantly upregulated on CD8

10.1016/j.celrep.2024.114089

Cite

Citations (8)

SAT-531-YI Testosterone modulates T cells in healthy individuals and women with autoimmune liver disease

Journal of Hepatology (2024)

Nico Will Lara Henze Christian Casar Victor H. Haas Jasper Meyer

10.1016/s0168-8278(24)01173-5

Cite

Citations (0)

[Reactivation of inhibited larvae of Ancylostoma caninum. Effect of estradiol and progesterone].

PubMed (1976)

M. Stoye Jenny Krause

Zusammenfassung Am Modell der impatent infizierten laktierenden ovariektomierten Hundin wurde der Einflus verschiedener Oestradiol-Progesteron-Kombinationen auf inhibierte Larven am Verlauf der Larvenausscheidung mit der Milch gepruft. Entsprechende Untersuchungen erfolgten an insgesamt 12 Hundinnen. Alle Versuchstiere waren helminthenfrei aufgezogen und einheitlich in den ersten Tagen nach der Geburt einmalig mit 20 000 dritten Larven von Ancylostoma caninum per os oder perkutan infiziert worden. Folgende Ergebnisse wurden erzielt: 1. Durch Applikation von Oestradiol und Progesteron in einem Verhaltnis von 1: 20 als Mikrokristallsuspension in einer Dosis von 2,5 mg und 50 mg/Tier konnte bei drei von vier Hundinnen eine Larvenausscheidung mit der Milch induziert werden. Die Zahl der bei diesen Tieren nach der Steroidgabe mit der Milch eliminierten Larven lag jedoch weit unter der, die als Ergebnis der Reaktivierung in der Folge einer Graviditat wahrend einer 2. Laktation p. i. zu erwarten gewesen ware. 2. Der Versuch, die doppelte und dreifache Dosis der Steroide an den gleichen Tieren 4 und 8 Wochen nach der ersten Stcroidgabe zu prufen, gelang nur bei zwei von vier Hundinnen. Bei einem dieser Tiere war die Larvenausscheidung nach der doppelten Dosis 8mal, nach der dreifachen Dosis 16mal groser als nach der Initialdosis. Die Dosisabhangigkeit der Steroidwirkung wurde bei der zweiten Hundin infolge zu geringer impatenter Infektion nicht deutlich. 3. Nach Applikation von Oestradiol und Progesteron in einem Verhaltnis von 1: 40 in oliger Losung bei taglich um 0,01 mg und 0,4 mg steigender Dosis von 0,08 mg und 3,2 mg bis 0,21 mg Oestradiol und 8,4 mg Progesteron am 14. Tag der Behandlung konnte wahrend und nach der Steroidgabe eine Larvenausscheidung mit der Milch induziert werden, die in Umfang und Ablauf weitgehend der entsprach, die als Ergebnis einer Reaktivierung wahrend der Graviditat in einer 2. Laktation p. i. zu erwarten gewesen ware. In allen Fallen, in denen eine Larvenausscheidung mit der Milch durch Oestradiol-Progesteron-Applikation zu induzieren war, bestanden zwischen der Larvenausscheidung mit der Milch und der oestrogenen Wirkung auf das Tier, gemessen am Eosinophilie- und Pyknose-Index des Scheidenepithels, signifikante Korrelationen. Die Untersuchungen erfolgten im Rahmen des Sonderforschungsbereiches 146 „Versuchstierforschung” der Deutschen Forschungsgemeinschaft. Bei der Durchfuhrung der Versuche wurden wir von den technischen Assistentinnen Jutta Lorrmann, Irenef Folle Gitta Betzhold und Petra Urbanski unterstutzt. Hierfur sagen wir unseren herzlichen Dank. Summary Studies on the reactivation of inhibited larvae of Ancylostomum caninum Effect of oestradiol and progesterone Using as a model the impatently infected lactating ovariectomized bitch the effect of various oestradiol-progesterone preparations on inhibited larvae so far as their excretion in the milk is concerned was studied. All animals were helminth-free and within a few days of birth each received a single dose of 20,000 third stage larvae of A. caninum per os or percutaneously. The results were as follows. 1. Oestradiol and progesterone in a ratio of 1: 20 given i. m. as a microcrystal suspension at a dosage of 2.5 and 50 mg./animal induced larval excretion in the milk in 3 of 4 dogs. The numbers of larvae excreted after the steroids were, however, far lower than resulted from the reactivation caused by the lactation following a second pregnancy. 2. Giving a twofold and threefold dose of steroids to the same animals 4 and 8 weeks after the first dose had an effect in only 2 of 4 bitches. In one of these larval excretion increased after double dosage to 8 times, after triple dosage to 16 times the level of excretion of larvae after the first dose. The dose-dependence of the steroid effect could not be demonstrated in the second dog because the non-patent infection was too small. 3. After giving oestradiol and progesterone in a ratio of 1: 40 in oily solution, the amount increasing daily by between 0.01 mg., and 0.4 mg. to levels of 0.08 and 3.2 mg. up to 0.21 mg. oestradiol and 8.4 mg. progesterone on the 14th day of treatment it was possible to induce larval excretion both during and following steroid dosage which in its degree and time relations resembled what would be expected during pregnancy during a second lactation. In all cases in which larval excretion was induced in the milk by oestradiol-progesterone application there was a significant correlation between larval milk excretion and oestrogenic effect on the animal, measured by eosinophilia and pycnosis indices in the vaginal epithelium. Resume Recherches sur une reactivation de larves inhibees d'Ancylostoma caninum Action de l'oestradiol et de la progesterone L'influence de differentes combinaisons oestradiol-progesterone sur des larves inhibees au cours de l'excretion lactee des larves fut testee avec un modele de chiennes infectees et ovariectomiees en lactation. Les recherches furent faites sur 12 chiennes. Tous les animaux d'experience furent eleves exempts d'helminthes et infectes en une fois de la meme maniere avec 20 000 troisiemes larves d'Ancylostoma caninum per os ou par voie percutanee dans les premiers jours apres la mise-bas. On a obtenu les resultats suivants: 1. Une excretion de larve dans le lait a pu etre induite chez 3 et 4 chiennes par une application d'oestradiol et de progesterone dans un rapport de 1: 20 en suspension microcristallisee et en dose de 2,5 mg et 50 mg par animal. Le nombre de larves eliminees dans le lait chez ces animaux apres l'application de steroides se situait bien au-dessous de celui attendu Durant une deuxieme lactation p. i. apres une reactivation suivant la gestation. 2. L'essai consistant a donner une double ou triple dose de steroides aux memes animaux 4 et 8 semaines apres la premiere injection n'a reussi que chez deux des quatre chiennes. L'excretion des larves fut 8 fois plus grande apres la double dose et 16 fois plus grande apres la triple dose qu'a la suite de la dose initiale chez une chienne. La dependance de la dose pour l'action des steroides ne fut pas nette chez la deuxieme chienne etant donne une infection trop faible. 3. On a pu induire une excretion des larves dans le lait apres l'application d'oestradiol et de progesterone dans un rapport de 1: 40 en solution huileuse et en augmentant la dose quotidiennement de 0,01 mg et 0,4 mg pour aller de 0′08 mg a 0,21 mg d'oestradiol et de 3,2 mg a 8,4 mg de progesterone au quatorzieme jour du traitement. Cette excretion a largement correspondu en volume et en ecoulement a celle attendue p. i. apres une reactivation pendant la gestation dans une seconde lactation. Il y eut des correlations significatives entre l'excretion des larves avec le lait et l'action des oestrogees sur l'animal mesuree par l'index eosinophiliepicnose de l'epithelium du vagin dans tous les cas ou l'excretion larvaire dans le lait fut provoquee par l'application d'oestradiol-progesterone. Resumen Ensayos sobre la reactivacion de larvas inhibidas de Ancylostoma caninum La accion de estradiol y progesterona Se examino en el modelo de perra ovariectomizada lactante infestada impatentemente el influjo de varias combinaciones estradiol-progesterona sobre larvas inhibidas en el curso de la expulsion de larvas con la leche. Se efectuaron experiencias de esta indole en 12 perras. Todos los animales de ensayo se habian criado libres de helmintos y fueron infestados de modo unitario durante los primeros dias despues del parto una vez sola con 20 000 larvas terciarias de Ancylostoma caninum per os o percutaneamente. Se obtuvieron los resultados siguientes: 1. Mediante aplicacion de estradiol y progesterona en la relacion de 1: 20 como suspension microcristalina en dosis de 2,5 mg. y 50 mg./animal se pudo inducir en tres de cuatro perras una expulsion de larvas con la leche. Sin embargo, la cantidad de larvas eliminadas con la leche por estos animales tras la administracion de esteroides se encontraba muy por debajo de aquella que se deberia esperar como resultado de la reactivacion a continuacion de una gestacion durante la lactacion 2° p. i. 2. El intento de contrastar la dosis doble y triple de esteroides en los mismos animales 4 y 8 semanas despues de la primera administracion esteroidea se logro solo en dos de cuatro perras. En uno de estos animales era 8 veces mayor la expulsion de larvas tras la dosis duplicada que tras la dosis inicial, mientras que 16 veces tras la dosis triple. La dependencia de la dosificacion de la actividad esteroidea no se hizo patente en la segunda perra debido a la infestacibn impatente demasiado escasa. 3. Tras aplicacion de estradiol y progesterona en la relacion de 1: 40 en suspension oleaginosa con dosis creciente cada dia en 0,01 mg. y 0,4 mg. desde 0,08 mg. y 3,2 mg. hasta 0,21 mg. estradiol y 8,4 mg. progesterona en el dia 14° de tratamiento, se pudo inducir durante y despues de la aplicacion de esteroides una expulsion de larvas con la leche, la cual correspondia, a grandes rasgos, en volumen y transcurso a la que se tendria que esperar como resultado de una reactivacion durante la gestacion en la lactacion 2° p. i. En todos los casos en que se habia inducido la eliminacion de larvas con la leche mediante aplicacion de estradiol-progesterona, existian correlaciones significantes entre la expulsion de larvas con la leche y la accion estrogena sobre el animal, medida con arreglo a los indices de eosinofilia y picnosis en el epitelio vaginal.

Ancylostoma caninum

Progesterone receptor

Source

Cite

Citations (12)

P.7.c.001 Akathisia as frequent side effect of anaesthesia with neuroleptics in patients with attention deficit/hyperactivity disorder

European Neuropsychopharmacology (2006)

Jenny Krause Kristina Krause

Akathisia

10.1016/s0924-977x(06)70728-3

Cite

Citations (0)

Diagnostik der endokrinen Pankreasinsuffizienz prä- und postoperativ – OGTT vs. i.v.GTT

Zeitschrift für Gastroenterologie (2010)

D. Sülberg Jenny Krause M. Janot AM Chromik W. Uhl

Einleitung: Der OGTT ist zur Diagnostik der endokrinen Pankreasinsuffizienz im Sinne einer gestörten Glucosetoleranz (ges. Glu-To.) bzw. Diabetes mellitus (DM) ein etabliertes Verfahren. Unerlässlich für die Aussagekraft des OGTT ist eine normale Morphologie des oberen GI-Traktes, welche v.a. nach Operationen gestört sein kann. Daher verglichen wir den OGTT mit dem i.v. GTT, um letzteren in der postoperativen Diagnostik zu etablieren.

10.1055/s-0030-1264013

Cite

Citations (0)

Supplementary Material for: Cancer associated fibroblasts induce proliferation and therapeutic resistance to everolimus in neuroendocrine tumors through STAT3 activation

Figshare (2022)

T. Amin Fabrice Viol Jenny Krause Martina Fahl Carrie M. Eggers

Introduction Cancer-associated fibroblasts (CAF) have been identified as relevant contributors to cancer progression and drug resistance in many tumors. Although neuroendo-crine tumors (NET) are often associated with a strong stromal reaction, no study has addressed whether CAF are involved in progression and therapeutic resistance in NET. The aim of this study was to characterize the role of CAF in NET. Methods We established primary CAF cultures derived from NET liver metastases to study the effect on NET cell lines NT-3 and BON. Immunohistochemistry was performed on tissue sections of primary and metastatic NET tissue. Results Immunohistochemistry identified CAF dispersed in between tumor cells and within fibrotic bands separating tumor cell clusters in NET. Stimulating NET cells with CAF decreased expression of SSTR2 and chromogranin A and induced expression of CXCR4. CAF induced a 2.3-fold increase in proliferation and completely reversed the response to everolimus in NT-3 cells. We identified STAT3 as the main signal-ing pathway induced by CAF. STAT3 targeting by small interfering RNA (siRNA) knockdown and inhibitors prevented CAF induced proliferation and restored evero-limus responsiveness. STAT3 activation in NET tissue was associated with de-creased chromogranin A expression, increased Ki-67 index and decreased 5-year overall and progression free survival. CAF directly influence proliferation and thera-peutic response in NET cells. Conclusion Identifying STAT3 as the contributing pathway of this so far neglected tumor-stroma interaction has the potential to become a new therapeutic target to halt tumor growth and to restore therapeutic responsiveness in NET.

Everolimus

10.6084/m9.figshare.21681455

Cite

Citations (0)

The role of TCR in regulating T cell function in acute and chronic infections and cancer

The Journal of Immunology (2024)

Jenny Krause Noah Veis Gavil Meagan R. Rollins Sathi Wijeyesinghe Courtney A. Matson

Abstract In contrast to naive T cells, memory T cells do not require TCR stimulation to survive and are maintained by cytokines to undergo homeostatic proliferation. However, permanent TCR stimulation of T cells by persistent antigen in chronic infections and cancer causes a dysfunctional state, termed T cell exhaustion (TEX). Yet, how TCR signaling influences the location, maintenance, and function of T cell subsets remains incompletely understood. Using an inducible TCR knockout model (UBC-CreERT2 x Trac flox/flox), longevity of tissue resident memory T cells (TRM) and persistent CD69 expression after TCR deletion was shown. However, this model was limited due to the polyclonal memory T cell population used. To study the role of TCR in the regulation of TRM and TEX in infections and cancer, we designed a rAAV6 vector construct that encodes the floxed P14 TCRa and TCRb to the endogenous TRAC locus using CRISPR/Cas9. We validated the construct in vitro by transfecting UBC-CreERT2 cells, adoptively transferred into CD45.1 mice and infected with LCMV Armstrong before TCR deletion after tamoxifen treatment. We next generated UBC-CreERT2 x P14a flox mice using the same approach, and confirmed the expression by PCR and H-2Db/gp33 MHC I tetramer stain by flow cytometry. We will use this model to understand how TCR signaling influences T cell differentiation, residence and exhaustion by inducing TCR ablation at the effector, contraction, memory and exhaustion state.

10.4049/jimmunol.212.supp.1229.5286

Cite

Citations (0)