1.
Düringer, Caroline, et al.
(author)
HAMLET; a novel tool to identify apoptotic pathways in tumor cells.
2005
In: Application of apoptosis to cancer treatment.. - Berlin/Heidelberg : Springer-Verlag. - 9781402033032 ; , s. 223-245
Book chapter (other academic/artistic) abstract
Tumor cells often carry mutations in genes that control cell survival, and become resistant to signals that trigger cell death. Yet, some cell death pathways remain intact in tumor cells. If identified, these pathways might be exploited to selectively remove tumor cells. HAMLET (human α-lactalbumin made lethal to tumor cells) is a protein-lipid complex derived from human milk that activates cell death programs in tumor cells but not in healthy differentiated cells. We use HAMLET as a tool to identify apoptosis and apoptosis-like cell death mechanisms in tumor cells and to understand if these mechanisms differ between tumor and healthy cells. HAMLET interacts with the cell surface, translocates into the cytoplasm and accumulates in cell nuclei, where it disrupts the chromatin. Recent in vivo studies have shown that HAMLET maintains the tumoricidal activity in glioblastoma, papilloma and bladder cancer models, with no significant side effects. The results suggest that HAMLET should be explored as a new therapeutic agent with selectivity for the tumor and with little toxicity for adjacent healthy tissue. Such therapies are a much-needed complement to conventional treatments, to reduce the side effects and improve the selectivity.
2.
3.
Szecsi, P. B., et al.
(author)
Seminal progastricsin
1995
In: Aspartic Proteinases : Structure, Function, Biology, and Biomedical Implications - Structure, Function, Biology, and Biomedical Implications. - Boston, MA : Springer US. - 0065-2598. - 9781461357612 - 9781461518716 ; 362, s. 101-105
Book chapter (peer-reviewed) abstract
Lundquist and Seedorff [1] demonstrated the presence of a zymogen in human seminal fluid, that could be activated into an active enzyme by acidification to pH 2. As the enzyme was purified, it became evident that it was in fact equivalent to the minor gastric enzyme originally named as progastricsin (EC 3.4.23.3) [2–6].This report provides a short review on the similarities and differences between human gastric and seminal progastricsin, and the possible function of the seminal progastricsin.
4.
Nijsingh, Niels, 1977, et al.
(author)
Justifying Antibiotic Resistance Interventions: Uncertainty, Precaution and Ethics
2020
In: Jamrozik E., Selgelid M.J. (eds) Ethics and Drug-Resistance: Collective Responsibility for Global Public Health. - Cham, Switzerland : Springer. - 2211-6680. - 9783030278731
Book chapter (peer-reviewed) abstract
This chapter charts and critically analyses the ethical challenge of assessing how much (and what kind of) evidence is required for the justification of interventions in response antibiotic resistance (ABR), as well as other major public health threats. Our ambition here is to identify and briefly discuss main issues, and point to ways in which these need to be further advanced in future research. This will result in a tentative map of complications, underlying problems and possible challenges. This map illustrates that the ethical challenges in this area are much more complex and profound than is usually acknowledged, leaving no tentatively plausible intervention package free of downsides. This creates potentially overwhelming theoretical conundrums when trying to justify what to do. We therefore end by pointing out two general features of the complexity we find to be of particular importance, and a tentative suggestion for how to create a theoretical basis for further analysis.
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6.
Collin, Mattias, et al.
(author)
Bacterial Modulation of Fc Effector Functions
2013
In: Antibody Fc : Linking Adaptive and Innate Immunity - Linking Adaptive and Innate Immunity. - 9780123948021 ; , s. 317-332
Book chapter (peer-reviewed) abstract
Immunoglobulins (Igs, antibodies) are key players in adaptive immunity, and pathways mediated through the effector Fc portion of Ig are instrumental in controlling bacterial infections. Therefore, it is not very surprising that bacterial pathogens and commensals through co-evolution with their hosts have learned many tricks to interfere with Fc effector functions. In this chapter, we describe three principally different bacterial strategies to interfere with immunoglobulins: Specific Ig binding, specific or unspecific Ig protelolysis, and, finally, specific and unspecific hydrolysis of functionally important carbohydrates on the immunoglobulins. Elucidating these bacterial immune evasion mechanism evidences bacteria-host co-evolution and provides insight into fundamental aspects of human adaptive immunity and pathogenesis of infection.
7.
8.
Heyman, Birgitta
(author)
Antibodies as Natural Adjuvants
2014
In: FC RECEPTORS. - Cham : Springer International Publishing. - 9783319079110 - 9783319079103 ; , s. 201-219
Book chapter (peer-reviewed) abstract
Antibodies in complex with specific antigen can dramatically change the antibody response to this antigen. Depending on antibody class and type of antigen, >99 % suppression or >100-fold enhancement of the response can take place. IgM and IgG3 are efficient enhancers and operate via the complement system. In contrast, IgG1, IgG2a, and IgG2b enhance antibody and CD4(+) T cell responses to protein antigens via activating Fc gamma-receptors. IgE also enhances antibody and CD4(+) T cell responses to small proteins but uses the low-affinity receptor for IgE, CD23. Most likely, IgM and IgG3 work by increasing the effective concentration of antigen on follicular dendritic cells in splenic follicles. IgG1, IgG2a, IgG2b, and IgE probably enhance antibody responses by increasing antigen presentation by dendritic cells to T helper cells. IgG antibodies of all subclasses have a dual effect, and suppress antibody responses to particulate antigens such as erythrocytes. This capacity is used in the clinic to prevent immunization of Rhesus-negative women to Rhesus-positive fetal erythrocytes acquired via transplacental hemorrage. IgG-mediated suppression in mouse models can take place in the absence of Fc gamma-receptors and complement and to date no knock-out mouse strain has been found where suppression is abrogated.
9.
Nilsson Ekdahl, Kristina, et al.
(author)
Evaluation of the blood compatibility of materials, cells and tissues: Basic concepts, test models and practical guidelines
2013
In: Complement Therapeutics. - Boston, MA : Springer. - 9781461441175 - 9781461441182 ; 735, s. 257-270
Book chapter (peer-reviewed) abstract
Medicine today uses a wide range of biomaterials, most of which make contact with blood permanently or transiently upon implantation. Contact between blood and nonbiological materials or cells or tissue of nonhematologic origin initiates activation of the cascade systems (complement, contact activation/coagulation) of the blood, which induces platelet and leukocyte activation.Although substantial progress regarding biocompatibility has been made, many materials and medical treatment procedures are still associated with severe side effects. Therefore, there is a great need for adequate models and guidelines for evaluating the blood compatibility of biomaterials. Due to the substantial amount of cross talk between the different cascade systems and cell populations in the blood, it is advisable to use an intact system for evaluation.Here, we describe three such in vitro models for the evaluation of the biocompatibility of materials and therapeutic cells and tissues. The use of different anticoagulants and specific inhibitors in order to be able to dissect interactions between the different cascade systems and cells of the blood is discussed. In addition, we describe two clinically relevant medical treatment modalities, the integration of titanium implants and transplantation of islets of Langerhans to patients with type 1 diabetes, whose mechanisms of action we have addressed using these in vitro models.
10.
