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Results for “Pathological effect”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 19 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS2002

Pathology effects at radiation doses below those causing increased mortality

Mortality data from experiments conducted at the Argonne National Laboratory (ANL) on the long-term effects of external whole-body irradiation on B6CF(1) mice were used to investigate radiation-induced effects at intermediate doses of (60)Co gamma rays or fission-spectrum neutrons either delivered as a single exposure or protracted over 60 once-weekly exposures. Kaplan-Meier analyses were used to identify the lowest dose in the ANL data (within radiation quality, pattern of exposure, and sex) at which radiation-induced mortality caused by primary tumors could be detected (approximately 1-2 Gy for gamma rays and 10-15 cGy for neutrons). Doses at and below these levels were then examined for radiation-induced shifts in the spectrum of pathology detected at death. To do this, specific pathology events were pooled into larger assemblages based on whether they were cancer, cardiovascular disease or non-neoplastic diseases detected within the lungs and pleura, liver and biliary tract, reproductive organs, or urinary tract. Cancer and cardiovascular disease were further subdivided into categories based on whether they caused death, contributed to death, or were simply observed at death. Counts of how often events falling within each of these combined pathology categories occurred within a mouse were then used as predictor variables in logistic regression to determine whether irradiated mice could be distinguished from control mice. Increased pathology burdens were detected in irradiated mice at doses lower than those causing detectable shifts in mortality-22 cGy for gamma rays and 2 cGy for neutrons. These findings suggest that (1) models based on mortality data alone may underestimate radiation effects, (2) radiation may have adverse health consequences (i.e. elevated health risks) even when mortality risks are not detected, and (3) radiation-induced pathologies other than cancer do occur, and they involve multiple organ systems.

Non-NASA Center↗
NASA NTRS1973

Rotary acceleration

Rotary acceleration is found to be a manifestation of angular acceleration, and is always present during steady state spinning or tumbling, even when the angular velocity is constant. Subjective reactions and tolerances, performance, physiological effects, and pathological effects are reviewed for rotary acceleration. Thresholds for stimulation perception by angular acceleration in man are presented in tabular form.

Fraser, T. M.↗
NASA NTRS1971

Late effects of 2.2 GeV protons on the central nervous system.

Investigation of late pathological effects of high-energy (2.2 GeV) protons on the brain of rabbits, in a postirradiation period of up to 16 months following exposure at fluxes of 30, 100, and 1000 billion protons per sq cm. At the latter two irradiation-intensity levels, the kinds of brain lesions inflicted include large venous dilatation, thickening of vessel walls with deposit of amorphous PAS positive substance, thrombosis, perivascular infiltration of leukocytes and macrophages, mobilization of microglia cells, gliosis, demyelinization, and multiple small pseudocyst formation.

Lippincott, S. W.↗
NASA NTRS1991

Pathophysiology of spontaneous venous gas embolism

The use of controllable degrees and durations of continuous isobaric counterdiffusion venous gas embolism to investigate effects of venous gas embolism upon blood, cardiovascular, and respiratory gas exchange function, as well as pathological effects upon the lung and its microcirculation is discussed. Use of N2O/He counterdiffusion permitted performance of the pathophysiologic and pulmonary microstructural effects at one ATA without hyperbaric or hypobaric exposures.

Lambertsen, C. J.↗
NASA NTRS1973

U.S. view of human problems to be addressed for long duration space flights

The Russian and American space programs have consisted of several thousands of hours of exposure of man to the space environment. In spite of numerous biological phenomena of adaptation observed, the space travellers have displayed, after their return, no enduring pathological effect. Although the usable data remain too limited to reflect fully the effects of space flight, it is possible to sketch the biological responses in the absence of gravity and to define the work bases for the future. Beyond its basic physiological effects, weightlessness has operational consequences in the daily life of the astronauts. These consequences will be still more evident during missions of long duration. The conclusions drawn in flight as well as on the ground are reviewed, and future requirements concerning prolonged flights are outlined. The gaps in actual knowledge are discussed and solutions are suggested. The problems of habitability are considered, particularly those which remain at present without satisfactory solutions: psychological responses to a confined life, cleaning, hygiene, and used material.

Berry, C. A.↗
NASA NTRS2003

The Cytoskeleton and Force Response Mechanisms

The long term aim of this project was to define the mechanisms by which cells sense and respond to the physical forces experienced at 1g and missing in microgravity. Identification and characterization of the elements of the cells force response mechanism could provide pathways and molecules to serve as targets for pharmacological intervention to mitigate the pathologic effects of microgravity. Mechanical forces experienced by the organism can be transmitted to cells through molecules that allow cells to bind to the extracellular matrix and through other types of molecules which bind cells to each other. These molecules are coupled in large complexes of proteins to structural elements such as the actin cytoskeleton that give the cell the ability to sense, resist and respond to force. Application of small forces to tissue culture cells causes local elevation of intracellular calcium through stretch activated ion channels, increased tyrosine phosphorylation and a restructuring of the actin cytoskeleton. Using collagen coated iron oxide beads and strong magnets, we can apply different levels of force to cells in culture. We have found that force application causes the cells to polymerize actin at the site of mechanical deformation and unexpectedly, to depolymerize actin across the rest of the cell. Observations of GFP- actin expressing cells demonstrate that actin accumulates at the site of deformation within the first five minutes of force application and is maintained for many tens of minutes after force is removed. Consistent with the reinforcement of the cytoskeletal structures underlying the integrin-bead interaction, force also alters the motion of bound magnetic beads. This effect is seen following the removal of the magnetic field, and is only partially ablated by actin disruption with cytochalsin B. While actin is polymerizing locally at the site of force application, force also stimulates a global reduction in actin filament content within the cells. We have examined the roles of several actin filament disassembly factors in the global reduction of cellular actin filaments. The calcium regulated actin filament severing protein gelsolin is not necessary for the increased actin turnover, as cells derived from gelsolin null and wildtype mice still show a reduction in total actin filament content. Instead, our work suggests that the actin binding protein cofilin may be important for these changes in actin dynamics. Cofilin binds to and enhances the disassembly of actin filaments. Using immunological methods, we observe transient changes in the phosphorylation state of cofilin upon force application that suggests that cofilin may mediate actin filament turnover. Early after force application, cofilin is transiently dephosphorylated, activating its actin disassembly activity. Subsequently, we find a hyper-phosphorylation of cofilin, rendering it inactive. This reduction in cofilin activity may explain the stability of the force induced actin structuttes. In testing this hypothesis, we aimed to generate cells that express the constituitively active kinase (LIM-kinase) that phosphorylates cofilin. lnidial attempts in the cell lines used for the our previous studies proved unsuccessful. While we prepare this work for pubication, we are continuing to study other cell lines and tissue sources to determine whether they show a reduction in F-actin content after force application.

Allen, Philip Goodwin↗
NASA NTRS2001

Mechanisms of cell signaling by nitric oxide and peroxynitrite: from mitochondria to MAP kinases

Many of the biological and pathological effects of nitric oxide (NO) are mediated through cell signaling pathways that are initiated by NO reacting with metalloproteins. More recently, it has been recognized that the reaction of NO with free radicals such as superoxide and the lipid peroxyl radical also has the potential to modulate redox signaling. Although it is clear that NO can exert both cytotoxic and cytoprotective actions, the focus of this overview are those reactions that could lead to protection of the cell against oxidative stress in the vasculature. This will include the induction of antioxidant defenses such as glutathione, activation of mitogen-activated protein kinases in response to blood flow, and modulation of mitochondrial function and its impact on apoptosis. Models are presented that show the increased synthesis of glutathione in response to shear stress and inhibition of cytochrome c release from mitochondria. It appears that in the vasculature NO-dependent signaling pathways are of three types: (i) those involving NO itself, leading to modulation of mitochondrial respiration and soluble guanylate cyclase; (ii) those that involve S-nitrosation, including inhibition of caspases; and (iii) autocrine signaling that involves the intracellular formation of peroxynitrite and the activation of the mitogen-activated protein kinases. Taken together, NO plays a major role in the modulation of redox cell signaling through a number of distinct pathways in a cellular setting.

Non-NASA Center↗
DOE OSTI2021

Cortical proteins may provide motor resilience in older adults

Motor resilience proteins may be a high value therapeutic target that offset the negative effects of pathologies on motor function. This study sought to identify cortical proteins associated with motor decline unexplained by brain pathologies that provide motor resilience. We studied 1226 older decedents with annual motor testing, postmortem brain pathologies and quantified 226 proteotypic peptides in prefrontal cortex. Twenty peptides remained associated with motor decline in models controlling for ten brain pathologies (FDR < 0.05). Higher levels of nine peptides and lower levels of eleven peptides were related to slower decline. A higher motor resilience protein score based on averaging the levels of all 20 peptides was related to slower motor decline, less severe parkinsonism and lower odds of mobility disability before death. Cortical proteins may provide motor resilience. Targeting these proteins in further drug discovery may yield novel interventions to maintain motor function in old age.

Buchman, Aron↗
NASA NTRS2003

The biomedical challenges of space flight

Space medicine has evolved considerably through past U.S. missions. It has been proven that humans can live and work in space for long durations and that humans are integral to mission success. The space medicine program of the National Aeronautics and Space Administration (NASA) looks toward future long-duration missions. Its goal is to overcome the biomedical challenges associated with maintaining the safety, health, and optimum performance of astronauts and cosmonauts. This program investigates the health effects of adaptation to microgravity: the nature of their pathologies, the effects of microgravity on pathophysiology, and the alterations in pharmacodynamics and treatment. A critical capability in performing research is the monitoring of the health of all astronauts and of the spacecraft environment. These data support the evidence-based approach to space medicine, incorporating past studies of microgravity-related conditions and their terrestrial counterparts. This comprehensive approach will enable safe and effective exploration beyond low Earth orbit.

Mir Project↗
NASA NTRS1975

Study report on combining diagnostic and therapeutic considerations with subsystem and whole-body simulation

Current applications of simulation models for clinical research described included tilt model simulation of orthostatic intolerance with hemorrhage, and modeling long term circulatory circulation. Current capabilities include: (1) simulation of analogous pathological states and effects of abnormal environmental stressors by the manipulation of system variables and changing inputs in various sequences; (2) simulation of time courses of responses of controlled variables by the altered inputs and their relationships; (3) simulation of physiological responses of treatment such as isotonic saline transfusion; (4) simulation of the effectiveness of a treatment as well as the effects of complication superimposed on an existing pathological state; and (5) comparison of the effectiveness of various treatments/countermeasures for a given pathological state. The feasibility of applying simulation models to diagnostic and therapeutic research problems is assessed.

Furukawa, S.↗