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Biomedical subjects

S J Anderson

Publications and source records attributed to S J Anderson.

At least 91 records · Page 5Linked to original sources

Post-receptoral undersampling in normal human peripheral vision.

In human far peripheral vision, drifting stimuli of particular periodicities appear to move in the opposite direction from their true direction of motion. This "reverse motion illusion" is a consequence of spatial undersampling of the retinal image. The illusion occurs for spatial frequencies an order of magnitude lower than that expected on the basis of anatomical measurements of human photoreceptor density. We conclude that for naturally imaged stimuli the site of undersampling in far peripheral vision must be post-receptoral.

Contrast Sensitivity↗

A comparison of levels of intrinsic single strand breaks/alkali labile sites associated with human melanoma cell invasion.

Intrinsic levels of protein-free single strand breaks/alkali-labile sites in human melanoma cell populations of varying in vitro invasive capacity have been assayed with DNA filter elution methodology. DNA from two human melanoma cell lines, A375P and C8161, and from a subpopulation selected from A375P, A375P-5, were assayed to test the hypothesis that increased levels of DNA damage may be associated with the phenotype of increased invasive and metastatic capacities. The elution profiles obtained reveal statistically significant increases in the level of single strand breaks and/or alkali-labile sites (SSB/ALS) which correlate with increasing invasive and metastatic capacities. The increased levels of SSB/ALS in A375P-5 observed in freshly selected cells decline as these cells are maintained in culture. The stability of this A375P-5 phenotype correlates with previously reported levels of double minute chromosomes, an indicator of genomic instability. Alterations in average intrinsic levels of cellular lesions are therefore an additional factor to be considered in the phenotypic characterization of invasive and metastatic tumor cells and may reflect or contribute to the genomic instability characteristic of tumor cell populations.

Alkalies↗

Genetic and environmental influences on echocardiographically determined left ventricular mass in black twins.

Genetic and environmental influences on left ventricular mass were examined in normotensive black twins. Left ventricular mass was measured echocardiographically in 7 sets of monozygotic (MZ) and 15 sets of dizygotic (DZ) twins and adjusted for body surface area (LVMI). Regression analyses showed significant effects of gender (R2 = 0.48; P less than .01), systolic blood pressure (R2 = 0.21; P less than .01) and age (R2 = 0.10; P less than .05) on LVMI but did not show an effect for either diastolic blood pressure or caloric expenditure. Monozygotic twins showed smaller within-pair differences (7 +/- 5) than DZ twins (17 +/- 11) for LVMI following adjustment for gender, systolic blood pressure and age (P less than .03). The intraclass correlation for MZ twins was 0.90 (P less than .01) and 0.33 (P = NS) for DZ twins. These results indicate that both genetic and environmental factors are important determinants of left ventricular mass in blacks, independent of gender, blood pressure and age.

Adult↗

Using smoothing splines for detecting ventilatory thresholds.

A recently developed nonparametric regression technique, called a polynomial smoothing spline, is presented for detecting the ventilatory threshold (VT) and respiratory compensation (RC) points from gas exchange response data taken during an incremental exercise test. This type of curve fitting has the advantage of not requiring investigators to specify, a priori, the form of the underlying model, as is required with all linear regression techniques. This procedure yields a mathematically optimal fitted curve through the O2 uptake (VO2) vs CO2 output (VCO2) data and estimates of the process' first and second derivatives. A breakpoint or threshold is indicated by an increase in the value of the derivative and a peak in the second derivative. To evaluate this approach we analyzed gas exchange data collected on nine healthy subjects during a ramp exercise test (15 W.min-1) to the limits of tolerance. Utilizing this procedure we detected VT and RC breakpoints in four subjects and only VT breakpoints in the remaining five subjects. Our results and those obtained using the more conventional linear regression method were similar for those subjects whose RC points were detected using the smoothing spline procedure. However, using regression techniques for subjects with low or otherwise undetectable RC breakpoints, the linear regression method yielded less reliable results in our hands.

Anaerobic Threshold↗

Supplemental fat source affects feedlot performance and carcass traits of finishing yearling steers and estimated diet net energy value.

Two trials that utilized 356 yearling steers were conducted to evaluate the effects of fat sources (3.5% of diet dry matter) in steam-flaked milo finishing diets. Fats differed in fatty acid composition and level of free fatty acids. In Trial 1, soybean oil, tallow and yellow grease were compared to a nonfat control. Feeding fat increased (P less than .05) daily gain, feed efficiency, estimated diet NE concentration, carcass weight and dressing percentage of steers. In Trial 2, fat treatments were control, acidulated soybean soapstock (SBSS), tallow, a blend of 70% SBSS:30% tallow, and yellow grease. Feeding tallow or the SBSS:tallow blend improved (P less than .05) feed efficiency and estimated dietary NE compared to control. Proportions of palmitic, stearic, oleic, linoleic and linolenic acid in longissimus muscle of steers were altered (P less than .05) by source of supplemental fat. Potential variability in animal response to fat blends was demonstrated by differences in animal response to yellow grease in the two trials. It was concluded that fats vary in feeding value and may alter carcass composition, contrary to putative thought. Further, potential associative effects of fat blends and interactions of fat with other dietary components in high-grain finishing diets require further investigation.

Animal Feed↗

The use of permeabilized cells to study the ion requirements of receptor-ligand dissociation in endosomes.

The mannose receptor mediates the transport of high-mannose glycoproteins from the cell surface to lysosomes in macrophages. The binding of ligand to the receptor is dependent on both pH and Ca2+. Upon internalization, ligands enter an acidic pre-lysosomal compartment where receptor-ligand dissociation takes place. Acidification is driven by an endosomal proton pump and anion transport is coupled to this acidification step. A permeabilized-cell assay has been designed to characterize the ionic requirements for receptor-ligand dissociation in endosomes. The plasma membrane of macrophages has been permeabilized selectively with digitonin without affecting endosomal membranes. Receptor-ligand dissociation in permeabilized cells required ATP and was blocked by proton ionophores. Di-isothiocyanostilbene-disulphonic acid and N-ethylmaleimide also blocked dissociation, but mitochondrial ATPase inhibitors and vanadate were ineffective. To explore the nature of the anion requirement for acidification, the ability of different anions to compensate for Cl- was tested. For the halide series, Br- was as equally effective as Cl- in supporting receptor-ligand dissociation, but I- was inhibitory. Citrate and gluconate were only partially effective, while SO4(2-), NO3- and PO4(2-) blocked dissociation. Addition of Ca2+ to permeabilized-cell preparations impaired ATP-dependent dissociation without affecting endosome acidification. These results suggest that the endosomal membrane has a Ca2+ conductance that would permit the rapid efflux of Ca2+ from endosomes during acidification, and this would appear to be a necessary step for efficient sorting of Ca2+-dependent receptors from their ligands.

Adenosine Triphosphate↗

Receptive field properties of human motion detector units inferred from spatial frequency masking.

This study was designed to investigate the spatial frequency selectivity and spatial structure of receptive fields of motion sensitive mechanisms in human vision. Spatial frequency selectivity was inferred from masking measurements, using dynamic test and mask stimuli. For test frequencies between 0.025 and 15.0 c/deg, maximal masking occurred when the mask frequency matched that of the test, suggesting that the test was detected by mechanisms tuned to (or near to) that frequency. For tests below 0.025 c/deg or above 15.0 c/deg, maximal masking occurred at 0.025 and 15.0 c/deg, respectively, suggesting that there exist no mechanisms selective to frequencies outside these limits. A masking model, suitable for interpreting results obtained with drifting test stimuli, was developed and used to calculate spatial frequency selectivity functions from masking data. Assuming small signal linearity, and a constant phase spectrum, the selectivity functions were inverse-Fourier transformed to yield estimates of the extent and structure of receptive fields. Field width was found to vary with test spatial frequency from 5.8 deg at 0.03 c/deg to 0.05 deg at 10.0 c/deg. These estimates were compared with width estimates previously obtained by a summation technique (Anderson & Burr, 1987), and found to be similar over a wide range of spatial frequencies (2.5 log units). Gabor functions provided a reasonable fit to the calculated field profiles at high spatial frequencies (above 1.0 c/deg), but not at low frequencies.

Fourier Analysis↗

Transcription from a murine T-cell receptor V beta promoter depends on a conserved decamer motif similar to the cyclic AMP response element.

We identified a regulatory region of the murine V beta promoter by both in vivo and in vitro analyses. The results of transient transfection assays indicated that the dominant transcription-activating element within the V beta 8.3 promoter is the palindromic motif identified previously as the conserved V beta decamer. Elimination of this element, by linear deletion or specific mutation, reduced transcriptional activity from this promoter by 10-fold. DNase I footprinting, gel mobility shift, and methylation interference assays confirmed that the palindrome acts as the binding site of a specific nuclear factor. In particular, the V beta promoter motif functioned in vitro as a high-affinity site for a previously characterized transcription activator, ATF. A consensus cyclic AMP response element (CRE) but not a consensus AP-1 site, can substitute for the decamer in vivo. These data suggest that cyclic AMP response element-binding protein (ATF/CREB) or related proteins activate V beta transcription.

Animals↗

Differentiation of human B lymphocyte subpopulations induced by an alloreactive helper T-cell clone.

We have used cloned alloreactive helper T cells to determine if direct T cell-B cell interaction can induce differentiation of human peripheral blood B cells which do not respond to pokeweed mitogen (PWM). T-cell clone 2F8 was derived from a one-way mixed lymphocyte reaction. 2F8 cells are T3+T4+T8-IL-2R+ and proliferate in response to irradiated stimulator cells, but not autologous cells, in the absence of exogenous interleukin-2. 2F8 cells provide allospecific help for polyclonal proliferation and differentiation of B cells in the absence of any other stimulus. The magnitude of this response is comparable to that of the response of the same B cells to PWM and fresh autologous T cells. 2F8 cells could also provide nonspecific help for unrelated donor B cells in the presence of PWM, with no requirement for costimulation by irradiated stimulator cells. Allospecific stimulation of B cells was completely inhibited by antibodies to class II major histocompatibility complex (MHC) framework determinants and was abrogated by 1000-rad irradiation. Cloned 2F8 T cells stimulated differentiation of both small, high-density B cells and larger B cells, generating up to 30% plasma cells with either fraction. B cells forming rosettes with mouse erythrocytes were also induced to differentiate by the helper T cell clone. As found previously, neither small, high-density B cells nor mouse rosette+ B cells responded well to PWM. Direct interaction with allospecific T cells induces differentiation of a broader spectrum of B cells than soluble growth and differentiation factors in conjunction with polyclonal activators such as PWM and protein A containing staphylococci.

Adult↗

Using smoothing splines to make inferences about the shape of gas-exchange curves.

Respiratory gas-exchange data from progressive exercise tests are typically interpreted by visual inspection. Attempts to objectify such interpretation have applied particular parametric models which limit the measures which can be studied and the inferences which can be made. We use a known spline-smoothing procedure which fits a continuous curve to such data, yielding confidence intervals for the curve and for its first and second derivatives. Rules can be made which use the derivatives to infer features of a curve's shape and to relate features from different curves in the same data set. In this way complex interpretations can be made objective, so that they may be adequately tested.

Algorithms↗

A conserved sequence in the T-cell receptor beta-chain promoter region.

The antigen-specific receptors of T and B lymphocytes are distinct, though structurally related, molecules. During development, lymphoid cells assemble functional variable (V) region genes for each receptor chain from separate multimember gene families by somatic DNA rearrangements of individual germ-line segments. Transcription may play a role in regulating the tissue and stage specificity of these rearrangements by controlling the accessibility of germ-line loci to the recombinational machinery. Immunoglobulin V-region genes are transcribed from tissue-specific promoters that have been well characterized. We report here the characterization of 14 T-cell receptor beta-chain V-region gene promoters. Sequence analysis indicates that these promoters do not contain the conserved octamer that is located upstream of all immunoglobulin genes. However, a unique decanucleotide sequence, not present in immunoglobulin genes, is conserved in the promoter region of murine and human V beta genes. We identify this sequence as a potential regulatory element, based on its position, conservation, and sequence homology to sites known to bind transcription-activating factors. The possibility that the distinct structures of immunoglobulin and T-cell receptor gene promoters may contribute to the tissue-specific rearrangement and expression of receptor gene families is discussed.

Animals↗

Identification of novel prognostic indicators in burned patients.

The size and depth of burn and patient age are useful early prognostic indicators in burned patients, but have limited value in predicting which patients in a given cohort are likely to die. The objective of this study was to identify additional variables in the first 10 days of burn injury which could better predict patient outcome. Variables consisting of demographic information, routine laboratory data, and clinical observations on 89 burned patients (63 survivors and 26 nonsurvivors) were analyzed. Compared to survivors, nonsurvivors had significantly larger burns (58 +/- 23% vs. 37 +/- 17%; p less than 0.0002) and a higher incidence of Gram-negative septicemia (20 of 26 [77%] vs. 24 of 63 [38%]; p less than 0.001). Potential prognostic variables were subjected to multivariate logistic regression analysis for each of the first 10 days following burn injury in order to identify a combination of parameters which predicted patient outcome. The regression analyses revealed that, as previously demonstrated, patient age and burn size were significant predictors of mortality on admission and throughout the first 10 days postburn. In addition, absolute monocyte count (AMC), absolute lymphocyte count (ALC), maximum daily temperature (Tmax), and BUN were also significant predictors (p less than 0.05). These data indicate that logistic regression models can identify simple prognostic variables in burned patients which may improve clinicians' ability to identify high-risk patients early in the course of their burn injuries.

Adult↗

Escape protein supplementation of yearling steers grazing smooth brome pastures.

Two grazing trials utilizing individually supplemented yearling steers were conducted to study the effect of supplemental escape protein on steer performance during the active growth periods, spring and fall, of smooth brome (Bromus inermis). Graded levels (0, .11, .23 and .34 kg.head-1.d-1) of an equal-protein-basis mixture of bloodmeal and corn gluten meal were offered daily, replacing corn starch, which was used as the negative control. All steers received 582 g supplemental dry matter per day. Supplementation with escape protein improved daily performance in both spring (P less than .01) and fall (P less than .02). Analysis of pooled data from both trials indicated a linear (P less than .01) and quadratic (P less than .05) increase in steer performance with increasing level of escape protein in the diet. Analysis of grass samples collected throughout and composited over each trial demonstrated that grass protein was highly degraded in the rumen. Using a modified dacron bag technique, 12-h degradability was found to be 80 to 90% of the potentially digestible protein fraction. Rates of protein degradability were 14 and 11.7%/h. Assuming 5%/h rate of passage, escape protein was calculated to be 9.2 and 13.1% of total protein. As a result of the significant growth response observed above that of the energy-supplemented controls and the high ruminal protein degradabilities of the grass observed in the laboratory, it was concluded that growing ruminants grazing actively growing smooth brome pastures were deficient in metabolizable protein.

Animal Feed↗

Expression of a murine polyclonal T cell receptor marker correlates with the use of specific members of the V beta 8 gene segment subfamily.

A series of murine T lymphocyte clones were examined for reactivity with the KJ16-133 and F23.1 mAbs. Clones that were KJ16-133+,F23.1+ and KJ16-133-,F23.1+ were identified, but no KJ16-133+,F23.1- clones were observed. Within our panel of clones, therefore, the KJ16-133 antibody identifies a subset of F23.1+ cells. All F23.1+ clones examined express members of the V beta 8 subfamily of beta chain variable region genes; clones expressing V beta 8.1 or V beta 8.2 reacted with both KJ16-133 and F23.1, while clones expressing V beta 8.3 reacted only with F23.1. Thus, the differential reactivity of the KJ16-133 and F23.1 antibodies with cloned T cells correlates with the V beta gene expression of each clone. Reactivity with these antibodies should therefore be of utility for predicting the V beta gene expression in some T cell clones.

Animals↗

Receptive field size of human motion detection units.

Receptive field sizes of motion detector units in the human visual system were determined using a summation technique. Contrast sensitivity was measured for detecting the direction of motion of a drifting (8 Hz) sinewave grating (0.01-30.0 c/deg) multiplied by a stationary Gaussian envelope, for various widths of the Gaussian envelope. For each test spatial frequency, sensitivity increased linearly with aperture width up to a certain limit, and thereafter at a rate consistent with a model incorporating probability summation over space and between channels. The limit of linear summation designates the limit of the receptive field. Results show that the receptive field size varies with spatial frequency, from 2' arc at high spatial frequencies to as large as 7 deg at low frequencies. The change in field size was progressive. The smallest aperture width (delta W) for directional discrimination was also measured. Results show delta W to vary from 0.03 cycles at low spatial frequencies to 0.30 cycles at high frequencies.

Discrimination, Psychological↗

LPS augments human B-cell differentiation by direct stimulation of PWM-responsive B cells.

Bacterial lipopolysaccharide (LPS) augments production of IgM and IgG by two- to seven-fold in cultures of peripheral blood lymphocytes (PBL) stimulated by pokeweed mitogen (PWM), but only if monocytes are rigorously depleted. When PBL were separated into adherent cell (AC), B-cell-enriched, and T-cell-enriched fractions, pulsed with LPS, and recombined in culture with PWM, increased generation of plasma cells was seen only in cultures containing LPS-treated B cells. This effect of LPS appears to be independent of soluble factors. Supernatants from LPS-stimulated B cells or AC did not consistently increase PWM responses when cultured with fresh B cells in the presence of polymyxin B. Furthermore, pulsing of B cells with purified interleukin 1 from two different commercial sources failed to augment PWM-induced differentiation. When B cells were depleted of surface IgD (sIgD)-bearing cells by panning, no effect on LPS-mediated augmentation of PWM-driven differentiation was seen. B cells were also fractionated by rosetting with mouse erythrocytes. Treatment of BMR+ cells with LPS did not induce them to respond to PWM, while treatment of BMR- cells with LPS augmented generation of plasma cells. These results indicate that LPS acts directly to augment differentiation of PWM-responsive B cells, rather than recruiting sIgD+, BMR+ cells to become PWM responsive.

Adult↗