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Biomedical subjects

S J Anderson

Publications and source records attributed to S J Anderson.

At least 73 records · Page 4Linked to original sources

A dominant-negative transgene defines a role for p56lck in thymopoiesis.

The lymphocyte-specific protein tyrosine kinase p56lck participates in T cell signaling through functional interactions with components of the T cell antigen receptor complex and the interleukin-2 receptor. Additional insight into the function of p56lck has now been obtained through the generation of transgenic animals expressing high levels of a catalytically inactive form of this kinase (p56lckR273). Mice bearing the lckR273 transgene manifested a severe defect in the production of virtually all T lymphocytes. Those exceptional CD3+ cells that escaped the effects of the lckR273 transgene were confined primarily to the T cell subset that expresses gamma/delta T cell receptors. Remarkably, construction of a dose-response curve for the effects of the lckR273 transgene revealed that developmental arrest of thymocytes occurred at a discrete stage in the normal T cell maturation pathway, corresponding to a point at which thymoblasts ordinarily begin a series of mitotic divisions that result in expansion and maturation. These results suggest that p56lck normally regulates T cell production by metering the replicative potential of immature thymoblasts.

Animals↗

Motion sensitivity and spatial undersampling in amblyopia.

The nature of the visual deficit in human amblyopia has been keenly sought over the last decade. Some confusion has arisen as to whether the motion-sensitive mechanisms known to exist in normal vision are selectively affected in humans with amblyopia. To address this issue we compare contrast thresholds for detection and direction discrimination of drifting sine-wave gratings in a group of humans with amblyopia. The results suggest that over the vast majority of the spatio-temporal range, direction of motion can be discriminated at detection threshold. Over a narrow part of the visible range there is a differential loss of sensitivity for direction discrimination over that of simple detection. However such an effect also occurs for normal vision under spatially scaled conditions and it seems likely that it is mediated by non-motion sensitive mechanisms. We show that one possible cause of this loss of direction discrimination, namely spatial undersampling within the central region of the amblyopic visual field, is not a viable explanation.

Amblyopia↗

Visual processing delays alter the perceived spatial form of moving gratings.

This study shows that there are delays in processing high spatial frequencies relative to low frequencies, and that these may affect the perceived brightness profile of drifting waveforms. The stimuli were complex waveforms consisting of 2-3 sinusoidal components, either drifting or stationary. The phase of the components was varied until the brightness profile of the waveform appeared as a square, triangle, ramp or bar. The results indicate that stationary waveforms are perceived veridically, but drifting waveforms are not. The harmonics of a drifting complex wave must be phase advanced, relative to the fundamental, in order to cancel motion-induced waveform distortions. This suggests that during visual processing the harmonics must be phase delayed, indicating that they are being processed more slowly than the fundamental. The most significant delays appear to be those between the fundamental and its second and third harmonic. Furthermore, the results show that the magnitude of the delays is dependent on the phase relationship between the components at perceptually significant points in the waveform: delays are less when the components are in sine phase than when they are in cosine phase. Separate experiments show that the detectability of phase shifts is least when the components are in sine phase. Together, these results may explain why drifting "sharp-edged" stimuli are not perceptually distorted: the human visual system appears to be relatively insensitive to phase shifts around square-wave phase and may therefore tolerate differences in the processing times of certain harmonics. A discussion of the possible origin of these processing delays is presented, together with the hypothesis that frequency dependent delays may reflect the spatiotemporal inseparability of cortical visual units.

Form Perception↗

The assessment of alaryngeal speech.

The objective measurement of alaryngeal speech is desirable so that results between different centres can be compared. We examined several phonatory parameters of alaryngeal speech with the Visi-pitch and correlated these with the subjective assessment of voice quality. Amplitude, percentage voiced and perturbation correlated extremely well with the subjective assessment of voice quality.

Adult↗

Blom-Singer prostheses--an 11 year experience of primary and secondary procedures.

Over the past 11 years, 25 primary and 29 secondary tracheo-oesophageal punctures have been performed in 51 laryngectomees. Pre-operative assessment is required for the secondary procedure. Both primary and secondary procedures require intensive speech therapy after fitting of the prosthesis. Fifty-four per cent of the primary and 37% of the secondary patients attained long-term speech, the latter figure rising to 58% with newer valves and increasing experience. Failures were commonly due to psychological or prosthesis-related problems. Complications were relatively minor, none being life threatening. Seventy per cent of the long-term users were self caring. Adequate rehabilitation counselling and support is necessary to ensure long-term use of the prosthesis.

Adult↗

The relationship between ankle-arm index and mortality in older men and women.

OBJECTIVE: To determine whether the ankle-arm blood pressure index is a useful predictor of mortality in a large group of patients aged 50 or older. DESIGN: Cohort study over a 13-year period. SETTING: Peripheral vascular laboratory in a hospital affiliated with an academic health center. PARTICIPANTS: 1,027 male and 903 female patients referred for arterial evaluation. OUTCOME MEASURES: All-cause and cause-specific mortality. RESULTS: A decrease in ankle-arm index was a strong independent predictor of all-cause mortality [relative risk (RR) for men = 1.8(95% CI 1.5, 1.9); for women = 1.5, (1.2, 2.0)] and atherosclerotic heart disease mortality [RR for men = 2.0 (1.4, 2.9); for women = 2.1 (1.4, 3.1)]. The risk of mortality was inversely proportional to the ankle-arm index. No relationship was found between the index and mortality due to stroke or cancer. CONCLUSIONS: These results suggest that a decreased ankle-arm index has important prognostic significance for mortality due to atherosclerotic heart disease in older men and women. Measurement of this index may be useful in identifying those at high risk who may benefit from aggressive therapeutic intervention.

Actuarial Analysis↗

Regulation of lymphocyte function by protein phosphorylation.

Variations in protein phosphorylation provide the predominant means of enzymatic regulation now known in biological systems, especially in the regulation of signal transduction from cell surface receptors. Analysis of these signaling pathways has proceeded especially rapidly in lymphocytes, in part because these cells can be isolated with relative ease and can in many cases be maintained in vitro for prolonged periods as clonal populations. During the past few years, both biochemical and genetic evidence has been adduced indicating that the antigen receptors of T and B lymphocytes associate functionally with nonreceptor protein tyrosine kinases. Similar data implicate protein tyrosine kinases in signaling from the CD4 and CD8 coreceptors and the beta chain of the IL-2 receptor. Protein serine/threonine kinases and several different phosphatases also participate in the intracellular propagation of antigen receptor-derived signals. Here we review the lymphocyte surface receptors that are believed to act by altering protein phosphorylation, the kinases and phosphatases that are believed to regulate signal transduction in lymphocytes, and the implications of these results for the broader study of cell signaling mechanisms.

Animals↗

Inhibition of T-cell receptor beta-chain gene rearrangement by overexpression of the non-receptor protein tyrosine kinase p56lck.

The variable region genes of the T cell receptor (TCR) alpha and beta chains are assembled by somatic recombination of separate germline elements. During thymocyte development, gene rearrangements display both an ordered progression, with beta chain formation preceding alpha chain, and allelic exclusion, with each cell containing a single functional beta chain rearrangement. Although considerable evidence supports the view that the individual loci are regulated independently, signaling molecules that may participate in controlling TCR gene recombination remain unidentified. Here we report that the lymphocyte-specific protein tyrosine kinase p56lck, when overexpressed in developing thymocytes, provokes a reduction in V beta--D beta rearrangement while permitting normal juxtaposition of other TCR gene segments. Our data support a model in which p56lck activity impinges upon a signaling process that ordinarily permits allelic exclusion at the beta-chain locus.

Animals↗

Mouse macrophages contain a truncated CD4 transcript.

Mouse macrophages do not express CD4 on their surfaces. We used the polymerase chain reaction to investigate CD4 gene transcription in individual clones of primary mouse splenic macrophages and cell lines of spleen and bone marrow macrophages. The results show only the presence of CD4 mRNA transcripts that are truncated in the 3' coding sequence, thus explaining the lack of expression of a mature CD4 gene product by these cells.

Animals↗

The use of cognitive style mapping as a predictor for academic success of first-semester diploma nursing students.

This study determined the relationship between the components of the cognitive map and the diploma nursing student's successful academic completion of the first semester. This ex post facto study applied the Modified Hill Cognitive Style Model (MHCSM) instrument; the final grade, the dependent variable, was intercorrelated with the instrument's 28 mapping elements. Data analysis indicated three positively correlated predictors: a preference for finding meaning from written words, for independent problem-solving, and for a logical deductive approach in decision-making. Four negatively correlated predictors included a preference for finding meaning from the spoken word, for finding meaning from sight, for problem-solving with peers, and for categorical reasoning. Implications applicable to nursing education are included.

Cognition↗

Germline transcripts of the immunoglobulin heavy-chain and T cell receptor genes in a murine hematopoietic stem cell line LyD9 and its derivative cell lines.

We compared germline transcript levels of immunoglobulin heavy chain and T cell receptor (TcR) genes in a murine hematopoietic stem cell line, LyD9, and its derivative cell lines. LyD9 cells can be induced to differentiate into at least three lineages, namely, B lymphocyte, macrophage, and granulocyte lineages. Although C mu transcripts were found in stem cells to B lymphocytes, other myeloid-committed cells also expressed significant amounts of C mu transcripts. Germline TcR transcripts did not show good correlation with differentiation potential and stages of hematopoietic cells. During this search we identified a novel germline transcript containing the JH-C microliter sequence in LyD9 and some of its derivative cells. Expression of mRNAs for immunoglobulin- and TcR-associated molecules (lambda 5, MB1 and CD3 delta) was widespread except for lambda 5 mRNA. Among three mRNAs encoding putative recombinase proteins, RAG-1 and RAG-2 mRNAs were not expressed in any cell lines tested, while RBP-2 mRNA was expressed ubiquitously.

Animals↗

Human peripheral spatial resolution for achromatic and chromatic stimuli: limits imposed by optical and retinal factors.

1. The aim of this study was to determine whether optical, receptoral or higher-order neural properties limit spatial resolution (acuity) in human vision, especially in the peripheral regions of the visual field. 2. Both achromatic and chromatic stimuli were used, and measures were taken to ensure that the resolution estimates were not contaminated by the detection of spatial sampling artifacts. Spatial contrast sensitivity functions were measured at retinal locations from 0 to 55 deg along the naso-temporal meridian for: (i) discriminating the direction of drift of luminance-modulated (black-white) sinusoidal stimuli drifting at 8 Hz (achromatic task); and (ii) for detecting isoluminant red-green sinusoidal stimuli drifting at 0.4 Hz (chromatic task). Achromatic contrast sensitivity functions were also measured along the vertical meridian for eccentricities of 8 and 40 deg. Each achromatic function was extrapolated to a contrast sensitivity of one (100% contrast) to estimate achromatic acuity. Chromatic acuities were obtained by expressing chromatic contrast in terms of cone contrasts and using the same method of extrapolation. We compared the results with recent data on human optical properties and retinal anatomy. 3. Both achromatic and chromatic acuity decline with distance from the fovea, but at a faster rate than that dictated by the known optical and/or receptoral properties of the human eye. We conclude that, for stimuli of either achromatic or chromatic contrast, peripheral spatial resolution is limited by post-receptoral mechanisms. Also, chromatic acuity declines more steeply than luminance acuity with eccentricity suggesting that there are additional post-receptoral limitations on colour resolution in the periphery. 4. A clear naso-temporal asymmetry is seen in the resolution whose dependence is qualitatively, but not quantitatively, similar to the Nyquist limits imposed by the asymmetric density of human retinal ganglion cells. We discuss the possibility that in peripheral vision (beyond the optic nerve head) the spacing of ganglion cells may pose a fundamental limit on the resolution of achromatic stimuli, but not chromatic stimuli.

Color Perception↗

Spatial summation properties of directionally selective mechanisms in human vision.

Our goal in this paper was to measure psychophysically the receptive-field size of motion units in human vision. To this aim, length and width spatial summation functions were measured for drifting (8-Hz) sinusoidal gratings of spatial frequencies 0.1, 1.0, and 10.0 cycles per degree (c/deg) with two threshold criteria: direction discrimination and simple detection. For each spatial frequency, contrast sensitivity for detection of the direction of drift increased with increasing stimulus size (length or width), at first rapidly (slope greater than or equal to 1.0) and then more gradually (slope 0.29). For most stimuli, the detection and direction-discrimination contrast thresholds were nearly the same. However, for stimuli severely curtailed in width, significantly more contrast was required for direction discrimination than for detection. These results were predicted with a summation model, which incorporated three-dimensional (space-space-time) linear input filters, and probability summation over space and among different filter types. The fit of the model gave an estimate of both the receptive-field length and width of motion-detector units in human vision. At each spatial frequency, the estimates of receptive-field width and length were similar, indicating that the receptive fields of motion-detector units are as long as they are wide at all spatial scales. Receptive-field size varied from approximately 0.12 cycle at 0.1 c/deg to 0.52 cycle at 10.0 c/deg.

Adult↗

Two-dimensional spatial and spatial-frequency selectivity of motion-sensitive mechanisms in human vision.

Thresholds for detecting the direction of motion of drifting (8-Hz) vertical gratings [of spatial frequencies 0.1, 1.0, and 10.0 cycles per degree (c/deg)] were measured in the presence of masks that varied in both spatial frequency and orientation. Masks with different temporal properties were used. The specificity of masking was also measured for a stationary test grating of spatial frequency 3.0 c/deg. After suitable scaling and transformation, the masking data gave an estimate of the two-dimensional spatial-frequency tuning surface of cortical detector units in human vision. With the assumption of small-signal linearity and zero phase, the tuning surfaces were inverse Fourier transformed to give an indication of the size and structure of the psychophysical receptive fields of detector units. The results obtained with drifting test gratings and jittering (random phase) mask gratings indicate that motion-detector receptive fields increase in size (in cycles) with increasing spatial frequency but, at all spatial scales, have a length-width ratio of 1. These results are in close agreement with the summation results reported in J. Opt. Soc. Am. A 8, 1330 (1991). Using the same jittering mask stimuli and stationary test gratings, we confirm reports by Daugman [Vision Res. 24, 891 (1984)] and Harvey and Doan [J. Opt. Soc. Am. A 7, 116 (1990)] that motion-independent units have elongated receptive fields with a length-width ratio near 1.8. We conclude that the receptive fields of motion-dependent and -independent mechanisms in human vision are fundamentally different. The possibility that the orientation selectivity of a motion unit is sharpened by its selectivity for direction of motion is discussed.

Contrast Sensitivity↗

Peripheral spatial vision: limits imposed by optics, photoreceptors, and receptor pooling.

We examined the contribution of optical and photoreceptor properties as well as receptor pooling to eccentricity-dependent variations in spatial vision by comparing the performance of ideal observers with that of human observers. We measured contrast sensitivity functions in human observers and calculated such functions in ideal observers for retinal eccentricities of 0-40 deg. Comparisons of human and ideal performance in a variety of tasks reveal that many aspects of the variation in spatial vision with eccentricity can be understood from an analysis of the discrimination information available at the retinal ganglion cells.

Contrast Sensitivity↗

Mixtures of wheat and high-moisture corn in finishing diets: feedlot performance and in situ rate of starch digestion in steers.

Wheat and high-moisture corn (HMC) were fed singly and in three combinations using dry-rolled wheat (DRW) (ratios of 75:25, 50:50, and 25:75, respectively, Trial 1), or singly and in two combinations using steam-rolled wheat (SRW) (ratios of 67:33 and 33:67, respectively, Trial 2) to finishing beef cattle fed a high-concentrate diet. In situ rate of starch digestion (Trial 3) was measured on grains used in Trial 1 (excluding the 25 HMC: 75 DRW mixture) and ground dry corn. In Trial 1 (132 d), gain/feed did not differ (P greater than .10); however, final weight, hot carcass weight, and ADG decreased linearly (P less than .05) and DMI exhibited a cubic response (P less than .05) as the percentage of wheat in the diet increased. Carcass characteristics were not different. In Trial 2 (113 d), there were no differences attributable to treatment for ADG, DMI, gain/feed, or carcass characteristics. Positive associative responses for gain efficiency (gain/feed) were greatest for the first increment of wheat addition (25% DRW and 33% SRW in Trials 1 and 2, respectively) and for the early portion of the feeding period (57 and 28 d for Trials 1 and 2, respectively), indicating a more rapid diet adaptation and(or) less propensity for subacute acidosis. In Trial 3, the treatment grains or mixtures did not differ in rate of starch digestion. Although the differences were not statistically significant, starch in the 100% wheat diet was digested twice as fast as the 100 or 75% HMC mixtures.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗

Evidence for tau expression in cells of monocyte lineage and its in vitro phosphorylation by v-fms kinase.

The v-fms encoded kinase, which is known to associate with cytoskeletal elements, was shown to phosphorylate histiocytic proteins that had physical and immunological attributes in common with tau. Tau is a microtubule associated protein that is aberrantly phosphorylated in Alzheimer's disease of the brain. Since c-fms expression is normally exclusive to cells of monocyte lineage, these cells were examined for expression of tau. Heat stable tau was identified in cultured peripheral blood monocytes. This represents the first molecular characterization of tau in cells of non-neural origin.

Cell Line↗

Polyacrylamide gel analysis of polypeptides in gene transfer cell lines.

Differential polypeptide expression in gene transfer cell lines of limited genetic complexity was analyzed as a gene mapping strategy. Subcellular fractionation preceding two-dimensional gel electrophoretic analysis simplified protein patterns and revealed subcellular location of differentially expressed polypeptides. As a model system, human MET oncogene polypeptide was identified in gene transfer lines by this approach. Genes encoding five putative human proteins were identified and provisionally assigned to chromosomal region 7q21-31 or to chromosome 1.

Amino Acids↗