Biomedical subjects

C S Lin

Publications and source records attributed to C S Lin.

At least 73 records · Page 4Linked to original sources

PubMed2000

Accommodation to depolarizing and hyperpolarizing currents in cutaneous afferents of the human median and sural nerves.

To determine whether accommodation to depolarizing and hyperpolarizing stimuli differs for cutaneous afferents in the median and sural nerves, studies were performed in normal human subjects using threshold electrotonus. The changes in threshold for compound sensory action potentials of 50 % of maximum were recorded when the nerves were subjected to long-lasting depolarizing and hyperpolarizing DC. The premise was that the threshold changes largely mirror the underlying electrotonic changes in membrane potential. The maximal threshold changes produced by depolarizing and hyperpolarizing currents were greater for median afferents, suggesting that the DC produced greater changes in membrane potential in these afferents. Median afferents underwent greater accommodation to depolarizing currents than sural afferents and a greater threshold undershoot at the end of the currents, suggesting greater activity of a slow K+ conductance. Median afferents also underwent greater accommodation to hyperpolarizing currents, suggesting greater inward rectification. These conductances are voltage dependent, and the differences in accommodation could be due to greater changes in membrane potential for the median nerve. The changes in threshold produced by long-lasting depolarizing and hyperpolarizing currents of graded intensity were therefore measured. When the threshold changes were matched for the two nerves, median afferents underwent 22.4 % more accommodation to depolarizing currents and 28.7 % more accommodation to hyperpolarizing currents. We conclude that there is greater expression of two internodally located conductances responsible for accommodation on median afferents. The biophysical differences identified in this study might contribute to the finding that sural afferents have a greater tendency to dysfunction than median afferents.

Action Potentials↗

PubMed2000

Epstein-barr virus nuclear antigen 2 retards cell growth, induces p21(WAF1) expression, and modulates p53 activity post-translationally.

The Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA2) has been shown to be required for promotion of cell-cycle progression in EBV-immortalized B-lymphocytes. However, other studies have indicated that EBNA2 alone, in the absence of other EBV genes, may retard cell growth. To resolve this discrepancy, we investigated the effect of EBNA2 on the growth of various cells, including EBV target nasopharyngeal carcinoma cells, NPC-TW01 and NPC-TW04. We found that EBNA2 could retard cell growth, in stable Vero, HEp-2, and U2OS cell clones expressing EBNA2, and in Vero, 293, NPC-TW01, and NPC-TW04 cells transiently transfected with EBNA2. While investigating the mechanism underlying the growth-retarding function of EBNA2, we found that EBNA2 induced p21(WAF1) expression in these cells. This induction of p21(WAF1) expression was mediated through p53. EBNA2 was found to stimulate p53 to bind to the p53-response element within the p21(WAF1) promoter, possibly by promoting p53 phosphorylation. This enhancement of p53 sequence-specific DNA-binding activity may be the mechanism through which EBNA2 activates the expression of p53-regulated genes, including p21(WAF1) and mdm-2. Together, these studies reveal a possible intrinsic function of EBNA2 in cell-growth regulation and elucidate a novel mechanism by which EBNA2 modulates transcription.

Animals↗

PubMed2000

Ischaemic changes in refractoriness of human cutaneous afferents under threshold-clamp conditions.

1. A technique was developed to counteract the changes in threshold to electrical stimuli of large myelinated cutaneous afferents in the human median nerve induced by ischaemia for 13 min. Intermittent application of polarizing currents was used in five subjects, in whom refractoriness, supernormality and the strength-duration time constant (tauSD) were tracked to determine whether compensating for the ischaemia-induced changes in threshold also controlled the ischaemic changes in these excitability parameters. 2. The threshold compensation prevented the ischaemic changes in tauSD, an excitability parameter dependent on nodal Na+ channels. Threshold compensation did not prevent the changes in refractoriness and supernormality, whether the compensation began 10, 100 or 200 ms prior to the test stimuli. 3. In three subjects, continuous polarizing current was injected for 13 min to compensate for the ischaemic change in threshold, thus clamping threshold at the pre-ischaemic level. Again, tauSD was effectively controlled, but there were still ischaemic changes in refractoriness and supernormality. 4. The effective control of tauSD suggests that both the intermittent threshold compensation and the continuous threshold clamp effectively controlled membrane potential at the node of Ranvier. 5. The ischaemic increase in refractoriness when threshold was kept constant could be due to interference with the processes responsible for refractoriness by a metabolic product of ischaemia. The ischaemic change in supernormality during effective compensation probably results from the intrusion of refractoriness into the conditioning-test intervals normally associated with maximal supernormality. 6. The present results indicate that ischaemia has effects on axonal excitability that cannot be readily explained by changes in membrane potential. Specifically, it is suggested that ischaemic metabolites interfere with the recovery of Na+ channels from inactivation.

Adaptation, Physiological↗

PubMed2000

Identification of three alternative first exons and an intronic promoter of human PDE5A gene.

In the accompanying paper we present evidence for the existence of three PDE5A isoforms that differed only in the 5' end of the mRNAs. In this paper we present evidence that the three isoform-specific 5' ends were encoded by three alternative first exons that were arranged in the order of A1-A3-A2. Because the isoform-specific mRNAs could be transcribed from individual promoters, DNA fragments of the two intronic regions (A1-A3 and A3-A2) were tested for possible promoter activities. The intron between A1- and A3-specific exons did not exhibit any promoter activities even in smooth muscle cells that expressed the A3 isoform (see accompanying paper). In contrast, the intron between A3- and A2-specific exons had promoter activities in PDE5A2-expressing COS-7 and smooth muscle cells. This intronic promoter was bound by transcription factors AP-2 and Sp1, but not by AP-1, as shown by DNase I footprint analysis. However, the sequence bound by AP-2 (5'-GGGAAACGCTCGCGGGAGAGTTGG) is unusual in that it bears little resemblance to the consensus AP-2-binding sequence.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2000

Expression of three isoforms of cGMP-binding cGMP-specific phosphodiesterase (PDE5) in human penile cavernosum.

Inhibition of cGMP-specific phosphodiesterase type V (PDE5) has been shown to improve penile erection in patients with erectile dysfunction. We report here the cloning of three PDE5 isoforms from human penile tissues. Two of the isoforms were identical to PDE5A1 and PDE5A2, respectively, which had been isolated from nonpenile tissues. The third isoform was novel and hence called PDE5A3. The deduced amino acid sequence of PDE5A3 was the same as the C-terminal 823-residue sequence of PDE5A1 and PDE5A2. While PDE5A1 and A2 isoforms were expressed in all tissues examined, the A3 isoform was confined to tissues with a smooth muscle or cardiac muscle component. When expressed in COS-7 cells, PDE5A1, A2, and A3 isoforms had similar cGMP-catalytic activities with K(m) of 6.2, 5.75, and 6.06 microM, respectively. Their cGMP-catalytic activities were inhibited by zaprinast with IC(50) values of 3.2 microM, 1.3 microM, and 1.6 microM, respectively, and by sildenafil with IC(50) of 28, 14, and 13 nM, respectively.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2000

Recovery of excitability of cutaneous afferents in the median and sural nerves following activity.

In acquired polyneuropathies, symptoms and signs are typically distal and symmetrical, more prominent in the lower limbs than the upper limbs. This study was undertaken to measure the extent of the decrease in excitability produced by single impulses and by impulse trains in cutaneous afferents in the median and sural nerves, and to compare the resulting changes in excitability of these afferents. Threshold tracking was used in 10 healthy subjects to measure the changes in threshold for a compound sensory action potential of 50% maximum produced by conditioning stimuli. Following a single supramaximal conditioning stimulus, the threshold changes occurring during the refractory and supernormal periods were identical for the two nerves, but there was a greater increase in threshold during the late subnormal period for median afferents. Following a train of 10 supramaximal conditioning stimuli, threshold increased by approximately 40% for median afferents and by approximately 20% for sural afferents. These differences are consistent with differences in a slow K(+) conductance. It is suggested that the hypo-excitability produced by brief trains of impulses may be sufficient to disturb conduction in diseased nerve fibers, and that the lesser expression of slow K(+) conductances on cutaneous afferents in the sural nerve could render them more sensitive to depolarizing stresses than median afferents. This could be a factor in the ease with which sural afferents become ectopically active in polyneuropathies.

Action Potentials↗

PubMed2000

2D CSI proton MR spectroscopy of human spinal vertebra: feasibility studies.

This report focuses on proton magnetic resonance spectroscopy (1H MRS) of spine vertebra acquired with two-dimensional chemical shift imaging (2D CSI), utilizing the stimulated echo acquisition mode (STEAM) sequence. Both validity and reproducibility studies were performed. To validate the 2D CSI method, its spectra were compared with those obtained with the single-voxel (SV) method. Five normal volunteers were scanned. The reproducibility of 2D CSI was examined by performing spectroscopy on two different occasions, on three normal volunteers. Data show that the STEAM 2D CSI technique results in MRI spectra comparable to those obtained with the STEAM SV method. 2D CSI offers significant time savings and convenient multi-voxel spectral analysis at a substantially higher signal-to-noise ratio. The 2D CSI method was then applied to a patient with a small vertebral hemangioma. The results demonstrated that the voxels containing the hemangioma exhibit different spectra than the neighboring voxels of the same vertebra. Additionally, a case of vertebral osteoporosis was investigated. Results showed a significant increase in the lipid-to-water ratio (LWR). It is suggested that 2D CSI may be powerful in identifying physiological as well as pathological changes of the bone marrow. Furthermore, covering a more extensive area of the vertebral body will maximize the chances of depicting a small focus of pathologic tissue. A more detailed bone marrow pattern was noticed in on one subject whose spectra show more lipid peaks.

Adult↗

PubMed2000

Excitability properties of median and peroneal motor axons.

Threshold tracking was used to compare excitability properties (stimulus-response curves, strength-duration properties, recovery cycle, and threshold electrotonus) of median motor axons at the wrist and peroneal motor axons at the ankle in 12 healthy subjects. Stimulus-response curves and strength-duration properties were similar, though higher stimulus intensities were required for peroneal axons. However, there were significant differences in the recovery cycle of excitability following a conditioning stimulus and in threshold electrotonus. In the recovery cycle, median axons had significantly greater supernormality and late subnormality. In threshold electrotonus, the initial slow threshold changes in response to subthreshold depolarizing and hyperpolarizing currents (S1) were significantly greater in median axons, and there was also greater accommodation to depolarizing currents (S2) and greater threshold undershoot after depolarization. Similar differences in supernormality and the S1 phase of threshold electrotonus were found between peroneal axons at ankle and knee, suggesting that these properties may be dependent on nerve length. When median motor axons at the wrist were compared with peroneal motor axons at the knee, there were no differences in refractoriness and supernormality and only small differences in S1, but the late subnormality and undershoot were significantly greater in the median axons. These findings suggest that, in addition to any length-dependent differences, peroneal axons have a less prominent slow K(+) conductance. We conclude that the properties of different motor axons are not identical and their responses to injury or disease may therefore differ.

Adult↗

PubMed2000

Strength-duration properties and their voltage dependence as measures of a threshold conductance at the node of Ranvier of single motor axons.

In a number of clinical studies, measurement of axonal strength-duration properties has been used to provide indirect insight into conductances at the node of Ranvier, particularly persistent Na(+) conductance. However, the specificity of any changes is limited because other factors can affect strength-duration behavior. The present study was undertaken to define the relationship between different strength-duration measures at rest and at different membrane potentials, and also to determine the limits within which strength-duration behavior can be used as a measure of nodal conductances. The strength-duration time constant (tau(SD)) and rheobase of 20 single motor units in the flexor carpi ulnaris were calculated from thresholds defined using threshold tracking. "True" rheobase and rheobasic latencies were measured using test stimuli of 100-ms duration. For ten units, the technique of latent addition was used to measure threshold changes directly attributable to nodal conductances, and for six units these were compared with strength-duration properties at different membrane potentials. The data indicate that measurements of tau(SD) and rheobase can provide sensitive indicators of conductances present at the node of Ranvier when membrane potential changes. There is a reciprocal relationship between tau(SD) and rheobase for single motor units at different membrane potentials, and this relationship may allow changes in tau(SD) due to depolarization and demyelination to be differentiated.

Action Potentials↗

PubMed2000

Magnetic resonance spectroscopy to detect lecithin in amniotic fluid and fetal lung.

BACKGROUND: Proton magnetic resonance spectroscopy is a noninvasive technique that detects molecules within a specified region in vivo. Lecithin, the major component of surfactant, has a characteristic magnetic resonance signal, but to our knowledge, it has never been reported in fetal lung or amniotic fluid (AF). The objective of this study was to characterize the lecithin signal in utero, which could lead to a noninvasive fetal lung maturity test. METHOD: Human fetal lung and AF pockets can be identified and studied with magnetic resonance spectroscopy with the use of a 1.5-tesla Vision whole-body magnetic resonance scanner (Siemens Medical Systems; Erlangen, Germany). Spectroscopy data are collected with a single-voxel-point-resolved spectroscopy sequence. After identification of fetal anatomy with the use of scout magnetic resonance images, magnetic resonance spectroscopy of human fetal lung and AF identifies a lecithin peak. EXPERIENCE: Three healthy gravidas near term were studied and lecithin peaks were identified in all. CONCLUSION: Lecithin can be identified in vivo with the use of volume-selected proton magnetic resonance spectroscopy. Patient comfort and extremely short scan times suggest that refined magnetic resonance spectroscopy might be a safe, quick, and comfortable test of fetal lung maturity.

Amniotic Fluid↗

PubMed2000

The effect of pregnancy and delivery on the function and ultrastructure of the rat bladder and urethra.

OBJECTIVE: To examine the effect of pregnancy and delivery on the function and ultrastructure of the bladder and urethra in rats. Material and methods The study comprised six virgin and 18 pregnant rats; both groups underwent cystometry (at the 19th day of gestation, and 2 days and 6 weeks after parturition). Tissues from the bladder and urethra were collected for electron microscopy, western blotting and immunostaining for caveolin-1 and caveolin-3. RESULTS: The bladder capacity was greater and the modified leak-point pressures lower in pregnant and 2-day postpartum rats than in virgin and 6-week postpartum rats. The residual volume was significantly higher in the pregnant group. Electron microscopy showed more sarcolemmal caveolae in the smooth muscle cells of both the bladder and urethra of virgin rats than in the other groups. Lipid droplets and subsarcolemmal mitochondria accumulated in pregnant and 2-day postpartum rats. Caveolin-1 protein was detected in the cytoplasmic membrane of urethra and bladder smooth muscle cells. Caveolin-3 was detected in the membrane of striated muscle in the intrinsic sphincter. Western blotting showed increased caveolin-1 protein expression in the bladder and urethra of 2-day postpartum rats; in contrast, levels of caveolin-1 were lower in pregnant rats than in virgin and 6-week postpartum rats. CONCLUSION: s During pregnancy there was a significant decrease in sarcolemmal caveolae and caveolin-1 in the smooth muscle cells of the rat bladder and urethra. The changes in caveolae and the membrane protein caveolin may play a role in the functional changes associated with pregnancy and after delivery.

Animals↗

PubMed2000

Upregulation of L-plastin gene by testosterone in breast and prostate cancer cells: identification of three cooperative androgen receptor-binding sequences.

L-Plastin is normally a leukocyte-specific actin-binding protein; it is also expressed in the majority of human cancer cell lines that are derived from many types of solid tumors. We have previously reported the isolation of the L-plastin gene promoter, in which we identified several potential steroid receptor-binding sequences. We now obtained evidence that L-plastin gene expression was positively regulated by testosterone in androgen receptor (AR)-positive prostate and breast cancer cells. DNase I footprint analysis identified three AR-binding elements (ARE) located in a 545-bp region approximately 1.1 kb upstream from the transcription initiation site. However, each of these three AREs exhibited very little testosterone/AR-responsive enhancer activities toward a test promoter (of the thymidine kinase gene) when tested in MCF-7 breast cancer cells. Their testosterone/AR responsiveness became evident only when two or three of them were combined. In PC-3 prostate cancer cells, cooperation among L-plastin AREs was still evident although individually they had moderate levels of testosterone/AR responsiveness. Thus, the three L-plastin AREs, despite their imperfect sequences compared with the consensus ARE, could cooperate with each other to become a potent testosterone/AR-responsive unit, which was likely responsible for the inducibility of the L-plastin gene by testosterone.

Base Sequence↗

PubMed2000

Prophylactic intravenous ondansetron reduces the incidence of intrathecal morphine-induced pruritus in patients undergoing cesarean delivery.

UNLABELLED: Pruritus is a common side effect of intrathecal morphine injection for postoperative pain control. Its incidence is especially high in patients undergoing cesarean delivery. We investigated the effectiveness of ondansetron in preventing intrathecal morphine-induced pruritus in such patients. We included 60 consecutive nonbreastfeeding women who were scheduled for elective cesarean delivery. After the administration of spinal anesthesia with bupivacaine and intrathecal morphine 0.15 mg injection, the patients were randomly divided into three groups. Group 1 received placebo (normal saline) IV injection, Group 2 diphenhydramine 30 mg IV injection, and Group 3 ondansetron 0.1 mg/kg IV injection. The incidence of pruritus was significantly lower in the ondansetron group (25%) when compared with that in the placebo group (85%) and in the diphenhydramine group (80%) (both P < 0.05). The postoperative pain score and time to flatus passage were not significantly different among the three groups. There were no headache or extrapyramidal signs associated with ondansetron use. In conclusion, ondansetron prophylaxis significantly reduced the incidence of intrathecal morphine-induced pruritus in patients undergoing cesarean delivery. IMPLICATIONS: Ondansetron prophylaxis significantly decreases the incidence of pruritus, a common side effect of intrathecal morphine used to treat postcesarean delivery pain.

Adolescent↗

PubMed2000

Induction of a futile Embden-Meyerhof-Parnas pathway in Deinococcus radiodurans by Mn: possible role of the pentose phosphate pathway in cell survival.

Statistical models were used to predict the effects of tryptone, glucose, yeast extract (TGY) and Mn on biomass formation of the highly radioresistant bacterium Deinococcus radiodurans. Results suggested that glucose had marginal effect on biomass buildup, but Mn was a significant factor for biomass formation. Mn also facilitated glucose interactions with other nutrient components. These predictions were verified by in vivo and in vitro experiments. TGY-grown cells metabolized glucose solely by the pentose phosphate pathway (PPP). Although only a fraction of glucose from the medium was transported into the cells, glucose was incorporated into the DNA efficiently after cells were exposed to UV light. The presence of glucose also enhanced the radioresistance of the culture. Mn could induce an Embden-Meyerhof-Parnas (EMP) pathway in D. radiodurans. The EMP pathway and the PPP of the Mn-treated cells oxidized glucose simultaneously at a 6:1 ratio. Although glucose was hydrolyzed rapidly by the Mn-treated cells, most glucose was released as CO(2). Mn-treated cultures retained less glucose per cell than cells grown without Mn, and still less glucose was incorporated into the DNA after cells were exposed to UV light. Mn-treated cells were also more sensitive to UV light. Results suggested that metabolites of glucose generated from the PPP enhanced the survival of D. radiodurans. Induction of the EMP pathway by Mn may deplete metabolites for DNA repair and may induce oxidative stress for the cell, leading to reduction of radioresistance.

Biomass↗

PubMed2000

Normal lumbar vertebrae: anatomic, age, and sex variance in subjects at proton MR spectroscopy--initial experience.

Fifty-seven subjects underwent proton magnetic resonance (MR) spectroscopy of the second lumbar vertebra to evaluate single-voxel and multivoxel techniques. Measurements included lipid-to-water ratios, lipid fractions, and line width. These data provide information about vertebral fat content. There was an age-dependent linear increase in fat content and sex dependence. A higher fat concentration was found in men. The observed spectra provide a basis for future study to determine clinical utility of vertebral proton MR spectroscopy.

Adolescent↗

PubMed2000

Dangerous impact--commotio cordis.

Sudden death following blunt chest trauma is a frightening occurrence known as 'commotio cordis' or 'concussion of the heart'. It is speculated that commotio cordis could be caused by ventricular fibrillation secondary to an impact-induced energy that was transmitted via the chest wall to the myocardium during its vulnerable repolarization period. We describe a survivor of commotio cordis caused by a baseball. In this patient, an initial ventricular fibrillation was documented and converted by direct current defibrillation. Serial electrocardiographic changes (bifascicular conduction block and T wave inversion in precordial leads) were noticed in this patient. Our case suggested that coronary vasospasm might also play a role in commotio cordis.

Baseball↗

PubMed2000

Radiofrequency catheter modification of atrioventricular junction in patients with COPD and medically refractory multifocal atrial tachycardia.

BACKGROUND: Multifocal atrial tachycardia (MAT) is a difficult clinical problem generally associated with acute cardiorespiratory illness. The purpose of this study was to assess the feasibility and clinical usefulness of atrioventricular (AV) junction modification as a nonpharmacologic therapy for medically refractory MAT. METHODS AND RESULTS: Thirteen patients with COPD and medically refractory MAT underwent AV junction modification. Complications and outcome of this procedure were monitored. Subjective perceptions of quality of life assessed by a semiquantitative questionnaire and cardiac performance study were obtained before ablation (baseline) and 1 and 6 months after ablation. Radiofrequency energy was applied until the average ventricular rate fell to < 100 beats/min. Ablation procedures controlled the ventricular response in 11 of 13 patients (84%). One patient had unsuccessful modification. Another patient developed delayed complete AV block on the second day after ablation. In these 13 patients, average ventricular rate was reduced from a mean of 145 +/- 11 to 89 +/- 22 beats/min immediately after the ablation (p < 0.01). One patient had recurrent symptomatic MAT at 1 month after ablation; this patient underwent a second procedure without late recurrence. All patients were followed up for at least 6 months (mean, 11 +/- 5 months; range, 6 to 18 months). General quality of life and frequency of significant symptoms improved significantly in patients with successful modification at 1 and 6 months. The left ventricular ejection fraction increased significantly after ablation (44.5 +/- 7.3% at baseline, 49.4 +/- 4. 2% at 1 month, and 50.0 +/- 4.9% at 6 months; all p < 0.05). However, right ventricular ejection fraction remained unchanged (34.7 +/- 6. 2% at baseline, 35.7 +/- 4.4% at 1 month, and 34.3 +/- 4.6% at 6 months; all p > 0.05). The consumption of health-care resources (including frequency of hospital admission and emergency department attendance, antiarrhythmic drug trials) decreased significantly 6 months after AV junction modification. Pulmonary function and theophylline level remained unchanged during follow-up. CONCLUSIONS: AV junction modification offers an effective therapy for controlling ventricular rate in medically refractory MAT. This procedure improves the quality of life and left ventricular function in selected patients with symptomatic and medically refractory MAT.

Aged↗

PubMed2000

Distribution and seasonal occurrence of Forcipomyia taiwana (Diptera: Ceratopogonidae) in the Nantou area in Taiwan.

We studied the distribution of Forcipomyia taiwana (Shiraki) in Taiwan, and found this species almost island-wide. Midge seasonality was studied for 4 yr at 3 sites in Nantou, central Taiwan, to identify the extent and causes of midge population outbreaks. The midge population in 1995 was significantly lower than in 3 other years because several typhoons inundated breeding sites. Maximum populations of F. taiwana occurred in June, July, and August. There was a highly significant correlation between the monthly abundance of F. taiwana and temperature and rainfall. A step-up multiple regression indicated that temperature was the most important factor leading to the outbreaks of F. taiwana. Temperature increases from 15 degrees C to near 30 degrees C will increase the midge abundance.

Animals↗