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All sourcesNASA NTRSDOE OSTI
NASA NTRS1992

Synergistic action of the benzene metabolite hydroquinone on myelopoietic stimulating activity of granulocyte/macrophage colony-stimulating factor in vitro

The effects of in vitro pretreatment with benzene metabolites on colony-forming response of murine bone marrow cells stimulated with recombinant granulocyte/macrophage colony-stimulating factor (rGM-CSF) were examined. Pretreatment with hydroquinone (HQ) at concentrations ranging from picomolar to micromolar for 30 min resulted in a 1.5- to 4.6-fold enhancement in colonies formed in response to rGM-CSF that was due to an increase in granulocyte/macrophage colonies. The synergism equaled or exceeded that reported for the effects of interleukin 1, interleukin 3, or interleukin 6 with GM-CSF. Optimal enhancement was obtained with 1 microM HQ and was largely independent of the concentration of rGM-CSF. Pretreatment with other authentic benzene metabolites, phenol and catechol, and the putative metabolite trans, trans-muconaldehyde did not enhance growth factor response. Coadministration of phenol and HQ did not enhance the maximal rGM-CSF response obtained with HQ alone but shifted the optimal concentration to 100 pM. Synergism between HQ and rGM-CSF was observed with nonadherent bone marrow cells and lineage-depleted bone marrow cells, suggesting an intrinsic effect on recruitment of myeloid progenitor cells not normally responsive to rGM-CSF. Alterations in differentiation in a myeloid progenitor cell population may be of relevance in the pathogenesis of acute myelogenous leukemia secondary to drug or chemical exposure.

NASA Discipline Environmental Health↗
NASA NTRS1992

Influence of exercise training on the oxidative capacity of rat abdominal muscles

Our purpose was to determine if endurance exercise training would increase the oxidative capacity of the abdominal expiratory muscles of the rat. Accordingly, 9 male rats were subjected to an endurance training protocol (1 h/day, 6 days/week, 9 weeks) and 9 litter-mates served as controls. Citrate synthase (CS) activity was used as an index of oxidative capacity, and was determined in the following muscles: soleus, plantaris, costal diaphragm, crural diaphragm, and in all four abdominal muscles: rectus abdominis, transversus abdominis, external oblique, and internal oblique. Compared to their non-trained litter-mates, the trained rats had higher peak whole body oxygen consumption rates (+ 16%) and CS activities in plantaris (+34%) and soleus (+36%) muscles. Thus, the training program caused substantial systemic and locomotor muscle adaptations. The CS activity of costal diaphragm was 20% greater in the trained animals, but no difference was observed in crural diaphragm. The CS activity in the abdominal muscles was less than one-half of that in locomotor and diaphragm muscles, and there were no significant changes with training except in the rectus abdominis where a 26% increase was observed. The increase in rectus abdominis CS activity may reflect its role in postural support and/or locomotion, as none of the primary expiratory pumping muscles adapted to the training protocol. The relatively low levels of CS activity in the abdominal muscles suggests that they are not recruited frequently at rest, and the lack of an increase with training indicates that these muscles do not contribute significantly to the increased ventilatory activity accompanying exercise in the rat.

Non-NASA Center↗
NASA NTRS1992

Contribution of vertebral deformities to chronic back pain and disability. The Study of Osteoporotic Fractures Research Group

Among 2992 white women aged 65-70 years recruited from population-based listings, we measured radiographic vertebral dimensions of T5-L4 and calculated ratios of heights: anterior/posterior, mid/posterior, and posterior/posterior of either adjacent vertebra. The degree of deformity for each vertebra was analyzed in terms of the number of standard deviations (SD) that ratio differed from the mean ratio calculated for the same vertebral level in this population. We correlated the severity of each woman's worst vertebral deformity with back pain, back disability in six activities of daily living, and height loss since age 25. Only 39.4% of the cohort had no vertebral deformity; 10.2% had a deformity greater than or equal to 4 SD. Vertebral deformities less than 4 SD below the mean were not associated with increased back pain, disability, or loss of height. In contrast, women whose deformity was greater than or equal to 4 SD had a 1.9 (95% CI, 1.5-2.4) times higher risk of moderate to severe back pain and a 2.6 (95% CI, 1.7-3.9) times higher risk of disability involving the back; they were also 2.5 (95% CI, 2.0-3.2) times more likely to have lost greater than or equal to 4 cm in height. All three types of vertebral deformity (wedge, end plate, and crush) were equally associated with these outcomes. Multiple deformities less than 4 SD did not increase the likelihood of these three outcomes, but multiple deformities greater than or equal to 4 SD tended to be associated with increased back pain, disability, and height loss. This large cross-sectional study suggests that vertebral deformities cause substantial pain, disability, or loss of height only if vertebral height ratios fall 4 SD below the normal mean. Much back pain could not be attributed to vertebral deformities, suggesting other causes.

Non-NASA Center↗
NASA NTRS2003

Effect of High Impact or Non-impact Loading Activity on Bone Bending Stiffness and Mineral Density

Material properties of conical bone, including mineral density (BMD) and its geometry is closely related to its load-carrying capacity. These two primary components determine the strength of conical bone. High impact loading involving acceleration and deceleration movements used in gymnastics induce higher BMD of the affected bone compared to the non-impact acceleration and deceleration movements used in swimming. Study of these two groups of athletes on bone bending stiffness has not been reported. The purpose of this study was to compare differences in bone bending stiffness and BMD between competitive female synchronized swimmers and female gymnasts. Thirteen world class female synchronized swimmers (SYN) and 8 female gymnasts (GYM), mean age 21 +/- 2.9 yr. were recruited for this study. We used a mechanical response tissue analyzer (Gaitscan, NJ) to calculate EI, where E is Young's modulus of elasticity and I is the cross-sectional moment of inertia. EI was obtained from tissue response to a vibration probe placed directly on the skin of the mid-region of tibia and ulna. BMD of the heel and wrist were measured with a probe densitometer (PIXI, Lunor, WI). The SYN were taller than (p < 0.05) the GYM but weighed the same as the GYM. EI obtained from tibia and ulna of the SYN (291 +/- 159 and 41 +/- 19.4, respectively) were not significantly different from thc GYM (285 +/- 140 and 44 +/- 18.3, respectively). BMD of the heel and wrist in GYM were higher than in SYN (p < 0.001). High impact weight-bearing activities promote similar bone strength but greater BMD response than non-impact activities performed in a buoyant environment.

Liang, Michael T. C.↗
NASA NTRS2005

Stardust@home: A Massively Distributed Public Search for Interstellar Dust in the Stardust Interstellar Dust Collector

In January 2006, the Stardust mission will return the first samples from a solid solar system body beyond the Moon. Stardust was in the news in January 2004, when it encountered comet Wild2 and captured a sample of cometary dust. But Stardust carries an equally important payload: the first samples of contemporary interstellar dust ever collected. Although it is known that interstellar (IS) dust penetrates into the inner solar system [2, 3], to date not even a single contemporary interstellar dust particle has been captured and analyzed in the laboratory. Stardust uses aerogel collectors to capture dust samples. Identification of interstellar dust impacts in the Stardust Interstellar Dust Collector probably cannot be automated, but will require the expertise of the human eye. However, the labor required for visual scanning of the entire collector would exceed the resources of any reasonably-sized research group. We are developing a project to recruit the public in the search for interstellar dust, based in part on the wildly popular SETI@home project, which has five million subscribers. We call the project Stardust@home. Using sophisticated chemical separation techniques, certain types of refractory ancient IS particles (so-called presolar grains) have been isolated from primitive meteorites (e.g., [4] ). Recently, presolar grains have been identified in Interplanetary Dust Particles[6]. Because these grains are not isolated chemically, but are recognized only by their unusual isotopic compositions, they are probably less biased than presolar grains isolated from meteorites. However, it is entirely possible that the typical interstellar dust particle is isotopically solar in composition. The Stardust collection of interstellar dust will be the first truly unbiased one.

Westphal, Andrew J.↗
NASA NTRS2007

Gender Consideration in Experiment Design for Airbrake in Prebreathe

If gender is a confounder of the decompression sickness (DCS) or venous gas emboli (VGE) outcomes of a proposed air break in oxygen prebreathe (PB) project, then decisions about the final experiment design must be made. We evaluated if the incidence of DCS and VGE from tests in altitude chambers over 20 years were different between men and women after resting and exercise prebreathe protocols. Nitrogen washout during PB is our primary risk mitigation strategy to prevent subsequent DCS and VGE in subjects. Bubbles in the pulmonary artery (venous blood) were detected from the precordial position using Doppler ultrasound bubble detectors. The subjects were monitored for VGE for four min at about 15 min intervals for the duration of the altitude exposure, with maximum bubble grade assigned a Spencer Grade of IV. There was no difference in DCS incidence between men and women in either PB protocol. The incidence of VGE and Grade IV VGE is statistically lower in women compared to men after resting PB. Even when 10 tests were compared with Mantel-Haenszel 2 where both men (n = 168) and women (n = 92) appeared, the p-value for VGE incidence was still significant at 0.03. The incidence of VGE and Grade IV VGE is not statistically lower in women compared to men after exercise PB. Even when six tests were compared with Mantel-Haenszel x2 where both men (n = 165) and women (n = 49) appeared, the p-value for VGE incidence was still not significant at 0.90. Our goal is to understand the risk of brief air breaks during PB without other confounding variables invalidating our conclusions. The cost to additionally account for the confounding role of gender on VGE outcome after resting PB is judged excessive. Our decision is to only evaluate air breaks in the exercise PB protocol. So there is no restriction to recruiting women as test subjects.

Conkin, Johnny↗
NASA NTRS2006

Miniature Wireless Sensors Size Up to Big Applications

Like the environment of space, the undersea world is a hostile, alien place for humans to live. But far beneath the waves near Key Largo, Florida, an underwater laboratory called Aquarius provides a safe harbor for scientists to live and work for weeks at a time. Aquarius is the only undersea laboratory in the world. It is owned by the National Oceanic and Atmospheric Administration (NOAA), administered by NOAA s National Undersea Research Program, and operated by the National Undersea Research Center at the University of North Carolina at Wilmington. Aquarius was first deployed in underwater operations in 1988 and has since hosted more than 200 scientists representing more than 90 organizations from around the world. For NASA, Aquarius provides an environment that is analogous to the International Space Station (ISS) and the space shuttle. As part of its NASA Extreme Environment Mission Operations (NEEMO) program, the Agency sends personnel to live in the underwater laboratory for up to 2 weeks at a time, some of whom are crew members or "aquanauts" who are subjected to the same tasks and challenges underwater that they would face in space. In fact, many participants have found the deep-sea diving experience to be much akin to spacewalking. To maintain Aquarius, the ISS, and the space shuttle as safe, healthy living/research habitats for its personnel, while keeping costs in mind, NASA, in 1997, recruited the help of Conroe, Texas-based Invocon, Inc., to develop wireless sensor technology that monitors and measures various environmental and structural parameters inside these facilities.

Source record↗
NASA NTRS2007

Involvement of DNA-PK(sub cs) in DSB Repair Following Fe-56 Ion Irradiation

When cells are exposed to radiation, cellular lesions are induced in the DNA including double strand breaks (DSBs), single strand breaks and clustered DNA damage, which if not repaired with high fidelity may lead to detrimental biological consequences. Complex DSBs are induced by ionizing radiation and characterized by the presence of base lesions close to the break termini. They are believed to be one of the major causes of the biological effects of IR. The complexity of DSBs increases with the ionization density of the radiation and these complex DSBs are distinct from the damage induced by sparsely ionizing gamma-radiation. It has been hypothesized that complex DSBs produced by heavy ions in space pose problems to the DNA repair machinery. We have used imm uno-cyto-chemical staining of phosphorylated histone H2AX (gamma-H2AX) foci, as a marker of DSBs. We have investigated the formation and loss of gamma-H2AX foci and RAD51 foci (a protein involved in the homologous recombination pathway) in mammalian cells induced by low fluences of low-LET gamma-radiation and high-LET Fe-56 ions (1GeV/n, 151 keV/micron LET). M059J and M059K cells, which are deficient and proficient in DNA-PK(sub cs) activity respectively, were used to examine the role of DNA-PK(sub cs), a key protein in the non-homologous end joining (NHEJ) pathway of DSB repair, along with HF19 human fibroblasts. Followi ng irradiation with Fe-56 ions the rate of repair was slower in M059J cells compared with that in M059K, indicating a role for DNA-PK(sub cs) in the repair of DSB induced by Fe-56 ions. However a small percentage of DSBs induced are rejoined within 5 h although many DSBs still persist up to 24 h. When RAD51 was examined in M059J/K cells, RAD51 foci are visible 24 hours after irradiation in approximately 40% of M059J cells compared with <5% of M059K cells indicating that persistent DSBs or those formed at stalled replication forks recruit RAD51 in DNA-PK(sub cs) deficient cells. Following 1 Gy gamma-radiation the induction of gamma-H2AX foci is similar in M059J and M059K cells. However, the repair rate of DSBs is slower in M059J cells than in M059K as shown previously but faster than seen with DSB induced by 56Fe ions. Vanillin, an inhibitor of DNA-PK(sub cs), reduces significantly the rate of DSB repair in HF19 cells following 1 Gy gamma-radiation but at 0.25 Gy gamma-irradiation the rate of DSB repair is similar in the presence or absence vanillin, thus suggesting the repair of a sub-set of DSBs induced by low dose, low-LET radiation does not require DNA-PK(sub cs). This sub-set of DSBs is formed in lower yield with high LET radiation. T he complexity of DNA DSBs induced by HZE radiation will be discussed in terms of reduced repair efficiency and provide scope to model different sub-classes of DSBs as precursors that may lead to the detrimental health effects of HZE radiation.

O'Neill, Peter↗
NASA NTRS2007

Research Infrastructure Challenges for Graduate Programs in STEM Disciplines at Minority Institutions

It is much more challenging to perform experimental research functions at many minority institutions, because of lack of adequate research infrastructure. This is especially true if one wishes to initiate and implement masters and doctoral degree program in physics. In the present paper, an attempt is made to discuss the various hurdles encountered by the authors in the establishment of Master's and Doctoral degree programs in physics at one of the HBCUs (Historically Black Colleges and Universities). The department got no special or necessary treatment and faculty members are asked to teach as much course work as any other undergraduate department on the campus. It was very hard to convince university administration that giving less teaching load to research producing department faculty, shall culminate in abundant funding for the future years. This scenario created an extra heavy pressure on the faculty to continue the program. Some of the challenges included the resistance of some faculty and administrators to change, lack of sufficient release time for research producing faculty, and potential variation in funding or support with changes in the state education budget proration or members of the administration. In spite of the indirect cost recovery, very little infrastructure facilities was provided and the federal funding agencies did not want to interfere in the administration of the university. Various issues of recruiting and mentoring minority students, retention in the STEM disciplines as well as research infrastructure challenges at an HBCU university are presented.

Aggarwal, M. D.↗
NASA NTRS2007

Unleashing Gen Y: Marketing Mars to Millennials

Space advocates need to engage Generation Y (born 1977-1999).This outreach is necessary to recruit the next generation of scientists and engineers to explore Mars. Space advocates in the non-profit, private, and government sectors need to use a combination of technical communication, marketing, and politics, to develop messages that resonate with Gen Y. Until now, space messages have been generated by and for college-educated white males; Gen Y is much more diverse, including as much as one third minorities. Young women, too, need to be reached. My research has shown that messages emphasizing technology, fun, humor, and opportunity are the best means of reaching the Gen Y audience of 60 million (US population is 300 million). The important things space advocates must avoid are talking down to this generation, making false promises, or expecting them to "wait their turn" before they can participate. This is the MTV generation! We need to find ways of engaging Gen Y now to build a future where human beings can live and work on the planet Mars. In addition to the messages themselves, advocates need to keep up with Gen Y' s social networking and use of iPods, cell phones, and the Internet. NASA and space advocacy groups can use these tools for "viral marketing," where young people share targeted space-related information via cell phones or the Internet because they like it. Overall, Gen Y is a socially dynamic and media-savvy group; advocates' space messages need to be sincere, creative, and placed in locations where Gen Y lives. Mars messages must be memorable!

Leahy, Bart D.↗
NASA NTRS2008

NASA's Elementary and Secondary Education Program: Review and Critique

The federal role in precollege science, technology, engineering, and mathematics (STEM) education is receiving increasing attention in light of the need to support public understanding of science and to develop a strong scientific and technical workforce in a competitive global economy. Federal science agencies, such as the National Aeronautics and Space Administration (NASA), are being looked to as a resource for enhancing precollege STEM education and bringing more young people to scientific and technical careers. For NASA and other federal science agencies, concerns about workforce and public understanding of science also have an immediate local dimension. The agency faces an aerospace workforce skewed toward those close to retirement and job recruitment competition for those with science and engineering degrees. In addition, public support for the agency s missions stems in part from public understanding of the importance of the agency s contributions in science, engineering, and space exploration.

Quinn, Helen R.↗
NASA NTRS2006

Fat-Soluble Vitamin Status in Self-Neglecting Elderly

Elder self-neglect is a form of elder mistreatment. The systematic characterization of self-neglecting individuals is the goal of the CREST project. Reported here is the evaluation of fat-soluble vitamin status. Self-neglect (SN) subjects were recruited and consented following referral from Adult Protective Services. Control (CN) subjects were matched for age, gender, race, and socioeconomic status, as possible. We report here on 47 SN subjects (age 77 plus or minus 7, mean plus or minus SD; body weight 76 kg plus or minus 26) and 40 CN subjects (77 y plus or minus 7, 79 kg plus or minus 20). Blood samples were analyzed for indices of fat-soluble vitamin status. Plasma retinol (p less than 0.01) was lower in SN subjects. Plasma tocopherol tended (p less than 0.06) to be lower in SN subjects, while gamma-tocopherol was unchanged. SN subjects tended to have lower serum 25-OH vitamin D (p less than 0.11), and to be vitamin D deficient (26% below 23 mmol/L). Hypercalcemia occurred more often in SN subjects (23% had values above 2.56 mmol/L), as did elevated parathyroid hormone concentrations (p less than 0.05). These data demonstrate that many nutrients are affected in the self-neglecting elderly, and that long-term deficits are evident by the nature of changes in fat soluble vitamins.

Kala, G.↗
NASA NTRS2006

Nutritional Status in Self-Neglecting Elderly

Elder self-neglect is the most common, and most compelling form of elder mistreatment. Individuals who cannot provide the basic needs for themselves may develop social, functional, and physical deficits. The CREST project has the goal of systematically characterizing these individuals, and the objective of the study reported here is to characterize aspects of their nutritional status. Self-neglect (SN) subjects referred from Adult Protective Services were recruited and consented. Control (CN) subjects were matched for age, gender, race, and socio-economic status when possible. Reported here are data on 47 SN subjects (age 77 +/- 7, mean +/- SD; body weight 76 kg +/- 26) and 40 CN subjects (77 +/- 7, 79 kg +/- 20). Blood samples were analyzed for indices of nutritional status. SN subjects had higher serum concentrations of homocysteine (p < 0.01) and methylmalonic acid (p < 0.05). Red blood cell folate levels were lower (p < 0.01) in the SN subjects and serum folate levels tended (p < 0.07) to be lower, also. C-reactive protein concentrations were higher than 10 mg/dL in 36% of SN subjects and 18% of CN subjects. Total cholesterol and triglyceride concentrations were similar in the two groups. These data demonstrate that the self-neglecting elderly population is at risk with respect to several markers of nutritional status.

Oliver, S. Mathews↗
NASA NTRS2008

GSFC Technical Outreach: The Capitol College Model

In February 2005, as part of the National Aeronautic and Space Administration (NASA) Technical Outreach Program, Goddard Space Flight Center (GSFC) awarded Capitol College of Laurel, Maryland an Educational Grant to establish a Space Operation academic curriculum to meet the future needs of mission operations engineers. This was in part due to the aerospace industry and GSFC concerns that a large number of professional engineers are projected to retire in the near term with evidence showing that current enrollment in engineering schools will not produce sufficient number of space operation trained engineers that will meet industry and government demands. Capitol College, under the agreement of the Educational Grant, established the Space Operations Institute (SOI) with a new curriculum in Space Operations that was approved and certified by the State of Maryland. The SO1 programs focuses on attracting, recruiting, and training a pipeline of highly qualified engineers with experience in mission operations, system engineering and development. The selected students are integrated as members of the engineering support team in any of the missions supported by the institute. The students are mentored by professional engineers from several aerospace companies that support GSFC. Initially, the institute was involved in providing console engineers and mission planning trainees for the Upper Atmosphere Research Satellite (UARS), the Earth Radiation Budget Satellite (ERBS) and the Total Ozone Mapping Spectrometer mission (TOMS). Subsequently, the students were also involved in the technology refresh of the TOMS ground system and other mission operations development. Further mission assignment by GSFC management included participation in the Tropical Rainfall Measuring Mission (TRMM) mission operations and ground system technology refresh. The SOI program has been very successful. Since October 2005, sixty-four students have been enrolled in the SOI program and twenty-five have already graduated from the program, nineteen of whom are employed by company's supporting GSFC. Due to the success of the program, the initial grant period was extended for another period of two years. This paper presents the process that established the SOI as a viable pipeline of mission operations engineers, the lessons learned in the process of dealing with grants, and experience gained in mentoring engineering students that are responsible for particular areas of expertise and functionality. This paper can also be considered a case study and model for integrating a student team with government and industry professionals in the real world of mission operations.

Marius, Julio L.↗
NASA NTRS2009

Tocopherol in Elder Self-Neglect

Although elder self-neglect is the most common form of elder mistreatment, its pathophysiology is not well understood. Alpha-tocopherol is a lipid soluble antioxidant required for the preservation of cell membranes. Since the association between tocopherol and cognitive impairment in older adults has been described, we explored the possibility of its role in elder self-neglect. OBJECTIVE: (1) To determine whether serum tocopherol levels are associated with elder self-neglect, and (2) to assess the association of serum tocopherol levels and cognitive function in elder self-neglect. METHODS: Serum tocopherol levels were measured in a cohort of 67 self-neglecting elders and 67 matched controls, recruited for the Consortium for Research in Elder Self-neglect of Texas. Pearson s correlation tests were performed to assess bivariate associations between serum tocopherol levels and cognitive function. RESULTS: Mean serum alpha-tocopherol levels were 10.8 +/- 4.7 ug/mL in self-neglect group and 13.0 +/- 4.9 ug/mL in control group (p = 0.006, unpaired student s t-test). None of the participants from either group had alpha-tocopherol level lower than the reference range. Mean serum gamma-tocopherol levels were 2.0 +/- 1.0 ug/mL in self-neglect group and 2.0 +/- 1.1 in control group (p=0.83). Proportion of the elders with gamma-tocopherol level lower than the reference range were 4.5% (3/66) in self-neglect group and 10.4% (7/67) in control group (p=0.32, Fisher s Exact Test). Among the self-neglecting elders, no association was found between serum alpha-tocopherol levels and the Mini-Mental State Examination (MMSE) or the Wolf-Klein Clock Drawing Test (CDT) scores (r =-0.42, p=0.75 for MMSE; r=0.08, p=0.54 for CDT). No association was found between serum gamma-tocopherol levels and the MMSE or the CDT (r=-0.12, p=0.35 for MMSE; r=0.05, p=0.68 for CDT). CONCLUSION: In our sample, neither alpha-tocopherol nor gamma-tocopherol appears to have a role in pathophysiology of elder self-neglect. Nevertheless, significantly lower serum alpha-tocopherol levels in the self neglect group merits further research.

Aung, K.↗
NASA NTRS2010

Influence of Ionizing Radiation on Stromal-Epithelial Intercellular Communication in Esophageal Carcinogenesis

Esophageal cancer is the 6th leading cause of cancer death worldwide. Its development is associated with a variety of risk factors including tobacco use, heavy alcohol consumption, human papilloma virus infection, and certain dietary factors such as trace mineral and vitamin deficiencies. An association with ionizing radiation exposure is revealed by the high excess relative risk for squamous cell carcinoma of the esophagus observed in the survivors of the atomic bomb detonations in Japan. It is also seen as a secondary malignancy in patients who received radiotherapy for breast and thoracic cancers; additionally, patients with head/neck and oral squamous cell cancers are at increased risk for metachronous esophageal squamous cell cancers. This malignancy is rapidly fatal, mainly because it remains asymptomatic until late, advanced stages when the disease is rarely curable. The stromal microenvironment plays an essential role in the maintenance and modulation of normal epithelial cell growth and differentiation and cross talk between the epithelial and stromal compartments can influence many aspects of malignant progression, including tumor cell proliferation, migration, invasion and recruitment of new blood vessels. To test the hypothesis that radiation exposure plays a role in esophageal carcinogenesis via non-targeted mechanisms involving stromal-epithelial cell communication, we are studying radiation effects on hTERT-immortalized human esophageal epithelial cells and genetic variants grown in co-culture with human esophageal stromal fibroblasts (Okawa et al., Genes & Dev. 2007. 21: 2788-2803). We examined how radiation treatment of stromal fibroblasts affected epithelial migration and invasion, behaviors associated with cancer promotion and progression. Chemotactic and haptotactic migration of epithelial cells stimulated by conditioned media from irradiated fibroblasts was measured using assays conducted in Transwell cell culture chambers. Our results using low LET radiation showed a dose-dependent increase in migration of epithelial cells when exposed to conditioned media from irradiated vs. non-irradiated fibroblasts. We also observed enhanced invasion through a basement membrane simulant. To identify chemotactic proteins secreted by irradiated stromal fibroblasts, we used antibody capture cytokine arrays and have identified several proteins as candidates. Increased secretion of these factors by irradiated fibroblasts was confirmed using ELISA. We are currently analyzing the contribution of these individual factors on epithelial migration and invasion, as well as their influence on cell survival and DNA repair. Studies using high-LET radiation will help determine radiation quality effects on these processes. These results should further our understanding of the mechanisms by which radiation impacts the tissue microenvironment and how it influences cancer development processes.

Patel, Zarana S.↗
NASA NTRS2000

T Lymphocyte Activation Threshold and Membrane Reorganization Perturbations in Unique Culture Model

Quantitative activation thresholds and cellular membrane reorganization are mechanisms by which resting T cells modulate their response to activating stimuli. Here we demonstrate perturbations of these cellular processes in a unique culture system that non-invasively inhibits T lymphocyte activation. During clinorotation, the T cell activation threshold is increased 5-fold. This increased threshold involves a mechanism independent of TCR triggering. Recruitment of lipid rafts to the activation site is impaired during clinorotation but does occur with increased stimulation. This study describes a situation in which an individual cell senses a change in its physical environment and alters its cell biological behavior.

Adams, C. L.↗
NASA NTRS2010

Preliminary Results of Bisphosphonate ISS Flight Experiment

Bone loss has been recognized as a potential problem from the beginning of human spaceflight. With the spaceflight missions lasting 6 months to potentially 3 years or longer this issue has assumed increased significance. Detailed measurements from the Mir and ISS long duration missions have documented losses in bone mineral density (BMD) from the total skeleton and critical sub-regions. The most important losses are from the femoral hip averaging about -1.6%/mo integral to -2.3%/mo trabecular BMD. Importantly these studies have documented the wide range in individual response from -0.5 to -5%/mo in BMD. Given the small size of any expedition crew, the wide range of responses has to be considered in the implementation of any countermeasure. Assuming that it is unlikely that the susceptibility for bone loss in any given crewmember will be known, a suite of bone loss countermeasures will likely be needed to insure protection of all crewmembers. The hypothesis for this experiment is that the combined effect of anti-resorptive drugs plus the standard in-flight exercise regimen will have a measurable effect on preventing space flight induced bone loss and strength and will reduce renal stone risk. To date, 4 crewmembers have completed the flight portion of the protocol in which crewmembers take a 70-mg alendronate tablet once a week before and during flight, starting 17 days before launch. Compared to previous ISS crewmembers (n=14) not taking alendronate, DXA measurements of the total hip BMD were significantly changed from -1.1 0.5%/mo to 0.04 0.3%/mo (p<0.01); QCT-determined trabecular BMD of the total hip was significantly changed from -2.3 1.0%/mo to -0.3 1.6%/mo (p<0.01). Significance was calculated from a one-tailed t test. While these results are encouraging, the current n (4) is small, and the large SDs indicate that while the means are improved there is still high variability in individual response. Four additional crewmembers have been recruited to participate in this experiment, with expected completion of these flights by late 2011.

LeBlanc, Adrian↗