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Effect of gravity change on thrombopoiesis in mice.

It is reported that the stay in the space develops anemia, thrombocytopenia, and altered function and structure of red blood cell. The mechanism of these abnormalities was not clarified yet. Therefore, it is necessary to elucidate the mechanism of the effect of the gravity change on the thrombocytopoiesis, which plays the important role for the hemostasis, using animal models. The cloning of thrombopoietin (TPO), followed by the analysis of TPO and c-mpl (its cellular receptor) knockout mice confirmed its role as the primary regulator of thrombopoiesis. TPO has been shown to stimulate both megakaryocyte colony growth from marrow progenitor cells and the maturation of immature megakaryocyte to form functional platelet. This process includes the massive cytoskeletal rearrangement, such as proplatelet formation and fragmentation of proplatelet. In this study we have focused on the thrombopoiesis in mice those were exposed to gravity change by parabolic flight (PF).

Animals↗

Effect of acute head-down tilt on skeletal muscle cross-sectional area and proton transverse relaxation time.

This study investigated changes in skeletal muscle cross-sectional area (CSA) evoked by fluid shifts that accompany short-term 6 degrees head-down tilt (HDT) or horizontal bed rest, the time course of the resolution of these changes after resumption of upright posture, and the effect of altered muscle CSA, in the absence of increased contractile activity, on proton transverse relaxation time (T2). Average muscle (CSA and T2 were determined by standard spin-echo magnetic resonance imaging. Analyses were performed on contiguous transaxial images of the neck and calf. After a day of normal activity, 24 h of HDT increased neck muscle CSA 19 +/- 4(SE)% (P < 0.05) while calf muscle CSA decreased 14 +/- 3% (P < 0.05). The horizontal posture (12 h) induced about one-half of these responses: an 11 +/- 2% (P < 0.05) in the neck muscle CSA and an 8 +/- 2% decrease (P < 0.05) in the calf. Within 2 h after resumption of upright posture, neck and calf muscle CSA returned to within 0.5% (P > 0.05) of the values assessed after a day of normal activity, with most of the change occurring within the first 30 min. No further change in muscle CSA was observed through 6 h of upright posture. Despite these large alterations in muscle CSA, T2 was not altered by more than 1.1 +/- 0.6% (P > 0.05) and did not relate to muscle size. These results suggest that postural manipulations and subsequent fluid shifts modeling micro-gravity elicit marked changes in muscle size. Because these responses were not associated with alterations in muscle T2, it does not appear that simple movement of water into muscle can explain the contrast shift observed after exercise.

Adult↗

Caloric stimulation of the vestibular system of the pigeon under minimal influence of gravity.

Vestibular microphonics in response to acoustical stimulation were recorded in cochlea-deprived pigeons. Endolymph flow in the semicircular canals alters this response. A caloric stimulus was applied to the horizontal canal or the posterior vertical canal close to the ampulla. To minimize the influence of gravity, the canal being studied was positioned in the horizontal plane. Local temperature changes were generated with an electrically heated miniature copper probe, producing an approximately trapezoidal temperature profile. Because of the opposite hair cell polarization in the horizontal and the vertical ampulla, we could prove that the observed effects were of (hydro-)mechanical origin and were not caused by a direct effect of sensory epithelium temperature change. The first effect of temperature increase was an utriculopetal endolymph flow, as predicted by the 'expansion theory'.

Acoustic Stimulation↗

Altered cytokine production by specific human peripheral blood cell subsets immediately following space flight.

In this study, flow cytometry was used to positively identify the specific lymphocyte subsets exhibiting space flight-induced alterations in cytokine production. Whole blood samples were collected from 27 astronauts at three points (one preflight, two postflight) surrounding four space shuttle missions. Assays performed included serum/urine stress hormones, white blood cell (WBC) phenotyping, and intracellular cytokine production following mitogenic stimulation. Absolute levels of peripheral granulocytes were significantly elevated following space flight, but the levels of circulating lymphocytes and monocytes were unchanged. Lymphocyte subset analysis demonstrated a decreased percentage of T cells, whereas percentages of B cells and natural killer (NK) cells remained unchanged after flight. Nearly all the astronauts exhibited an increased CD4/CD8 T cell ratio. Assessment of naive (CD45RA+) vs. memory (CD45RO+) CD4+ T cell subsets was ambiguous, and subjects tended to group within specific missions. Although no significant trend was seen in absolute monocyte levels, a significant decrease in the percentage of the CD14+ CD16+ monocytes was seen following space flight in all subjects tested. T cell (CD3+) production of interleukin-2 (IL-2) was significantly decreased after space flight, as was IL-2 production by both CD4+ and CD8+ T cell subsets. Production of interferon-gamma (IFN-gamma) was not altered by space flight for the CD8+ cell subset, but there was a significant decrease in IFN-gamma production for the CD4+ T cell subset. Serum and urine stress hormone analysis indicated significant physiologic stresses in astronauts following space flight. Altered peripheral leukocyte subsets, altered serum and urine stress hormone levels, and altered T cell cytokine secretion profiles were all observed postflight. In addition, there appeared to be differential susceptibility to space flight regarding cytokine secretion by T cell subsets. These alterations may be the result of either microgravity exposure or the physiologic stresses of landing and readaptation to unit gravity. Future studies, including in-flight analysis or sampling, will be necessary to determine the cause of these alterations.

CD4-Positive T-Lymphocytes↗

Ethylene modulates flavonoid accumulation and gravitropic responses in roots of Arabidopsis.

Plant organs change their growth direction in response to reorientation relative to the gravity vector. We explored the role of ethylene in Arabidopsis (Arabidopsis thaliana) root gravitropism. Treatment of wild-type Columbia seedlings with the ethylene precursor 1-aminocyclopropane carboxylic acid (ACC) reduced root elongation and gravitropic curvature. The ethylene-insensitive mutants ein2-5 and etr1-3 had wild-type root gravity responses, but lacked the growth and gravity inhibition by ACC found in the wild type. We examined the effect of ACC on tt4(2YY6) seedlings, which have a null mutation in the gene encoding chalcone synthase, the first enzyme in flavonoid synthesis. The tt4(2YY6) mutant makes no flavonoids, has elevated indole-3-acetic acid transport, and exhibits a delayed gravity response. Roots of tt4(2YY6), the backcrossed line tt4-2, and two other tt4 alleles had wild-type sensitivity to growth inhibition by ACC, whereas the root gravitropic curvature of these tt4 alleles was much less inhibited by ACC than wild-type roots, suggesting that ACC may reduce gravitropic curvature by altering flavonoid synthesis. ACC treatment induced flavonoid accumulation in root tips, as judged by a dye that becomes fluorescent upon binding flavonoids in wild type, but not in ein2-5 and etr1-3. ACC also prevented a transient peak in flavonoid synthesis in response to gravity. Together, these experiments suggest that elevated ethylene levels negatively regulate root gravitropism, using EIN2- and ETR1-dependent pathways, and that ACC inhibition of gravity response occurs through altering flavonoid synthesis.

Acyltransferases↗

[Alterations in postural control: the use of spectral analysis in stability measurement].

UNLABELLED: Static posturography studies the frequency at which the center of gravity in the human body oscillates. There is no universal agreement as to the importance of this index or whether it is specific in identifying alterations in the postural control systems (vestibular, proprioceptive and visual). Nevertheless, some hypotheses appear generally accepted: a) visual information dominates; b) proprioception affects anterior-posterior oscillation; c) relatively low frequency body oscillation is affected by vestibular input while higher frequency oscillations are controlled by proprioceptive information. In order to check these hypotheses, four groups of patients underwent spectral analysis of bodily oscillations recorded with static posturography. The four groups of patients were similar in terms of age and broken down as follows: Group A-peripheral diabetic neuropathy (10 cases); Group B-diabetic neuropathy-free patients (10 cases); Group C-pure peripheral vestibulopathy (10 cases); Group D-normal subjects (20 cases). Analysis was performed dividing the frequency spectrum (FFT) into three groups: gr. I) 0.01-0.7 Hz; gr. II) 0.7-1 Hz; gr. III) > 1 Hz. Analysis of the spectra for Group A showed a significant increase in high frequency bodily oscillation (gr. III) with the eyes open in the anterior-posterior direction (M = 8.6 +/- 5.5; p < 0.05) and in the lateral direction (M = 4.0 +/- 2.0; p < 0.05); an increase was also found in both directions with the eyes closed (M = OCX II: 7.4 +/- 1.5; p < 0.05) (M = OCX III: 5.6 +/- 1.6; p < 0.01) (M = OCY II: 16.8 +/- 5.0; p < 0.05) (M = OCY II: 9.2 +/- 4.4; p < 0.05). In Group B the increase was limited to high frequency anterior-posterior oscillations (gr. III) at open eyes (M = 3.6 +/- 1.6; p < 0.05) and at closed eyes (M = 4.4 +/- 1.5; p < 0.05). In Group C there was an increase in high frequency lateral oscillations (gr. III) at open eyes (M = 4.2 +/- 0.5; p < 0.01) and panfrequency oscillations at closed eyes (M = OCX I: 47.7 +/- 5.6; p < 0.01) (M = OCX II: 23.2 +/- 4.9; p < 0.01) (M = OCX III: 7.2 +/- 2.3; p < 0.05). CONCLUSIONS: The diabetic proprioceptive deficit appears to lead to multiplanar destabilization at the medium-to-high frequency range. The labyrinthine deficit, on the other hand, appears to cause lateral destabilization at all frequencies. The method of analysis used appears to provide useful parameters with which to evaluate static posture since they can specifically identify alterations in orthostatic bodily control of various origins.

Adult↗

Pulmonary function in space.

The lung is exquisitely sensitive to gravity, and so it is of interest to know how its function is altered in the weightlessness of space. Studies on National Aeronautics and Space Administration (NASA) Spacelabs during the last 4 years have provided the first comprehensive data on the extensive changes in pulmonary function that occur in sustained microgravity. Measurements of pulmonary function were made on astronauts during space shuttle flights lasting 9 and 14 days and were compared with extensive ground-based measurements before and after the flights. Compared with preflight measurements, cardiac output increased by 18% during space flight, and stroke volume increased by 46%. Paradoxically, the increase in stroke volume occurred in the face of reductions in central venous pressure and circulating blood volume. Diffusing capacity increased by 28%, and the increase in the diffusing capacity of the alveolar membrane was unexpectedly large based on findings in normal gravity. The change in the alveolar membrane may reflect the effects of uniform filling of the pulmonary capillary bed. Distributions of blood flow and ventilation throughout the lung were more uniform in space, but some unevenness remained, indicating the importance of nongravitational factors. A surprising finding was that airway closing volume was approximately the same in microgravity and in normal gravity, emphasizing the importance of mechanical properties of the airways in determining whether they close. Residual volume was unexpectedly reduced by 18% in microgravity, possibly because of uniform alveolar expansion. The findings indicate that pulmonary function is greatly altered in microgravity, but none of the changes observed so far will apparently limit long-term space flight. In addition, the data help to clarify how gravity affects pulmonary function in the normal gravity environment on Earth.

Humans↗

[Clinical symptoms, origin, and therapy of the "pusher syndrome"].

Stroke patients may exhibit the peculiar behavior of actively pushing away from the nonhemiparetic side, leading to lateral postural imbalance and a tendency to fall towards the paralyzed side. These patients use the nonparetic extremities to stem actively against attempts of passive correction towards upright orientation. This phenomenon has been called the "pusher syndrome". Recent findings disclose that the deficit leading to contraversive pushing is an altered perception of the body's orientation in relation to gravity. Pusher patients experience their body as upright when they are actually tilted to the nonhemiparetic side. In contrast, processing of visual and vestibular inputs for the determination of visual vertical was undisturbed. The results argue for a separate pathway in humans for sensing gravity apart from that for perception of the visual world. This second graviceptive system decisively contributes to our control of upright body posture. The present article describes this still largely unknown neurological disease. The clinical examination of contraversive pushing, its underlying disturbance, lesion location, and approaches for therapy are considered.

Humans↗

Prognosis of contraversive pushing.

Stroke patients with 'pusher syndrome' actively push away from the non-hemiparetic side leading to a loss of postural balance and falling towards the paralysed side. The behaviour is due to an altered perception of the body's orientation in relation to gravity. Here, we studied the prognosis of the disorder. Twelve pusher patients first investigated immediately after the stroke were re-examined 6 months later. Pusher symptoms had nearly completely recovered. The aim for physiotherapy of patients with contraversive pushing thus is to shorten the period of necessary treatment and enable earlier discharge from residential care.

Adult↗

Gravitational biology and the mammalian circadian timing system.

Mammals have evolved under the influence of many selective pressures. Two of these pressures have been the static force of gravity and the daily variations in the environment due to the rotation of the earth. It is now clear that each of these pressures has led to specific adaptations which influence how organisms respond to changes in either gravity or daily time cues. However, several unpredicted responses to altered gravitational environments occur within the homeostatic and circadian control systems. These results may be particularly relevant to biological and medical issues related to spaceflight. This paper demonstrates that the homeostatic regulation of rat body temperature, heart rate, and activity become depressed following exposure to a 2 G hyperdynamic field, and recovers within 5-6 days. In addition, the circadian rhythms of these same variables exhibit a depression of rhythm amplitude; however, recovery required a minimum of 7 days.

Adaptation, Physiological↗

Human reproductive issues in space.

Animal studies in space or analogous environments have suggested that there may be problems in the reproductive sphere; such factors might limit mankind's ability to live and work for extended periods of time in microgravity or on non-terrestrial planetary surfaces. A review of reproductive functioning in animal species studied during space flight demonstrated that most species were affected significantly by the absence of gravity and/or the presence of radiation. These two factors induced alterations in normal reproductive functioning independently of, as well as in combination with, each other. Based on animal models, we have identified several potential problem areas regarding human reproductive physiology and functioning in the space environment. While there are no current space flight investigations, the animal studies suggest priorities for future research in human reproduction. Such studies will be critical for the successful colonization of the space frontier.

Animals↗

Short term microgravity effect on isometric hand grip and precision pinch force with visual and proprioceptive feedback.

Experiments executed on the upper limb are assuming increasing significance in the frame of the Human Physiology in space, for at least two reasons: the upper limb is the principal means of locomotion for the subject living in a space station; furthermore, fatigue can have a significant effect on the hand, for the ordinary work on board, and in particular for the extra-vehicular activities. The degradation of the performances affecting the muscular-skeletal apparatus can be easily recognized on the upper limb, by exerting specific scientific protocols, to be repeated through the permanence of the subject in weightlessness conditions. Another aspect relevant to the effect of microgravity on the upper limb is associated with the alteration of the motor control programs due to the different gravity factor, affecting not only the bio-mechanics of the subject, but in general all his/her psycho-physical conditions, induced by the totally different environment. Specific protocols on the upper limb can facilitate the studies on learning mechanisms for the motor control. The results of such experiments can be transferred to the Earth, useful for treatment of subjects with local traumas or diseases of the Central Nervous System.

Adaptation, Physiological↗

Revised one-step method for determination of cardiac output.

Cardiac output (Q) is a determinant of blood pressure and O(2) delivery and is critical in the maintenance of homeostasis, particularly during environmental stress and exercise. Cardiac output can be determined invasively in patients; however, indirect methods are required for other situations. Soluble gas techniques are widely used to determine (Q). Historically, measurements during a breathhold, prolonged expiration and rebreathing to CO(2) equilibrium have been used; however, with limitations, especially during stress. Farhi and co-workers developed a single-step CO(2) rebreathing method, which was subsequently revised by his group, and has been shown to be reliable and compared closely to direct, invasive measures. V(CO2), P(ACO2), and P(VCO2) are determined during a 12-25s rebreathing, using the appropriate tidal volume, and (Q) is calculated. This method can provide accurate data in laboratory and field experiments during exercise, increased or decreased gravity, water immersion, lower body pressure, head-down tilt, altered ambient pressure or changes in inspired gas composition.

Algorithms↗

The neural representation of postural control in humans.

Lesion of the "vestibular cortex" in the human posterior insula leads to a tilted perception of visual vertical but not to tilted body posture and loss of lateral balance. However, some stroke patients show the reverse pattern. Although their processing of visual and vestibular inputs for orientation perception of the visual world is undisturbed, they push away actively from the ipsilesional side (the side of lesion location), leading to a contraversive tilt of the body (tilt toward the side opposite to the lesion) and falling to that side. Recently, the origin of contraversive pushing was identified as an altered perception of the body's orientation in relation to gravity. These patients experience their body as oriented "upright" when actually tilted enormously to the ipsilesional side (18 degrees on average). The findings argued for a separate pathway in humans for sensing body orientation in relation to gravity apart from the one projecting to the vestibular cortex. The present study aimed at identifying this brain area. The infarcted brain regions of 23 consecutively admitted patients with severe contraversive pushing were projected onto a template MRI scan, which had been normalized to Talairach space. The overlapping area of these infarctions centered on the posterolateral thalamus. Our finding necessitates reinterpretation of this area as being only a "relay structure" of the vestibular pathway on its way from the brainstem to the vestibular cortex. The ventral posterior and lateral posterior nuclei of the posterolateral thalamus (and probably its cortical projections) rather seem to be fundamentally involved in the neural representation of a second graviceptive system in humans decisive for our control of upright body posture.

Adult↗

Impact of adulterants on RIA analysis of urine for drugs of abuse.

The effect of various adulterants on radioimmunoassay (RIA) tests for amphetamine, cannabinoids, cocaine (metabolite), phencyclidine (PCP), barbiturate, and morphine was evaluated. A total of 16 readily available agents, at concentrations ranging from 1 to 25%, were tested with negative and positive urine samples. The results demonstrate that both false positive and false negative RIA results can be produced by easily achievable levels of different agents in urine specimens. Of the RIA tests evaluated, the one for cannabinoids was most sensitive to the presence of adulterants, whereas the PCP assay was most resistant. Although the presence of some adulterants could be detected by measuring the pH or specific gravity of the urine, other agents, at concentrations sufficient to alter the RIA results, could not be as easily detected. Gas chromatography/mass spectrometry (GC/MS) analysis of adulterated samples with false positive RIA results showed no detectable drug, indicating that the adulterants interfered with the RIA test itself. In contrast, GC/MS analysis of samples with false negative RIA results confirmed that at least some adulterants acted by reducing the drug concentrations in the specimen.

Drug Contamination↗

Numerical modeling of facial aging.

Facial aging is a biological phenomenon. Skin properties change with time, and gravity and facial expressions exert mechanical deformation. Knowledge of these alterations may suggest ways to reverse them by identifying the corresponding distortional forces. The aim of this study was to determine a pattern of change for parameters of the face during the aging process, based on the numerical fitting of measures from a sample of patients. The first aspect of this study was to define adequate facial parameters and means of measuring them. Subsequently, each parameter was defined individually, and these data were analyzed as a set. The sample for the research was restricted to a group of 40 white female patients with a history of limited exposure to the sun, with ages ranging from 25 to 65. The reason for choosing this sample was the availability of frontal pattern photographs at different ages. The parameters for each patient were measured at two different ages. A strong correlation was found between age and behavior of the parameters. This aging model can be verified qualitatively by comparing photographs of a patient with manipulated photographs simulating aging. The quantitative verification of the model was done through the comparison of the measured and the predicted parameters.

Adult↗

Hematologic changes associated with weekly low-dose cisplatin administration in dogs.

This study prospectively describes the systemic toxicity of cisplatin (20 mg/m(2),IV) when given in weekly doses prior to localized irradiation in dogs with solid malignancies. Eleven dogs received a total of 54 weekly doses of cisplatin. Two dogs did not complete the 5-week protocol due to progressive disease and two dogs received 6 weekly doses of cisplatin. Repeated administration of cisplatin caused a significant decline in the leukocyte count, segmented neutrophil count, and platelet count. These changes were related to the number of cisplatin doses. The dogs did not have any significant alteration of blood urea nitrogen, serum creatinine, or urine specific gravity during the treatment period. Weekly low-dose cisplatin, as used in this study, is safe for use in tumor-bearing dogs. However, the significant decline in the leukocyte, segmented neutrophil, and platelet counts in these 11 dogs suggest that cisplatin prescribed at 20 mg/m(2) IV once per week should not exceed five consecutive treatments.

Journal Article↗

Characterization of estrogen-induced adenohypophyseal tumors in the Fischer 344 rat.

Pituitary tumors were induced in F344 female rats by chronic treatment with diethylstilbestrol (DES, 8-10 mg) implanted subcutaneously in silastic capsules. Over a range of 1-150 days of DES treatment, pairs of control and DES-treated rats were sacrificed, and their pituitaries dissociated enzymatically into single-cell preparations. The cell populations were examined regarding total cell recovery correlated with gland weight, intracellular prolactin (PRL) content and subsequent release in primary culture, immunocytochemical PRL staining, density and/or size alterations via separation on Ficoll-Hypaque and by unit gravity sedimentation, and cell cycle analysis, after acriflavine DNA staining, by laser flow cytometry. Total cell yields from DES-treated pituitaries increased from 1.3 times control yields at 8 days of treatment to 58.9 times control values by day 150. Intracellular PRL content ranged from 1.9 to 9.4 times control levels, and PRL release in vitro was significantly and consistently higher than controls, after at least 8 days of DES exposure. Beyond 8 days of DES exposure, the immunochemically PRL-positive proportion of cells increased to over 50% of the total population. Increased density and/or size and PRL content were indicated for the majority of the PRL cell population in both types of separation protocols. All these effects of DES were more pronounced among previously ovariectomized animals. The data extend the findings of other investigators, further establishing the DES-induced tumor as a model for study of PRL cellular control mechanisms.

Animals↗