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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 55 records · Page 3
All sourcesNASA NTRSDOE OSTI
NASA NTRS1973

Prodromal disease: Immune responses of the host macrophage system to humoral factors

A composite is presented of nine studies, each yielding information contributing toward an understanding of methods designed to detect disease during the prodromal stages. The data further point to new areas of study that might be useful in early diagnoses. Five of the none experiments were done in mice. Four of these involved acute infectious disease states and one involved a chronic autoimmune type disease. Of the numerous perimeters studied of the acute diseases, the uptake of H3- thymidine by peripheral blood lymphocytes appeared to yield the earliest indication of disease. This test was not useful in studying the chronic disease state. Four of the nine studies involved application of diagnostic technics to human disease. A normal baseline for H3-thymidine incorporation by human lymphocytes was determined. A subject with severe combined immunodeficiency disease was studied. A human volunteer study was done using Influenza A live attenuated vaccine. Finally, a human volunteer study of subjects infected with Influenza A was done.

Criswell, B. S.↗
NASA NTRS1973

Effects of oxygen-augmented atmosphere on the immune response.

Antibovine serum albumin antibody and nonspecific protein production was evaluated in female rabbits (11-14.5 kg) housed in special cages ventilated with 20% or 40% oxygen at normal barometric pressure. Animals exposed to 40% oxygen do not show normal steady increase of serum antibody. Instead, their titers show a pattern of undershoot, overshoot, undershoot, and finally equilibration at a subnormal level; they have a depressed popliteal node polysome level and have an abnormally low proportion of membrane-bound polysomes. They also show reduced capability of popliteal nodes to synthesize protein (as expected from the reduced number of polysomes). However, the ratio of newly-synthesized specific antibody: nonspecific protein remains normal.

Guttman, H. N.↗
NASA NTRS1974

Early detection of disease program: Evaluation of the cellular immune response

The early cellular responses of specific components of the leukocyte and epithelial cell populations to foreign challenges of both an infectious and noninfectious character were evaluated. Procedures for screening potential flight crews were developed, documented, and tested on a control population. Methods for preparing suitable populations of lymphocytes, polymorphonuclear leukocytes, macrophages, and epithelial cells were first established and evaluated. Epithelial cells from viral infected individuals were screened with a number of anti-viral antisera. This procedure showed the earliest indication of disease as well as providing a specific diagnosis to the physicians. Both macrophages and polymorphonuclear leukocytes were studied from normal individuals, smokers, and patients with viral infections. Newer techniques enabling better definition of lymphocyte subpopulations were then developed, namely the E and EAC rosette procedures for recognition of T (thymus-derived) and B (bone-marrow-derived) lymphocyte subpopulations. Lymphocyte and lymphocyte subpopulation response to multiple mitogens have been evaluated.

Criswell, B. S.↗
NASA NTRS1975

Early detection of disease program: Evaluation of the cellular immune response

Surfaces of normal, cultured, and mitogen-stimulated mouse lymphoid cells were examined by scanning electron microscopy (SEM). Lymphocytes with smooth, highly villous and intermediate surfaces were observed in cell suspensions from both spleens and thymuses of normal mice and from spleens of congenitally athymic (nude) mice. Several strain-specific surface features were noted, including the spine-like appearance of microvilli on C57B1/6 lymphocytes. Although thymus cell suspensions contained somewhat more smooth cells than did spleen cell preparations, lymphocyte derivation could not be inferred from SEM examination. Studies of cells stimulated with mitogenic agents for thymus-derived lymphocytes (concanavalin A) or for bone marrow-derived lymphocytes (lipopolysaccharide) suggested that, in the mouse, development of a complex villous surface is a general concomitant of lymphocyte activation and transformation.

Criswell, B. S.↗
NASA NTRS1983

Human cellular immune responsiveness following space flight

Peripheral circulating lymphocytes were separated from astronaut blood samples three times before and two times after the first four US Space Shuttle flights. The ability of the in vitro T lymphocytes to respond to Phytohemagglutinin by blastogenesis was found to be reduced for each crewmember following spaceflight. In addition, the astronauts experienced a postflight increase in neutrophils and a decrease in eosinophils. These postflight changes in leukocytes are shown to increase with subjectively-evaluated increases in the incidence of inflight stress, indicating that stress, and not hypogravity, is likely to be the major effector of these changes.

Taylor, G. R.↗
NASA NTRS1999

Update on the Effects of Space Flight on Development of Immune Responses

This study has been completed, and the following is an update of the results as published. Pregnant rats were flown on the Space Shuttle in the NIH.R I mission for 11 days, and pregnant control rats were maintained in animal enclosure modules in a ground-based chamber under conditions approximating those in flight. Additional controls were in standard housing. The effects of the flight on immunological parameters (including blastogenesis, interferon-gamma production, response to colony stimulating factor and total immunoglobulin levels) of dams, fetuses, and pups was determined.

Sonnenfeld, G.↗
NASA NTRS2005

Early immune response and regulation of IL-2 receptor subunits

Affymetrix oligonucleotide arrays were used to monitor expression of 8796 genes and probe sets in activated T-cells; analysis revealed that 217 genes were significantly upregulated within 4 h. Induced genes included transcription factors, cytokines and their receptor genes. Analysis by semi-quantitative RT-PCR confirmed the significant induction of IL-2, IL-2R(gamma) and IL-2R(alpha). Forty-eight of the 217 induced genes are known to or predicted to be regulated by a CRE promoter/enhancer. We found that T-cell activation caused a significant increase in CREB phosphorylation furthermore, inhibition of the PKC pathway by GF109203 reduced CREB activation by 50% and inhibition of the PKA pathway caused a total block of CREB phosphorylation and significantly reduced IFN(gamma), IL-2 and IL-2R(alpha) gene expression by approximately 40% (p<0.001). PKC(theta) plays a major role in T-cell activation: inhibition of PKC significantly reduced the expression of IFN(gamma), IL-2 and IL-2R(alpha). Since PKC blocked activation of CREB, we studied potential cross-talk between the PKC and the PKA/MAPK pathways, PMA-stimulated Jurkat cells were studied with specific signal pathway inhibitors. Extracellular signal-regulated kinase-2 (ERK2) pathway was found to be significantly activated greater than seven-fold within 30 min; however, there was little activation of ERK-1 and no activation of JNK or p38 MAPK. Inhibition of the PKA pathway, but not the PKC pathway, resulted in inhibition of ERK1/2 activation at all time points, inhibition of MEK1 and 2 significantly blocked expression of IL-2 and IL-2R(alpha). Gene expression of IL-2R(alpha) and IFN(gamma) was dependent on PKA in S49 wt cells but not in kin- mutants. Using gel shift analysis, we found that forskolin activation of T-cells resulted in activation of AP1 sites; this increase in nuclear extract AP1 was significantly blocked by MEK1 inhibitor U0126. Taken together, these results suggest that the PKA in addition to PKC and MAPK pathways plays a role in early T-cell activation and induction of IL-2, IL-2R(alpha) and IFN(gamma) gene expression.

Non-NASA Center↗
NASA NTRSDate not supplied

Spaceflight-Induced Changes in Microbial Virulence and the Impact to the Host Immune Response

Over the past 50 years, microorganisms have displayed unexpected responses relevant to infectious disease when grown in spaceflight and spaceflight analogues, including changes in final cell concentration, biofilm production, stress resistance, antibiotic sensitivity, gene expression, and virulence. •Seminal studies demonstrated that the foodborne pathogen, Salmonella enterica serovar Typhimurium, increased its virulence and pathogenesis-related characteristics in response to both spaceflight and spaceflight analogue culture. Since those experiments, alterations in the pathogenesis-related characteristics of other pathogens have been documented in response to growth in these environments4,5,6, and a recent study has demonstrated an increase in virulence of Serratia marcescens cultured during spaceflight7. However, our overall knowledge of which microorganisms will alter their virulence in response to spaceflight and spaceflight analogue culture remains very limited

C. M. Ott↗
NASA NTRS2006

Stress, and pathogen response gene expression in modeled microgravity

Purpose: Immune suppression in microgravity has been well documented. With the advent of human exploration and long-term space travel, the immune system of the astronaut must be optimally maintained. It is important to investigate the expression patterns of cytokine genes, because they are directly related to immune response. Heat shock proteins (HSPs), also called stress proteins, are a group of proteins that are present in the cells of every life form. These proteins are induced when a cell responds to stressors such as heat, cold and oxygen deprivation. Microgravity is another stressor that may regulate HSPs. Heat shock proteins trigger immune response through activities that occur both inside the cell (intracellular) and outside the cell (extracellular). Knowledge about these two gene groups could lead to establishment of a blueprint of the immune response and adaptation-related genes in the microgravity environment. Methods: Human peripheral blood cells were cultured in 1g (T flask) and modeled microgravity (MMG, rotating-wall vessel) for 24 and 72 hours. Cell samples were collected and subjected to gene array analysis using the Affymetrix HG_U95 array. Data was collected and subjected to a two-way analysis of variance. The genes related to immune and stress responses were analyzed. Results and Conclusions: HSP70 was up-regulated by more than two fold in microgravity culture, while HSP90 was significantly down-regulated. HSP70 is not typically expressed in all kinds of cells, but it is expressed at high levels in stress conditions. HSP70 participates in translation, protein translocation, proteolysis and protein folding, suppressing aggregation and reactivating denatured proteins. Increased serum HSP70 levels correlate with a better outcome for heat-stroke or severe trauma patients. At the same time, elevated serum levels of HSP70 have been detected in patients with peripheral or renal vascular disease. HSP90 has been identified in the cytosol, nucleus and endoplasmic reticulum, and exists in many tissue types. HSP90 associates with actin filaments in certain conditions and aids cell motility. The down-regulation of HSP90 could lead to deleterious effects in the lymphocytes, thereby contributing to suppressed immune function in microgravity. Interleukins such as IL 1 alpha, IL11 receptor chain alpha, IL7R, and IL4R were significantly down regulated in modeled microgravity. Further analysis of the genes involved in immune response at the protein level may provide a basis for prophylactic and countermeasure strategies to augment the human immune system for space exploration.

Sundaresan, Alamelu↗
NASA NTRS1996

Immunological and Hematopoietic Biotechnology Studies

The purpose of the work carried under this interchanges was to support the development of space flight biotechnology experiments in the areas of immunology and hematopoiesis to facilitate the commercial development of space. The studies involved the interaction and development of experiments with biotechnology companies for necessary ground-based studies to allow the development of flight studies. The thrust of the work was to develop experiments with the Chiron Corporation and Bioserve involving the use of interleukin-2 to modulate the effects of spaceflight on immune responses. Spaceflight has been shown to have multiple effects on immune responses (1). lnterleukin-2 is an immuno-regulator that could have potential to counter some of the alterations induced in immune responses by spaceflight (1). To test this possibility before flight, rats were suspended antiorthostatically (2) and treated with interleukin-2. Antiorthostatic suspension is a model for some of the effects of spaceflight on immune responses (2). The interleukin-2 was given to see if it could alter some of the effects of suspension. This was achieved. As a result of these studies, two flight experiments were developed and flown with the Chiron Corp. And Bioserve to determine if use of interleukin-2 could prevent or attenuate the effects of space flight on immune responses.

Fernandez-Botran, Rafael↗
NASA NTRS1996

Neuroendocrine and Immune System Responses with Spaceflights

Despite the fact that the first human was in space during 1961 and individuals have existed in a microgravity environment for more than a year, there are limited spaceflight data available on the responses of the neuroendocrine and immune systems. Because of mutual interactions between these respective integrative systems, it is inappropriate to assume that the responses of one have no impact on functions of the other. Blood and plasma volume consistently decrease with spaceflight; hence, blood endocrine and immune constituents will be modified by both gravitational and measurement influences. The majority of the in-flight data relates to endocrine responses that influence fluids and electrolytes during the first month in space. Adrenocorticotropin (ACTH), aldo-sterone. and anti-diuretic hormone (ADH) appear to be elevated with little change in the atrial natriuretic peptides (ANP). Flight results longer than 60 d show increased ADH variability with elevations in angiotensin and cortisol. Although post-flight results are influenced by reentry and recovery events, ACTH and ADH appear to be consistently elevated with variable results being reported for the other hormones. Limited in-flight data on insulin and growth hormone levels suggest they are not elevated to counteract the loss in muscle mass. Post-flight results from short- and long-term flights indicate that thyroxine and insulin are increased while growth hormone exhibits minimal change. In-flight parathyroid hormone (PTH) levels are variable for several weeks after which they remain elevated. Post-flight PTH was increased on missions that lasted either 7 or 237 d, whereas calcitonin concentrations were increased after 1 wk but decreased after longer flights. Leukocytes are elevated in flights of various durations because of an increase in neutrophils. The majority of post-flight data indicates immunoglobulin concentrations are not significantly changed from pre-flight measurements. However, the numbers of T-lymphocytes and natural killer cells are decreased with post-flight conditions. Of the lymphokines, interleukin-2 production, lymphocyte responsiveness, and the activity of natural killer cells are consistently reduced post-flight. Limited head-down tilt (HDT) data suggest it is an effective simulation model for microgravity investigations. Neuroendocrine and pharmacological countermeasures are virtually nonexistent arid should become high priority items for future research. Although exercise has the potential to be an effective countermeasure for various neuroen-docrine-immune responses in microgravity, this concept must be tested before flights to Mars are scheduled.

Tipton, Charles M.↗
NASA NTRS1976

Increased concentration of Pseudomonas aeruginosa and Staphylococcus sp. in small animals exposed to aerospace environments

The effects of increased concentrations of PSEUDOMONAS AERUGINOSA AND STAPHYLOCOCCUS in the total bacterial flora of small animals exposed to simulated spacecraft environments were evaluated. Tests to detect changes in infectivity, effects of antibiotic treatments, immune responses to bacterial antigens, and effectiveness of immune responses in the experimental environment were conducted. The most significant results appear to be the differences in immune responses at simulated altitudes and the production of infection in the presence of a specific antibody.

Guthrie, R. K.↗