TY - JOUR AB - Protein-energy malnutrition is a state of disordered catabolism resulting from metabolic derangements or starvation. It is associated with chronic disease, hypoglycemia, hypothermia, serious infections, and even an increased prevalence of morbidity and mortality in countries with poor socioeconomic or environmental factors. Adequate food administration is essential to satisfy the main caloric and nutritional demands of humans. The most significant factors seen in the development of protein-energy malnutrition in areas of high incidence, such as underdeveloped countries, are inadequate food and nutrient supplies. It has been well established that one of the strategies to alleviate undernourishment is the biofortification of staple crops. This is because vegetables and plants are significant sources of crucial nutrients for human growth and development. To enhance plant nutrition, recent tactics aim to formulated balanced and diverse diets with acceptable levels of vitamins and minerals that benefit human health. New advances in plant biotechnology and animal productivity could control key enzymes in several metabolic pathways, enriching important nutrients such as iron and vitamins and decreasing the content of disadvantageous compounds such as acrylamide-forming amino acids and phytic acids. Numerous biofortified crops such as rice, maize, and wheat have been created to resolve the problem of nutrition deficiencies. Some examples of these methodologies are genome editing engineered nucleases, transcriptional activator-like effector nucleases, zinc finger nucleases, and clustered regularly interspaced short palindromic repeats and associated Cas9 endonuclease which have been created and widely studied for their application, efficiency, and specificity. AU - Moreno-Nombela, S.* AU - Romero-Parra, J.* AU - Ruiz Ojeda, F.J. AU - Solis-Urra, P.* AU - Baig, A.T.* AU - Plaza-Díaz, J.* C1 - 66843 C2 - 53315 SP - 215-232 TI - Genome editing and protein energy malnutrition. JO - Adv. Exp. Med. Biol. VL - 1396 PY - 2023 SN - 0065-2598 ER - TY - JOUR AB - The extracellular matrix (ECM) plays an important role in lung health and disease. Collagen is the main component of the lung ECM, widely used for the establishment of in vitro and organotypic models of lung disease, and as scaffold material of general interest for the field of lung bioengineering. Collagen also is the main readout for fibrotic lung disease, where collagen composition and molecular properties are drastically changed and ultimately result in dysfunctional "scarred" tissue. Because of the central role of collagen in lung disease, quantification, determination of molecular properties, and three-dimensional visualization of collagen is important for both development and characterization of translational models of lung research. In this chapter, we provide a comprehensive overview on the various methodologies currently available for quantification and characterization of collagen including their detection principles, advantages, and disadvantages. AU - Staab-Weijnitz, C.A. AU - Onursal, C. AU - Nambiar, D.* AU - Vanacore, R.* C1 - 67928 C2 - 54406 CY - Gewerbestrasse 11, Cham, Ch-6330, Switzerland SP - 213-244 TI - Assessment of collagen in translational models of lung research. JO - Adv. Exp. Med. Biol. VL - 1413 PB - Springer International Publishing Ag PY - 2023 SN - 0065-2598 ER - TY - JOUR AB - Nuclear receptors are master regulators of energy metabolism through the conversion of extracellular signals into gene expression signatures. The function of the respective nuclear receptor is tissue specific, signal and co-factor dependent. While normal nuclear receptor function is central to metabolic physiology, aberrant nuclear receptor signaling is linked to various metabolic diseases such as type 2 diabetes mellitus, obesity, or hepatic steatosis. Thus, the tissue specific manipulation of nuclear receptors is a major field in biomedical research and represents a treatment approach for metabolic syndrome. This chapter focuses on key nuclear receptors involved in regulating the metabolic function of liver, adipose tissue, skeletal muscle, and pancreatic β-cells. It also addresses the importance of nuclear co-factors for fine-tuning of nuclear receptor function. The mode of action, role in energy metabolism, and therapeutic potential of prominent nuclear receptors is outlined. AU - Walth-Hummel, A.A. AU - Herzig, S. AU - Rohm, M. C1 - 66242 C2 - 52704 CY - Gewerbestrasse 11, Cham, Ch-6330, Switzerland SP - 61-82 TI - Nuclear receptors in energy metabolism. JO - Adv. Exp. Med. Biol. VL - 1390 PB - Springer International Publishing Ag PY - 2022 SN - 0065-2598 ER - TY - BOOK AB - The C-C motif chemokine ligand 2 (CCL2) is a crucial mediator of immune cell recruitment during microbial infections and tissue damage. CCL2 is also frequently overexpressed in cancer cells and other cells in the tumor microenvironment, and a large body of evidence indicates that high CCL2 levels are associated with more aggressive malignancies, a higher probability of metastasis, and poorer outcomes in a wide range of cancers. CCL2 plays a role in recruiting tumor-associated macrophages (TAMs), which adopt a pro-tumorigenic phenotype and support cancer cell survival, facilitate tumor cell invasion, and promote angiogenesis. CCL2 also has direct, TAM-independent effects on tumor cells and the tumor microenvironment, including recruitment of other myeloid subsets and non-myeloid cells, maintaining an immunosuppressive environment, stimulating tumor cell growth and motility, and promoting angiogenesis. CCL2 also plays important roles in the metastatic cascade, such as creating a pre-metastatic niche in distant organs and promoting tumor cell extravasation across endothelia. Due to its many roles in tumorigenesis and metastatic processes, the CCL2-CCR2 signaling axis is currently being pursued as a potential therapeutic target for cancer. AU - O'Connor, T. AU - Heikenwälder, M. C1 - 62652 C2 - 50983 CY - Gewerbestrasse 11, Cham, Ch-6330, Switzerland SP - 1-14 TI - CCL2 in the tumor microenvironment. JO - Adv. Exp. Med. Biol. VL - 1302 PB - Springer International Publishing Ag PY - 2021 SN - 0065-2598 ER - TY - JOUR AB - The proteasome is involved in the regulation of all cellular pathways and consequently plays a central role in the control of cellular homeostasis. Together with its regulators, it is at the frontline, both as an actor and as a target, in human health and when homeostasis is disturbed in disease. In this review, we aim to provide an overview of the many levels at which the functions of the proteasome and its regulators can be regulated to cope with cellular needs or are altered in pathological conditions. AU - Coux, O.* AU - Zieba, B.A.* AU - Meiners, S. C1 - 58885 C2 - 48610 CY - Gewerbestrasse 11, Cham, Ch-6330, Switzerland SP - 55-100 TI - The proteasome system in health and disease. JO - Adv. Exp. Med. Biol. VL - 1233 PB - Springer International Publishing Ag PY - 2020 SN - 0065-2598 ER - TY - BOOK AB - Tobacco smoke is a multicomponent mixture of chemical, organic, and inorganic compounds, as well as additive substances and radioactive materials. Many studies have proved the carcinogenicity of various of these compounds through the induction of DNA adducts, mutational potential, epigenetic changes, gene fusions, and chromosomal events. The tumor microenvironment plays an important role in malignant tumor formation and progression through the regulation of expression of key molecules which mediate the recruitment of immune cells to the tumor site and subsequently regulate tumor growth and metastasis. In this chapter, we discuss the effects of inhaled tobacco smoke in the tumor microenvironment of the respiratory tract. The mechanisms underlying these effects as well as their link with tumor progression are analyzed. AU - Giotopoulou, G.A. AU - Stathopoulos, G.T. C1 - 58104 C2 - 48200 CY - Gewerbestrasse 11, Cham, Ch-6330, Switzerland SP - 53-69 TI - Effects of inhaled tobacco smoke on the pulmonary tumor microenvironment. JO - Adv. Exp. Med. Biol. VL - 1225 PB - Springer International Publishing Ag PY - 2020 SN - 0065-2598 ER - TY - BOOK AB - Mitochondrial dysfunction is discussed as a key player in the pathogenesis of type 2 diabetes mellitus (T2Dm), a highly prevalent disease rapidly developing as one of the greatest global health challenges of this century. Data however about the involvement of mitochondria, central hubs in bioenergetic processes, in the disease development are still controversial. Lipid and protein homeostasis are under intense discussion to be crucial for proper mitochondrial function. Consequently proteomics and lipidomics analyses might help to understand how molecular changes in mitochondria translate to alterations in energy transduction as observed in the healthy and metabolic diseases such as T2Dm and other related disorders. Mitochondrial lipids integrated in a tool covering proteomic and functional analyses were up to now rarely investigated, although mitochondrial lipids might provide a possible lynchpin in the understanding of type 2 diabetes development and thereby prevention. In this chapter state-of-the-art analytical strategies, pre-analytical aspects, potential pitfalls as well as current proteomics and lipidomics-based knowledge about the pathophysiological role of mitochondria in the pathogenesis of type 2 diabetes will be discussed. AU - Kappler, L.* AU - Kollipara, L.* AU - Lehmann, R. AU - Sickmann, A.* C1 - 56804 C2 - 47398 SP - 143-182 TI - Investigating the role of mitochondria in type 2 diabetes - lessons from lipidomics and proteomics studies of skeletal muscle and liver. JO - Adv. Exp. Med. Biol. VL - 1158 PY - 2019 SN - 0065-2598 ER - TY - BOOK AB - Mitochondrial dysfunction is discussed as a key player in the pathogenesis of type 2 diabetes mellitus (T2Dm), a highly prevalent disease rapidly developing as one of the greatest global health challenges of this century. Data however about the involvement of mitochondria, central hubs in bioenergetic processes, in the disease development are still controversial. Lipid and protein homeostasis are under intense discussion to be crucial for proper mitochondrial function. Consequently proteomics and lipidomics analyses might help to understand how molecular changes in mitochondria translate to alterations in energy transduction as observed in the healthy and metabolic diseases such as T2Dm and other related disorders. Mitochondrial lipids integrated in a tool covering proteomic and functional analyses were up to now rarely investigated, although mitochondria]. lipids might provide a possible lynchpin in the understanding of type 2 diabetes development and thereby prevention. In this chapter state-of-the-art analytical strategies, pre -analytical aspects, potential pitfalls as well as current proteomics and lipidomics-based knowledge about the pathophysiological role of mitochondria in the pathogenesis of type 2 diabetes will be discussed. AU - Kappler, L.* AU - Kollipara, L.* AU - Lehmann, R. AU - Sickmann, A.* C1 - 58564 C2 - 48225 CY - Gewerbestrasse 11, Cham, Ch-6330, Switzerland SP - 143-182 TI - Investigating the role of mitochondria in type 2 diabetes lessons from lipidomics and proteomics studies of skeletal muscle and liver. JO - Adv. Exp. Med. Biol. VL - 1158 PB - Springer International Publishing Ag PY - 2019 SN - 0065-2598 ER - TY - JOUR AB - Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Early response to therapy, especially the measurement of minimal residual disease (MRD), remains the most reliable and strongest independent prognostic parameter. Intriguingly, little is known on the mechanisms sustaining MRD in that disease. Here, we summarize existing evidence on the influences of molecular genetics and clonal architecture of childhood ALL on disease persistence. Also, the impact of the leukemic niche on residual leukemia cells in the bone marrow and extramedullary compartments is reviewed. We further discuss existing in vivo models of minimal residual disease based on different cellular labelling strategies and engraftment of ALL cells in immunodeficient mouse strains. We finally draw some conclusions on potential strategies targeting residual ALL cells, with a focus on cellular and antibodybased immunotherapy. AU - Jeremias, I. AU - Schewe, D.M.* C1 - 54765 C2 - 45864 CY - Gewerbestrasse 11, Cham, Ch-6330, Switzerland SP - 127-139 TI - Characteristics and therapeutic targeting of minimal residual disease in childhood acute lymphoblastic leukemia. JO - Adv. Exp. Med. Biol. VL - 1100 PB - Springer International Publishing Ag PY - 2018 SN - 0065-2598 ER - TY - JOUR AB - Radiotherapy (RT) predominantly is aimed to induce DNA damage in tumour cells that results in reduction of their clonogenicity and finally in tumour cell death. Adaptation of RT with higher single doses has become necessary and led to a more detailed view on what kind of tumour cell death is induced and which immunological consequences result from it. RT is capable of rendering tumour cells immunogenic by modifying the tumour cell phenotype and the microenvironment. Danger signals are released as well as the senescence-associated secretory phenotype. This results in maturation of dendritic cells and priming of cytotoxic T cells as well as in activation of natural killer cells. However, RT on the other hand can also result in immune suppressive events including apoptosis induction and foster tumour cell proliferation. That's why RT is nowadays increasingly combined with selected immunotherapies. AU - Frey, B.* AU - Derer, A.* AU - Scheithauer, H.R.* AU - Wunderlich, R. AU - Fietkau, R.* AU - Gaipl, U.S.* C1 - 49328 C2 - 41756 SP - 151-72 TI - Cancer cell death-inducing radiotherapy: Impact on local tumour control, tumour cell proliferation and induction of systemic anti-tumour immunity. JO - Adv. Exp. Med. Biol. VL - 930 PY - 2016 SN - 0065-2598 ER - TY - JOUR AB - Age-related macular degeneration (AMD) is a medical condition usually affecting older adults and resulting in a loss of vision in the macula, the center of the visual field. The dry form of this disease presents with atrophy of the retinal pigment epithelium, resulting in the detachment of the retina and loss of photoreceptors. Cigarette smoke is one main risk factor for dry AMD and increases the risk of developing the disease by three times. In order to understand the influence of cigarette smoke on retinal pigment epithelial cells, cultured human ARPE-19 cells were treated with cigarette smoke extract for 24 h. Using quantitative mass spectrometry more than 3000 proteins were identified and their respective abundances were compared between cigarette smoke-treated and untreated cells. Altogether 1932 proteins were quantified with at least two unique peptides, with 686 proteins found to be significantly differentially abundant with p > 0.05. Of these proteins the abundance of 64 proteins was at least 2-fold down-regulated after cigarette smoke treatment while 120 proteins were 2-fold up-regulated. The analysis of associated biological processes revealed an alteration of proteins involved in RNA processing and transport as well as extracellular matrix remodelling in response to cigarette smoke treatment. AU - Merl-Pham, J. AU - Gruhn, F. AU - Hauck, S.M. A2 - Bowes Rickman, C.* ; LaVail, M.M.* ; Anderson, R.E.* ; Grimm, C.* ; Hollyfield, J.G.* ; Ash, J.* C1 - 46974 C2 - 39098 CY - Cham SP - 785-791 TI - Proteomic profiling of cigarette smoke induced changes in retinal pigment epithelium cells. JO - Adv. Exp. Med. Biol. VL - 854 PB - Springer Int Publishing Ag PY - 2016 SN - 0065-2598 ER - TY - JOUR AB - Caveolin-1 (Cav-1), the scaffolding protein of caveolae, is expressed in several retinal cell types and is associated with ocular pathologies. Cav-1 modulates neuroinflammatory/neuroprotective responses to central nervous system injury. We have shown that loss of Cav-1 results in a blunted cytokine response in retinas challenged with inflammatory stimuli. As neuroinflammatory and neuroprotective signaling overlap in their cytokine production and downstream signaling pathways, we hypothesized that loss of Cav-1 may also suppress neuroprotective signaling in the retina. To test this, we subjected mice in which Cav-1 was deleted specifically in the retina to a neurodegenerative insult induced by sodium iodate (NaIO3) and measured STAT3 activation, a measure of neuroprotective signaling. Our results show that Cav-1 ablation blunts STAT3 activation induced by NaIO3. STAT3 activation in response to intravitreal administration of the IL-6 family cytokine, leukemia inhibitory factor (LIF), was not affected by Cav-1 deletion indicating a competent gp130 receptor response. Thus, Cav-1 modulates neuroprotective signaling by regulating the endogenous production of neuroprotective factors. AU - Reagan, A.* AU - Gu, X.* AU - Hauck, S.M. AU - Ash, J.D.* AU - Cao, G.* AU - Thompson, T.C.* AU - Elliott, M.H.* A2 - Bowes Rickman, C.* ; LaVail, M.M.* ; Anderson, R.E.* ; Grimm, C.* ; Hollyfield, J.G.* ; Ash, J.* C1 - 46975 C2 - 39099 CY - Cham SP - 411-418 TI - Retinal caveolin-1 modulates neuroprotective signaling. JO - Adv. Exp. Med. Biol. VL - 854 PB - Springer Int Publishing Ag PY - 2016 SN - 0065-2598 ER - TY - JOUR AB - We present the development of novel biomedical imaging methods based on optoacoustics. These novel tools can revolutionize biomedical discovery and clinical healthcare. We focus in particular in multispectral optoacoustic tomography (MSOT). This technology, now recipient of numerous awards and acclaim, shows two important developments: on one hand on how it can break through the limits of conventional optical imaging to shift the paradigm of biomedical observation and on the other how biomedical technology offers a necessary leverage point in scientific discovery but also economic growth, even at moderate investments. AU - Ntziachristos, V. A2 - Vlamos, P.* ; Alexiou, A.* C1 - 42840 C2 - 35414 TI - Optoacoustics as a bioengineering model for neuroscience discovery. JO - Adv. Exp. Med. Biol. VL - 820 PY - 2015 SN - 0065-2598 ER - TY - JOUR AB - Late-stage age-related macular degeneration (AMD) is a common sight-threatening disease of the central retina affecting approximately 1 in 30 Caucasians. Besides age and smoking, common genetic variants from at least 19 gene loci have reproducibly been associated with AMD likely explaining a large proportion of disease. Based on the current knowledge, several models were calculated to predict disease risk each with its own strength and weakness. Here, we review and compare published genetic risk models for AMD with or without additionally accounting for non-genetic factors. AU - Grassmann, F.* AU - Heid, I.M. AU - Weber, B.H.F.* A2 - Ash, J.D.* ; Grimm, C.* ; Hollyfield, J.G.* ; Anderson, R.E.* ; LaVail, M.M.* ; Bowes Rickman, C.* C1 - 31546 C2 - 34546 CY - New York SP - 291-300 TI - Genetic risk models in age-related macular degeneration. JO - Adv. Exp. Med. Biol. VL - 801 PB - Springer PY - 2014 SN - 0065-2598 ER - TY - JOUR AB - Retinal Müller glial cells (RMG) are recognized as essential players providing neurotrophic, metabolic and structural support for retinal neurons as well as mediating inflammatory responses in the retina. While some key neuroprotective molecules in the context of retinal degeneration, such as FGF2, LIF, PEDF have been demonstrated to be of RMG origin, there is yet no comprehensive understanding on the multifaceted role of RMG in orchestrating diverse intercellular functions. In order to systematically as well as functionally analyse RMG reactivity to retinal degeneration and thus explore the RMG-derived signalling molecules in depth, we combined genomics and proteomics approaches based on profiling primary RMGs from mouse and pig. However, since modulations in cell to cell communication by secretion of molecules may not necessarily present with changes in the mRNA profile, we developed shotgun proteomics approaches enabling direct protein profiling of the RMG lysates and secretomes using label-free and SILAC quantitations. We have identified a pool of novel proteins relevant for pro-survival effects transmitted from RMG to retinal neurons and functionally valdidated selected molecules. Additionally, our approach allows to identify RMG reactions to intrinsic and extrinsic stimuli and thus enables to molecularly dissect RMG reactivity relevant for retinal health and disease. AU - Hauck, S.M. AU - von Toerne, C. AU - Ueffing, M. A2 - Ash, J.D.* ; Grimm, C.* ; Hollyfield, J.G.* ; Anderson, R.E.* ; LaVail, M.M.* ; Bowes Rickman, C.* C1 - 31547 C2 - 34545 CY - New York SP - 381-387 TI - The neuroprotective potential of retinal Müller glial cells. JO - Adv. Exp. Med. Biol. VL - 801 PB - Springer PY - 2014 SN - 0065-2598 ER - TY - JOUR AB - Exposure of tumourous tissue to ionizing radiation initiates a wound-healing response involving remodelling of the extracellular microenvironment. The initial reaction involves direct damage to the matrix proteins and the secretion and activation of proteolytic enzymes that lead to local destruction of the extracellular matrix. Subsequently the wounded area may undergo complete repair, may enter a prolonged period of heightened proteolysis, or may overproduce matrix proteins leading to fibrosis. The source of matrix degrading enzymatic activity may be the tumour cells and the tumour stroma. Additional complexity is provided by proteolytic activity released from tissue macrophages, mast cells and by invading inflammatory cells. The local production of growth factors, including VEGF and TGF-β play a key role in coordinating the response. It is anticipated that the application of modern proteomic technologies will reveal hitherto unrecognised levels of complexity in these processes. Hopefully this will lead to the development of new therapeutic strategies to prevent long-term health implications of radiation exposure. AU - Atkinson, M.J. C1 - 26074 C2 - 32056 CY - New York SP - 49-60 TI - Radiation treatment effects on the proteome of the tumour microenvironment. JO - Adv. Exp. Med. Biol. VL - 990 PB - Springer PY - 2013 SN - 0065-2598 ER - TY - JOUR AB - This chapter will review the proteome alterations induced by ionizing radiation in cellular systems or using animal models with whole body or localised exposure. The recent developments in qualitative and quantitative proteome analysis using formalin-fixed paraffin-embedded material from radiobiology archives will be illustrated. The development of promising protein targets to be used as radiation biomarkers in future molecular epidemiology studies is described. AU - Tapio, S. C1 - 23127 C2 - 31002 CY - New York SP - 37-48 TI - Ionizing radiation effects on cells, organelles and tissues on proteome level. JO - Adv. Exp. Med. Biol. VL - 990 PB - Springer PY - 2013 SN - 0065-2598 ER - TY - JOUR AB - The detailed examination of eye structure and function in numerous Drosophila mutants has provided unprecedented insights into retinal physiology and pathology. Many Drosophila mutants that undergo retinal degeneration (RD) exhibit structural and/or dynamic alterations of the photon receptor rhodopsin, and similar defects cause retinitis pigmentosa (RP) in humans. Here, we consider how the use of Drosophila has advanced our understanding of RP and highlight new mechanisms underlying rhodopsin-mediated pathologies in the retina. AU - Griciuc, A. AU - Aron, L.* AU - Ueffing, M. C1 - 7284 C2 - 29863 SP - 415-423 TI - Looking into eyes: Rhodopsin pathologies in Drosophila. JO - Adv. Exp. Med. Biol. VL - 723 IS - 6 PB - Springer PY - 2012 SN - 0065-2598 ER - TY - BOOK AB - The process of differentiation of embryonic stem cells (ESCs) is currently becoming the focus of many systems biologists not only due to mechanistic interest but also since it is expected to play an increasingly important role in regenerative medicine, in particular with the advert to induced pluripotent stem cells. These ESCs give rise to the formation of the three germ layers and therefore to the formation of all tissues and organs. Here, we present a computational method for inferring regulatory interactions between the genes involved in ESC differentiation based on time resolved microarray profiles. Fully quantitative methods are commonly unavailable on such large-scale data; on the other hand, purely qualitative methods may fail to capture some of the more detailed regulations. Our method combines the beneficial aspects of qualitative and quantitative (ODE-based) modeling approaches searching for quantitative interaction coefficients in a discrete and qualitative state space. We further optimize on an ensemble of networks to detect essential properties and compare networks with respect to robustness. Applied to a toy model our method is able to reconstruct the original network and outperforms an entire discrete boolean approach. In particular, we show that including prior knowledge leads to more accurate results. Applied to data from differentiating mouse ESCs reveals new regulatory interactions, in particular we confirm the activation of Foxh1 through Oct4, mediating Nodal signaling. AU - Lutter, D. AU - Bruns, P. AU - Theis, F.J. A2 - Goryanin, I.I.* ; Goryachev, A.B.* C1 - 7130 C2 - 29467 CY - New York SP - 247-260 TI - An ensemble approach for inferring semi-quantitative regulatory dynamics for the differentiation of mouse embryonic stem cells using prior knowledge. JO - Adv. Exp. Med. Biol. VL - 736 PB - Springer PY - 2012 SN - 0065-2598 ER - TY - JOUR AB - The tryptophan system present in Escherichia coli represents an important regulatory unit described by multiple feedback loops. The role of these feedback loops is crucial for the analysis of the dynamical behavior of the tryptophan synthesis. We analyze the robust stability of this system which models the dynamics of both fast state, such as transcription and synthesis of free operator, and slow state, such as translation and tryptophan synthesis under consideration of nonlinear uncertainties. In addition, we analyze the role of these feedback loops as key design components of this regulatory unit responsible for its physiological performance. The range of allowed parameter perturbations and the conditions that ensure the existence of asymptotically stable equilibria of the perturbed system are determined. We also analyze two important alternate regulatory designs for the tryptophan synthesis pathway and derive the stability conditions. AU - Meyer-Bäse, A.* AU - Theis, F.J. AU - Emmett, M.R.* C1 - 1798 C2 - 28099 CY - Heidelberg [u.a.] SP - 189-197 TI - Robust stability analysis and design under consideration of multiple feedback loops of the tryptophan regulatory network of Escherichia coli. JO - Adv. Exp. Med. Biol. VL - 680 PB - Springer PY - 2010 SN - 0065-2598 ER - TY - JOUR AB - 1. CPA does not only induce the formation of DNA adducts but also of mutations in female rat liver. 2. The mutation frequency exhibited a characteristic time course. Within a period of 3 days post administration, a tremendous increase was noted, which remained at a high level until 2 weeks post exposure. Thereafter, most mutation-carrying cells were eliminated within a period of 2 weeks leaving a cell population remaining at a constant level for another 4 weeks. Thus, the length of the observation period post exposure, i. e. the manifestation time, seems to be a critical factor for the strength of the mutagenic response. The highest as observed between 1 and 2 weeks post exposure. Correspondingly, the dose response curve recorded 2 weeks post exposure showed a higher mutagenic response than the curve after 6 weeks of exposure recorded previously. 3. When CPA-induced mutations were recorded as a function of the dose, mutation frequencies at the lower dose range were found that did not differ from those of controls. The non-effective dose recorded 2 weeks post exposure was much lower than that recorded after 6 weeks of exposure indicating that it is a function of the manifestation time. Since DNA adducts were formed in high amounts at the non-effective doses, we assume that the mitogenic activity required for the conversion of DNA adducts into mutations was not sufficiently strong. The liver of adult animals exhibits a very low endogeneous proliferation rate, which is not likely to contribute significantly to the expression of mutations. We conclude that it is the mitogenic activity of CPA itself, which stimulates the expression of mutations. AU - Wolff, T. AU - Topinka, J.* AU - Deml, E.* AU - Oesterle, D.* AU - Schwarz, L.R.* C1 - 23891 C2 - 31396 SP - 687-696 TI - Dose dependent induction of DNA adducts, gene mutations, and cell proliferation by the antiandrogenic drug cyproterone acetate in rat liver. JO - Adv. Exp. Med. Biol. VL - 500 PB - Springer PY - 2001 SN - 0065-2598 ER - TY - JOUR AU - Gütlich, M. AU - Schott, K. AU - Werner, T. AU - Bacher, A. AU - Ziegler, I. C1 - 40264 C2 - 0 SP - 167-170 TI - Detection and quantification of GTP cyclohydrolase I m RNA. JO - Adv. Exp. Med. Biol. VL - 338 PY - 1993 SN - 0065-2598 ER - TY - JOUR AB - Recent evidence has shown that H4biopterin is synthesized in cells which undergo cytokine-directed proliferation and do not use H4biopterin as a hydroxylation cofactor. H4biopterin, in turn, enhances the proliferation of erythroleukemic cells and modulates various aspects of the interleukin-2-induced clonal expansion of T cells.1 In these cells the activity of sepiapterin reductase (SR) is in the range of 100 pmol min-1 mg-1.Lectin Stimulation of resting T cells causes a slowly progressing increase, starting from levels below detection and a transient enhancement of SR activity is found after treatment of activated T cells by interferon-γ plus interleukin-2.1 The NK-like human cell line YT and the murine erythroleukemic cell line B8/3 lack any SR activity. The molecular basis of SR regulation has not been explained in any of these cases. AU - Maier, J. AU - Schott, K. AU - Werner, T. AU - Bacher, A. AU - Ziegler, I. C1 - 40290 C2 - 0 SP - 195-198 TI - Northern blot analysis of sepiapterin reductase mRNA in mammalian cell lines and tissues. JO - Adv. Exp. Med. Biol. VL - 338 PY - 1993 SN - 0065-2598 ER - TY - JOUR AB - Recently H4biopterin was found to be synthesized in cells which do not use it as a hydroxylation cofactor. This is the case during cytokine-directed proliferation and differentiation of cells which participate in hematopoiesis or immune response. AU - Maier, J. AU - Ziegler, I. C1 - 40334 C2 - 0 SP - 199-202 TI - Purification and properties of human sepiapterin reductase from placenta. JO - Adv. Exp. Med. Biol. VL - 338 PY - 1993 SN - 0065-2598 ER - TY - JOUR AU - Ziegler, I. AU - Schott, K. AU - Hültner, L. C1 - 40274 C2 - 0 SP - 211-216 TI - Interferon-γ and kit ligand are primary regulators of GTP cyclohydrolase activity: Mechanisms and implications. JO - Adv. Exp. Med. Biol. VL - 338 PY - 1993 SN - 0065-2598 ER - TY - JOUR AU - Bors, W. AU - Heller, W.E. AU - Michel, C. AU - Saran, M. C1 - 42145 C2 - 0 SP - 165-170 TI - Radical chemistry of flavonoid antioxidants. JO - Adv. Exp. Med. Biol. VL - 264 PY - 1990 SN - 0065-2598 ER -