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Biomedical subjects

J Gordon

Publications and source records attributed to J Gordon.

At least 145 records · Page 8Linked to original sources
PubMed1995

Impairments of reaching movements in patients without proprioception. II. Effects of visual information on accuracy.

1. The aim of this study was to determine how vision of a cursor indicating hand position on a computer screen or vision of the limb itself improves the accuracy of reaching movements in patients deprived of limb proprioception due to large-fiber sensory neuropathy. In particular, we wished to ascertain the contribution of such information to improved planning rather than to feedback corrections. We analyzed spatial errors and hand trajectories of reaching movements made by subjects moving a hand-held cursor on a digitizing tablet while viewing targets displayed on a computer screen. The errors made when movements were performed without vision of their arm or of a screen cursor were compared with errors made when this information was available concurrently or prior to movement. 2. Both monitoring the screen cursor and seeing their limb in peripheral vision during movement improved the accuracy of the patients' movements. Improvements produced by seeing the cursor during movement are attributable simply to feedback corrections. However, because the target was not present in the actual workspace, improvements associated with vision of the limb must involve more complex corrective mechanisms. 3. Significant improvements in performance also occurred in trials without vision that were performed after viewing the limb at rest or during movements. In particular, prior vision of the limb in motion improved the ability of patients to vary the duration of movements in different directions so as to compensate for the inertial anisotropy of the limb. In addition, there were significant reductions in directional errors, path curvature, and late secondary movements. Comparable improvements in extent, direction, and curvature were produced when subjects could see the screen cursor during alternate movements to targets in different directions. 4. The effects of viewing the limb were transient and decayed during a period of minutes once vision of the limb was no longer available. 5. It is proposed that the improvements in performance produced after vision of the limb were mediated by the visual updating of internal models of the limb. Vision of the limb at rest may provide configuration information while vision of the limb in motion provides additional dynamic information. Vision of the cursor and the resulting ability to correct ongoing movements, however, is considered primarily to provide information about the dynamic properties of the limb and its response to neural commands.

Adult↗
PubMed1995

Learning a visuomotor transformation in a local area of work space produces directional biases in other areas.

1. The dependence of directional biases in reaching movements on the initial position of the hand was studied in normal human subjects moving their unseen hand on a horizontal digitizing tablet to visual targets displayed on a vertical computer screen. 2. When initial hand positions were to the right of midline, movements were systematically biased clockwise. Biases were counterclockwise for starting points to the left. Biases were unaffected by the screen location of the starting and target positions. 3. Vision of the hand in relation to the target before movement, as well as practice with vision of the cursor during the movement, temporarily eliminated these biases. The spatial organization of the biases suggests that, without vision of the limb, the nervous system underestimates the distance of the hand from an axis or plane that includes its most common operating location. 4. To test the hypothesis that such an underestimate might represent an adaptation to a local area of work space or range effect, subjects were trained to reach accurately from right or left positions. After training, movements initiated from other locations, including ones that were previously error free, showed new biases that again represented underestimates of the distance of the initial hand position from the new trained location. 5. We conclude that hand path planning is dependent on learned representations of the location of the hand in the work space.

Adult↗
PubMed1995

Contrast-dependent responses in the human visual system: childhood through adulthood.

Visual evoked potentials (VEPs) to temporal modulation of spatial patterns, recorded from humans ranging in age from 4-42 years, demonstrated that contrast-dependent responses exist in early childhood and change dramatically throughout childhood. Bright or dark isolated-check stimuli were used to emphasize contributions from ON or OFF pathways to the VEP. (ON and OFF pathways constitute one major pair of parallel subsystems, which process brightness [positive-contrast] and darkness [negative-contrast] information, respectively.) The developmental effects observed for each pathway were similar in magnitude and time course, suggesting maturation of a common physiological mechanism dependent on spatial contrast. Children's responses were more variable and larger than those of adults, and exhibited a relative phase lag. In addition, we recorded transient VEPs to a conventional contrast-reversing checkerboard pattern. The latency of the major positive wave (P100) was found to decrease, while the latency of the initial positive wave (P60) was found to increase, with increasing age. We propose a vector-summation model, which posits a relative decrease in cortical excitation with increasing age, to explain our major findings.

Adolescent↗
PubMed1994

Measurement of nucleoside diphosphate kinase-Nm23 activity by anion-exchange high-performance liquid chromatography.

A first-order assay to detect the activity of nucleoside diphosphate kinase (NDP-kinase; EC 2.7.4.6) was developed. In this assay, the activity of NDP-kinase is measured using various deoxy- and ribonucleotide triphosphates as phosphate donors and dADP as phosphate acceptor. The enzyme activity is determined by quantifying, after anion-exchange HPLC, the amount of newly synthesized dATP. Contrary to the most common coupled enzymic assays or isotopic assays the use of different donor-acceptor pairs is not restricted. The resolution of the procedure described is limited only by the chromatographic separation of substrate and product pairs participating in the reaction.

Animals↗
PubMed1994

Protein tyrosine kinases couple the surface immunoglobulin of germinal center B cells to phosphatidylinositol-dependent and -independent pathways of rescue from apoptosis.

Considerable progress has been made recently in elucidating the intracellular signal transduction pathways which couple surface immunoglobulin (sIg) of resting B lymphocytes (BH) to the proliferative cycle. By contrast, nothing is known of the signals which couple the sIg of germinal center (GC) B cells not to mitogenesis but, instead, to the suppression of apoptosis: the present study examines the signaling pathways through which this response is achieved. GC B cells treated with anti-Ig exhibited enhanced phosphorylation on tyrosine for a number substrates: this was accompanied by a transient increase in inositol 1,4,5-trisphosphate, an increase in [Ca2+]i, and translocation of PKC from the cytosol. These changes could be provoked with Abs specific for IgG or IgA, the major sIg on GC B cells. Herbimycin A, an inhibitor of protein tyrosine kinases (PTK), uncoupled sIg on GC B cells from both the increase in [Ca2+]i and the rescue from apoptosis: the latter was only partially blocked by inhibitors of PKC and chelators of intracellular and extracellular Ca2+. These data indicate that not only do PTK link the antigen receptor (AgR) of GC B cells to both phosphatidylinositol (PI)-dependent and -independent routes of survival but also that tyrosine phosphorylation is critical for sIg-mediated rescue of this population from apoptosis. Moreover, despite the distinct functional responses observed following ligation of the AgR of resting BH lymphocytes and GC B cells, anti-Ig initiates a very similar pattern of second messenger change in these populations suggesting that bifurcation must occur at a more distal stage of the signaling process.

Apoptosis↗
PubMed1994

Occupational lead poisoning: who should conduct surveillance and training?

This commentary challenges the current employer-controlled model for delivering occupational health services. Problems emanating from traditional employer-based medical surveillance and worker education programs for occupational lead poisoning are identified. A new public health model for delivering these services is proposed. This model utilizes a case-based and hazard-based method for bringing workplaces and employers into the program and features direct delivery of surveillance and training services by public health agencies.

Environmental Monitoring↗
PubMed1994

Antibodies to murine CD40 protect normal and malignant B cells from induced growth arrest.

We have previously described the production of polyclonal anti-murine CD40 antibodies that specifically bind recombinant murine CD40 expressed on L cells and induce vigorous proliferation of normal murine B lymphocytes. The current study utilizes these antibodies to explore the distribution and function of CD40 in murine B cell development. Murine CD40 is expressed at high levels by normal splenic B cells and all Ig-positive B cell lymphomas tested to date. It is not expressed by the 70Z/3 pre-B cell line, BaF3 pre-B cell line, or by numerous T cell and myeloid cell lines. 70Z/3 pre-B cells can be induced to express CD40 by LPS stimulation of the cells. Stimulation of purified splenic B cells with anti-CD40 antibodies causes upregulation of class II MHC antigens, CD23, and ICAM-1 and results in extensive aggregation of the cells. Antibodies to murine CD40 are extremely effective at rescuing malignant and normal B cells from induced growth arrest. Anti-CD40 antibodies protect WEHI-231 and CH31 B lymphoma cells from growth arrest induced by soluble anti-IgM antibodies, TGF beta, or a combination of both stimulants. Similarly, anti-IgM preactivated normal splenic B cells which normally die rapidly from growth arrest after 1 or 2 days culture produce a vigorous proliferative response to subsequent stimulation with anti-CD40 antibodies plus IL-4. Interestingly, anti-CD40 antibodies provide little to no protection against B lymphoma growth arrest induced by immobilized anti-IgM antibodies. These data confirm and extend functional properties assigned previously to human CD40 and identify numerous defined murine model systems to explore the molecular basis of CD40-mediated protection from induced B cell growth arrest.

Animals↗
PubMed1994

Physiologically inactive nucleoli contain nucleoplasmic ribonucleoproteins: immunoelectron microscopy of mouse spermatids and early embryos.

Physiologically inactivating or reactivating nucleoli represent a good model to investigate modifications of the nucleolar activity, which influence to a great extent the morphology of this organelle. We have studied the nucleoli of mouse spermatids during gradual inactivation, as well as those of early mouse preimplantation embryos, which undergo reactivation. In the 2-cell systems, inactive nucleoli are represented by homogeneously, finely fibrillar spherical bodies. With the aim of clarifying the composition of these nucleoli, we have analyzed them by means of immunoelectron microscopy using specific antibodies directed against nucleoplasmic snRNPs, hnRNPs, ribosomal proteins, or fibrillarin as well as by cytochemical methods for visualizing DNA and RNA. Our results indicate that RNA is present in zygote and 2-cell nucleolus precursor bodies (NPBs) as well as in 4- to 8-cell or more advanced embryo nucleoli, but not in inactive spermatid nucleoli. DNA is absent from inactive spermatid nucleoli and NPBs but is present within the nucleolus-associated chromatin and the nucleolonema of active nucleoli. The dense masses constituting the NPBs of the zygote and 2-cell embryos contain ribosomal proteins and fibrillarin but also hnRNPs and nucleoplasmic snRNPs. Of these, only fibrillarin is present in the spermatid residual nucleoli.

Animals↗
PubMed1994

Accuracy of planar reaching movements. I. Independence of direction and extent variability.

This study examined the variability in movement end points in a task in which human subjects reached to targets in different locations on a horizontal surface. The primary purpose was to determine whether patterns in the variable errors would reveal the nature and origin of the coordinate system in which the movements were planned. Six subjects moved a hand-held cursor on a digitizing tablet. Target and cursor positions were displayed on a computer screen, and vision of the hand and arm was blocked. The screen cursor was blanked during movement to prevent visual corrections. The paths of the movements were straight and thus directions were largely specified at the onset of movement. The velocity profiles were bell-shaped, and peak velocities and accelerations were scaled to target distance, implying that movement extent was also programmed in advance of the movement. The spatial distributions of movement end points were elliptical in shape. The major axes of these ellipses were systematically oriented in the direction of hand movement with respect to its initial position. This was true for both fast and slow movements, as well as for pointing movements involving rotations of the wrist joint. Using principal components analysis to compute the axes of these ellipses, we found that the eccentricity of the elliptical dispersions was uniformly greater for small than for large movements: variability along the axis of movement, representing extent variability, increased markedly but nonlinearly with distance. Variability perpendicular to the direction of movement, which results from directional errors, was generally smaller than extent variability, but it increased in proportion to the extent of the movement. Therefore, directional variability, in angular terms, was constant and independent of distance. Because the patterns of variability were similar for both slow and fast movements, as well as for movements involving different joints, we conclude that they result largely from errors in the planning process. We also argue that they cannot be simply explained as consequences of the inertial properties of the limb. Rather they provide evidence for an organizing mechanism that moves the limb along a straight path. We further conclude that reaching movements are planned in a hand-centered coordinate system, with direction and extent of hand movement as the planned parameters. Since the factors which influence directional variability are independent of those that influence extent errors, we propose that these two variables can be separately specified by the brain.

Adult↗
PubMed1994

Accuracy of planar reaching movements. II. Systematic extent errors resulting from inertial anisotropy.

This study examines the source of direction-dependent errors in movement extent made by human subjects in a reaching task. As in the preceding study, subjects were to move a cursor on a digitizing tablet to targets displayed on a computer monitor. Movements were made without concurrent visual feedback of cursor position, but movement paths were displayed on the monitor after the completion of each movement. We first examined horizontal hand movements made at waist level with the upper arm in a vertical orientation. Targets were located at five distances and two directions (30 degrees and 150 degrees) from one of two initial positions. Trajectory shapes were stereotyped, and movements to more distant targets had larger accelerations and velocities. Comparison of movements in the two directions showed that in the 30 degrees direction responses were hypermetric, accelerations and velocities were larger, and movement times were shorter. Since movements in the 30 degrees direction required less motion of the upper arm than movements in the 150 degrees direction, we hypothesized that the differences in accuracy and acceleration reflected a failure to take into account the difference in total limb inertia in the two directions. To test this hypothesis we simulated the initial accelerations of a two-segment limb moving in the horizontal plane with the hand at shoulder level when a constant force was applied at the hand in each of 24 directions. We compared these simulated accelerations to ones produced by our subjects with their arms in the same position when they aimed movements to targets in the 24 directions and at equal distances from an initial position. The magnitudes of both simulated and actual accelerations were greatest in the two directions perpendicular to the forearm, where inertial resistance is least, and lowest for movements directed along the axis of the forearm. In all subjects, the directional variation in peak acceleration was similar to that predicted by the model and shifted in the same way when the initial position of the hand was displaced. The pattern of direction-dependent variations in initial acceleration did not depend on the speed of movement. It was also unchanged when subjects aimed their movements toward targets presented within the workspace on the tablet instead of on the computer monitor. These findings indicate that, in programming the magnitude of the initial force that will accelerate the hand, subjects do not fully compensate for direction dependent differences in inertial resistance.(ABSTRACT TRUNCATED AT 400 WORDS)

Acceleration↗
PubMed1994

Xist is expressed in female embryonal carcinoma cells with two active X chromosomes.

The Xist gene resides on the X chromosome and is expressed in female but not male somatic cells. In female cells, only the Xist allele on the inactive X chromosome is transcribed. We investigated the expression of Xist in diploid P10 female embryonal carcinoma cells that have two active X chromosomes. Xist RNA was present in these P10 cells. The X chromosomes in P10 cells carry different Xist alleles whose transcripts can be distinguished by restriction digestion of their cDNAs. Both alleles were expressed. Clones of P10 cells that had lost an X chromosome did not express Xist from the remaining allele. Thus Xist is expressed in cultured cells developmentally arrested prior to X chromosome inactivation, indicating that the Xist transcript is not always derived from an inactive X chromosome. Therefore, Xist expression per se cannot be a sufficient signal to inactivate an X chromosome.

Alleles↗
PubMed1994

Stimulation of human B lymphocytes by phorbol esters reported to be selective in the protein kinase C isoforms they activate.

It is reported here that B cells can be stimulated by two phorbol esters which, in cell free substrate phosphorylation assays, are selective in the PKC isoforms they activate: thymeleatoxin (Thy) stimulates all of the classical (c) or Group A PKCs (alpha, beta 1, beta 2 and gamma) but not PKC delta and epsilon which belong to the novel (n) or Group B PKCs, while 12-deoxyphorbol-13-O-phenylacetate-20-acetate (dPPA) is a specific activator of PKC beta 1. By itself, phorbol 12-myristate, 13-acetate (PMA)--which activates all cPKC and nPKC--was, on a molar basis, some 40-times more potent than either Thy or dPPA which were themselves equipotent at promoting DNA synthesis in resting B cells: the peak response achieved with Thy and dPPA was higher (1.4 x) than that obtained with PMA. In the presence of calcium ionophore, PMA, Thy and dPPA all stimulated a higher (and equivalent) peak response which was achieved at a lower phorbol ester concentration in each case: however, whereas Thy now approached PMA in potency, dPPA remained some 40-times less potent.

B-Lymphocytes↗
PubMed1994

B-cell signalling via the C-type lectins CD23 and CD72.

Although CD23 and CD72 are well-known B-cell signalling molecules, the intracellular signal transduction pathways through which they operate remain poorly elucidated. This may partly reflect their somewhat dubious histories, with claims and counterclaims being made for functions and ligands. Here, John Gordon discusses why such controversy should surround the two B-cell-associated C-type lectins and provides speculation as to their respective roles in regulating an immune response that may be different in mice and humans.

Amino Acid Sequence↗
PubMed1994

Describing color appearance: hue and saturation scaling.

Most of the fully elaborated systems for describing color appearance rely on matching to samples from some standard set. Since this is not satisfactory in all situations, various forms of direct linguistic description have been used, ranging from color naming to continuous numerical scaling of sensations. We have developed and extensively applied a particular variant in which subjects use percentage scales to describe their sensations of the four unique hue sensations (red, yellow, green, blue) and of the apparent saturation of colored lights. In this paper we explore the properties of this procedure, including its statistical properties and reliability both between and within subjects, in different contexts. We conclude that the technique is robust, easy to use, and provides direct access to sensory experience.

Adolescent↗