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At least 451 records · Page 25

Probability of cell hits in selected organs and tissues by high-LET particles at the ISS orbit

The fluence of high-LET particles (HLP) with LET infinity H2O greater than 15 keV micrometers-1 in selected organs and tissues were measured with plastic nuclear track detectors using a life-size human phantom on the 9th Shuttle-Mir Mission (STS-91). The planar-track fluence of HLP during the 9.8-day mission ranged from 1.9 x 10(3) n cm-2 (bladder) to 5.1 x 10(3) n cm-2 (brain) by a factor of 2.7. Based on these data, a probability of HLP hits to a matured cell of each organ or tissue was roughly estimated for a 90-day ISS mission. In the calculation, all cells were assumed to be spheres with a geometric cross-sectional area of 500 micrometers2 and the cell-hit frequency from isotropic space radiation can be described by the Poisson-distribution function. As results, the probability of one or more than 1 hit to a single cell by HLP for 90 days ranged from 17% to 38%; that of two or more than 2 hits was estimated to be 1.3-8.2%. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

NASA Discipline Radiation Health↗

Monte Carlo transport model comparison with 1A GeV accelerated iron experiment: heavy-ion shielding evaluation of NASA space flight-crew foodstuff

Deep-space manned flight as a reality depends on a viable solution to the radiation problem. Both acute and chronic radiation health threats are known to exist, with solar particle events as an example of the former and galactic cosmic rays (GCR) of the latter. In this experiment Iron ions of 1A GeV are used to simulate GCR and to determine the secondary radiation field created as the GCR-like particles interact with a thick target. A NASA prepared food pantry locker was subjected to the iron beam and the secondary fluence recorded. A modified version of the Monte Carlo heavy ion transport code developed by Zeitlin at LBNL is compared with experimental fluence. The foodstuff is modeled as mixed nuts as defined by the 71st edition of the Chemical Rubber Company (CRC) Handbook of Physics and Chemistry. The results indicate a good agreement between the experimental data and the model. The agreement between model and experiment is determined using a linear fit to ordered pairs of data. The intercept is forced to zero. The slope fit is 0.825 and the R2 value is 0.429 over the resolved fluence region. The removal of an outlier, Z=14, gives values of 0.888 and 0.705 for slope and R2 respectively. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

NASA Discipline Radiation Health↗

Temazepam, but not zolpidem, causes orthostatic hypotension in astronauts after spaceflight

Insomnia is a common symptom, not only in the adult population but also in many astronauts. Hypnotics, such as temazepam (a benzodiazepine) and zolpidem (an imidazopyridine), are often taken to relieve insomnia. Temazepam has been shown clinically to have hemodynamic side effects, particularly in the elderly; however, the mechanism is not clear. Zolpidem does not cause hemodynamic side effects. The purpose of this study was to determine whether the use of different hypnotics during spaceflight might contribute significantly to the high incidence of postflight orthostatic hypotension, and to compare the findings in astronauts with clinical research. Astronauts were separated into three groups: control (n = 40), temazepam (15 or 30 mg; n = 9), and zolpidem (5 or 10 mg; n = 8). In this study, temazepam and zolpidem were only taken the night before landing. The systolic and diastolic blood pressures and heart rates of the astronauts were measured during stand tests before spaceflight and on landing day. On landing day, systolic pressure decreased significantly and heart rate increased significantly in the temazepam group, but not in the control group or in the zolpidem group. Temazepam may aggravate orthostatic hypotension after spaceflight when astronauts are hemodynamically compromised. Temazepam should not be the initial choice as a sleeping aid for astronauts. These results in astronauts may help to explain the hemodynamic side effects in the elderly who are also compromised. Zolpidem may be a better choice as a sleeping aid in these populations.

STS Shuttle Project↗

Locomotion in simulated microgravity: gravity replacement loads

BACKGROUND: When an astronaut walks or runs on a treadmill in microgravity, a subject load device (SLD) is used to return him or her back to the treadmill belt. The gravity replacement load (GRL) in the SLD is transferred, via a harness, to the pelvis and/or the shoulders. This research compared comfort and ground reaction forces during treadmill running in a microgravity locomotion simulator at GRLs of 60%, 80%, and 100% of body weight (BW). Two harness designs (shoulder springs only (SSO) and waist and shoulder springs (WSS)) were used. HYPOTHESES: 1) The 100% BW gravity replacement load conditions would be comfortably tolerated and would result in larger ground reaction forces and loading rates than the lower load conditions, and 2) the WSS harness would be more comfortable than the SSO harness. METHODS: Using the Penn State Zero Gravity Locomotion Simulator (ZLS), 8 subjects ran at 2.0 m x s(-1) (4.5 mph) for 3 min at each GRL setting in each harness. Subjective ratings of harness comfort, ground reaction forces, and GRL data were collected during the final minute of exercise. RESULTS: The 100% BW loading conditions were comfortably tolerated (2.3 on a scale of 0-10), although discomfort increased as the GRL increased. There were no overall differences in perceived comfort between the two harnesses. The loading rates (27.1, 33.8, 39.1 BW x s(-1)) and the magnitudes of the first (1.0, 1.4, 1.6 BW) and second (1.3, 1.7, 1.9 BW) peaks of the ground reaction force increased with increasing levels (60, 80, 100% BW respectively) of GRL. CONCLUSIONS: Subjects were able to tolerate a GRL of 100% BW well. The magnitude of the ground reaction force peaks and the loading rate is directly related to the magnitude of the GRL.

NASA Discipline Musculoskeletal↗

Tetracycline rapidly reaches all the constituent cells of uropathogenic Escherichia coli biofilms

We have developed a method for visualizing Escherichia coli cells that are exposed to tetracycline in a biofilm, based on a previous report that liposomes containing the E. coli TetR(B) protein fluoresce when exposed to this antibiotic. By our method, cells devoid of TetR(B) also exhibited tetracycline-dependent fluorescence. At 50 microg of tetracycline ml(-1), planktonic cells of a uropathogenic E. coli (UPEC) strain developed maximal fluorescence after 7.5 to 10 min of exposure. A similar behavior was exhibited by cells in a 24- or 48-h UPEC biofilm, as examined by confocal laser microscopy, regardless of whether they lined empty spaces or occupied densely packed regions. Further, a comparison of phase-contrast and fluorescent images of corresponding biofilm zones showed that all the cells fluoresced. Thus, all the biofilm cells were exposed to tetracycline and there were no pockets within the biofilm where the antibiotic failed to reach. It also appeared unlikely that niches of reduced exposure to the antibiotic existed within the biofilms.

Non-NASA Center↗

Differential effects of catecholamines on in vitro growth of pathogenic bacteria

Supplementation of minimal medium inoculated with bacterial cultures with norepinephrine, epinephrine, dopamine, or isoproterenol resulted in marked increases in growth compared to controls. Norepinephrine and dopamine had the greatest enhancing effects on growth of cultures of Pseudomonas aeruginosa and Klebsiella pneumoniae, while epinephrine and isoproterenol also enhanced growth to a lesser extent. The growth of Escherichia coli in the presence of norepinephrine was greater than growth in the presence of the three other neurochemicals used in the study. Growth of Staphylococcus aureus was also enhanced in the presence of norepinephrine, but not to the same degree as was the growth of gram negative bacteria. Addition of culture supernatants from E. coli cultures that had been grown in the presence of norepinephrine was able to enhance the growth of K. pneumoniae. Addition of the culture supernatant fluid culture from E. coli cultures that had been grown in the presence of norepinephrine did not enhance growth of P. aeruginosa or S. aureus. Culture supernatant fluids from bacteria other than E. coli grown in the presence of norepinephrine were not able to enhance the growth of any bacteria tested. The results suggest that catecholamines can enhance growth of pathogenic bacteria, which may contribute to development of pathogenesis; however, there is no uniform effect of catecholamines on bacterial growth.

Non-NASA Center↗

Plasma membrane NADH oxidase of maize roots responds to gravity and imposed centrifugal forces

NADH oxidase activities measured with excised roots of dark-grown maize (Zea mays) seedlings and with isolated plasma membrane vesicles from roots of dark-grown maize oscillated with a regular period length of 24 min and were inhibited by the synthetic auxin 2,4-dichlorophenoxyacetic [correction of dichorophenoxyacetic] acid. The activities also responded to orientation with respect to gravity and to imposed centrifugal forces. Turning the roots upside down resulted in stimulation of the activity with a lag of about 10 min. Returning the sections to the normal upright position resulted in a return to initial rates. The activity was stimulated reversibly to a maximum of about 2-fold with isolated plasma membrane vesicles, when subjected to centrifugal forces of 25 to 250 x g for 1 to 4 min duration. These findings are the first report of a gravity-responsive enzymatic activity of plant roots inhibited by auxin and potentially related to the gravity-induced growth response. c2001 Editions scientifiques et medicales Elsevier SAS.

NASA Discipline Cell Biology↗

Baroreflex modulation of muscle sympathetic nerve activity during cold pressor test in humans

The purpose of this project was to test the hypothesis that baroreceptor modulation of muscle sympathetic nerve activity (MSNA) and heart rate is altered during the cold pressor test. Ten subjects were exposed to a cold pressor test by immersing a hand in ice water for 3 min while arterial blood pressure, heart rate, and MSNA were recorded. During the second and third minute of the cold pressor test, blood pressure was lowered and then raised by intravenous bolus infusions of sodium nitroprusside and phenylephrine HCl, respectively. The slope of the relationship between MSNA and diastolic blood pressure was more negative (P < 0.005) during the cold pressor test (-244.9 +/- 26.3 units x beat(-1) x mmHg(-1)) when compared with control conditions (-138.8 +/- 18.6 units x beat(-1) x mmHg(-1)), whereas no significant change in the slope of the relationship between heart rate and systolic blood pressure was observed. These data suggest that baroreceptors remain capable of modulating MSNA and heart rate during a cold pressor test; however, the sensitivity of baroreflex modulation of MSNA is elevated without altering the sensitivity of baroreflex control of heart rate.

NASA Discipline Cardiopulmonary↗

Overexpression of neurofilament H disrupts normal cell structure and function

Studying exogenously expressed tagged proteins in live cells has become a standard technique for evaluating protein distribution and function. Typically, expression levels of experimentally introduced proteins are not regulated, and high levels are often preferred to facilitate detection. However, overexpression of many proteins leads to mislocalization and pathologies. Therefore, for normative studies, moderate levels of expression may be more suitable. To understand better the dynamics of intermediate filament formation, transport, and stability in a healthy, living cell, we inserted neurofilament heavy chain (NFH)-green fluorescent protein (GFP) fusion constructs in adenoviral vectors with tetracycline (tet)-regulated promoters. This system allows for turning on or off the synthesis of NFH-GFP at a selected time, for a defined period, in a dose-dependent manner. We used this inducible system for live cell imaging of changes in filament structure and cell shape, motility, and transport associated with increasing NFH-GFP expression. Cells with low to intermediate levels of NFH-GFP were structurally and functionally similar to neighboring, nonexpressing cells. In contrast, overexpression led to pathological alterations in both filament organization and cell function. Copyright 2002 Wiley-Liss, Inc.

Non-NASA Center↗

The response of tissue-equivalent proportional counters to heavy ions

The paper presents a theoretical model for the response of a tissue-equivalent proportional counter (TEPC) irradiated with charged particles. Heavy ions and iron ions in particular constitute a significant part of radiation in space. TEPCs are used for all space shuttle and International Space Station (ISS) missions to estimate the dose and radiation quality (in terms of lineal energy) inside spacecraft. The response of the tissue-equivalent proportional counters shows distortions at the wall/cavity interface. In this paper, we present microdosimetric investigation using Monte Carlo track structure calculations to simulate the response of a TEPC to charged particles of various LET (1 MeV protons, 2.4 MeV alpha particles, 46 MeV/nucleon 20Ne, 55 MeV/nucleon 20Ne, 45 MeV/nucleon 40Ar, and 1.05 GeV/nucleon 56Fe). Data are presented for energy lost and energy absorbed in the counter cavity and wall. The model calculations are in good agreement with the results of Rademacher et al. (Radiat. Res. 149, 387-389, 1998), including the study of the interface between the wall and the sensitive region of the counter. It is shown that the anomalous response observed at large event sizes in the experiment is due to an enhanced entry of secondary electrons from the wall into the gas cavity.

NASA Discipline Radiation Health↗

Genomic instability and bystander effects: a paradigm shift in radiation biology?

A basic paradigm in radiobiology is that, following exposure to ionizing radiation, the deposition of energy in the cell nucleus and the resulting damage to DNA, the principal target, are responsible for the radiation's deleterious biological effects. Findings in two rapidly expanding fields of research--radiation-induced genomic instability and bystander effects--have caused us to reevaluate these central tenets. In this article, the potential influence of induced genomic instability and bystander effects on cellular injury after exposure to low-level radiation will be reviewed.

NASA Discipline Radiation Health↗

Evidence for factors modulating radiation-induced G2-delay: potential application as radioprotectors

Manipulation of checkpoint response to DNA damage can be developed as a means for protecting astronauts from the adverse effects of unexpected, or background exposures to ionizing radiation. To achieve this goal reagents need to be developed that protect cells from radiation injury by prolonging checkpoint response, thus promoting repair. We present evidence for a low molecular weight substance excreted by cells that dramatically increases the duration of the G2-delay. This compound is termed G2-Arrest Modulating Activity (GAMA). A rat cell line (A1-5) generated by transforming rat embryo fibroblasts with a temperature sensitive form of p53 plus H-ras demonstrates a dramatic increase in radiation resistance after exposure to low LET radiation that is not associated with an increase in the efficiency of rejoining of DNA double strand breaks. Radioresistance in this cell line correlates with a dramatic increase in the duration of the G2 arrest that is modulated by a GAMA produced by actively growing cells. The properties of GAMA suggest that it is a low molecular weight heat-stable peptide. Further characterization of this substance and elucidation of its mechanism of action may allow the development of a biological response modifier with potential applications as a radioprotector. GAMA may be useful for protecting astronauts from radiation injury as preliminary evidence suggests that it is able to modulate the response of cells exposed to heavy ion radiation, similar to that encountered in outer space.

NASA Discipline Radiation Health↗

Arthromitus (Bacillus cereus) symbionts in the cockroach Blaberus giganteus: dietary influences on bacterial development and population density

The filamentous spore-forming bacterium Arthromitus, discovered in termites, millipedes, sow bugs and other soil-dwelling arthropods by Leidy (1850), is the intestinal stage of Bacillus cereus. We extend the range of Arthromitus habitats to include the hindgut of Blaberus giganteus, the large tropical American cockroach. The occurrence and morphology of the intestinal form of the bacillus were compared in individual cockroaches (n=24) placed on four different diet regimes: diurnally maintained insects fed (1) dog food, (2) soy protein only, (3)purified cellulose only, and (4) a dog food-fed group maintained in continuous darkness. Food quality exerted strong influence on population densities and developmental stages of the filamentous bacterium and on fecal pellet composition. The most dramatic rise in Arthromitus populations, defined as the spore-forming filament intestinal stage, occurred in adult cockroaches kept in the dark on a dog food diet. Limited intake of cellulose or protein alone reduced both the frequency of Arthromitus filaments and the rate of weight gain of the insects. Spores isolated from termites, sow bugs, cockroaches and moths, grown on various hard surfaces display a branching mobility and resistance to antibiotics characteristic to group I Bacilli whose members include B. cereus, B. circulans, B. alvei and B. macerans. DNA isolated from pure cultures of these bacilli taken from the guts of Blaberus giganteus (cockroach), Junonia coenia (moth), Porcellio scaber (sow bug) and Cryptotermes brevis (termite) and subjected to Southern hybridization with a 23S-5S B. subtilis ribosomal sequence probe verified that they are indistinguishable from laboratory strains of Bacillus cereus.

NASA Discipline Exobiology↗

Extracellular signaling through the microenvironment: a hypothesis relating carcinogenesis, bystander effects, and genomic instability

Cell growth, differentiation and death are directed in large part by extracellular signaling through the interactions of cells with other cells and with the extracellular matrix; these interactions are in turn modulated by cytokines and growth factors, i.e. the microenvironment. Here we discuss the idea that extracellular signaling integrates multicellular damage responses that are important deterrents to the development of cancer through mechanisms that eliminate abnormal cells and inhibit neoplastic behavior. As an example, we discuss the action of transforming growth factor beta (TGFB1) as an extracellular sensor of damage. We propose that radiation-induced bystander effects and genomic instability are, respectively, positive and negative manifestations of this homeostatic process. Bystander effects exhibited predominantly after a low-dose or a nonhomogeneous radiation exposure are extracellular signaling pathways that modulate cellular repair and death programs. Persistent disruption of extracellular signaling after exposure to relatively high doses of ionizing radiation may lead to the accumulation of aberrant cells that are genomically unstable. Understanding radiation effects in terms of coordinated multicellular responses that affect decisions regarding the fate of a cell may necessitate re-evaluation of radiation dose and risk concepts and provide avenues for intervention.

NASA Discipline Radiation Health↗

Rejoining of isochromatid breaks induced by heavy ions in G2-phase normal human fibroblasts

We reported previously that exposure of normal human fibroblasts in G2 phase of the cell cycle to high-LET radiation produces a much higher frequency of isochromatid breaks than exposure to gamma rays. We concluded that an increase in the production of isochromatid breaks is a signature of initial high-LET radiation-induced G2-phase damage. In this paper, we report the repair kinetics of isochromatid breaks induced by high-LET radiation in normal G2-phase human fibroblasts. Exponentially growing human fibroblasts (AG1522) were irradiated with gamma rays or energetic carbon (290 MeV/nucleon), silicon (490 MeV/nucleon), or iron (200 MeV/nucleon) ions. Prematurely condensed chromosomes were induced by calyculin A after different postirradiation incubation times ranging from 0 to 600 min. Chromosomes were stained with Giemsa, and aberrations were scored in cells at G2 phase. G2-phase fragments, the result of the induction of isochromatid breaks, decreased quickly with incubation time. The curve for the kinetics of the rejoining of chromatid-type breaks showed a slight upward curvature with time after exposure to 440 keV/microm iron particles, probably due to isochromatid-isochromatid break rejoining. The formation of chromatid exchanges after exposure to high-LET radiation therefore appears to be underestimated, because isochromatid-isochromatid exchanges cannot be detected. Increased induction of isochromatid breaks and rejoining of isochromatid breaks affect the overall kinetics of chromatid-type break rejoining after exposure to high-LET radiation.

NASA Center JSC↗

Latency and activation in the control of TGF-beta

The biological activity of the transforming growth factor-beta's (TGF-beta)3 is tightly controlled by their persistence in the extracellular compartment as latent complexes. Each of the three mammalian isoform genes encodes a product that is cleaved intracellularly to form two polypeptides, each of which dimerizes. Mature TGF-beta, a 24 kD homodimer, is noncovalently associated with the 80 kD latency-associated peptide (LAP). LAP is a fundamental component of TGF-beta that is required for its efficient secretion, prevents it from binding to ubiquitous cell surface receptors, and maintains its availability in a large extracellular reservoir that is readily accessed by activation. This latent TGF-beta complex (LTGF-beta) is secreted by all cells and is abundant both in circulating forms and bound to the extracellular matrix. Activation describes the collective events leading to the release of TGF-beta. Despite the importance of TGF-beta regulation of growth and differentiation in physiological and malignant tissue processes, remarkably little is known about the mechanisms of activation in situ. Recent studies of irradiated mammary gland reveal certain features of TGF-beta 1 activation that may shed light on its regulation and potential roles in the normal and neoplastic mammary gland.

Non-NASA Center↗

Gravity and light control of the developmental polarity of regenerating protoplasts isolated from prothallial cells of the fern Ceratopteris richardii

A procedure has been developed for isolating protoplasts from prothalli of Ceratopteris richardii which can be cultured and are capable of regeneration. Protoplasts were isolated from 2-week-old gametophytes in a medium containing wall-digesting enzymes in 0.5 M sucrose, followed by purification of the released protoplasts by floating them up into a 0.5 M sorbitol layer. Regeneration occurred over a period of 10-24 days, and, under optimal osmotic conditions, followed the developmental pattern seen during spore germination, in that the first division gave rise to a primary rhizoid. Thus, prothallial protoplasts are comparable to germinating spores as suitable models for studies of developmental polarity in single cells. As in germinating spores, the polarity of development in regenerating protoplasts is influenced by the vectors of gravity and unilateral light. However, the relative influence of light in fixing this polarity is greater in regenerating protoplasts, while in germinating spores, the influence of gravity is greater.

NASA Discipline Plant Biology↗

Spermine stimulation of a nuclear NII kinase from pea plumules and its role in the phosphorylation of a nuclear polypeptide

We have previously demonstrated that spermine stimulates the phosphorylation of a 47 kilodalton nuclear polypeptide from pea plumules (N Datta, LK Hardison, SJ Roux 1986 Plant Physiol 82: 681-684). In this paper we report that spermine stimulates the activity of a cyclic AMP independent casein kinase, partially purified from a chromatin fraction of pea plumule nuclei. This effect of spermine was substrate specific; i.e. with casein as substrate, spermine stimulated the kinase activity, and with phosvitin as substrate, spermine completely inhibited the activity. The stimulation by spermine of the casein kinase was, in part, due to the lowering of the Mg2+ requirement of the kinase. Heparin could partially inhibit this casein kinase activity and spermine completely overcame this inhibition. By further purification of the casein kinase extract on high performance liquid chromatography, we fractionated it into an NI and an NII kinase. Spermine stimulated the NII kinase by 5- to 6-fold but had no effect on the NI kinase. Using [gamma-32P]GTP, we have shown that spermine promotes the phosphorylation of the 47 kilodalton polypeptide(s) in isolated nuclei, at least in part by stimulating an NII kinase.

NASA Discipline Plant Biology↗