Activated charcoal is as effective as fuller's earth or bentonite in paraquat poisoning

Summary In vitro investigations have shown that the adsorption capacity of activated charcoal (Kohle-Compretten, Ultracarbon, E. Merck, Darmstadt, FRG) is just as high as that of Fuller's earth (Surrey powder, Laporte Industries Ltd., Luton, GB) or Bentonite BP W.B. (Steetley Minerals Ltd., Milton Keynes, GB). Fuller's earth (Fullererde) from another manufacturer has had very poor adsorption properties and is thus not suitable for the treatment of paraquat poisoning. Animal experiments have shown that the curative effect of activated charcoal given 0.5, 1, 2, and 3 h after ingestion of 200 and 300 mg paraquat/kg body weight is equally as good or even better than that of Fuller's earth or Bentonite BP W.B.. Activated charcoal is a substitute of equal value to these mineral soils.     

Modulation of corticospinal excitability and intracortical inhibition during motor imagery is task-dependent

Previous studies have clearly shown that motor imagery modulates corticospinal excitability. However, there is no clear evidence for the modulation of intracortical inhibition (ICI) during imagined task performance. The aim of this study was to use transcranial magnetic stimulation (TMS) to assess changes in corticospinal excitability and ICI during the imagined performance of two types of task. In Experiment 1, eight subjects performed phasic depression of a computer mouse button using the dominant index finger in time with a 1 Hz auditory metronome. Single and paired pulse magnetic stimuli were delivered at rest, and during the on and off phases of actual and imagined task performance. Motor evoked potentials (MEPs) were recorded from FDI and APB. In Experiment 2, eight subjects performed phasic isometric abduction of the dominant thumb in time with a 1 Hz auditory metronome. As before, single and paired pulse magnetic stimuli were delivered at rest, and during the on and off phases of actual and imagined task performance. In both experiments, the conditioning stimulus intensity was set to produce 50% inhibition at rest, to enable both increases and decreases in ICI during task performance to be detected. No significant temporal or spatial modulation of MEP amplitude or ICI was observed in Experiment 1. In contrast, MEP amplitude was significantly greater, and ICI significantly lower during the on phase of imagined task performance in Experiment 2. These results are most likely related to the higher levels of target muscle activation required during actual task performance and the greater anatomical distance between target and control muscles in Experiment 2. These task characteristics may influence the observed degree of corticospinal excitability and ICI modulation.     

The tubular vacuolation process in amphibian skeletal muscle

The exposure of amphibian muscle to osmotic shock through the introduction and subsequent withdrawal of extracellular glycerol causes vacuolation in the transverse tubules. Such manoeuvres can also electrically isolate the transverse tubules from the surface (detubulation), particularly if followed by exposures to high extracellular [Ca2+] and/or gradual cooling. This study explored factors influencing vacuolation in Rana temporaria sartorius muscle. Vacuole formation was detected using phase contrast microscopy and through the trapping or otherwise of lissamine rhodamine dye fluorescence within such vacuoles. The preparations were also examined using electron microscopy, for penetration into the transverse tubules and tubular vacuoles of extracellular horseradish peroxidase introduced following the osmotic procedures. These comparisons distinguished for the first time two types of vacuole, open and closed, whose lumina were respectively continuous with or detached from the remaining extracellular space. The vacuoles formed close to and between the Z-lines, but subsequently elongated along the longitudinal axis of the muscle fibres. This suggested an involvement of tubular membrane material; the latter appeared particularly concentrated around such Z-lines in the electron-micrograph stereopairs of thick longitudinal sections. Open vacuoles formed following osmotic shock produced by extracellular glycerol withdrawal from a glycerol-loaded fibre at a stage when one would expect a net water entry to the intracellular space. This suggests that vacuole formation requires active fluid transport into the tubular lumina in response to fibre swelling. Closed vacuoles only formed when the muscle was subsequently exposed to high extracellular [Ca2+] and/or gradual cooling following the initial osmotic shock. Their densities were similar to those shown by open vacuoles in preparations not so treated, suggesting that both vacuole types resulted from a single process initiated by glycerol withdrawal. However, vacuole closure took place well after formation of open vacuoles, over 25 min after glycerol withdrawal. Its time course closely paralleled the development of detubulation reported recently. It was irreversible, in contrast to the reversibility of open vacuole formation. These findings identify electrophysiological detubulation of striated muscle with closure of initially open vacuoles. The reversible formation of open vacuoles is compatible with some normal membrane responses to some physiological stresses such as fatigue, whereas irreversible formation of closed vacuoles might only be expected in pathological situations as in dystrophic muscle.This revised version was published online in September 2005 with corrections to the Cover Date.     

Are proteasomes involved in the formation of the kinetochore?

Proteasomes catalyse the degradation of proteins responsible for the regulation of mitosis enabling the cell to complete cell division. We have studied the effect of an inhibitor of the chymotrypsin-like activity of the proteasome on the trilaminar structure of the kinetochore in HeLa cells. Whereas a role for the proteasome in the degeneration of the kinetochore was predicted, we found instead that the inhibitor strongly retarded kinetochore development. We observed different developmental stages of the kinetochore from the fibrous ball of a prekinetochore to the mature kinetochore in one cell. The data presented here support the proposition that proteasomes are involved in kinetochore formation.accepted for publication by H. C. MacgregorDedicated to the memory of Prof. Dr. Daniel Mazia, a fatherly friend.     

Changes in sizes of the adrenaline-containing vesicles and their cores in frog cardiac sympathetic nerves after pharmacological treatments

Summary The sizes of adrenergic vesicles and their cores, as made visible by an acrylic aldehyde in sodium dichromate fixative, have been measured in electron micrographs of the sympathetic nerves amongst the frog's ventricular muscle. The animals were either normal or previously treated with drugs expected to affect the catecholamine content of the heart. The sympathetic nerves contain two overlapping populations of vesicles. A graphical method was used to separate these and determine the mean diameter of each population. The distribution of vesicles between the large and small populations is variable in normal animals. No changes could be detected in the experimental animals. The mean size of the large vesicles is variable in normal animals. No changes could be detected in the experimental animals. Four injections of 5-hydroxydopamine caused a 5.8% increase in the diameter of the small vesicles. No other treatment produced significant changes in vesicle size. Four injections of 5-hydroxydopamine caused a 50% increase in the diameter of the cores of the small vesicles. Two injections of reserpine caused a 20% reduction in the diameter of the visible cores in the small vesicles, and 34% of the vesicles lost their cores entirely. One injection of 6-hydroxydopamine or ten injections of -methyl-tyrosine caused small reductions in small core diameter. It is postulated that core formation in adrenergic nerves under these conditions is not solely dependent on their catecholamine content, but on this and another factor which may be part of the storage complex.     

Relation between work and power calculated from force-velocity curves to that done during oscillatory work

Summary The force-velocity relation during oscillatory work was compared with that measured in the traditional way with quick release and force clamps using toad sartorius, frog sartorius, and mouse soleus muscles. Plotting the force and corresponding velocity data in this way produces a power-loop. The power-loop has less intuitive value than the frequently reported work-loops but it is useful because it permits comparison with the force-velocity curve produced using traditional methods. The force/velocity combinations for oscillatory work during a contraction often exceed those that would be predicted from the force-velocity curve. Although it has been known for many years that more force is developed by stimulated muscle when it is being stretched than can be developed during an isometric contraction, my results show that the increase in force is of importance at stretch velocities that probably occur in vivo during locomotion.     

Do ‘evaluation potentials’ reflect cognitive assessment?

Summary Event-related potentials were recorded when a subject evaluated the outcome of a simple TV game as successful/unsuccessful, where the goal was specified randomly as one of two areas on the screen. The evaluation potential elicited by the outcome was consistently larger for unsuccessful outcomes, regardless of the location of the goal.     

The synaptonemal complex — the chaperone of crossing over

During meiosis homologous chromosomes pair and exchange homologous chromosome segments. The synaptonemal complex (SC) forms between paired chromosomes. The role of the SC in the process of reciprocal exchange of flanking markers is a matter of debate. I propose a dual pathway for reciprocal exchange of flanking markers (REFM). In the first, SC-independent, path, two half-nodules and an independent REFM protein combine to form a functional recombination nodule (RN). The RN binds to paired chromosomes and accomplishes reciprocal exchange of flanking markers. In the other, SC-dependent, pathway half-nodules occur at pairing initiation sites. Half-nodules move along the SC as it forms. Assisted by an SC-bound REFM protein, half-nodules combine to form functional RNs. I propose that different organisms rely to different extents on the two pathways, and hence rely to different extents on the SC.accepted for publication by H. C. Macgregor     

Thrombus formation,hemostasis, adhesiveness of leukocytes and morphological abnormalities in the microcirculation of adjuvant arthritic rats

Microcirculatory alterations which may be responsible for the chronicity of adjuvant-induced arthritis in the rat were investigated. Thrombus formation in the mesenteric microcirculation was investigated by laser-technique. In arthritic rats thrombus formation for a given stimulus was increased significantly and a correlation was found between the intensity of the arthritic changes and this thrombotic reaction.Adherence of leukocytes to the venous endothelium was studied by an in vivo technique. The number of rolling and sticking leukocytes was greatly increased in the mesenteric venules of arthritic rats. Acute treatment of severely arthritic rats with aspirin greatly reduced the increased adhesiveness of granulocytes. By the use of an atraumatic technique for vital microscopy of the microcirculation of skin of arthritic rats, striking morphologic changes with stasis of erythrocytes were observed. Morphological aberrations were also found in the mesenteric microvessels of diseased animals.Presented in part at the International Meeting on Inflammation Future Trends in Inflammation II, Paris, May 1975.     

Human perception of horizontal trunk and head rotation in space during vestibular and neck stimulation

Summary The vestibular signal of head motion in space must be complemented by a neck signal of the trunk-to-head excursion in order to provide the individual with information on trunk motion in space. This consideration led us to study psychophysically the role of vestibular-neck interaction for human self-motion perception. Subjects (Ss) were presented with passive horizontal rotations of their trunk and/or head (sinusoidal rotations, f=0.025 –0.4 Hz) in the dark for vestibular and neck stimulation, as well as for combinations of both. Ss' perception was evaluated in terms of gain (veridical perception of stimulus magnitude, G=1), phase, and detection threshold. (1) Perception of trunk rotation in space. During vestibular stimulation (whole-body rotation) and neck stimulation (trunk rotation with the head kept stationary) the frequency-transfer characteristics underlying this perception were very similar. The gain fell short; it was only about 0.7 at 0.4 and 0.2 Hz stimulus frequency and was further attenuated with decreasing frequency. In contrast, the phase was close to that of actual trunk position. The gain attenuation was found to be a function of the peak angular velocity of the stimulus, a fact, which we related to a velocity threshold of the order of 1 deg/s. During the various vestibular-neck combinations used, Ss' perception was again erroneous, reflecting essentially the sum of its two non-ideal constituents. However, there was one noticeable exception; during the combination head rotation on stationary trunk, Ss veridically perceived their trunk as stationary (compatible with the notion that the sum yielded zero). (2) Perception of head rotation in space. During vestibular stimulation, Ss' estimates showed the same non-ideal gain-vs.-frequency characteristics as described above for the trunk. Neck stimulation induced an illusion as if the head had been rotated in space. This neck contribution was such that, when it was combined with its vestibular counterpart during head rotation on stationary trunk, the perception became almost veridical. On closer inspection, however, this neck contribution was found to reflect the sum of two components; one was the non-ideal neck signal contributing to the perception of trunk in space, the other was an almost ideal neck signal of head-on-trunk rotation. (3) The results could be described by a simple model. In this model, the erroneous vestibular signal head in space is primarily used to create an internal representation of trunk in space. To this end, it is combined with the closely matching neck signal of trunk to head. The perception of head rotation in space is achieved by summing this trunk in space signal with the almost ideal head on trunk signal, again of nuchal origin. These seeming complex interactions have two implications: (i) the head is referred to trunk coordinates, whereas the trunk is referred to space coordinates; (ii) there is at least one condition in the dark where orientation is correct (despite an erroneous vestibular signal), i.e., during head rotation on stationary trunk.Supported by Deutsche Forschungsgemeinschaft, SFB 325     

Oxidative Stress Level in Circulating Neutrophils Is Linked to Neurodegenerative Diseases

Alzheimers and Parkinsons diseases are the most common neurodegenerative conditions. Oxidative lesions are a hallmark of both diseases, but the respective roles of systemic and cerebral dysfunction are not elucidated. As circulating neutrophils are the most powerful sources of reactive oxygen species, we measured oxidative stress levels in resting neutrophils from 44 Alzheimers and Parkinsons disease patients and compared them to 40 healthy counterparts. Significantly increased oxidative stress levels were observed in patients groups, while control groups had very similar levels irrespective of age. One-third of the neurodegenerative patients presented with oxidative stress levels higher than those of any healthy donor. This increase was not due to an elevated production of reactive oxygen species during the neutrophil oxidative burst. Mitochondrial mass and activity were altered in neutrophils of the Parkinsonian group compared to controls, but not in those from Alzheimers disease group. To our knowledge, this is the first report linking oxidative stress and mitochondrial parameters in circulating neutrophils from neurodegenerative and normal donors. Our results indicate that oxidative stress levels in circulating neutrophils are of interest for further mechanistic studies of neurodegenerative diseases and might open the perspective of a diagnostic tool.     

A new approach for evaluation of the in vitro haemolytic potential of a solution of a new medicine

In the process of developing an intravenously injectable drug, its haemolytic potential must be considered. There are no Regulatory Guidelines for this kind of test. Many authors have set up different models, attempting to obtain early information about the behaviour of test compounds when injected into the bloodstream.In the present work, an in vitro static model is presented, which takes into account the injection rate (R _inj.) of the drug, and the blood flow rate (Q _v) of the vein in which the drug must be injected. From the relationship between these two parameters, the C_max, expressed as mg/ml, can be calculated. This latter parameter allows us to calculate the drug concentration which, at any moment during injection, comes into contact with a known aliquot of new' blood passing through the injection site. Furthermore, a dynamic test has been developed, which simulates an injection into the blood flow using a tubing system and infusion pumps set for the same R _ini. and Q _v values used in static test. Two injectable drugs, Valium® and Lanoxin®, and a commonly used vehicle, propylene glycol, have been tested by both the methods. These compounds have also been tested with another in vitro method (Prieur et al. 1973), in which a volumetric blood-to-test solution ratio of 1:1 is adopted for every drug tested, with neither R _inj. nor Q _v being taken into account. Results of the haemolytic potential obtained with the three tests have been compared.A good correlation has been observed between the static and the dynamic tests, whereas Prieur's model, which uses a drug-to-blood ratio which is far higher than in vivo, has been shown to give false positive results.It is concluded that a test for the evaluation of the haemolytic potential of drugs must take into account the pharmacodynamic characteristics of the formulation intended to be injected, and at least the blood flow rate. The proposed static test has been demonstrated to be an easy and reliable method of obtaining a true picture of the in vivo situation.     

Localization of epitopes and functional effects of two novel monoclonal antibodies against skeletal muscle myosin

Summary Two skeletal myosin monoclonal antibodies, raised against human skeletal myosin, were used to study the correlation between function, primary and tertiary structure of S-1 prepared from rabbit skeletal myosin. The heavy chain of S-1 is cleaved into three fragments by trypsin—27 kDa, 50 kDa and 20 kDa—aligned in this order from the N-terminus. The epitope of the first antibody was assigned to the N-terminal 1–23 amino acid stretch of S-1, since it reacted with the 27 kDa N-terminal tryptic fragment of S-1 but not with a derivative of the 27 kDa fragment, which lacks the above amino acid stretch. The epitope of the second antibody was assigned to the 3 kDa N-terminal region of the central 50 kDa domain of S-1. This assignment was based on proteolytic and photochemical cleavage of S-1 and on the labelling of its N-terminus by a specific antibody. The antibodies were visualized binding to the myosin head on electron micrographs of rotary-shadowed complexes of antibodies with myosin. Measurements on the micrographs indicated that the distances between the head-tail junction of myosin and the anti-27 K and anti-50 K epitopes are 14 nm and 17 nm, respectively. Both antibodies have a high affinity to S-1. The affinity of the anti-50 K to S-1 decreased upon actin binding, while that of the anti-27 K was not affected by binding of S-1 to F-actin. The anti-50 K antibody inhibited the K⁺ (EDTA) and the actin-activated ATPase activity of S-1, while the anti-27 K had no effect. The results indicate that either the epitope of the anti-50 K is near to the actin or to the ATP-binding sites of S-1, or that there is communication, expressed as propagated conformational changes, between these sites and the epitope.     

The effect of central retinal lesions on optokinetic nystagmus in the monkey

Summary In alert monkeys (Macaca mulatta and fascicularis) the effect of central retinal lesions on fast optokinetic responses was investigated during high velocity optokinetic and visual-vestibular conflict stimulation. The fast component of the optokinetic response manifests itself as a rapid rise in the slow-phase eye velocity after light-on, during high velocity optokinetic stimulation; and a sudden drop in eye velocity after light-off. In contrast, the velocity storage component leads only to gradual changes in eye velocity during continuous optokinetic stimulation and after light-off (optokinetic after-nystagmus).Retinal lesions were placed by laser coagulation in and around the fovea. Responses of the normal and lesioned eye were compared. It was found that central lesions up to 12 deg (fovea diameter 6 deg) had only a negligible effect on fast optokinetic responses. With lesions of more than 25–30 deg diameter centered on the fovea definite fast responses could still be obtained, on average reduced to about 50% of the responses of the normal eye. Some monkeys showed initially no fast optokinetic responses and had, therefore, to be excluded from lesion experiments.The results demonstrate that fast optokinetic responses also can be obtained from extrafoveal areas, i.e. areas which are not generally involved in smooth pursuit eye movements. These results are discussed in relation to reports that the smooth pursuit eye movement system is also used to generate fast optokinetic responses.Supported by Swiss National Foundation for Scientific Research 3.343-2.78 and Deutsche Forschungsgemeinschaft, SFB 200 A2These experiments were performed at the Dept. of Neurology, University of Zürich. A preliminary report of this work was presented at the workshop on Physiological and pathological aspects of eye movements in Habay-la-Neuve (Belgium) and at the 8th Extraordinary Meeting of the Barany Society in Basel (Switzerland)     

Adrenaline inhibits muscarinic transmission in bullfrog sympathetic ganglia

The effect of adrenaline (Ad) on muscarinic transmission was examined in B neurones of bullfrog sympathetic ganglia by using intracellular and voltage-clamp recording methods. Bath-application of Ad (5–500 M) caused a depression of the slow excitatory postsynaptic potential (EPSP) elicited by repetitive stimulations of preganglionic nerve fibres in the presence of curare (30 M). Ad also depressed the muscarinic ACh potential induced by ionophoretic application of ACh directly to curarized sympathetic neurones in a concentration-dependent manner. Isoprenaline mimicked the effect of Ad in producing the inhibition of the muscarinic ACh potential. Propranolol antagonized the inhibitory action of Ad. Dibutyryl adenosine 3,5-monophosphate had no significant effect on the muscarinic ACh potential. Under voltage-clamp conditions, Ad caused an inward current associated with inhibition of the M-current (Brown and Adams 1980). Ad depressed the amplitude of slow postsynaptic currents produced by applications of ACh and muscarine. At a concentration of 100 M, Ad produced a 68±8% (n=12) depression of the amplitude of the muscarinic ACh current. The inhibition of muscarinic transmission induced by Ad is due to a direct suppression of the muscarinic current at the postsynaptic membrane in bullfrog sympathetic ganglia.     

Pretectal jerk neuron activity during saccadic eye movements and visual stimulations in the cat

Summary The activity of jerk neurons was recorded extracellularly in the pretectum of the awake cat. The characteristic response of jerk neurons was a short, high-frequency burst that occurred after fast movements (jerks) of a large, structured visual stimulus, during saccadic eye movements in the light, and after on or off visual stimulation. Mean burst latency to pure visual jerks was 50 ms, whereas it was 30 ms to saccadic eye movements. Bursts were found to be stereotyped; the highest discharge rate was always at burst onset. Jerk neurons were not selective for stimulus parameters (such as movement amplitude or direction) except that in some neurons a weak correlation between stimulus velocity and discharge frequency was found. During saccades in the dark, clear bursts were only rarely found. In about half of the neurons, however, there was a slight but significant increase in the number of spikes above spontaneous frequency. Visual receptive fields were very large (46° horizontal and 35° vertical extent, on average). Nevertheless, the pretectal jerk neurons showed a rough retinotopic order, which was in accordance with the published retinotopy of the pretectum. Jerk neurons were found throughout the whole superficial pretectum, but preferentially in an area that corresponds to the nucleus of the optic tract (NOT) and the nucleus pretectalis posterior (NPP). Saccades were elicited by electrical stimulations at the sites where jerk neurons were recorded. The direction of the elicited saccades depended strongly on the pretectal stimulation site. A possible role of the jerk neurons as a visuomotor relay to elicit saccades or to modulate perception and attention is discussed.     

An in vitro model to study myocardial ischemic injury

Summary This report describes a method to study ischemic and reperfusion damage in cultured ventricular cardiomyocytes. The cardiomyocytes were made ischemic by oxygen deprivation and volume restriction. The ischemic intervals studied were 60, 90, and 120 min. An oxygen tension of 0 mmHg was maintained throughout ischemia. Reperfusion was simulated by bathing the cells in a large volume of normally oxygenated PBSG following ischemia. Ischemia and reperfusion resulted in increased lactate production, increased membrane damage, and ATP degradation. Ischemia caused a decrease in pH. Although 90 min of ischemia caused cell structural changes and alteration of metabolism, a prolonged ischemic interval of 120 min exacerbated these abnormalities. We have found our in vitro ischemia and reperfusion model to closely mimic the in vivo condition. This model using human ventricular cardiomyocytes is a means to studying the effect and mechanism of ischemia and reperfusion at the cellular level under defined conditions.     

Psilocybin-induced contraction of nearby visual space

Using apparent fronto-parallel plane (AFP) monitoring techniques, the relative stability of the abathic plane, i.e. Euclidean visual space, was investigated in 16 volunteers with a median age of 23.5 years under 160 g/kg psilocybininduced ergotropic arousal. Handwriting area and pressure were also measured in the same subjects.Drug-induced contraction of nearby visual space was inferred from changes of AFP curvature and tilt, as well as from increased handwriting area at drug peak. The rising horizon (Rennert) in the drawings of schizophrenics is also considered a manifestation of the contraction of visual space and is described in terms of an arousal-dependent transformation of constancies. The projection of central nervous system activity as experience out there is also discussed as an arousal-dependent learned constancy.     

INK4a-ARF alterations in Barrett’s epithelium,intraepithelial neoplasia and Barrett’s adenocarcinoma

Introduction The INK4a-ARF [CDKN2A]- locus on chromosome 9p21 encodes for two tumour suppressor proteins, p16^INK4a and p14^ARF, which act as upstream regulators of the Rb-CDK4 and p53 pathways. To study the contribution of each pathway to the carcinogenesis of Barretts adenocarcinoma, we analysed the alterations of p14^ARFand p16^INK4a in preneoplastic and neoplastic lesions of this disease.Materials and methods After microdissection, DNA of 15 Barretts adenocarcinomas, 40 Barretts intraepithelial neoplasms (n=20 low- and n=20 high-grade) and 15 Barretts mucosa without neoplasia was analysed for INK4-ARF inactivation using DNA sequence and loss of heterozygosity (LOH) analysis, methylation-specific polymerase chain reaction, restriction-enzyme-related polymerase chain reaction and immunohistochemistry.Results We detected 9p21 LOH, p16^INK4a methylation and p16^INK4a mutations in Barretts adenocarcinomas in 5 of 15 (33%), 8 of 15 (53%) and 1 of 15 (7%) patients, respectively. P14^ARF was methylated in 3 of 15 (20%) adenocarcinomas. In Barretts intraepithelial neoplasia, p16^INK4a was altered in 12 of 20 (60%) high-grade and in 4 of 20 (20%) low-grade intraepithelial neoplasms. In Barretts mucosa without intraepithelial neoplasia p16^INK4a was methylated in one case (7%). P14^ARF was intact in Barretts mucosa without intraepithelial neoplasia.Conclusions We conclude that most Barretts intraepithelial neoplasms contain genetic and/or epigenetic INK4a-ARF alterations. Methylation of p16^INK4a appears to be the most frequent epigenetic defect in the neoplastic progression of Barretts tumourigenesis.     

Observations bearing upon semi-circular canal dynamics

Summary It can be shown that following an angular velocity step stimulus delivered in darkness, the nystagmic responses can be effectively dumped after any interval in time by the application of an appropriate step decrement in velocity. In practise the null velocity is bracketed between those step decrements inducing just detectable nystagmus to left and right and can be determined within a range of ±1.5 ° s^-1. With test stimuli of 22, 44, and 64 ° s^-1the dump velocities have been established at varying intervals in time on four normal subjects. Contrary to expectations the dump velocity/time relations for all three test stimuli follow a convergent linear course. The dump velocities are unaffected by fixation suppression of the nystagmus induced by the test stimuli. The seeming irrelevance of nystagmus generation to dump velocity values is confirmed by the good correspondence with the results of a separate study using the oculogyral illusion as a guide in place of nystagmus. These findings are difficult to relate to conventional concepts of cupular dynamics.