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Biomedical subjects

D N Lee

Publications and source records attributed to D N Lee.

At least 19 recordsLinked to original sources

Guiding contact by coupling the taus of gaps.

Animals control contact with surfaces when locomoting, catching prey, etc. This requires sensorily guiding the rate of closure of gaps between effectors such as the hands, feet or jaws and destinations such as a ball, the ground and a prey. Control is generally rapid, reliable and robust, even with small nervous systems: the sensorimotor processes are therefore probably rather simple. We tested a hypothesis, based on general tau theory, that closing two gaps simultaneously, as required in many actions, might be achieved simply by keeping the taus of the gaps coupled in constant ratio. tau of a changing gap is defined as the time-to-closure of the gap at the current closure-rate. General tau theory shows that tau of a gap could, in principle, be directly sensed without needing to sense either the gap size or its rate of closure. In our experiment, subjects moved an effector (computer cursor) to a destination zone indicated on the computer monitor, to stop in the zone just as a moving target cursor reached it. The results indicated the subjects achieved the task by keeping tau of the gap between effector and target coupled to tau of the gap between the effector and the destination zone. Evidence of tau-coupling has also been found, for example, in bats guiding landing using echolocation. Thus, it appears that a sensorimotor process used by different species for coordinating the closure of two or more gaps between effectors and destinations entails constantly sensing the taus of the gaps and moving so as to keep the taus coupled in constant ratio.

Adult↗

Detecting motor abnormalities in preterm infants.

As a consequence of the fragility of various neural structures, preterm infants born at a low gestation and/or birthweight are at an increased risk of developing motor abnormalities. The lack of a reliable means of assessing motor integrity prevents early therapeutic intervention. In this paper, we propose a new method of assessing neonatal motor performance, namely the recording and subsequent analysis of intraoral sucking pressures generated when feeding nutritively. By measuring the infant's control of sucking in terms of a new development of tau theory, normal patterns of intraoral motor control were established for term infants. Using this same measure, the present study revealed irregularities in sucking control of preterm infants. When these findings were compared to a physiotherapist's assessment six months later, the preterm infants who sucked irregularly were found to be delayed in their motor development. Perhaps a goal-directed behaviour such as sucking control that can be measured objectively at a very young age, could be included as part of the neurological assessment of the preterm infant. More accurate classification of a preterm infant's movement abnormalities would allow for early therapeutic interventions to be realised when the infant is still acquiring the most basic of motor functions.

Bottle Feeding↗

Chromium-induced glucose uptake, superoxide anion production, and phagocytosis in cultured pulmonary alveolar macrophages of weanling pigs.

The dose-dependent effects of chromium chloride (CrCl3) and chromium picolinate (CrPic) were evaluated for their glucose uptake, superoxide anion (O2-) production, activity of glucose-6-phosphate dehydrogenase, and phagocytosis of incubated pulmonary alveolar macrophages in medium containing no or 5 x 10(-8)M insulin. Glucose uptake was found to increase in cells treated with 20 microg/L CrCl3. Incubation with 20 microg/L of CrPic enhanced glucose uptake and O2- production in an insulin-dependent manner. However, the inclusion of CrPic to 100 microg/L in the medium absent of insulin also increased O2- production. The activity of glucose-6-phosphate dehydrogenase was not affected by either the addition of Cr or insulin. The phagocytosis of Escherichia coli by macrophages was enhanced significantly (p < 0.05) in medium containing 10-100 microg/L CrCl3 or 20-100 microg/L CrPic in the presence of insulin. These results suggest that the addition of 10-20 microg/L CrCl3 enhances directly the cellular activity of macrophages, whereas the effect of CrPic requires the cooperative action of insulin in enhancing their glucose uptake and phagocytosis.

Animals↗

Sensory and intrinsic coordination of movement.

A recently generalized theory of perceptual guidance (general tau theory) was used to analyse coordination in skilled movement. The theory posits that (i) guiding movement entails controlling closure of spatial and/or force gaps between effectors and goals, by sensing and regulating the tau s of the gaps (the time-to-closure at current closure rate), (ii) a principal way of coordinating movements is keeping the tau s of different gaps in constant ratio (known as tau-coupling), and (iii) intrinsically paced movements are guided and coordinated by tau-coupling onto a tau-guide, tau g, generated in the nervous system and described by the equation tau g = 0.5 (t-T 2/t) where T is the duration of the body movement and t is the time from the start of the movement. Kinematic analysis of hand to mouth movements by human adults, with eyes open or closed, indicated that hand guidance was achieved by maintaining, during 80 85% of the movement, the tau-couplings tau alpha-tau r and tau r-tau g, where tau r is tau of the hand-mouth gap, tau alpha is tau of the angular gap to be closed by steering the hand and tau g is an intrinsic tau-guide.

Adult↗

Evidence for on-line visual guidance during saccadic gaze shifts.

Rapid orientating movements of the eyes are believed to be controlled ballistically. The mechanism underlying this control is thought to involve a comparison between the desired displacement of the eye and an estimate of its actual position (obtained from the integration of the eye velocity signal). This study shows, however, that under certain circumstances fast gaze movements may be controlled quite differently and may involve mechanisms which use visual information to guide movements prospectively. Subjects were required to make large gaze shifts in yaw towards a target whose location and motion were unknown prior to movement onset. Six of those tested demonstrated remarkable accuracy when making gaze shifts towards a target that appeared during their ongoing movement. In fact their level of accuracy was not significantly different from that shown when they performed a 'remembered' gaze shift to a known stationary target (F3,15 = 0.15, p > 0.05). The lack of a stereotypical relationship between the skew of the gaze velocity profile and movement duration indicates that on-line modifications were being made. It is suggested that a fast route from the retina to the superior colliculus could account for this behaviour and that models of oculomotor control need to be updated.

Adult↗

Neonatal control of nutritive sucking pressure: evidence for an intrinsic tau-guide.

Human newborns appear to regulate sucking pressure when bottle feeding by employing, with similar precision, the same principle of control evidenced by adults in skilled behavior, such as reaching (Lee et al., 1998a). In particular, the present study of 12 full-term newborn infants indicated that the intraoral sucking pressures followed an internal dynamic prototype - an intrinsic tau-guide. The intrinsic tau-guide, a recent hypothesis of general tau theory is a time-varying quantity, tau(g), assumed to be generated within the nervous system. It corresponds to some quantity (e.g., electrical charge), changing with a constant second-order temporal derivative from a rest level to a goal level, in the sense that tau(g) equals tau of the gap between the quantity and its goal level at each time t. (tau of a gap is the time-to-closure of the gap at the current closure-rate.) According to the hypothesis, the infant senses tau(p), the tau of the gap between the current intraoral pressure and its goal level, and regulates intraoral pressure so that tau(p) and tau(g), remain coupled in a constant ratio, k; i.e., tau(p)=k tau(g). With k in the range 0-1, the tau-coupling would result in a bell-shaped rate of change pressure profile, as was, in fact, found. More specifically, the high mean r2 values obtained when regressing tau(p) on tau(g), for both the increasing and decreasing suction periods of the infants' suck, supported a strong tau-coupling between tau(p) and tau(g). The mean k values were significantly higher in the increasing suction period, indicating that the ending of the movement was more forceful, a finding which makes sense given the different functions of the two periods of the suck.

Bottle Feeding↗

Modulations in breathing patterns during intermittent feeding in term infants and preterm infants with bronchopulmonary dysplasia.

As infants with bronchopulmonary dysplasia (BPD) have difficulty maintaining adequate levels of oxygenation during rest, it was decided to investigate how the additional respiratory demands associated with nutritive feeding disrupt their breathing rates. The sucking and breathing patterns of six (three male, three female) preterm infants (between 23 and 29 weeks gestational age at birth), classified as having BPD were individually compared with the patterns observed in 12 (six male, six female) healthy term (control) infants (> or = 38 weeks gestational age at birth) with no known respiratory ailments. All infants were recruited from the neonatal unit at Simpson's Maternity Pavilion, Edinburgh, Scotland. In general, the breathing patterns recorded for the infants with BPD during the pause periods of intermittent feeding lacked the striking regularity observed in the term infants. It was found that the severity of the BPD affected breathing rates by significantly reducing the duration and the regularity of a breath (P<0.05) while sucking during the intermittent phase of feeding.

Bronchopulmonary Dysplasia↗

The effectiveness of parents in promoting the development of road crossing skills in young children.

BACKGROUND: Young children show poor judgment when asked to select a safe place to cross the road, frequently considering dangerous sites to be safe. Correspondingly, child pedestrian accidents are over-represented at such locations. Increasing the child's ability to recognise such dangers is a central challenge for road safety education. AIMS: Practical training methods have proved effective in improving such judgments but are labour-intensive, time-consuming and therefore difficult to implement on a realistic scale. The study examined the possibility that volunteers from the local community might be capable of using such methods to promote children's pedestrian competence. SAMPLE: Sixty children from the Primary 1 (Reception) classes of three Glasgow schools took part. Volunteers were ordinary parents from the same areas. None had 'formal' experience of working with children other than through being parents. METHOD: Volunteers received experience of training children at courses organised in each school. Children learned in small groups, receiving two sessions of roadside training followed by four on a table-top model. Pre- and post-tests allowed the effectiveness of training to be assessed. RESULTS: Significant improvements relative to controls were found in all children following training. Improvements proved robust and no deterioration was observed two months after the programme ended. Comparison with a previous study in which training was undertaken by highly qualified staff showed that the volunteers were as effective as 'expert' trainers. CONCLUSIONS: Parent volunteers can significantly increase the pedestrian competence of children as young as five years. They constitute a most valuable 'resource' in road safety education. The opportunities afforded by involving the local community in educational interventions should be further explored.

Accidents, Traffic↗

Lifting weights in neonates: developing visual control of reaching.

To test whether newborn babies take account of external forces in moving their limbs, spontaneous arm-waving movements were measured while the baby lay supine with its head turned to one side. Free-hanging weights, attached to each wrist by strings passing over pulleys, pulled on the arms in the direction of the toes. The results showed the babies applied compensatory forces to keep the hand they faced moving in the same region. In contrast, the (invisible) contra-lateral hand was pulled down by the weights. In a second experiment, where the arms were occluded, both arms were pulled down, suggesting that sight of the arm was necessary in compensating for the weight. In a third, conclusive experiment the babies viewed the arm they were not facing on a small video-monitor and this time the babies kept the visible contra-lateral hand up despite the weights. The results challenge the general view that spontaneous arm movements of neonates are purposeless and either reflexive or due to spontaneous patterned efference to the muscles. Instead, the findings suggest that in waving their arms, neonates are developing visual control of reaching.

Attention↗

[Pre- and intra-operative administration of epidural morphine provides good postoperative pain relief after laminectomy].

BACKGROUND: To evaluate the postoperative analgesic effect of epidural morphine administered at different timing in lumbar spine surgery. METHODS: Eighty-four patients who were scheduled for elective lumbar spine surgery were randomized in three groups. Seventeen patients in group I who received non-steroid analgesics postoperatively (diclophenac sodium 50 mg, iv, q4h) served as control while thirty-six patients in group II who received single dose epidural morphine 3 mg in combination with 10 ml 2% lidocaine given at the lesion site (L4-5 or L5-S1) just before general anesthesia and thirty-one patients in group III who received 3 mg morphine in combination with 3 ml 2% lidocaine administered to the targeted epidural space by means of slow drippings just before wound closure were studied subjects. RESULTS: During the first 24 h postoperatively, the patients in group II and group III suffered a pain which was significantly less in intensity as compared with those in group I (p < 0.05). We used the 10 cm visual analog pain score (VAS) to scale post-operative pain with "no pain" and "worst pain" respectively anchored at 0 and 10 cm. The incidence of side effects such as pruritus, nausea and vomiting was higher in group II and III than in group I. We did not evaluate the occurrence of urinary retention because routine retention urinary catheterization in all patients hampered us to do so. There were no significant differences in the quality and duration of analgesia between group II and III. Respiratory depression of clinical significance was not observed. Neither decrease in oxygen saturation below 92% registered on pulse oximetry nor decrease in respiratory rate below 12 cycles/min was found in the PACU. CONCLUSIONS: Preoperative or intraoperative administration of epidural morphine could provide satisfactory analgesia in lumbar spine surgery during the first 24 h postoperatively.

Adult↗

Discontinuous movements of DNA and RNA in RNA polymerase accompany formation of a paused transcription complex.

A central enigma of transcriptional regulation is how the normally efficient transcription elongation complex stops at pause and termination signals. One possibility, raised by the discovery that RNA polymerase sometimes contracts its DNA footprint, is that discontinuous movements contribute to recognizing these signals. We report that E. coli RNA polymerase responds to sequences immediately downstream and upstream from the his leader pause site by changing neither its downstream DNA contact nor its upstream RNA contact for 8 bp preceding the pause. This compressed complex isomerizes to a paused conformation by an approximately 10 bp jump of its downstream DNA contact and simultaneous extrusion of an RNA hairpin that stabilizes the paused conformation. We suggest pausing and termination could be alternative outcomes of a similar isomerization that depend on the strength of contacts to 3'-proximal RNA remaining after the jump.

Base Sequence↗

The functional significance of arm movements in neonates.

Arm movements made by newborn babies are usually dismissed as unintentional, purposeless, or reflexive. Spontaneous arm-waving movements were recorded while newborns lay supine facing to one side. They were allowed to see only the arm they were facing, only the opposite arm on a video monitor, or neither arm. Small forces pulled on their wrists in the direction of the toes. The babies opposed the perturbing force so as to keep an arm up and moving normally, but only when they could see the arm, either directly or on the video monitor. The findings indicate that newborns can purposely control their arm movements in the face of external forces and that development of visual control of arm movement is underway soon after birth.

Arm↗

Steering by echolocation: a paradigm of ecological acoustics.

1. Flights of three big brown bats (Eptesicus fuscus) landing on a hand and catching a suspended mealworm were video analysed. 2. Results were consistent with the bats using the same basic control procedure in the quite different approach tasks--namely keeping tau (r) = kr and tau (a)/tau (r) = k alpha r. Here r is the current distance to the destination; alpha is the angle between the current direction of the destination and the goal direction of final approach (beta min); tau (r) = r/r, tau (alpha) = alpha/alpha; and kr, k alpha r are constants. 3. The bats were each quite consistent on a particular task (hand or mealworm) in the values they used for the control parameters kr, k alpha r and beta min. However, different values were used in the two tasks, which reflected the different behaviour required at the destination. Flights to hand required twisting and landing upside down and approach angle beta min was closer to vertical and kr was smaller and corresponded to decelerating nearly to a stop. In contrast, the mealworms were caught in mid flight and approach angle beta min was shallower and speed of approach was about constant. 4. tau (r) might be registered acoustically by tau (echo-delay) or by tau (echo-intensity). tau (alpha) might be registered by the bat's directional hearing and gravity sense. 5. The bat's learned the tasks easily, suggesting that the control procedure they used in the experiments was part and parcel of the natural skills they had developed in the wild.

Acoustics↗

Development of prospective control of catching moving objects in preterm at-risk infants.

Healthy term infants and infants classified as neurologically at-risk because of low birthweight and preterm birth were tested longitudinally between 20 and 48 weeks on the ability to use visual information predictively. Reaching for an object moving at different speeds was assessed; the object was occluded from view by a screen during the last part of its approach. At each infant's first reaching session, gaze anticipated the reappearance of the moving toy; however, onset of reaching and prospective control of gaze and hand varied considerably between the normal and at-risk groups. In addition, some at-risk infants geared their actions not to the time but to the distance that the toy was from the catching place, causing problems with faster-moving toys. The two children who anticipated least well were the only two of the at-risk group who were later diagnosed as having cerebral palsy.

Case-Control Studies↗

GreA-induced transcript cleavage in transcription complexes containing Escherichia coli RNA polymerase is controlled by multiple factors, including nascent transcript location and structure.

The Escherichia coli GreA and GreB proteins induce cleavage of 3' fragments from nascent transcripts in halted transcription complexes. We have overproduced and purified the GreA protein and tested how it affects initiation, pausing, and termination by E. coli RNA polymerase. Recombinant GreA induced cleavage of two to three nucleotide fragments in two promoter-proximal complexes, whereas an apparently endogenous cleavage removed a single larger fragment. Both types of cleavage stopped once the transcript was shortened to approximately 10 nucleotides. However, during initiation, GreA induced cleavage of transcripts as short as four nucleotides, inhibiting their release as abortive products and stimulating both productive initiation and "primer-shifting" at a weak promoter. GreA induced repetitive cleavage over a long distance in complexes containing a long G-less nascent transcript. However, reverse translocation was inhibited in transcription complexes that contained a G-rich, C-less nascent transcript. Substituting IMP for GMP in the transcript relieved inhibition. Finally, GreA had little effect on transcription through the his and trp leader pause sites or on termination at nine different p-independent terminators. We propose that transcript cleavage and reverse translocation are controlled in part by backsliding of the nascent transcript through an RNA-binding site.

Bacterial Proteins↗

GreA-induced transcript cleavage is accompanied by reverse translocation to a different transcription complex conformation.

GreA- and GreB-induced transcript cleavage drives reverse translocation of Escherichia coli RNA polymerase on a DNA template in the absence of NTPs (Feng, G.-H., Lee, D. N., Wang, D., Chan, C. L., and Landick, R. (1994) J. Biol. Chem. 269, 22282-22294, accompanying report). During transcript elongation, the sizes of the DNA footprint and the single-stranded transcription bubble vary markedly among transcription complexes halted at different template positions. To test whether transcription complex intermediates formed during transcript cleavage-induced reverse translocation also display heterogeneous conformations at different template positions, we examined the structures of two different transcription complexes before and after GreA treatment. Transcription complexes halted at position +16 after initiation at the T7 A1 promoter or paused at the trpL pause site exhibited strong blocks to transcript cleavage after removal of 6 to 10 nucleotides. In both cases, the down-stream contact between RNA polymerase and DNA moved little during transcript cleavage, thereby increasing its distance from the active site, whereas the upstream DNA contact and the borders of the transcription bubble moved in approximate register with the transcript 3'-end. The backward movements of halted E. coli RNA polymerase are similar to a recently postulated model for discontinuous translocation during transcription, but differ from those reported for arrested RNA polymerase II transcription complexes.

Bacterial Proteins↗

Where we look when we steer.

Steering a car requires visual information from the changing pattern of the road ahead. There are many theories about what features a driver might use, and recent attempts to engineer self-steering vehicles have sharpened interest in the mechanisms involved. However, there is little direct information linking steering performance to the driver's direction of gaze. We have made simultaneous recordings of steering-wheel angle and drivers' gaze direction during a series of drives along a tortuous road. We found that drivers rely particularly on the 'tangent point' on the inside of each curve, seeking this point 1-2 s before each bend and returning to it throughout the bend. The direction of this point relative to the car's heading predicts the curvature of the road ahead, and we examine the way this information is used.

Automobile Driving↗