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Biomedical subjects

S J Anderson

Publications and source records attributed to S J Anderson.

At least 55 records · Page 3Linked to original sources
PubMed1995

Parvocellular neurons limit motion acuity in human peripheral vision.

It is generally believed that the perception of moving targets is mediated by the magnocellular (M) pathway in primate vision, but evidence is emerging that the parvocellular (P) pathway may also play a role in motion perception. Human peripheral vision is susceptible to anomalous motion perception because of spatial aliasing, and in this study we used this fact to determine if the P pathway can mediate information about low- and high-velocity stimuli. Psychometric functions relating visual performance to stimulus spatial frequency were measured for the directional discrimination of drifting sinusoidal gratings presented at 40 degrees eccentricity. Applying the sampling theorem to our results, we estimated that the Nyquist frequency of the limiting sampling array for directional discrimination is 1.7 cycles per degree. This result was compared with the Nyquist limit and spatial filtering properties of M and P ganglion cells in the human peripheral retina, calculated from histological data on their density and dendritic field size. Our results provide evidence to suggest that the reversed motion illusion in human peripheral vision is due to spatial aliasing by the P ganglion cell mosaic. We conclude that the sampling density of P ganglion cells limits veridical motion acuity in human peripheral vision, even for high-velocity targets. This provides further evidence that the P pathway is involved in processing information about motion.

Discrimination, Psychological↗
PubMed1995

Smoothing splines for longitudinal data.

In a longitudinal data model with fixed and random effects, polynomials are used to model the fixed effects and smoothing polynomial splines are used to model the within-subject random effect curves. The splines are generated by modelling the data for each subject as observations of an integrated random walk with observational error. The initial conditions for each subject's deviation from the fixed effect curve are assumed to have zero mean and arbitrary covariance matrix which is estimated by maximum likelihood, producing an empirical Bayes estimate. This is in contrast to modelling a single curve using a diffuse prior. An example is presented using unbalanced longitudinal data from a pilot study in breast cancer patients.

Bayes Theorem↗
PubMed1995

Determinants of bone mineral density in older men.

Osteoporosis is a significant health problem and contributor to disability and premature mortality among older men. Incidence rates for hip fracture have stabilized in women, but continue to increase in men. A major risk factor for hip fracture is bone mineral density level. The determinants of bone mineral density (BMD) are well defined in women, but not in men. The primary goal of the current research was to increase our understanding of the determinants of BMD of the proximal femur in a large community-based sample of older male volunteers. Eligibility requirements included age of 50 years or older, ambulatory, and not having undergone a bilateral hip replacement. Five hundred twenty-three men, mean mean age 66.6 years, met all eligibility requirements and participated in the Study of Osteoporotic Risk in Men or STORM. Information on demographics, medical history, anthropometry, leisure-time and occupational physical activity, muscular strength, cigarette smoking, alcohol consumption, dietary calcium intake, and medication use (thiazide diuretics and glucocorticoids) were obtained by questionnaire, interview, and examination, BMD of the proximal femur (femoral neck, greater trochanter, and Ward's triangle) was measured by dual-energy X-ray absorptiometry using the Hologic QDR-1000 and QDR-2000. The cross-sectional determinants of BMD included age, blond hair color, current body weight, thiazide diuretic use, historical physical activity, and quadriceps strength. Several variables commonly thought to be determinants of BMD were not related to BMD in this population of older men, including current cigarette smoking, alcohol consumption, current leisure-time physical activity, dietary calcium intake, vitamin D use, and caffeine intake. However, failure to find associations among BMD and some of the potential determinants may be due to lack of statistical power. Identification of the determinants of BMD could lead to the development of interventions aimed at maximizing BMD in men and could potentially decrease the risk of hip fractures.

Absorptiometry, Photon↗
PubMed1995

Characterization of the effects of an airborne mixture of chemicals on the respiratory tract and smoothing polynomial spline analysis of the data.

We expanded a previously published (Vijayaraghavan et al. 1994) computerized system to analyze the breathing pattern of unanesthetized mice in order better to recognize and quantify the effects of an airborne mixture of chemicals at three different levels of the respiratory tract. The airborne chemical mixture used was a machining fluid. Such fluids are widely used in industry and a large number of workers are exposed to these airborne mixtures. We found this mixture to be capable of inducing three types of effects on the respiratory tract: sensory irritation of the upper respiratory tract (S), airflow limitation along the conducting airways (A) and pulmonary irritation (P). Depending upon the exposure concentration, mainly S or P effects were obtained but an A effect was also identified. The three types of effects occurred at various times during the exposures and, furthermore, within a group of exposed animals some exhibited one type of effect while others exhibited another type. In order to analyze such complex data sets, two statistical methods for smoothing polynomial splines were utilized: the maximum likelihood (ML) method and generalized cross validation (GCV) method. The results indicated the previous methods used to characterize a single effect of airborne chemicals can now be extended to evaluate mixtures likely to induce multiple types of effects. However, statistical analysis methods, either the ML or GCV methods, or other appropriate methods are needed to evaluate the responses obtained due to the complex effects that a mixture can induce in comparison to single chemicals.

Aerosols↗
PubMed1995

A signaling pathway governing early thymocyte maturation.

Recent evidence supports the view that p56lck, a non-receptor protein tyrosine kinase, serves as the signaling element that 'senses' synthesis of a functional T-cell receptor beta chain, thereby promoting thymocyte maturation. Here, Steven Anderson and Roger Perlmutter review current data, and outline the features of this developmental program.

Animals↗
PubMed1995

Night driving: effects of glare from vehicle headlights on motion perception.

Elderly drivers often experience disability glare at night from the headlights of oncoming vehicles. To assess the effect of glare from vehicle headlights on visual performance for seeing moving targets, experiments were performed at night on a dimly lit road with observers seated in a stationary motor car viewing a computer-generated stimulus display at a distance of 23 m (the stopping distance for 50 kph). The display was set 2 m to the side of a second stationary car whose position on the road was that of an oncoming vehicle with respect to the observer. The headlights of the observer's car were on low-beam while those of those of the opposing car were switched off (contro condition), on lpw-beam or on high-beam. Experiments were performed using mean display luminances of 50 cd/m2 and 0.5 cd/m2. Spatial contrast sensitivity functions for the directional discrimination of drifting (8 Hz sinusoidal gratings were measured using three different viewing conditions: normal vision (binocular visual acuity (BVA) = 6/6); blurred vision (BVA = 6/9-); and simulated intraocular lens opacities (BVA = 6/6-). The data were fitted with an exponential function, which was extrapolated to 100% contrast to estimate dynamic visual acuity. The results show that simulated lens opacities, which have little or no effect on standard day time measures of visual acuity, have a marked effect on night-time measures of contrast sensitivity for moving targets. Taking into account the average luminance of objects lit by road lighting, we estimate that high-beam glare reduces maximum contrast sensitivity by an order of magnitude in persons affected by mild lens opacities, giving a dynamic acuity of 1.0 c/deg (6/180 Snellen equivalent) or less. From this and other studies we argue that there is now a strong case for the introduction of vehicle-licensing sight re-testing at regular intervals in the UK. In addition, we suggest that vehicle-licensing authorities consider the feasibility of introducing sight tests under night-time driving conditions.

Adult↗
PubMed1994

Specific suppression of human CD4 surface expression by Nef from the pathogenic simian immunodeficiency virus SIVmac239open.

HIV-1 Nef down-modulates expression of human CD4, the human immunodeficiency virus (HIV) receptor, at the cell surface. Down-modulation of retrovirus receptors has been shown to be important in the survival of infected cells. To relate this observation to AIDS pathogenesis, we compared the ability of Nef from the SIVmac239open and HIV-1 SF2 isolates to suppress CD4 surface levels. We first obtained the simian immunodeficiency virus (SIV)nef gene by PCR and cloned it into the retroviral vector pLXSN. We then established high titer (1 x 10(6) CFU/ml) amphotropic retrovirus producer lines (PA317/LSnefSN). Using LSnefSN we obtained populations of CD4+ human and mouse T-cells, human B-cells, and mouse fibroblasts that expressed SIV or HIV Nef. In the two human cell lines, both HIV and SIV Nef expression correlated with a significant decrease in CD4 cell surface levels. However, Nef expression did not alter the cell surface levels of CD3, CD18, and MHC class I. Both Nef proteins also suppressed human CD4 surface expression in mouse fibroblasts. Interestingly, SIV Nef failed to suppress cell surface expression of mouse CD4 under conditions where HIV-1 Nef did. Human CD4 down-modulation is a conserved function of SIV and HIV Nef likely to be important for pathogenesis.

Amino Acid Sequence↗
PubMed1994

Visual evoked potentials to flash and pattern reversal stimulation after administration of systemic or topical scopolamine.

It has previously been shown that 0.6 mg of scopolamine produces a delay in the flash visual evoked potential of young normal volunteers, while the pattern-reversal response does not change in latency. Recent work has shown that this drug differentially affects parvocellular and magnocellular systems. To investigate this effect, two studies were performed. In the first study, 0.4 mg of scopolamine was injected intramuscularly into 11 young, healthy male volunteers who had fasted overnight. The visual evoked potential was recorded to both binocular flash stimulation and monocular pattern-reversal stimulation by means of a checker-board consisting of 56' checks in a 28 degrees field. Responses were recorded before administration of the drug and then 1, 2, 4 and 6 hours after administration. The scopolamine produced a slowing of the flash P2 latency of approximately 6 ms (p < 0.05) two hours after drug administration. There was no effect on the latency of the flash N2 or pattern-reversal N75 or P100. There was an increase in amplitude of the flash N2-P2 component 6 hours after drug administration and an increase in the amplitude of the N75 and P100 2, 4 and 6 hours after the drug. Further subjects were investigated with the use of topical administration of 0.125% scopolamine applied monocularly. In all studies the other eye acted as a control. The subjects were again young healthy volunteers. The visual evoked potential was recorded to both flash and pattern-reversal stimulation with a checkerboard consisting of 60' checks counterphasing at 2 Hz within a 5 degrees field. Results suggest that systemic scopolamine affects the tectal pathway but has no peripheral effect.

Administration, Topical↗
PubMed1994

Topographic mapping of the pattern onset evoked magnetic response to stimulation of different portions of the visual field.

Visual evoked magnetic responses to pattern onset/offset stimuli were recorded in 5 normal subjects. The outgoing and ingoing magnetic currents were seen maximally over the contralateral visual cortex to the half field stimulated in the majority of subjects. The distribution of magnetic currents with half field stimulation would be consistent with a dipole on the midline with the positive end pointing laterally. Quadrantic stimuli produced dipoles which would be consistent with a vector sum of dipoles situated, in the case of upper quarter field stimulation, in the lingual gyri on the floor of the calcarine fissure. Lower quadrantic stimulation produced a vector consistent with dipoles on the cuneal gyrus and on the ceiling of the calcarine fissure producing a resultant vector. The use of paired octant stimuli to improve localisation was demonstrated on both right left and upper and lower half fields.

Adult↗
PubMed1994

Effect of dopamine and acetylcholine on the visual evoked potential.

Visual evoked potentials were measured on patients with Parkinson's disease and Alzheimer's disease and normal controls to assess the function of dopamine and acetylcholine in the visual system. Dopamine is a neurotransmitter known to be present in the retina of primates and is found to be severely depleted in the substantia nigra of patients with Parkinson's disease. Acetylcholine is also known to be present in the retina, visual cortex, and superior colliculus and is found to be grossly reduced in patients with Alzheimer's disease. Stimuli were designed to preferentially activate functionally separate pathways in the visual system described as magnocellular and parvocellular. The four stimuli were a diffuse flash; an achromatic, 73' check counterphasing at 6 Hz at a contrast of 30%; an achromatic 10' check counterphasing at 2 Hz at a contrast of 85%; and an isoluminant red/green grating of 4 cpd presented using an on and off cosine ramp of 200 ms. The results indicate that an acetylcholine deficit produces a delay to the flash P2 component of the visual evoked potential. No change was detected when other stimuli were used.

Acetylcholine↗
PubMed1994

An activated lck transgene promotes thymocyte development in RAG-1 mutant mice.

Expression of the T cell receptor beta (TCR beta) chain is necessary for the transition from the CD4CD8- stage in the major alpha beta thymocyte lineage. The protein tyrosine kinase p56lck has been implicated in the regulation of early thymocyte differentiation and of allelic exclusion at the TCR beta locus. Using mice overexpressing an activated lck transgene and mice with a disruption of the lck gene, we demonstrate that p56lck participates in a pathway that regulates the expansion of the pool of CD4+CD8+ thymocytes to wild-type levels. In addition, p56lck may be involved in the down-regulation of the putative pre-TCR on CD4+CD8+ thymocytes.

Animals↗
PubMed1994

The cytoplasmic domain of CD4 is sufficient for its down-regulation from the cell surface by human immunodeficiency virus type 1 Nef.

Human immunodeficiency virus type 1 Nef down-regulates surface expression of murine and human CD4 but not human CD8. We recently reported that the cytoplasmic domain of CD4 is required for its down-regulation by Nef. Using a chimeric molecule composed of the extracellular and transmembrane domains of human CD8 fused to the cytoplasmic domain of human CD4, we show here that the cytoplasmic domain of CD4 is sufficient for down-regulation by Nef. Since the cytoplasmic domain of CD4 is also the site of its association with p56lck, we used a series of CD4 mutants to determine whether the regions of the cytoplasmic domain of CD4 required for down-regulation by Nef are the same as those required for p56lck binding. Our results indicate that the portion of the cytoplasmic domain required for the down-regulation of CD4 by Nef overlaps with the binding site of p56lck, but the cysteine residues which are essential for the association of CD4 with p56lck are not required. This observation raised the possibility that Nef competes with p56lck for binding to CD4. However, under conditions which are considerably milder than those permissive for coimmunoprecipitation of CD4 and p56lck, we found no evidence for an association between Nef and CD4. While a decrease in total CD4 was observed in lysates of cells expressing Nef, the levels of p56lck were not significantly affected. Pulse-chase experiments further revealed a decrease in the half-life of CD4 in Nef-expressing cells. These results show that the decrease in surface CD4 expression induced by Nef is mediated at least in part by a decrease in the half-life of CD4 protein. These results also indicate that a large portion of p56lck is free of CD4 in T cells expressing Nef, which could have a significant effect on T-cell function.

Amino Acid Sequence↗
PubMed1994

The formation of flashbulb memories.

A large group of subjects took part in a multinational test-retest study to investigate the formation of flashbulb (FB) memories for learning the news of the resignation of the British prime minister, Margaret Thatcher. Over 86% of the U.K. subjects were found to have FB memories nearly 1 year after the resignation; their memory reports were characterized by spontaneous, accurate, and full recall of event details, including minutiae. In contrast, less than 29% of the non-U.K. subjects had FB memories 1 year later; memory reports in this group were characterized by forgetting, reconstructive errors, and confabulatory responses. A causal analysis of secondary variables showed that the formation of FB memories was primarily associated with the level of importance attached to the event and level of affective response to the news. These findings lend some support to the study by R. Brown and Kulik (1977), who suggest that FB memories may constitute a class of autobiographical memories distinguished by some form of preferential encoding.

Affect↗
PubMed1993

Regulation of CD4 and CD8 expression on mouse T cells. Active removal from the cell surface by two mechanisms.

Phorbol esters are known to induce a loss of CD4 from the surface of mouse and human T cells, presumably through activation of protein kinase C. Here we describe additional, calcium-dependent processes that remove CD4 and CD8 from the surface of T cells and thymocytes, and that differ from the protein kinase C-mediated effect in that they require the expression of new gene products. Whereas PMA causes the disappearance of almost all CD4 from the surface of mouse CD4+8+ thymocytes, it induces only a partial (approximately 60%) and transient (10 to 12 h) loss of CD4 from the surface of mouse peripheral T cells, with no effect on CD8 expression. When T cells are exposed to a combination of PMA and the calcium ionophore, ionomycin (Cal), surface CD4 virtually disappears for a period of at least 24 h, and CD8 expression is also diminished. This additional, calcium-dependent effect, on both CD4 and CD8 expression, is abrogated by either cycloheximide or actinomycin D, and so depends on new RNA and protein synthesis. There appear, therefore, to be two distinct mechanisms for the removal of CD4 and CD8 from mouse peripheral T cells: one induced by PMA alone, the second by the combination of PMA and Cal. The second mechanism, but not the first, depends on the expression of new gene products. In contrast to mouse peripheral T cells, mouse thymocytes and human peripheral blood T cells respond to PMA alone with virtually a complete loss of surface CD4, and partial loss of CD8 expression. The addition of Cal has no synergistic effect on CD4 expression in either of these populations, but augments the loss of CD8 in mouse thymocytes.

Animals↗
PubMed1993

Protein tyrosine kinase p56lck controls allelic exclusion of T-cell receptor beta-chain genes.

During T-cell development, site-specific DNA rearrangements mediating assembly of beta- and alpha-chain genes of the T-cell receptor (TCR) are developmentally ordered. In particular, assembly and expression of a complete beta-chain gene blocks further rearrangements at the beta-locus (a process referred to as allelic exclusion) and drives the generation and expansion of CD4+8+ cells. Although the mechanism used by TCR beta chains to deliver such signals is unknown, studies in transgenic animals have suggested that the lymphocyte-specific protein tyrosine kinase p56lck may impinge on a similar signalling pathway. The hypothesis that TCR beta chains deliver intracellular signals via p56lck makes an explicit prediction: that interference with p56lck function will mitigate the effects of a simultaneously expressed TCR beta chain. Here we confirm this prediction through examination of allelic exclusion in mice expressing both a functional TCR beta chain transgene and a catalytically inactive form of p56lck.

Alleles↗
PubMed1993

The protein tyrosine kinase p56lck regulates thymocyte development independently of its interaction with CD4 and CD8 coreceptors [corrected].

The lck gene encodes a lymphocyte-specific protein tyrosine kinase of the nonreceptor type that is implicated in signal transduction pathways emanating from the CD4 and CD8 coreceptors. Previous studies also support a role for p56lck in regulating T cell receptor beta gene rearrangements and, more generally, thymocyte development. Here we report that a mutant form of p56lck, which is incapable of interacting with CD4 or CD8, behaves indistinguishably from association-competent p56lck with respect to its ability to affect thymocyte maturation. The effects of p56lck remained specific in that the closely related src-family kinase p59hck was incapable of substituting for p56lck in arresting beta locus gene rearrangements. These data support the view that src-family kinases perform highly specialized and often nonoverlapping functions in hematopoietic cells, and that p56lck acts independently of its association with CD4 and CD8 to regulate thymocyte development.

Animals↗