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Biomedical subjects

B Bishop

Publications and source records attributed to B Bishop.

At least 19 recordsLinked to original sources

Swallowing outcomes following laryngectomy and pharyngolaryngectomy.

OBJECTIVES: To determine the incidence of dysphagia (defined as the inability to manage a diet of normal consistencies) at hospital discharge and beyond 1 year postsurgery and examine the impact of persistent dysphagia on levels of disability, handicap, and well-being in patients. DESIGN: Retrospective review and patient contact. SETTING: Adult acute care tertiary hospital. PATIENTS: The study group, consecutively sampled from January 1993 to December 1997, comprised 55 patients who underwent total laryngectomy and 37 patients who underwent pharyngolaryngectomy with free jejunal reconstruction. Follow-up with 36 of 55 laryngectomy and 14 of 37 pharyngolaryngectomy patients was conducted 1 to 6 years postsurgery. MAIN OUTCOME MEASURES: Number of days until the resumption of oral intake; swallowing complications prior to and following discharge; types of diets managed at discharge and follow-up; and ratings of disability, handicap, and distress levels related to swallowing. RESULTS: Fifty four (98%) of the laryngectomy and 37 (100%) of the pharyngolaryngectomy patients experienced dysphagia at discharge. By approximately 3 years postsurgery, 21 (58%) of the laryngectomy and 7 (50%) of the pharyngolaryngectomy patients managed a normal diet. Pharyngolaryngectomy patients experienced increased duration of nasogastric feeding, time to resume oral intake, and incidence of early complications affecting swallowing. Patients experiencing long-term dysphagia identified significantly increased levels of disability, handicap, and distress. Patients without dysphagia also experienced slight levels of handicap and distress resulting from taste changes and increased durations required to complete meals of normal consistency. CONCLUSIONS: The true incidence of patients experiencing a compromise in swallowing following surgery has been underestimated. The significant impact of impaired swallowing on a patient's level of perceived disability, handicap, and distress highlights the importance of providing optimal management of this negative consequence of surgery to maximize the patient's quality of life.

Adult↗

Reengineering granulocyte colony-stimulating factor for enhanced stability.

Granulocyte colony-stimulating factor is a long-chain cytokine that has both biological and therapeutic applications. It is involved in the production and maturation of neutrophilic progenitor cells and neutrophils and is administered to stimulate the production of white blood cells to reduce the risk of serious infection in immunocompromised patients. We have reengineered granulocyte colony-stimulating factor to improve the thermodynamic stability of the protein, focusing on enhancing the alpha-helical propensity of residues in the antiparallel 4-helix bundle of the protein. These redesigns resulted in proteins with substantially enhanced stability while retaining wild-type levels of biological activity, measured as the ability of the reengineered proteins to stimulate the proliferation of murine myeloid cells transfected with the granulocyte colony-stimulating factor receptor.

Animals↗

Ambient temperature modulates hypoxic-induced changes in rat body temperature and activity differentially.

When rats, acclimated to an ambient temperature (T(a)) of 29 degrees C, are exposed to 10% O(2) for 63 h, the circadian rhythms of body temperature (T(b)) and level of activity (L(a)) are abolished, T(b) falls to a hypothermic nadir followed by a climb to a hyperthermic peak, L(a) remains depressed (Bishop B, Silva G, Krasney J, Salloum A, Roberts A, Nakano H, Shucard D, Rifkin D, and Farkas G. Am J Physiol Regulatory Integrative Comp Physiol 279: R1378-R1389, 2000), and overt brain pathology is detected (Krasney JA, Farkas G, Shucard DW, Salloum AC, Silva G, Roberts A, Rifkin D, Bishop B, and Rubio A. Soc Neurosci Abstr 25: 581, 1999). To determine the role of T(a) in these hypoxic-induced responses, T(b) and L(a) data were detected by telemetry every 15 min for 48 h on air, followed by 63 h on 10% O(2) from rats acclimated to 25 or 21 degrees C. Magnitudes and rates of decline in T(b) after onset of hypoxia were inversely proportional to T(a), whereas magnitudes and rates of T(b) climb after the hypothermic nadir were directly proportional to T(a). No hyperthermia, so prominent at 29 degrees C, occurred at 25 or 21 degrees C. The hypoxic depression of L(a) was least at 21 degrees C and persisted throughout the hypoxia. In contrast, T(a) was a strong determinant of the magnitudes and time courses of the initial fall and subsequent rise in T(b). We propose that the absence of hyperthermia at 21 and 25 degrees C as well as a persisting hypothermia may protect the brain from overt pathology.

Abdomen↗

Dramatic structural and thermodynamic consequences of repacking a protein's hydrophobic core.

BACKGROUND: Rop is an RNA binding, dimeric, four-helix bundle protein with a well-defined, regular hydrophobic core ideally suited for redesign studies. A family of Rop variants in which the hydrophobic core was systematically redesigned has previously been created and characterized. RESULTS: We present a structural and thermodynamic analysis of Ala2Ile2-6, a variant of Rop with an extensively redesigned hydrophobic core. The structure of Ala2Ile2-6 reveals a completely new fold formed by a conformational "flip" of the two protomers around the dimeric interface. The free-energy profile of Ala2Ile2-6 is also very different from that of wild-type Rop. Ala2Ile2-6 has a higher melting temperature than Rop, but undergoes a slightly smaller free-energy change on unfolding. CONCLUSIONS: The structure of Ala2Ile2-6, along with molecular modeling results, demonstrate the importance of tight packing of core residues and the adoption of favorable core side chain rotamer values in determining helix-helix interactions in the four-helix bundle fold. Structural disorder at the N and C termini of Ala2Ile2-6 provides a basis for the large differences in the enthalpy and entropy of Ala2Ile2-6 folding compared with wildtype Rop.

Amino Acid Sequence↗

Ventilatory responses to hypercapnia and hypoxia following chronic hypercapnia in the rat.

This study investigated the effects of an 18 week exposure to 10% CO(2) in air on minute ventilation (V(E)), breathing pattern and the chemoresponiveness of rats to hypoxic and hyperoxic stimuli. We found that V(E) remained elevated over the 18 weeks. Nonetheless, the breathing pattern changed significantly. Tidal volume increased and the durations of inspiration and the total cycle decreased. After the sustained hypercapnia the mean Pa(CO(2)) was 72.0+/-5.1 (S. D.) mmHg. Every 6 weeks the chemoresponiveness of the CO(2)-exposed rats was tested by an acute exposure sequentially to room air, then a 6% O(2), 10% CO(2) and 84% N(2) gas mixture, and finally a 90% O(2) in 10% CO(2) mixture. On either room air or the hyperoxic-hypercapnic mixture V(E) fell to its pre-hypercapnic level. On the hypoxic-hypercapnic mixture V(E) increased significantly. These results demonstrate that the initial stimulating effect of 10% CO(2) on V(E) persisted for the entire 18 weeks without altering hypoxic or hyperoxic ventilatory responses.

Animals↗

Circadian rhythms of body temperature and activity levels during 63 h of hypoxia in the rat.

The hypothermic response of rats to only brief ( approximately 2 h) hypoxia has been described previously. The present study analyzes the hypothermic response in rats, as well as level of activity (L(a)), to prolonged (63 h) hypoxia at rat thermoneutral temperature (29 degrees C). Mini Mitter transmitters were implanted in the abdomens of 10 adult Sprague-Dawley rats to continuously record body temperature (T(b)) and L(a). After habituation for 7 days to 29 degrees C and 12:12-h dark-light cycles, 48 h of baseline data were acquired from six control and four experimental rats. The mean T(b) for the group oscillated from a nocturnal peak of 38.4 +/- 0.18 degrees C (SD) to a diurnal nadir of 36.7 +/- 0.15 degrees C. Then the experimental group was switched to 10% O(2) in N(2). The immediate T(b) response, phase I, was a disappearance of circadian rhythm and a fall in T(b) to 36.3 +/- 0.52 degrees C. In phase II, T(b) increased to a peak of 38.7 +/- 0.64 degrees C. In phase III, T(b) gradually decreased. At reoxygenation at the end of the hypoxic period, phase IV, T(b) increased 1.1 +/- 0.25 degrees C. Before hypoxia, L(a) decreased 70% from its nocturnal peak to its diurnal nadir and was entrained with T(b). With hypoxia L(a) decreased in phase I to essential quiescence by phase II. L(a) had returned, but only to a low level in phase III, and was devoid of any circadian rhythm. L(a) resumed its circadian rhythm on reoxygenation. We conclude that 63 h of sustained hypoxia 1) completely disrupts the circadian rhythms of both T(b) and L(a) throughout the hypoxic exposure, 2) the hypoxia-induced changes in T(b) and L(a) are independent of each other and of the circadian clock, and 3) the T(b) response to hypoxia at thermoneutrality has several phases and includes both hypothermic and hyperthermic components.

Activity Cycles↗

Abdominal motor unit activity during respiratory and nonrespiratory tasks.

Abdominal muscles serve multiple roles, but the functional organization of their motoneurons remains unclear. To gain insight, we recorded single motor unit potentials from the internal oblique (IO) and transversus abdominis (TA) muscles of three standing subjects during quiet breathing, a leg lift, and an expiratory threshold load. Inspiratory airflow, recorded from a pneumotachometer, provided tidal volumes and respiratory cycle timing. Fine wires, implanted under ultrasonic imaging, detected single motor unit potentials that were visually distinguished by their spike morphology. From the number of spikes, firing profiles, times of occurrence in the respiratory cycle, and their onset, instantaneous, mean, and peak firing frequencies we deduced that 1) breathing patterns varied across tasks, 2) different motor units were recruited for each task with essentially no overlap, 3) their firing displayed prominent expiratory activity during each task, and 4) the recruitment levels and discharge patterns of IO and TA were different. We conclude that the IO and TA motor pools receive a strong central respiratory drive, yet each pool receives its own distinct, task-dependent synaptic input.

Abdominal Muscles↗

Centralization of low back pain and perceived functional outcome.

McKenzie's methods for evaluating and treating low back pain are used often but studied little. When using the McKenzie system, it is important to observe signs of symptom movement to a central location (centralization). This study investigated the relationships between centralization of low back pain and/or radiculopathy and the subjects' rating of functional outcome. Thirty-six subjects with low back pain volunteered to participate and were evaluated and treated by six researchers. Subjects were tested initially and again 14 days after initiation of treatment using the Oswestry Low Back Pain Disability Questionnaire and the Performance Assessment and Capacity Testing Spinal Function Sort (SFS). Symptoms were monitored for the occurrence of "complete centralization." Of the 36 subjects, 25 showed complete centralization within 14 days. The SFS score changes were significantly higher for subjects who completely centralized (p = 0.015). The results supported the hypothesis that subjects who centralize will have improved functional outcome and, thus, quality of life. However, shorter time to occurrence of complete centralization does not necessarily correlate with improved outcome.

Adult↗

Role of parasympathetic (vagal) cardiac control in elevated heart rates of smokers.

Smokers may develop chronic increases in cardiac rate and alterations in cardiovascular control. If the increased mean heart rate (HR) in cigarette smokers is due in part to a deficit in vagal cardiac rate control, this should be reflected in a decreased amplitude of respiratory sinus arrhythmia (RSA). To test this hypothesis we studied 36 smokers and 36 non-smokers, matched for age, race, gender and blood pressure. All subjects were studied in the supine and seated positions. Mean heart rate was determined from the ECG during 30 s of quiet breathing; RSA was determined for 10 consecutive deep (>50% vital capacity) slow (5-7/min) breaths. Mean HRs in smokers were significantly higher than in non-smokers, but the increases in mean HRs evoked by a shift from the supine to seated position were lower in smokers than in non-smokers, suggesting that chronic tobacco use may alter the relative contributions of sympathetic and parasympathetic control of cardiac rate. Because neither the RSAs nor the position-dependent increase in RSA were different between smokers and non-smokers, we conclude that the elevated mean HRs in smokers were not the result of decreased respiratory or vasomotor modulation of vagal cardiac control, but instead were the result primarily of sympathetic stimulation.

Journal Article↗

Patterns of jaw muscle activity during voluntary chewing.

Mastication is controlled by central rhythm and burst generators, but whether this control is similar under automatic and voluntary chewing is not clear. Our first aim was to determine whether increased chewing frequency led to a proportional decrease in both the burst duration (the time of muscle activity) and the interburst interval (time of inactivity) of each muscle or to a minimal decrease in the burst duration and a substantial decrease in the interburst interval. Our second aim was to determine whether these two manifestations of control differed between the opening and closing muscles. Electromyograms from digastric, medial pterygoid, masseter and anterior temporalis muscles were obtained during gum chewing by five subjects at four frequencies. A nearly fourfold decrease in total cycle duration (TCD) with increased chewing frequencies was accompanied by minimal changes in burst duration in the digastric muscle but proportional changes in the jaw closing muscles. The onset latency of the digastric muscle as a percentage of TCD decreased and became negative (i.e. occurred before opening started) as the TCD decreased. The onset latencies of the jaw closing muscles remained roughly 10-20% of the TCD for the three lower chewing frequencies. Control of the opening muscle appears to differ from control of the closing muscles.

Chewing Gum↗

Depression of an inhibitory reflex, the masseteric silent period, in recovering alcoholics.

Because inhibitory deficits may contribute to motor incoordination of alcoholics, we proposed that the duration of the masseteric silent period (SP), an inhibitory reflex, might be shorter in alcoholics (ALs) than in nonalcoholics (NAs). To test this hypothesis, we measured the SP in a racially mixed group of 12 ALs and 12 NAs matched for age (31-49 years) and sex. All subjects were normotensive, had full dentition, and reported no major medical problems. Sensory and motor conduction velocities of the anterior tibialis, ulnar, and medial nerves were measured for each subject, and were not different in ALs and NAs. Jaw jerk and SP were evoked by tapping the chin manually with a rubber hammer containing a circuit to trigger the oscilloscope display of the masseter EMGs. Averaged mean latencies and durations of the SPs were not significantly different between the right and left masseters. SP latencies were significantly (0.7 msec) shorter in ALs than NAs (p < 0.01). The mean SP duration for ALs (13.9 +/- 1.6 msec) was also significantly shorter than that of the NAs (24.4 +/- 2.4 msec; p < 0.001). Results support the hypothesis that chronic alcoholism may interfere with inhibitory mechanisms in the CNS.

Adult↗

Control of breathing patterns and abdominal muscles during graded loads and tilt.

Tilting from supine to upright purportedly enhances both segmental and pulmonary proprioceptive feedback, whereas an expiratory threshold load (ETL) preferentially enhances pulmonary feedback. To test this we studied 13 adults when supine and 60 degrees and 90 degrees head up. We measured tidal volume, inspiratory duration (TI), and expiratory duration (TE) from flow; estimated end-expiratory lung volume from inspiratory capacity; and determined burst amplitudes and durations from abdominal electromyograms (EMGs). ETLs were incremented from 0 (control) to 25 cmH2O in 5-cmH2O steps. Tidal volume was significantly increased by ETL but was unaffected by body position. Every load prolonged TE, whereas TI remained unchanged. When subjects were supine, abdominal EMGs were silent but became tonically active when subjects were upright. During ETL, abdominal activity became rhythmical and phase locked to expiration. Bursts amplitudes were enhanced with each increment in ETL, but burst durations did not change even though TE was prolonged. The altered breathing pattern and active expiration augmented inspiratory flow and decreased end-tidal PCO2. Responses were greatest when subjects were 90 degrees head up. The load-related increments in abdominal recruitment, with no change in burst durations, fit the concept of two central pattern generators: one controlling pattern and the other controlling rhythm of the central respiratory drive.

Abdominal Muscles↗

Hyperbaric oxygenation increases arousal and breathing movements in fetal lambs.

Oxygenation produced by distending the lungs with 100% O2 increases the occurrence of arousal and fetal breathing movements (FBM), particularly during non-rapid-eye-movement (NREM) sleep, in fetal sheep of > or = 135 days of gestation. We studied the breathing and behavioral responses to a rise in arterial PO2 (PaO2) without lung distension in fetuses between 128 and 132 days of gestation. Twelve fetuses were chronically instrumented to record FBM, behavioral state, blood pressure, arterial blood gas tensions, and pH. Fetal PaO2 was raised by having the ewe breathe 100% O2 at 3 atmosphere absolute pressure spontaneously (group 1, n = 5, 129 +/- 1 days of gestation) or with mechanical ventilation to control fetal arterial PCO2 (group 2, n = 7, 131 +/- 1 days of gestation). Hyperbaric oxygenation raised fetal PaO2 by 20 Torr in both groups. During hyperbaric oxygenation, the occurrence of arousal increased severalfold in both groups. The occurrence of FBM increased during arousal in both groups, during rapid-eye-movement sleep in group 1, and during NREM sleep in group 2. The timing of diaphragmatic activity during arousal and the variability of diaphragmatic activity during NREM sleep were different than those in rapid-eye-movement sleep. We conclude that oxygenation without lung distension increases the occurrence of arousal and of FBM, principally during arousal and NREM sleep, in fetuses of < or = 135 days of gestation.

Animals↗

Kinematics of jaw movements during chewing at different frequencies.

The three-dimensional jaw movement trajectory and its velocity profile were investigated to provide information regarding the motor control of chewing. This was done on a cycle-by-cycle basis across three voluntarily guided chewing frequencies to test the lack of invariance at the velocity level and the evidence for a cost function. The data revealed that an increase in chewing frequencies resulted in a significant reduction of the three-dimensional path, being significantly higher in opening than closing. The ratio of peak speed/three-dimensional distance, a kinematic index of stiffness, increased with increase in chewing frequency; higher stiffness being associated with faster chewing, the stiffness being significantly higher in opening than in closing. The ratio of peak velocity to mean velocity decreased as a function of increase in chewing frequency only at the highest frequency and this decrease again was different in opening than in closing. The results demonstrated that the velocity profile of chewing movements, like that of speech movements, lacked invariance. Rather than minimizing one cost function, the system used an efficient trade-off between time, space and effort, based on the objective of movements.

Adult↗

Lysine requirement of broiler chicks as affected by protein source and method of statistical evaluation.

1. An experiment was designed to test if the lysine requirement, expressed as g lysine/kg CP, was the same for several protein sources. 2. Groundnut meal, groundnut meal adjusted with indispensable amino acids or sesame meal supplied the dietary CP at 180 g/kg diet. Increments of lysine (1.5 g/kg diet) were added to each of these diets. 3. The gain, food intake and food efficiency responses of broiler chicks were analysed using a quadratic equation and a two-slope method. An estimate of lysine requirements was also obtained from a survey of college students. 4. The different methods produced widely different estimates of lysine requirement. 5. The average lysine requirement was estimated at 50.1 g lysine/kg CP for groundnut meal, 61.7 for adjusted groundnut meal and 54.9 for sesame meal. 6. Reasons for the effect of statistical analysis and protein source on lysine requirement are discussed.

Animals↗

Recovery of respiratory sinus arrhythmia in detoxified alcoholic subjects.

Although most alcoholic subjects show little autonomic dysfunction, severe alcoholic subjects may have pathological changes in autonomic nerves. We asked if respiratory sinus arrhythmia amplitude (RSA), an index of vagal cardiac control, is decreased in alcoholism and, if so, whether the decrease is reversed with abstinence. RSA was assessed in 17 normotensive alcoholic subjects (A) at 1, 4, 12, and 24 wk of abstinence after detoxification and at similar intervals in 17 controls (C) matched for age, race, and gender. Subjects were studied in both supine and seated positions while breathing in a prescribed deep (> 50% vital capacity) and slow (5-7/min) pattern. Mean heart rate (HR) was determined over 30 s from the electrocardiogram; RSA (the difference between maximum and minimum instantaneous HRs after inspiratory onset) was determined from 10 consecutive breaths. In C, both HR (supine: 61.5 +/- 2.2 beats/min; seated: 71.3 +/- 1.7 beats/min; P < 0.002) and RSA (supine: 22.5 +/- 1.0 beats/min; seated: 28.4 +/- 1.4 beats/min; P < 0.003) were higher when seated than when supine, but neither HR nor RSA varied over 24 wk. At week 1 of abstinence, HRs for A were higher than those for C (supine: 74.2 +/- 2.3 beats/min, P < 0.001; seated: 83.2 +/- 2.7 beats/min, P < 0.003), but by week 24, both seated and supine values returned to control levels. RSA in A at week 1, was only one-half that of C (supine: 11.1 +/- 1.4 beats/min, P < 0.001; seated: 14.7 +/- 1.9 beats/min, P < 0.001) and independent of body position.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Respiratory and abdominal muscle responses to expiratory threshold loading in cystic fibrosis.

We hypothesized that the hyperinflation and pulmonary dysfunction of cystic fibrosis (CF) would distort feedback and therefore alter the abdominal muscle response to graded expiratory threshold loads (ETLs). We compared the respiratory and abdominal muscle responses with graded ETLs of seven CF patients with severe lung dysfunction with those of matched healthy control subjects in the supine and 60 degrees head-up positions. Breathing frequency, tidal volume, and ventilatory timing were determined from inspiratory flow recordings. Abdominal electromyograms (EMGs) were detected with surface electrodes placed unilaterally over the external and internal oblique and the rectus abdominis muscles. Thresholds, times of onset, and durations of phasic abdominal activity were determined from raw EMGs; peak amplitudes were determined from integrated EMGs. Graded ETLs were imposed by submerging a tube from the expiratory port of the breathing valve into a column of water at depths of 0-25 cmH2O. We found that breathing frequency, tidal volume, and expired minute ventilation were higher in CF patients than in control subjects during low ETLs; a change in body position did not alter these ventilatory responses in the CF patients but did in the control subjects. All CF patients, but none of the control subjects, had tonic abdominal activity while supine. CF patients recruited abdominal muscles at lower loads, earlier in the respiratory cycle, and to a higher recruitment level in both positions than the control subjects, but burst duration of phasic activity was not different between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Muscles↗