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Biomedical subjects

C Spence

Publications and source records attributed to C Spence.

At least 19 recordsLinked to original sources

A microfabricated device for sizing and sorting DNA molecules.

We have demonstrated a microfabricated single-molecule DNA sizing device. This device does not depend on mobility to measure molecule size, is 100 times faster than pulsed-field gel electrophoresis, and has a resolution that improves with increasing DNA length. It also requires a million times less sample than pulsed-field gel electrophoresis and has comparable resolution for large molecules. Here we describe the fabrication and use of the single-molecule DNA sizing device for sizing and sorting DNA restriction digests and ladders spanning 2-200 kbp.

Bacteriophage lambda

Cross-modal links in spatial attention.

A great deal is now known about the effects of spatial attention within individual sensory modalities, especially for vision and audition. However, there has been little previous study of possible cross-modal links in attention. Here, we review recent findings from our own experiments on this topic, which reveal extensive spatial links between the modalities. An irrelevant but salient event presented within touch, audition, or vision, can attract covert spatial attention in the other modalities (with the one exception that visual events do not attract auditory attention when saccades are prevented). By shifting receptors in one modality relative to another, the spatial coordinates of these cross-modal interactions can be examined. For instance, when a hand is placed in a new position, stimulation of it now draws visual attention to a correspondingly different location, although some aspects of attention do not spatially remap in this way. Cross-modal links are also evident in voluntary shifts of attention. When a person strongly expects a target in one modality (e.g. audition) to appear in a particular location, their judgements improve at that location not only for the expected modality but also for other modalities (e.g. vision), even if events in the latter modality are somewhat more likely elsewhere. Finally, some of our experiments suggest that information from different sensory modalities may be integrated preattentively, to produce the multimodal internal spatial representations in which attention can be directed. Such preattentive cross-modal integration can, in some cases, produce helpful illusions that increase the efficiency of selective attention in complex scenes.

Attention

Inhibition of return following an auditory cue. The role of central reorienting events.

It is currently controversial whether auditory events produce inhibition of return (IOR). Although some authors argue that this can arise, others propose that peripheral auditory cues do not produce the characteristic IOR pattern of delayed detection latencies for ipsilaterally presented auditory or visual targets, unless a saccade is made to the cued location. We suggest that these previous discrepancies may depend on whether attention is reoriented centrally following the peripheral sound. We presented spatially uninformative peripheral auditory cues prior to visual targets requiring speeded detection responses. IOR was found in the absence of eye movements, provided an auditory reorienting event was presented at central fixation between onset of the peripheral cue and the subsequent target, but not when the central reorienting event was visual. A subsequent experiment demonstrated that auditory IOR between successive targets is similarly significantly reduced in the absence of an appropriate central reorienting event. These results imply that auditory stimuli can induce IOR directly. Previous failures to demonstrate IOR following auditory cues may have been due to an opposing influence of long-lasting attentional facilitation at the cued location, rather than to the putative inability of auditory stimuli to engage oculomotor processes generating IOR.

Acoustic Stimulation

Crossmodal attention.

Most selective attention research has considered only a single sensory modality at a time, but in the real world, our attention must be coordinated crossmodally. Recent studies reveal extensive crossmodal links in attention across the various modalities (i.e. audition, vision, touch and proprioception). Attention typically shifts to a common location across the modalities, despite the vast differences in their initial coding of space. These spatial synergies in attention can be maintained even when receptors are realigned across the modalities by changes in posture. Some crossmodal integration can arise preattentively. The mechanisms underlying these crossmodal links can be examined in a convergent manner by integrating behavioural studies of normal subjects and brain-damaged patients with neuroimaging and neurophysiological studies.

Attention

Cross-modal links in exogenous covert spatial orienting between touch, audition, and vision.

Three experiments investigated cross-modal links between touch, audition, and vision in the control of covert exogenous orienting. In the first two experiments, participants made speeded discrimination responses (continuous vs. pulsed) for tactile targets presented randomly to the index finger of either hand. Targets were preceded at a variable stimulus onset asynchrony (150, 200, or 300 msec) by a spatially uninformative cue that was either auditory (Experiment 1) or visual (Experiment 2) on the same or opposite side as the tactile target. Tactile discriminations were more rapid and accurate when cue and target occurred on the same side, revealing cross-modal covert orienting. In Experiment 3, spatially uninformative tactile cues were presented prior to randomly intermingled auditory and visual targets requiring an elevation discrimination response (up vs. down). Responses were significantly faster for targets in both modalities when presented ipsilateral to the tactile cue. These findings demonstrate that the peripheral presentation of spatially uninformative auditory and visual cues produces cross-modal orienting that affects touch, and that tactile cues can also produce cross-modal covert orienting that affects audition and vision.

Adolescent

Auditory and audiovisual inhibition of return.

Two experiments examined any inhibition-of-return (IOR) effects from auditory cues and from preceding auditory targets upon reaction times (RTs) for detecting subsequent auditory targets. Auditory RT was delayed if the preceding auditory cue was on the same side as the target, but was unaffected by the location of the auditory target from the preceding trial, suggesting that response inhibition for the cue may have produced its effects. By contrast, visual detection RT was inhibited by the ipsilateral presentation of a visual target on the preceding trial. In a third experiment, targets could be unpredictably auditory or visual, and no peripheral cues intervened. Both auditory and visual detection RTs were now delayed following an ipsilateral versus contralateral target in either modality on the preceding trial, even when eye position was monitored to ensure central fixation throughout. These data suggest that auditory target-target IOR arises only when target modality is unpredictable. They also provide the first unequivocal evidence for cross-modal IOR, since, unlike other recent studies (e.g., Reuter-Lorenz, Jha, & Rosenquist, 1996; Tassinari & Berlucchi, 1995; Tassinari & Campara, 1996), the present cross-modal effects cannot be explained in terms of response inhibition for the cue. The results are discussed in relation to neurophysiological studies and audiovisual links in saccade programming.

Adolescent

Audiovisual links in exogenous covert spatial orienting.

Subjects judged the elevation (up vs. down, regardless of laterality) of peripheral auditory or visual targets, following uninformative cues on either side with an intermediate elevation. Judgements were better for targets on either modality when preceded by an uninformative auditory cue on the side of the target. Experiment 2 ruled out nonattentional accounts for these spatial cuing effects. Experiment 3 found that visual cues affected elevation judgments for visual but not auditory targets. Experiment 4 confirmed that the effect on visual targets was attentional. In Experiment 5, visual cues produced spatial cuing when targets were always auditory, but saccades toward the cue may have been responsible. No such visual-to-auditory cuing effects were found in Experiment 6 when saccades were prevented, though they were present when eye movements were not monitored. These results suggest a one-way cross-modal dependence in exogenous covert orienting whereby audition influences vision, but not vice versa. Possible reasons for this asymmetry are discussed in terms of the representation of space within the brain.

Adult

On measuring selective attention to an expected sensory modality.

Perceptual judgments can be affected by expectancies regarding the likely target modality. This has been taken as evidence for selective attention to particular modalities, but alternative accounts remain possible in terms of response priming, criterion shifts, stimulus repetition, and spatial confounds. We examined whether attention to a sensory modality would still be apparent when these alternatives were ruled out. Subjects made a speeded detection response (Experiment 1), an intensity or color discrimination (Experiment 2), or a spatial discrimination response (Experiments 3 and 4) for auditory and visual targets presented in a random sequence. On each trial, a symbolic visual cue predicted the likely target modality. Responses were always more rapid and accurate for targets presented in the expected versus unexpected modality, implying that people can indeed selectively attend to the auditory or visual modalities. When subjects were cued to both the probable modality of a target and its likely spatial location (Experiment 4), separable modality-cuing and spatial-cuing effects were observed. These studies introduce appropriate methods for distinguishing attention to a modality from the confounding factors that have plagued previous normal and clinical research.

Adult

Still alight.

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HIV Infections

Audiovisual links in endogenous covert spatial attention.

In 7 experiments we investigated cross-modal links for endogenous covert spatial orienting in hearing and vision. Participants judged the elevation (up vs. down) of auditory or visual targets regardless of their laterality or modality. When participants were informed that targets were more likely on 1 side, elevation judgments were faster on that side, even if the modality of the target was uncertain. When participants expected a target on a particular side in just 1 modality, corresponding shifts of covert attention also took place in the other modality, as evidenced by faster elevation judgments on that side. However, it was possible to "split" auditory and visual attention when targets in the 2 modalities were expected on constant but opposite sides throughout a block, although covert orienting effects were larger when targets were expected on the same side in both modalities. These results show that although endogenous covert attention does not operate exclusively within a supramodal system, there are strong spatial links between auditory and visual attention.

Adolescent

Humanized antibody directed to the IL-2 receptor beta-chain prolongs primate cardiac allograft survival.

IL-2Rs are expressed by T cells activated in response to foreign histocompatibility Ags but not by normal cells. This difference in IL-2R expression is exploited by blockade of IL-2Rs to achieve immunosuppression. High affinity IL-2Rs involve three subunits, IL-2R alpha, IL-2R beta, and IL-2R gamma. Murine Mik beta 1, a mAb that blocks IL-2 binding to IL-2R beta, was developed as an immunosuppressive agent. There was modest prolongation of cynomolgus cardiac allograft survival in animals treated with murine Mik beta 1 (mean survival 11.8 +/- 1.6 days compared with 8.2 +/- 0.4 days in untreated animals; p = 0.06). However, murine Mik beta 1 is ineffective in recruiting primate effector cells and is neutralized by monkey Abs directed toward the infused Ab. To circumvent these limitations, a humanized form of Mik beta 1, which is a largely human IgG1k Ab, except that murine hypervariable regions are retained, was developed. In vivo plasma survival of humanized Mik beta 1 was threefold longer than simultaneously administered murine Mik beta 1 (terminal t1/2, 104 +/- 10 h vs 37 +/- 2 h). Furthermore, humanized Mik beta 1 manifests Ab-dependent cellular cytotoxicity, an activity that is absent with the parental murine Mik beta 1. Graft survival was significantly prolonged by humanized Mik beta 1 treatment with survivals of 22, 22, 24, 27, 44, and > 300 days (p vs control < 0.01; p vs murine Mik beta 1 < 0.01). Survival was not prolonged further (p > 0.3) by the addition of humanized anti-Tac, which blocks interaction of IL-2 with IL-2R alpha subunits. There was no toxicity attributable to the use of Mik beta 1 Abs. Thus, humanized Mik beta 1 prolonged cardiac allograft survival in primates without toxicity and may be effective as an adjunct to standard immunosuppressive therapy.

Animals

The use of a confirmatory assay to increase the sensitivity and specificity of the Chlamydiazyme test.

The blocking assay was used to reexamine 15,662 patient specimens (2,565 male specimens, 13,097 female specimens) that were submitted for Chlamydia detection using the Chlamydiazyme EIA assay (Abbott Laboratories, North Chicago, IL). Specimens that gave optical density (OD) readings between 1.99 to cutoff and between cutoff to 3 times the negative control in the Chlamydiazyme EIA assay were analyzed further by the blocking assay during the phase 1 study. In the phase 2 study, another 1,120 specimens (473 male specimens and 647 female specimens) that had the above mentioned OD range in the Chlamydiazyme assay were tested with the blocking assay and the direct fluorescent antibody test using the cytospin method. Significant finding from phase 1 study demonstrated that 42.3% of the male specimens with optical density between cutoff to three times the negative control can be blocked by blocking assay (confirmed positive), whereas only 50% of the female specimens with OD range between cutoff to .5 were blocked by the blocking assay. In the phase 2 study, similar results were obtained with the blocking assay. The direct fluorescent antibody test showed excellent correlation with the blocking assay. These data showed that both blocking or direct fluorescent antibody tests can be used for confirmation purposes to increase the sensitivity and specificity of the assay. However, for specimens with OD values below the cutoff to 3 times the negative control, it was necessary to reassess the specimens by either of the methods. This was true especially with the male specimens.

Antibodies, Monoclonal

Cyclooxygenase and lipoxygenase inhibition by BW-755C reduces acrolein smoke-induced acute lung injury.

Inhalation of smoke containing acrolein, the most common toxin in urban fires after carbon monoxide, causes vascular injury with non-cardiogenic pulmonary edema containing potentially edematogenic eicosanoids such as thromboxane (Tx) B2, leukotriene (LT) B4, and the sulfidopeptide LTs (LTC4, LTD4, and LTE4). To determine which eicosanoids are important in the acute lung injury, we pretreated sheep with BW-755C (a combined cyclooxygenase and lipoxygenase inhibitor), U-63557A (a specific Tx synthetase inhibitor), or indomethacin (a cyclooxygenase inhibitor) before a 10-min exposure to a synthetic smoke containing carbon particles (4 microns) with acrolein and compared the results with those from control sheep that received only carbon smoke. Acrolein smoke induced a fall in arterial PO2 and rises in peak inspiratory pressure, main pulmonary arterial pressure, pulmonary vascular resistance, lung lymph flow, and the blood-free wet-to-dry weight ratio. BW-755C delayed the rise in peak inspiratory pressure and prevented the fall in arterial PO2, the rise in lymph flow, and the rise in wet-to-dry weight ratio. Neither indomethacin nor U-63557A prevented the increase in lymph flow or wet-to-dry weight ratio, although they did blunt and delay the rise in airway pressure and did prevent the rises in pulmonary arterial pressure and pulmonary vascular resistance. Thus, cyclooxygenase products, probably Tx, are responsible for the pulmonary hypertension after acrolein smoke and to some extent for the increased airway resistance but not the pulmonary edema. Prevention of high-permeability pulmonary edema after smoke with BW-755C suggests that LTB4, may be etiologic, as previous work has eliminated LTC4, LTD4, and LTE4.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz

Implementing computerized tracking at a community health center: challenges and solutions.

A computerized tracking system for both preventive care and chronic disease tracking was implemented at a community health center, using a PC based local area network interfaced with a mainframe scheduling and billing system. Initial database construction used downloads of historical billing data, but ongoing database maintenance is accomplished by using an optical mark-sense scanner to construct both billing and clinical tracking files from custom-designed encounter forms. In this way, expanded clinical data is collected with an actual reduction in manually keyed data, reducing the ongoing cost of the system.

Ambulatory Care Information Systems

Child abuse and mental health among adolescents in dependent care.

Do adolescents in dependent care who have been abused or neglected demonstrate more mental health problems than their nonabused peers? This study examined relationships of child abuse, depression, and self-esteem among 82 adolescents (mean age 14.5 years, 52% male, 82.9% white) living in a dependent care facility. Of these, 32 adolescents were victims of child abuse or neglect. Upon admission, 54 adolescents were identified as depressed on the Beck Depression Inventory. Initial scores on the depression and self-esteem instruments did not differ by age, race, or history of maltreatment, though trends among subtypes of abuse were identified. Females had significantly lower self-esteem and tended toward more depression. Repeat evaluation 6 months after admission revealed significant improvement in both depression and self-esteem scores for the entire sample. As a group, however, the maltreated adolescents did not demonstrate significant improvement in depression, and a history of neglect was associated with less improvement. Depression in this dependent care sample was common, however, we did not identify the maltreated adolescents as having significantly more problems with self-esteem or depression. For some adolescents, dependent care may be an appropriate and helpful alternative.

Adolescent

Reduced immunogenicity and improved pharmacokinetics of humanized anti-Tac in cynomolgus monkeys.

The anti-Tac mAb has been shown to bind to the p55 chain of the IL-2R, block IL-2 binding and inhibit T cell proliferation. A humanized form of anti-Tac (HAT) has been constructed that retains the binding properties of murine anti-Tac (MAT). These two mAb were evaluated in cynomolgus monkeys to compare relative immunogenicity and pharmacokinetic properties. Monkeys treated with HAT daily for 14 days exhibited anti-HAT antibody titers which were 5- to 10-fold lower than their MAT-treated counterparts and these antibodies developed later than in the MAT-treated monkeys. Two of four monkeys receiving a single injection of MAT developed anti-MAT antibodies, whereas none of four monkeys developed antibodies after a single treatment with HAT. In monkeys injected with either HAT or MAT daily for 14 days, the anti-antibody titers induced were inversely related to the amount of anti-Tac administered. Antibodies that developed against MAT were both anti-isotypic and anti-idiotypic, whereas those developed against HAT appeared to be predominantly anti-idiotypic. The pharmacokinetic properties, that is the half-life and area under the curve values, of HAT were also significantly different from those of MAT. The area under the curve values for HAT in naive monkeys were approximately twofold more than those for MAT, and the mean serum half-life of HAT was 214 h, approximately four- to fivefold more than MAT. These pharmacokinetic values were reduced in monkeys previously sensitized with HAT or MAT suggesting that the presence of anti-antibodies altered these parameters.

Animals