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At least 91 records · Page 5

NASA SMART Probe: Breast Cancer Application

There is evidence in breast cancer and other malignancies that the physiologic environment within a tumor correlates with clinical outcome. We are developing a unique percutaneous Smart Probe to be used at the time of needle biopsy of the breast. The Smart Probe will simultaneously measure multiple physiologic parameters within a breast tumor. Direct and indirect measurements of tissue oxygen levels, blood flow, pH, and tissue fluid pressure will be analyzed in real-time. These parameters will be interpreted individually and collectively by innovative neural network techniques using advanced intelligent software. The goals are 1) develop a pecutaneous Smart Probe with multiple sensor modalities and applying advanced Information Technologies to provide real time diagnostic information of the tissue at tip of the probe, 2) test the percutaneous Smart Probe in women with benign and malignant breast masses who will be undergoing surgical biopsy, 3) correlate probe sensor data with benign and malignant status of breast masses, 4) determine whether the probe can detect physiologic differences within a breast tumor, and its margins, and in adjacent normal breast tissue, 5) correlate probe sensor data with known prognostic factors for breast caner, including tumor size, tumor grade, axillary lymph node metastases, estrogen receptor and progesterone receptor status.

Mah, Robert W.↗

Immune responses in humans after 60 days of confinement

A confinement experiment in a normobaric diving chamber was undertaken to better understand the effect of confinement and isolation on human psychology and physiology. Pre- and postconfinement blood samples were obtained from four test subjects and control donors to analyze immune responses. No modification in the levels of CD2+, CD3+, CD4+, CD8+, CD19+, and CD56+ cells was observed after confinement. Mitogen-induced T-lymphocyte proliferation and interleukin-2 receptor expression were not altered significantly. Whole blood interferon-alpha and gamma-induction and plasma cortisol levels were also unchanged, as was natural killer cell activity. These data suggest that in humans, no specific components of the immune response are affected by a 2-month isolation and confinement of a small group.

NASA Discipline Number 18-10↗

Karyotypes of Human Lymphocytes Exposed to High-Energy Iron Ions

Chromosomal aberrations were analyzed using multicolor fluorescence in situ hybridization (mFISH) in human peripheral blood lymphocytes after in vitro exposure to gamma rays or accelerated (56)Fe ions (1 GeV/nucleon, 145 keV/microm) at Brookhaven National Laboratory (Upton, NY). Doses of 0.3 and 3 Gy were used for both radiation types. Chromosomes were prematurely condensed by a phosphatase inhibitor (calyculin A) to avoid the population selection bias observed at metaphase as a result of the severe cell cycle delays induced by heavy ions. A total of 1053 karyotypes (G(2) and M phases) were analyzed in irradiated lymphocytes. Results revealed different distribution patterns for chromosomal aberrations after low- and high-LET radiation exposures: Heavy ions induced a much higher fraction of cells with multiple aberrations, while the majority of the aberrant cells induced by low doses of gamma rays contained a single aberration. The high fraction of complex-type exchanges after heavy ions leads to an overestimation of simple-type asymmetrical interchanges (dicentrics) from analysis of Giemsa-stained samples. However, even after a dose of 3 Gy iron ions, about 30% of the cells presented no complex-type exchanges. The involvement of individual chromosomes in exchanges was similar for densely and sparsely ionizing radiation, and no statistically significant evidence of a nonrandom involvement of specific chromosomes was detected.

NASA Center JSC↗

Justification of permissible doses of radiation during prolonged space flights

Maximum permissible radiation doses for astronauts are reported based on chronic radiation experiments with dogs and actual measurements during space flights. Observed were clinical conditions, peripheral blood and marrow, the state of the cardiovascular system, higher nervous activity, the state of the vestibular analyzer, the organ of vision, spermatogenic function and the ability to reproduce, the state of immunity and a number of biological indices in blood and tissues. The following maximum permissible doses are determined as preliminary values: 1 year of flight - 200 rem; 2 years of flight - 250 rem; 3 years of flight - 275 rem.

Grigoryev, Y. G.↗

Development of a Point of Care Technology for Military Medical Applications in Austere Environments

NASA, Lawrence Livermore National Laboratory (LLNL) and the Department of Defense (DoD) share a common interest in compact medical diagnostic technologies—also known as “point of care testing” (POCT) technologies. For NASA, the need is to take care of astronauts on deep space missions. For LLNL, the focus is on technologies needed to support homeland security applications. For DoD, the need is to support warfighters in military theaters of operation, especially for prolonged field care and en route care. A recently patented technology, “Portable Medical Diagnosis Instrument” (U.S. Patent 9824870), co-invented by NASA and LLNL, is being developed further in a partnership between NASA, LLNL and Travis Air Force Base, with a focus on military applications. This instrument, the NASA-LLNL Medical Tricorder, can be used for a wide range of clinical samples including breath, saliva and blood. One component of the Tricorder is the NASA E-Nose, a carbon nanotube-based chemical sensor, integrated into a hand-held smart phone, that can detect and measure “breath biomarkers” in the gas phase of exhaled breath. The response of the NASA E-Nose is rapid, which makes it possible to detect various gas-phase substances in real time. The NASA E-Nose, with modification, can also be used for breath condensate analysis. Another component of the Tricorder is a miniaturized microfluidic analyzer, under development by LLNL, that does not require any pumps. The microfluidic analyzer can detect and measure biomarkers in liquid samples, such as blood, saliva and breath condensate. This microfluidic system requires small quantities of liquid sample and can perform analysis very rapidly (seconds to minutes), which makes it possible to detect relevant biomarkers in near real time in the field. The Clinical Investigation Facility (CIF) at Travis Air Force Base is currently conducting research with the goal to develop improved field-able technologies and procedures for the emergency response to life threatening injuries soldiers may receive in theater. This work includes experimental large animal systems and comprehensive collection of clinical specimens and physiological data. NASA and LLNL are partnering with Travis to test and further develop the Tricorder technology for high priority military applications, initially focused on lung injury models and traumatic brain injury.

Loftus, David J.↗

Effects of spaceflight on rat peripheral blood leukocytes and bone marrow progenitor cells

The white blood cell (WBC) elements and the bone marrow myeloid progenitor cell populations were analyzed to ascertain adaptation to micro-gravity and subsequent readaptation to 1 G in rats flown on the 14-day Spacelab Life Sciences-2 (SLS-2) mission. Bone marrow cells were harvested from one group of rats killed inflight (FD13) and blood was drawn from three other groups at various times. The WBC level was normal on FD14 with the exception of neutrophilia. On FD13, numbers of colony-forming units-granulocyte (CFU-G), CFU-GM, and CFU-M from flight animals were decreased compared with ground controls when incubated with recombinant rat interleukin-3 (rrIL-3) alone or in combination with recombinant human erythropoietin (rhEpo). On recovery (R + 0), flight rats had decreased numbers of total leukocytes and absolute numbers of lymphocytes and monocytes with elevated neutrophils compared with control rats. They had lower numbers of CD4, CD8, CD2, CD3, and B cells in the peripheral blood but no differences in spleen lymphocytes.

NASA Discipline Number 00-00↗

Effect of 14 days of bed rest on urine metabolite excretion and plasma enzyme levels

After 1 week of ambulatory base-line measurement, a group of 8 men 19-26 years of age remained continuously recumbent for 14 days. Studies were continued for 1 week following the prolonged recumbency. Urine excretion rates for a number of constituents were determined 2 days before bed rest, on day 14 of bed rest, and day 6 after bed rest. Blood plasma samples were also obtained at these times, and analyzed for several enzymes. On day 14 of bed rest significant increases were observed in urine excretion of total osmotically-active substances, magnesium, calcium, phosphate, creatinine, hydroxyproline, and 17-OH corticosteroids. A decrease occurred in urinary glucose excretion. Plasma levels of alkaline phosphatase and LDH-3 were depressed, while plasma GPT was elevated. Many of these changes persisted on day 6 after bed rest, and are interpreted as concomitants of the disuse atrophy of the musculoskeletal system that characterizes prolonged bed rest and weightlessness.

Pace, N.↗

Biodosimetry of ionizing radiation by selective painting of prematurely condensed chromosomes in human lymphocytes

Painting of interphase chromosomes can be useful for biodosimetric purposes in particular cases such as radiation therapy, accidental exposure to very high radiation doses and exposure to densely ionizing radiation, for example during space missions. Biodosimetry of charged-particle radiation is analyzed in the present paper. Target cells were human peripheral blood lymphocytes irradiated in vitro with gamma rays, protons and iron ions. After exposure, lymphocytes were incubated for different times to allow repair of radiation-induced damage and then fused to mitotic hamster cells to promote premature condensation in the interphase chromosomes. Chromosome spreads were then hybridized with whole-chromosome DNA probes labeled with fluorescent stains. Dose-response curves for the induction of chromatin fragments shortly after exposure, as well as the kinetics of rejoining and misrejoining, were not markedly dependent on linear energy transfer. However, after exposure to heavy ions, more aberrations were scored in the interphase cells after incubation for repair than in metaphase samples harvested at the first postirradiation mitosis. On the other hand, no significant differences were observed in the two samples after exposure to sparsely ionizing radiation. These results suggest that interphase chromosome painting can be a useful tool for biodosimetry of particle radiation.

NASA Center JSC↗

What Threats to Human Health Does Space Radiation Pose in Orbit

The Space Shuttle program spanned more than the entire length of a solar cycle. Investigations aimed towards understanding the health risks of the astronauts from exposures to space radiation involved mostly physical measurements of the dose and the linear energy transfer (LET) spectrum. Measurement of the dose rate on the Shuttle provided invariable new data for different periods of the solar cycle, whereas measurement of the LET spectrum using the tissue equivalent proportional counter (TEPC) produced the most complete mapping of the radiation environment of the low Earth orbits (LEO). Exposures to the Shuttle astronauts were measured by the personal dosimeter worn by the crewmembers. Analysis of over 300 personal dosimeter readings indicated a dependence on the mission duration, the altitude and inclination of the orbit, and the solar cycle, with the crewmembers on the launch and repair of the Hubble telescope receiving the highest doses due to the altitude of the mission. Secondary neutrons inside the Shuttle were determined by recoil protons or with Bonner spheres, and may contribute significantly to the risks of the crewmembers. In addition, the skin dose and the doses received at different organs were compared using a human phantom onboard a Shuttle mission. A number of radiobiology investigations wer e also performed. The biological doses were determined on six astronauts/cosmonauts on long-duration Shuttle/Mir missions and on two crewmembers on a Hubble repair mission by analyzing the damages in the chromosomes of the crewmembers? white blood cells. Several experiments were also conducted to address the question of possible synergistic effects of spaceflight, microgravity in particular, on the repair of radiation-induced DNA damages. The experimental design included exposure of cells before launch, during flight, or after landing. These physical and biological studies were invaluable in predicting the health risks for astronauts on ISS and future exploration missions. Educational Objectives: A group of high school students flew color negative films on tw o Shuttle missions to detect the radiation environment in orbit. This and other experiments onboard of the Shuttle were aimed at educating the general public of the space program.

Wu, Honglu↗

Altered Immune Differentials Between Male and Female Mice Independent of Ionizing Irradiation

As upcoming exploratory missions to the Lunar surface and Mars during the Artemis Program will send both female and male crewmembers, studies identifying sex-specific effects are necessary. It is well-documented that the immune system engages different responses between females and males following exposures to infectious challenge, tumors surveillance, and autoimmune development. Yet, the immune effects of spaceflight-like exposures between the sexes are limited. Therefore, this study sought to address the effects of spaceflight-like conditions on immune differentials in female and male mice. We hypothesized that the spaceflight factor, ionizing radiation, will have sex-specific effects on immune differentials. To test this, singly-housed, 12-month old female and male wildtype (Wt) mice were exposed to acute ionizing gamma irradiation (50 cGy), followed by retro-orbital blood collections at 7-days post-irradiation. Leukocytes were analyzed by flow cytometry characterizing, granulocytes, monocytes, lymphocytes (cytotoxic/helper T cells and B cells), neutrophils, eosinophils, and NK/NKT cells. Briefly, minimal sex-specific effects were observed across the cell types listed at this time point, including changes in granulocyte and lymphocyte populations. The results revealed females displayed elevated granulocytes and reduced lymphocytes compared to their male counterparts, independent of irradiation exposure. These results suggest female mice may be more capable to produce innate inflammatory mediators but may be adaptively immune compromised. In brief, this study provides insight into the sex-specific immune risks following ionizing radiation that may be experienced during spaceflight, which is relevant for future countermeasure development.

spaceflight stressors↗

Altered Immune Differentials Between Male and Female Mice Independent of Ionizing Irradiation

As upcoming exploratory missions to the Lunar surface and Mars during the Artemis Program will send both female and male crewmembers, studies identifying sex-specific effects are necessary. It is well-documented that the immune system engages different responses between females and males following exposures to infectious challenge, tumors surveillance, and autoimmune development. Yet, the immune effects of spaceflight-like exposures between the sexes are limited. Therefore, this study sought to address the effects of spaceflight-like conditions on immune differentials in female and male mice. We hypothesized that the spaceflight factor, ionizing radiation, will have sex-specific effects on immune differentials. To test this, singly-housed, 12-month old female and male wildtype (Wt) mice were exposed to acute ionizing gamma irradiation (50 cGy), followed by retro-orbital blood collections at 7-days post-irradiation. Leukocytes were analyzed by flow cytometry characterizing, granulocytes, monocytes, lymphocytes (cytotoxic/helper T cells and B cells), neutrophils, eosinophils, and NK/NKT cells. Briefly, minimal sex-specific effects were observed across the cell types listed at this time point, including changes in granulocyte and lymphocyte populations. The results revealed females displayed elevated granulocytes and reduced lymphocytes compared to their male counterparts, independent of irradiation exposure. These results suggest female mice may be more capable to produce innate inflammatory mediators but may be adaptively immune compromised. In brief, this study provides insight into the sex-specific immune risks following ionizing radiation that may be experienced during spaceflight, which is relevant for future countermeasure development.

spaceflight stressors↗

Blood flow and oxygen uptake during exercise

A model is developed for predicting oxygen uptake, muscle blood flow, and blood chemistry changes under exercise conditions. In this model, the working muscle mass system is analyzed. The conservation of matter principle is applied to the oxygen in a unit mass of working muscle under transient exercise conditions. This principle is used to relate the inflow of oxygen carried with the blood to the outflow carried with blood, the rate of change of oxygen stored in the muscle myoglobin, and the uptake by the muscle. Standard blood chemistry relations are incorporated to evaluate venous levels of oxygen, pH, and carbon dioxide.

Mitchell, J. W.↗

Mechanical Unloading Effects Hematopoiesis and Subsequent Red Blood Cell Life Cycle Evaluated at Singe Cell Resolution

Red blood cell formation or erythropoiesis in the bone marrow and exit into circulation are known to be affected by mechanical loading. Specifically, space anemia is a condition observed during prolonged microgravity unloading in which the red blood cell (RBC) mass in circulation is reduced. However, the mechanisms causing space anemia are yet to be clearly established, but may include increased hemolysis of RBC in circulation, decreased RBC production or a combination of both factors. The presentation of space anemia is comparable to chronic anemia conditions associated with aging, disuse, and poor health. Molecular dysregulation in the RBC's life cycle is poorly defined and is a significant concern in the context of disuse anemia as mechanotransduction significantly alters of gene expression, protein synthesis and cell signaling pathways. Our study analyzes mouse single cell RNA sequencing libraries from the bone marrow, circulating blood, and spleen and integrates the RBC lineage populations from the tissues into a RBC life cycle atlas. This study also probes how age at time of spaceflight contributes to the molecular signature of space anemia. The overarching objective of the study is to develop a mechanistic understanding of space anemia and translate the findings to a better understanding of aging, disuse, and poor health-related anemia to defining the role of mechanical loading in health and devise potential therapeutic interventions. Important findings of our study are: 1) that mechanical unloading in microgravity alters the proportion of developmental RBC lineage cells, skewing toward progenitor, indicating that fewer RBCs may be present in blood; 2) that late reticulocyte number is elevated in the bone marrow of older animals, suggesting a failure to enter circulation; and 3) that the molecular signature of the circulating RBCs is not significantly altered in microgravity. However, expression markers for eryptosis and erythrophagocytosis are elevated in circulating and spleen RBCs, suggesting spaceflight may shorten the lifetime of RBCs after exit from the marrow. In conclusion our results suggest early stages of erythropoiesis proliferation and differentiation in the marrow are key factors in space anemia and mechanical loading may be a necessary step of RBC entry in circulation.

blood↗

Assessment of the Utility of the Oral Fluid and Plasma Proteome for Hydrocodone Usage

Non-medical use and abuse of prescription opioids is a growing problem in both the civilian and military communities, with minimal technologies for detecting hydrocodone use. This study explored the proteomic changes that occur in the oral fluid and blood plasma following controlled hydrocodone administration in twenty subjects. The global proteomic profile was determined for samples taken at four time points per subject of pre-exposure and 4, 6, or 168 hours post-exposure. The oral fluid samples analyzed herein provided greater differentiation between “baseline” and “response” time points than was observed with blood plasma, at least partially due to significant person-to-person variability in the plasma proteome. A total of 399 proteins were identified from oral fluid samples, and the abundance of 102 of those proteins was determined to be significantly different upon metabolism of hydrocodone (4 and 6 hour time points) as compared to baseline levels in the oral fluid (pre-dose and 168 hour). This is the first, to our knowledge, assessment of the oral fluid and blood plasma proteome following hydrocodone administration, which demonstrates the potential of oral fluid as a non-invasive sample that may reveal features of hydrocodone or other opioid use and/or misuse.

Kaiser, Brooke LD↗

Large-Scale Interlaboratory DI-FT-ICR MS Comparability Study Employing Various Systems

We report ultra-high resolution mass spectrometry (UHR-MS) coupled with direct infusion (DI) electrospray ionization offers a fast solution for accurate untargeted profiling. Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometers have been shown to produce a wealth of insights into complex chemical systems because they enable unambiguous molecular formula assignment even if the vast majority of signals is of unknown identity. Inter-laboratory comparisons are required to apply this type of instrumentation in quality control (for food industry or pharmaceutics), large-scale environmental studies or clinical diagnostics. Extended comparisons employing different FT-ICR MS instruments with qualitative direct infusion analysis are scarce since the majority of detected compounds cannot be quantified. The extent to which observations can be reproduced by different laboratories remains unknown. We set up a preliminary study which encompassed a set of seventeen laboratories around the globe, diverse in instrumental characteristics and applications, to analyze the same sets of extracts from commercially available standard human blood plasma and Standard Reference Material (SRM) for blood plasma (SRM1950), which were delivered at different dilutions or spiked with different concentrations of pesticides. The aim of this study was to assess the extent to which the outputs of differently tuned FTICR mass spectrometers, with different technical specifications, are comparable for setting the frames of a future DI-FT-ICR MS ring trial. We concluded that a cluster of five laboratories, with diverse instrumental characteristics showed comparable and representative performance across all experiments, setting a reference to be used in a future ring trial on blood plasma.

47 OTHER INSTRUMENTATION↗

Electron microprobe analysis program for biological specimens: BIOMAP

BIOMAP is a Univac 1108 compatible program which facilitates the electron probe microanalysis of biological specimens. Input data are X-ray intensity data from biological samples, the X-ray intensity and composition data from a standard sample and the electron probe operating parameters. Outputs are estimates of the weight percentages of the analyzed elements, the distribution of these estimates for sets of red blood cells and the probabilities for correlation between elemental concentrations. An optional feature statistically estimates the X-ray intensity and residual background of a principal standard relative to a series of standards.

Edwards, B. F.↗

Validation of Spectral Analysis as a Noninvasive Tool to Assess Autonomic Regulation of Cardiovascular Function

A major focus of our program has been to develop a sensitive noninvasive procedure to quantify early weightlessness-induced changes in cardiovascular function or potential dysfunction. Forty studies of healthy young volunteers (10 men and 10 women, each studied twice) were conducted to determine changes in the sympatho-vagal balance of autonomic control of cardiovascular regulation during graded headward and footward blood volume shifts. Changes in sympatho-vagal balance were classified by changes in the mean levels and spectral content of cardiovascular variables and verified by changes in circulating levels of catecholamines and pancreatic polypeptide. Possible shifts in intra/extravascular fluid were assessed from changes in hematocrit and plasma mass density while changes in the stimulus to regulate plasma volume were determined from Plasma Renin Activity (PRA). Autonomic blockade was used to unmask the relative contribution of sympathetic and parasympathetic efferent influences in response to 10 min each of 0, 20 and 40 mmHg Lower Body Negative Pressure (LBNP) and 15 and 30 mmHg Positive Pressure (LBPP). The combination of muscarinic blockade with graded LBNP and LBPP was used to evoke graded increases and decreases in sympathetic activity without parasympathetic contributions. The combination of beta blockade with graded LBNP and LBPP was used to produce graded increases and decreases in parasympathetic activity without beta sympathetic contributions. Finally, a combination of both beta and muscarinic blockades with LBNP and LBPP was used to determine the contribution from other, primarily alpha adrenergic, sources. Mean values, spectral analyses and time frequency analysis of R-R interval (HR), Arterial Pressure (AP), peripheral blood flow (RF), Stroke Volume (SV) and peripheral resistance (TPR) were performed for all phases of the study. Skin blood Flow (SF) was also measured in other studies and similarly analyzed. Spectra were examined for changes in three frequency regions (low 0.006 - 0.005 Hz (LF), mid 0.05 - 0.15 Hz (W), and high 0.15 - 0.45 Hz (EF)). The primary objective of the study was to indicate which changes in the mean values and/or spectra of cardiovascular variables consistently correlated with changes in sympatho-vagal balance in response to headward and footward fluid shifts. A secondaey objective was to quantify the vascular and extravascular fluid shifts evoked by LBNP and LBPP. The principal hypothesis being tested was that headward fluid shifts would evoke an increase in parasympathetic activity and footward fluid shifts would evoke an increase in sympathetic activity both of which would be detected by spectral analysis and verified by circulating hormones. Hematocrit (HCT), plasma mass density and plasma renin activity increased with muscarinic blockade and with LBNP, a response indicative of a plasma shift to extravascular spaces. Beta blockade alone or after muscarinic blockade had no effect on HCT or plasma mass density. With respect to intravascular fluid volume distribution, LBNP and LBPP produced sufficient upper body vascular fluid shifts to evoke appropriate autonomic regulatory responses.

Knapp, Charles F.↗

Aging and the complexity of cardiovascular dynamics

Biomedical signals often vary in a complex and irregular manner. Analysis of variability in such signals generally does not address directly their complexity, and so may miss potentially useful information. We analyze the complexity of heart rate and beat-to-beat blood pressure using two methods motivated by nonlinear dynamics (chaos theory). A comparison of a group of healthy elderly subjects with healthy young adults indicates that the complexity of cardiovascular dynamics is reduced with aging. This suggests that complexity of variability may be a useful physiological marker.

Non-NASA Center↗