Biomedical subjects

J F Yang

Publications and source records attributed to J F Yang.

At least 37 records · Page 2Linked to original sources

PubMed1998

Physical association between the EBV protein EBNA-1 and P32/TAP/hyaluronectin.

Epstein-Barr virus (EBV) nuclear antigen-1 (EBNA-1) is a protein expressed constitutively during EBV latency. It is required to support the replication of the EBV genome once per cell cycle via the latent origin of replication, oriP. EBNA-1 also can activate transcription through binding to the family repeats of oriP. We wished to identify candidate cellular protein(s) that may interact with EBNA-1 and mediate these functions. A 32-kd protein was co-immunoprecipitated with EBNA-1 from 293 cells using a monoclonal antibody EBNA.OT1x. The regions of EBNA-1 which interact with this protein were studied using two deletion clones and mapped to EBNA-1 residues 1-102 and 325-357. Deletion of this region was shown previously in a mutant of EBNA-1 which had dominant-negative effects on both DNA replication and transactivation assays. The 32-kd protein was found to react with a polyclonal antiserum against P32/TAP (HIV Tat associated protein), which is known to interact with other RNA binding proteins and the RNA splicing factor SF2. The function of P32 was therefore proposed to involve RNA processing. In addition, this molecule was recently identified as hyaluronectin, which binds hyaluronic acid. Because several reports documented that intracellular hyaluronic acid can potentially affect cell proliferation, the association between EBNA-1 and P32/TAP/hyaluronectin may help the maintenance of episomal viral DNA within proliferating cells.

Animals↗

PubMed1998

Transient disturbances to one limb produce coordinated, bilateral responses during infant stepping.

Transient disturbances were applied to the lower limbs of infants (3-10 mo of age) while they were supported to stepped on a treadmill. The aim was to determine how stepping infants respond to novel disturbances that would disrupt equilibrium during independent walking. Their responses were also compared with those from lower mammals and adult humans. In the first series of experiments, the motion of the limb in the swing phase was transiently stopped by the experimenter grasping the limb for a short time (0.1-1.7 s). During such disturbances, the stance phase was prolonged in the contralateral limb, and the onset of the swing phase was delayed. The degree to which the stepping was modified in the contralateral limb depended on the amount of load experienced by that limb. If the contralateral limb was bearing very little weight at the time of the disturbance, its rhythm did not change appreciably. In the second series of experiments, load was added to the infant by pushing down on the pelvis during the stance phase. This greatly prolonged the stance phase and delayed the swing phase. It did not increase the amplitude of the extensor electromyogram (EMG) of the loaded limb. In conclusion, the neural circuitry controlling stepping in the infants responds to disturbances in an organized fashion that is conducive to maintaining equilibrium and forward progression.

Biomechanical Phenomena↗

PubMed1997

NG108-15 cells express neuregulin that induces AChR alpha-subunit synthesis in cultured myotubes.

A cholinergic neuroblastoma x glioma hybrid cell line NG108-15 is able to form functional synapses, and contains both AChR-aggregating and AChR-inducing activities when cocultured with myotubes. Several lines of evidence indicate that the AChR-inducing activity of NG108-15 cells is derived from neuregulin. The conditioned medium of cultured NG108-15 cells induced the expression of AChR alpha-subunit as well as the tyrosine phosphorylation of erbB-3 receptor. NG108-15 cells expressed neuregulin with a protein of approximately 100 kDa in size and transcripts of approximately 6.8 kbp, approximately 2.6 kbp and approximately 1.8 kbp; mRNAs encoding beta1 and alpha2 isoforms of neuregulin were revealed. NG108-15 cells were induced to differentiate by chemicals, and the chemical-induced differentiation of NG108-15 cells increased the level of neuregulin mRNA expression approximately 3-fold while the expression of a housekeeping gene remained relatively unchanged. The activity of neuregulin in the conditioned medium of NG108-15 cells was reduced by treating the medium with heparin and anti-neuregulin antibody. In addition, NG108-15 cells were transfected with antisense neuregulin cDNA and its expression of neuregulin was reduced, while its neuregulin-induced tyrosine phosphorylation activity was markedly decreased. This is the first direct demonstration that the NG108-15 cell-induced AChR upregulation on cultured myotubes is mediated by neuron-derived neuregulin.

Animals↗

PubMed1997

The EGF-like domain of chick acetylcholine receptor-inducing activity (ARIA) contains its full biological activity.

Acetylcholine receptor-inducing activity (ARIA) is a glycoprotein initially purified from chick brain based on its ability to increase the synthesis of acetylcholine receptor (AChR) on cultured myotubes. cDNA encoding ARIA contains different domains and the functions of each domain in ARIA activity are not known. We used molecular genetic methods to construct a chimeric fusion protein, designated ARIA(S136-K205)-Fc, that contained the leader sequence, the EGF-like domain of chick ARIA (S136 to K205) and the Fc region of human immunoglobulin. The ARIA(S136-K205)-Fc cDNA was transfected into HEK 293 cells and stable cell lines secreting soluble ARIA(S136-K205)-Fc were obtained. The secreted ARIA(S136-K205)-Fc has a molecular mass of approximately 60 kDa and can be purified by protein G chromatography. The purified ARIA(S136-K205)-Fc retained its full biological activity of chick ARIA that included: (i) induction of tyrosine phosphorylation of erbB 3 receptor in C2C12 myotubes; and (ii) approximately 12-fold stimulation of AChR alpha-subunit mRNA synthesis when applied onto cultured chick myotubes. This Fc-tagged ARIA could be rapidly purified and provides a very useful ligand for identifying its true receptor(s) on muscle cell surface.

Animals↗

PubMed1997

Chick muscle expresses various ARIA isoforms: regulation during development, denervation, and regeneration.

Acetylcholine receptor inducing activity (ARIA) is a glycoprotein released from the motor neuron to stimulate the synthesis of acetylcholine receptors (AChRs) on the postsynaptic muscle fiber. Transcripts encoding ARIA were detected not only in brain but also in muscle, and immunohistochemical staining showed that muscle-derived ARIA was restricted to the neuromuscular junctions. RT-PCR analysis revealed three biological active isoforms of ARIA in chick muscle, namely ARIA beta 1, ARIA alpha 2, and ARIA beta 2 that were classified based on their variation in the carboxylterminus of the EGF-like domain. The expression of these ARIA isoforms in muscle change during development denervation, and nerve regeneration. ARIA beta 1, ARIA alpha 2, and ARIA beta 2 were expressed in embryonic and young chick muscles, while ARIA beta 1 was the major isoform expressed in adult chicken. The embryonic-like expression of ARIA alpha 2 and ARIA beta 2 was induced after nerve injury in adult chicken. However, the prominent expression of ARIA beta 1 in adult-like profile was restored after nerve regeneration. A splicing variation in the region between Ig-like and EGF-like domains of ARIA was also revealed; a zero-amino acid insertion (ARIASP0), a 17-amino acid insertion (ARIASP17), or a 34-amino acid insertion (ARIASP34) were identified. Unlike ARIASP0, the expression of ARIASP17 and ARIASP34 was found in muscle and sciatic nerve only. The expression of ARIASP0, ARIASP17, and ARIASP34 in chick muscle remained unchanged during development and after nerve injury. Moreover, the specific expression of these ARIA isoforms in cultured myotubes was not affected by drug treatments or by coculturing with neurons. Our findings provide strong evidence that muscle ARIA may play an important role in the formation of neuromuscular junctions.

Aging↗

PubMed1997

Agrin-deficient myotube retains its acetylcholine receptor aggregation ability when challenged with agrin.

Agrin is a synapse-organizing molecule that mediates the nerve-induced aggregation of acetylcholine receptors (AChRs) and other postsynaptic components at the developing and regenerating vertebrate neuromuscular junctions. At the neuromuscular junction, three different cell types can express agrin, i.e., neuron, muscle, and Schwann cell. Several lines of evidence suggested that neuron-derived agrin is the AChR-aggregating factor, but the possible roles of muscle-derived agrin in the formation of AChR aggregate are not known. By using the recombinant DNA method, a clonal stable C2C12 cell line transfected with antisense agrin cDNA was created. RNA dot blot and western blot analysis indicated that the expression of agrin in the transfected cell was abolished by DNA transfection. When the agrin-deficient C2C12 cells were induced to form myotubes and subsequently cocultured with agrin cDNA transfected fibroblasts, AChR aggregates were formed in the cocultures. In addition, acetylcholinesterase (AChE) aggregates in agrin-deficient myotubes were also induced by exogenous agrin and the AChE aggregates were colocalized with the AChR aggregates. The agrin-deficient myotubes could also respond to neuron-induced AChR aggregation after coculturing with neuroblastoma cells. Thus, the agrin-deficient myotubes retain their ability to exhibit the agrin- or neuron-induced AChR aggregation. This result suggests that the formation of postsynaptic specializations during development and regeneration is mediated by neuron-derived agrin but not the agrin from muscle.

Acetylcholinesterase↗

PubMed1996

Short latency, non-reciprocal group I inhibition is reduced during the stance phase of walking in humans.

Activation of group Ib afferents from extensor muscles produces an inhibition in the parent muscle and its synergists in a resting cat. This reflex switches to excitation of the parent muscle and its synergists when the cat walks. This study determined if a similar reflex undergoes the same type of reversal in the intact human. A putative Ib reflex was elicited by conditioning the Hoffmann (H) reflex in the soleus muscle with stimuli to the nerve innervating the medial gastrocnemius muscle. The reflex was observed while subjects: (1) sat quietly; (2) sat and activated the triceps surae muscle isometrically at a low level; (3) stood and activated the triceps surae to the same level as (2); and (4) walked on a treadmill. Condition-test intervals of 1 to 16 ms were used. Ten out of the 15 subjects studied in quiet sitting showed an early, presumably disynaptic inhibition. Walking resulted in a significant reduction in the size of this inhibition at condition-test intervals of 4, 5, 6, and 8 ms for these subjects. No significant differences were observed at longer condition-test intervals. As a group, the inhibition of the conditioned H-reflex was diminished during walking, but not significantly excited. Four out of the 10 subjects, however, showed a significant excitation of the conditioned H-reflex during walking. The inhibition was significantly reduced at a condition-test interval of 7 ms when the triceps surae group was activated isometrically. No differences were seen in the reflex between matched levels of contraction in sitting and standing. It is concluded that the short latency group I inhibition seen at rest is reduced during walking, in a manner similar to that seen in spinal and decerebrate cats. The reduction may be accounted for, at least partially, by activation of the triceps surae.

Afferent Pathways↗

PubMed1996

The modified Gait Abnormality Rating Scale for recognizing the risk of recurrent falls in community-dwelling elderly adults.

BACKGROUND AND PURPOSE: The purpose of this study was to determine the reliability and validity of measurements obtained with a seven-item modified version of the Gait Abnormality Rating Scale (GARS-M), an assessment of gait designed to predict risk of falling among community-dwelling, frail older persons. SUBJECTS: Fifty-two community-dwelling, frail older persons, with a mean age of 74.8 years (SD = 6.75), participated. METHODS: A history of falls was determined from self-report or by proxy report. The GARS-M was scored from videotapes of subjects walking at self-selected paces. Gait characteristics were recorded during a timed walk on a 6-m brown-paper walkway. RESULTS: Scores obtained by three raters for 23 subjects demonstrated moderate to substantial intrarater and interrater reliability. Concurrent validity, as assessed by Spearman rank-order correlation coefficients, was demonstrated for the relationship between GARS-M scores and stride length (r = -.754) and for the relationship between GARS-M scores and walking speed (r = -.679). Mean GARS-M scores distinguished between frail older persons with and without a history of recurrent falls (mean GARS-M scores of 9.0 and 3.8, respectively). CONCLUSION AND DISCUSSION: The GARS-M is a reliable and valid measure for documenting gait features associated with an increased risk of falling among community-dwelling, frail older persons and may provide a clinically useful alternative to established quantitative gait-assessment methods.

Accidental Falls↗

PubMed1996

Use of bacterially expressed GST/EBNA-1 fusion proteins for detection of antibodies in sera from patients with nasopharyngeal carcinoma and healthy donors.

Epstein-Barr virus nuclear antigen-1 (EBNA-1) is a protein expressed consistently in EBV infected cells and in EBV related malignant tissues. Antibodies against EBNA-1 may therefore possibly be used as a marker for disease screening. Western blot analysis of serum antibodies was performed using GST (glutathione-S-transferase) fusion proteins containing different regions of EBNA-1 as antigens. Serum samples were collected from 38 patients with nasopharyngeal carcinoma (NPC) and 38 healthy individuals in Taiwan. All samples were found IgG positive for EBNA-1 when a truncated protein GST/E1 (70-102, 325-641) was used as the antigen. Thirty-three out of 38 NPC sera (86.8%) were positive for IgA antibody against EBNA-1. The positive rate was higher in comparison with IgA antibody against VCA (65.7%) or antibody against DNase (60.5%). Only 2.6% of sera from normal individuals were positive for an IgA response against EBNA-1. The major antigenic determinants for NPC serum IgA response were between amino acid(aa) 390 to aa 459 when different portions of EBNA-1 were used as antigens. The results suggest that IgA response against EBNA-1 could be used in combination with other EBV serology markers for NPC screening.

Animals↗

PubMed1995

Mechanism for reflex reversal during walking in human tibialis anterior muscle revealed by single motor unit recording.

1. A reversal in the sign of a cutaneous reflex during walking was recently described in the human. Such reversals were most clearly seen in muscles that were active in two parts of the step cycle, such as the tibialis anterior (TA). The current study determined whether the reversal resulted from differential activation of a single group of motor units. 2. Single motor units were recorded from the TA muscle of healthy human subjects while they walked on a treadmill with a splint that limited motion of the ankle joint. The majority of motor units from which recordings were made (43 out of 46) were active in both the swing phase and the transition from swing to stance, indicating that the two bursts of activity from the TA muscle do not represent the activity of two separate populations of motor units. 3. The firing behavior of three motor units was observed during walking steps when stimuli were applied to the posterior tibial nerve during either the swing phase or the transition from swing to stance. The post-stimulus time histograms indicated that the same motor unit was excited during the swing phase, and inhibited during the transition from swing to stance. 4. The results support the hypothesis that there are parallel excitatory and inhibitory pathways from cutaneous afferents to single motoneurones of the TA muscle. A shift in balance between the two pathways as a function of the step cycle most probably generates the reflex reversal observed.

Electromyography↗

PubMed1994

Reflex behavior during walking in incomplete spinal-cord-injured subjects.

Reflexes evoked by stimulation of the posterior tibial nerve at the ankle during walking were investigated in 10 subjects with incomplete injury of the spinal cord. Low-intensity stimuli (1.5 to 1.7 times the motor threshold) were delivered during treadmill walking. Reflexes were recorded by surface electromyography from the tibialis anterior (TA) and soleus (SOL) muscles. Responses were evoked at early, medium, and late latencies in all subjects. The reflex activity at a medium latency (50 to 80 ms) was cyclically modulated in all of the subjects during walking in both muscles, but the pattern of modulation was different from that seen in normal subjects (Yang and Stein, J. Neurophysiol., 63, 1109-1117). Most spinal-cord-injured subjects did not show inhibitory responses in the TA; excitatory responses were seen in the swing phase and occasionally in the stance phase. Inhibitory responses were typically evoked in the SOL muscle during the stance phase, but abnormal excitatory responses were also seen during the swing phase in the majority of subjects. Excitatory responses were seen in some subjects during the stance phase as well. Functional walking ability and clinical measures of muscle tone were not correlated with the degree of reflex modulation in walking. The lack of correlation between these measures could be related to many factors including the small number of subjects, the subjectivity of clinical measures, and the different movement conditions under which these measures were taken. The results demonstrated that most spinal-cord-injured subjects retained the ability to modulate this reflex during walking, but the pattern of modulation was abnormal. Moreover, excitatory responses were more frequently evoked than inhibitory responses.

Adult↗

PubMed1993

Neural mechanisms that contribute to cyclical modulation of the soleus H-reflex in walking in humans.

The amplitude of the Hoffmann reflex (H-reflex) of the human soleus muscle is modulated in a cyclical way during walking. This paper addresses two questions associated with the neural mechanisms that might generate this modulation: (1) Does the amplitude of the H-reflex simply rise and fall as a function of the background excitability of the soleus motoneuron pool? (2) Is the modulation of the H-reflex dependent on events associated with activation of the antagonist muscle? The amplitude of the soleus H-reflex was compared under three conditions: natural walking, walking without activating the tibialis anterior muscle, and walking with activation of the soleus muscle in the swing phase. Human subjects were able to perform these three tasks with minimal training. The results indicated that the soleus H-reflex remained very depressed in the swing phase of walking, even when a voluntary contraction of the soleus muscle was superimposed during this time. Moreover, the presence of tibialis anterior activity had a very minor effect on the amplitude of the soleus H-reflex during walking. It is concluded that modulation of the soleus H-reflex is not simply a reflection of the background excitability of the motoneuron pool, and the modulation is not dependent on activation of the antagonist muscle. Other more powerful mechanisms are acting to modulate the reflex, most likely presynaptic inhibition of the primary afferents.

H-Reflex↗

PubMed1993

Recovery potential of muscle after partial denervation: a comparison between rats and humans.

The response to partial denervation is compared for the tibialis anterior muscle in the rat and the thenar muscle group in the human. Partial denervation in the human was a result of spinal cord injury, while partial denervation in the rat was induced by sectioning of the L4 ventral root. In some animals, a spinal cord transection at the T12-13 level was also performed to determine whether spinal cord injury affected the sprouting capability of motoneurons caudal to the injury site. Motor units were isolated by intramuscular microstimulation in the human and by ventral root splitting in a terminal experiment in the rat. Motor unit numbers were estimated by dividing the amplitude of the electromyogram (EMG) and the peak twitch force in response to maximum stimulation of the muscle nerve by the average unit EMG and twitch force, respectively. In both the rat and the human, surviving motor units enlarged as a function of the degree of partial denervation. Moreover, all surviving motor units appeared to enlarge proportionately. The limit to sprouting was tested systematically in the rat. On average, single motor units enlarged up to about five times their original size, resulting in the ability to compensate for up to 80% of motoneuron loss. The reason for this limit remains unclear, but histological data suggest that sprouting may be confined to the more distal regions of the motor axon, such that reinnervation of denervated muscle fibers is confined to the territory of the original motor unit.

Animals↗

PubMed1993

Modification of reflexes in normal and abnormal movements.

The trajectories observed for the limb during human locomotion are determined by a mixture of influences, some arising from neural circuits entirely within the central nervous system and others arising from a variety of sensory receptors. Muscle reflexes are highly modulated during locomotion in an adaptive manner within each phase of the step cycle. Furthermore, the modulation can be modified quickly for different tasks such as standing, walking and running, probably by changes in presynaptic inhibition. This modulation is often lost or severely reduced in patients with spasticity after spinal cord or head injury. In normal subjects cutaneous reflexes can be completely reversed from exciting to inhibiting a muscle during each step cycle, particularly in muscles that normally show two bursts of activity per cycle (e.g., tibialis anterior). In some patients stimulation of a mixed nerve (e.g., common peroneal) can directly produce muscle contraction, generate a reflex response (flexor reflex) and transiently reduce spasticity in antagonist (extensor) muscles. Thus, simple systems employing stimulation can enhance gait to a certain extent in patients with incomplete injuries.

Electric Stimulation↗

PubMed1993

A study of siliceous pneumoconiosis in a desert area of Sunan County, Gansu Province, China.

Three hundred and ninety five residents in a desert area were examined with chest radiographs and 28 cases with siliceous pneumoconiosis were found. The prevalence of siliceous pneumoconiosis was 7.09%, and that over 40 years of age was 21%. The histological findings of lungs from a camel living in that area for 20 years also confirmed to have siliceous pneumoconiosis.

Adult↗

PubMed1992

Optimal stimulation of paralyzed muscle after human spinal cord injury.

Muscle properties change profoundly as a result of disuse after spinal cord injury. To study the extent to which these changes can be reversed by electrical stimulation, tibialis anterior muscles in complete spinal cord-injured subjects were stimulated for progressively longer times (15 min, 45 min, 2 h, and 8 h/day) in 6-wk intervals. An index of muscle endurance to repetitive stimulation doubled (from 0.4 to 0.8), contraction and half-relaxation times increased markedly (from 70 to approximately 100 ms), but little or no change was measured in twitch or tetanic tension with increasing amounts of stimulation. The changes observed with 2 h/day of stimulation brought the physiological values close to those for normal (control) subjects. A decrease in the stimulation period produced a reversal of the changes. No effects were observed in the contralateral (unstimulated) muscle at any time, nor was there evidence of decreased numbers of motor units in these subjects secondary to spinal cord injury. Motor unit properties changed in parallel with those of the whole muscle. The occasional spasms occurring in these subjects are not sufficient to maintain normal muscle properties, but these properties can largely be restored by 1-2 h/day of electrical stimulation.

Adaptation, Physiological↗

PubMed1992

Collagenase activity in oral submucous fibrosis.

Oral submucous fibrosis (OSF) is characterized by an abnormal accumulation of collagen fiber in oral submucosa. OSF is a collagen disease and is also regarded as a precancerous lesion. In the previous study, we discovered that the collagen content in oral mucosa of OSF is statistically higher than in normal mucosa. This research examined the relationship between the fibrosis and collagenase activity. Collagenase activity was determined by using soluble 14C-glycine-labeled collagen (9813 cpm/200 micrograms/tube) as a substrate in a solution incubated for 30 hours at 35 degrees C. The results showed that the collagenase activity of the OSF was much lower than that of normal oral mucosa (65.23 +/- 19.49 units/g tissue in normal mucosa vs. 29.48 +/- 5.69 units/g tissue in OSF). Furthermore, the cleavage pattern revealed by SDS-Polyacrylamid gel electrophoresis (SDS-PAGE) confirmed that the partially purified OSF collagenase was likely to be typical mammalian collagenase, with a molecular weight of about 68.0 kDa.

Chromatography, Gel↗

PubMed1991

Contribution of peripheral afferents to the activation of the soleus muscle during walking in humans.

Small, rapid stretches were applied to the soleus muscle during the stance phase of walking by lifting the forefoot with a pneumatic device. Stretch responses were induced in the soleus muscle by the disturbance. The amplitude and time course of the responses from the soleus muscle were a function of both the kinematics of the disturbance and the time in the step cycle when the disturbance was applied. The step cycle was divided into 16 equal time parts, and data obtained within each of these parts were averaged together. The electromyographic (EMG) response of the soleus muscle showed a time course that was similar to the time course of the angular velocity induced by the disturbance at the ankle. Three linear equations were used to predict the EMG response from the soleus muscle as a function of the angular kinematics of the disturbance: 1) velocity, 2) velocity and displacement, 3) velocity, displacement and acceleration. Introduction of a pure delay between the EMG and the kinematics substantially improved the predictions. Most of the variance (70%) in the EMG response could be accounted for by the velocity of the disturbance alone with an optimal delay (average 38 ms). Inclusion of a displacement term significantly increased the variance accounted for (85%), but further addition of an acceleration term did not. Since the velocity of the disturbance accounted for most of the variance, the reflex gain was estimated from the velocity coefficient. This coefficient increased in a ramp-like fashion through the early part of the stance phase, qualitatively similar to the increase in the H-reflex.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗