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Biomedical subjects

R B Trelease

Publications and source records attributed to R B Trelease.

16 recordsLinked to original sources

A qualitative process system for modeling NF-kappaB and AP-1 gene regulation in immune cell biology research.

An experiment-oriented integrated model of the regulation of the biologically ubiquitous NF-kappaB and AP-1 gene transcription promoters was built by extending a previously developed qualitative process system for simulating cell behavior in the immune system. The core knowledge base (KB) implemented a deep biological ontology including molecular, ultrastructural, cytological, histological, and organismic definitions. KB states, relationships, predicates, and heuristics also represented process interactions between reactive oxygen species, growth factors, and a variety of kinases phosphorylating intermediate molecules in the NF-kappaB and AP-1 regulatory signaling pathways. The system successfully simulated the molecular process steps underlying outcomes of eight different molecular genetics laboratory experiments, including those dealing with NF-kappaB and AP-1 regulation in immunodeficiency virus infection and tumor necrosis factor responses.

Antibody Formation

The virtual anatomy practical: a stereoscopic 3D interactive multimedia computer examination program.

Continuing advances in computer visualization and interface technologies have enabled development of "virtual reality" programs that allow users to perceive and to interact with objects in artificial three-dimensional environments. Such technologies were used to create an image database and program for administering a practical examination in human gross anatomy. Stereoscopic image pairs of prepared laboratory dissections were digitized from multiple views of the thorax, abdomen, pelvic region, and upper and lower extremities. For each view, the stereo pairs were interlaced into a single, field-sequential stereoscopic picture using an image processing program. The resulting color-corrected, interlaced image files were organized in a database stored on a large-capacity hard disk. Selected views were provided with structural identification pointers and letters (A and B). For each view, appropriate two-part examination questions were spoken by a human narrator, digitally recorded, and saved as universal audio format files on the archival hard disk. Images and digital narration were organized in an interactive multimedia program created with a high-level multimedia authoring system. At run-time, 24-bit color 3D images were displayed on a large-screen computer monitor and observed through liquid crystal shutter goggles. A 90-second interval timer and tone were provided to give student users a time limit for each question comparable to that of a conventional practical examination. Users could control the program and select regional "subexams" using a mouse and cursor to point-and-click on screen-level control words ("buttons").

Anatomy, Regional

Toward virtual anatomy: a stereoscopic 3-D interactive multimedia computer program for cranial osteology.

Advances in computer visualization and user interface technologies have enabled development of "virtual reality" programs that allow users to perceive and to interact with objects in artificial three-dimensional environments. Such technologies were used to create an image database and program for studying the human skull, a specimen that has become increasingly expensive and scarce. Stereoscopic image pairs of a museum-quality skull were digitized from multiple views. For each view, the stereo pairs were interlaced into a single, field-sequential stereoscopic picture using an image processing program. The resulting interlaced image files are organized in an interactive multimedia program. At run-time, gray-scale 3-D images are displayed on a large-screen computer monitor and observed through liquid-crystal shutter goggles. Users can then control the program and change views with a mouse and cursor to point-and-click on screen-level control words ("buttons"). For each view of the skull, an ID control button can be used to overlay pointers and captions for important structures. Pointing and clicking on "hidden buttons" overlying certain structures triggers digitized audio spoken word descriptions or mini lectures.

Adult

Qualitative process modeling of cell-cell-pathogen interactions in the immune system.

We present a general cell behavior modelling system for immune functions, based on qualitative process theory. Model system heuristics integrate known characteristics and processes of cells, pathogens, antibodies, antigens, and cytokines. The system generates qualitative simulations of primary immune responses to bacterial and viral infections. Model heuristics can be mapped to a free-running cellular automata-like simulation that demonstrates quantitative behaviors of actor populations. This system serves as a tool for testing assumptions about cellular functions in immunity, as well the basis for a qualitative discovery system that may infer new process heuristics based on evaluation of experimental data.

Artificial Intelligence

Patterns of beat-to-beat heart rate variability in advanced heart failure.

Diminished heart rate variability is associated with high sympathetic tone and an increased mortality rate in heart failure cases. We constructed Poincaré plots of each sinus R-R interval plotted against the subsequent R-R interval from 24-hour Holter recordings of 24 healthy subjects (control group) and 24 patients with heart failure. Every subject in the control group had a comet-shaped Poincaré plot resulting from an increase in beat-to-beat dispersion as heart rate slowed. No patient with heart failure had this comet-shaped pattern. Instead, three distinctive patterns were identified: (1) a torpedo-shaped pattern resulting from low R-R interval dispersion over the entire range of heart rates, (2) a fanshaped pattern resulting from restriction of overall R-R interval ranges with enhanced dispersion, and (3) complex patterns with clusters of points characteristic of stepwise changes in R-R intervals. Poincaré pattern could not be predicted from standard deviations of R-R intervals. This first use of Poincaré plots in heart rate variability analysis reveals a complexity not readily perceived from standard deviation information. Further study is warranted to determine if this method will allow refined assessment of cardiac-autonomic integrity in heart failure, which could help identify patients at highest risk for sudden death.

Death, Sudden

Non-linear dynamics of electrocardiographic waveforms following cocaine administration.

We examined dynamics of ECG waveforms preceding and following 10 mg/kg intravenous administration of cocaine in freely moving cats. Cocaine induced substantial variation in ECG waveforms, as demonstrated by non-linear procedures of phase-plane plots and Poincaré analyses. Phase-plane plots revealed that waveform variation following cocaine administration was not randomly or uniformly distributed, but instead followed patterns of clustered organization with unvisited regions. These patterns are characteristic of chaotic distributions, and support the hypothesis that ECG waveform variation following cocaine does not degenerate into random patterns; instead, the variation follows deterministic, though chaotic patterns.

Animals

Differential effects of scopolamine on nocturnal cortisol secretion, sleep architecture, and REM latency in normal volunteers: relation to sleep and cortisol abnormalities in depression.

Scopolamine (SCOP) (3.0 mu/kg and 6.0 micrograms/kg) and saline were administered intramuscularly at 11:00 PM to eight normal male volunteers in a randomized design, and the effects on the sleep electroencephalogram (EEG) and nocturnal cortisol secretion (via blood sampling every 15 min) were evaluated. Compared to saline, SCOP produced a significant dose-related delay in rapid eye movement (REM) latency. In contrast, neither dose of SCOP significantly affected nocturnal plasma cortisol concentrations. These results suggest that the central cholinergic system that regulates the onset of REM sleep is more sensitive to dysregulation than the cholinergic system that controls the degree of nocturnal cortisol secretion. If central cholinergic overactivity is responsible for both the REM sleep latency and cortisol abnormalities in depressed patients, then our findings with SCOP might help explain why the incidences of these abnormalities are different.

Adult

Respiratory inhibition induced by transient hypertension during sleep in unrestrained cats.

The effects of transient blood pressure elevation, induced by intravenous injection of phenylephrine, were studied in drug-free, unrestrained cats during sleep and waking. Transient hypertension evoked an increase in respiratory cycle duration (Ttot), an effect which was most prominent during quiet sleep. Transient hypertension evoked no overall change in inspiratory duration (Tdi) during any sleep-waking state, although reduction of diaphragmatic EMG amplitude was observed. Thus, the ratio of diaphragmatic activity time to total respiratory cycle duration (Tdi/Ttot) was decreased following blood pressure elevation. Apneic episodes occasionally occurred, and these occurrences were more frequent during sleep states. Apneas induced during quiet sleep were often associated with transient or sustained arousal.

Animals

State-dependent alteration of respiratory cycle timing by stimulation of the central nucleus of the amygdala.

The effect of electrical stimulation of the amygdaloid central nucleus (ACE) on respiration was studied in unanesthetized, unrestrained cats during sleep-waking states. Single 0.5-ms 500-microA constant-current pulses delivered to the ACE at various points on the respiratory cycle, produced a transient inspiratory effort which summated with ongoing inspiratory activity and reduced inspiratory time. Stimulus pulses delivered during the expiratory phase resulted in an earlier shift to inspiration. Repetitive single pulse stimuli delivered to the ACE at a rate slightly faster than the spontaneous respiratory cycle during the alert state, were capable of 'entraining' respiration at the stimulus frequency. This entrainment disappeared in quiet sleep. Atropine, however, which produced synchronous high voltage slow waves and 12-14-Hz EEG spindle activity in the alert cat, did not impair this entrainment. Short (300-500 ms) 100-Hz trains of 0.5-ms pulses to the ACE produced rapid onset, sustained inspiration and a rise in blood pressure in the alert animal. During quiet sleep the response was attenuated but qualitatively similar, and also aroused the animal. Single pulse stimuli, however, were not associated with cardiovascular changes or generalized arousal. These results suggest that the ACE contributes to excitation of the inspiratory cycle, possibly through the large projection of this nucleus to the parabrachial pons.

Amygdala

Sleep states attenuate the pressor response to central amygdala stimulation.

We examined the cardiovascular response to electrical stimulation of the region of the central nucleus of the amygdala during sleep and waking states in the intact cat. Stimulation for 0.5 s produced a profound pressor response in the awake animal. This response was attenuated by quiet sleep and greatly attenuated during REM sleep. The attenuation was present even when the animal aroused from the sleep state in which the stimulus was delivered. The degree of sinus arrhythmia during the bradycardia associated with the hypertensive phase was greater during waking than during quiet sleep. We speculate that REM sleep entails a "functional dissociation" between forebrain and brain stem systems involved in cardiovascular regulation.

Amygdala

Sleep influences on diaphragmatic motor unit discharge.

The discharge of motor units in the costal and crural regions of the diaphragm was studied in unrestrained cats during defined sleep and waking states. Changes in motor unit recruitment and pattern of activity were observed for different sleep-waking states. During periods of active waking, many motor units were recruited and discrimination of single-unit waveforms was difficult. However, in the transition from active to quiet waking, many diaphragmatic motor units ceased discharging, thus making it possible to discern single-unit waveforms. This cessation of motor unit activity continued during the transition from quiet waking (AW) to quiet sleep (QS) and from QS to rapid eye movement (REM) sleep. In some diaphragmatic motor units, discharge stopped completely during REM sleep and resumed only upon arousal. Thus, it was apparent that the recruitment of diaphragmatic motor units was markedly affected by the sleep-waking state. Changes in the patterns of discharge of diaphragmatic motor units also occurred during different sleep-waking states. Motor unit firing rate was typically slower in QS than AW. The rate of motor unit discharge during REM sleep varied considerably. Autocorrelation histograms demonstrated periodic patterns of motor unit discharge within inspiratory bursts. Intervals of repetitive peaks in the autocorrelation histograms ranged from 40 to 110 ms. These periodic patterns were strongest during AW and REM sleep and generally attenuated during QS. Cross-correlation histograms revealed the presence of synchronous activity between motor units in the diaphragm. This coupling of diaphragmatic motor unit discharge was also attenuated during QS compared with AW and REM sleep. Together, these results demonstrated a marked influence of the sleep-waking state on the neuromotor control of the diaphragm.

Animals

Cardiac arrhythmias induced by transient hypertension during sleep-waking states.

Effects of transient hypertension on cardiac rhythm during sleep and waking states in unrestrained cats were investigated. Blood pressure elevation, produced either by phenylephrine injection or by aortic occlusion, was followed by progressive bradycardia in all cats during each sleep-waking state. With phenylephrine, the heart rate response to induced hypertension consisted solely of reflex sinus bradycardia in 67% of the trials, whereas non-sinus cardiac arrhythmias developed during the period of reflex bradycardia in 33% of the trials. In all trials where hypertension was produced by aortic obstruction, non-sinus cardiac arrhythmias occurred. The observed non-sinus rhythms included both atrioventricular junctional and ventricular escape beats. The occurrence of non-sinus arrhythmias after phenylephrine injection was more frequent during sleep states than during waking. Overall, the incidence of escape rhythms varied from a brief burst of non-sinus beats at the onset of bradycardia to repeated trains of non-sinus beats occurring over the span of blood pressure elevation. Respiratory gating of cardiomotor activity was manifested both as respiratory sinus arrhythmia and as inspiratory 'gating' of escape rhythms. Both forms of respiratory gating continued during periods of induced hypertension.

Animals

A new technique for acute and chronic recording of crural diaphragm EMG in cats.

We have developed a percutaneous technique for placement of electromyogram electrodes in cat diaphragmatic crura. The technique is convenient and relatively atraumatic. Guided by external landmarks, small gauge hypodermic needles are used to advance electrodes through implant sites within or in contact with the crural portions of the diaphragm. Satisfactory EMG is reliably obtained from both acute and chronic preparations.

Animals