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Enhancement of Antiviral T-Cell Responses by Vitamin C Suggests New Strategies to Improve Manufacturing of Virus-Specific T Cells for Adoptive Immunotherapy.
No full textAllogeneic and autologous transplantation of hematopoietic stem cells (HSCT) are being routinely used to treat patients with leukemia and lymphoma. Due to the required immunosuppression after stem cell transplantation, infection and reactivation by viruses are life-threatening complications. In recent years, adoptive transfer using virus-specific T cells (VSTs) has emerged as alternative to conventional therapies. Since vitamins are described to influence the immune system and its cellular components, the aim of this study was to examine whether vitamins modulate VST function and thereby enable an improvement of therapy. For that, we investigated the impact of vitamin C and D on the functionality of cytomegalovirus (CMV)-specific T cells isolated from CMV-seropositive healthy donors. We were able to show that vitamin C increases the expansion and activation state of CMV-specific T cells, and an increased influence of vitamin C was observed on cells isolated from male donors and donors above 40 years of age. A higher frequency of the terminally differentiated effector memory CD8+ T-cell population in these donors indicates a connection between these cells and the enhanced response to vitamin C. Thus, here we provide insights into the impact of vitamin C on cytotoxic T cells as well as possible additional selection criteria and strategies to improve VST functionality
Morbiditätskompression oder -expansion in der gesundheitsbezogenen Lebensqualität in Deutschland?: Analyse der Veränderung der körperlichen und psychischen Lebensqualität sowie der Lebenserwartung ohne deutliche Einschränkungen zwischen 2002 und 2014 auf der Datenbasis des Soziökonomischen Panels
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Kappa Free Light Chains in Cerebrospinal Fluid in Inflammatory and Non-Inflammatory Neurological Diseases.
No full textOligoclonal bands represent intrathecal immunoglobulin G (IgG) synthesis and play an important role in the diagnosis of multiple sclerosis (MS). Kappa free light chains (KFLC) are increasingly recognized as an additional biomarker for intrathecal Ig synthesis. However, there are limited data on KFLC in neurological diseases other than MS. This study, conducted at two centers, retrospectively enrolled 346 non-MS patients. A total of 182 patients were diagnosed with non-inflammatory and 84 with inflammatory neurological diseases other than MS. A further 80 patients were classified as symptomatic controls. Intrathecal KFLC production was determined using different approaches: KFLC index, Reiber's diagram, Presslauer's exponential curve, and Senel's linear curve. Matching results of oligoclonal bands and KFLC (Reiber's diagram) were frequently observed (93%). The Reiber's diagram for KFLC detected intrathecal KFLC synthesis in an additional 7% of the patient samples investigated (4% non-inflammatory; 3% inflammatory), which was not found by oligoclonal band detection. The determination of both biomarkers (KFLC and oligoclonal bands) is recommended for routine diagnosis and differentiation of non-inflammatory and inflammatory neurological diseases. Due to the high sensitivity and physiological considerations, the assessment of KFLC in the Reiber's diagram should be preferred to other evaluation methods
Shopping-related decisions, materialistic values endorsement, compulsive buying-shopping disorder symptoms and everyday moral decision making
No full textDie Daten wurden von Juni bis September 2019 i. R. eines SoSci Online Survey (SoSci Survey GmbH, Munich, Germany) von der Arbeitsgruppe "Substanzungebundene Abhängigkeitserkrankungen" der Klinik für Psychosomatik und Psychotherapie der MHH erhoben. Das Projekt wurde von Prof'in Dr. med. Dr. phil. Astrid Müller geleitet. Die Daten wurden für folgende Publikation verwendet: Müller et al. The relationship of shopping-related decisions with materialistic values endorsement, compulsive buying-shopping disorder symptoms and everyday moral decision making. Int. J. Environ. Res. Public Health 2022, in press. Im Sinne einer Open-Access-Policy werden die Daten im SPSS-Format für andere Wissenschaftler:innen zugängig gemacht. Am Ende des Manuskripts findet sich folgendes Data Availability Statement: "The data presented in study 2 are openly available in RepoMed at [10.26068/mhhrpm/20220404-001].
Preliminary application of native Nephila edulis spider silk and fibrin implant causes granulomatous foreign body reaction in vivo in rat's spinal cord.
No full textAfter spinal cord injury, gliomesenchymal scaring inhibits axonal regeneration as a physical barrier. In peripheral nerve injuries, native spider silk was shown to be an effective scaffold to facilitate axonal re-growth and nerve regeneration. This study tested a two-composite scaffold made of longitudinally oriented native spider silk containing a Haemocomplettan fibrin sheath to bridge lesions in the spinal cord and enhance axonal sprouting. In vitro cultivation of neuronal cells on spider silk and fibrin revealed no cytotoxicity of the scaffold components. When spinal cord tissue was cultured on spider silk that was reeled around a metal frame, migration of different cell types, including neurons and neural stem cells, was observed. The scaffold was implanted into spinal cord lesions of four Wistar rats to evaluate the physical stress caused on the animals and examine the bridging potential for axonal sprouting and spinal cord regeneration. However, the implantation in-vivo resulted in a granulomatous foreign body reaction. Spider silk might be responsible for the strong immune response. Thus, the immune response to native spider silk seems to be stronger in the central nervous system than it is known to be in the peripheral body complicating the application of native spider silk in spinal cord injury treatment
Single Application of Low-Dose, Hydroxyapatite-Bound BMP-2 or GDF-5 Induces Long-Term Bone Formation and Biomechanical Stabilization of a Bone Defect in a Senile Sheep Lumbar Osteopenia Model
No full textEffects of hydroxyapatite (HA) particles with bone morphogenetic BMP-2 or GDF-5 were compared in sheep lumbar osteopenia; in vitro release in phosphate-buffered saline (PBS) or sheep serum was assessed by ELISA. Lumbar (L) vertebral bone defects (Ø 3.5 mm) were generated in aged, osteopenic female sheep (n = 72; 9.00 ± 0.11 years; mean ± SEM). Treatment was: (a) HA particles (2.5 mg; L5); or (b) particles coated with BMP-2 (1 µg; 10 µg) or GDF-5 (5 µg; 50 µg; L4; all groups n = 6). Untouched vertebrae (L3) served as controls. Three and nine months post-therapy, bone formation was assessed by osteodensitometry, histomorphometry, and biomechanical testing. Cumulative 14-day BMP release was high in serum (76-100%), but max. 1.4% in PBS. In vivo induction of bone formation by HA particles with either growth factor was shown by: (i) significantly increased bone volume, trabecular and cortical thickness (overall increase HA + BMP vs. control close to the injection channel 71%, 110%, and 37%, respectively); (ii) partial significant effects for bone mineral density, bone formation, and compressive strength (increase 17%; 9 months; GDF-5). Treatment effects were not dose-dependent. Combined HA and BMPs (single low-dose) highly augment long-term bone formation and biomechanical stabilization in sheep lumbar osteopenia. Thus, carrier-bound BMP doses 20,000-fold to 1000-fold lower than previously applied appear suitable for spinal fusion/bone regeneration and improved treatment safety
Identification of Novel Micropeptides Derived from Hepatocellular Carcinoma-Specific Long Noncoding RNA.
No full textIdentification of cancer-specific target molecules and biomarkers may be useful in the development of novel treatment and immunotherapeutic strategies. We have recently demonstrated that the expression of long noncoding (lnc) RNAs can be cancer-type specific due to abnormal chromatin remodeling and alternative splicing. Furthermore, we identified and determined that the functional small protein C20orf204-189AA encoded by long intergenic noncoding RNA Linc00176 that is expressed predominantly in hepatocellular carcinoma (HCC), enhances transcription of ribosomal RNAs and supports growth of HCC. In this study we combined RNA-sequencing and polysome profiling to identify novel micropeptides that originate from HCC-specific lncRNAs. We identified nine lncRNAs that are expressed exclusively in HCC cells but not in the liver or other normal tissues. Here, DNase-sequencing data revealed that the altered chromatin structure plays a key role in the HCC-specific expression of lncRNAs. Three out of nine HCC-specific lncRNAs contain at least one open reading frame (ORF) longer than 50 amino acid (aa) and enriched in the polysome fraction, suggesting that they are translated. We generated a peptide specific antibody to characterize one candidate, NONHSAT013026.2/Linc013026. We show that Linc013026 encodes a 68 amino acid micropeptide that is mainly localized at the perinuclear region. Linc013026-68AA is expressed in a subset of HCC cells and plays a role in cell proliferation, suggesting that Linc013026-68AA may be used as a HCC-specific target molecule. Our finding also sheds light on the role of the previously ignored 'dark proteome', that originates from noncoding regions in the maintenance of cancer
Test of the Rehabilitation Goal Screening (ReGoS) Tool to Support Decision Making and Goal Setting in Physical and Rehabilitation Medicine Practice
Get PDFBackground It has already been shown that it is feasible to use International Classification of Functioning, Disability and Health (ICF) Sets as self-assessment instruments. We used this idea to design an ICF-based screening tool to assess patients of a broadly based rehabilitation department. It was developed for the purpose of having a screening tool before taking the anamnesis, as well as for rehabilitation planning and follow-up. Methods and materials The Rehabilitation Goal Screening (ReGoS) instrument is a self-report questionnaire which was developed based on the most relevant domains from the ICF Core Sets for chronic pain and rehabilitation. The ICF categories were translated into plain language and 0-10 Likert scales were used. A retrospective analysis of routine clinical data using the ReGoS tool, Work Ability Index (WAI) and Hospital Anxiety and Depression Scale (HADS) in paper- or tablet-based form was performed. Results The average age of the N = 1.008 respondents was 53.9 years (SD = 16.2). Of the respondents, 66% (n = 665) were female. At the time of the survey, 48.3% (n = 487) of the patients were employed. ReGoS results demonstrated that the highest restrictions on a scale from 0 to 10 were found in the areas of energy and drive (M = 5.79, SD = 2.575) and activities of daily living (M = 5.54, SD = 2.778). More than a third of the respondents rated their work ability as critical. Conclusion The use of the ReGoS instrument as an ICF-based screening tool based on a self-report questionnaire provides relevant information for clinical diagnosis, participative goal setting and a detailed functional capacity profile