Klinik und Poliklinik für Allgemein-, Viszeral-, Gefäß- und Kinderchirurgie (Chirurgische Klinik I)
Refine
Has Fulltext
- yes (232)
Is part of the Bibliography
- yes (232) (remove)
Year of publication
Document Type
- Journal article (215)
- Conference Proceeding (11)
- Doctoral Thesis (4)
- Other (2)
Language
- English (232) (remove)
Keywords
- Chirurgie (26)
- Medizin (9)
- inflammation (9)
- Immunbiologie (8)
- colorectal cancer (8)
- obesity (8)
- cytokines (6)
- Immunobiologie (4)
- Roux-en-Y gastric bypass surgery (4)
- bariatric surgery (4)
- inflammatory bowel disease (4)
- Ureaplasma parvum (3)
- anastomotic leakage (3)
- chemotherapy (3)
- evidence-based medicine (3)
- guidelines (3)
- incisional hernia (3)
- indication for surgery (3)
- intestinal epithelial barrier (3)
- laparoscopic ventral hernia repair (3)
- liraglutide (3)
- open abdomen (3)
- perioperative management (3)
- sepsis (3)
- 5-Fluorouracil (2)
- Aspergillus (2)
- COVID-19 (2)
- CRC (2)
- Caco2 cells (2)
- Cancer (2)
- Crohn's disease (2)
- DNA damage (2)
- Fn14 (2)
- Germany (2)
- Krebs (2)
- Krebs <Medizin> (2)
- Langerhans-Inseln (2)
- MYC (2)
- NAFLD (2)
- NFκB (2)
- Rectal cancer (2)
- SARS-CoV-2 (2)
- Surgery (2)
- TWEAK (2)
- Transplantation (2)
- Ureaplasma urealyticum (2)
- adaptive immunity (2)
- adrenocortical carcinoma (2)
- agonistic antibodies (2)
- animal model (2)
- anticoagulation (2)
- antimicrobial stewardship (2)
- atrial fibrillation (2)
- biomarker (2)
- bridging (2)
- cancer (2)
- case report (2)
- cell death (2)
- colon cancer (2)
- complication (2)
- dendritic cells (2)
- desmosome (2)
- endoluminal (2)
- enzyme activation (2)
- enzyme inhibitors (2)
- extracorporeal membrane oxygenation (2)
- gastric bypass (2)
- gastric cancer (2)
- giant ventral hernia (2)
- gut barrier (2)
- ileocecal resection (2)
- immunoassay (2)
- ischemia (2)
- islets of Langerhans (2)
- laparostomy (2)
- malignant melanoma (2)
- meta-analysis (2)
- metabolism (2)
- metastasis (2)
- microbial spectrum (2)
- mortality (2)
- negative pressure (2)
- oxaliplatin (2)
- pancreatic cancer (2)
- parastomal hernia (2)
- pediatric (2)
- peptide tyrosine tyrosine (PYY) (2)
- peritoneal carcinomatosis (2)
- phosphodiesterase (2)
- postoperative bleeding (2)
- preterm infants (2)
- primary ventral hernia (2)
- rat (2)
- rectum (2)
- skin (2)
- surgery (2)
- surgical therapy (2)
- swine (2)
- synthetic mesh (2)
- therapy (2)
- thromboembolism (2)
- translational research (2)
- transplantation (2)
- treatment (2)
- umbilical hernia (2)
- vacuum conditioning (2)
- vacuum-assisted closure (2)
- ventral hernia (2)
- 15-Deoxyspergualin (1)
- 1st-line treatment (1)
- 5-fluorouracil (1)
- 6-percent hydroxyethyl starch (1)
- AAA (1)
- ALCL (1)
- Activation (1)
- Adrenocortical Carcinoma (1)
- Allergie (1)
- Allopeptidb (1)
- Allotransplantatabstossung (1)
- Apoptosis (1)
- Attentional performance (1)
- Autologous (1)
- BM (1)
- Barrett-Ösophagus (1)
- Bauchspeicheldrüsenkrebs (1)
- Beta-catenin (1)
- Blood–brain barrier (1)
- Brain μ-opioid receptors (1)
- C-MYC (1)
- CA19-9 (1)
- CASP (1)
- CCR7 (1)
- CD62L (1)
- CD8+ T cells (1)
- CIP2A (1)
- CNS integrity (1)
- COVID-19 pandemic (1)
- CT angiography (1)
- CX3CL1 (1)
- CX5461 (1)
- CXCL13 (1)
- Cancer immunotherapy (1)
- Carcinoma cells (1)
- Carcinomatosis (1)
- Central venous access (1)
- Central venous-pressure (1)
- ChIPseq (1)
- Chemotherapeutic resistance (1)
- Class II antigen blockade (1)
- Claudin2 (1)
- Cognitive (1)
- Coronary artery bypass graft (1)
- Coronavirus Disease 2019 (1)
- Critically-ill patients (1)
- Crohn’s Disease (1)
- Crohn’s disease (1)
- Cryolesion (1)
- Cushing (1)
- DNA repair (1)
- Danish hernia database (1)
- Diabetes (1)
- Dickdarmkrebs (1)
- Dsg2 (1)
- Dünndarm (1)
- EDS (1)
- EHS classification (1)
- ERK (1)
- Ehlers-Danlos syndrome (1)
- Elective cesarean-section (1)
- Electrical impedance tomography (1)
- EndoVAC and small bowel (1)
- Epstein-Barr virus (1)
- Experimental brain trauma (1)
- Expression (1)
- Extra-anatomical (1)
- FWGE (1)
- Fascia transversalis (1)
- FcγR (1)
- Femoral vein (1)
- Fibroblasts (1)
- Fluorouracil (1)
- Foxp3 (1)
- GDNF5 (1)
- GIST (1)
- GLP-1 (1)
- General anaesthesia (1)
- Groin infection (1)
- Growth-factor receptor (1)
- Göttingen (1)
- HBMEC (1)
- Heterotransplantation (1)
- Hickman catheter (1)
- High-fat diet (1)
- Hypertonic saline 7.5-percent (1)
- IL-6 (1)
- IVF-methods (1)
- Ileal conduit (1)
- Ileum-Conduit (1)
- Immunologie (1)
- Immunosenescence (1)
- Immunotherapy (1)
- Improved survival (1)
- In vitro models (1)
- Inhibition (1)
- Invasion (1)
- Inzisionale Hernie (1)
- Inzisionalhernie (1)
- KIT (1)
- Kono-S anastomosis (1)
- LAMN (1)
- LND (1)
- LNE (1)
- Lactated ringers solution (1)
- Laparoscopy (1)
- Leistenhernie (1)
- Leptin (1)
- Lernkurve (1)
- Linea alba (1)
- Low-fat diet (1)
- LyP (1)
- Lymph nodes (1)
- MAPK pathway (1)
- MAPK signaling cascades (1)
- MHC I (1)
- MHC Klasse II (1)
- MHC-Klass I (1)
- MITF (1)
- MIZ1 (1)
- MPFL (1)
- MRI (1)
- MTL30 (1)
- Major abdominal surgery (1)
- Makrophage (1)
- Mammalian target (1)
- Matrix (1)
- Melanom (1)
- Melanoma (1)
- Merkel cell carcinoma (1)
- Merkelzellkarzinom (1)
- Mesh Augmentation (1)
- Metastatic breast cancer (1)
- Mice (1)
- Minimalinvasiv (1)
- Minimalinvasive Leistenhernienversorgung (1)
- Minimally invasive surgery (1)
- Minischwein (1)
- Modifizierte Sugarbaker-Technik (1)
- Monoclonal antibody (1)
- Multicenter randomized-trial (1)
- NASH (1)
- NFATc1 (1)
- NPWT (1)
- Niere (1)
- Obturator bypass (1)
- Oncology (1)
- Organoids (1)
- Organtransplantation (1)
- P-glycoprotein (1)
- PCI (1)
- PCR (1)
- PDE (1)
- PDE4-I (1)
- PDGF (1)
- PET (1)
- PET imaging (1)
- PI-3-kinase (1)
- PI3K/Akt/mTOR (1)
- PLAG1 rearrangement (1)
- POEM (1)
- PYY3-36 (1)
- Parastomale Hernie (1)
- Pathway (1)
- Pauli procedure (1)
- Pauli-Verfahren (1)
- Pediatric malignancy (1)
- Peptidanaloge (1)
- Port (1)
- Posteriore Komponentenseparation (1)
- Postoperative complications (1)
- Predict fluid responsiveness (1)
- Primary hyperparathyroidism (pHPT) (1)
- Pulmonary function tests (1)
- Puls-pressure variation (1)
- RET6 (1)
- RNAPOL1 (1)
- RYGB (1)
- Radical prostatectomy (1)
- Radiochemotherapy (1)
- Randomized controlled-trial (1)
- Ratte (1)
- Regulatorischer T-Lymphozyt (1)
- Regulatory T cells (1)
- Retromuskuläres Netz (1)
- Retrorektus Netz (1)
- Robotik (1)
- Roux-en-Y gastric bypass (1)
- SSI (1)
- ST18 (1)
- Secondary traumatic brain damage (1)
- Serom (1)
- Severe Acute Respiratory Syndrome Coronavirus 2 (1)
- Surgical and invasive medical procedures (1)
- Surgical oncology (1)
- T cell receptors (1)
- T cells (1)
- TCR (1)
- TCR signaling cascade (1)
- TEER (1)
- TLR2 (1)
- TLR4 (1)
- TLR7 (1)
- TLR8 (1)
- TLR9 (1)
- TME (1)
- TNF (1)
- TNF receptor superfamily (1)
- TREC (1)
- Telomere (1)
- Thrombosis (1)
- Time interval (1)
- Tissue (1)
- Toll-like receptor signaling (1)
- Toll-like-Rezeptoren (1)
- Trichternetz (IPST) (1)
- Tumorerkrankungen (1)
- Umbilikalhernie (1)
- Up-regulation (1)
- V. saphena magna (1)
- VAC (1)
- VLBW (1)
- Ventrale Hernie (1)
- Y-gastric bypass (1)
- ZfKD (1)
- Zucker fatty fa/fa rats (1)
- [11C]-Choline PET/CT (1)
- [11C]-Methionine (1)
- [18F]FDG-PET-CT (1)
- [99mTc]-Sestamibi scan (1)
- abdominal compartment syndrome (1)
- abdominal lymph node metastases (1)
- abdominal surgery (1)
- abdominal trauma (1)
- abdominal wall hernia (1)
- abdominal wall surgery (1)
- accumulation (1)
- achalasia (1)
- acute (1)
- acute appendicitis (1)
- acute kidney injury (1)
- acute liver failure (1)
- acute respiratory distress syndrome (1)
- adipose-derived stromal/stem cells (ASCs) (1)
- adiposity (1)
- adjuvant (1)
- adrenal cancer (1)
- adrenal surgery (1)
- adrenal tumors (1)
- adrenalectomia (1)
- adrenocortical (1)
- adrenocortical adenocarcinoma (1)
- allograft rejection (1)
- allopeptide (1)
- alternative splicing (1)
- alveolar epithelium (1)
- anal atresia (1)
- anaplastic large cell lymphoma (1)
- anastomosis (1)
- anastomotic leak (1)
- anorectal abscess (1)
- anorectal angl (1)
- anorectal malformation (1)
- anti-tumor effects (1)
- antibiotic prescribing quality (1)
- antibiotic prescription behavior (1)
- antibiotic resistance (1)
- antibiotics (1)
- antithrombotic therapy (1)
- appendectomy (1)
- appendicitis (1)
- appendix (1)
- assisted reproductive techniques (1)
- autophagy (1)
- barrier models (1)
- benzoquinone (1)
- beta cells (1)
- biliopancreatic diversion (1)
- biological models (1)
- birth defects (1)
- bladder (1)
- blood (1)
- blood samples (1)
- blood-nerve barrier (1)
- blood–brain barrier (1)
- body fat (1)
- body mass index (BMI; kg/m\(^2\)) (1)
- body weight (1)
- bone marrow (1)
- brain metastases (1)
- brain plasticity (1)
- breast cancer (1)
- bronchopulmonary dysplasia (1)
- brown adipose tissue (1)
- bullae (1)
- burst abdomen (1)
- caco-2 cells (1)
- cadaver multiorgan preservation (1)
- caloric-restriction (1)
- cancer cells (1)
- cancer diagnosis (1)
- cancer risk (1)
- cancer treatment (1)
- cancers and neoplasms (1)
- capture (1)
- carcinogenesis (1)
- carcinoma metastases to pancreas (1)
- carcinomas (1)
- cardiogenic (1)
- catheterization (1)
- catheters (1)
- cell cycle and cell division (1)
- cellular senescence (1)
- cerebEND (1)
- cerebral metastases (1)
- chemistry (1)
- chemokine receptor (1)
- children (1)
- children born (1)
- cholestasis (1)
- chylomicron (1)
- colloids (1)
- colon (1)
- colon carcinoma cells (1)
- colon resection (1)
- colorectal carcinoma (1)
- comet assay (1)
- complications (1)
- computed tomography angiography (CTA) (1)
- congenital malformations (1)
- continuous extracorporeal femoral perfusion model (1)
- conventional laparoscopic appendectomy (1)
- cord blood (1)
- cost-effectiveness (1)
- cotransporter SGLT1 (1)
- creatinine (1)
- curative resection (1)
- cytostatic (1)
- cytotoxicity (1)
- dass II antigen blockade (1)
- deconstruction into key steps (1)
- definition (1)
- dendritische Zellen (1)
- descriptive epidemiology (1)
- desmoglein (1)
- dexamethasone (1)
- diabetes (1)
- diagnosis (1)
- diagnostics (1)
- digital subtraction angiography (DSA) (1)
- discharge definition (1)
- drug-eluting beads (1)
- dual-room whole-body CT (1)
- duodenal jejunal bypass (1)
- duodenal perforation (1)
- duodenal trauma (1)
- elective surgery (1)
- endoscopic (1)
- endoscopic full thickness resection (eFTR) (1)
- endoscopic groin hernia repair (1)
- endosponge (1)
- endotoxemia (1)
- endovascular repair (1)
- energy homeostasis (1)
- enteric glial cells (1)
- enteric nervous system (1)
- enteroids (1)
- ephitelial cells (1)
- epidemiology (1)
- epidural block (1)
- epigastric hernia (1)
- epithelial cells (1)
- epithelium (1)
- erratum (1)
- esophageal perforation (1)
- expenditure (1)
- experimental models of disease (1)
- experimental therapy (1)
- extremity trauma (1)
- fascial closure (1)
- fat absorption (1)
- fat appetite (1)
- fatty liver (1)
- femoral arteries (1)
- femoral hernia (1)
- fish bone (1)
- fistulizing Crohn’s Disease (1)
- flow cytometry (1)
- focused surgical approach (1)
- folinic acid (1)
- food intake (1)
- foreign body ingestion (1)
- fracture-associated vascular damage (1)
- full-thickness resection device (FTRD) (1)
- funnel mesh (IPST) (1)
- gastric-bypass surgery (1)
- gastrointestinal cancer (1)
- gastrointestinal infections (1)
- gastrointestinal perforation (1)
- gastrointestinal tract (1)
- gemcitabine (1)
- gene regulation (1)
- generation (1)
- geriatric (1)
- germline mutation (1)
- glucagon like peptide-1 (1)
- glucocorticoid receptor (1)
- glucose homeostasis (1)
- glucose metabolism (1)
- glucose starvation (1)
- groin hernia (1)
- growth differentiation factor 15 (1)
- gut hormones (1)
- hematology (1)
- hemorrhagic (1)
- henoch-schönlein purpura (1)
- hepatic resection (1)
- hepatocellular carcinoma (1)
- hernia (1)
- hernia defect (1)
- hernia repair material (1)
- heterologous (1)
- histologic diversity (1)
- histopathology (1)
- human biomonitoring (1)
- human cancer (1)
- human melanoma (1)
- hypersensitivity (1)
- hypothalamic gene expression (1)
- hypoxia (1)
- idiopathic fecal incontinence (1)
- imaging (1)
- immaturity (1)
- immundominant (1)
- immune check inhibitor (1)
- immune response (1)
- immunity (1)
- immunodominant (1)
- immunosuppression (1)
- immunotherapeutics (1)
- impedance spectroscopy (1)
- imperforate anus (1)
- in vitro model (1)
- in vivo (1)
- in-vitro fertilization (1)
- incisional abdominal wall hernia (1)
- induced obesity (1)
- infants born (1)
- inflammation-induced tissue demage (1)
- inflammatory cell model (1)
- inguinal hernia (1)
- inguinal lymph node dissection (1)
- insulin resistance (1)
- intercellular junctions (1)
- intestinal barrier (1)
- intestinal glucose (1)
- intestinal microbiota (1)
- intestinal organoids (1)
- intestine (1)
- intraabdominal abscess (1)
- intragastric balloon (1)
- intravascular ultrasound (IVUS) (1)
- intravenous glucose tolerance test (1)
- ionizing radiation (1)
- irinotecan (1)
- islet transplantation (1)
- isocaloric intake (1)
- isosteviol sodium (STVNA) (1)
- kappa-B (1)
- ketogenic dients (1)
- ketogenic diet (1)
- ketone bodies (1)
- kidney (1)
- kidneys (1)
- la antigens (1)
- laparoscopic appendectomy (1)
- laparoscopic course (1)
- laparoscopic right colectomy (1)
- laparoscopic skills (1)
- laparoscopy (1)
- late onset sepsis (1)
- learning curve (1)
- left hemicolectomy (1)
- leptin (1)
- leptin system (1)
- leukemia (1)
- level of evidence: IV (1)
- linea alba (1)
- lipoblastoma (1)
- lipodystrophy (1)
- liver resection (1)
- locally advanced disease (1)
- low molecular heparin (1)
- low-grade mucinous neoplasm (1)
- low-molecular heparin (1)
- low-risk intra-abdominal infections (1)
- lung resection (1)
- lymph node dissection (1)
- lymph nodes (1)
- lymphadenectomy (1)
- lymphomatoid papulosis (1)
- magnetic resonance imaging (1)
- maintain immune homeostasis (1)
- management (1)
- mass (1)
- mastocytosis (1)
- measles virus (1)
- medial patellofemoral ligament (1)
- meningitis (1)
- mesenchymal stem cells (1)
- mesh augmentation (1)
- mesh repair (1)
- metaanalysis (1)
- metabolic profile (1)
- metabolically unhealthy obesity (1)
- metachronous (1)
- miRNA expression (1)
- mice (1)
- microbiota (1)
- mild hypothermia (1)
- minimally invasive (1)
- modified Sugarbaker technique (1)
- mold exposure (1)
- molecular diagnostics (1)
- monocyte subsets (1)
- monocytes (1)
- mortality rate (1)
- mucormycosis (1)
- mucosal healing (MH) (1)
- multimodal (1)
- myeloid (1)
- nab-paclitaxel (1)
- negative pressure wound therapy (1)
- neoadjuvant (1)
- neoadjuvant chemotherapy (1)
- neonatal immunology (1)
- neonatal meningitis (1)
- neonatal outcome (1)
- netrin-1 (1)
- neuroblastoma – diagnosis (1)
- neuroendocrine tumor (NET) (1)
- neuroinflammation (1)
- neuropathic pain (1)
- neurotrophic factors (1)
- noradrenaline (1)
- noradrenaline transporter (1)
- novel human cadaveric perfusion model (1)
- obesity surgery (1)
- octogenarians (1)
- octogenerians (1)
- older adult (1)
- oncogene-induced senescence (1)
- open appendectomy (1)
- open wound treatment (1)
- operative (1)
- oral anticoagulants (1)
- organoid (1)
- outcome (1)
- pancreas Islets (1)
- pancreatectomy (1)
- pancreatic adenocarcinoma (PDAC) (1)
- pancreatic head cancer (1)
- parathyroid adenoma (1)
- parathyroid carcinoma (1)
- patella alta (1)
- patella dislocation (1)
- patella instability (1)
- pathway analysis (1)
- patient-derived organoid (PDOs) (1)
- patient-derived tumor organoid (PDTO) (1)
- pediatric adrenocortical adenoma (1)
- pediatric adrenocortical cancer (1)
- pediatric adrenocortical tumor (1)
- pelvic trauma (1)
- pembrolizumab (1)
- pemphigus (1)
- penetrating ileitis (1)
- peptide analogs (1)
- peptide tyrosine tyrosine 3-36 (PYY3-36) (1)
- peptide tyrosine tyrosine 3-36 (PYY\(_{3-36}\)) (1)
- perianal fistulas (1)
- perioperative antibiotic prophylaxis (1)
- perioperative chemotherapy (1)
- periphery-brain interactions (1)
- peritonitis (1)
- permeability (1)
- peroral endoscopic myotomy (1)
- phosphodiesterase-4 (1)
- phosphodiesterase-inhibitors (1)
- photon-counting computed tomography (CT) (1)
- pig or swine (1)
- platelet dysfunction (1)
- popliteal aneurysm (1)
- positron emission tomography imaging (1)
- post-mortem heart recovery (1)
- post-operative antibiotic treatment (1)
- posterior component separation (1)
- postoperative inflammation (1)
- preclinical research (1)
- preoperative localization (1)
- preterm birth (1)
- prevalence (1)
- primary hyperparathyroidism (1)
- primär ventrale Hernie (1)
- prognosis (1)
- prognostic factors (1)
- prospective studies (1)
- protein expression (1)
- protein kinase D2/PKD2/PRKD2 (1)
- protein synthesis (1)
- quality of life (1)
- radiotracer (1)
- reactivating p53 and inducing tumor apoptosis (RITA) (1)
- reactive oxygen (1)
- reactive oxygen species (1)
- real-time glucose monitoring (1)
- rectal cancer (1)
- rectal resection (1)
- recurrence survival (1)
- recurrent abdominal wall hernia (1)
- regeneration (1)
- regenerative medicine (1)
- regional recurrence (1)
- regionalization and organoids (1)
- registries (1)
- regulatory T cells (1)
- renal transplantation (1)
- repeat surgery (1)
- repeated surgery (1)
- reproductive medicine (1)
- resuscitation time (1)
- retromuscular mesh (1)
- retroperitoneal tumor (1)
- retrorectus mesh (1)
- retrospective study (1)
- reverse transcriptase-polymerase chain reaction (1)
- review (1)
- ribosome (1)
- risk factor (1)
- risk factors (1)
- robotic surgery (1)
- robotic surgical procedures (1)
- rolipram (1)
- rygb (1)
- sacral nerve stimulation (1)
- sacral neuromodulation (1)
- screening (1)
- seahorse (1)
- secondary skin closure (1)
- secretion (1)
- seminoma (1)
- septic (1)
- seroma (1)
- serotonin (1)
- serotonin transporter (1)
- shock (1)
- single-port appendectomy (1)
- sleeve gastrectomy (1)
- small bowel (1)
- small interferring RNA (1)
- small pixel effect (1)
- streptozotocin (1)
- super-obesity (1)
- superior (1)
- surgical (1)
- surgical and invasive medical procedures (1)
- surgical care (1)
- surgical complications (1)
- surgical intra-abdominal infections (1)
- surgical management (1)
- surgical oncology (1)
- surgical outcome (1)
- surgical procedures (1)
- surgical resection (1)
- surgical site infection (1)
- surgical site infections (1)
- surgical trauma room (1)
- surgical treatment (1)
- survival (1)
- survival analysis (1)
- sympathetic nervous system (1)
- systematic review (1)
- systemic and cutaneous CD30+ lymphoproliferations (1)
- systemic endotoxemia (1)
- teaching methods (1)
- technology (1)
- terminal ileitis (1)
- thermogenesis (1)
- thyroid gland (1)
- thyroiditis (1)
- tight junction (1)
- tight junction proteins (1)
- tissue (1)
- tolerance (1)
- total pancreatectomy (1)
- transanal endoscopic microsurgery (TEM) (1)
- transarterial chemoembolization (1)
- translation (1)
- translation initiation (1)
- transplant (1)
- transstomal endoluminal vacuum therapy (1)
- transverse fascia (1)
- trauma centre (1)
- trauma management (1)
- trochlear dysplasia (1)
- trophic factors (1)
- tumor disease (1)
- tumor growth (1)
- type 2 diabetes (1)
- ultrahigh resolution (1)
- uncoupling protein 1 (1)
- urinary tract infections (1)
- urine (1)
- vascular type (1)
- vasculitis (1)
- ventral hernia model (1)
- visceral fat (1)
- vitamin D (1)
- volume (1)
- warfarin interruption (1)
- weight-gain (1)
- wound infection (1)
- xenogeneic transplantation (1)
- xenogenic transplantation (1)
- β-Hydroxybutyrate (1)
Institute
- Klinik und Poliklinik für Allgemein-, Viszeral-, Gefäß- und Kinderchirurgie (Chirurgische Klinik I) (232)
- Theodor-Boveri-Institut für Biowissenschaften (34)
- Medizinische Klinik und Poliklinik II (23)
- Comprehensive Cancer Center Mainfranken (20)
- Medizinische Klinik und Poliklinik I (19)
- Institut für diagnostische und interventionelle Radiologie (Institut für Röntgendiagnostik) (16)
- Klinik und Poliklinik für Anästhesiologie (ab 2004) (15)
- Kinderklinik und Poliklinik (14)
- Pathologisches Institut (13)
- Institut für Anatomie und Zellbiologie (8)
Sonstige beteiligte Institutionen
Because successful human islet transplantation requires large quantities of viable islets that must be separated from the highly immunogenic exocrine tissue and because handpicking is too time-consuming and laborious to be clinically relevant, a new approach for solving this problem has been established in rat models. It is based on the principle that magnetic microspheres (MMSs) coupled to lectins with binding specificity for the exocrine tissue portion are trapped in an electromagnetic field, thus providing effluent islets of a high degree of purity. In this study our aim was to adapt this princip'le to human islet preparations. In this context our prime interest was focused on a lectin suitable for human pancreatic tissue. Of 19 different lectins tested, only 1, Wisteria floribunda agglutinin (WFA), is suitable, as shown by immunofluorescence, MMS-Iectin binding, and magnetic separation
An immunogold-silver enhancement technique, which combines effective labeling of viable isolated islets with the ultrastructural resolution of cytological details, was applied in electron microscopy to identify major histocompatibility complex (MHC) structures on islet cells. Incubation of freshly isolated islets from CAP (RT1C) and LEW (RT1') rats with OX18, an MHC class I antibody, showed strong positive reactivity in macrophages and/or dendritic-like cells (M0-DCs) and vascular endothelial cells (VEs) and a comparatively weaker reactivity in endocrine a-, p-, and 8-ce"s. With MHC class" antibody OX6 (anti-I-A), M0-DCs were strongly labeled in both rat strains on the surface and on internal structures. Three of five particularly high titered batches of OX6 revealed MHC class" expression on VE and p-ce"s. Four days of in vitro culture in combination with a high concentration of glucose and interferon-'Y induced strong enhancement of MHC class I structures and, to a lesser extent, class " structures on p-ce"s.
Total immunoreactive insulin (IRI) is conventionally determined by radioimmunoassays. IR! measurement in rats can be made more sensitive, accurate, and practical, as demonstrated by a new modified enzyme-linked immunosorbent assay (ELlSA). It is characterized by indirect binding of an anti-insulin antibody by an antiglobulin antibody and uses the principle of competitive saturation. In this ELlSA, IRI can be determined in a wide range of concentrations, corresponding to the standards. The standard curve ranges from 100 to 0.049 ng/mllRI (1 ng/ml - 23.4 JLU/ml - 172 pM rat insulin). The statistical analysis shows between- and within-assay coefficients of variation of :515%. Diabetes 37:321-26,1988
Solid organ transplantation is an established therapeutic approach in modern medicine to extend and to improve the life of patients in the final stages of organ failure. Transplantation between genetically non-identical individuals leads to the activation of the transplant recipient's immune system. This alloimmune response is a consequence of the recognition of foreign MHC molecules by alloreactive host T cells. To prevent their activation and the subsequently induced activation of further cell subsets (e.g. B cells, cytotoxic T cells, macrophages)immunosuppressive drugs are absolutely necessary in the clinic. However,permanent immunosuppression leads to severe side effects such as nephrotoxicity, diabetes and hyperlipidaemia, and a reduced immunity to infections and malignant diseases. At the moment, there is no real alternative to immunosuppression. The purpose of this study was to analyse the importance of rat dendritic cells with immune inhibitory properties to prevent the immune activation after experimental transplantation. The rat is one of the most important animal models for experimental organ transplantation in a clinic-relevant procedure. In order to modulate the immune response after transplantation in an antigenspecific manner, the strategy should include the alloantigens. These antigens have to be presented by immature dendritic cells in the absence of costimulatory signals in order to turn alloreactive T cells into anergic or regulatory T cells instead of effector T cells. For a certain rat model of allograft rejection,the immunodominant peptide P1 was identified as an important alloantigen which accelerates graft rejection. Such a model offers an attractive and practical approach to analyse the potential of host tolerogeneic dendritic cells pulsed with P1 to suppress the allograft-induced immune response in an antigen-specific manner without the need of chronic immunosuppression. A homogenous population of rat immature dendritic cells was generated from bone marrow precursors cultured with GM-CSF and IL-4 (= IL-4 DCs) or GM65 CSF and IL-10 (= IL-10 DCs). These cells with an identical immature phenotype showed no or a very low surface expression of costimulatory molecules like CD80 and CD86 and a 10-fold reduced expression of MHC class II molecules in comparison to mature splenic DCs. No obvious difference was observed between the phenotype of the IL-4 DCs and the IL-10 DCs. Neither IL-4 DCs nor IL-10 DCs were able to activate naïve T cells or to restimulate antigen-specific T cells. This strong inhibitory effect, mediated within 24 hours, was dependent on the number of immature dendritic cells added to the proliferation assay. Antigen-specific T cells pre-incubated with IL-4 DCs and IL-10 DCs, respectively, were not able to proliferate in the presence of P1-pulsed mature DCs. This anergic state was reversible with the addition of exogenous IL-2. T cells incubated with IL-4 DCs (= IL-4 DC-Ts) were able to inhibit the T cell proliferation in a cell number dependent manner. In contrast, antigen-specific T cells pre-incubated with P1-pulsed IL-10 DCs (= IL-10 DC-Ts)showed no effect on the proliferation assay. This was the unique difference between IL-4 DCs and IL-10 DCs found in the present study. Immature DCs influenced also the immune response after transplantation. Different numbers of P1-loaded immature IL-4 DCs and IL-10 DCs were transferred intravenously into Lewis rats one day before transplantation. The best results were obtained with 30 million P1-pulsed immature DCs which prolonged the survival time to a median of 11.2 ± 1.6 days. In addition, the antigen specificity of this effect was demonstrated with a third-party graft from Brown Norway donors. These findings suggest that an antigen-specific modulation of the immune response is possible using immature dendritic cells loaded with the allogeneic antigens. Even more, the protocols described in the present study show that the immune system can be, at least temporarily, controlled after transplantation without the use of immunosuppressive drugs.
Transplantation is now firmly established as a therapeutic approach to extend and improve the life of patients in the final stages of organ failure. It has been demonstrated that transplantation between genetically non-identical individuals leads to the activation of the recipient’s alloimmune response as a major determinant of transplant outcome. T cell recognition of foreign MHC molecules plays a key role in initiating and sustaining allograft rejection. To prevent the risk of rejection, patients are given immunosuppressive drugs, which are non-specific and have major side-effects (infections, malignancies). It has been shown that the alloreactive T cells specifically recognize donor MHC-derived peptides. This implies that it may be possible to develop antigen-specific strategies in order to modulate the alloimmune response by peptide analogues and specifically altered peptide ligands. The purpose of this study was to explore the potential of “recipient-adapted” analogues from the dominant MHC class I peptide to modulate the alloimmune response. Beside the significant role of donor dominant determinants in the rejection process, we tested seven 13-to-24-mer peptides from the Wistar-Furth MHC class I molecule (WF, RT1.Au) for their possible immunogenicity in a fully MHC-mismatched WF to Lewis (LEW, RT1l) rat strain combination. Secondly, the immunodominant allopeptide was selected to generate analogues in order to investigate their modulatory capacity. All peptides were tested in vitro in a standard proliferation assay and in vivo using a heterotopic heart transplantation model. Our findings show that five peptides (P1-P5) were able to induce specific T cell proliferation in LEW responders. Furthermore, we found a hierarchical distribution of the determinants: peptide P1 as a good candidate for the immunodominant determinant, while P2, P3, P4, and P5 as subdominant epitopes and the other two peptides, P6 and P7, as non-immunogenic determinants of WF MHC class I molecule. Furthermore, the dominance of P1 was confirmed by the strong proliferation induced after immunization with a mixture of peptides in the presence of P1. This hierarchical distribution of the proliferative response correlated with the cytokine production. Peptide P1, comprising only 3 allogeneic amino acids (L5, L9, and T10) induced the strongest T cell proliferation and produced high levels of cytokines, especially IL-2 and IFN-g. In addition, the immunodominance of peptide P1 was confirmed by the significant reduction in the allograft survival time in comparison to the non-immunized control animals. Since the TCR Vß repertoire of rejected graft-infiltrating cells in rejected allografts was similar to the profile observed after in vitro restimulation of P1-primed T cells, we concluded that peptide P1 is able to activate the alloreactive T cell population. Our results demonstrate the particular role of the dominant peptide P1 (residues 1-19) in the allograft rejection in WF to LEW rat strain combination. In the second set of experiments, we investigated the fine specificity of the dominant peptide P1-activated T cells using peptide analogues from P1. The “recipient-adapted” analogues were designed by changing the allogeneic RT1.Au amino acids (L5, L9, T10) one-by-one with the correspondent syngeneic RT1.Al amino acids (M5, D9, I10) in the sequence of peptide P1. The six peptide analogues (A1.1-A1.6) consisting of either one or two allogeneic amino acids were able to induce a specific T cell proliferative response and cytokine production. Analogue A1.5 with only one allogeneic amino acid (L5) was of particular interest because it induced a low T cell proliferation and high cytokine levels, especially IL-4 and IL-10. In addition, immunization with A1.5 did not influence the allograft survival time in comparison to the non-immunized LEW recipients. A1.5 was the only analogue able to down-regulate the proliferation of P1-primed T cells. Our results reveal that A1.5 is an MHC competitor as confirmed by the in vitro MHC competition assay and the inhibition of the negative effect of P1 on the allograft survival time when recipients were immunized with a mixture of P1 and A1.5. These findings suggest that it is possible to design peptide analogues, such as A1.5, which do not stimulate the dominant peptide P1-specific T cell population and even more, are able to block its presentation in the MHC molecule. In all, the results indicate that the specific suppression of indirect allorecognition can be achieved by using peptide analogues of the dominant allopeptide.