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At least 37 records · Page 2
All sourcesNASA NTRSDOE OSTI
NASA NTRS1978

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.

Hardin, J. C.↗
NASA NTRS1980

Genesis of breath sounds-Preliminary verification of theory

Experimental results are presented which tend to validate a previously developed theory of sound production in the human lung over a particular Reynolds number range. In addition, a new, presently nonunderstood, phenomenon was observed at higher Reynolds number. These results, which show how sound generation in the lung depends upon the physiologically important variables of volume flow rate and bronchial diameter, have potentially important application in noninvasive lung examination and the diagnosis of lung disease.

Patterson, J. L.↗
NASA NTRS1994

Estimates of cellular mutagenesis from cosmic rays

A parametric track structure model is used to estimate the cross section as a function of particle velocity and charge for mutations at the hypoxanthine guanine phosphoribosyl transferase (HGPRT) locus in human fibroblast cell cultures. Experiments that report the fraction of mutations per surviving cell for human lung and skin fibroblast cells indicate small differences in the mutation cross section for these two cell lines when differences in inactivation rates between these cell lines are considered. Using models of cosmic ray transport, the mutation rate at the HGPRT locus is estimated for cell cultures in space flight and rates of about 2 to 10 x 10(exp -6) per year are found for typical spacecraft shielding. A discussion of how model assumptions may alter the predictions is also presented.

Cucinotta, Francis A.↗
NASA NTRS2006

Lunar Dust Activation and Related Studies

The primary objective of the presentation is to identify a set of experiments to activate the lunar dust and monitor the mode of deactivation process using various analytical methods. To satisfy the objective, a large set of experiments will be carried out using lunar dust stimulant (JSC-1a-vf obtained from Dr. V. Carter from University of Texas at Dallas) to optimize the methodology. After refining the methodology to carry out the experiments using the simulant, real lunar dust will be used to obtain the necessary results. The secondary objective of the presentation is to identify a set of experiments to assess the potential toxicity of the dust using cellular systems. One of the cell lines that we identified is WI-38 human lung cell line.

Jeevarajan, Antony↗
NASA NTRS2009

Effect of Lunar Dust Simulant on Human Epithelial Cell Lines

The purpose of this project is to assess the potential toxicity of lunar dust to cause the release of pro-inflammatory cytokines by human lung cells. Some of this dust is on the scale of 1-2 micrometers and could enter the lungs when astronauts track dust into the habitat and inhale it. This could be a serious problem as NASA plans on going back to the moon for an extended period of time. Literature shows that quartz, which has a known cytoxicity, can cause acute cases of silicosis within 6 months, and in most cases cause silicosis after 3 years. The activation of lunar dust through impacts creates surface based radicals which, upon contact with water create hydroxl radicals and peroxyl radicals which are very reactive and potentially might even be as cytotoxic as quartz. These radicals could then react with lung cells to produce pro-inflammatory mediators such as interleukin-6 and interleukin-8, and TNF-alpha.

Myers, Nicholas J.↗
NASA NTRS2015

Summer 2015 Internship Abstract

Green fluorescent protein (GFP) visually shows the expression of proteins by fluorescing when exposed to certain wavelengths of light. The GFP in this experiment was used to identify cells actively releasing viruses. The experiment focused on the effect of microgravity on the GFP expression of Akata B-cells infected with Epstein Barr Virus (EBV). Two flasks were prepared with 30 million cells each and two bioreactors were prepared with 50 million cells each. All four cultures were incubated for 16 days and fed every four days. Cellometer readings were taken on the feeding days to find cell size, viability, and GFP expression. In addition, the cells were treated with Propodium monoazide (PMA) and run through real time PCR to determine viral load on the feeding days. On the International Space Station air samples are taken to analyze the bacterial and fungal organisms in the air. The Sartorius Portable Airport is being investigated for potential use on the ISS to analyze for viral content in the air. Multiple samples were taken around Johnson Space Center building 37 and in Clear Lake Pediatric Clinic. The filter used was the gelatin membrane filter and the DNA was extracted directly from the filter. The DNA was then run through real time PCR for Varicella Zoster Virus (VZV) and EBV as well as GAPDH to test for the presence of DNA. The results so far have shown low DNA yield and no positive results for VZV or EBV. Further inquiry involves accurately replicating an atmosphere with high viral load from saliva as would be found on the ISS to run the air sampler in. Another line of research is stress hormones that may be correlated to the reactivation of latent viruses. The stress hormones from saliva samples are analyzed rather than blood samples. The quantity found in saliva shows the quantity of the hormones actually attached to cells and causing a reaction, whereas in the blood the quantity of hormones is the total amount released to cause a reaction. The particular hormones tested for were cortisol, alpha-amylase, and DHEA. The DHEA was very high in the two control samples tested. Regularly, samples came into the lab from local clinics to be tested for various viruses. Saliva, blood, body scrapes, and tears were received from the clinics and then run for VZV, EBV, and Human Simplex Virus 1 (HSV-1) with the results then reported back to the clinician. Blood, saliva, and urine from astronauts were also tested for viruses and logged. In addition, several cell cultures were brought up and grown, including adherent Human Lung Fibroblast (HFL) cells infected with VZV, and Akata B-cells infected with EBV.

Smith, Courtney↗
NASA NTRS1998

Contributions of tidal lung inflation to human R-R interval and arterial pressure fluctuations

We studied the effects of mechanical lung inflation on respiratory frequency R-R interval and arterial pressure fluctuations in nine healthy young adults undergoing elective orthopedic surgery. We conducted this research to define the contribution of pulmonary and thoracic stretch receptor input to respiratory sinus arrhythmia. We compared fast Fourier transform spectral power during three modes of ventilation: (1) spontaneous, frequency-controlled (0.25 Hz) breathing, (2) intermittent positive pressure ventilation (0.25 Hz, with a tidal volume of 8 ml/kg) and (3) high frequency jet ventilation (5.0 Hz, 2.5 kg/cm2), after sedation and vecuronium paralysis. Mean R-R intervals, arterial pressures and arterial blood gas levels were comparable during all three breathing conditions. Respiratory frequency systolic pressure spectral power was comparable during spontaneous breathing and conventional mechanical ventilation, but was significantly reduced during high frequency jet ventilation (P < 0.05). Respiratory frequency R-R interval spectral power (used as an index of respiratory sinus arrhythmia) declined dramatically with sedation and muscle paralysis (P < 0.05), but was greater during conventional mechanical, than high frequency jet ventilation (P < 0.05). These results suggest that although phasic inputs from pulmonary and thoracic stretch receptors make a statistically significant contribution to respiratory sinus arrhythmia, that contribution is small.

Clinical Trial↗
NASA NTRS2015

Toxicity of Mineral Dusts and a Proposed Mechanism for the Pathogenesis of Particle-Induced Lung Diseases

Humans will set foot on the moon again. The lunar surface has been bombarded for 4 billion years by micrometeoroids and cosmic radiation, creating a layer of fine dust having a potentially reactive particle surface. To investigate the impact of surface reactivity (SR) on the toxicity of particles, and in particular, lunar dust (LD), we ground 2 Apollo 14 LD samples to increase their SR and compare their toxicity with those of unground LD, TiO2 and quartz. Intratracheally instilled at 0, 1, 2.5, or 7.5 mg/rat, all dusts caused dose-dependent increases in pulmonary lesions, and enhancement of biomarkers of toxicity assessed in bronchoalveolar lavage fluids (BALF). The toxicity of LD was greater than that of TiO2 but less than that of quartz. Three LDs differed 14-fold in SR but were equally toxic; quartz had the lowest SR but was most toxic. These results show no correlation between particle SR and toxicity. Often pulmonary toxicity of a dust can be attributed to oxidative stress (OS). We further observed dose-dependent and dustcytotoxicity- dependent increases in neutrophils. The oxidative content per BALF cell was also directly proportional to both the dose and cytotoxicity of the dusts. Because neutrophils are short-lived and release of oxidative contents after they die could initiate and promote a spectrum of lesions, we postulate a general mechanism for the pathogenesis of particle-induced diseases in the lung that involves chiefly neutrophils, the source of persistent endogenous OS. This mechanism explains why one dust (e.g., quartz or nanoparticles) is more toxic than another (e.g., micrometer-sized TiO2), why dust-induced lesions progress with time, and why lung cancer occurs in rats but not in mice and hamsters exposed to the same duration and concentration of dust.

Lam, C.‐W.↗
NASA NTRS1997

Activation and proliferation of lymphocytes and other mammalian cells in microgravity

The experimental findings reviewed in this chapter support the following conclusions: Proliferation. Human T-lymphocytes, associated with monocytes as accessory cells, show dramatic changes in the centrifuge, in the clinostat and in space. In free-floating cells the mitogenic response is depressed by 90% in microgravity, whereas in cells attached to a substratum activation is enhanced by 100% compared to 1-G ground and inflight controls. The duration of phase G1 of the mitotic cycle of HeLa cells is reduced in hypergravity, resulting in an increased proliferation rate. Other systems like Friend cells and WI38 human embryonic lung cells do not show significant changes. Genetic expression and signal transduction. T-lymphocytes and monocytes show important changes in the expression of cytokines like interleukin-1, interleukin-2, interferon-gamma and tumor necrosis factor. The data from space experiments in Spacelab, Space Shuttle mid-deck, and Biokosmos have helped to clarify certain aspects of the mechanism of T-cell activation. Epidermoid A431 cells show changes in the genetic expression of the proto-oncogenes c-fos and c-jun in the clinostat and in sounding rockets. Membrane function, in particular the binding of ligates as first messengers of a signal, is not changed in most of the cell systems in microgravity. Morphology and Mortility. Free cells, lymphocytes in particular, are able to move and form aggregates in microgravity, indicating that cell-cell contacts and cell communications do take place in microgravity. Dramatic morphological and ultrastructural changes are not detected in cells cultured in microgravity. Important experiments with single mammalian cells, including immune cells, were carried out recently in three Spacelab flights, (SL-J, D-2, and IML-2 in 1992, 1993, and 1994, respectively). The results of the D-2 mission have been published in ref. 75; those of the IML-2 mission in ref. 76. Finally, many cell biology experiments in space have suffered in the past from a lack of adequate controls (like 1-G centrifuges) and of proper experimental conditions (like well-controlled temperature). In this respect the availability of Biorack, outfitted with proper incubators with 1-G control centrifuge as well as a glovebox with a microscope, is a great advantage. It is also desirable that cell biology experiments in space are accompanied or even preceded by a program of ground-based investigations in the fast rotating clinostat and in the centrifuge, and that preparatory experiments be done in parabolic flights and sounding rockets, whenever possible. Proper publication of the results of space experiments is another important need. A great number of data have been published in proceedings and reports that are not available to the broad scientific community. To guarantee the credibility and the international recognition of space biology it is important that the results be published in international, peer reviewed journals.

manned↗
NASA NTRS1974

The response of single human cells to zero gravity

The SO15 experiment was designed to extend observations of the effects of zero-gravity to living human cells during and subsequent to a 59-day flight on Skylab 3. A strain of diploid human embryonic lung cells, WI-38, was chosen for this purpose. The studies were concerned with observations designed to detect the effects of zero-gravity on cell growth rates and on cell structure as observed by light microscopy, transmission and scanning electron microscopy and histochemistry. Studies of the effects of zero-gravity on the cell function and the cell cycle were performed by time lapse motion picture photography and microspectrophotometry. Subsequent study of the returned living cells included karotyping, G- and C-banding, and analyses of the culture media used. Some of the living cells returned were banked by deep freeze techniques for possible future experiments.

Montgomery, P. O., Jr.↗
NASA NTRS1975

The response of single human cells to zero gravity

Twenty separate cultures of Wistar-38 human embryonic lung cells were exposed to a zero-gravity environment on Skylab for periods of time ranging from one to 59 days. Duplicate cultures were run concurrently as ground controls. Ten cultures were fixed on board the satellite during the first 12 days of flight. Growth curves, DNA microspectrophotometry, phase microscopy, and ultrastructural studies of the fixed cells revealed no effects of a zero-gravity environment on the ten cultures. Two cultures were photographed with phase time lapse cinematography during the first 27 days of flight. No differences were found in mitotic index, cell cycle, and migration between the flight and control cells. Eight cultures were returned to earth in an incubated state. Karyotyping and chromosome banding tests show no differences between the flight and control cells.

Montgomery, P. O., Jr.↗
NASA NTRS1977

The response of single human cells to zero-gravity

Microscopic and histochemical evaluations of human embrionic lung cells after exposure to zero-gravity are reported. Growth curves, DNA microspectrophotometry, phase microscopy, and ultrastructural studies of fixed cells revealed no effects on the cultures. Minor unexplained differences have been found in biochemical constituents of the samples.

Montgomery, P. O., Jr.↗
NASA NTRS2003

MRI of the lung gas-space at very low-field using hyperpolarized noble gases

In hyperpolarized (HP) noble-gas magnetic resonance imaging, large nuclear spin polarizations, about 100,000 times that ordinarily obtainable at thermal equilibrium, are created in 3He and 129Xe. The enhanced signal that results can be employed in high-resolution MRI studies of void spaces such as in the lungs. In HP gas MRI the signal-to-noise ratio (SNR) depends only weakly on the static magnetic field (B(0)), making very low-field (VLF) MRI possible; indeed, it is possible to contemplate portable MRI using light-weight solenoids or permanent magnets. This article reports the first in vivo VLF MR images of the lungs in humans and in rats, obtained at a field of only 15 millitesla (150 Gauss).

NASA Discipline Life Sciences Technologies↗
NASA NTRS2005

Aerosols in the study of convective acinar mixing

Convective mixing (CM) refers to the different transport mechanisms except Brownian diffusion that irreversibly transfer inspired air into resident air and can be studied using aerosol bolus inhalations. This paper provides a review of the present understanding of how each of these mechanisms contributes to CM. Original data of the combined effect of stretch and fold and gravitational sedimentation on CM are also presented. Boli of 0.5 microm-diameter particles were inhaled at penetration volumes (V(p)) of 300 and 1200 ml in eight subjects. Inspiration was followed by a 10-s breath hold, during which small flow reversals (FR) were imposed, and expiration. There was no physiologically significant dependence in dispersion and deposition with increasing FR. The results were qualitatively similar to those obtained in a previous study in microgravity in which it was speculated that the phenomenon of stretch and fold occurred during the first breathing cycle without the need of any subsequent FR.

Convection↗
NASA NTRS2007

Subclinical Reactivation and Shed of Infectious Varicella Zoster Virus in Saliva of Astronauts

We have previously detected VZV in healthy astronauts both during spaceflight and shortly after landing. Herein, we show that VZV shed in seropositive astronauts is infectious. A total of 40 saliva samples were obtained from each of the 3 astronauts. From each astronaut, 14 samples were taken 109 to 133 days before liftoff, 1 sample was taken every day during 12 days in space, and one sample was taken for 14 consecutive days beginning the second day after landing. Quantitative PCR was used to detect VZV DNA in saliva. None of 42 preflight saliva samples contained VZV DNA. VZV DNA was detected in saliva from 2 of 3 astronauts. In 1 astronaut, 6 of 12 samples obtained during space flight contained 120 to 2,500 copies of VZV DNA per ml; after landing, 1250 copies of VZV DNA were present on day 2, 45 copies on day 3, and 110 copies on day 5. All samples taken 6 to 15 days after touchdown were negative for VZV DNA. In the second astronaut, 5 of 12 samples obtained during space flight contained 18 to 650 copies of VZV DNA per ml; after landing, 560 copies of VZV DNA were present in saliva on day 2, 340 copies on day 4, 45 copies on day 5, and 23 copes on day 6. All samples taken 7 to 15 days after touchdown were negative for VZV DNA. Saliva taken 2 to 6 days after landing from all 3 astronauts was cultured on human fetal lung cells. After one subcultivation, a cytopathic effect developed in cultures inoculated with saliva from the two astronauts whose saliva contained VZV DNA. Both PCR and immunostaining identified the isolates to be VZV and not HSV-1. Importantly, the astronaut in whom no VZV was detected had a history of zoster 9 years earlier. It is possible that a boost in cell-mediated immunity to VZV which is known to develop after zoster protected him from subclinical reactivation. The genotype of the two VZV isolates was determined by VZV ORF22-based PCR/sequencing along with FRET-based PCR assays that target specific nucleotide polymorphisms. Both VZV isolates were found to be the European genotype which also contained a rare MspI restriction enodnuclease site in VZV ORF62 at position 107,252. These findings extend our previous demonstration of VZV DNA in saliva of astronauts by showing that infectious VZV is also present. Thus, like HSV-1 and HSV-2, VZV can reactivate and shed infectious virus in the absence of clinical disease.

Cohrs, Randall J.↗
NASA NTRS2007

Subclinical Shed of Infectious Varicella zoster Virus in Astronauts

Aerosol borne varicella zoster virus (VZV) enters the nasopharynx and replicates in tonsillar T-cells, resulting in viremia and varicella (chickenpox). Virus then becomes latent in cranial nerve, dorsal root and autonomic nervous system ganglia along the entire neuraxis (1). Decades later, as cell-mediated immunity to VZV declines (4), latent VZV can reactivate to produce zoster (shingles). Infectious VZV is present in patients with varicella or zoster, but shed of infectious virus in the absence of disease has not been shown. We previously detected VZV DNA in saliva of astronauts during and shortly after spaceflight, suggesting stress induced subclinical virus reactivation (3). We show here that VZV DNA as well as infectious virus in present in astronaut saliva. VZV DNA was detected in saliva during and after a 13-day spaceflight in 2 of 3 astronauts (Fig. panel A). Ten days before liftoff, there was a rise in serum anti-VZV antibody in subjects 1 and 2, consistent with virus reactivation. In subject 3, VZV DNA was not detected in saliva, and there was no rise in anti-VZV antibody titer. Subject 3 may have been protected from virus reactivation by having zoster <10 years ago, which provides a boost in cell-medicated immunity to VZV (2). No VZV DNA was detected in astronaut saliva months before spaceflight, or in saliva of 10 age/sex-matched healthy control subjects sampled on alternate days for 3 weeks (88 saliva samples). Saliva taken 2-6 days after landing from all 3 subjects was cultured on human fetal lung cells (Fig. panel B). Infectious VZV was recovered from saliva of subjects 1 and 2 on the second day after landing. Virus specificity was confirmed by antibody staining and DNA analysis which showed it to be VZV of European descent, common in the US (5). Further, both antibody staining and DNA PCR demonstrated that no HSV-1 was detected in any infected culture. This is the first report of infectious VZV shedding in the absence of clinical disease. Spaceflight presents a uniquely stressful environment which includes physical isolation and confinement, anxiety, sleep deprivation, as well as exposure to increased radiation and microgravity. It is interesting that in our study, VZV and not HSV-1 reactivation was detected, since stress-induced HSV-1 reactivation has been reported (6). Future studies are needed to determine the specific inducer of VZV reactivation.

Cohrs, Randall J.↗
NASA NTRS2009

Microgravity Analogues of Herpes Virus Pathogenicity: Human Cytomegalovirus (hCMV) and Varicella Zoster (VZV) Infectivity in Human Tissue Like Assemblies (TLAs)

The old adage we are our own worst enemies may perhaps be the most profound statement ever made when applied to man s desire for extraterrestrial exploration and habitation of Space. Consider the immune system protects the integrity of the entire human physiology and is comprised of two basic elements the adaptive or circulating and the innate immune system. Failure of the components of the adaptive system leads to venerability of the innate system from opportunistic microbes; viral, bacteria, and fungal, which surround us, are transported on our skin, and commonly inhabit the human physiology as normal and imunosuppressed parasites. The fine balance which is maintained for the preponderance of our normal lives, save immune disorders and disease, is deregulated in microgravity. Thus analogue systems to study these potential Risks are essential for our progress in conquering Space exploration and habitation. In this study we employed two known physiological target tissues in which the reactivation of hCMV and VZV occurs, human neural and lung systems created for the study and interaction of these herpes viruses independently and simultaneously on the innate immune system. Normal human neural and lung tissue analogues called tissue like assemblies (TLAs) were infected with low MOIs of approximately 2 x 10(exp -5) pfu hCMV or VZV and established active but prolonged low grade infections which spanned .7-1.5 months in length. These infections were characterized by the ability to continuously produce each of the viruses without expiration of the host cultures. Verification and quantification of viral replication was confirmed via RT_PCR, IHC, and confocal spectral analyses of the respective essential viral genomes. All host TLAs maintained the ability to actively proliferate throughout the entire duration of the experiments as is analogous to normal in vivo physiological conditions. These data represent a significant advance in the ability to study the triggering mechanisms which surround Herpes vial reactivation and proliferation. Additionally, prolonged replication of these viruses will allow the tracking of viral genomic shift.

Goodwin, T. J.↗
NASA NTRS1997

Hypergravity Alters the Susceptibility of Cells to Anoxia-Reoxygenation Injury

Gravity is a physical force, much like shear stress or mechanical stretch, and should affect organ and cellular function. Researchers have shown that gravity plays a role in ventilation and blood flow distribution, gas exchange, alveolar size and mechanical stresses within the lung. Short exposure to microgravity produced marked alterations in lung blood flow and ventilation distribution while hypergravity exaggerated the regional differences in lung structure and function resulting in reduced ventilation at the base and no ventilation of the upper half of the lung. Microgravity also decreased metabolic activity in cardiac cells, WI-38 embryonic lung cells, and human lymphocytes. Rats, in the tail-suspended head-down tilt model, experienced transient loss of lung water, contrary to an expected increase due to pooling of blood in the pulmonary vasculature. Hypergravity has also been found to increase the proliferation of several different cell lines (e.g., chick embryo fibroblasts) while decreasing cell motility and slowing liver regeneration following partial hepatectomy. These studies show that changes in the gravity environment will affect several aspects of organ and cellular function and produce major change in blood flow and tissue/organ perfusion. However, these past studies have not addressed whether ischemia-reperfusion injury will be exacerbated or ameliorated by changes in the gravity environment, e.g., space flight. Currently, nothing is known about how gravity will affect the susceptibility of different lung and vascular cells to this type of injury. We conducted studies that addressed the following question: Does the susceptibility of lung fibroblasts, vascular smooth muscle, and endothelial cells to anoxia/reoxygenation injury change following exposure to hypergravity conditions?

McCloud, Henry↗