Prof. Dr. Annette Schmidt - Academia.edu (original) (raw)

Papers by Prof. Dr. Annette Schmidt

Cardiovascular Risk Factors, 2012

Journal of Science in Sport and Exercise

Purpose The fact that CrossFit® is the best-known and rapidly growing concept for high-intensity ... more Purpose The fact that CrossFit® is the best-known and rapidly growing concept for high-intensity interval training (HIIT) and high-intensity functional training (HIFT) results in a continuous increase of athletes performing CrossFit®. In the more than 15,000 CrossFit® Affiliates worldwide, the training concept is usually offered in 1-h training sessions containing the CrossFit®-related workout of the day (WOD), as well as a general warm-up, movement demonstrations, and skill training. Here, we report how physiological parameters measured by heart rate (HR) values vary during four different 1-h CrossFit® training sessions of non-elite athletes (n = 27) in a local affiliated training center and what influencing factors may exist. Methods The duration of the 1-h training sessions were divided into a warm-up part (WU-part), a skill development part combined with strength exercises (A-part), followed by the WOD part (B-part). Results Analysis of HR values shows high training intensity (≥...

Sports, 2021

In the trend sport CrossFit®, international competition is held at the CrossFit® Games, known wor... more In the trend sport CrossFit®, international competition is held at the CrossFit® Games, known worldwide as the definitive fitness test. Since American athletes are the best in the world regarding CrossFit®, there might be influencing factors on international competition performance. Here, we characterize the benchmark performance profile of American and German CrossFit® athletes (n = 162). To collect the common benchmark performance by questionnaire, 66 male and 96 female CrossFit® athletes (32.6 ± 8.2 years) participated in our survey in both nations. By comparing the individual performance variables, only a significant difference in total power lift performance by males was identified between the nations (p = 0.034). No other significant differences were found in the Olympic lift, running, or the “Girl” Workout of the Day (Fran, Grace, Helen) performance. Very large to extremely large (r = 0.79–0.99, p < 0.01) positive correlations were found between the power lift and Olympic ...

Rejuvenation Research, 2008

PLoS ONE, 2012

Adoptive therapy of malignant diseases with tumor-specific cytotoxic T cells showed remarkable ef... more Adoptive therapy of malignant diseases with tumor-specific cytotoxic T cells showed remarkable efficacy in recent trials. Repetitive T cell receptor (TCR) engagement of target antigen, however, inevitably ends up in hypo-responsive cells with terminally differentiated KLRG-1 + CD57 + CD7 2 phenotype limiting their therapeutic efficacy. We here revealed that hyporesponsiveness of CMV-specific late-stage CD8 + T cells is due to reduced TCR synapse formation compared to younger cells. Membrane anchoring of TCR components contributes to T cell hypo-responsiveness since dislocation of galectin-3 from the synapse by swainsonine restored both TCR synapse formation and T cell response. Transgenic expression of a CD3-zeta signaling chimeric antigen receptor (CAR) recovered hypo-responsive T cells to full effector functions indicating that the defect is restricted to TCR membrane components while synapse formation of the transgenic CAR was not blocked. CAR engineered late-stage T cells released cytokines and mediated redirected cytotoxicity as efficiently as younger effector T cells. Our data provide a rationale for TCR independent, CAR mediated activation in the adoptive cell therapy to avoid hyporesponsiveness of late-stage T cells upon repetitive antigen encounter.

Molecular Therapy, 2011

Adoptive T-cell transfer showed promising efficacy in recent trials raising interest in T cells w... more Adoptive T-cell transfer showed promising efficacy in recent trials raising interest in T cells with redirected specificity against tumors. T cells were engineered with a chimeric antigen receptor (CAR) with predefined binding and CD3ζ signaling to initiate T-cell activation. CD28 costimulation provided by a CD28-CD3ζ signaling CAR moreover improved T cell activation and persistence; however, it failed to meet the expectations with respect to mounting attacks against solid tumors infiltrated with regulatory T (Treg) cells. We revealed that a CD28 CAR-redirected T-cell attack is accompanied by higher numbers of Treg cells infiltrating the tumor and is less efficient against cancer cells in presence of Treg cells than a CD3ζ CAR T-cell attack. Deletion of the lck binding moiety in the CD28 CAR endodomain, however, improved redirected anti-tumor activity in presence of Treg cells without impairing interferon-γ (IFN-γ) secretion, proliferation, and cytolysis. CD28 modification abrogated interleukin-2 (IL-2) induction upon CAR engagement which in turn is no longer available to sustain Treg cell persistence. CARs with the modified CD28 endodomain thereby expedite the implementation of adoptive T-cell therapy in patients with a variety of cancer types that are heavily infiltrated by Treg cells.

Journal of Stem Cell Research & Therapy, 2016

Embryoid bodies (EB) derived from pluripotent embryonic stem cells (ES) are powerful tools for di... more Embryoid bodies (EB) derived from pluripotent embryonic stem cells (ES) are powerful tools for different purposes. One interesting aspect is vessel development and the use for simulating angiostatic effects of drugs. Unfortunately, it is difficult to compare the impacts of different drugs. Current methods allow the description of observations, but quantifying methods are missing. To overcome that gap, we have developed a score system to transfer microscopic observations into quantifiable values. The score system summarizes different vessel characteristics within few categories and allows the comparison of drug effects in view of time and dosage. We analysed score behaviour with respect to normal vessel development as well as under presence of angiotstatic drugs. The vessel score showed a time-dependent increase under normal conditions while under presence of an angiogenesis-inhibitor the score increase was slowed, and under angiogenesis enhancing conditions the score increase was accelerated. The presented vessel development score seems to be a helpful tool to transfer microscopic observations in EB vessel development into a quantifiable and comparable value.

Stem Cells and Development, 2008

In addition to their multilineage potential, mesenchymal stem cells (MSCs) also have a wide range... more In addition to their multilineage potential, mesenchymal stem cells (MSCs) also have a wide range of functionality. Not only can MSCs reconstruct a tissue, but they also have the ability to control or cure other cells and can reconstruct a coordinating function. The opportunity to control other cells depends on MSCs being able to secrete factors like cytokines and chemokines. Therefore, we focused on asking, Which factors can be secreted by human MSCs? To answer this question, we analyzed the secreting profile of in vitro-expanded MSCs by using cytokine arrays. The media concentrations of 44 of the 120 analyzed cytokines were significantly increased by MSCs. Conversely, concentrations of 40 cytokines given with the sera were significantly decreased. The data presented here provide an overview about a large range of factors that were secreted by MSCs under cell culture conditions. These data indicate that MSCs demonstrate all previously described functions in cellular interactions without an external stimulus. The MSCs secreted angiogenic, immunosuppressive, anti-apoptotic, and proliferation-stimulating factors.

International Journal of Impotence Research, 2002

Nitric oxide (NO) is an important mediator in the cavernosal smooth muscle relaxation that causes... more Nitric oxide (NO) is an important mediator in the cavernosal smooth muscle relaxation that causes erections. The purpose of this study was to examine the existence, distribution and phosphorylation stage of two recently discovered key enzymes for NO regulation in human cavernosal tissue, the MAP Kinase 1=2 (Erk 1=2) and the serine=threonine specific protein kinase Akt=PKB. The expression of the enzymes was examined in corpus cavernosum specimens taken from both potent men and from patients with long-term impotence. There was a distinct difference in the activation stage of the MAP Kinase 1=2 (Erk 1=2) between endothelium and smooth muscle cells in potent patients. This finding gives evidence for a cell-type-specific regulation of the eNOS-dependent NO release. Furthermore, we found a higher basal level of active MAP Kinase 1=2 (Erk 1=2) in impotent patients. This finding gives the first evidence for an inhibitory influence of MAP Kinase 1=2 (Erk 1=2) on cavernosal eNOS activity.

Circulation Research, 2007

Migration of endothelial precursor cells (so-called “angioblasts” in embryos and “endothelial pro... more Migration of endothelial precursor cells (so-called “angioblasts” in embryos and “endothelial progenitor cells” in adults) during vasculogenesis is a requirement for the formation of a primary vascular plexus. The migration is initiated by the change of endothelial precursors to their migratory phenotype. The endothelial precursor cells are then guided to the position where the primary vascular plexus is formed. Migration is stopped by the reversion of the cells to their nonmigratory phenotype. A combination of regulatory mechanisms and factors controls this process. These include gradients of soluble factors, extracellular matrix–cell interaction and cell–cell interaction. In this review, we give an overview of the regulation of angioblast migration during embryonic vasculogenesis and its relationship to the migration of endothelial progenitors during postnatal vascular development.

BMC Sports Science, Medicine and Rehabilitation

Background To combat the spread of SARS-CoV-2, CrossFit® training centers, and fitness studios we... more Background To combat the spread of SARS-CoV-2, CrossFit® training centers, and fitness studios were closed during the first lockdown in Germany from mid-March until June 2020, and as a result, CrossFit® (CFA) or weightlifting athletes (WLA) faced a major challenge for the first time. Therefore, this study aimed to investigate the impact of the first lockdown on the training behavior and to analyze the way the athletes dealt with the new situation. In detail, we focus on habits of purchase and examine the acceptance of digital sports offers between CFA and WLA in response to the restrictions of the nationwide lockdown. Methods An online survey was used to characterize the purchasing behavior and use of digital sports offers of CFA and WLA. In total, 484 volunteers (192 women, 290 men, 2 diverse) responded to the online questionary, allowing us to identify changes in training behavior and differences between the sports disciplines. Results Our data shows both CFA and WLA purchase new ...

Archives of Toxicology, 2021

Wound healing is a complex process, and disturbance of even a single mechanism can result in chro... more Wound healing is a complex process, and disturbance of even a single mechanism can result in chronic ulcers developing after exposure to the alkylating agent sulfur mustard (SM). A possible contributor may be SM-induced chronic senescent mesenchymal stem cells (MSCs), unable to fulfil their regenerative role, by persisting over long time periods and creating a proinflammatory microenvironment. Here we show that senescence induction in human bone marrow derived MSCs was time- and concentration-dependent, and chronic senescence could be verified 3 weeks after exposure to between 10 and 40 µM SM. Morphological changes, reduced clonogenic and migration potential, longer scratch closure times, differences in senescence, motility and DNA damage response associated genes as well as increased levels of proinflammatory cytokines were revealed. Selective removal of these cells by senolytic drugs, in which ABT-263 showed initial potential in vitro, opens the possibility for an innovative treat...

Toxicology letters, Jan 16, 2017

The chemical warfare agent sulfur mustard (SM) can cause long-term health effects that may occur ... more The chemical warfare agent sulfur mustard (SM) can cause long-term health effects that may occur even years after a single exposure. The underlying pathophysiology is unknown, but epigenetic mechanisms are discussed as feasible explanation. "Epigenetics" depicts regulation of gene function without affecting the DNA sequence itself. DNA-methylation and covalent histone modifications (methylation or acetylation) are regarded as important processes. In the present in vitro study using early endothelial cells (EEC), we analyzed SM-induced DNA methylation over time and compared results to an in vivo skin sample that was obtained approx. one year after an accidental SM exposure. EEC were exposed to low SM concentrations (0.5 and 1.0μM). DNA methylation and histone acetylation (H3-K9, H3-K27, H4-K8) or histone di-methylation (H3-K9, H3-K27, H3-K36) were investigated 24h after exposure, and after 2 or 4 additional cell passages. The human skin sample was assessed in parallel. SM h...

International Journal of Sports Medicine, 2007

For many years, it was believed that the sole mechanism for postnatal growth of new blood vessels... more For many years, it was believed that the sole mechanism for postnatal growth of new blood vessels is angiogenesis, occurring through vascular sprouting and intucesseption. Today, accumulating evidence indicates that peripheral blood contains marrow-derived endothelial progenitor cells with similar properties to those of embryonal angioblasts [34]. These progenitor cells have the potential to differentiate into mature endothelial cells. Therefore, these cells were termed endothelial progenitor cells (EPCs), which can contribute to postnatal vessel growth and repair (postnatal vasculogenesis). The phenotypic characterization and derivation of EPCs remains controversial. The attempt to accurately characterize these cells seems to be extremely difficult because of the many different possible origins of EPCs. Additionally , specific surface markers found on EPCs are fractionally expressed on other cell types. The following general definition of EPCs has been given: 1. EPCs are circulating marrow-derived stem cells that are functional and phenotypically distinct from mature endothelial cells, 2. EPCs can differentiate into endothelial cells, 3. EPCs can contribute to postnatal vasculogenesis and to vascular homeostasis. [23] This rather general definition does not take into account that EPCs can derive from different cell populations:

Toxicology Letters, 2017

Inhalation of zinc chloride (ZnCl 2) may result in severe adverse health effects  The underlying... more Inhalation of zinc chloride (ZnCl 2) may result in severe adverse health effects  The underlying molecular toxicology is not known  TRPA1 channels are important for sensing toxic chemicals  ZnCl 2-induced TPRA1 activation and cytotoxicity was investigated in vitro  Although TRPA1 is activated by ZnCl 2 , this does not mediate toxicity in vitro

Archives of Toxicology, 2016

Transient receptor potential family channels (TRPs) have been identified as relevant targets in m... more Transient receptor potential family channels (TRPs) have been identified as relevant targets in many pharmacological as well as toxicological studies. TRP channels are ubiquitously expressed in different tissues and act among others as sensors for different external stimuli, such as mechanical stress or noxious impacts. Recent studies suggest that one member of this family, the transient receptor potential ankyrin 1 cation channel (TRPA1), is involved in pain, itch, and various diseases, suggesting TRPA1 as a potential therapeutic target. As a nociceptor, TRPA1 is mainly activated by noxious or electrophilic compounds, including alkylating substances. Previous studies already revealed an impact of 2-chloroethyl-ethyl sulfide on the ion channel TRPA1. In this study, we demonstrate that sulfur mustard (bis-(2-chloroethyl) sulfide, SM) activates the human TRPA1 (hTRPA1) in a dose-dependent manner measured by the increase in intracellular Ca(2+) concentration ([Ca(2+)]i). Besides that, SM-induced toxicity was attenuated by antioxidants. However, very little is known about the underlying mechanisms. Here, we demonstrate that N-acetyl-L-cysteine (NAC) prevents SM-induced hTRPA1-activation. HEK293-A1-E cells, overexpressing hTRPA1, show a distinct increase in [Ca(2+)]i immediately after SM exposure, whereas this increase is reduced in cells pretreated with NAC in a dose-dependent manner. Interestingly, glutathione, although being highly related to NAC, did not show an effect on hTRPA1 channel activity. Taken together, our results provide evidence that SM-dependent activation of hTRPA1 can be diminished by NAC treatment, suggesting a direct interaction of NAC and the hTRPA1 cation channel. Our previous studies already showed a correlation of hTRPA1-activation with cell damage after exposure to alkylating agents. Therefore, NAC might be a feasible approach mitigating hTRPA1-related dysregulations after exposure to SM.

Journal of Allergy and Clinical Immunology, 2016

Toxicology letters, Jan 18, 2015

Victims that were exposed to the chemical warfare agent Sulfur mustard (SM) suffer from chronic d... more Victims that were exposed to the chemical warfare agent Sulfur mustard (SM) suffer from chronic dermal and ocular lesions, severe pulmonary problems and cancer development. It has been proposed that epigenetic perturbations might be involved in that process but this has not been investigated so far. In this study, we investigated epigenetic modulations in vitro using early endothelial cells (EEC) that were exposed to different SM concentrations (0.5, 1.0, 23.5 and 50μM). A comprehensive analysis of 78 genes related to epigenetic pathways (i.e. DNA-methylation and post-translational histone modifications) was performed. Moreover, we analyzed global DNA methylation in vitro in EEC after SM exposure as a maker for epigenetic modulations and in vivo using human skin samples that were obtained from a patient 1 year after an accidently exposure to pure SM. SM exposure resulted in a complex regulation pattern of epigenetic modulators which was accompanied by a global increase of DNA methyl...