Levent Akyüz

• Head of Department at Charité Universitätsmedizin Berlin

Background Proximal humerus fractures (PHFs) are the third most common fractures in elderly patients. Over 70% of PHFs in patients aged over 60 are displaced fractures, often necessitating surgical treatment. However, osteosynthesis is associated with a high rate of complications, highlighting the urgent need for additional therapeutic approaches t...

IMPORTANCE: Postoperative delirium (POD) is a multietiological condition and affects 20% of older surgical patients. It is associated with poor clinical outcome and increased mortality. OBJECTIVE: We aimed to develop and validate a risk prediction algorithm for POD based on a multimodal biomarker database exploiting preoperative data (predisposing...

Lymphocyte depletion via anti-CD52 monoclonal antibody (mAb) therapy is an effective treatment strategy for relapsing–remitting multiple sclerosis (MS) but is associated with infusion/injection-associated reactions (IARs) and autoimmune-related adverse events (AEs). Gatralimab is a next-generation humanized anti-CD52 mAb. Two first-in-human trials...

Cytokine and chemokine levels in body fluid provide information of altered conditions in patients. The parallel analysis of multiple factors, such as cytokines, from small sample sizes is an interesting approach for the assessment of in vivo activation signatures and functionality after ex vivo stimulation. One interesting application is for therap...

Chimeric Antigen Receptor (CAR) redirected T-cells are potent therapeutic options against hematological malignancies. The current dominant manufacturing approach for CAR T cells depends on retroviral transduction. With the advent of gene editing, insertion of a CD19-CAR into the T cell receptor (TCR) alpha constant (TRAC) locus using adeno-associat...

Objective: Studies have suggested that inflammation contributes to the pathogenesis of postoperative delirium, but previous results on the proinflammatory cytokine IL-8 in plasma are contradictory. Additionally, a significant fraction of IL-8 is bound to erythrocytes, but the relevance of whole blood IL-8 in delirium has not been studied. In this...

Background Quadriceps tendon ruptures (QTRs) are rare but debilitating injuries, often associated with chronic metabolic conditions or long-term steroid treatment. While the surgical treatment for acute QTRs is described thoroughly, no common strategy exists for the often frustrating treatment of chronic, reoccurring QTRs. The pro-angiogenic and im...

Chimeric Antigen Receptor (CAR) redirected T cells are a potent treatment option for certain hematological malignancies. Recently, site-specific insertion of CARs into the T cell receptor (TCR) alpha constant (TRAC) locus using gene editing and adeno-associated viruses was shown to generate CAR T cells with improved functionality over their retrovi...

Background: Anecdotally, cholinergic stimulation has been used to treat delirium and reduce cognitive dysfunction. Objective: The aim of this investigation was to evaluate whether physostigmine reduced the incidence of postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) in patients undergoing liver resection. Design: Th...

Chemotherapy has direct toxic effects on cancer cells; however, long-term cancer control and complete remission are likely to involve CD8 ⁺ T cell immune responses. To study the role of CD8 ⁺ T cell infiltration in the success of chemotherapy, we examined patients with muscle invasive bladder cancer (MIBC) who were categorized on the basis of the r...

Introduction Haemophagocytic lymphohistiocytosis (HLH) in adults is characterised by toxic immune activation and a sepsis-like syndrome, leading to high numbers of undiagnosed cases and mortality rates of up to 68%. Early diagnosis and specific immune suppressive treatment are mandatory to avoid fatal outcome, but the diagnostic criteria (HLH-2004)...

The intestine mediates a delicate balance between tolerogenic and inflammatory immune responses. The continuous pathogen encounter might also augment immune cell responses contributing to complications observed upon intestinal transplantation (ITx). We thus hypothesized that ITx patients show persistent signs of immune cell activation affecting bot...

The discovery of the highly efficient site-specific nuclease system CRISPR-Cas9 from Streptococcus pyogenes has galvanized the field of gene therapy. The immunogenicity of Cas9 nuclease has been demonstrated in mice. Preexisting immunity against therapeutic gene vectors or their cargo can decrease the efficacy of a potentially curative treatment an...

The hypothalamus has emerged as a novel neurogenic niche in the adult brain during the past decade. However, little is known about its regulation and the role hypothalamic neurogenesis might play in body weight and appetite control. High-fat diet (HFD) has been demonstrated to induce an inflammatory response and to alter neurogenesis in the hypotha...

Background Most current cell‐based regenerative therapies are based on the indirect induction of the affected tissues repair. Xenogeneic cell‐based treatment with expanded human placenta stromal cells, predominantly from fetal origin (PLX‐RAD cells), were shown to mitigate significantly acute radiation syndrome (ARS) following high dose irradiation...

Background: Parkinson's disease (PD) is characterized by dopaminergic cell loss and inflammation in the substantia nigra (SN) leading to motor deficits but also to hippocampus-associated non-motor symptoms such as spatial learning and memory deficits. The cognitive decline is correlated with impaired adult hippocampal neurogenesis resulting from d...

The parallel analysis of multiple factors, such as cytokines, from small sample size is an interesting approach for assessment of in vivo activation signatures and functionality after ex vivo stimulation. One interesting application is for therapy monitoring, such as safety data, pharmacodynamics, evidences for mode-of-action and side effects, part...

Bone marrow (BM) failure occurs in individuals who fail to produce sufficient red blood cells, white blood cells, or platelets. This may be a result of damage to hematopoietic stem cells by a congenital defect or by exposure to a noxious substance or factor. PLX-R18 are 3D-expanded placenta-derived cells, with biological properties including a prof...

Background and purpose: Temporary immunosuppression has been identified as a major risk factor for the development of pneumonia after acute central nervous system injury. Although overactivation of the sympathetic nervous system was previously shown to mediate suppression of systemic cellular immune responses after stroke, the role of the parasymp...

Although the immunomodulatory potency of mesenchymal stromal cells (MSC) is well established, the mechanisms behind are still not clear. The crosstalk between myeloid dendritic cells (mDC) and natural killer (NK) cells and especially NK cell-derived interferon-gamma (IFN-g) play a pivotal role in the development of Type 1 helper (Th1) cell immune r...

Mesenchymal stem cells (MSC) are easily harvested, and possess anti-inflammatory and trophic properties. Furthermore, MSC promote neuroprotection and neurogenesis, which could greatly benefit neurodegenerative disorders, such as Parkinson's disease. MSC were transplanted one week after 6-hydroxydopamine lesioning and effects were evaluated after 6...

We previously showed that the T cell activation inhibitor, mitochondrial (Tcaim) is highly expressed in grafts of tolerance-developing transplant recipients and that the encoded protein is localized within mitochondria. In this study, we show that CD11c(+) dendritic cells (DCs), as main producers of TCAIM, downregulate Tcaim expression after LPS st...

Lung diseases including pneumonia and asthma are among the most prevalent human disorders, and murine models have been established to investigate their pathobiology and develop novel treatment approaches. Whereas in patients bronchoscopy is valuable for diagnostic and therapeutic procedures, no equivalent for small rodents has been established. Her...

Einleitung: Die Bronchoskopie konnte bisher in kleinen Versuchstieren wie der Maus aufgrund der Größenverhältnisse nicht angewendet werden. Intratracheale und -bronchiale Applikationen erfolgten in vivo ausschließlich ohne direkte Sichtkontrolle. Methoden: In Zusammenarbeit mit der Polydiagnost GmbH wurde ein Mikroendoskop für kleine Labortiere en...

There is growing evidence that adaptive immunity contributes to endogenous regeneration processes: For example, endogenous bone fracture repair is modulated by T cells even in the absence of infection. Because delayed or incomplete fracture healing is associated with poor long-term outcomes and high socioeconomic costs, we investigated the relation...

Human cytomegalovirus infections have a major negative effect on morbidity and mortality of immunosuppressed allograft recipients and indirectly on graft function and survival. The adoptive antiviral T-cell therapy is a novel therapeutic tool to restore immune competence after solid organ transplantation. Till now, the antiviral T-cell products mai...

The transmembrane envelope protein gp41 of the human immunodeficiency virus HIV-1 plays an important role during infection allowing fusion of the viral and cellular membrane. In addition, there is increasing evidence that gp41 may contribute to the immunodeficiency induced by HIV-1. Recombinant gp41 and a synthetic peptide corresponding to a highly...

Absence of a correlation between the IL-6 release by PBMCs from 7 different donors and their SNP in the IL-10 promotor. Their PBMCs were incubated with the isu peptide homopolymer for 24 hrs at two different time point, the promoter of each donor was sequenced and the genetically expected IL-6 release is indicated. Donor B was not available at day...

Probes for the real-time RT-PCR analysis. (DOC)

Primers used for sequencing. (DOC)

Fifty cytokines with the highest increase in expression upon incubation of PBMCs with isu peptide polymers. The order is the result of a microarray comparing RNA from PBMCs incubated with the isu peptide homopolymer and from PBMCs incubated with medium. The expression of 27,000 genes was analysed. (DOCX)

Dependence of the Il-10 and IL-6 release on the donor PBMCs and the isu peptide polymer. A, PBMCs from one donor (A) was treated with 25 µg each of 3 different isu homopolymers (HP1-HP3), b, PBMCs from 9 donors (B to J) were treated with one and the same batch of an isu peptide homopolymer (HP4), c, PBMCs from one donor (L) was treated with 5 diffe...

Primers for the real-time RT-PCR analysis. (DOC)

Evolutionary conservation of the sequence of the isu domain. Human and simian immunodeficiency viruses were analysed, (.) marks identical amino acids, (*) marks deletions. Hatched amino acids represent conservative exchanges (A = S = T, I = L = M = V, R = K). (TIF)

Absence of a correlation between the IL-10 release by PBMCs from 7 different donors and their SNP in the IL-10 promotor. The PBMCs were incubated with the isu peptide homopolymer for 24 hrs at three different time points, the sequence of the relevant promoter region of each donor was determined and genetically expected IL-10 production is indicated...

Abbreviation and full names of the cytokines studied in the microarrays ( Table 1 ). (DOCX)

Fifty cytokines with the highest reduction in expression upon incubation of PBMCs with isu peptide polymers. The order is the result of a microarray comparing RNA from PBMCs incubated with the isu peptide homopolymer and from PBMCs incubated with medium. The expression of 27,000 genes was analysed. (DOCX)