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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 163 records · Page 9
All sourcesNASA NTRSDOE OSTI
NASA NTRS1997

Latent transforming growth factor beta1 activation in situ: quantitative and functional evidence after low-dose gamma-irradiation

The biological activity of transforming growth factor beta1 (TGF-beta) is controlled by its secretion as a latent complex in which it is noncovalently associated with latency-associated peptide (LAP). Activation is the extracellular process in which TGF-beta is released from LAP, and is considered to be a primary regulatory control. We recently reported rapid and persistent changes in TGF-beta immunoreactivity in conjunction with extracellular matrix remodeling in gamma-irradiated mouse mammary gland. Our hypothesis is that these specific changes in immunoreactivity are indicative of latent TGF-beta activation. In the present study, we determined the radiation dose response and tested whether a functional relationship exists between radiation-induced TGF-beta and collagen type III remodeling. After radiation exposures as low as 0.1 Gy, we detected increased TGF-beta immunoreactivity in the mammary epithelium concomitant with decreased LAP immunostaining, which are events consistent with activation. Quantitative image analysis demonstrated a significant (P=0.0005) response at 0.1 Gy without an apparent threshold and a linear dose response to 5 Gy. However, in the adipose stroma, loss of LAP demonstrated a qualitative threshold at 0.5 Gy. Loss of LAP paralleled induction of collagen III immunoreactivity in this tissue compartment. We tested whether TGF-beta mediates collagen III expression by treating animals with TGF-beta panspecific monoclonal antibody, 1D11.16, administered i.p. shortly before irradiation. Radiation-induced collagen III staining in the adipose stroma was blocked in an antibody dose-dependent manner, which persisted through 7 days postirradiation. RNase protection assay revealed that radiation-induced elevation of total gland collagen III mRNA was also blocked by neutralizing antibody treatment. These data provide functional confirmation of the hypothesis that radiation exposure leads to latent TGF-beta activation, support our interpretation of the reciprocal shift in immunoreactivity as evidence of activation, and implicate TGF-beta as a mediator of tissue response to ionizing radiation. The sensitivity of activation to low radiation doses points to a potential role for TGF-beta in orchestrating tissue response to oxidative stress. As such, radiation may be useful as a probe to delineate the consequences of latent TGF-beta activation in situ.

NASA Discipline Radiation Health↗
NASA NTRS2002

Biomaterials and scaffolds in reparative medicine

Most approaches currently pursued or contemplated within the framework of reparative medicine, including cell-based therapies, artificial organs, and engineered living tissues, are dependent on our ability to synthesize or otherwise generate novel materials, fabricate or assemble materials into appropriate 2-D and 3-D forms, and precisely tailor material-related physical and biological properties so as to achieve a desired clinical response. This paper summarizes the scientific and technological opportunities within the fields of biomaterials science and molecular engineering that will likely establish new enabling technologies for cellular and molecular therapies directed at the repair, replacement, or reconstruction of diseased or damaged organs and tissues.

Non-NASA Center↗
NASA NTRS2011

Expression of Enzymes that Metabolize Medications

INTRODUCTION: Increased exposure to radiation is one physiological stressor associated with spaceflight and it is feasible to conduct ground experiments using known radiation exposures. The health of the liver, especially the activity rate of its metabolic enzymes, determines the concentration of circulating drugs as well as the duration of their efficacy. While radiation is known to alter normal physiological function, how radiation affects liver metabolism of administered medications is unclear. Crew health could be affected if the actions of medications used in spaceflight deviated from expectations formed during terrestrial medication use. This study is an effort to identify liver metabolic enzymes whose expression is altered by spaceflight or by radiation exposures that mimic features of the spaceflight environment. METHODS: Using procedures approved by the Animal Care and Use Committee, mice were exposed to either 137Cs (controls, 50 mGy, 6Gy, or 50 mGy + 6Gy separated by 24 hours) or 13 days of spaceflight on STS 135. Animals were anesthetized and sacrificed at several time points (4 hours, 24 hours or 7 days) after their last radiation exposure, or within 6 hours of return to Earth for the STS 135 animals. Livers were removed immediately and flash-frozen in liquid nitrogen. Tissue was homogenized, RNA extracted, purified and quality-tested. Complementary DNA was prepared from high-quality RNA samples, and used in RT-qPCR experiments to determine relative expression of a wide variety of genes involved in general metabolism and drug metabolism. RESULTS: Results of the ground radiation exposure experiments indicated ~65 genes of the 190 tested were significantly affected by at least one of the radiation doses. Many of the affected genes are involved in the metabolism of drugs with hydrophobic or steroid-like structures, maintenance of redox homeostasis and repair of DNA damage. Most affected genes returned to near control expression levels by 7 days post-treatment. Not all recovered completely by the final time point tested: with 6 Gy exposure, metallothionein expression was 132-fold more than control at the 4 hr time point, and fell at each later time point (11-fold at 24 hrs, and 8-fold at 7 days). In contrast, there were other genes whose expression was altered and remained relatively constant through the 7 day period we tested. One examples is Cyp17a1, which showed a 4-fold elevation at 4 hrs after exposure and remained constant for 7 days after the last treatment. Spaceflight samples evaluated with similar methods and comparisons will be made between the radiation-treated groups and the spaceflight samples. CONCLUSION It seems likely that radiation exposure triggers homeostatic mechanisms, which could include alterations of gene expression. Better understanding of these pathways could aid in optimizing medications doses given to crewmembers who require treatment and eventually, to development of new countermeasures to ameliorate or prevent radiation-induced damage to cells and tissues.

Wotring, V. E.↗
NASA NTRS2014

Radiation Quality Effects on Transcriptome Profiles in 3-D Cultures After Charged Particle Irradiation

In this work, we evaluated the differential effects of low- and high-LET radiation on 3-D organotypic cultures in order to investigate radiation quality impacts on gene expression and cellular responses. Current risk models for assessment of space radiation-induced cancer have large uncertainties because the models for adverse health effects following radiation exposure are founded on epidemiological analyses of human populations exposed to low-LET radiation. Reducing these uncertainties requires new knowledge on the fundamental differences in biological responses (the so-called radiation quality effects) triggered by heavy ion particle radiation versus low-LET radiation associated with Earth-based exposures. In order to better quantify these radiation quality effects in biological systems, we are utilizing novel 3-D organotypic human tissue models for space radiation research. These models hold promise for risk assessment as they provide a format for study of human cells within a realistic tissue framework, thereby bridging the gap between 2-D monolayer culture and animal models for risk extrapolation to humans. To identify biological pathway signatures unique to heavy ion particle exposure, functional gene set enrichment analysis (GSEA) was used with whole transcriptome profiling. GSEA has been used extensively as a method to garner biological information in a variety of model systems but has not been commonly used to analyze radiation effects. It is a powerful approach for assessing the functional significance of radiation quality-dependent changes from datasets where the changes are subtle but broad, and where single gene based analysis using rankings of fold-change may not reveal important biological information.

Patel, Zarana S.↗
NASA NTRS2014

Radiation Quality Effects on Transcriptome Profiles in 3-d Cultures After Particle Irradiation

In this work, we evaluate the differential effects of low- and high-LET radiation on 3-D organotypic cultures in order to investigate radiation quality impacts on gene expression and cellular responses. Reducing uncertainties in current risk models requires new knowledge on the fundamental differences in biological responses (the so-called radiation quality effects) triggered by heavy ion particle radiation versus low-LET radiation associated with Earth-based exposures. We are utilizing novel 3-D organotypic human tissue models that provide a format for study of human cells within a realistic tissue framework, thereby bridging the gap between 2-D monolayer culture and animal models for risk extrapolation to humans. To identify biological pathway signatures unique to heavy ion particle exposure, functional gene set enrichment analysis (GSEA) was used with whole transcriptome profiling. GSEA has been used extensively as a method to garner biological information in a variety of model systems but has not been commonly used to analyze radiation effects. It is a powerful approach for assessing the functional significance of radiation quality-dependent changes from datasets where the changes are subtle but broad, and where single gene based analysis using rankings of fold-change may not reveal important biological information. We identified 45 statistically significant gene sets at 0.05 q-value cutoff, including 14 gene sets common to gamma and titanium irradiation, 19 gene sets specific to gamma irradiation, and 12 titanium-specific gene sets. Common gene sets largely align with DNA damage, cell cycle, early immune response, and inflammatory cytokine pathway activation. The top gene set enriched for the gamma- and titanium-irradiated samples involved KRAS pathway activation and genes activated in TNF-treated cells, respectively. Another difference noted for the high-LET samples was an apparent enrichment in gene sets involved in cycle cycle/mitotic control. It is plausible that the enrichment in these particular pathways results from the complex DNA damage resulting from high-LET exposure where repair processes are not completed during the same time scale as the less complex damage resulting from low-LET radiation.

Patel, Z. S.↗
NASA NTRS2000

Evidence that simulated microgravity may alter the vascular nonreceptor tyrosine kinase second messenger pathway

Simulated microgravity (hind limb unweighting; HU) reduces maximal contractile capacity to norepinephrine (NE) but not 5-hydroxytryptamine (5-HT) in the rat abdominal aorta of male Wistar rats. Our earlier study showed that voltage-operated calcium channels, the MAPK pathway [1], and vasoconstrictive prostaglandins contribute to the NE-induced contraction of control (C) but not HU, aorta rings. Genistein, a general tyrosine kinase inhibitor, caused a significant reduction in vascular contractility in C but not HU arteries. The present study explored the role of protein kinase C (PKC) and extracellular receptor-activated kinase 1 and 2 (ERK1/2) in the HU-induced vascular hyporesponsiveness to NE. Microgravity was simulated in Wistar rats by 20 day HU. The abdominal aorta was removed from control and HU rats, cut into 3 mm rings, and mounted in tissue baths to measure isometric contraction. Protein levels were determined using Western blot analysis. PD98059, a selective MAPKK inhibitor, caused a marked inhibition of NE-induced contraction in both C and HU arteries. Calphostin C, a PKC inhibitor, completely abolished the contractile response to NE in both C and HU tissues. Phosphorylated (activated) ERK1/2 protein mass was greater in C, compared to HU, aortas, and was reduced by genistein only in C tissues. MAPK total protein levels in the rat aorta were increased in the HU-treated, compared to C, animals. These results indicate that PKC represents an early transduction step in the contractile response to NE in the rat abdominal aorta. That inhibition of the step immediately before activation of MAPK reduced contraction in both C and HU tissues, while general tyrosine kinase inhibition with genistein blocked only the control responses, suggests that a nonreceptor tyrosine kinase may be involved in HU-induced vascular hyporesponsiveness to NE.

Non-NASA Center↗
NASA NTRS1977

Method of adhering bone to a rigid substrate using a graphite fiber reinforced bone cement

A method is described for adhering bone to the surface of a rigid substrate such as a metal or resin prosthesis using an improved surgical bone cement. The bone cement has mechanical properties more nearly matched to those of animal bone and thermal curing characteristics which result in less traumatization of body tissues and comprises a dispersion of short high modulus graphite fibers within a bonder composition including polymer dissolved in reactive monomer such as polymethylmethacrylate dissolved in methylmethacrylate monomer.

Knoell, A. C.↗
NASA NTRS1986

Biological and Medical Experiments on the Space Shuttle, 1981 - 1985

This volume is the first in a planned series of reports intended to provide a comprehensive record of all the biological and medical experiments and samples flown on the Space Shuttle. Experiments described have been conducted over a five-year period, beginning with the first plant studies conducted on STS-2 in November 1981, and extending through STS 61-C, the last mission to fly before the tragic Challenger accident of January 1986. Experiments were sponsored within NASA not only by the Life Sciences Division of the Office of Space Science and Applications, but also by the Shuttle Student Involvement Program (SSIP) and the Get Away Special (GAS) Program. Independent medical studies were conducted as well on the Shuttle crew under the auspices of the Space Biomedical Research Institute at Johnson Space Center. In addition, cooperative agreements between NASA and foreign government agencies led to a number of independent experiments and also paved the way for the joint US/ESA Spacelab 1 mission and the German (DFVLR) Spacelab D-1. Experiments included: (1) medically oriented studies of the crew aimed at identifying, preventing, or treating health problems due to space travel; (2) projects to study morphological, physiological, or behavioral effects of microgravity on animals and plants; (3) studies of the effects of microgravity on cells and tissues; and (4) radiation experiments monitoring the spacecraft environment with chemical or biological dosimeters or testing radiation effects on simple organisms and seeds.

Halstead, Thora W.↗
NASA NTRS2011

CPRIT/Johnson Space Center, September, 2011 (Cancer Prevention and Research Institute of Texas)

JSC researchers study carcinogenesis, cancer prevention and treatment along with epidemiological (primarily retrospective and longitudinal) studies, modeling, and interactions with the environment such as radiation, nutritional, and endocrine changes related to space flight along with behaviors such as smoking. Cancer research is a major focus for human space flight due to the exposure to space radiation which consists of particles of varying charges and energies, and secondary neutrons. The JSC laboratories collaborate with investigators from the U.S. as well as our European and Japanese partners. We use accelerator facilities at the Brookhaven National Laboratory, Loma Linda University and Los Alamos National Laboratory that generate high energy charged particles and neutrons to simulate cosmic radiation and solar particle events. The research using cultured cells and animals concentrates on damage and repair from the level of DNA to organ tissues, due to exposure to simulated space radiation exposure, that contribute to the induction of leukemia and solid tumors in most major tissues such as lung, colon, liver and breast. The goal of the research is to develop a mathematical model that can predict cancer morbidity and mortality risks with sufficient accuracy for a given space mission.

Davis, Jeffrey↗
NASA NTRS1995

Connective tissue integrity is lost in vitamin B-6-deficient chicks

The objective of the present investigation was to characterize further the connective tissue disorder produced by pyridoxine (vitamin B-6) deficiency, as previously evidenced by electron microscopy. Following the second post-natal week, fast growing male chicks were deprived of pyridoxine for a 1-mo period. Six weeks post-natally, blood concentrations in the experimental deficiency group had declined to deficiency levels as registered by low concentrations of pyridoxal phosphate (coenzyme form) in erythrocytes, but did not reach levels associated with neurological symptoms. Light microscopic study showed abnormalities in the extracellular matrix of the connective tissues. Collagen cross-links and the aldehyde contents were not significantly lower in cartilage and tendon collagens of vitamin B-6-deficient animals than in age-matched controls; also, their proteoglycan degrading protease and collagenase activities measured in articular cartilages were not greater. Thus, proteolysis was an unlikely alternative mechanism to account for the loss of connective tissue integrity. These results point to the need for further investigation into adhesive properties of collagen associated proteoglycans or other proteins in vitamin B-6-deficient connective tissue.

Non-NASA Center↗
NASA NTRS1972

Effect of continuous gamma-ray exposure on performance of learned tasks and effect of subsequent fractionated exposures on blood-forming tissue

Sixteen monkeys trained to perform continuous and discrete-avoidance and fixed-ratio tasks with visual and auditory cues were performance-tested before, during, and after 10-day gamma-ray exposures totaling 0, 500, 750, and 1000 rads. Approximately 14 months after the performance-test exposures, surviving animals were exposed to 100-rad gamma-ray fractions at 56-day intervals to observe injury and recovery patterns of blood-forming tissues. The fixed-ratio, food-reward task performance showed a transient decline in all dose groups within 24 hours of the start of gamma-ray exposure, followed by recovery to normal food-consumption levels within 48 to 72 hours. Avoidance tasks were performed successfully by all groups during the 10-day exposure, but reaction times of the two higher dose-rate groups in which animals received 3 and 4 rads per hour or total doses of 750 and 1000 rads, respectively, were somewhat slower.

Spalding, J. F.↗
NASA NTRS1995

Integrin-extracellular matrix interactions in connective tissue remodeling and osteoblast differentiation

The differentiaton of bone cells is a complex multistep process. Bone is somewhat unusual in that it is very actively and continually remodeled in the adult and that maintenance of its mass in the mature organism is exquisitely sensitive to mechanical as well as chemical signals. Bone is also unique because it consists of a very large amount of extracellular matrix (ECM) that is mineralized. The integrin family of ECM receptors has been shown to play an important role in tissue morphogenesis in several systems. Our studies on the regulation of matrix remodeling enzymes by integrins in rabbit synovial fibroblasts show that two b1 integrin fibronectin (FN) receptor complexes (alpha 5 beta 1 and alpha 4 beta 1) cooperate in detecting subtle changes in the composition of the ECM. As a result of signal transduction by these integrins, the levels of mRNA and protein for several members of the metalloproteinase family are regulated in these cells. We have also used antibody and RGD peptide perturbation studies to determine the significance of cell/ECM interactions to normal osteogenesis. We found that interactions between the cell binding domain of FN and integrins are required for both normal morphogenesis and gene expression in cultured osteoblasts that differentiate to form bone-like tissue in culture. These data lead us to propose that beta 1 integrins play an important role in osteoblast differentiation as well as in bone remodeling.

NASA Discipline Number 26-10↗
NASA NTRS1984

Effect of dietary vitamin E or selenium on prostaglandin dehydrogenase in hyperoxic rat lung

Weanling male rats were fed semipurified diets supplemented with 0, 60, or 600 IU/kg vitamin E or 0, 100, or 1000 ppb selenium. One group was injected daily with vitamin E at a rate equivalent to consumption of 60 IU/kg. Animals from all groups were sacrificed after exposure to normobaric oxygen or air for 48 h. Lung tissue was analyzed for the combined activity of prostaglandin dehydrogenase and reductase. Using the decline in enzyme activity as an indicator of susceptibility to oxygen poisoning, protection against hyperoxia was directly related to the level of vitamin E supplementation. Selenium supplemented at 100 ppb provided significant protection when compared to 0 ppb or 1000 ppb. The latter dose may have been marginally toxic. Thus dietary supplementation of vitamin E and selenium may influence the relative susceptibility of an animal to pulmonary oxygen poisoning.

North, L. N.↗
NASA NTRS1983

A study of stress-free living bone and its application to space flight

Observations of animals and human subjects in weightless space flight (Skylab and COSMOS) document altered bone metabolism. Bone metabolism is affected by a number of local and systemic factors. The calcification and growth of transplanted bone is independent of local muscle, nervous, and mechanical forces; therefore, transplanted bone would provide data on the role of local vs. systematic factors. Bone metabolism in living transplanted bone, devoid of stress, was investigated as a possible tool for the investigation of countermeasures against disuse bone loss. An animal model using Sprague-Dawley rats was developed for transplantation of femur bone tissue on a nutrient vascular pedicel. The long term course of these implants was assessed through the measure of regional and total bone mineral, blood flow, and methylene diphosphonate (MDP) uptake. Clomid, an estrogen agonist/antagonist, was shown to protect bone from disuse loss of minerals by retarding trabecular and cortical resorption.

Leblanc, A.↗
NASA NTRS2002

Neurovestibular modulation of circadian and homeostatic regulation: vestibulohypothalamic connection?

Chronic exposure to increased force environments (+G) has pronounced effects on the circadian and homeostatic regulation of body temperature (T(b)), ambulatory activity (Act), heart rate, feeding, and adiposity. By using the Brn 3.1 knockout mouse, which lacks vestibular hair cells, we recently described a major role of the vestibular system in mediating some of these adaptive responses. The present study used the C57BL6JEi-het mouse strain (het), which lacks macular otoconia, to elucidate the contribution of specific vestibular receptors. In this study, eight het and eight WT mice were exposed to 2G for 8 weeks by means of chronic centrifugation. In addition, eight het and eight WT mice were maintained as 1G controls in similar conditions. Upon 2G exposure, the WT exhibited a decrease in T(b) and an attenuated T(b) circadian rhythm. Act means and rhythms also were attenuated. Body mass and food intake were significantly lower than the 1G controls. After 8 weeks, percent body fat was significantly lower in the WT mice (P < 0.0001). In contrast, the het mice did not exhibit a decrease in mean T(b) and only a slight decrease in T(b) circadian amplitude. het Act levels were attenuated similarly to the WT mice. Body mass and food intake were only slightly attenuated in the het mice, and percent body fat, after 8 weeks, was not different in the 2G het group. These results link the vestibular macular receptors with specific alterations in homeostatic and circadian regulation.

NASA Discipline Regulatory Physiology↗