Biomedical subjects

J F Baker

Publications and source records attributed to J F Baker.

At least 19 recordsLinked to original sources

PubMed2003

High-grade surface osteosarcoma in a dog.

A case of a high-grade surface osteosarcoma in the thoracic limb of a dog is reported. Radiographically, there was no bone involvement but there was increased soft tissue opacity. An aggressive osteosarcoma was diagnosed on the basis of early metastatic disease and histopathological examination. Previously reported surface osteosarcomas in the dog have been periosteal and parosteal osteosarcomas which are generally considered to have a low to intermediate biological activity. The tumour described here had radiographical, gross pathological, histopathological and biological features consistent with human high-grade surface osteosarcoma. The characteristics of surface osteosarcomas are briefly reviewed.

Animals↗

PubMed2003

Evaluation of maternal performance of daughters from high and low milk EPD sires.

Angus bulls (n = 24) were selected for either high or low milk EPD, but with similar growth EPD and mated within location (n = 6) at random to Angus cows. Daughters from these matings were bred to calve first at 2 yr of age to common reference sires across locations. Lactation records for 192 daughters were used to evaluate 12-h milk yield, percentage of milk fat and protein, and weaning weight of offspring. Milk production was measured four times during the lactation at regular intervals within location. Dams were separated from their calves the night before milking and milked with a portable milking machine the next morning to estimate 12-h milk yield. A sample of the milk was collected from each cow and analyzed for percentages of milk fat and protein. Data were analyzed as repeated records of the dam. Fixed effects were location, genetic line of sire, gender of calf within location, and milking period, with postpartum interval used as a covariate. Fixed effects and the random effects of sire of dam nested within line, sire of calf, and year were estimated by REML. Genetic line was an important source of variation for milk yield (P < 0.01) and percentage of milk fat (P = 0.03) but not for percentage of milk protein (P = 0.49). Location was significant for all three milk variables (P < 0.01), but the interactions between line and location were not significant. Gender of calf was significant for milk yield (P = 0.04) but not for percentage of milk fat or protein. Line (P = 0.02), location (P = 0.01), calf gender (P = 0.01), and age at weaning (P = 0.01) were significant sources of variation for weaning weight but the interaction of line and location was not (P = 0.69). The correlation coefficient between the sire's milk EPD and 12-h milk yield was significantly different from zero (r = 0.56). The difference between the least squares means for high and low lines for milk yield was 0.66 kg/12 h and the difference was 15.3 kg for weaning weight. The results indicate that there was not evidence for a genotype by environment interaction in milk production for daughters from divergent sires selected for high or low milk EPD.

Animals↗

PubMed2003

Evaluation of age of dam effects on maternal performance of multilactation daughters from high- and low-milk EPD sires at three locations in the southern United States.

Angus bulls (n = 16) selected for either high- or low-milk EPD but similar growth EPD were mated within location at random to Angus cows. Daughters were bred to calve at 2 yr of age and annually until 6 yr of age. Milk yield was measured four times during lactation with a portable milking machine to estimate 12-h milk yield. Milk was collected for analysis of the percentage of fat and protein. A mixed model procedure was used to analyze the weaning weight, milk yield, and milk component data. The model for weaning weight included location, genetic line of sire, gender of calf, and age of dam. Calf age at weaning was used as a covariate. The model for the milk yield and components included location, genetic line of sire, gender of calf, period, and age of dam. Random effects for all models included sire of dam nested within line, sire of calf, and year. Genetic line was a significant source of variation for milk yield (P < 0.01) and weaning weight (P < 0.01) but not for percentage of fat or protein. Location was significant for milk yield (P < 0.01), fat (P < 0.01), protein (P < 0.01), and weaning weight (P < 0.01). The interaction of line with location was not significant except for percentage of protein (P < 0.01). Age of dam was significant for milk yield (P < 0.01), weaning weight (P < 0.01), and percentage of protein (P < 0.01), but not for percentage of fat (P = 0.29). Line difference for mean weaning weight was 18.1 kg, which is similar to the difference between lines for milk EPD (19 kg). Weaning weights from high-milk EPD line daughters were heavier (P < 0.01) than low-milk EPD line daughters at each age of dam evaluated. Cows nursed by males had higher milk yields (4.33 kg/12 h) than cows nursed by heifers (4.0 kg/12 h). The difference in yields for gender was significant for 2-, 3-, and 5-yr-old cows, but not for 4- (P < 0.052) and 6-yr old (P < 0.15) cows. Correlation coefficients between weaning weight and weaning EPD, milk EPD, and total maternal EPD were greater than zero (P < 0.01) (0.76, 0.65, and 0.89, respectively). Daughters of sires with high-milk EPD produced more milk at each age and weaned heavier calves than daughters of sires with low-milk EPD. These results confirm the value of milk EPD for improvement of weaning weights in beef cattle and also validate age of dam effects on milk yield and the associated effects on weaning weights.

Age Factors↗

PubMed2002

Evaluations of genotypexenvironment interactions of beef bulls performance-tested in feedlot or pasture.

Purebred Angus (n = 96) and Polled Hereford (n = 96) bull calves sired by bulls of either low or high yearling weight performance lines were assigned to either creep-fed or non-creep-fed treatment before weaning for four calf crops. For each breed, after weaning in the fall, half of the calves within each of the four groups were fed a high concentrate diet for 189 d after weaning in a feedlot and the remainder were put on winter temporary pastures (rye or ryegrass) followed by summer grazing on pearl millet and bermudagrass pastures for 329 d after weaning. Dependent variables were ADG for various intervals and the complete test period, weight, height and scrotal circumference at periodic intervals, and weight per day of age at regular intervals during the test. The model included breed, performance line, sire nested within breed and line, year, age of dam, preweaning treatment, postweaning treatment, and two- and three-factor interactions. Age of calf was included as a covariate for weight, height, and scrotal circumference measurements. Line and breed differences generally were significant for weight but not for height. The interaction of primary interest (line by preweaning treatment by postweaning treatment) was not significant. The high growth performance line gained faster than low growth performance line for all intervals and were 45 kg heavier by 189 d after weaning. Preweaning treatment did not affect postweaning ADG but did affect weight per day of age. Creep-fed calves were heavier than non-creep-fed calves and maintained this advantage during the postweaning treatment periods in both the feedlot and pasture. Both preweaning treatment groups had similar ADG after weaning. Angus were 23 kg heavier at weaning than Polled Herefords; however, breed weight means were similar by 16 mo of age. In summary, bulls from different selection lines for growth were identified in feedlot and pasture when adjustments were made for prior management effects. The lack of significant interactions in these data indicates that central test station data, appropriately adjusted, are useful for ranking bulls on genetic merit for growth in feedlot and on pasture.

Animal Feed↗

PubMed2001

Directional sensitivity of anterior, posterior, and horizontal canal vestibulo-ocular neurons in the cat.

Neurons subserving the vestibulo-ocular reflex transform the directionality and timing of input from semicircular canals into commands that are appropriate to rotate the eyes in a compensatory fashion. In order to assess the degree to which this transformation is evident in vestibular nucleus neurons of alert cats, we recorded the extracellular discharge properties of 138 second-order vestibular neurons in the superior and medial vestibular nucleus, including 64 neurons identified as second-order vestibulo-ocular neurons by antidromic responses to oculomotor nucleus stimulation and short-latency orthodromic responses to labyrinth stimulation (1.3 ms or less). Neuronal response gains and phases were recorded during 0.5-Hz sinusoidal oscillations about many different horizontal axes and during vertical axis rotations to define neuronal response directionality more precisely than in past studies. Neurons with spatial responses similar to anterior semicircular canal afferents were found to have more diverse maximal activation direction vectors than neurons with responses resembling those of posterior or horizontal canal afferents. The mean angle from neuron response vector to the axis of the nearest canal or canal pair was 19 degrees for anterior canal second-order neurons (n=28) and 20 degrees for anterior canal second-order vestibulo-ocular neurons (n=18), compared with 11 degrees for posterior canal second-order neurons (n=43) and 11 degrees for posterior canal second-order vestibulo-ocular neurons (n=25). Only two second-order vestibulo-ocular neurons (3%) showed a marked dependence of response phase on rotation direction, which is indicative of convergent inputs that differ in both dynamics and directionality. This suggests that spatiotemporal convergence is uncommon in the three-neuron vestibulo-ocular reflex arc of the cat. Neuron vectors included many that were closely aligned with canal axes and several that were better aligned with oblique or superior rectus extraocular muscle excitation axis vectors. Only single examples of second-order vestibulo-ocular neuron vectors were approximately aligned with the pitch and roll coordinate axes. We conclude that second-order vestibulo-ocular neurons do not exclusively represent either the semicircular canal sensory coordinate frame or the extraocular muscle excitation motor coordinate frame, and instead are mostly distributed on a continuum between the input and output coordinate frames, with anterior canal neurons having the widest distribution of directionality.

Action Potentials↗

PubMed2000

Immature CD4+CD8+ thymocytes do not polarize lipid rafts in response to TCR-mediated signals.

TCR-mediated stimulation induces activation and proliferation of mature T cells. When accompanied by signals through the costimulatory receptor CD28, TCR signals also result in the recruitment of cholesterol- and glycosphingolipid-rich membrane microdomains (lipid rafts), which are known to contain several molecules important for T cell signaling. Interestingly, immature CD4(+)CD8(+) thymocytes respond to TCR/CD28 costimulation not by proliferating, but by dying. In this study, we report that, although CD4(+)CD8(+) thymocytes polarize their actin cytoskeleton, they fail to recruit lipid rafts to the site of TCR/CD28 costimulation. We show that coupling of lipid raft mobilization to cytoskeletal reorganization can be mediated by phosphoinositide 3-kinase, and discuss the relevance of these findings to the interpretation of TCR signals by immature vs mature T cells.

Actins↗

PubMed2000

The effect of gravity on the horizontal and vertical vestibulo-ocular reflex in the rat.

Horizontal and vertical eye movements were recorded in alert pigmented rats using chronically implanted scleral search coils or temporary glue-on coils to test the dependence of the vestibulo-ocular reflex (VOR) upon rotation axis and body orientation. The contributions of semicircular-canal versus otolith-organ signals to the VOR were investigated by providing canal-only (vertical axis) and canal plus otolith (horizontal axis) stimulation conditions. Rotations that stimulated canals only (upright yaw and nose-up roll) produced an accurate VOR during middle- and high-frequency rotations (0.2-2 Hz). However, at frequencies below 0.2 Hz, the canal-only rotations elicited a phase-advanced VOR. The addition of a changing gravity stimulus, and thus dynamic otolith stimulation, to the canal signal (nose-up yaw, on-side yaw, and upright roll) produced a VOR response with accurate phase down to the lowest frequency tested (0.02 Hz). In order to further test the dependence of the VOR on gravitational signals, we tested vertical VOR with the head in an inverted posture (inverted roll). The VOR in this condition was advanced in phase across all frequencies tested. At low frequencies, the VOR during inverted roll was anticompensatory, characterized by slow-phase eye movement in the same direction as head movement. The substantial differences between canalonly VOR and canal plus otolith VOR suggest an important role of otolith organs in rat VOR. Anticompensatory VOR during inverted roll suggests that part of the otolith contribution arises from static tilt signals that are inverted when the head is inverted.

Animals↗

PubMed2000

Maternal birth weight breeding value as an additional factor to predict calf birth weight in beef cattle.

A total of 1,028 birth weight (BWT) and gestation length (GL) records were collected for calves from 1994 to 1997 in five U.S. Angus herds. Parental BWT EPD and dam BWT maternal breeding values (MBV) computed from the entire U.S. Angus data base after each breeding season were also available. A full model was fit to BWT that contained contemporary group (CG), sire BWT EPD, dam BWT EPD, and dam BWT MBV. A reduced model that dropped dam BWT MBV was also fit. The full model had smaller (P < .01) sum of squares for error than the reduced model. Calf BWT records were then adjusted for CG. Two data sets were formed to include adjusted BWT progeny records from sires with BWT EPD > or = .75 or > or = 1.0 SD above the mean of sires in the data set. Adjusted birth weights were assigned to either > or = .75 or other < .75 SD and > or = 1.0 or < 1.0 SD categories based on the mean BWT of calves in the entire data set. Dams were assigned to either > or =2 .75 or < .75 SD and > or = 1.0 or < 1.0 SD categories based on dam BWT EPD, MBV, or total maternal genetic contribution (TMGC = EPD + MBV). Chi-square analyses showed that dam BWT EPD, MBV, or TMGC categories were not independent (P < .10) of BWT SD categories, indicating that both dam BWT EPD and BWT MBV provide useful information to attenuate calf BWT. Calf BWT records were then adjusted for the overall mean, CG, sire and dam BWT EPD, and dam BWT MBV. Dams were then assigned to five categories: high dam EPD and MBV (HH), high dam EPD and low MBV (HL), low dam EPD and high MBV (LH), low dam EPD and MBV (LL), and other (OTH). High was > or = .75 or > or = 1.0 SD and low was < .75 or < 1.0 SD based on the mean BWT EPD or MBV of dams in the data set. In all adjusted BWT analyses, HH, HL, and LH categories did not differ (P > .05) from each other; however, the LL category was less (P < .05) than all other categories, indicating that calves from LL dams were lighter at birth than expected. For GL, LL was significantly different (P < .05) from only HH. The large differences in birth weight for the LL dams compared to other groups did not seem to be primarily due to shorter GL. Results showed that MBV provided additional information to control BWT; however, when both dam MBV and EPD were low, birth weight of calves was less than expected. Future research should focus on explanations for this interaction.

Animals↗

PubMed1999

Pharmacokinetics, safety, and tolerability of gadoversetamide injection (OptiMARK) in subjects with central nervous system or liver pathology and varying degrees of renal function.

The pharmacokinetic parameters, safety, and tolerability of OptiMARK (gadoversetamide injection), a gadolinium-based magnetic resonance imaging (MRI) contrast agent, were evaluated in 163 subjects with either central nervous system (CNS) or liver pathology with and without renal insufficiency, for which a contrast-enhanced MRI was indicated. A multicenter, double-blind, randomized, placebo-controlled, parallel-group design was used in which subjects received 0.1, 0.3, or 0.5 mmol/kg of OptiMARK or placebo intravenously. Samples were analyzed for total gadolinium by inductively coupled plasma/mass spectrometry. Gadolinium pharmacokinetics were affected by renal impairment: area under the curve, half-life, and steady-state distribution volume significantly increased with declining renal function, while total body clearance decreased. In subjects with normal renal function, neither age, gender, nor liver versus CNS pathology altered gadolinium pharmacokinetics. No clinically significant changes from baseline were noted in vital signs, laboratory measures, electrocardiograms, or physical examinations. OptiMARK is safe and well-tolerated following a single intravenous injection in subjects with either liver or CNS pathology despite a prolonged elimination half-life in subjects with renal impairment.

Adult↗

PubMed1999

Spatial alignment of rotational and static tilt responses of vestibulospinal neurons in the cat.

The responses of vestibulospinal neurons to 0.5-Hz, whole-body rotations in three-dimensional space and static tilts of whole-body position were studied in decerebrate and alert cats. The neurons' spatial properties for earth-vertical rotations were characterized by maximum and minimum sensitivity vectors (R(max) and R(min)) in the cat's horizontal plane. The orientation of a neuron's R(max) was not consistently related to the orientation of its maximum sensitivity vector for static tilts (T(max)). The angular difference between R(max) and T(max) was widely distributed between 0 degrees and 150 degrees, and R(max) and T(max) were aligned (i.e., within 45 degrees of each other) for only 44% (14/32) of the neurons. The alignment of R(max) and T(max) was not correlated with the neuron's sensitivity to earth-horizontal rotations, or to the orientation of R(max) in the horizontal plane. In addition, the extent to which a neuron exhibited spatiotemporal convergent (STC) behavior in response to vertical rotations was independent of the angular difference between R(max) and T(max). This suggests that the high incidence of STC responses in our sample (56%) reflects not only canal-otolith convergence, but also the presence of static and dynamic otolith inputs with misaligned directionality. The responses of vestibulospinal neurons reflect a complex combination of static and dynamic vestibular inputs that may be required by postural reflexes that vary depending on head, trunk, and limb orientation, or on the frequency of stimulation.

Afferent Pathways↗

PubMed1998

Modeling learning in brain stem and cerebellar sites responsible for VOR plasticity.

A simple model of vestibuloocular reflex (VOR) function was used to analyze several hypotheses currently held concerning the characteristics of VOR plasticity. The network included a direct vestibular pathway and an indirect path via the cerebellum. An optimization analysis of this model suggests that regulation of brain stem sites is critical for the proper modification of VOR gain. A more physiologically plausible learning rule was also applied to this network. Analysis of these simulation results suggests that the preferred error correction signal controlling gain modification of the VOR is the direct output of the accessory optic system (AOS) to the vestibular nuclei vs. a signal relayed through the cerebellum via floccular Purkinje cells. The potential anatomical and physiological basis for this conclusion is discussed, in relation to our current understanding of the latency of the adapted VOR response.

Algorithms↗

PubMed1998

Chronic recording of the vestibulo-ocular reflex in the restrained rat using a permanently implanted scleral search coil.

A technique is described which allows accurate long-term monitoring of eye movements in the rat using permanently implanted scleral search coils. Search coils permanently sutured around the sclera yield vestibulo-ocular reflex (VOR) gain and phase values which are comparable to those reported previously in the literature using acutely implanted coils or electrooculographic electrodes. Considerations related to strain, sex and surgical procedures which permit measurement of responses in the chronically restrained rat are described. VOR gain and phase show a time course to their recovery following the implant surgery, with asymptotic performance typically attained approximately 10 days post-surgically. This technique, with the ability to monitor eye movements over weeks to months, appears ideal for development of rodent models of reflex adaptation which require observation of reflex behavior over extended periods of time. Development of a chronic procedure for monitoring eye movement in rodents is especially important given their initial response to restraint (extensive struggling). Finally, adaptation of this technique to smaller species (e.g., mouse) appears technically feasible which should permit the application of transgenic and knockout techniques to the determination of various vestibular reflex functions requiring long-term monitoring.

Animals↗

PubMed1998

Processing of spatial information by floccular and non-floccular target neurons in the alert cat.

In five alert chronically-prepared cats we studied the response to sinusoidal 3-D whole body rotation of well-isolated vestibular nucleus neurons which were tested for monosynaptic input from the vestibular labyrinth, direct projection to the oculomotor nucleus and, in some cases, inhibition from cerebellar flocculus stimulation. Neurons directly inhibited by flocculus stimulation had significantly greater horizontal-vertical semicircular canal signal convergence than did neurons not inhibited by flocculus stimulation.

Animals↗

PubMed1998

Interdependence of spatial properties and projection patterns of medial vestibulospinal tract neurons in the cat.

Activity of vestibular nucleus neurons with axons in the ipsi- or contralateral medial vestibulospinal tract was studied in decerebrate cats during sinusoidal, whole-body rotations in many planes in three-dimensional space. Antidromic activation of axon collaterals distinguished between neurons projecting only to neck segments from those with collaterals to C6 and/or oculomotor nucleus. Secondary neurons were identified by monosynaptic activation after labyrinth stimulation. A three-dimensional maximum activation direction vector (MAD) summarized the spatial properties of 151 of 169 neurons. The majority of secondary neurons (71%) terminated above the C6 segment. Of these, 43% had ascending collaterals to the oculomotor nucleus (VOC neurons), and 57% did not (VC neurons). The majority of VOC and VC neurons projected contralaterally and ipsilaterally, respectively. Most C6-projecting neurons could not be activated from oculomotor nucleus (V-C6 neurons) and projected primarily ipsilaterally. All VO-C6 neurons projected contralaterally. The distributions of MADs for secondary neurons with different projection patterns were different. Most VOC (84%) and contralaterally projecting VC (91%) neurons had MADs close to the activation vector of a semicircular canal pair, compared with 54% of ipsilaterally projecting VC (i-VC) and 39% of V-C6 neurons. Many i-VC (44%) and V-C6 (48%) neurons had responses suggesting convergent input from horizontal and vertical canal pairs. Horizontal and vertical gains were comparable for some, making it difficult to assign a primary canal input. MADs consistent with vertical-vertical canal pair convergence were less common. Type II yaw or type II roll responses were seen for 22% of the i-VC neurons, 68% of the V-C6 neurons, and no VOC cells. VO-C6 neurons had spatial properties between those of VOC and V-C6 neurons. These results suggest that secondary VOC neurons convey semicircular canal pair signals to both ocular and neck motor centers, perhaps linking eye and head movements. Secondary VC and V-C6 neurons carry more processed signals, possibly to drive neck and forelimb reflexes more selectively. Two groups of secondary i-VC neurons exhibited vertical-horizontal canal convergence similar to that present on neck muscles. The vertical-vertical canal convergence present on many neck muscles, however, was not present on medial vestibulospinal neurons. Spatial transformations achieved by the vestibulocollic reflex may occur in part on secondary neurons but further combination of canal signals must take place to generate compensatory muscle activity.

Animals↗

PubMed1998

Relation between axon morphology in C1 spinal cord and spatial properties of medial vestibulospinal tract neurons in the cat.

Twenty-one secondary medial vestibulospinal tract neurons were recorded intraaxonally in the ventromedial funiculi of the C1 spinal cord in decerebrate, paralyzed cats. Antidromic stimulation in C6 and the oculomotor nucleus identified the projection pattern of each neuron. Responses to sinusoidal, whole-body rotations in many planes in three-dimensional space were characterized before injection of horseradish peroxidase or Neurobiotin. The spatial response properties of 19 neurons were described by a maximum activation direction vector (MAD), which defines the axis and direction of rotation that maximally excites the neuron. The other two neurons had spatio-temporal convergent behavior and no MAD was calculated. Collateral morphologies were reconstructed from serial frontal sections to reveal terminal fields in the C1 gray matter. Axons gave off multiple collaterals that terminated ipsilaterally to the stem axon. Collaterals of individual axons rarely overlapped longitudinally but projected to similar regions in the ventral horn when viewed in transverse sections. The number of primary collaterals in C1 was different for vestibulo-collic, vestibulo-oculo-collic, and C6-projecting neurons: on average one every 1.34, 1.72, and 4.25 mm, respectively. The heaviest arborization and most terminal boutons were seen in the ventral horn, in laminae VIII and IX. Varicosities on terminal branches in lamina IX were observed adjacent to large cell bodies-putative neck motoneurons-in counterstained tissue. Some collaterals had branches that extended dorsally to lamina VII. Neurons with different spatial properties had terminal fields in different regions of the ventral horn. Axons with type I responses and MADs near those of a semicircular canal pair had widely distributed collateral branches and numerous terminations in the dorsomedial, ventromedial, and spinal accessory nuclei and in lamina VIII. Axons with type I responses that suggested convergent canal pair input, with type II responses, and with spatio-temporal convergent behavior had smaller terminal fields. Some neurons with these more complex spatial properties projected to the dorsomedial and spinal accessory but not to the ventromedial nuclei. Others had focused projections to dorsolateral regions of the ventral horn with few branches in the motor nuclei.

Afferent Pathways↗

PubMed1998

Organization of reaching and grasping movements in the primate cerebellar nuclei as revealed by focal muscimol inactivations.

Two monkeys were trained to point to targets and to retrieve fruit bits from a Kluver board, bottles, and tubes. Once proficient in the tasks, the macaques underwent aseptic surgical implantation of a recording chamber over the cerebellar nuclei on the side of their preferred hand. After recovery from surgery, a series of mapping penetrations were completed to identify task-related areas within the cerebellar nuclei. Muscimol (4- 16 microgram; 1-2 microgram/microliter) was pressure injected at different sites within the forelimb zone, and the resultant deficits were observed as the monkeys performed the behavioral tasks. Quantitative measures of task performance were supplemented by direct observation of live and videotaped performance. The locations of nuclear inactivation sites were reconstructed from marking lesions and tracks visible in histological sections. Injections placed in the cerebellar interpositus nucleus and adjacent regions of dentate caused a variety of deficits in forelimb function. A prominent anteroposterior specialization was apparent within the forelimb zone of this intermediate nuclear region. Injections into the anterior interpositus nucleus and adjacent dentate impaired preshaping of the hand and the manipulation of objects, whereas injections placed more posteriorly in posterior interpositus nucleus and adjacent dentate produced deficits in the aiming of reach and the stability of the arm. During anterior injections, the monkeys failed to adequately extend their fingers in preparation for target contact, as documented for >85% of the reaches in the pointing task of monkey J. Up to 38% of the fruit bits it attempted to retrieve from the Kluver board were dropped. In comparison, during posterior inactivations, 15% were dropped and during control conditions 3% were dropped. The monkeys made significantly greater pointing errors during posterior inactivations (11 times for monkey J and 4 times for monkey C) than during anterior inactivations (8 times for monkey J and 2 times for monkey C). We refer to the region producing hand deficits as the anterior hand zone and the region producing reaching deficits as the posterior reach zone. These results are discussed in relation to the problem of achieving spatiotemporal coordination in the large population of nuclear cells that participate in any given movement. The results do not favor the hypothesis that coordination is achieved through a selection of Purkinje cells along beams of parallel fibers. Instead, it is proposed that distal and proximal musculature is coordinated by the adaptive influences of climbing fiber input to Purkinje cells. We envision a relatively nonspecific recruitment of anterior and posterior nuclear cells due to positive feedback in the limb premotor network, which then is shaped into an appropriate spatiotemporal pattern of discharge through the inhibitory input from Purkinje cells.

Animals↗

PubMed1998

Alterations in rat horizontal vestibulo-ocular reflex phase as a function of orientation in gravity.

The effect of changes in static and dynamic gravity signals on the phase accuracy of the horizontal vestibulo-ocular reflex (HVOR) was studied in rats using chronically implanted scleral search coils to monitor eye movements. Rats were sinusoidally rotated using a range of different frequencies (0.035-2 Hz) in a plane which always activated the horizontal semicircular canals but in one of three different orientations with regard to gravity which differentially activated the otolith organs: 1) upright-normal static gravity signal, no dynamic otolith activation; 2) inverted-inverted static gravity signal, no dynamic otolith activation; 3) on-side-dynamic activation of the otolith organs. In the upright orientation, the HVOR shows a phase advance at 0.2 Hz and below but not at 0.5 Hz and above. Phase accuracy of the HVOR was further degraded in the inverted orientation with rats showing large phase leads at 0.2 Hz and below. In contrast, accuracy of the HVOR was significantly improved at 0.2 Hz and below in the on-side orientation with phase accurate eye movements down to the lowest frequency tested. The results further support the idea that otolith organs play an important role in VOR generation by supplementing the semicircular canals' response to angular head movements.

Animals↗

PubMed1997

Monosodium urate, hydroxyapatite, and calcium pyrophosphate crystals induce tumor necrosis factor-alpha expression in a mononuclear cell line.

OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) is thought to be important in chronic inflammation of joints characteristic of crystal induced arthritis. Monocytes are instrumental in maintaining that inflammation. We investigated production of mRNA and protein for TNF-alpha in vitro in a murine mononuclear cell line, after exposure to relevant crystal types. METHODS: Using the cell line designated RAW 264.7, cells were grown in standard medium and exposed to varying amounts of monosodium urate (MSU), hydroxyapatite (HA), and calcium pyrophosphate dihydrate (CPPD) crystals for differing time periods. Analysis of TNF-alpha mRNA induced by such exposure was by Northern hybridization; analysis of TNF-alpha protein was by ELISA: RESULTS: RNA analyses of cells treated with various levels of MSU, HA, and CPPD crystals showed strong induction of TNF-alpha transcripts. ELISA on culture supernatants confirmed high level TNF-alpha peptide secretion resulting from that transcriptional upregulation. Time course studies showed peak accumulation of TNF-alpha mRNA 1-6 h post-treatment. Study of the signalling pathway involved in TNF-alpha transcriptional upregulation indicated that increased phospholipase A2 activity was required. CONCLUSION: These observations suggest that crystals in joints can directly stimulate production of TNF-alpha, and that the source of that cytokine may be the monocytes known to be present and playing an important role in chronic joint disease.

Acetophenones↗