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At least 19 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS2008

Three-Dimensionally Engineered Normal Human Lung Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

In vitro three-dimensional (3D) human lung epithelio-mesenchymal tissue-like assemblies (3D hLEM TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and the detection of membrane bound glycoproteins over time confirm productive infection with the virus. Therefore, we assert TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host s immune system.

Goodwin, Thomas J.↗
NASA NTRS2010

Next Generation Respiratory Viral Vaccine System: Advanced and Emerging Bioengineered Human Lung Epithelia Model (HLEM) Organoid Technology

Acute respiratory infections, including pneumonia and influenza, are the S t" leading cause of United States and worldwide deaths. Newly emerging pathogens signaled the need for an advanced generation of vaccine technology.. Human bronchial-tracheal epithelial tissue was bioengineered to detect, identify, host and study the pathogenesis of acute respiratory viral disease. The 3-dimensional (3D) human lung epithelio-mesechymal tissue-like assemblies (HLEM TLAs) share characteristics with human respiratory epithelium: tight junctions, desmosomes, microvilli, functional markers villin, keratins and production of tissue mucin. Respiratory Syntial Virus (RSV) studies demonstrate viral growth kinetics and membrane bound glycoproteins up to day 20 post infection in the human lung-orgainoid infected cell system. Peak replication of RSV occurred on day 10 at 7 log10 particles forming units per ml/day. HLEM is an advanced virus vaccine model and biosentinel system for emergent viral infectious diseases to support DoD global surveillance and military readiness.

Goodwin, Thomas J.↗
NASA NTRS1979

Radiographic Comparison of Human Lung Shape During Normal Gravity and Weightlessness

Chest radiographs in five seated normal volunteers at 1 G and 0 G were made with a view toward comparing human lung shape during normal gravity and weightlessness. Lung shape was assessed by measuring lung heights and widths in upper, middle and lower lung regions. No significant differences were found between any of the 1-G and 0-G measurements, although there was a slight tendency for the lung to become shorter and wider at 0 G. The evidence that gravity causes regional differences in ventilation by direct action on the lung is consistent with the theoretical analysis of West and Matthews (1972).

Michels, D. B.↗
NASA NTRS2003

Three-Dimensional Engineered High Fidelity Normal Human Lung Tissue-Like Assemblies (TLA) as Targets for Human Respiratory Virus Infections

Unlike traditional two-dimensional (2D) cell cultures, three-dimensional (3D) tissue-like assemblies (TLA) (Goodwin et aI, 1992, 1993, 2000 and Nickerson et aI. , 2001,2002) offer high organ fidelity with the potential to emulate the infective dynamics of viruses and bacteria in vivo. Thus, utilizing NASA micro gravity Rotating Wall Vessel (RWV) technology, in vitro human broncho-epithelial (HBE) TLAs were engineered to mimic in vivo tissue for study of human respiratory viruses. These 3D HBE TLAs were propagated from a human broncho-tracheal cell line with a mesenchymal component (HBTC) as the foundation matrix and either an adult human broncho-epithelial cell (BEAS-2B) or human neonatal epithelial cell (16HBE140-) as the overlying element. Resulting TLAs share several characteristic features with in vivo human respiratory epithelium including tight junctions, desmosomes and cilia (SEM, TEM). The presence of epithelium and specific lung epithelium markers furthers the contention that these HBE cells differentiate into TLAs paralleling in vivo tissues. A time course of infection of these 3D HBE TLAs with human respiratory syncytial virus (hRSV) wild type A2 strain, indicates that virus replication and virus budding are supported and manifested by increasing virus titer and detection of membrane-bound F and G glycoproteins. Infected 3D HBE TLAs remain intact for up to 12 days compared to infected 2D cultures that are destroyed in 2-3 days. Infected cells show an increased vacuolation and cellular destruction (by transmission electron microscopy) by day 9; whereas, uninfected cells remain robust and morphologically intact. Therefore, the 3D HBE TLAs mimic aspects of human respiratory epithelium providing a unique opportunity to analyze, for the first time, simulated in vivo viral infection independent of host immune response.

Goodwin, T. J.↗
NASA NTRS1998

Deposition and dispersion of 1-micrometer aerosol boluses in the human lung: effect of micro- and hypergravity

We performed bolus inhalations of 1-micrometer particles in four subjects on the ground (1 G) and during parabolic flights both in microgravity (microG) and in approximately 1.6 G. Boluses of approximately 70 ml were inhaled at different points in an inspiration from residual volume to 1 liter above functional residual capacity. The volume of air inhaled after the bolus [the penetration volume (Vp)] ranged from 200 to 1,500 ml. Aerosol concentration and flow rate were continuously measured at the mouth. The deposition, dispersion, and position of the bolus in the expired gas were calculated from these data. For Vp >/=400 ml, both deposition and dispersion increased with Vp and were strongly gravity dependent, with the greatest deposition and dispersion occurring for the largest G level. At Vp = 800 ml, deposition and dispersion increased from 33.9% and 319 ml in microG to 56.9% and 573 ml at approximately 1.6 G, respectively (P < 0.05). At each G level, the bolus was expired at a smaller volume than Vp, and this volume became smaller with increasing Vp. Although dispersion was lower in microG than in 1 G and approximately 1.6 G, it still increased steadily with increasing Vp, showing that nongravitational ventilatory inhomogeneity is partly responsible for dispersion in the human lung.

Parabolic Flight↗
NASA NTRS2007

Toxicity and Radioprotective Effects of DF-1 and Carbon Nanotubes in Human Lung and Liver Cell Lines

The DF-1 compound, a sixty carbon fullerene derivative, has been shown to have antioxidant effects and is thought to possibly help mediate the effects of radiation on cells. While this is potentially useful, it is important to first understand the effect that the DF-1 has on the cells and the growth rate of the cells to determine if the material itself has any innate toxicity. A growth curve was established for both HF-19 cells, human fibroblasts, and HepG2 cells, liver tissue cells in the presence of two different concentrations of DF-1 and for untreated controls. The cells were plated in triplicate in 60mm dishes and were lifted and counted with a hemocytometer daily for one week. The growth curve data for the HF-19 cells show that while the low concentration of DF-1 had no apparent effect on the growth rate, the high concentration of DF-1 appeared to severely inhibit the growth of the HF-19 cells. The growth curve data for the HepG2 cells shows that the DF-1 compound had no significant effect on the rate at which the cells grew. A second growth curve study was performed plain carbon nanotubes, but with only 24 hour exposure to a high and low concentration of material. The carbon nanotubes are another carbon compound similar to DF-1, but in the shape of a tube, rather than a ball. We hypothesize that nanotubes may also mediate the effect of radiation on cells. This time, nanotubes did not showed any significant effect on the growth rate HF-19 or HepG2 cells. A third growth curve study is underway to further determine the effect of DF-1, nanotubes, and a derivatized nanotube (BHT-nanotubes). This derivatized nanotube has been modified with a compound that is known to be very effective at neutralizing free radicals. We expect that the high concentration of DF-1 and possibly the nanotubes and BHT-nanotubes may inhibit the growth of the HF-19 cells while the low concentration will resemble the growth of the control. We also hypothesize that there will be no significant effect on the growth of the HepG2 cells by the nanotubes, and BHT-nanotubes. In order to examine the usefulness of the DF-1, nanotubes, and BHT-nanotubes in mediating the effects of radiation a clonogenic assay is being performed. The HF-19 cells were plated in different concentrations of the various compounds and exposed to varying amounts of radiation. The cells are being allowed to grow in a small enough concentration so that the ability of each cell to divide can be seen by the development of cell clusters. By comparing the irradiated control to the un-irradiated control the effects of radiation alone can be seen. By comparing the compound treated irradiated cells to the irradiated control the usefulness of each compound can be seen. It is thought that Amifostine, the positive control, will have more regularly dividing cells then the irradiated control, as will DF-1 and hopefully both nanotube materials as well.

Burgoyne, Madeline↗
NASA NTRS2009

Cytotoxic Effects of Re-Activated Lunar Dust Stimulant on Human Lung Cells

Lunar dust has been of significant concern due to various problems observed on the Apollo missions. Reports from astronauts have shown that the dust may have caused eye and nasal irritation as well as possible hay fever like symptoms. As NASA hopes to go to the Moon within the next few years, we hope to understand the possible toxic effects the dust might have. In these studies, we are looking at the effect of "re-activated" lunar dust stimulant on human bronchial cells. A simple grinding analog as a method of simulating micrometeorite crushing on the moon is used to "activate" the dust stimulant, i.e. capable of producing hydroxyl radicals. These radicals could then interact with human cells and may lead to a loss in membrane integrity and cell death. (Castranova, 1994) Cells are exposed to the dust for 6 and 24 hour intervals to assess cytotoxicity. Cytotoxicity is measured by looking at the production of inflammatory cytokines. Cells are exposed to ground and unground stimulant and compared to cytokine production from cells exposed to quartz which have a known toxicity. Here we look at the cytotoxicity of the lunar dust stimulant relative to quartz by measuring the production of inflammatory cytokines.

Upadhyaya, Krishna↗
NASA NTRS2002

Mode shift of an inhaled aerosol bolus is correlated with flow sequencing in the human lung

We studied the effects on aerosol bolus inhalations of small changes in convective inhomogeneity induced by posture change from upright to supine in nine normal subjects. Vital capacity single-breath nitrogen washout tests were used to determine ventilatory inhomogeneity change between postures. Relative to upright, supine phase III slope was increased 33 +/- 11% (mean +/- SE, P < 0.05) and phase IV height increased 25 +/- 11% (P < 0.05), consistent with an increase in convective inhomogeneity likely due to increases in flow sequencing. Subjects also performed 0.5-microm-particle bolus inhalations to penetration volumes (V(p)) between 150 and 1,200 ml during a standardized inhalation from residual volume to 1 liter above upright functional residual capacity. Mode shift (MS) in supine posture was more mouthward than upright at all V(p), changing by 11.6 ml at V(p) = 150 ml (P < 0.05) and 38.4 ml at V(p) = 1,200 ml (P < 0.05). MS and phase III slope changes correlated positively at deeper V(p). Deposition did not change at any V(p), suggesting that deposition did not cause the MS change. We propose that the MS change results from increased sequencing in supine vs. upright posture.

NASA Discipline Cardiopulmonary↗
NASA NTRS1997

Effect of microgravity and hypergravity on deposition of 0.5- to 3-micron-diameter aerosol in the human lung

We measured intrapulmonary deposition of 0. 5-, 1-, 2-, and 3-micron-diameter particles in four subjects on the ground (1 G) and during parabolic flights both in microgravity (microG) and at approximately 1.6 G. Subjects breathed aerosols at a constant flow rate (0.4 l/s) and tidal volume (0.75 liter). At 1 G and approximately 1.6 G, deposition increased with increasing particle size. In microG, differences in deposition as a function of particle size were almost abolished. Deposition was a nearly linear function of the G level for 2- and 3-micron-diameter particles, whereas for 0.5- and 1.0-micron-diameter particles, deposition increased less between microG and 1 G than between 1 G and approximately 1.6 G. Comparison with numerical predictions showed good agreement for 1-, 2-, and 3-micron-diameter particles at 1 and approximately 1.6 G, whereas the model consistently underestimated deposition in microG. The higher deposition observed in microG compared with model predictions might be explained by a larger deposition by diffusion because of a higher alveolar concentration of aerosol in microG and to the nonreversibility of the flow, causing additional mixing of the aerosols.

Flight Experiment↗
NASA NTRS2007

Effects of Lunar Dust Simulant (JSC-1A-vf) on WI-38 Human Embryonic Lung Cells

In order to develop appropriate countermeasures for NASA's return mission to the moon, the potential toxicity of lunar dust needs to be examined. Due to its abrasiveness, reactivity, composition and small size, lunar dust may pose a serious health risk to astronauts who inhale it. This project focuses on the toxicity of lunar dust simulant (JSC-1A-vf) using WI-38 human embryonic lung cells. Past results show that the simulant has toxic effects on small animals using intratracheal instillation. Earlier studies in this lab suggest that the dust remaining in media after low speed centrifugation is toxic. In order to better assess its toxicity, the simulant has been diluted in media, filtered with a 5 micron filter before combining it with media. This filtered dust is compared with dust centrifuged in media. Whole dust toxicity is also tested. Toxicity is estimated using a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) toxicity test which measures the activity of reducing enzymes in the mitochondria of viable cells. Preliminary results suggest that simulant which is diluted in media at different concentrations is slightly toxic. Interestingly, the cells appear to sweep up and collect the simulant. Whether this contributes to its toxicity is unclear. This project provides possible toxicity testing protocols for lunar dust and contributes to the knowledge of nanosize particle toxicity.

Currie, Stephen↗
NASA NTRS2009

Aluminum is More Cytotoxic than Lunar Dust in Human Skin and Lung Fibroblasts

NASA plans to build a permanent space station on the moon to explore its surface. The surface of the moon is covered in lunar dust, which consists of fine particles that contain silicon, aluminum and titanium, among others. Because this will be a manned base, the potential toxicity of this dust has to be studied. Also, toxicity standards for potential exposure have to be set. To properly address the potential toxicity of lunar dust we need to understand the toxicity of its individual components, as well as their combined effects. In order to study this we compared NASA simulant JSC-1AVF (volcanic ash particles), that simulates the dust found on the moon, to aluminum, the 3rd most abundant component in lunar dust. We tested the cytotoxicity of both compounds on human lung and skin fibroblasts (WTHBF-6 and BJhTERT cell lines, respectively). Aluminum oxide was more cytotoxic than lunar dust to both cell lines. In human lung fibroblasts 5, 10 and 50 g/sq cm of aluminum oxide induced 85%, 61% and 30% relative survival, respectively. For human skin fibroblasts the same concentrations induced 58%, 41% and 58% relative survival. Lunar dust was also cytotoxic to both cell lines, but its effects were seen at higher concentrations: 50, 100, 200 and 400 g/sq cm of lunar dust induced a 69%, 46%, 35% and 30% relative survival in the skin cells and 53%, 16%, 8% and 2% on the lung cells. Overall, for both compounds, lung cells were more sensitive than skin cells. This work was supported by a NASA EPSCoR grant through the Maine Space Grant Consortium (JPW), the Maine Center for Toxicology and Environmental Health., a Fulbright Grant (JM) and a Delta Kappa Gamma Society International World Fellowship (JM).

Hammond, D.↗
NASA NTRS1979

Monitoring the state of the human airways by analysis of respiratory sound

A mechanism whereby sound is generated by the motion of vortices in the human lung is described. This mechanism is believed to be responsible for most of the sound which is generated both on inspiration and expiration in normal lungs. Mathematical expressions for the frequencies of sound generated, which depend only upon the axial flow velocity and diameters of the bronchi, are derived. This theory allows the location within the bronchial tree from which particular sounds emanate to be determined. Redistribution of pulmonary blood volume following transition from Earth gravity to the weightless state probably alters the caliber of certain airways and doubtless alters sound transmission properties of the lung. We believe that these changes can be monitored effectively and non-invasively by spectral analysis of pulmonary sound.

Lung/anatomy & histology/physiology↗
NASA NTRS2016

Characterization of Particulate Matter Profiling and Alveolar Deposition from Biomass Burning in Northern Thailand: The 7-SEAS Study

Biomass burning (BB) frequently occurs in SouthEast Asia (SEA), which significantly affects the air quality and could consequently lead to adverse health effects. The aim of this study was to characterize particulate matter (PM) and black carbon (BC) emitted from BB source regions in SEA and their potential of deposition in the alveolar region of human lungs. A 31-day characterization of PM profiling was conducted at the Doi Ang Khang (DAK) meteorology station in northern Thailand in March 2013. Substantial numbers of PM (10147 +/- 5800 # per cubic centimeter) with a geometric mean diameter (GMD) of 114.4 +/- 9.2 nm were found at the study site. The PM of less than 2.5 micron in aerodynamic diameter (PM sub 2.5) hourly-average mass concentration was 78.0 +/- 34.5 per cubic microgram whereas the black carbon (BC) mass concentration was 4.4 +/- 2.6 micrograms per cubic meter. Notably, high concentrations of nanoparticle surface area (100.5 +/- 54.6 square micrometers per cubic centimeter) emitted from biomass burning can be inhaled into the human alveolar region. Significant correlations with fire counts within different ranges around DAK were found for particle number, the surface area concentration of alveolar deposition, and BC. In conclusion, biomass burning is an important PM source in SEA, particularly nanoparticles, which has high potency to be inhaled into the lung environment and interact with alveolar cells, leading to adverse respiratory effects. The fire counts within 100 to 150 km shows the highest Pearson's r for particle number and surface area concentration. It suggests 12 to 24 hr could be a fair time scale for initial aging process of BB aerosols. Importantly, the people lives in this region could have higher risk for PM exposure.

biomass burning↗
NASA NTRS1978

Medical Image Analysis Facility

To improve the quality of photos sent to Earth by unmanned spacecraft. NASA's Jet Propulsion Laboratory (JPL) developed a computerized image enhancement process that brings out detail not visible in the basic photo. JPL is now applying this technology to biomedical research in its Medical lrnage Analysis Facility, which employs computer enhancement techniques to analyze x-ray films of internal organs, such as the heart and lung. A major objective is study of the effects of I stress on persons with heart disease. In animal tests, computerized image processing is being used to study coronary artery lesions and the degree to which they reduce arterial blood flow when stress is applied. The photos illustrate the enhancement process. The upper picture is an x-ray photo in which the artery (dotted line) is barely discernible; in the post-enhancement photo at right, the whole artery and the lesions along its wall are clearly visible. The Medical lrnage Analysis Facility offers a faster means of studying the effects of complex coronary lesions in humans, and the research now being conducted on animals is expected to have important application to diagnosis and treatment of human coronary disease. Other uses of the facility's image processing capability include analysis of muscle biopsy and pap smear specimens, and study of the microscopic structure of fibroprotein in the human lung. Working with JPL on experiments are NASA's Ames Research Center, the University of Southern California School of Medicine, and Rancho Los Amigos Hospital, Downey, California.

Source record↗
NASA NTRS2000

IR spectroscopic characteristics of cell cycle and cell death probed by synchrotron radiation based Fourier transform IR spectromicroscopy

Synchrotron radiation based Fourier transform IR (SR-FTIR) spectromicroscopy allows the study of individual living cells with a high signal to noise ratio. Here we report the use of the SR-FTIR technique to investigate changes in IR spectral features from individual human lung fibroblast (IMR-90) cells in vitro at different points in their cell cycle. Clear changes are observed in the spectral regions corresponding to proteins, DNA, and RNA as a cell changes from the G(1)-phase to the S-phase and finally into mitosis. These spectral changes include markers for the changing secondary structure of proteins in the cell, as well as variations in DNA/RNA content and packing as the cell cycle progresses. We also observe spectral features that indicate that occasional cells are undergoing various steps in the process of cell death. The dying or dead cell has a shift in the protein amide I and II bands corresponding to changing protein morphologies, and a significant increase in the intensity of an ester carbonyl C===O peak at 1743 cm(-1) is observed. Copyright John Wiley & Sons, Inc. Biopolymers (Biospectroscopy) 57: 329-335, 2000.

Non-NASA Center↗
NASA NTRS1973

Recent NASA aerospace medicine technology developments

Areas of life science are being studied to obtain baseline data, strategies, and technology to permit life research in the space environment. The reactions of the cardiovascular system to prolonged weightlessness are also being investigated. Particle deposition in the human lung, independent respiratory support system, food technology, and remotely controlled manipulators are mentioned briefly.

Jones, W. L.↗
NASA NTRS1973

Detection techniques for tenuous planetary atmospheres

The research performed during this period is reported. The studies discussed include: dust grinding and electrification, effects of metallic impurities on exoelectron emission, the connection between the charge acquired by the dust and the effect of the dust on human lung tissue. A list of publications generated by this research is included.

Hoenig, S. A.↗
NASA NTRS1972

Effects of geophysical extra-terrestrial and terrestrial physical stimuli on living organisms - Effects of gravity fields on living organisms

The biologic effects of greatly reduced gravity resulting from space flight are examined. Aspects of U.S. space biology during the period from 1960 to 1972 are discussed, giving attention to the Discoverer satellites, the Gemini series, the OV1-4 satellite, the biosatellite project, the orbiting frog otolith experiment, and the Apollo program. Other studies considered are related to the effects of galactic particles on nonproliferating cells, a recoverable tissue culture experiment, cell cycle maintenance in human lung cells, and effects of space flight on circadian rhythms. Viking will land on the planet Mars in 1975 in search for life forms.

Saunders, R. J. F.↗