Simulation of space adaptation syndrome on earth

Summary The three Spacelab D-1 Scientist Astronauts were exposed to a 11/2 h 3 g centrifuge run in the supine position, resulting in a linear 3 g acceleration in the x-direction. They used their space experience to evaluate their readapting to normal gravity and compared their observations with Space Adaptation Syndrome. After the centrifuge runs, the vestibular visual system appeared to be modified in a very specific and reproducible manner. Readapting to the normal 1 g environment took at least 6 h. During this period there was a striking similarity to the astronaut's experience during adaptation to weightlessness in space. A series of vestibular tests were then performed, confirming these subjective findings.     

Complement-derived polypeptide C3adesArg as a mediator of inflammation at the blood-brain barrier in a new experimental cat model

Summary The effect of the complement-derived polypeptide C3adesArg as a mediator of inflammation in the central nervous system was examined. Twenty-five anesthetized cats received 4 mg of this polypeptide by intraventricular injection, 20 cats who served as controls received saline. Cerebrospinal fluid (CSF) was sampled 3 h after intraventricular injection and the brains were removed. For assessment of the permeability of the blood-brain barrier the CSF penetration of four antibiotics, which were given intravenously, was measured. Five control animals were employed for each antibiotic (tobramycin, ampicillin, imipenem, fosfomycin), whereas six C3adesArg-treated animals were used for each antibiotic and seven for tobramycin. Besides CSF levels of glucose, the prostanoids 6-keto-prostaglandin F₁, thromboxane B₂ and prostaglandin E₂ were measured. The morphological examinations in the CSF sediments and histological brain sections in the C3adesArg-treated animals disclosed a distinct inflammation with leptomeningeal and perivascular infiltration of polymorphonuclear granulocytes compared to normal findings in the controls. The CSF/serum ratios of all of the antibiotics were markedly elevated compared to controls, indicating a blood-brain barrier disruption. The levels of all prostanoids were significantly higher in the treatment group than in the control group, whereas the glucose levels were lower. These findings are in accordance with a granulocytic meningitis as seen in some infections at the acute stage. It is concluded that C3adesArg acts as a mediator of inflammation in the central nervous system.     

Humoral and cellular effects of the K+-channel activator cromakalim in man

Summary The effect of cromakalim, a K⁺-channel activator, on the plasma renin-angiotensin-aldosterone system, catecholamines and -atrial natriuretic peptide, and on the intraerythrocyte concentration and transmembrane fluxes of Na⁺ and K⁺ has been investigated in 18 normal male subjects, in a double-blind parallel study. After a run-in period on placebo for 1 week, the subjects were treated either with placebo (n=6) or cromakalim (n=12) for 1 week.Plasma renin activity was significantly increased during cromakalim. No effect of cromakalim on plasma angiotensin II, aldosterone, adrenaline, noradrenaline and -atrial natriuretic peptide was demonstrated. The intra-erythrocyte K⁺ concentration was decreased during cromakalim administration and Ca²⁺-dependent K⁺-channels in red blood cells were increased.     

Lactic dehydrogenase virus (LDV) impairs the antigen-presenting capacity of macrophages yet fails to affect their phagocytic activity

The effect of acute infection of mice with lactic dehydrogenase virus (LDV) on two major functions of peritoneal macrophages was tested. Using a macrophage-dependent T cell proliferative assay to test the antigen-presenting capacity of LDV-infected macrophages we found that LDV impairs the capacity of antigen-presenting cells to trigger memory T lymphocytes. Endocytosis of antigen by LDV-infected macrophages was similar to that of uninfected cells. In addition, the proportion of intracellular antigen versus membrane-bound antigen in LDV-infected cells were similar to that observed in uninfected mice. It appears therefore, that the impaired immunogenic effect of LDV-infected macrophages results from reduced immunogenicity of the membrane-bound antigen.Testing the phagocytic activity of peritoneal macrophages we found that the uptake of radiolabeled antibody-coated sheep erythrocytes or bacteria (E. coli) by infected cells was similar to that by uninfected macrophages. In addition, LDV failed to affect the ability of peritoneal macrophages in a nitroblue tetrazolium reduction reaction which serves as an alternative parameter for measuring phagocytic activity. Our results support the assumption that LDV, which probably propagates in the cells of the reticuloendothelial system, impairs some of the immunogenic functions of macrophages and thereby affects macrophage-dependent immune responses.     

Computer simulations and the use of radiolabelled sulphur colloid to measure the efficiency of the mononuclear phagocyte system

Technique are described whereby the clearance of the radiolabelled blood borne colloid can be continuously and reproducibly measured non-invasively from the same animal in vivo or from the isolated perfused intact liver in vitro. Using these techniques, the rate of removal of radiolabelled sulphur colloid by the mononuclear phagocytes in vivo and in vitro was shown to be biexponential. The pattern of clearance of colloid and the factors contributing to this were analysed with the aid of a computer program which mimicked the in vitro liver perfusion.     

Rezidivierende Meningitis bei familiärem Mangel der achten Komponente des Komplementsystems

Summary An 18-year-old man suffered from recurrent bacterial meningitis. Investigation of the complement system revealed deficiency of the 8th complement component (C8) in the patient and his sister. Genetic defects of the terminal complement components C5 to C8 predispose toNeisseria infections, probably due to a lack in bacteriolytic activity. It is to be noted that 1 year ago the patient had been hospitalized for a culture-proved pneumococcal meningitis.

     

Sigma-movement and optokinetic nystagmus elicited by stroboscopically illuminated stereopatterns

Summary Sigma-movement is an apparent movement seen when a stationary periodic visual pattern of the period P_s is illuminated Stroboscopically at the flash frequency f_s and smooth gaze pursuit eye movements are performed across the pattern at an angular velocity V_e = P_s · f_s deg · s^–1. Sigma-movement leads to an optokinetic nystagmus (Sigma OKN) which in turn sustains Sigma-movement perception. (1) Sigma-movement was also seen in an apparent three-dimensional periodic stripe pattern generated by two periodic monocular stimulus patterns with a certain degree of horizontal binocular disparity. (2) Sigma-movement perception and Sigma-OKN were also elicited by a Stroboscopically illuminated, stationary, random dot stereostripe pattern. The periodicity P_s of this pattern is generated on the cyclopean retina (Julesz 1971). The equation described above was also valid. When the time delay t between left eye and right eye flashes was varied, the apparent depth of the random dot stereostripe pattern decreased with increasing t, but the Sigmaeffects were not affected. (3) Sigma-movement illusion and Sigma-pursuit movements can also be induced when real three-dimensional objects composed of periodic components are Stroboscopically illuminated and adequate gaze or eye pursuit movements are induced. Sigma-movement is related to gaze movement and is therefore elicitable by eye, head or body movements. (4) Sigma-movement is presumably caused by the interaction of efference copy signals (generated in a cortical gaze pursuit system) and afferent visual signals. The present data indicate that neuronal mechanisms for this interaction are located — at least in part — at or beyond the level of binocular fusion and stereopsis.Supported by grants of the Deutsche Forschungsgemeinschaft (Gr161)     

Habituation and adaptation of the vestibuloocular reflex: a model of differential control by the vestibulocerebellum

Summary We habituated the dominant time constant of the horizontal vestibuloocular reflex (VOR) of rhesus and cynomolgus monkeys by repeated testing with steps of velocity about a vertical axis and adapted the gain of the VOR by altering visual input with magnifying and reducing lenses. After baseline values were established, the nodulus and ventral uvula of the vestibulocerebellum were ablated in two monkeys, and the effects of nodulouvulectomy and flocculectomy on VOR gain adaptation and habituation were compared. The VOR time constant decreased with repeated testing, rapidly at first and more slowly thereafter. The gain of the VOR was unaffected. Massed trials were more effective than distributed trials in producing habituation. Regardless of the schedule of testing, the VOR time constant never fell below the time constant of the semicircular canals (5 s). This finding indicates that only the slow component of the vestibular response, the component produced by velocity storage, was habituated. In agreement with this, the time constant of optokinetic after-nystagmus (OKAN) was habituated concurrently with the VOR. Average values for VOR habituation were obtained on a per session basis for six animals. The VOR gain was adapted by natural head movements in partially habituated monkeys while they wore ×2.2 magnifying or ×0.5 reducing lenses. Adaptation occurred rapidly and reached about ±30%, similar to values obtained using forced rotation. VOR gain adaptation did not cause additional habituation of the time constant. When the VOR gain was reduced in animals with a long VOR time constant, there were overshoots in eye velocity that peaked at about 6–8 s after the onset or end of constant-velocity rotation. These overshoots occurred at times when the velocity storage integrator would have been maximally activated by semicircular canal input. Since the activity generated in the canals is not altered by visual adaptation, this finding indicates that the gain element that controls rapid changes in eye velocity in the VOR is separate from that which couples afferent input to velocity storage. Nodulouvulectomy caused a prompt and permanent loss of habituation, returning VOR time constants to initial values. VOR gain adaptation, which is lost after flocculectomy, was unaffected by nodulouvulectomy. Flocculectomy did not alter habituation of the VOR or of OKAN. Using a simplified model of the VOR, the decrease in the duration of vestibular nystagmus due to habituation was related to a decrement in the dominant time constant of the velocity storage integrator (1/h ₀). Nodulouvulectomy, which reversed habituation, would be effected by decreasing h ₀, thereby increasing the VOR time constant. Small values of h ₀ would cause velocity storage to approach an ideal integrative process, leading the system to become unstable. By controlling the VOR time constant through habituation, the nodulus and uvula can stabilize the slow component of the VOR. VOR gain adaptation was related to a modification of the direct vestibular path gain g ₁, without altering the coupling to velocity storage g ₀ or its time constant (1/h ₀). The mismatched direct- and indirect-pathway gains simulated the overshoots in the dynamic response to a step in velocity, that were observed experimentally. We conclude that independent distributed elements in the VOR modify its dynamic response, under control of separate parts of the vestibulocerebellum.     

Cell-Growth Kinetics and Karyotype Analysis of Human Memory Lymphocytes Responding to Alloantigen and Mitogen

Peripheral-blood lymphocytes were primed in vitro with the mitogen phytohemagglutinin (PHA) or with allogeneic cells and their memory responses studied following sequential restimulation with either mitogen or alloantigen. Chromosome preparations were made every 12 hours following exposure to the stimulating agents. Cultures were labeled with BUdR for sister-chromatid staining of the chromosomes which provided information about the kinetics of cell growth and rates of sister chromatid exchange. Cultures containing no BUdR were used for the investigation of cell karyotypes after chromosome-banding.Following PHA as well as alloantigen restimulation, an earlier reaction of the responding cells was observed. The peak response after the first stimulation was found at 120 h with allogeneic stimulation and at 60 h with mitogen stimulation. In the second round of stimulation, the peak occurred after 48 h (allogeneic) and 36 h (PHA) and following the third stimulation after 36 h (allogeneic) and 24 h (PHA). The speed of cell growth was decreased following restimulation with either alloantigen and mitogen. In contrast to the allogeneic restimulation, the number of cells responding after PHA restimulation was decreased.No systematic numerical or structural aberration of the karyotype was detected following repeated stimulation with either alloantigen or mitogen. In this sense, the lymphocyte subpopulations selected by repeated stimulation did not differ from the starting material. On the other hand, the sister-chromatid exchange (SCE) frequency was increased following allogeneic restimulation, whereas it remained constant with PHA restimulation.