TY  - JOUR
A1  - Biermann, Daniel
A1  - Heilmann, Andreas
A1  - Didié, Michael
A1  - Schlossarek, Saskia
A1  - Wahab, Azadeh
A1  - Grimm, Michael
A1  - Römer, Maria
A1  - Reichenspurner, Hermann
A1  - Sultan, Karim R.
A1  - Steenpass, Anna
A1  - Ergün, Süleyman
A1  - Donzelli, Sonia
A1  - Carrier, Lucie
A1  - Ehmke, Heimo
A1  - Zimmermann, Wolfram H.
A1  - Hein, Lutz
A1  - Böger, Rainer H.
A1  - Benndorf, Ralf A.
T1  - Impact of AT2 Receptor Deficiency on Postnatal Cardiovascular Development
JF  - PLoS One
N2  - Background: The angiotensin II receptor subtype 2 (AT2 receptor) is ubiquitously and highly expressed in early postnatal life. However, its role in postnatal cardiac development remained unclear. 
Methodology/Principal Findings: Hearts from 1, 7, 14 and 56 days old wild-type (WT) and AT2 receptor-deficient (KO) mice were extracted for histomorphometrical analysis as well as analysis of cardiac signaling and gene expression. Furthermore, heart and body weights of examined animals were recorded and echocardiographic analysis of cardiac function as well as telemetric blood pressure measurements were performed. Moreover, gene expression, sarcomere shortening and calcium transients were examined in ventricular cardiomyocytes isolated from both genotypes. KO mice exhibited an accelerated body weight gain and a reduced heart to body weight ratio as compared to WT mice in the postnatal period. However, in adult KO mice the heart to body weight ratio was significantly increased most likely due to elevated systemic blood pressure. At postnatal day 7 ventricular capillarization index and the density of \(\alpha\)-smooth muscle cell actin-positive blood vessels were higher in KO mice as compared to WT mice but normalized during adolescence. Echocardiographic assessment of cardiac systolic function at postnatal day 7 revealed decreased contractility of KO hearts in response to beta-adrenergic stimulation. Moreover, cardiomyocytes from KO mice showed a decreased sarcomere shortening and an increased peak Ca\(^{2+}\) transient in response to isoprenaline when stimulated concomitantly with angiotensin II. 
Conclusion: The AT2 receptor affects postnatal cardiac growth possibly via reducing body weight gain and systemic blood pressure. Moreover, it moderately attenuates postnatal vascularization of the heart and modulates the beta adrenergic response of the neonatal heart. These AT2 receptor-mediated effects may be implicated in the physiological maturation process of the heart.
KW  - mice
KW  - II type-2 receptor
KW  - human endothelial cells
KW  - chronic kidney disease
KW  - angiotensin II
KW  - blood pressure
KW  - in vitro
KW  - cardiac hyperthrophy
KW  - tube formation
KW  - rat heart
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134902
VL  - 7
IS  - 10
ER  - 
TY  - JOUR
A1  - Riquelme, Paloma
A1  - Haarer, Jan
A1  - Kammler, Anja
A1  - Walter, Lisa
A1  - Tomiuk, Stefan
A1  - Ahrens, Norbert
A1  - Wege, Anja K.
A1  - Goecze, Ivan
A1  - Zecher, Daniel
A1  - Banas, Bernhard
A1  - Spang, Rainer
A1  - Fändrich, Fred
A1  - Lutz, Manfred B.
A1  - Sawitzki, Birgit
A1  - Schlitt, Hans J.
A1  - Ochando, Jordi
A1  - Geissler, Edward K.
A1  - Hutchinson, James A.
T1  - TIGIT\(^+\) iTregs elicited by human regulatory macrophages control T cell immunity
JF  - Nature Communications
N2  - Human regulatory macrophages (Mreg) have shown early clinical promise as a cell-based adjunct immunosuppressive therapy in solid organ transplantation. It is hypothesised that recipient CD4(+) T cell responses are actively regulated through direct allorecognition of donor-derived Mregs. Here we show that human Mregs convert allogeneic CD4(+) T cells to IL-10-producing, TIGIT(+) FoxP3(+)-induced regulatory T cells that non-specifically suppress bystander T cells and inhibit dendritic cell maturation. Differentiation of Mreg-induced Tregs relies on multiple non-redundant mechanisms that are not exclusive to interaction of Mregs and T cells, including signals mediated by indoleamine 2,3-dioxygenase, TGF-beta, retinoic acid, Notch and progestagen-associated endometrial protein. Preoperative administration of donor-derived Mregs to living-donor kidney transplant recipients results in an acute increase in circulating TIGIT(+) Tregs. These results suggest a feed-forward mechanism by which Mreg treatment promotes allograft acceptance through rapid induction of direct-pathway Tregs.
KW  - Allotransplantation
KW  - Immunosuppression
KW  - Monocytes and macrophages
KW  - Regulatory T cells
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226321
VL  - 9
IS  - 9
ER  - 
TY  - JOUR
A1  - Kämmerer, Peer W.
A1  - Tribius, Silke
A1  - Cohrs, Lena
A1  - Engler, Gabriel
A1  - Ettl, Tobias
A1  - Freier, Kolja
A1  - Frerich, Bernhard
A1  - Ghanaati, Shahram
A1  - Gosau, Martin
A1  - Haim, Dominik
A1  - Hartmann, Stefan
A1  - Heiland, Max
A1  - Herbst, Manuel
A1  - Hoefert, Sebastian
A1  - Hoffmann, Jürgen
A1  - Hölzle, Frank
A1  - Howaldt, Hans-Peter
A1  - Kreutzer, Kilian
A1  - Leonhardt, Henry
A1  - Lutz, Rainer
A1  - Moergel, Maximilian
A1  - Modabber, Ali
A1  - Neff, Andreas
A1  - Pietzka, Sebastian
A1  - Rau, Andrea
A1  - Reichert, Torsten E.
A1  - Smeets, Ralf
A1  - Sproll, Christoph
A1  - Steller, Daniel
A1  - Wiltfang, Jörg
A1  - Wolff, Klaus-Dietrich
A1  - Kronfeld, Kai
A1  - Al-Nawas, Bilal
T1  - Adjuvant radiotherapy in patients with squamous cell carcinoma of the oral cavity or oropharynx and solitary ipsilateral lymph node metastasis (pN1) — a prospective multicentric cohort study
JF  - Cancers
N2  - (1) Background: Evaluation of impact of adjuvant radiation therapy (RT) in patients with oral squamous cell carcinoma of the oral cavity/oropharynx (OSCC) of up to 4 cm (pT1/pT2) and solitary ipsilateral lymph node metastasis (pN1). A non-irradiated group with clinical follow-up was chosen for control, and survival and quality of life (QL) were compared; (2) Methods: This prospective multicentric comprehensive cohort study included patients with resected OSCC (pT1/pT2, pN1, and cM0) who were allocated into adjuvant radiation therapy (RT) or observation. The primary endpoint was overall survival. Secondary endpoints were progression-free survival and QL after surgery; (3) Results: Out of 27 centers, 209 patients were enrolled with a median follow-up of 3.4 years. An amount of 137 patients were in the observation arm, and 72 received adjuvant irradiation. Overall survival did not differ between groups (hazard ratio (HR) 0.98 [0.55–1.73], p = 0.94). There were fewer neck metastases (HR 0.34 [0.15–0.77]; p = 0.01), as well as fewer local recurrences (HR 0.41 [0.19–0.89]; p = 0.02) under adjuvant RT. For QL, irradiated patients showed higher values for the symptom scale pain after 0.5, two, and three years (all p < 0.05). After six months and three years, irradiated patients reported higher symptom burdens (impaired swallowing, speech, as well as teeth-related problems (all p < 0.05)). Patients in the RT group had significantly more problems with mouth opening after six months, one, and two years (p < 0.05); (4) Conclusions: Adjuvant RT in patients with early SCC of the oral cavity and oropharynx does not seem to influence overall survival, but it positively affects progression-free survival. However, irradiated patients report a significantly decreased QL up to three years after therapy compared to the observation group.
KW  - oral squamous cell carcinoma
KW  - oropharyngeal carcinoma
KW  - surgery
KW  - resection
KW  - radiotherapy
KW  - survival
KW  - progression-free survival
KW  - quality of life
KW  - prospective
KW  - multicentric
KW  - lymph node
KW  - pN1
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-311024
SN  - 2072-6694
VL  - 15
IS  - 6
ER  -