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Biomedical subjects

B S Cheung

Publications and source records attributed to B S Cheung.

At least 19 recordsLinked to original sources
PubMed2000

Apolipoprotein E affects the amount, form, and anatomical distribution of amyloid beta-peptide deposition in homozygous APP(V717F) transgenic mice.

Apolipoprotein E (apoE) has been implicated as a risk factor for Alzheimer's disease and in the deposition, fibrillogenesis, and clearance of the amyloid beta-peptide (Abeta). To examine the in vivo interactions between apoE and Abeta deposition, we examined 12-month-old transgenic (tg) mice expressing human amyloid precursor protein (APP) with the V717F mutation (APP(V717F) homozygous) on an APOE null background. Elimination of APOE resulted in a redistribution and alteration in the character of Abeta deposition in homozygous APP(V717F) tg mice, with a dramatic reduction in cortical and dentate gyrus deposition, prominent increase in diffuse CA1 and CA3 deposition, and prevention of the formation of thioflavin-S-positive deposits. These alterations in Abeta deposition were not mediated by significant changes in regional APP expression, low-density lipoprotein receptor-related protein expression, or soluble Abeta levels. Thus, apoE in APP(V717F) tg mice not only affects the amount and form of Abeta deposition, but also the anatomical distribution of diffuse Abeta deposits. The APP(V717F) tg mouse can serve as a model to investigate genetic influences on the vulnerability of specific neuroanatomical regions to Abeta deposition.

Amyloid beta-Peptides↗
PubMed1999

Lack of independent associations of apolipoprotein E promoter and intron 1 polymorphisms with Alzheimer's disease.

Several studies have demonstrated genetic associations between Alzheimer's disease (AD) and polymorphisms in the promoter/enhancer regions of the apolipoprotein E (APOE) gene. These studies raise the possibility that APOE transcription control may be involved in altered risks for AD. We evaluated polymorphic sites in the intron-1 enhancer element (IE-1G/C) and in the APOE promoter (-219G/T). For the IE-1 polymorphism, we analyzed 433 individuals (183 AD and 250 controls), and found a strong linkage between the IE-1G allele and APOE-epsilon4. When we controlled for this linkage using log-linear model analysis, we found no independent association between the IE-1 polymorphism and AD. For the -219 polymorphism, we analyzed 475 individuals (168 AD cases, 234 controls, and 73 cases of cerebral amyloid angiopathy (CAA)). We found strong linkages between the -219G allele and APOE-epsilon2 and between the -219 T allele and APOE-epsilon4. Controlling for these linkages, we found no independent association between the -219 polymorphism and AD or CAA. Thus, our studies do not support independent associations between AD and either the IE-1 or the -219 polymorphisms.

Alleles↗
PubMed1999

Lack of allelic imbalance in APOE epsilon3/4 brain mRNA expression in Alzheimer's disease.

Although the APOE epsilon4 allele is a strong risk factor for Alzheimer's disease (AD), it is not deterministic, as many APOE epsilon3/4 individuals do not develop AD. It has been hypothesized that this incomplete penetrance is due, in part, to an imbalance of allele expression in heterozygous individuals. In this regard, Lambert et al. (1998) reported that AD individuals have a higher APOE epsilon4/total APOE ratio than non-demented control subjects. We tested this hypothesis using radioactive RT-PCR to quantitate APOE epsilon3 and epsilon4 allele expression levels in AD and non-AD brain samples from APOE epsilon3/4 individuals. Quantitative analyses of amplified products within the linear range of amplification (18-20 cycles) revealed no difference from the expected 1:1 ratio in genomic DNA and in cDNA from AD and control brains. Using high PCR cycle numbers (approximately 30), we observed an artificial elevation of the APOE epsilon3/total APOE ratio in both DNA and cDNA samples, possibly due to DNA heteroduplex formation. Our results do not support the hypothesis that allelic imbalance contributes to the risk of developing AD among APOE epsilon3/4 heterozygote individuals.

Alleles↗
PubMed1999

Influence of body roll on visually induced sensations of self-tilt and rotation.

Illusory self-tilt and illusory self-motion (vection) produced by rotation of a 360 degrees visual scene about the subject's roll axis was measured as a function of the presence or absence of actual rotation of the subject during acceleration of the visual scene. Rotation of the subject to a tilt of 15 degrees was at two levels of acceleration (onset) and with or without a delay between initial rotation and subsequent return (washout) to the vertical position. In one set of conditions, visual motion and subject motion were in opposite directions (concordant) and in another set they were in the same direction (discordant). In two control conditions, the subject was rotated while the visual scene remained stationary. For concordant motion the main effect of body rotation was to reduce the time taken by the subject to indicate self-tilt as compared with the response time to visual motion alone. The magnitude of estimated self-tilt was increased by actual body tilt as could be expected from addition of the perceived actual body tilt and the illusory body tilt induced by visual rotation. This effect of augmented body tilt did not persist after the body was returned to the vertical. The magnitude of vection was not markedly influenced by body rotation and washout. For discordant motion of body and the visual scene, subjects were confused and their responses were very variable, suggesting a nonlinear visual--vestibular interaction.

Adult↗
PubMed1998

Control of isometric force in hypergravity.

BACKGROUND: Previous work suggests that proprioceptive signals are degraded in hypergravity (hyper-G). We therefore, expected that production of finely graded force is disturbed as well. METHODS: Subjects produced isometric force with their thumb and index finger upon verbal instruction, before, during and after exposure to +1.5 Gz and +3 Gz. Produced force was orthogonal to the direction of gravity. RESULTS: In hyper-G, responses to a given target value were significantly higher (by about 400 pond) than in normal gravity, while the modulation of produced force with target force didn't change. The results in +1.5 Gz and +3 Gz were quantitatively similar, and a positive aftereffect was found. CONCLUSIONS: Subjects underestimate by a constant amount the force they produce in hyper-G. Our results are reminiscent of similar findings with pointing and grasping movements in hyper-G.

Adult↗
PubMed1996

Combined head and eye tracking system for dynamic testing of the vestibular system.

We present a combined head-eye tracking system suitable for use with free head movement during natural activities. This system provides an integrated head and eye position measurement while allowing for a large range of head movement (approx 1.8 m of head translation is tolerated). Six degrees of freedom of head motion and two degrees of freedom of eye motion are measured by the system. The system was designed to be useful for the evaluation of the vestibulo-ocular reflex (VOR). The VOR generates compensatory eye movements in order to stabilize gaze during linear or rotational motion of the head. Current clinical and basic research evaluation of the VOR has used a restricted range of head motion, mainly low-frequency, yaw rotation. An integrated eye-head tracking system such as the one presented here allows the VOR response to linear and angular head motion to be studied in a more physiologically relevant manner. Two examples of the utility of the integrated head and eye tracking system in evaluating the vestibular response to linear and angular motion are presented.

Electrooculography↗
PubMed1996

Performance of a simple aiming task in hypergravity: I. overall accuracy.

BACKGROUND: Visuo-motor performance is known to be affected by exposure to hyper-gravity (hyper-G), but the underlying mechanisms remain to be determined; the present study investigated the role of target mislocalization. METHOD: Subjects pointed before, during and after exposure to hyper-G at targets without seeing their hand. Target positions were displayed: a) throughout each pointing response; b) before response onset; or c) in normal gravity prior to a set of movements. RESULTS AND CONCLUSIONS: For all display conditions, subjects pointed higher in hyper-G than in normal gravity from the first movement on. We attribute the discrepancy between this finding and previous results (8, 12) to different movement strategies. The effects of hyper-G on pointing performance were small, but sustained when targets were displayed before or throughout each movement, but they were large and transient when targets were memorized in normal-G. We conclude that too-high pointing in hyper-G cannot be simply explained by the "elevator illusion," and propose a tentative interpretation based on known perceptual deficits.

Adult↗
PubMed1996

Performance of a simple aiming task in hypergravity: II. detailed response characteristics.

BACKGROUND: Literature proposes three hypotheses for impaired movement execution in hyper-G. The present study attempted to discriminate between these hypotheses by comparing kinematic characteristics and final accuracy of pointing movements in different gravity levels. METHOD: Subjects pointed without seeing their hand at targets presented before, during and after exposure to hyper-G. RESULTS: After factoring out movement amplitude, peak vertical velocity and the skewness of velocity profiles tended to increase, while movement duration tended to decrease with increasing G-level. Further, final response position was slightly less modulated by target position in hyper-G than in normal-G. CONCLUSION: Although not all findings reached statistical significance, the observed pattern of results corroborates the hypothesis (2) that the motor system re-interprets hyper-G as increased arm weight.

Adult↗
PubMed1995

Dynamics of torsional optokinetic nystagmus under altered gravitoinertial forces.

The purpose of the present study was to investigate the influence of varying gravitoinertial forces on torsional optokinetic nystagmus during parabolic flights. Using the scleral search-coil technique, we measured the gain and phase lag of torsional optokinetic nystagmus (OKN) induced by a hemispherical visual display rotating about the roll axis either at constant velocity or sinusoidally at various frequencies during level flight, hypogravity, and hypergravity. Compared with level flight, there was a significant increase in slow-phase eye velocity during hypogravity and an increase in nystagmic frequency. An absence of well-developed torsional optokinetic afternystagmus was observed in all three gravity conditions. Other characteristics included a lack of a slow rise component. These data suggest that otolith inputs do affect torsional optokinetic afternystagmus suggests that the velocity storage pathways do not contribute significantly to the torsional OKN system in humans.

Acceleration↗
PubMed1994

Etiologic significance of arginine vasopressin in motion sickness.

There is abundant evidence implicating the role of arginine vasopressin in motion sickness. The effects of AVP analogs on motion sickness were investigated in squirrel monkeys. Two specific V1 antagonists (SK&F 100273 and SK&F 103561) and three mixed V1/V2 antagonists (SK&F 101926, SK&F 105494, and SK&F 104146-D) were tested on six highly susceptible monkeys. Intravenous injections of 200 ug of a V1 antagonist abolished emesis in all six monkeys, and few prodromal symptoms remained (latency to emesis > 120 minutes, P < .001). Mixed V1/V2 antagonists failed to abolish emesis in all monkeys. However, there was a slight increase in the latency to the first bout of emesis/retching with the mixed antagonists when compared with the baseline. The dose-response relationship and rate of onset of action of the V1 antagonists (SK&F 100273) were explored. Latency to the first bout of emesis/retching increased to about twice that of the baseline when half of the effective antiemetic dose was used. The efficacy demonstrated by the specific V1 antagonists indicates that V1 receptors may modulate emesis.

Animals↗
PubMed1994

Human gaze instability during brief exposure to reduced gravity.

The stability of gaze in three dimensions (horizontal, vertical and torsional) was investigated with the electromagnetic scleral search-coil technique during the microgravity phase of parabolic flights under two visual fixation conditions: fixation on a real target and on an imagined target. Subjects were secured upright with the head immobilized by a dental bite. There were torsional eye movements in response to the imposition of reduced gravitoinertial forces under both visual fixation conditions. The pattern of these movements was consistent with our previous findings on six other subjects. No significant horizontal eye movements were observed in either fixation condition. Under the condition of fixation on an imagined target, direction-specific vertical nystagmus was observed with slow phase directed upwards during transition from hypergravity to microgravity. The slow phase was directed downwards during transition from microgravity to hypergravity, although the nystagmus was of lower frequency and the magnitude of the slow phase velocity appeared to be smaller than during transition from hypergravity to microgravity. The vertical eye movements could be attributed to a change of otolithic stimulation along the subject's z axis since the rate of pitch rotation of the aircraft during parabolic flight was too slow to produce an effective canal input. These kinds of reflex eye movements could degrade vision during manoeuvres or turbulence in flight.

Adult↗
PubMed1992

Investigation of anti-motion sickness drugs in the squirrel monkey.

Early attempts to develop an animal model for anti-motion sickness drugs, using dogs and cats; were unsuccessful. Dogs did not show a beneficial effect of scopolamine (probably the best single anti-motion sickness drug for humans thus far) and the findings in cats were not definitive. The authors have developed an animal model using the squirrel monkey (Saimiri sciureus) of the Bolivian phenotype. Unrestrained monkeys in a small lucite cage were tested in an apparatus that induces motion sickness by combining vertical oscillation and horizontal rotation in a visually unrestricted laboratory environment. Signs of motion sickness were scored using a rating scale. Ten susceptible monkeys (weighing 800-1000 g) were given a total of five tests each, to establish the baseline susceptibility level. Based on the anticholinergic activity of scopolamine, the sensitivity of squirrel monkey to scopolamine was investigated, and the appropriate dose of scopolamine for this species was determined. Then various anti-motion sickness preparations were administered in subsequent tests: 100 ug scopolamine per monkey; 140 ug dexedrine; 50 ug scopolamine plus 70 ug dexedrine; 100 ug scopolamine plus 140 ug dexedrine; 3 mg promethazine; 3 mg promethazine plus 3 mg ephedrine. All these preparations were significantly effective in preventing motion sickness in the monkeys. Ephedrine, by itself, which is marginally effective in humans, was ineffective in the monkeys at the doses tried (0.3-6.0 mg). The squirrel monkey appears to be a good animal model for antimotion sickness drugs. Peripherally acting antihistamines such as astemizole and terfenadine were found to be ineffective, whereas flunarizine, and an arginine vasopressin V1 antagonist, showed significant activity in preventing motion sickness.

Animals↗
PubMed1992

Human ocular torsion during parabolic flights: an analysis with scleral search coil.

Rotation of the eyes about the visual axis is known as ocular torsion. A lateral inclination (a "roll") of the head induces ocular torsion in the opposite direction, a response known as ocular counterrolling. For six subjects, we recorded the static (head still) and dynamic (head in oscillatory roll motion) ocular torsion in normal 1 g condition and also during the microgravity and hypergravity periods of parabolic flight, using the electromagnetic scleral search coil technique. With the head still, the direction and magnitude of torsion that occurred in response to microgravity and hypergravity differed substantially from one individual to another, but there was a significant difference in torsional magnitude between the microgravity and hypergravity periods, for all static head positions including the upright position. Under normal 1 g conditions, counterrolling compensated for about 16% of (voluntary) static head roll, while dynamic counterroll was much larger, up to 36% of head roll at 0.55 Hz. With increasing frequency of head oscillation between 0.33 Hz and 0.55 Hz, the gain of counterrolling increased and there was no change in the phase relationship. The gain of dynamic counterroll (in response to voluntary head rolling) was not significantly less in hypogravity, suggesting that on the ground at these frequencies the contribution of gravity and gravity receptors to this reflex is redundant: this reflex is probably driven by the semicircular canals. In some subjects, the torsional displacement in microgravity is accompanied by micro-torsional oscillatory motion.

Adult↗
PubMed1992

The influence of age on susceptibility to motion sickness in monkeys.

A longitudinal study on the effects of age on the susceptibility to motion sickness in the squirrel monkey was carried out over a 10-year period (1982 to 1991). The typical life span of squirrel monkeys is 15 years. Ten mature male squirrel monkeys of the Bolivian subspecies were found to be susceptible to motion sickness induced by a combination of vertical oscillation at 0.5 Hz and rotation in the horizontal plane at 25 rotations per minute (RPM) in a visually unrestricted environment. Signs of motion sickness were quantified according to a rating scale based on Graybiel's diagnostic criteria. Latency to vomiting/retching and severity of sickness obtained from year 1 (baseline), 3, 5, 7 and 10 were subjected to repeated-measures design analysis. There were no significant differences in the susceptibility level (as measured by latency to vomiting/retching and cumulative sickness scores) in the monkeys throughout the 10-year period. The habituation to 7 consecutive daily exposures remained the same throughout the same period. We conclude that, in the squirrel monkeys from maturity to near the end of their life span, there is no change in susceptibility to motion sickness with aging.

Aging↗
PubMed1991

Bilirubin inhibits the activation of superoxide-producing NADPH oxidase in a neutrophil cell-free system.

We studied the effect of bilirubin on the NADPH-dependent superoxide production induced by sodium dodecyl sulfate in a cell-free system consisting of the membrane and cytosolic fractions of pig neutrophils. Preincubation of the cytosolic fraction with bilirubin before the addition of sodium dodecyl sulfate resulted in the time- and dose-dependent inhibition of the superoxide production while the preincubation of the membrane fraction with the tetrapyrrole did not result in the inhibition. When the pigment was added after the initiation of the reaction, the ongoing production was not affected by the addition. Other tetrapyrroles, such as hemin, protoporphyrin and biliverdin, also inhibited the production. The results indicate that bilirubin inhibits the activation process of the superoxide producing NADPH oxidase by decreasing the potency of the cytosolic fraction and its inhibitory effect seems to be due to the hydrophobic nature of the tetrapyrrole.

Animals↗
PubMed1991

Optokinetic torsion: dynamics and relation to circularvection.

Continuous records of optokinetic torsion to sinusoidal inputs were obtained using the electromagnetic scleral search-coil technique. We measured the gain and phase lag of optokinetic torsion in response to a spherical visual display rotating steadily at various angular velocities and sinusoidally at frequencies from 0.2 to 2.0 Hz and at amplitudes from 10 to 80 deg. Gain (peak slow-phase eye velocity over stimulus angular velocity) of up to 0.12 were obtained with stimulus frequencies of 0.2 Hz and declined to an average value of about 0.02 at a frequency of 2.0 Hz. Phase lag was virtually zero at a frequency of 0.2 Hz and increased to over 80 deg at 2.0 Hz. The records from the sinusoidal stimuli show very few quick phases. With increasing stimulus amplitudes, the amplitude of the response increased but its gain declined. We found no evidence of torsional after-nystagmus nor any relation between the torsional response and reports of vection or sensation of body tilt induced by the rotating display. Torsional optokinetic nystagmus is most suited to compensate for low-amplitude, low-frequency stimulus rotation and normally supplements torsion induced by head tilt.

Adult↗
PubMed1991

Visually-induced sickness in normal and bilaterally labyrinthine-defective subjects.

A group of nine normal subjects (with no overt vestibular dysfunction) and a group of 6 bilaterally labyrinthine-defective subjects were exposed to a visual field rotating about an Earth-horizontal axis (orthogonal to the gravity axis). The visual stimulus was provided by a 3-m diameter sphere with random dots rotating at 30, 45, and 60 degrees per second (degree/s) about the stationary subject's roll, pitch and yaw axes. The subject's head was positioned at the center of the sphere such that it experienced apparent motion in all three axes. Results indicated that in the normal group, symptoms of motion sickness were reported in 21 of 27 test-trials. When labyrinthine-defective subjects were exposed to the roll and pitch stimulus, no sickness symptoms were reported or observed. These results strongly suggest that the vestibular system is necessary for sickness induced by moving visual fields.

Adult↗