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PubMed1994

Exploration and motor coordination in dystonia musculorum mutant mice.

Dystonia musculorum (dt) mutant mice, characterized by degeneration of spinocerebellar tracts, were impaired in terms of horizontal and vertical motor activity, hole poking, exploration, and motor coordination. In tests of motor coordination, their deficits were more severe than those of previously tested mutant mice with degeneration of cerebellar cells. However, unlike other cerebellar mutants, dt mutants alternated above chance levels in a two-trial spontaneous alternation test, which is a test of inhibitory tendencies and spatial orientation, and so dt mutants may not be impaired in these functions.

Animals↗

PubMed1995

Olfactory bulbectomy temporarily impairs Morris maze performance: an ACTH(4-9) analog accellerates return of function.

Rats with a bilateral lesion of the olfactory bulb are permanently anosmic. However, this lesion also produces nonspecific behavioral effects that recover over time. In this study olfactory bulb-lesioned animals are given a spatial orientation task--the Morris maze--which supposedly relies on visual and not olfactory cues. In exp. 1 this assumption was verified by subjecting animals with peripherally induced anosmia to the Morris maze (olfactory neurons in the nasal mucosae were destroyed by flushing the nose with ZnSO4). Anosmia did not affect the acquisition rate of the animals. In exp. 2 anosmia was produced by a central lesion to the bulbus olfactorius. Two weeks after lesioning the Morris maze performance is severely impaired. Interestingly, chronic administration (10 micrograms/48 h/rat, during these 14 days, SC) of the ACTH(4-9) analog ORG 2766 diminished the impairment in performance. In exp. 3 olfactory bulb-lesioned animals were allowed 6 wk to recover before Morris maze testing began, to investigate if spontaneous recovery of performance occurred. No difference was seen in the acquisition performance of lesioned animals when compared to sham animals at this timepoint. The effect of the peptide is discussed in the context of an acceleration of the recovery of nonspecific consequences of brain lesioning.

Adrenocorticotropic Hormone↗

PubMed1989

Induction of peroxisomal beta-oxidation in the rat liver in vivo and in vitro by tetrazole-substituted acetophenones: structure-activity relationships.

LY171883, a leukotriene D4 antagonist in the tetrazole-substituted acetophenone structural class, previously was demonstrated to cause peroxisome proliferation in rodents. In the present studies, several analogs were tested to determine if there are structural requirements for the induction of peroxisomal beta-oxidation in the rat liver in vivo and in cultured rat hepatocytes. Liver weight and serum triglycerides also were measured in vivo. The increases in peroxisomal beta-oxidation caused by the tetrazole-substituted acetophenones in vivo ranged from negligible to greater than 17-fold and there was good agreement with the structure-activity relationships found in cultured hepatocytes. N-methylation of the acidic nitrogen of the tetrazole blocked the peroxisomal effects, indicating that the free acid was required for activity. The length of the alkyl chain linked to the tetrazole also influenced the activity of the compounds. However, the more important determinant of peroxisomal activity may be the spatial orientation of the acidic tetrazole with respect to the planar backbone of the molecule. The data indicate there is a target site for peroxisome proliferation in the liver that is able to distinguish between structurally similar analogs. This site appears to be distinct from the leukotriene receptor since both inducers and noninducers of peroxisomal beta-oxidation were shown previously to be potent leukotriene antagonists.

Acetophenones↗

PubMed1982

Directional changes in the vestibular ocular response as a result of adaptation to optical tilt.

Before and after exposure to clockwise optical tilt, subjects' compensatory eye movements were recorded, as the head was oscillated around a vertical axis by the experimenter. An analysis of the horizontal and vertical components of eye movements showed a change in eye movement path in the clockwise direction. This corresponded to similar changes in visual spatial orientation judgments indicative of perceptual adaptation. It was suggested that long-term visual feedback serves to restore the compensatory nature of the eye movements which was altered by the introduction of the prism transformation.

Adaptation, Ocular↗

PubMed1994

Extensive integration field beyond the classical receptive field of cat's striate cortical neurons--classification and tuning properties.

Length- and width-summation curves of striate cortex cells revealed that there exist facilitatory, inhibitory or disinhibitory integration fields (IF) beyond the sides and ends of the classical receptive field (RF). The extent of the IFs is most frequently 2-5 times the size of the RFs. The tuning properties of IFs were studied using an annular surround grating patch while an optimal centre patch was placed at the excitatory RF to continuously activate the cell. The results show that, for most cells, the orientation, spatial frequency and speed tuning of the IFs were similar to, but broader than, the tuning of the RF, whereas the direction selectivity of the IF was not as pronounced as that of the RF. The possible functional significance of the IF is discussed.

Animals↗

PubMed1994

Levemopamil injection after cerebral oligemia reduces spatial memory deficits in rats.

Transient reduction of cerebral blood flow to oligemic levels as produced by bilateral clamping of carotid arteries (BCCA) in pentobarbital anesthetized Wistar rats leads to spatial orientation deficiencies in a water maze test 8-10 days after surgery. These deficiencies are more pronounced in 4-month-old than in 6-week-old animals. Levemopamil [(2S)-2-isopropyl-5-(methylphenethylamino)-2-phenylvaleronitril e hydrochloride], a Ca2+ channel blocker and 5-HT2 antagonist, prevents the deficiencies in groups of animals of both ages, even when administered 24 h after the transient vessel occlusion. Levemopamil did not influence the maze performance of sham-operated control rats. Levemopamil, therefore, appears to modulate mechanisms that are altered specifically either by, or as a consequence of, the BCCA procedure. Levemopamil did not influence the altered GABA or ACh content in different vulnerable brain structures following BCCA, showing that the substance acts via additional mechanisms affected by the BCCA procedure.

Acetylcholine↗

PubMed1995

Effect of chronic piracetam on age-related changes of cross-maze exploration in mice.

Normal aging is known to deteriorate memory, spatial orientation, and perceptual recognition. Experiment 1 examined behavioral manifestations of aging by using a cross-maze exploration test in 2-, 6-, and 10-month-old hybrid mice (CBA x C57BL). A decrease in explorative patrolling and an increase in arm reentries, a latency to start and a total time of exploration were found in 10-month-old mice. In Experiment 2, administration of the cognition enhancer piracetam (2-oxo-1-pirrolidone acetamide) (400 mg/kg, IP, once a day for 10 days) enhanced arm patrolling and decreased reentries in 10-month-old mice to the level displayed by the 2-month-old animals. The results suggest that the cross-maze test may be useful for a preliminary screening of antisenescent drugs.

Aging↗

PubMed1996

ACTH(4-9) analog ORG2766 treatment 7 months delayed still improves morris maze performance of fimbria-lesioned rats.

The ACTH(4-9) analog ORG2766 has been known to affect recovery of damaged functions resulting from injury to neural tissue. The peptides efficacy has often been ascribed to a facilitation of existing recovery, and immediate treatment seemed a prerequisite for efficacy. However, various results in other recovery paradigms do not refer to the neurotrophic properties of the peptide, but rather ascribe the effectiveness of ORG2766 to a general change in attention that indirectly affects functional recovery. Such a change in state is theoretically independent of the occurrence of spontaneous recovery, and, thus, treatment would not be required to coincide with recovery immediately after the damage. To see if ORG2766 can influence the recovery of function without the simultaneous occurrence of spontaneous recovery, this study employed a delay of 7 months after the occurrence of a fimbria lesion before ORG2766 was administered. The selective fimbria lesion produced an impairment in Morris maze performance, which could be attenuated by chronic treatment with ORG2766 immediately after the lesion as well as after 7 months. With respect to spatial orientation, no improvement is assessed in untreated lesioned rats, as the impairment of Morris maze performance in untreated fimbria-lesioned rats is as severe as right after the lesion. The data indicates that efficacy of the ACTH(4-9) analog does not rely on the acceleration of spontaneous recovery processes in this paradigm. The behavioral effects of ORG2766 are discussed in the context of a peptide-induced state of enhanced attention.

Adrenocorticotropic Hormone↗

PubMed1980

An immunoglobulin heavy chain variable region gene is generated from three segments of DNA: VH, D and JH.

We have determined the sequences of separate germline genetic elements which encode two parts of a mouse immunglobulin heavy chain variable region. These elements, termed gene segments, are heavy chain counterparts of the variable (V) and joining (J) gene segments of immunoglobulin light chains. The VH gene segment encodes amino acids 1-101 and the JH gene segment encodes amino acids 107-123 of the S107 phosphorylcholine-binding VH region. This JH gene segment and two other JH gene segments are located 5' to the mu constant region gene (Cmu) in germline DNA. We have also determined the sequence of a rearranged VH gene encoding a complete VH region, M603, which is closely related to S107. In addition, we have partially determined the VH coding sequences of the S107 and M167 heavy chain mRNAs. By comparing these sequences to the germline gene segments, we conclude that the germline VH and JH gene segments do not contain at least 13 nucleotides which are present in the rearranged VH genes. In S107, these nucleotides encode amino acids 102-106, which form part of the third hypervariable region and consequently influence the antigen-binding specificity of the immunoglobulin molecule. This portion of the variable region may be encoded by a separate germline gene segment which can be joined to the VH and JH gene segments. We term this postulated genetic element the D gene segment, referring to its role in the generation of heavy chain diversity. Essentially the same noncoding sequences are found 3' to the VH gene segment and as inverse complements 5' to two JH gene segments. These are the same conserved nucleotides previously found adjacent to light chain V and J gene segments. Each conserved sequence consists of blocks of seven and ten conserved nucleotides which are separated by a spacer of either 11 or 22 nonconserved nucleotides. The highly conserved spacing, corresponding to one or two turns of the DNA helix, maintains precise spatial orientations between blocks of conserved nucleotides. Gene segments which can join to one another (VK and JK, for example) always have spacers of different lengths. Based on these observations, we propose a model for variable region gene rearrangement mediated by proteins which recognize the same conserved sequences adjacent to both light and heavy chain immunoglobulin gene segments.

Animals↗

PubMedDate not supplied

Changes in the vestibular function during space flight.

An analysis of observations and investigations carried out in space flight has shown that some cosmonauts and astronauts have experienced vestibular disorders during the transition to weightlessness. Vestibular-sensory disorders include: Spatial illusions (the feelings of falling down, being in an upside-down position, the sensations of rotation of the craft or the body) and vertigo occurring during the onset of the orbital flight and head movements; Feelings, similar to those experienced in response to Coriolis accelerations on the Earth, which occasionally develop in weightlessness during the spacecraft rotation upon abrupt head and body movements and restrained feet; Feelings "of the load on the vestibular analyser which is unlike any Earth-bound effects" upon abrupt head movements during the first hours of an orbital flight and "a prolonged movement" during the switch-off of thrusters in weightlessness. Vestibular-vegetative disorders comprise a complex of symptoms similar to those of motion sickness: loss of appetite, stomach awareness (12%), hypersalination, nausea (9.6%) and vomiting (4.8%). Soviet studies suggest that the vestibular tolerance to the flight effects depends on the natural stability and training to the cumulative effect of adequate vestibular stimuli. This has been used in the development of the system of vestibular selection. Changes in the vestibular function seem to play the major role in the development of motion sickness in weightlessness, extra-labyrinthine factors being contributory. The current hypotheses have not yet been adequately confirmed in experiments. A detailed physiological analysis allows the conclusion that the decisive factor in the development of motion sickness may be the disturbance of the function of analysers responsible for spatial orientation which take the form of sensory conflicts as well as an altered reactivity of the organism due to the hemodynamic rearrangement.

Aerospace Medicine↗

PubMed1982

Cell morphological, ontogenic, and genetic reactions to 0-g simulation and hyper-g.

Organisms use gravity for spatial orientation, and differentiation into species during evolution follows geological processes which are caused by gravity. On the other hand, the task of most organismic functions which have or may have a relation to gravity is to compensate gravity. Furthermore, today it is very obvious that organisms do not disintegrate under the conditions of weightlessness, at least for the currently tested durations. These previous statements indicate a large field of still unknown regulation and adaptation mechanisms. Experiments to simulate weightlessness on the fast clinostat and with hyper-g show a highly developed ability of the genetic chain and of differentiating cells in being autonomous against mechanical stresses caused by outer accelerations. Nevertheless, different strong and slight changes of different tested end points were found. The question remains if the cells react actively or only passively.

Animals↗

PubMed1992

Results of the ESA study on psychological selection of astronaut applicants for Columbus Missions I: aptitude testing.

European participation in the Space Station Freedom brought about new challenges for the psychological selection of astronaut candidates, particularly in respect to specific demands of long duration space flights. For this reason existing selection criteria and methods were reassessed. On these grounds a study was undertaken applying a unique composition of aptitude tests to a group of 97 ESA scientists and engineers who are highly comparable to the expected astronaut applicants with respect to age and education. The tests assessed operational aptitudes such as logical reasoning, memory function, perception, spatial orientation, attention, psychomotor function, and multiple task capacity. The study goals were: 1) Verification of psychometric qualities and applicability of tests in a normative group; 2) Search for culture-fair tests by which multi-national groups can be examined; 3) Identification of test methods which consider general and special operational demands of long duration space flights. Based on the empirical findings a test battery was arranged for use in the selection of ESA astronaut applicants. Results showed that 16 out of the 18 employed tests have good psychometric qualities and differentiate reliably in the special group of testees. The meta structure of the test battery as described by a factorial analysis is presented. Applicability of tests was generally high. Tests were culture-fair, however, a relation between English language skills and test results was identified. Since most item material was language-free, this was explained with the importance of English language skills for the understanding of test instructions. Solutions to this effect are suggested.

Adult↗

PubMedDate not supplied

Gravity perception and signal transduction in single cells.

Cellular signal processing in multi-, as well as in unicellular organisms, has to rely on fundamentally similar mechanisms. Free-living single cells often use the gravity vector for their spatial orientation (gravitaxis) and show distinct gravisensitivities. In this investigation the gravisensitive giant ameboid cell Physarum polycephalum (Myxomycetes, acellular slime molds) is used. Its gravitaxis and the modulation of its intrinsic rhythmic contraction activity by gravity was demonstrated in 180 degrees-turn experiments and in simulated, as well as in actual, near-weightlessness studies (fast-rotating clinostat; Spacelab D1, IML-1). The stimulus perception was addressed in an IML-2 experiment, which provided information on the gravireceptor itself by the determination of the cell's acceleration-sensitivity threshold. Ground-based experiments designed to elucidate the subsequent steps in signal transduction leading to a motor response, suggest that an acceleration stimulus induces changes in the level of second messenger, adenosine 3',5'-cyclic monophosphate (cAMP), indicating also that the acceleration-stimulus signal transduction chain of Physarum uses an ubiquitous second messenger pathway.

Acceleration↗

PubMed1996

Construction and application of a new class of sequential oligopeptide carriers (SOCn) for multiple anchoring of antigenic peptides--application to the acetylcholine receptor (AChR) main immunogenic region.

A new class of sequential oligopeptide carriers (SOCn), namely (Lys-Aib-Gly)n (n = 2-7), for anchoring antigenic peptides, is presented. These SOCn have been designed in order to assume a determined structural motif, exhibiting defined spatial orientations of the Lys-N epsilon H2 anchoring groups. The NMR study showed that SOCn adopt a rigid conformation with some regularity, initiated from the C-terminus of the carrier, while molecular dynamics simulation confirmed the occurrence of a distorted 3(10)-helix. It was also demonstrated, by 1HNMR, that all the antigenic peptides bound to the SOCn retain their original, folded active, structure and that probably they do not interact to each other. It is concluded that the beneficial structural elements of the SOCn impose a favorable disposition of the anchored peptides so that potent antigens with maximum molecular recognition are generated.

Antibodies, Monoclonal↗

PubMed1984

Platanna (Xenopus laevis) as a test organism for determining the embryotoxic effects of environmental chemicals.

It has been successfully demonstrated that platanna (Xenopus laevis) allows the artificial induction of spawning at any time during the year. The number of eggs collected from a female ranged between 500 and 2400, the fertilization rate varying between 10 and 85%. When unaffected by chemicals, the embryonic development of the larvae took between 8 and 30 weeks. Di(2-ethylhexyl) phthalate (DEHP), methylmercury chloride, and the thalidomide analog EM 12 were used for the experiments described. DEHP at a concentration of 2 ppm retarded the development of the larvae and caused reduced pigmentation of the tadpoles. Methylmercury chloride has been found to have teratogenic and embryolethal effects at a concentration as low as 0.01 ppm. The following teratogenic effects have been determined: bent tails of the larvae, retarded development of the filter system, disturbed osmotic regulation, deranged positional and spatial orientation. EM 12 has been proven to have embryolethal effects at concentrations around 100 ppm. At lower concentrations this substance has teratogenic effects, i.e., it interferes in various ways with the development of the limbs.

Abnormalities, Drug-Induced↗

PubMed1984

Case report: CT findings in lumbosacral agenesis.

This case describes a newborn paraplegic male with lumbosacral agenesis and related congenital anomalies, including bilateral hip dislocations, arthrogryposis, talipes equinovarus, as well as neurogenic bladder with urine incontinence. An extra-dural tumor, surgically excised and diagnosed as a lipoma, was identified on computed transaxial scans to be adjacent to an abruptly terminating dural sac. Caudal to the sac the scans demonstrated partial fatty replacement of muscle bundles and direct articulation of the iliac wings. A follow-up myelogram delineated the subarachnoid space, but could not distinguish the tumor from a deformed sac secondary to lumbar defects. Computed tomography is thus recommended as part of the general radiologic protocol for fully evaluating the spatial orientation and anomalies of this spinal defect.

Abnormalities, Multiple↗

PubMed1984

Functions of the frontal cortex of the rat: a comparative review.

This review summarizes the anatomical and functional organization of the frontal cortex of the rat in comparison to primates. Lesions of the primary motor or of the prefrontal cortex of both primates and rodents produce a consistent constellation of symptoms that are strikingly similar across species as diverse as rats and humans. Thus, in spite of the tremendous difference in the relative volume of the frontal cortex of mammals, as well as the obvious diversity of behavioral repertoires across mammalian phylogeny, there appears to be a remarkable unity in frontal cortex function across the class mammalia. Hence, motor and prefrontal lesions produce analogous alterations in motor control in rodents and primates even though humans walk upright and have fine control of digit movement and rats walk on all fours and have less dextrous control of distal movements. Similarly, there are analogous changes in behaviors that can be labeled response inhibition, temporal ordering, spatial orientation, social or affective behavior, behavioral spontaneity, olfaction and habituation following prefrontal cortex lesions in both primates and rodents. Finally, it is proposed that the principal function of the prefrontal cortex of mammals is the temporal organization of behavior.

Animals↗

PubMed1986

The metric analysis of three-dimensional dendritic tree patterns: a methodological review.

Metric analysis methods used to study neuronal arborizations are reviewed and discussed. The analysis methods considered are those examining the spatial orientation and density of the whole dendritic field of a neuron, the metrics of dendritic segments and the bifurcation angles. General variables indicating the size of the soma and the dendritic field are indicated. In addition, the instrumentation used for providing 3-dimensional data for metric analyses and the shrinkage of Golgi-stained neurons are discussed.

Animals↗