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PubMed1993

Evaluation of muscle injury using magnetic resonance imaging.

The objective of this study was to investigate spin echo T2 relaxation time changes in thigh muscles after intense eccentric exercise in healthy men. Spin echo and calculated T2 relaxation time images of the thighs were obtained on several occasions after exercise of one limb; the contralateral limb served as control. Muscle damage was verified by elevated levels of serum creatine kinase (CK). Thirty percent of the time no exercise effect was discernible on the magnetic resonance (MR) images. In all positive MR images (70%) the semitendinosus muscle was positive, while the biceps femoris, short head, and gracilis muscles were also positive in 50% and 25% of the total cases, respectively. The peak T2 relaxation time and serum CK were correlated (r = 0.94, p<0.01); temporal changes in muscle T2 relaxation time and serum CK were similar, although T2 relaxation time remained positive after serum CK returned to background levels. We conclude that magnetic resonance imaging can serve as a useful tool in the evaluation of eccentric exercise muscle damage by providing a quantitative indicator of damage and its resolution as well as the specific areas and muscles.

Adult↗
PubMed1996

Control of red blood cell mass in spaceflight.

The effect of spaceflight on red blood cell mass (RBCM), plasma volume (PV), erythron iron turnover, serum erythropoietin, and red blood cell (RBC) production and survival and indexes were determined for six astronauts on two shuttle missions, 9 and 14 days in duration, respectively. PV decreased within the first day. RBCM decreased because of destruction of RBCs either newly released or scheduled to be released from the bone marrow. Older RBCs survived normally. On return to Earth, plasma volume increased, hemoglobin concentration and RBC count declined, and serum erythropoietin increased. We propose that entry into microgravity results in acute plethora as a result of a decrease in vascular space. PV decreases, causing an increase in hemoglobin concentration that effects a decrease in erythropoietin or other growth factors or cytokines. The RBCM decreases by destruction of recently formed RBCs to a level appropriate for the microgravity environment. Return to Earth results sequentially in acute hypovolemia as vascular space dependent on gravity is refilled, an increase in plasma volume, a decrease in hemoglobin concentration (anemia), and an increase in serum erythropoietin.

Adaptation, Physiological↗
PubMed1995

Regional muscle loss after short duration spaceflight.

BACKGROUND: Muscle strength and limb girth measurements during Skylab and Apollo missions suggested that loss of muscle mass may occur as a result of spaceflight. Extended duration spaceflight is important for the economical and practical use of space. The loss of muscle mass during spaceflight is a medical concern for long duration flights to the planets or extended stays aboard space stations. Understanding the extent and temporal relationships of muscle loss is important for the development of effective spaceflight countermeasures. HYPOTHESIS: We hypothesized that significant and measurable changes in muscle volume would occur in Shuttle crewmembers following 8 d of weightlessness. METHODS: MRI was used to obtain the muscle volumes of the calf, thigh and lower back before and after the STS-47 Shuttle mission. RESULTS: Statistical analyses demonstrated that the soleus-gastrocnemius (-6.3%), anterior calf (-3.9%), hamstrings (-8.3%), quadriceps (-6.0%) and intrinsic back (-10.3%) muscles were decreased, p < 0.05, compared to baseline, 24 h after landing. At 2 weeks post recovery, the hamstrings and intrinsic lower back muscles were still below baseline, p < 0.05. CONCLUSIONS: These results demonstrate that even short duration spaceflight can result in significant muscle atrophy.

Adult↗
PubMed1996

Cardiovascular deconditioning and venous air embolism in simulated microgravity in the rat.

BACKGROUND: Astronauts conducting extravehicular activities undergo decompression to a lower ambient pressure, potentially resulting in gas bubble formation within the tissues and venous circulation. Additionally, exposure to microgravity produces fluid shifts within the body leading to cardiovascular deconditioning. A lower incidence of decompression illness in actual spaceflight compared with that in ground-based altitude chamber flights suggests that there is a possible interaction between microgravity exposure and decompression illness. HYPOTHESIS: The purpose of this study was to evaluate the cardiovascular and pulmonary effects of simulated hypobaric decompression stress using a tail suspension (head-down tilt) model of microgravity to produce the fluid shifts associated with weightlessness in conscious, chronically instrumented rats. METHODS: Venous bubble formation resulting from altitude decompression illness was simulated by a 3-h intravenous air infusion. Cardiovascular deconditioning was simulated by 96 h of head-down tilt. Heart rate, mean arterial blood pressure, central venous pressure, left ventricular wall thickening and cardiac output were continuously recorded. Lung studies were performed to evaluate edema formation and compliance measurement. Blood and pleural fluid were examined for changes in white cell counts and protein concentration. RESULTS: Our data demonstrated that in tail-suspended rats subjected to venous air infusions, there was a reduction in pulmonary edema formation and less of a decrease in cardiac output than occurred following venous air infusion alone. Mean arterial blood pressure and myocardial wall thickening fractions were unchanged with either tail-suspension or venous air infusion. Heart rate decreased in both conditions while systemic vascular resistance increased. CONCLUSIONS: These differences may be due in part to a change or redistribution of pulmonary blood flow or to a diminished cellular response to the microvascular insult of the venous air embolization.

Animals↗
PubMed1994

Computer simulation of the effect of dDAVP with saline loading on fluid balance after 24-hour head-down tilt.

Fluid loading (FL) before Shuttle reentry is a countermeasure currently in use by NASA to improve the orthostatic tolerance of astronauts during reentry and postflight. The fluid load consists of water and salt tablets equivalent to 32 oz (946 ml) of isotonic saline. However, the effectiveness of this countermeasure has been observed to decrease with the duration of spaceflight. The countermeasure's effectiveness may be improved by enhancing fluid retention using analogs of vasopressin such as lypressin (LVP) and desmopressin (dDAVP). In a computer simulation study reported previously, we attempted to assess the improvement in fluid retention obtained by the use of LVP administered before FL. The present study is concerned with the use of dDAVP. In a recent 24-hour, 6 degree head-down tilt (HDT) study involving seven men, dDAVP was found to improve orthostatic tolerance as assessed by both lower body negative pressure (LBNP) and stand tests. The treatment restored Luft's cumulative stress index (cumulative product of magnitude and duration of LBNP) to nearly pre-bedrest level. The heart rate was lower and stroke volume was marginally higher at the same LBNP levels with administration of dDAVP compared to placebo. Lower heart rates were also observed with dDAVP during stand test, despite the lower level of cardiovascular stress. These improvements were seen with only a small but significant increase in plasma volume of approximately 3 percent. This paper presents a computer simulation analysis of some of the results of this HDT study.

Computer Simulation↗
PubMed1995

Vestibular plasticity following orbital spaceflight: recovery from postflight postural instability.

Results of previous studies suggested that the vestibular mediated postural instability observed in astronauts upon return to earth from orbital spaceflight may be exacerbated by an increased weighting of visual inputs for spatial orientation and control of movement. This study was performed to better understand the roles of visual and somatosensory contributions to recovery of normal sensori-motor postural control in returning astronauts. Preflight and postflight, 23 astronaut volunteers were presented randomly with three trials of six sensory organization test (SOT) conditions in the EquiTest system test battery. Sagittal plane center-of-gravity (COG) excursions computed from ground reaction forces were significantly higher on landing day than preflight for those test conditions presenting sway-referenced visual and/or somatosensory orientation cues. The ratio of summed peak-to-peak COG sway amplitudes on the two sway-referenced vision tests (SOTs 3 + 6) compared to the two eyes closed tests (SOTs 2 + 5) was increased on landing day, indicating an increased reliance on visual orientation cues for postural control. The ratio of peak-to-peak COG excursions on sway-referenced surfaces (SOTs 4, 5 & 6) to an earth fixed support surfaces (SOTs 1, 2 & 3) increased even more after landing suggesting primary reliance on somatosensory orientation cues for recovery of postflight postural stability. Readaptation to sway-referenced support surfaces took longer than readaptation to sway-referenced vision. The increased reliance on visual and somatosensory inputs disappeared in all astronauts 4-8 days following return to earth.

Astronauts↗
PubMed1993

The role of psychoneuroendocrine factors on spaceflight-induced immunological alterations.

This paper summarizes previous in-flight infections and novel conditions of spaceflight that may suppress immune function. Granulocytosis, monocytosis, and lymphopenia are routinely observed following short duration orbital flights. Subtle changes within the monocyte and T cell populations can also be noted by flow cytometric analysis. The similarity between the immunological changes observed after spaceflight and other diverse environmental stressors suggest that most of these alterations may be neuroendocrine-mediated. Available data support the hypothesis that spaceflight and other environmental stressors modulate normal immune regulation via stress hormones, other than exclusively glucocorticoids. It will be essential to simultaneously collect in-flight endocrine, immunologic, and infectious illness data to determine the clinical significance of these results. Additional research that delineates the neuroendocrine mechanisms of stress-induced changes in normal immune regulation will allow clinicians in the future to initiate prophylactic immunomodulator therapy to restore immune competence altered by the stress of long-duration spaceflight and therefore reduce morbidity from infectious illness, autoimmune disease, or malignancy.

Humans↗
PubMed1994

Production and action of cytokines in space.

B6MP102 cells, a continuously cultured murine bone marrow macrophage cell line, were tested for secretion of tumor necrosis factor-alpha and Interleukin-1 during space flight. We found that B6MP102 cells secreted more tumor necrosis factor-alpha and interleukin-1 when stimulated in space with lipopolysaccharide than controls similarly stimulated on earth. This compared to increased secretion of interferon-beta and -gamma by lymphocytes that was measured on the same shuttle flights. Although space flight enhanced B6MP102 secretion of tumor necrosis factor-alpha, an experiment on a subsequent space flight (STS-50) found that cellular cytotoxicity, mediated by tumor necrosis factor-alpha, was inhibited.

Animals↗
PubMed1990

Effects of spaceflight on levels and activity of immune cells.

Experiments were carried out on cells from rats that had been flown on Soviet Biosputnik Cosmos 1887 to explore the effects of spaceflight on immune responses. Rat bone marrow cells were examined for their response to colony stimulating factor-M. Rat spleen and bone marrow cells were stained with antibodies directed against cell surface antigenic markers. The results of the studies indicate that bone marrow cells from flown rats showed a decreased response to colony stimulating factor. There was a higher percentage of spleen cells from flown rats staining positively for pan-T-cell, suppressor-T-cell and interleukin-2 receptor cell surface antigens. A small increase in the percentage of cells staining positively for helper-T-cell antigens was also noted. In addition, a higher percentage of cells that appeared to be part of the myelogenous population of bone marrow cells from flown rats stained positively for surface immunoglobulin.

Animals↗
PubMed1989

Studies of the horizontal vestibulo-ocular reflex in spaceflight.

Changes in the vestibulo-ocular reflex (VOR) during space flight have been suspected of contributing to space motion sickness. The horizontal VOR was studied in nine subjects on two space shuttle missions. Active unpaced head oscillation at 0.3 Hz was used as the stimulus to examine the gain and phase of the VOR with and without visual input, as well as the visual suppression of the reflex. No statistically significant changes were noted inflight in the gains or phase shifts of the VOR during any test condition, or between space motion sickness susceptible and nonsusceptible populations. Although VOR suppression was unaffected by spaceflight, the space motion sickness-susceptible group tended to exhibit greater error in the suppression than the nonsusceptible group. It is concluded that at this stimulus frequency, VOR gain is unaffected by spaceflight, and any minor individual changes do not seem to contribute to space motion sickness.

Adult↗
PubMed2000

Epstein-Barr virus reactivation associated with diminished cell-mediated immunity in antarctic expeditioners.

Epstein-Barr virus (EBV) reactivation and cell-mediated immune (CMI) responses were followed in 16 Antarctic expeditioners during winter-over isolation at 2 Australian National Antarctic Research Expedition stations. Delayed-type hypersensitivity (DTH) skin testing was used as an indicator of the CMI response, that was evaluated 2 times before winter isolation and 3 times during isolation. At all 5 evaluation times, 8 or more of the 16 subjects had a diminished CMI response. Diminished DTH was observed on every test occasion in 4/16 subjects; only 2/16 subjects exhibited normal DTH responses for all 5 tests. A polymerase chain reaction (PCR) assay was used to detect EBV DNA in saliva specimens collected before, during, and after the winter isolation. EBV DNA was present in 17% (111/642) of the saliva specimens; all 16 subjects shed EBV in their saliva on at least 1 occasion. The probability of EBV shedding increased (P = 0.013) from 6% before or after winter isolation to 13% during the winter period. EBV appeared in saliva during the winter isolation more frequently (P < 0.0005) when DTH response was diminished than when DTH was normal. The findings indicate that the psychosocial, physical, and other stresses associated with working and living in physical isolation during the Antarctic winter result in diminished CMI and an accompanying increased reactivation and shedding of latent viruses.

Adult↗
PubMed1996

Calcium kinetics with microgram stable isotope doses and saliva sampling.

Studies of calcium kinetics require administration of tracer doses of calcium and subsequent repeated sampling of biological fluids. This study was designed to develop techniques that would allow estimation of calcium kinetics by using small (micrograms) doses of isotopes instead of the more common large (mg) doses to minimize tracer perturbation of the system and reduce cost, and to explore the use of saliva sampling as an alternative to blood sampling. Subjects received an oral dose (133 micrograms) of 43Ca and an i.v. dose (7.7 micrograms) of 46Ca. Isotopic enrichment in blood, urine, saliva and feces was well above thermal ionization mass spectrometry measurement precision up to 170 h after dosing. Fractional calcium absorptions determined from isotopic ratios in blood, urine and saliva were similar. Compartmental modeling revealed that kinetic parameters determined from serum or saliva data were similar, decreasing the necessity for blood samples. It is concluded from these results that calcium kinetics can be assessed with micrograms doses of stable isotopes, thereby reducing tracer costs and with saliva samples, thereby reducing the amount of blood needed.

Administration, Oral↗
PubMed1999

Development of a whole blood staining device for use during space shuttle flights.

BACKGROUND: Exposure to microgravity during space flight results in profound physiologic changes. Numerous studies have shown changes in circulating populations of peripheral blood immune cells immediately after space flight. It is currently unknown if these changes result from exposure to microgravity or are caused by the stress of reentry and readaptation to gravity. METHODS: We have developed the whole blood staining device (WBSD) as a system for the staining of whole blood collected during space flight for subsequent flow cytometric analysis. This device contains all liquids to address safety issues concerned with space flight and also moves the cells through the staining, lyse/fixation, and dilution steps. RESULTS: Data from flow cytometric analysis of samples stained in the WBSD was found to be comparable to data from samples stained by the conventional methods. Cells stained with the WBSD remain stable in the device for up to 14 days. The necessary manipulations required to use the device were tested on the KC-135 aircraft during the reduced gravity segment of parabolic flight. CONCLUSIONS: With the WBSD immunophenotype analysis can be performed at various time points for the duration of an entire Shuttle flight. In addition, this device has significant terrestrial applications for rapid and easy immunofluorescence labeling of whole blood in remote and isolated locations where immediate access to specialized equipment and skilled laboratory personnel may not be available. The WBSD provides a simple mechanism to design specific immunophenotyping tests for use by nontechnical personnel at bedside or in field locations. Cytometry 37:74-80, 1999. Published 1999 Wiley-Liss, Inc.

Blood Cells↗
PubMed1997

Initiation of oncogenic transformation in human mammary epithelial cells by charged particles.

Experimental studies have shown that high linear-energy transfer (LET) charged particles can be more effective than x-rays and gamma-rays in inducing oncogenic transformation in cultured cells and tumors in animals. Based on these results, experiments were designed and performed with an immortal human mammary epithelial cell line (H184B5), and several clones transformed by heavy ions were obtained. Cell fusion experiments were subsequently done, and results indicate that the transforming gene(s) is recessive. Chromosome analysis with fluorescence in situ hybridization (FISH) techniques also showed additional translocations in transformed human mammary epithelial cells. In addition, studies with these cell lines indicate that heavy ions can effectively induce deletion, break, and dicentrics. Deletion of tumor suppressor gene(s) and/or formation of translocation through DNA double strand breaks is a likely mechanism for the initiation of oncogenic transformation in human mammary epithelial cells.

Breast↗
PubMed1999

Enhanced protein electrophoresis technique for separating human skeletal muscle myosin heavy chain isoforms.

Talmadge and Roy (J. Appl. Physiol. 1993, 75, 2337-2340) previously established a sodium dodecyl sulfate - polyacrylamide gel electrophoresis (SDS-PAGE) protocol for separating all four rat skeletal muscle myosin heavy chain (MHC) isoforms (MHC I, IIa, IIx, IIb); however, when applied to human muscle, the type II MHC isoforms (Ila, IIx) are not clearly distinguished. In this brief paper we describe a modification of the SDS-PAGE protocol which yields distinct and consistent separation of all three adult human MHC isoforms (MHC I, IIa, IIx) in a minigel system. MHC specificity of each band was confirmed by Western blot using three monoclonal IgG antibodies (mAbs) immunoreactive against MHCI (mAb MHCs, Novacastra Laboratories), MHCI+IIa (mAb BF-35), and MHCIIa+IIx (mAb SC-71). Results provide a valuable SDS-PAGE minigel technique for separating MHC isoforms in human muscle without the difficult task of casting gradient gels.

Adult↗
PubMed2001

NASA/American Cancer Society High-Resolution Flow Cytometry Project-I.

BACKGROUND: The NASA/American Cancer Society (ACS) flow cytometer can simultaneously analyze the electronic nuclear volume (ENV) and DNA content of cells. This study describes the schematics, resolution, reproducibility, and sensitivity of biological standards analyzed on this unit. METHODS: Calibrated beads and biological standards (lymphocytes, trout erythrocytes [TRBC], calf thymocytes, and tumor cells) were analyzed for ENV versus DNA content. Parallel data (forward scatter versus DNA) from a conventional flow cytometer were obtained. RESULTS: ENV linearity studies yielded an R value of 0.999. TRBC had a coefficient of variation (CV) of 1.18 +/- 0.13. DNA indexes as low as 1.02 were detectable. DNA content of lymphocytes from 42 females was 1.9% greater than that for 60 males, with a noninstrumental variability in total DNA content of 0.5%. The ENV/DNA ratio was constant in 15 normal human tissue samples, but differed in the four animal species tested. The ENV/DNA ratio for a hypodiploid breast carcinoma was 2.3 times greater than that for normal breast tissue. CONCLUSIONS: The high-resolution ENV versus DNA analyses are highly reliable, sensitive, and can be used for the detection of near-diploid tumor cells that are difficult to identify with conventional cytometers. ENV/DNA ratio may be a useful parameter for detection of aneuploid populations.

American Cancer Society↗
PubMed2004

Continuous glucose monitoring and control in a rotating wall perfused bioreactor.

A glucose control system consisting of a single in-line glucose sensor, concentrated glucose solution, and computer hardware and software were developed. The system was applied to continuously control glucose concentrations of a perfusion medium in a rotating wall perfused vessel (RWPV) bioreactor culturing BHK-21 cells. The custom-made glucose sensor was based on a hydrogen peroxide electrode. The sensor continuously and accurately measured the glucose concentration of GTSF-2 medium in the RWPV bioreactor during cell culture. Three sets of two-point calibrations were applied to the glucose sensor during the 55-day cell culture. The system first controlled the glucose concentration in perfusing medium between 4.2 and 5.6 mM for 36 days and then at different glucose levels for 19 days. A stock solution with a high glucose concentration (266 mM) was used as the glucose injection solution. The standard error of prediction (SEP) for glucose measurement by the sensor, compared to measurement by the Beckman glucose analyzer, was +/-0.4 mM for 55 days.

Animals↗