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Sams, Clarence F.

Publications and source records attributed to Sams, Clarence F..

At least 19 records

Re-evaluation of IIH as the Ideal Terrestrial Analog for Sans: Is There a Better Model to Consider?

While astronauts are returning from long duration spaceflight with multiple ocular signs that mimic those seen in terrestrial patients with elevated intracranial pressure (ICP), evidence has yet to prove a clinically significant increase in ICP during space.1 Preliminary research evidence may even suggest that ICP decreases in microgravity. Idiopathic intracranial hypertension (IIH) has long been considered the ideal terrestrial analogue to Spaceflight Associated Neuro-ocular Syndrome (SANS).1 However, there are several critical features of SANS that do not complement any reported case of IIH on Earth. These findings mandate a closer look at the accuracy of IIH as a terrestrial SANS analog.

Batliwala, Shehzad

Multidimensional Processing and Visual Rendering of Complex 3D Biomedical Images

The proposed technology uses advanced image analysis techniques to maximize the resolution and utility of medical imaging methods being used during spaceflight. We utilize COTS technology for medical imaging, but our applications require higher resolution assessment of the medical images than is routinely applied with nominal system software. By leveraging advanced data reduction and multidimensional imaging techniques utilized in analysis of Planetary Sciences and Cell Biology imaging, it is possible to significantly increase the information extracted from the onboard biomedical imaging systems. Year 1 focused on application of these techniques to the ocular images collected on ground test subjects and ISS crewmembers. Focus was on the choroidal vasculature and the structure of the optic disc. Methods allowed for increased resolution and quantitation of structural changes enabling detailed assessment of progression over time. These techniques enhance the monitoring and evaluation of crew vision issues during space flight.

Sams, Clarence F.

Risk of Crew Adverse Health Event Due to Altered Immune Response

Determining the effect of space travel on the human immune system has proven to be extremely challenging. Limited opportunities for in-flight studies, varying mission durations, technical and logistical obstacles, small subject numbers, and a broad range of potential assays have contributed to this problem. Additionally, the inherent complexity of the immune system, with its vast array of cell populations, sub-populations, diverse regulatory molecules, and broad interactions with other physiological systems, makes determining precise variables to measure very difficult. There is also the challenge of determining the clinical significance of any observed immune alterations. Will such a change lead to disease, or is it a transient subclinical observation related to short-term stress? The effect of this problem may be observed by scanning publications associated with immunity and spaceflight, which began to appear during the 1970s. Although individually they are each valid studies, the comprehensive literature to date suffers from widely varying sampling methods and assay techniques, low subject counts, and sometimes a disparate focus on narrow aspects of immunity. The most clinically relevant data are derived from in-flight human studies, which have demonstrated altered cell-mediated immunity and reactivation of latent herpes viruses. Much more data are available from post-flight testing of humans, with clear evidence of altered cytokine production patterns, altered leukocyte distribution, continued latent viral reactivation, and evidence of dramatically altered virus-specific immunity. It is unknown if post-flight assessments relate to the in-flight condition or are a response to landing stress and readaptation. In-flight culture of cells has clearly demonstrated that immune cells are gravity-sensitive and display altered functional characteristics. It is unknown if these data are related to in vivo immune cell function or are an artifact of microgravity culture. Ground analog testing of humans and animals, as well as microgravity-analog cell culture, has demonstrated utility. However, in all cases, it is not known with certainty if these data would reflect similar testing during space travel. Given their ready availability, ground analogs may be extremely useful for assay development and the evaluation of potential countermeasures. In general, the evidence base suffers from widely disparate studies on small numbers of subjects that do not directly correlate well with each other or spaceflight itself. Also lacking are investigations of the effect of gender on adaption to spaceflight. This results in significant knowledge 'gaps' that must be filled by future studies to completely determine any clinical risk related to immunity for human exploration-class space missions. These gaps include a significant lack of in-flight data, particularly during long-duration space missions. The International Space Station represents an excellent science platform with which to address this knowledge gap. Other knowledge gaps include lack of a single validated ground analog for the phenomenon and a lack of flight-compatible laboratory equipment capable of monitoring astronauts (for either clinical or research purposes). However, enough significant data exist, as described in this manuscript, to warrant addressing this phenomenon during the utilization phase of the ISS. A recent Space Shuttle investigation has confirmed the 31 in-flight nature of immune dysregulation, demonstrating that it is not merely a post-flight phenomenon. Several current studies are ongoing onboard the ISS that should thoroughly characterize the phenomenon. NASA recognizes that if spaceflight-associated immune dysregulation persists during exploration flights in conjunction with other dangers, such as high-energy radiation, the result may be a significant clinical risk. This emphasizes the need for a continued integrated comprehensive approach to determining the effect of prolonged spaceflight, separated from transient launch and landing stresses, on human immunity. After such studies, the phenomenon will be understood, and, hopefully, a monitoring strategy will have been developed that could be used to monitor the effectiveness of countermeasure

Crucian, Brian

Plasma Cytokine Concentrations Indicate In-vivo Hormonal Regulation of Immunity is Altered During Long-Duration Spaceflight

Background: Aspects of immune system dysregulation associated with long‐duration spaceflight have yet to be fully characterized, and may represent a clinical risk to crewmembers during deep space missions. Plasma cytokine concentration may serve as an indicator of in vivo physiological changes or immune system mobilization. Methods: The plasma concentrations of 22 cytokines were monitored in 28 astronauts during long‐duration spaceflight onboard the International Space Station. Blood samples were collected three times before flight, 3‐5 times during flight (depending on mission duration), at landing and 30 days post‐landing. Analysis was performed by bead array immunoassay. Results: With few exceptions, minimal detectable mean plasma levels (<10 pg/ml) were observed at baseline (launch minus 180) for innate inflammatory cytokines or adaptive regulatory cytokines, however IL‐1ra and several chemokines were constitutively present. An increase in the plasma concentration IL‐8, IL‐1ra, Tpo, CCL4, CXCL5, TNF(alpha), GM‐CSF and VEGF was observed associated with spaceflight. Significant post‐flight increases were observed for IL‐6 and CCL2. No significant alterations were observed during or following spaceflight for adaptive/T‐regulatory cytokines (IL‐2, IFN(gamma), IL‐17, IL4, IL‐5, IL‐10). Conclusions: This pattern of cytokine dysregulation suggests multiple physiological adaptations persist during flight, including inflammation, leukocyte recruitment, angiogenesis and thrombocyte regulation.

Crician, Brian E.

Evidence Report: Risk of Crew Adverse Health Event Due to Altered Immune Response

The Risk of Crew Adverse Health Event Due to Altered Immune Response is identified by the National Aeronautics and Space Administration (NASA) Human Research Program (HRP) as a recognized risk to human health and performance in space. The HRP Program Requirements Document (PRD) defines these risks. This Evidence Report provides a summary of the evidence that has been used to identify and characterize this risk. It is known that human immune function is altered in‐ and post‐flight, but it is unclear at present if such alterations lead to increased susceptibility to disease. Reactivation of latent viruses has been documented in crewmembers, although this reactivation has not been directly correlated with immune changes or with observed diseases. As described in this report, further research is required to better characterize the relationships between altered immune response and susceptibility to disease during and after spaceflight. This is particularly important for future deep‐space exploration missions.

Crucian, Brian

Alterations of Cellular Immune Reactions in Crew Members Overwintering in the Antarctic Research Station Concordia

Background: Concordia Station is located inside Antarctica about 1000km from the coast at an altitude of 3200m (Dome C). Hence, individuals living in this harsh environment are exposed to two major conditions: 1.) hypobaric hypoxia and 2.) confinement and extreme isolation. Both hypoxia and confinement can affect human immunity and health, and are likely to be present during exploration class space missions. This study focused on immune alterations measured by a new global immunity test assay, similar to the phased out delayed type hypersensitivity (DTH) skin test. Methods: After informed written consent 14 healthy male subjects were included to the CHOICE-study (Consequences-of-longterm-Confinement-and-Hypobaric-HypOxia-on-Immunity-in-the Antarctic-Concordia-Environment). Data collection occurred during two winter-over periods lasting each one year. During the first campaign 6 healthy male were enrolled followed by a second campaign with 8 healthy males. Blood was drawn monthly and incubated for 48h with various bacterial, viral and fungal antigens followed by an analysis of plasma cytokine levels (TNF-alpha, IL2, IFN-gamma, IL10). As a control, blood was incubated without stimulation ("resting condition"). Goals: The scope of this study was to assess the consequences of hypoxia and confinement on cellular immunity as assessed by a new in vitro DTH-like test. Results: Initial results indicate that under resting conditions the in vitro DTH-like test showed low cytokine levels which remained almost unchanged during the entire observation period. However, cytokine responses to viral, bacterial and fungal antigens were remarkably reduced at the first month after arrival at Concordia when compared to levels measured in Europe prior to departure for Antarctica. With incrementing months of confinement this depressed DTH-like response tended to reverse, and in fact to show an "overshooting" immune reaction after stimulation. Conclusion: The reduced in vitro DTH-like test response in the early phase of Antarctic wintering over con rms distinct immune suppressive effects seen after (sub-)acute hypobaric hypoxia. The reversal and overshooting reaction of cellular immune responses upon stimulation, but not the resting state, indicate either a) priming of immune answers and/or b) an uncoupled or disregulated control of cellular immune answers by auto-, para- and endocrine pathways. Further analyses and correlations are warranted. Acknowledgement: Supported by the European Space Agency (ESA), the French (IPEV) and Italian (PNRA) polar institutes, the German National Space Program (DLR, 50WB0719/WB0919), by BELSPO/PROEDEX/ESA (C90-380/-391), NASA and by the Concordia crews who have participated with great enthusiasm.

Crucian, Brian

Improved Whole-Blood-Staining Device

Dramatic improvements have been made in NASA s Whole Blood Staining Device (WBSD) since it was last described in "Whole-Blood-Staining Device," NASA Tech Briefs, Vol. 23, No. 10 (October 1999), page 64. The new system has a longer shelf life, a simpler and more effective operational procedure, improved interface with instrumentation, and shorter processing time. More specifically, the improvements have targeted bag and locking clip materials, sampling ports, and air pocket prevention. The WBSD stains whole blood collected during spaceflight for subsequent flow cytometric analysis. In short, the main device stains white blood cells by use of monoclonal antibodies conjugated to various fluorochromes, followed by lysing and fixing of the cells by use of a commercial reagent that has been diluted according to NASA safety standards. This system is compact, robust, and does not require electric power, precise mixing, or precise incubation times. Figure 1 depicts the present improved version for staining applications, which is a poly(tetrafluoroethylene) bag with a Luer-lock port and plastic locking clips. An InterLink (or equivalent) intravenous- injection port screws into the Luer-lock port. The inflatable/collapsible nature of the bag facilitates loading and helps to minimize the amount of air trapped in the fully loaded bag. Some additional uses have been identified for the device beyond whole blood staining. The WBSD has been configured for functional assays that require culture of live cells by housing sterile culture media, mitogens, and fixatives prior to use [Figure 2(a)]. Simple injection of whole blood allows cell-stimulation culture to be performed in reduced gravity conditions, and product stabilization prior to storage, while protecting astronauts from liquid biohazardous materials. Also, the improved WBSD has reconstituted powdered injectable antibiotics by mixing them with diluent liquids [Figure 2(b)]. Although such mixing can readily be performed on Earth by shaking in glass vials, it cannot readily be performed this way in outer space without entraining air bubbles. The present device can be preloaded with the powder and diluent(s) in separate compartments. The powder and diluent( s) can be mixed, without introducing air bubbles, by removing the clip(s), then shaking. This use of the device could also be advantageous in terrestrial applications because it maintains the isolation of the constituents until the time of use.

Sams, Clarence F.

Plasma Cytokine Levels During Long-Duration Spaceflight

Determine the in-flight status of immunity, physiological stress, viral immunity/reactivation. Specific measurements include leukocyte distribution, T cell function, cytokine production profiles (mRNA, intracellular, secreted, plasma), virus-specific T cell number/function, latent herpesvirus reactivation, stress hormone levels. Determine the clinical risk related to immune dysregulation for exploration class spaceflight, as well as an appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures. Specific Study Objectives: Determine the nutritional status of astronauts before, during, and after spaceflight ensure adequate intake of energy, protein, and vitamins during missions. The Clinical Nutritional Status Assessment measures dietary intake, body composition, protein, bone, iron, mineral, vitamin, and antioxidant status (60 total analytes). Currently, it is a medical requirement for U.S. crewmembers on-board the ISS. The results of data analysis are used both to understand the connections between nutrition and human health during space flight, and to develop effective dietary strategies to reduce adverse health impacts (including bone loss, loss of important vitamins and minerals, and increased genetic damage from radiation).

Crucian, Brian E.

Combined Effects of Gamma Radiation and High Dietary Iron on Peripheral Leukocyte Distribution and Function

Both radiation and increased iron stores can independently increase oxidative damage, resulting in protein, lipid and DNA oxidation. Oxidative stress increases the risk of many health problems including cancer, cataracts, and heart disease. This study, a subset of a larger interdisciplinary investigation of the combined effect of iron overload on sensitivity to radiation injury, monitored immune parameters in the peripheral blood of rats subjected to gamma radiation, high dietary iron or both. Specific immune measures consisted of: (1) peripheral leukocyte distribution, (2) plasma cytokine levels and (3) cytokine production profiles following whole blood mitogenic stimulation

Crucian, Brian E.

Altered Innate and Lymphocytic Immune Responses in Mouse Splenocytes Post-Flight

Space flight is known to affect immune responses of astronauts and animals, decreasing lymphocytic responses to mitogenic stimuli, delayed typed hypersensitivity reactions, and T-cell activation. Despite changes in immune suppression, there are no reports of consistent adverse clinical events post flight. To further investigate the spectrum of affected immune responses, murine splenocytes were stimulated immediately post-shuttle flight (14 days on STS-135) with T-cell stimulators or toll-like receptor agonists. Comparisons were made to ground control splenocytes from age-matched mice. Cell phenotypes were assessed, as well as activation markers and associated cytokine production. The CD4+ population decreased with no concurrent decrease in CD8+ cells from shuttle mice post flight compared to ground controls. Regarding antigen presenting cell populations, the number of CD11c+ cells were slightly elevated post flight, compared to ground controls, with increased MHC Class I expression (I-A(sup b)) and no change in Class II expression (H-2K(sup b)). CD86+ populations were also significantly diminished. However, the decreased markers did not correlate with activity. Stimulation of splenocytes post flight showed significant increase in bead uptake, increased Class I expression, increased TNF-alpha and IL-6 production in response to TLR-2 (zymosan) and TLR-4 (LPS) agonists. While most activated (ConA or anti-CD3/anti-CD28) CD4+ cells showed markedly diminished responses (reduced IL-2 production), non-specific T cell responses to superantigen (SEA/SEB) increased post flight as determined by expression of early activation markers. Production of additional cytokines was also dysregulated postflight. Overall, persistent immune changes during space flight could represent unique clinical risks for exploration class missions. The consequences of pathogenic encounter remain an important concern that should be addressed.

Hwang, ShenAn

Evaluation of the Combined Effects of Gamma Radiation and High Dietary Iron on Peripheral Leukocyte Distribution and Function

NASA is concerned with the health risks to astronauts, particularly those risks related to radiation exposure. Both radiation and increased iron stores can independently increase oxidative damage, resulting in protein, lipid and DNA oxidation. Oxidative stress increases the risk of many health problems including cancer, cataracts, and heart disease. This study, a subset of a larger interdisciplinary investigation of the combined effect of iron overload on sensitivity to radiation injury, monitored immune parameters in the peripheral blood of rats subjected to gamma radiation, high dietary iron or both. Specific immune measures consisted of (A) peripheral leukocyte distribution; (B) plasma cytokine levels; (C) cytokine production profiles following whole blood stimulation of either T cells or monocytes.

Crucian, Brian E.

Altered Innate and Lymphocytic Immunity in Murine Splenocytes Following Short-Duration Spaceflight

Immune dysregulation has been demonstrated following spaceflight of varying durations and limited in-flight studies indicate this phenomenon may persist during spaceflight. Causes may include microgravity, physiological stress, isolation, confinement and disrupted circadian rhythms. To further investigate the mechanisms associated with flight-associated immune changes, murine splenocytes immune parameters were assessed following 14 day space flight on Space Shuttle mission STS-135.

Crucian, Brian E.

Plasma Cytokine Levels During Long-Duration Spaceflight

Reduced T cell, granulocyte, NK and monocyte function have all been reported following both long and short duration spaceflight, however these data indicate crews are generally not experiencing inflammatory or adaptive immune activation during spaceflight. There appear to be varied individual crew responses, and specific relationships between cytokines and markers of iron status and muscle turnover that warrant further evaluation. Increases in growth factors and chemokines may indicate other types of adaptation occurring during spaceflight, such as attempts to overcome diminished immunocyte function.

Crucian, Brian E.

The Human in Space: Lesson from ISS

This viewgraph presentation reviews the lessons learned from manned space flight on the International Space Station. The contents include: 1) Overview of space flight effects on crewmembers; 2) General overview of immune system; 3) How does space flight alter immune system? 4) What factors associated with space flight inteact with crewmember immune function and impact health risks? 5) What is the current understanding of space flight effects on the immune system? and 6) Why should NASA be interested in immunology? Why is it significant?

Sams, Clarence F.

NASA Human Research Program (HRP). International Space Station Medical Project (ISSMP)

This viewgraph presentation describes the various flight investigations performed on the International Space Station as part of the NASA Human Research Program (HRP). The evaluations include: 1) Stability; 2) Periodic Fitness Evaluation with Oxygen Uptake Measurement; 3) Nutrition; 4) CCISS; 5) Sleep; 6) Braslet; 7) Integrated Immune; 8) Epstein Barr; 9) Biophosphonates; 10) Integrated cardiovascular; and 11) VO2 max.

Sams, Clarence F.

Renal Stone Risk during Spaceflight: Assessment and Countermeasure Validation

NASA's Vision for Space Exploration centers on exploration class missions including the goals of returning to the moon and landing on Mars. One of NASA's objectives is to focus research on astronaut health and the development of countermeasures that will protect crewmembers during long duration voyages. Exposure to microgravity affects human physiology and results in changes in the urinary chemical composition favoring urinary supersaturation and an increased risk of stone formation. Nephrolithiasis is a multifactorial disease and development of a renal stone is significantly influenced by both dietary and environmental factors. Previous results from long duration Mir and short duration Shuttle missions have shown decreased urine volume, pH, and citrate levels and increased calcium. Citrate, an important inhibitor of calcium-containing stones, binds with urinary calcium reducing the amount of calcium available to form stones. Citrate inhibits renal stone recurrence by preventing crystal growth, aggregation, and nucleation and is one of the most common therapeutic agents used to prevent stone formation. Methods: Thirty long duration crewmembers (29 male, 1 female) participated in this study. 24-hour urines were collected and dietary monitoring was performed pre-, in-, and postflight. Crewmembers in the treatment group received two potassium citrate (KCIT) pills, 10 mEq/pill, ingested daily beginning 3 days before launch, all in-flight days and through 14 days postflight. Urinary biochemical and dietary analyses were completed. Results: KCIT treated subjects exhibited decreased urinary calcium excretion and maintained the levels of calcium oxalate supersaturation risk at their preflight levels. The increased urinary pH levels in these subjects reduced the risk of uric acid stones. Discussion: The current study investigated the use of potassium citrate as a countermeasure to minimize the risk of stone formation during ISS missions. Results suggest that supplementation with potassium citrate decreases the risk of stone formation during and immediately after spaceflight.

Whitson, Peggy A.

Renal Stone Risk During Spaceflight: Assessment and Countermeasure Validation

This viewgraph presentation describes the risks of renal stone formation in manned space flight. The contents include: 1) Risk; 2) Evidence; 3) Nephrolithiasis -A Multifactorial Disease; 4) Symptoms/signs; 5) Urolithiasis and Stone Passage; 6) Study Objectives; 7) Subjects; 8) Methods; 9) Investigation Results; 10) Potassium Citrate; 11) Calcium Balance; 12) Case Study; 13) Significant Findings; 14) Risk Mitigation Strategies and Recommended Actions; and 15) Future Potential.

Pietrzyk, Robert A.

Biomedical Results of ISS Expeditions 1-12

A viewgraph presentation on biomedical data from International Space Station (ISS) Expeditions 1-12 is shown. The topics include: 1) ISS Expeditions 1-12; 2) Biomedical Data; 3) Physiological Assessments; 4) Bone Mineral Density; 5) Bone Mineral Density Recovery; 6) Orthostatic Tolerance; 7) Postural Stability Set of Sensory Organ Test 6; 8) Performance Assessment; 9) Aerobic Capacity of the Astronaut Corps; 10) Pre-flight Aerobic Fitness of ISS Astronauts; 11) In-flight and Post-flight Aerobic Capacity of the Astronaut Corps; and 12) ISS Functional Fitness Expeditions 1-12.

Fogarty, Jennifer