Immune system

The mild inflammatory response against stented bioprosthetic heart valves in the sheep model is often opposed by a more distinct response in failing human implants. With the emergence of stentless root prostheses with their significantly larger proportion of tissue interacting with the immune system of the host, a more relevant animal model than the sheep may be needed. Valved, porcine aortic roots of 5 cm length were fixed in 0.2% glutaraldehyde and implanted in the upper descending aorta of Merino sheep (n = 5; 43+/-3 kg) and Chacma baboons (n = 5; 17+/-3 kg). After 6 weeks of tissue calcification, pannus outgrowth and inflammation were assessed by atomic absorption spectrophotometry, histologic damage scoring (0 to 3), image analysis, and transmission electron microscopy. The main difference between the two animal models was in aortic wall calcification (64.8+/-39.8 microg/mg in the sheep model versus 4.1+/-5.9 microg/mg in the primate model; p > 0.005). In both models, leaflet calcification was negligible (2.6+/-2.4 microg/mg in the sheep versus 2.5+/-1.9 microg/mg in the primate), and the overall extent of inflammation was comparable (1.2+/-0.8 versus 0.98+/-0.7; p = 0.18 in the sheep and the primate, respectively). Qualitatively, the sheep demonstrated a macrophage-dominated reaction whereas the inflammatory demarcation often resembled a granulocyte-dominated xenograft response in the primate. Pannus outgrowth was comparable in length (8.4+/-2.3 mm versus 9.1+/-4.3 mm proximally and 7.1+/-3.4 mm versus 7.4+/-5.1 mm distally, in the sheep and baboon, respectively; p > 0.05). Our results confirm the sheep as a significantly stronger calcification model for stentless aortic heart valves than the primate. Remaining antigenicity of porcine tissue as a result of incomplete cross-linking, however, elicits a distinctly stronger xenograft-type reaction in the primate model.

Susceptibility to systemic lupus erythematosus (SLE) is associated with genetic, hormonal, immunological, and environmental factors. Many genes have been related with the appearance of SLE, including several loci that code different complement components and their receptors. Some genetic deficiencies of complement molecules are strongly associated with SLE, probably because these deficiencies could cause decreased clearance of apoptotic cell material. As a consequence of the apoptotic material accumulation, high levels of autoantigens can be presented inappropriately to the immune system in an inflammatory context, resulting in an imbalance on the mechanisms of immunological tolerance, immune system activation, and autoantibody production. Recent studies proposed a role to the mannose-binding lectin (MBL) in the SLE physiopathogenesis. This protein activates the complement system, and the presence of several polymorphisms at the promoter and coding regions of the MBL-2 gene determines alterations at the plasma levels of MBL. Some of these polymorphisms have been associated with SLE susceptibility, as well as with clinical and laboratory typical features of this disease, cardiovascular events, and infections. Besides, it has been described that the presence of anti-MBL autoantibodies in sera of SLE patients can influence MBL plasma levels and its functional activity.

Abstract A multidisciplinary approach is being used to identify and validate virulence factors and determinants of bacteria of the Burkholderia cepacia complex (Bcc). Bcc is a group of problematic opportunistic pathogenic bacteria, particularly among cystic fibrosis patients, ...

Acute stress increases resistance to infection. The alteration of this mechanism in chronically stressed people impairs the organism's ability to mount a strong immune response with a resultant increase in morbidity. Acute stress induces a probable sympatho–adrenergically mediated increase in chemotaxis and adhesion molecules expression, thus promoting immune cells migration to sites of infection and/or inflammation, while chronic stress impairs this mechanism. Protracted stressful conditions decrease NK cytotoxic capacity. There is a substance P, which under stressful circumstances mediates the increase in macrophage cytokine production. Acute stress increases T cell mobilization through a beta2–adrenergically mediated process, which is blunted during chronic stress. Psychological stress impairs the immune system's ability to produce antibodies in response to a vaccine, thereby making the organism more vulnerable to infections. Abbreviations: CRH = corticotrophin–releasing hormone; HPA = hypothalamic–pituitary–adrenocortical; IL = interleukin; NE = norepinephrine; NK = natural killer; SAM = sympathetic–adrenal medullary; S–IgA = secretory immunoglobulin A; SNS = sympathetic nervous system; TGF = transforming growth factor; Th = T helper; TNF = tumor necrosis factor

This paper explores the intersections within bodily materialism and future textiles by inquiring into embodied practices and materiality in care. By placing the body as a site of research, it centres around concepts of bodily care and the body as an ecosystem, one that is always in flux and considers the fluidity of bodies and bodily fluids, such as urine, discharge, breath and sweat, as fluids with potential to design with. It looks at how bodies are acted upon by outside forces, and explore more-than-human relations as co-creators in co-habiting the space of the body and that around it. To illustrate this, the paper introduces a series of design research artefacts that take a variety of approaches to exploring the materiality of care in the everyday. First, an eTextile toolkit that aims to create bodily awareness through hands-on engagement with textile crafting technology, then a biotextile harvesting toolkit that involves the raw material of the intimate body that explores DIYbio in the context of the home, and lastly a set of wearable living material-based explorations that recognize biomimicry and symbiotic relationships in designing for chronic stress. In embracing notions of bodily materialism, this paper explores the bodily abject i.e. fluids and the more-than-human as crucial to engendering new modes of knowing in intimate and personal care through textile-based materials. The paper engages critically with textile design research and practice by placing material that embraces care as ambivalent at the forefront and thus challenging traditional approaches to health and care and, importantly, the design of future textiles.

Low cortisol levels have been observed in patients with different stress-related disorders such as chronic fatigue syndrome, fibromyalgia, and post-traumatic stress disorder. Data suggest that these disorders are characterized by a symptom triad of enhanced stress sensitivity, pain, and fatigue. This overview will present data on the development, mechanisms and consequences of hypocortisolism on different bodily systems. We propose that the phenomenon of hypocortisolism may occur after a prolonged period of hyperactivity of the hypothalamic-pituitary-adrenal axis due to chronic stress as illustrated in an animal model. Further evidence suggests that despite symptoms such as pain, fatigue and high stress sensitivity, hypocortisolism may also have beneficial effects on the organism. This assumption will be underlined by some studies suggesting protective effects of hypocortisolism for the individual.

Aviscumine is an Escherichia coli-derived recombinant type II ribosome-inactivating protein with potent antitumor activity in vitro and in vivo. It is the recombinant counterpart of natural mistletoe lectin-I. The current study was performed to determine the safety profile, dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of the intravenous (i.v.) administration of aviscumine in cancer patients. Translational research included the evaluation of pharmacokinetics and monitoring of plasma cytokine and anti-aviscumine antibody induction after administration of the drug. Aviscumine was given twice weekly as a 1 h central i.v. infusion in patients with advanced, refractory progressive, solid malignant tumors who had not been previously exposed to natural mistletoe preparations. They had histologically or cytologically verified disease, were > or =18 years old, had an Eastern Cooperative Oncology Group performance status < or =2 and adequate bone marrow, liver and renal ...

Interleukin (IL)-12 was cloned on the basis of its ability to activate natural killer (NK) cells and promote the development of cytolytic T cells. With further understanding of its activities, IL-12 has emerged as an important cytokine, affecting both immune and hematologic functions. It has been shown to be necessary for the T cell independent induction of interferon (IFN)-γ, critical for the initial suppression of bacterial and parasitic infection; for the development of a Th1 response, critical for effective host defense against intracellular pathogens; and for the activation of differentiated T lymphocytes of both CD4+ and CD8+ phenotype. IL-12 thus functions to activate and to link the innate and acquired immune responses. The therapeutic potential of these activities is suggested by studies in tumor and microbial models. IL-12 has suppressed tumor growth in all murine models examined. Antimicrobial activity has been demonstrated in bacterial, yeast, parasitic, and viral models of infection. In many of these models, activity has been linked to production of IFN-γ and, in the parasite model, to development of a Th1 response. In addition to the therapeutic potential associated with IL-12 activity in these disease models, the understanding of its role in immune development and interaction with other cytokines, particularly antagonists, such as IL-4 and IL-10, has clarified and extended our understanding of immune regulation and should lead to significant developments in understanding the progression of AIDS and the development of vaccine adjuvants able to direct the immune response.

The general overexpression of p53 by different types of tumor cells suggests that p53 immunity might be generally useful for tumor ininiu- notherapy. We describe here the induction of immunity to p53 and resistance to tumor metastasis using an idiotypic network. Mice were immunized with domain-specific anti-p53 monoclonal antibodies (Abl): PAb-248 directed to the N-terminus; PAb-246 directed to the specific

Procedures in the commercial production of animals involve stressful situations which lessen the animal's welfare. This study on Japanese quail evaluated whether an environmental enrichment manipulation can affect avian immune responses and if combined with a chronic stressor exposure can help to counteract the negative effects of stress on the immune system. Potential gender effects were also considered. After hatch, half of the birds were housed in non-enriched boxes and half were housed in environmentally enriched boxes. From day 33 to 42 of age, all birds within half of the non-enriched and enriched boxes remained undisturbed while the other half were daily exposed to a 15 min restraint stressor (chronic stressor). The inflammatory response (lymphoproliferation after phytohemagglutinin-p), percentage of lymphocytes, heterophil/lymphocyte (H/L) ratio and primary antibody response against sheep red blood cells were assessed. The chronic stressor application and the enrichment ...

In this paper, we propose and analyse the model of competition between a single cell cancer and the immune system. The model is a system of integro-differential bilinear equations and it describes both very early stage of a solid tumor and all stages of leukemias.