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At least 1,297 records · Page 72
All sourcesNASA NTRSDOE OSTI
NASA NTRS1997

Prostaglandin E2 increases the skeletal response to mechanical loading

The study tested the influence of prostaglandin E2 (PGE2) on the skeletal response to increased in vivo mechanical loading through a four-point bending device. One hundred and twenty Sprague-Dawley female rats (6 months old, 354 +/- 34 g) were divided into 12 groups to accommodate all possible combinations of doses of loads (25, 30, or 35 N) and PGE2 (0, 0.1, 0.3, or 1 mg/kg). Rats received subcutaneous injections of PGE2 daily and in vivo loading of the right tibia every Monday, Wednesday, and Friday for four weeks. Histomorphometric analysis of the periosteal and endocortical surfaces following in vivo dual fluorochrome labeling was performed on both the loaded region of the right tibial diaphysis and a similar region of the left tibial diaphysis. Without PGE2, the threshold for loading to stimulate bone formation was 30 N (peak strain 1360 mu epsilon) at the periosteal surface and 25 N (peak strain 580 mu epsilon) at the endocortical surface. Without loading, the minimum dose of PGE2 to stimulate bone formation at all surfaces was 1 mg/kg/day. When 1 mg/kg/day PGE2 was combined with the minimum effective load, an additive effect of PGE2 and loading on bone formation was observed at the endocortical surface, but a synergistic effect was noted at the periosteal surface. No combined effect of ineffective doses of loading and PGE2 was found. A synergistic effect at peak strains of approximately 1625 mu epsilon on the periosteal surface could suggest either the involvement of locally produced growth factors or autoregulation of endogenous synthesis of PGE2 by exogenously administered PGE2.

NASA Program Space Physiology and Countermeasures↗
NASA NTRS1997

Psychosocial value of space simulation for extended spaceflight

There have been over 60 studies of Earth-bound activities that can be viewed as simulations of manned spaceflight. These analogs have involved Antarctic and Arctic expeditions, submarines and submersible simulators, land-based simulators, and hypodynamia environments. None of these analogs has accounted for all the variables related to extended spaceflight (e.g., microgravity, long-duration, heterogeneous crews), and some of the stimulation conditions have been found to be more representative of space conditions than others. A number of psychosocial factors have emerged from the simulation literature that correspond to important issues that have been reported from space. Psychological factors include sleep disorders, alterations in time sense, transcendent experiences, demographic issues, career motivation, homesickness, and increased perceptual sensitivities. Psychiatric factors include anxiety, depression, psychosis, psychosomatic symptoms, emotional reactions related to mission stage, asthenia, and postflight personality, and marital problems. Finally, interpersonal factors include tension resulting from crew heterogeneity, decreased cohesion over time, need for privacy, and issues involving leadership roles and lines of authority. Since future space missions will usually involve heterogeneous crews working on complicated objectives over long periods of time, these features require further study. Socio-cultural factors affecting confined crews (e.g., language and dialect, cultural differences, gender biases) should be explored in order to minimize tension and sustain performance. Career motivation also needs to be examined for the purpose of improving crew cohesion and preventing subgrouping, scapegoating, and territorial behavior. Periods of monotony and reduced activity should be addressed in order to maintain morale, provide meaningful use of leisure time, and prevent negative consequences of low stimulation, such as asthenia and crew member withdrawal. Leadership roles and lines of authority need to be studied further to understand the factors leading to status leveling, leadership competition, and role confusion. Finally, the relationship between crews and ground personnel should be characterized in order to minimize the displacement of anger and tension to the outside, to counter the effects of inter-group miscommunications, and to develop support strategies that can help to counter in-group/out-group conflicts. Ground-based space simulations still have a role to play in terms of understanding the impact of these factors and ways of dealing with them. In particular, issues involving language, cultural differences, gender biases, career motivation, monotonous conditions, use of free time, leadership, lines of authority, and the relationship between crews and outside monitoring personnel need to be further characterized and examined under controlled conditions. Until such time as these factors can be studied directly in space, simulations provide an opportunity to learn more about these psychosocial issues and to plan ways of minimizing their negative consequences during actual space missions.

NASA Discipline Number 00-00↗
NASA NTRS1996

Identification of the cAMP response element that controls transcriptional activation of the insulin-like growth factor-I gene by prostaglandin E2 in osteoblasts

Insulin-like growth factor-I (IGF-I), a multifunctional growth factor, plays a key role in skeletal growth and can enhance bone cell replication and differentiation. We previously showed that prostaglandin E2 (PGE2) and other agents that increase cAMP activated IGF-I gene transcription in primary rat osteoblast cultures through promoter 1 (P1), the major IGF-I promoter, and found that transcriptional induction was mediated by protein kinase A. We now have identified a short segment of P1 that is essential for full hormonal regulation and have characterized inducible DNA-protein interactions involving this site. Transient transfections of IGF-I P1 reporter genes into primary rat osteoblasts showed that the 328-base pair untranslated region of exon 1 was required for a full 5.3-fold response to PGE2; mutation in a previously footprinted site, HS3D (base pairs +193 to +215), reduced induction by 65%. PGE2 stimulated nuclear protein binding to HS3D. Binding, as determined by gel mobility shift assay, was not seen in nuclear extracts from untreated osteoblast cultures, was detected within 2 h of PGE2 treatment, and was maximal by 4 h. This DNA-protein interaction was not observed in cytoplasmic extracts from PGE2-treated cultures, indicating nuclear localization of the protein kinase A-activated factor(s). Activation of this factor was not blocked by cycloheximide (Chx), and Chx did not impair stimulation of IGF-I gene expression by PGE2. In contrast, binding to a consensus cAMP response element (CRE; 5'-TGACGTCA-3') from the rat somatostatin gene was not modulated by PGE2 or Chx. Competition gel mobility shift analysis using mutated DNA probes identified 5'-CGCAATCG-3' as the minimal sequence needed for inducible binding. All modified IGF-I P1 promoterreporter genes with mutations within this CRE sequence also showed a diminished functional response to PGE2. These results identify the CRE within the 5'-untranslated region of IGF-I exon 1 that is required for hormonal activation of IGF-I gene transcription by cAMP in osteoblasts.

NASA Discipline Musculoskeletal↗
NASA NTRS1996

Contribution of oxygen-sensitive neurons of the rostral ventrolateral medulla to hypoxic cerebral vasodilatation in the rat

1. We sought to determine whether hypoxic stimulation of neurons of the rostral ventrolateral reticular nucleus (RVL) would elevate regional cerebral blood flow (rCBF) in anaesthetized paralysed rats. 2. Microinjection of sodium cyanide (NaCN; 150-450 pmol) into the RVL rapidly (within 1-2 s), transiently, dose-dependently and site-specifically elevated rCBF1 measured by laser Doppler flowmetry, by 61.3 +/- 22.1% (P < 0.01), increased arterial pressure (AP; +30 +/- 8 mmHg; P < 0.01)1 and triggered a synchronized 6 Hz rhythm of EEG activity. 3. Following cervical spinal cord transection, NaCN and also dinitrophenol (DNP) significantly (P < 0.05) elevated rCBF and synchronized the EEG but did not elevate AP; the response to NaCN was attenuated by hyperoxia and deepening of anaesthesia. 4. Electrical stimulation of NaCN-sensitive sites in the RVL in spinalized rats increased rCBF measured autoradiographically with 14C iodoantipyrine (Kety method) in the mid-line thalamus (by 182.3 +/- 17.2%; P < 0.05) and cerebral cortex (by 172.6 +/- 15.6%; P < 0.05) regions, respectively, directly or indirectly innervated by RVL neurons, and in the remainder of the brain. In contrast regional cerebral glucose utilization (rCGU), measured autoradiographically with 14C-2-deoxyglucose (Sokoloff method), was increased in proportion to rCBF in the mid-line thalamus (165.6 +/- 17.8%, P < 0.05) but was unchanged in the cortex. 5. Bilateral electrolytic lesions of NaCN sensitive sites of RVL, while not altering resting rCBF or the elevation elicited by hypercarbia (arterial CO2 pressure, Pa,CO2, approximately 69 mmHg), reduced the vasodilatation elicited by normocapnic hypoxaemia (arterial O2 pressure, Pa,O2, approximately 27 mmHg) by 67% (P < 0.01) and flattened the slope of the Pa,O2-rCBF response curve. 6. We conclude that the elevation of rCBF produced in the cerebral cortex by hypoxaemia is in large measure neurogenic, mediated trans-synaptically over intrinsic neuronal pathways, and initiated by excitation of oxygen sensitive neurons in the RVL.

Non-NASA Center↗
NASA NTRS1996

Cerebral cortical neurons with activity linked to central neurogenic spontaneous and evoked elevations in cerebral blood flow

We recorded neurons in rat cerebral cortex with activity relating to the neurogenic elevations in regional cerebral blood flow (rCBF) coupled to stereotyped bursts of EEG activity, burst-cerebrovascular wave complexes, appearing spontaneously or evoked by electrical stimulation of rostral ventrolateral medulla (RVL) or fastigial nucleus (FN). Of 333 spontaneously active neurons only 15 (5%), in layers 5-6, consistently (P < 0.05, chi-square) increased their activity during the earliest potential of the complex, approximately 1.3 s before the rise of rCBF, and during the minutes-long elevation of rCBF elicited by 10 s of stimulation of RVL or FN. The results indicate the presence of a small population of neurons in deep cortical laminae whose activity correlates with neurogenic elevations of rCBF. These neurons may function to transduce afferent neuronal signals into vasodilation.

NASA Discipline Cardiopulmonary↗
NASA NTRS1996

Promoter-dependent and -independent activation of insulin-like growth factor binding protein-5 gene expression by prostaglandin E2 in primary rat osteoblasts

Insulin-like growth factor (IGF) action is mediated by high affinity cell surface IGF receptors and modulated by a family of secreted IGF binding proteins (IGFBPs). IGFBP-5, the most conserved of six IGFBPs characterized to date, uniquely potentiates the anabolic actions of IGF-I for skeletal cells. In osteoblasts, IGFBP-5 production is stimulated by prostaglandin E2 (PGE2), a local factor that mediates certain effects induced by parathyroid hormone, cytokines such as interleukin-1 and transforming growth factor-beta, and mechanical strain. In this study, we show that transcriptional and post-transcriptional events initiated by PGE2 collaborate to enhance IGFBP-5 gene expression in primary fetal rat osteoblast cultures. PGE2 treatment stimulated up to a 7-fold rise in steady-state levels of IGFBP-5 mRNA throughout 32 h of incubation. Analysis of nascent IGFBP-5 mRNA suggested that PGE2 had only a modest stimulatory effect on IGFBP-5 gene transcription, and transient transfection studies with IGFBP-5 promoter-reporter genes confirmed that PGE2 enhanced promoter activity by approximately 2-fold. Similar stimulatory effects were seen with forskolin. A DNA fragment with only 51 base pairs of the 5'-flanking sequence retained hormonal responsiveness, which may be mediated by a binding site for transcription factor AP-2 located at positions -44 to -36 in the proximal IGFBP-5 promoter. Incubation of osteoblasts with the mRNA transcriptional inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole demonstrated that PGE2 enhanced IGFBP-5 mRNA stability by 2-fold, increasing the t1/2 from 9 to 18 h. The effects of PGE2 on steady-state IGFBP-5 transcripts were abrogated by preincubating cells with cycloheximide, indicating that the effects of PGE2 on both gene transcription and mRNA stability required ongoing protein synthesis. Therefore, both promoter-dependent and -independent pathways converge to enhance IGFBP-5 gene expression in response to PGE2 in osteoblasts.

Non-NASA Center↗
NASA NTRS1996

Use of bed rest and head-down tilt to simulate spaceflight-induce immune system changes

Bed rest, both with and without head-down tilt, has been extensively used as an earth-bound analog to study physiologic effects mimicking those occurring in weightlessness during spaceflight. We have been able to show in six subjects that 4 weeks of head-down tilt bed rest induces a significant decrease in interleukin-2 secretion by PHA-stimulated T lymphocytes. Another study, lasting 113 days, with two subjects showed a decreased interleukin-2 receptor expression in PHA-stimulated peripheral blood mononuclear cells but a decreased interleukin-2 production in one subject only. Under the same conditions, interleukin-1 production was largely increased in both subjects. Several other immune parameters were also analyzed. Increased interleukin-1 production could contribute to bone mineral loss encountered during bed rest and decreased interleukin-2 secretion could play a role in the appearance of infectious diseases often observed during bed red.

NASA Discipline Neuroscience↗
NASA NTRS1996

The regulation and regulatory role of collagenase in bone

Interstitial collagenase plays an important role in both the normal and pathological remodeling of collagenous extracellular matrices, including skeletal tissues. The enzyme is a member of the family of matrix metalloproteinases. Only one rodent interstitial collagenase has been found but there are two human enzymes, human collagenase-1 and -3, the latter being the homologue of the rat enzyme. In developing rat and mouse bone, collagenase is expressed by hypertrophic chondrocytes, osteoblasts, and osteocytes, a situation that is replicated in a fracture callus. Cultured osteoblasts derived from neonatal rat calvariae show greater amounts of collagenase transcripts late in differentiation. These levels can be regulated by parathyroid hormone (PTH), retinoic acid, and insulin-like growth factors, as well as the degree of matrix mineralization. Much of the work on collagenase in bone has been derived from studies on the rat osteosarcoma cell line, UMR 106-01. All bone-resorbing agents stimulate these cells to produce collagenase mRNA and protein, with PTH being the most potent stimulator. Determination of secreted levels of collagenase has been difficult because UMR cells, normal rat osteoblasts, and rat fibroblasts possess a scavenger receptor that removes the enzyme from the extracellular space, internalizes and degrades it, thus imposing another level of control. PTH can also regulate the abundance of the receptor as well as the expression and synthesis of the enzyme. Regulation of the collagenase gene by PTH appears to involve the cAMP pathway as well as a primary response gene, possibly Fos, which then contributes to induction of the collagenase gene. The rat collagenase gene contains an activator protein-1 sequence that is necessary for basal expression, but other promoter regions may also participate in PTH regulation. Thus, there are many levels of regulation of collagenase in bone perhaps constraining what would otherwise be a rampant enzyme.

NASA Discipline Musculoskeletal↗
NASA NTRS1996

Blood vessel adaptation to gravity in a semi-arboreal snake

The effects of vasoactive agonists on systemic blood vessels were examined with respect to anatomical location and gravity acclimation in the semi-arboreal snake, Elaphe Obsoleta. Major blood vessels were reactive to putative neurotransmitters, hormones or local factors in vessel specific patterns. Catecholamines, adenosine triphosphate, histamine and high potassium (80 mM) stimulated significantly greater tension per unit vessel mass in posterior than anterior arteries. Anterior vessels were significantly more sensitive to catecholamines than midbody and posterior vessels. Angiotensin II stimulated significantly greater tension in carotid artery than in midbody and posterior dorsal aorta. Arginine vasotocin strongly contracted the left and right aortic arches and anterior dorsal aorta. Veins were strongly contracted by catecholamines, high potassium and angiotensin II, but less so by adenosine triphosphate, arginine vasotocin and histamine. Precontracted vessel were relaxed by acetylcholine and sodium nitroprusside, but not by atrial natriuretic peptide or bradykinin. Chronic exposure of snakes to intermittent hypergravity stress ( + 1.5 Gz at tail) did not affect the majority of vessel responses. These data demonstrate that in vitro tension correlates with that catecholamines, as well as other agonists, are important in mediating vascular responses to gravitational stresses in snakes.

NASA Discipline Number 14-10↗
NASA NTRS1994

Full-wave and half-wave rectification in second-order motion perception

Microbalanced stimuli are dynamic displays which do not stimulate motion mechanisms that apply standard (Fourier-energy or autocorrelational) motion analysis directly to the visual signal. In order to extract motion information from microbalanced stimuli, Chubb and Sperling [(1988) Journal of the Optical Society of America, 5, 1986-2006] proposed that the human visual system performs a rectifying transformation on the visual signal prior to standard motion analysis. The current research employs two novel types of microbalanced stimuli: half-wave stimuli preserve motion information following half-wave rectification (with a threshold) but lose motion information following full-wave rectification; full-wave stimuli preserve motion information following full-wave rectification but lose motion information following half-wave rectification. Additionally, Fourier stimuli, ordinary square-wave gratings, were used to stimulate standard motion mechanisms. Psychometric functions (direction discrimination vs stimulus contrast) were obtained for each type of stimulus when presented alone, and when masked by each of the other stimuli (presented as moving masks and also as nonmoving, counterphase-flickering masks). RESULTS: given sufficient contrast, all three types of stimulus convey motion. However, only one-third of the population can perceive the motion of the half-wave stimulus. Observers are able to process the motion information contained in the Fourier stimulus slightly more efficiently than the information in the full-wave stimulus but are much less efficient in processing half-wave motion information. Moving masks are more effective than counterphase masks at hampering direction discrimination, indicating that some of the masking effect is interference between motion mechanisms, and some occurs at earlier stages. When either full-wave and Fourier or half-wave and Fourier gratings are presented simultaneously, there is a wide range of relative contrasts within which the motion directions of both gratings are easily determinable. Conversely, when half-wave and full-wave gratings are combined, the direction of only one of these gratings can be determined with high accuracy. CONCLUSIONS: the results indicate that three motion computations are carried out, any two in parallel: one standard ("first order") and two non-Fourier ("second-order") computations that employ full-wave and half-wave rectification.

Motion Perception/physiology↗
NASA NTRS1994

Orthostatic hypotension in patients, bed rest subjects, and astronauts

Orthostatic hypotension after even short space flights has affected a significant number of astronauts. Given the need for astronauts to function at a high level of efficiency during and after their return from space, the application of pharmacologic and other treatments is strongly indicated. This report addresses the clinical problem of orthostatic hypotension and its treatments to ascertain whether pharmacologic or physiologic treatment may be useful in the prevention of orthostatic hypotension associated with space flight. Treatment of orthostatic hypotension in patients now includes increasing intravascular volume with high sodium intake and mineralocorticoids, or increasing vascular resistance through the use of drugs to stimulate alpha or block beta vascular receptors. Earlier treatment used oral sympathomimetic ephedrine hydrochloride alone or with "head-up" bed rest. Then long-acting adrenocortical steroid desoxycorticosterone preparations with high-salt diets were used to expand volume. Fludrocortisone was shown to prevent the orthostatic drop in blood pressure. The combination of the sympathomimetic amine hydroxyamphetamine and a monoamine oxidase inhibitor tranylcypromine has been used, as has indomethacin alone. Davies et al. used mineralocorticoids at low doses concomitantly with alpha-agonists to increase vasoconstrictor action. Schirger et al used tranylcypromine and methylphenidate with or without a Jobst elastic leotard garment or the alpha-adrenergic agonist midodrine (which stimulates both arterial and venous systems without direct central nervous system or cardiac effects). Vernikos et al established that the combination of fludrocortisone, dextroamphetamine, and atropine exhibited a beneficial effect on orthostatic hypotension induced by 7-day 6 degrees head-down bed rest (a model used to simulate the weightlessness of space flight). Thus, there are numerous drugs that, in combination with mechanical techniques, including lower body negative pressure to elevate transmural pressure, could be studied to treat orthostatic hypotension after space flight.

Review↗
NASA NTRS1995

Regulation of cyclic nucleotide-gated channels and membrane excitability in olfactory receptor cells by carbon monoxide

1. The effect of the putative neural messenger carbon monoxide (CO) and the role of the cGMP second-messenger system for olfactory signal generation was examined in isolated olfactory receptor neurons (ORNs) of the tiger salamander. 2. With the use of whole cell voltage-clamp recordings in combination with a series of ionic and pharmological tests, it is demonstrated that exogenously applied CO is a potent activator (K1/2 = 2.9 microM) of cyclic nucleotide-gated (CNG) channels previously described to mediate odor transduction. 3. Several lines of evidence suggest that CO mediates its effect through stimulation of a soluble guanylyl cyclase (sGC) leading to formation of the second-messenger cGMP. This conclusion is based on the findings that CO responses show an absolute requirement for guanosine 5'-triphosphate (GTP) in the internal solution, that no direct effect of CO on CNG currents in the absence of GTP is detectable, and that a blocker of sGC activation, LY85383 (10 microM), completely inhibits the CO response. 4. The dose-response curve for cGMP at CNG channels is used as a calibration to provide a quantitative estimate of the CO-stimulated cGMP formation. This analysis implies that CO is a potent activator of olfactory sGC. 5. Perforated patch recordings using amphotericin B demonstrate that low micromolar doses of CO effectively depolarize the membrane potential of ORNs through tonic activation of CNG channels. This effect in turn regulates excitable and adaptive properties of ORNs and modulates neuronal responsiveness. 6. These data argue for an important role of the cGMP pathway in olfactory signaling and support the idea that CO may function as a diffusible messenger in the olfactory system.

NASA Discipline Neuroscience↗
NASA NTRS1995

Psychosocial correlates of immune responsiveness and illness episodes in US Air Force Academy cadets undergoing basic cadet training

This study examined psychosocial correlates of immune function and illness in 89 male first-year US Air Force Academy cadets. A psychosocial questionnaire was administered to cadets prior to their arrival at the academy and was readministered during cadet orientation and during the stressful environment of Basic Cadet Training (BCT). Immune responsiveness was analyzed by PHA-, PMA-, or anti-CD3-stimulated thymidine uptake in mononuclear leucocytes. Illness episodes were assessed via medical chart review and self-reported symptoms. There were significant increases in distress levels as cadets entered BCT. No psychosocial measure assessed prior to arrival at the academy predicted level of PHA-, PMA-, and anti-CD3-stimulated thymidine uptake or risk of illness. However, hostility levels reported during BCT predicted risk of illness in the four weeks following psychosocial assessment (odds ratio = 7.1; 95% confidence interval: 1.4-36.1). Elevated response to environmental stressors and lower well-being levels also predicted impending illness, but only in the cohort of cadets who had not contracted food poisoning prior to assessment during BCT (OR = 9.3, CI = 1.9-46.7; OR = 0.09, CI = 0.02-0.53). These results suggest that self-report measures of hostility, response to environmental stressors and well-being may be useful predictors of impending illness episodes in males encountering high stress environments.

NASA Discipline Regulatory Physiology↗
NASA NTRS1995

Human parathyroid hormone-(1-38) restores cancellous bone to the immobilized, osteopenic proximal tibial metaphysis in rats

The purpose of this study was to determine if human parathyroid hormone-(1-38) (hPTH(1-38)) can restore cancellous bone mass to the established osteopenic, immobilized proximal tibial metaphyses of female rats. The right hindlimbs of 6-month-old female Sprague-Dawley rats were immobilized by bandaging the right hindlimbs to the abdomen. After 30 days of right hindlimb immobilization, the rats were subcutaneously injected with 200 micrograms hPTH(1-38)/kg/day for 15 days (short-term treatment) or 75 days (longer-term treatment). Static bone histomorphometry was performed on the primary spongiosa, and both static and dynamic histomorphometry were performed on the secondary spongiosa of the right proximal tibial metaphyses. Immobilization for 30 days without treatment decreased trabecular bone area, number, and thickness in both primary and secondary spongiosa, and induced an increase in eroded perimeter and a decrease in tissue referent-bone formation rate in the secondary spongiosa. These changes reached a new steady state thereafter. Treatment with 200 micrograms hPTH(1-38)/kg/day for 15 days, beginning 30 days after immobilization, significantly increased trabecular bone area, thickness, and number in both primary and secondary spongiosa despite continuous immobilization when compared with controls. The short-term PTH treatment (15 days) significantly increased labeling perimeter, mineral apposition rate, and tissue referent-bone formation rate in the secondary spongiosa and stimulated longitudinal bone growth as compared with the controls. Longer PTH treatment (75 days) further increased trabecular bone area, thickness, and number as compared with controls and groups given short-term PTH treatment (15 days). The bone formation indices in the secondary spongiosa of the longer-term treated rats were lower than those of the short-term treated group, but they were still higher than those of controls. Our findings indicate that PTH treatment stimulates cancellous bone formation, and restores and adds extra cancellous bone to the established, disuse-osteopenic proximal tibial metaphysis of female rats with continuously immobilized right hindlimbs. These results suggest that PTH may be useful in treating disuse-induced osteoporosis in humans.

NASA Program Space Physiology and Countermeasures↗
NASA NTRS1993

Decreased catecholamine secretion from the adrenal medullae of chronically diabetic BB-Wistar rats

Many humans with IDDM eventually lose the capacity to secrete epinephrine from their adrenal medullae. The mechanism for this pathological change is unknown. We hypothesized that this abnormality is attributable to neuropathic changes in the greater splanchnic nerves or in the chromaffin cells that they innervate. To study this hypothesis, we isolated rat adrenal glands, perfused them ex vivo, and measured the epinephrine content of the perfusate under various conditions of stimulation. We used transmural electrical stimulation (20-80 V, at 10 Hz) to induce epinephrine secretion indirectly by selectively activating residual splanchnic nerve terminals within the isolated glands. Under these conditions, epinephrine secretion was severely attenuated in glands from female BB-Wistar rats with diabetes of 4 mo duration compared with their age-matched, nondiabetic controls. These perfused diabetic adrenal medullae also demonstrated decreased catecholamine release in response to direct chromaffin cell depolarization with 20 mM K+, evidence that a functional alteration exists within the chromaffin cells themselves. Nonetheless, total catecholamine content of adrenal medullae from these diabetic rats was not significantly different from controls, indicating that the secretory defect was not simply attributable to a difference in the amount of catecholamines stored and available for release. Herein, we also provide histological evidence of degenerative changes within the cholinergic nerve terminals that innervate these glands.

NASA Discipline Musculoskeletal↗
NASA NTRS1992

Altering the cellular mechanical force balance results in integrated changes in cell, cytoskeletal and nuclear shape

Studies were carried out with capillary endothelial cells cultured on fibronectin (FN)-coated dishes in order to analyze the mechanism of cell and nuclear shape control by extracellular matrix (ECM). To examine the role of the cytoskeleton in shape determination independent of changes in transmembrane osmotic pressure, membranes of adherent cells were permeabilized with saponin (25 micrograms/ml) using a buffer that maintains the functional integrity of contractile microfilaments. Real-time videomicroscopic studies revealed that addition of 250 microM ATP resulted in time-dependent retraction and rounding of permeabilized cells and nuclei in a manner similar to that observed in intact living cells following detachment using trypsin-EDTA. Computerized image analysis confirmed that permeabilized cells remained essentially rigid in the absence of ATP and that retraction was stimulated in a dose-dependent manner as the concentration of ATP was raised from 10 to 250 microM. Maximal rounding occurred by 30 min with projected cell and nuclear areas being reduced by 69 and 41%, respectively. ATP-induced rounding was also accompanied by a redistribution of microfilaments resulting in formation of a dense net of F-actin surrounding retracted nuclei. Importantly, ATP-stimulated changes in cell, cytoskeletal, and nuclear form were prevented in permeabilized cells using a synthetic myosin peptide (IRICRKG) that has been previously shown to inhibit actomyosin filament sliding in muscle. In contrast, both the rate and extent of cell and nuclear rounding were increased in permeabilized cells exposed to ATP when the soluble FN peptide, GRGDSP, was used to dislodge immobilized FN from cell surface integrin receptors.(ABSTRACT TRUNCATED AT 250 WORDS).

Non-NASA Center↗
NASA NTRS1992

Glucose transporters and maximal transport are increased in endurance-trained rat soleus

Voluntary wheel running induces an increase in the concentration of the regulatable glucose transporter (GLUT4) in rat plantaris muscle but not in soleus muscle (K. J. Rodnick, J. O. Holloszy, C. E. Mondon, and D. E. James. Diabetes 39: 1425-1429, 1990). Wheel running also causes hypertrophy of the soleus in rats. This study was undertaken to ascertain whether endurance training that induces enzymatic adaptations but no hypertrophy results in an increase in the concentration of GLUT4 protein in rat soleus (slow-twitch red) muscle and, if it does, to determine whether there is a concomitant increase in maximal glucose transport activity. Female rats were trained by treadmill running at 25 m/min up a 15% grade, 90 min/day, 6 days/wk for 3 wk. This training program induced increases of 52% in citrate synthase activity, 66% in hexokinase activity, and 47% in immunoreactive GLUT4 protein concentration in soleus muscles without causing hypertrophy. Glucose transport activity stimulated maximally with insulin plus contractile activity was increased to roughly the same extent (44%) as GLUT4 protein content in soleus muscle by the treadmill exercise training. In a second set of experiments, we examined whether a swim-training program increases glucose transport activity in the soleus in the presence of a maximally effective concentration of insulin. The swimming program induced a 44% increase in immunoreactive GLUT4 protein concentration. Glucose transport activity maximally stimulated with insulin was 62% greater in soleus muscle of the swimmers than in untrained controls. Training did not alter the basal rate of 2-deoxyglucose uptake.(ABSTRACT TRUNCATED AT 250 WORDS).

Non-NASA Center↗
NASA NTRS1992

Immunological characterization of pulmonary intravascular macrophages

Pulmonary intravascular macrophages (PIMs) are lung macrophages found apposed to the endothelium of pulmonary capillaries. In many species, they are responsible for the clearance of blood-borne particulates and pathogens; however, little else is known about their roles as immunologic effector cells. We compared PIMs with pulmonary alveolar macrophages (PAMs) to determine the relative immunological activities of these two cell populations. Our results suggested that both populations possess similar phagocytic and bactericidal activities. In assays measuring cytotoxicity, PIMs were more cytotoxic than PAMs against virally infected target cells; however, differences between these macrophage populations were not as marked when noninfected targets were used. LPS-stimulated PIMs produced more T-cell proliferative cytokines than PAMs, and both populations of nonstimulated macrophages produced similar amounts of the cytokines. In contrast, PAMs produced more TNF alpha and NO2- than PIMs when both populations were stimulated with LPS; however, nonstimulated PAMs and PIMs produced similar amounts of TNF alpha and NO2. These data suggest that bovine PIMs are immunologically active. Differences between the degrees of activity of PIMs and PAMs indicate that these macrophage populations may have different roles in lung surveillance.

NASA Discipline Cell Biology↗