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Biomedical subjects

Y J Lai

Publications and source records attributed to Y J Lai.

14 recordsLinked to original sources

Heterogeneity of myocardial sleeve morphology and gap junctions in canine superior vena cava.

BACKGROUND: The myocardial sleeve of the superior vena cava (SVC) has been identified as a potential initiating focus in atrial fibrillation, but information on cell-to-cell linkage at this site is lacking. METHODS AND RESULTS: We examined the SVC in 8 dogs by immunoconfocal and electron microscopy. Cardiomyocytes outlined with vinculin and bearing striations positive for alpha-actinin are found in the proximal segment of the SVC. These cells, grouped in bundles of various orientations according to location, extend cephalically as far as 3 cm from the right atrium (RA)-SVC junction. Comparison between the junctional level and the level 2 cm distal shows that the myocardial layer in the latter is thinner and not as compact and is composed of longer cells (87.3+/-15.7 versus 71.6+/-14.4 micrometer, P<0.01). Gap junctions made of connexin43 (Cx43), Cx40, and Cx45 are aggregated mainly at the intercalated disks, and colocalization of connexins is a common feature throughout the myocardial sleeve. Areas of atypical expression exist, however, characterized by a center of abundant Cx43 labels surrounded by a periphery of scattered tiny Cx40-labeled spots. Although in the ventral subluminal compact myocardial layer, individual cells at both levels are surrounded by similar numbers of cells, the number of aggregation of labeled gap junctions at the distal level is less (2.3+/-0.6 versus 3.7+/-0.9, P<0.01). In addition, electron-microscopic examination demonstrates that the gap junctions at the distal level are smaller in size (0.37+/-0.30 versus 0.55+/-0.34 micrometer, P<0.01). CONCLUSIONS: The myocardial sleeve in the canine SVC is a heterogeneous structure, which could potentially form a substrate for heterogeneity of electrical coupling.

Actinin↗

Defects and particle motions in the nonuniform melting of a two-dimensional Coulomb cluster.

The defect excitation and nonuniform melting of a two-dimensional Coulomb cluster with 300 charged particles (interacting with 1/r type force) in a uniform neutralizing background are studied numerically. Intrinsic defects exist around the outer circular shells surrounding the inner triangular lattice. They are the source regions for anisotropic particle thermal vibrations and then cyclic hoppings with the increasing temperature. It leads to the nonuniform melting associated with the thermal motion of intrinsic defects, and then the thermal excitation of dislocation pairs and disclinations. The intrinsic defect free center core has the highest melting temperature. It shows the sequential losses of translational and then orientational orders.

Journal Article↗

Effects of ascorbate in microdialysis perfusion medium on the extracellular basal concentration of glutamate in rat's striatum.

There are many evidences suggest that ascorbate in the extracellular space can affect glutamate concentration in the rat's brain. In this report, we studied how ascorbate in microdialysis perfusion medium affected glutamate level at the striatum in freely-moving rats. Three perfusion mediums were used: 0, 250, and 400 microM of ascorbate in perfusion medium. The extracellular basal concentrations of glutamate were determined to be 1.29+/-0.52 microM for the no ascorbate group, 0.86+/-0.35 microM for the low ascorbate group and 4.76+/-1.48 microM for the high ascorbate group. By using 400 microM of ascorbate in a perfusion medium, we found that the extracellular basal concentration of glutamate significantly increased and its in vivo recovery significantly decreased. This indicated that ascorbate concentration in a perfusion medium was important and must be carefully considered while using microdialysis technique to monitor glutamate concentration in vivo.

Animals↗

An outbreak of enterovirus 71 infection in Taiwan, 1998. II. Laboratory diagnosis and genetic analysis.

BACKGROUND: An epidemic of enterovirus 71 (EV71) occurred in Taiwan from April to December of 1998, with two peaks, one in June and the other in October. Many enteroviruses were isolated in our laboratory from 258 cases during this outbreak. Approximately half of the enteroviruses isolated were EV71 and one fifth were coxsackievirus A16. OBJECTIVES: To analyze laboratory findings in the EV71 epidemic of 1998 in Taiwan, various EV71 specimens in different cell lines were examined. In addition, genetic analysis of 5' non-coding region (NCR) was performed to analyze the strain variation in this outbreak. RESULTS: The cytopathic effect induced by EV71 was observed 2-13 (mean of 4.5) days post-inoculation in Vero cells and 4-15 (mean of 6.6) days in green monkey kidney (GMK) cells inoculated with throat swabs. Of the total positive EV71 cases, virus was most frequently obtained from throat swabs (91.7%), less from stools (64.8%), and none from cerebral spinal fluid (CSF). Molecular analyses of EV71 by sequencing the 5' NCR of 34 strains obtained from different clinical categories and various geographic areas showed that their sequences differed (0-13 bp in 681 bp sequenced) by approximately 0-2%. The sequences of these isolates differed from EV71 prototype BrCr or MS strain by 17.5-19%, with the exception of two samples which exhibited nucleotide variation by only 8.9 and 8.2%, when compared to the MS strain. CONCLUSION: EV71 was most frequently isolated from throat swab specimens in Vero cells. The molecular analyses of the 5' NCR of EV71 revealed that most isolates from this epidemic belonged to a group of closely related clones and only two were in a different group which was clustered with the EV71 MS strain.

Adolescent↗

Multiple connexin expression in regenerating arterial endothelial gap junctions.

Endothelial cells form gap junctions that, according to vessel type, may be composed of up to 3 types of connexin, connexin37, connexin40, and connexin43. Although changes in connexin expression have been linked to growth and injury in cultured endothelial cells, information on connexin expression in regenerating endothelium in situ is lacking. We investigated gap junction distribution and expression of all 3 endothelial connexins during healing in rat carotid artery after denudation injury. En face viewing of the vascular luminal surface by means of immunoconfocal microscopy was used to examine the spatial and temporal expression pattern of the endothelial connexins. Gap junction spots labeled by specific antisera against connexin37, connexin40, and connexin43 were quantified 7, 14, and 28 days after injury, and the relations among the connexins were examined by using colocalization analysis. Complementary electron microscopy was also conducted. After injury, the regenerating endothelium initially expressed small, sparse gap junctions, the numbers of which progressively increased to values equivalent to those of controls. Although connexin40 gap-junctional spot size and area returned to uninjured levels by 28 days after injury, connexin37 and connexin43 spot size and area exceeded those of the uninjured artery (P<0.05). Double-label analysis showed that even though colocalization of connexins to the same gap-junctional spot is a common feature, the extent of colocalization was time dependent (>80% in the intact artery at postinjury day 28 and <70% at postinjury days 7 and 14, P<0.01). We conclude that distinct alterations in expression of the 3 connexins are associated with regeneration of the arterial endothelium in situ, implying different intercellular communication requirements during the various phases of the healing process.

Animals↗

Packings and defects of strongly coupled two-dimensional Coulomb clusters: numerical simulation.

The packings and defects of the strongly coupled two-dimensional Coulomb clusters with particle number N from a few to a few hundred with different forms of mutual repulsion and central confining potentials at zero temperature are investigated using molecular-dynamics simulation through many annealing cycles. The circular symmetry of the confining potential and the interplay with the mutual repulsion lead to the strong competition between the outer circular shells and the inner triangular lattice. Generic packing behaviors, such as the concentric shells with the classical periodic packing sequence at small N, and the triangular latticelike inner core surrounded by a few outer circular shells at large N are observed. The effects of changing the interaction and confining potentials on the detailed packing sequence, the radial variation of packing density, and the positions of the shell-triangular core interface are investigated with a detailed study of the cluster structures along with the formation and distribution of topological defects.

Journal Article↗

The effect of tetrandrine and extracts of Centella asiatica on acute radiation dermatitis in rats.

Radiation injury to the skin is one of the major limiting factors in radiotherapy. We designed this study using Sprague-Dawley rats to evaluate the reduction in skin injury achieved using natural products from plant extracts as protection. The acute skin reaction in tetrandrine- and Madecassol-treated animals appeared earlier, but was significantly less severe, than in the control group. The peak skin reactions in the tetrandrine group were less serious than those of the control group at three different radiation doses. At a high dose irradiation, the healing effect of tetrandrine is better than Madecassol and vaseline. The histologic findings indicate that tetrandrine and Madecassol are able to reduce acute radiation reactions by their anti-inflammatory activity.

Acute Disease↗

Effects of different perfusion medium on the extracellular basal concentration of dopamine in striatum and medial prefrontal cortex: a zero-net flux microdialysis study.

The zero-net flux microdialysis method was used to determine (1) the basal concentration of dopamine (DA) in the extracellular space, and (2) the in vivo recovery of Da in the striatum and the medial prefrontal cortex by using three different kinds of perfusion medium. They were, (a) commercial Ringer's solution, (b) low Ca2+ Ringer's solution, and (c) artificial cerebrospinal fluid (aCSF). Our results not only support previous findings that the high Ca2+ concentration in the perfusion medium could increase the baseline concentration of DA in the dialysate, which was collected from extracellular space through dialysis probe; but also provides evidence that this baseline increase was primarily due to an increase of basal DA concentration, and not from the increase of the in vivo recovery. Additionally, there was no significant difference in the basal DA concentration by using either commercial Ringer's solution or aCSF. This indicates that both commercial Ringer's solution and aCSF are suitable as good perfusion medium to determine the basal DA in the rat's brain.

Animals↗

Anesthetics decreased the microdialysis extraction fraction of norepinephrine but not dopamine in the medial prefrontal cortex.

We evaluated the effects of chloral hydrate and pentobarbital sodium on the basal extracellular concentrations of dopamine (DA) and norepinephrine (NA) as well as their in vivo extraction fraction (relative recovery) at the medial prefrontal cortex (mPFC) in rats by using zero-net flux microdialysis method. Adult, male Sprague-Dawley rats anesthetized with either chloral hydrate (400 mg/kg, i.p., with 80 mg/kg i.v. supplements) or pentobarbital sodium (50 mg/kg, i.p., with 10 mg/kg i.v. supplements) were used as treatment groups. Conscious rats were used as a control group. The basal extracellular concentration and in vivo recovery of DA in the conscious group were 2.38 +/- 0.70 nM and 41 +/- 6%. In comparison with the chloral hydrate group (1.51 +/- 0.55 nM and 41 +/- 9%) and the pentobarbital sodium group (2.81 +/- 1.20 nM and 42 +/- 4%), there were no significant effects of anesthesia on the basal extracellular concentration and the in vivo recovery of DA at the mPFC. Additionally, the basal extracellular concentration and the in vivo recovery of NA in the conscious group were 1.59 +/- 0.37 nM and 51 +/- 8%. There also were no significant differences of the basal extracellular concentration of NA among these three groups (chloral hydrate group: 4.38 +/- 1.39 nM; pentobarbital group: 3.67 +/- 0.90 nM). However, the conscious group had a higher in vivo recovery than the two anesthetized groups (chloral hydrate group: 16 +/- 2%; pentobarbital group: 27 +/- 5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics↗

Differential effects of chloral hydrate and pentobarbital sodium on a cocaine level and its catecholamine response in the medial prefrontal cortex: a comparison with conscious rats.

Adult male Sprague-Dawley rats anesthetized with chloral hydrate and pentobarbital sodium were used as two different treatment groups. Conscious rats were used as a control group. By using baseline (precocaine) concentration as 100%, after cocaine administration (3.0 mg/kg i.v.), the maximal dopamine (DA) increase occurring at the first microdialysis collection period (20 min) in the medial prefrontal cortex was 299 +/- 46% for the chloral hydrate group, 168 +/- 12% for the pentobarbital sodium group, and 325 +/- 23% for the conscious group. At the same time, norepinephrine (NA) increases reached a maximum and were 162 +/- 20%, 100 +/- 5%, and 141 +/- 17%, respectively. The maximal changes of DA and NA in the chloral hydrate group and in the control group were both significantly higher than that in the pentobarbital sodium group. Meanwhile, the cocaine concentration was higher over a 100-min period of time in the chloral hydrate group when compared with the pentobarbital group and the control group. The peak cocaine concentration in dialysate occurred in the same time slot of maximal DA and NA responses, which were 0.65 +/- 0.08, 0.30 +/- 0.02, and 0.41 +/- 0.05 microM, respectively. Anesthetics suppress the pharmacologic response of neurons, which may explain the difference in catecholamine response between the pentobarbital sodium and the conscious groups. Conversely, because there was no significant difference in DA and NA response between the chloral hydrate group and the conscious group, it may possible be due to the balancing effect between the higher existing cocaine concentration and the anesthetic suppression on pharmacological response of neurons in the chloral hydrate group. The effect of guide cannula implantation on the cocaine-induced catecholamine response was also evaluated.

Anesthesia↗

Differential effects of chloral hydrate and pentobarbital sodium on cocaine-induced electroencephalographic desynchronization at the medial prefrontal cortex in rats.

We evaluated the effects of two anesthetics on the cocaine-induced electroencephalographic (EEG) desynchronization in male, Sprague-Dawley rats. One group was anesthetized with chloral hydrate (400 mg/kg, i.p., 80 mg/kg/h i.v. supplement; group A). The other group was anesthetized with pentobarbital sodium (50 mg/kg, i.p., 10 mg/kg/h i.v. supplement; group B). The degree of EEG desynchronization after cocaine administration (1.5 mg/kg, i.v.) was expressed as an increase in the mean power frequency (MPF) and a decrease in the root mean square (RMS). These maximal increases and decreases were observed to be larger in group A (MPF: 43.3 +/- 7.0% increase; RMS: 47.4 +/- 5.0% decrease) than in group B (MPF: 17.8 +/- 3.6% increase; RMS: 19.2 +/- 2.5% decrease). Our laboratory previously proved that dopaminergic neurotransmission at the medial prefrontal cortex (mPFC) participated in the cocaine-induced EEG desynchronization and that both D-1 and D-2 receptors were involved in the process. Therefore, in vivo microdialysis coupled with high performance liquid chromatography was used to quantify the changes of extracellular dopamine (DA) concentrations at the mPFC for 90 minutes at 10 minute intervals after 1.5 mg/kg cocaine i.v. injection. The extracellular DA increases in both groups was rapid and reached the maximal peak within 10 min. There was no significant difference in the maximal increase of DA between groups (group A: 375.2 +/- 35.77% versus group B: 332.2 +/- 16.69% over basal value). These results suggest that different anesthetics may differentially affect cocaine-induced EEG desynchronization and this difference has no bearing on the DA response in the mPFC.

Animals↗

Studies on quinazolines. 5. 2,3-dihydroimidazo[1,2-c]quinazoline derivatives: a novel class of potent and selective alpha 1-adrenoceptor antagonists and antihypertensive agents.

A series of 2-[(substituted phenylpiperazin-1-yl)methyl]- and 2-[(substituted phenylpiperidin-1-yl)methyl]-2,3-dihydroimidazo[1,2- c]quinazolin-5(6H)-ones or -5(6H)-thiones, and 3-[(substituted phenylpiperazin-1-yl)methyl]-2,3-dihydroimidazo[1,2-c]quinaz oline derivatives were synthesized, as conformationally restricted analogues of SGB-1534 and ketanserin, for evaluation as alpha-antagonists and antihypertensive agents. Most compounds containing a (substituted phenylipiperazinyl)methyl side chain displayed high binding affinity for alpha 1-adrenoceptor with no significant activity at alpha 2-sites. Compounds having a (substituted phenylpiperazinyl)methyl at the 3-position of 2,3-dihydroimidazo[1,2-c]quinazolin-5(6H)-one ring system had a better activity than those with the same substituent at the 2-position. Structure-activity relationships for alpha 1-adrenoceptor affinity are presented and indicate that compounds with substitution at the ortho position on the benzene ring of the phenylpiperazine side chain moiety are more potent than those without substitution and/or substitutions at the 3- and 4-positions. Computer-assisted superimposition of SGB-1534 and 20b showed little structural correspondence between the quinazolinone and 2,3-dihydroimidazo[1,2-c]quinazoline nucleus, and specific interactions of these molecular fragments with the receptor protein appear unlikely. Antihypertensive activity was evaluated via intravenous administration of each compound to spontaneously hypertensive rats, and compounds (16a, 16b, 20b, and 28b) illustrated similar efficacy to SGB-1534 when assessed after 6 h. The pA2 value for 16a against phenylephedrine in rat aorta was much higher than that of prazosin. On the basis of alpha 1-adrenoceptor affinity/selectivity in vitro and duration of antihypertensive action in vivo, compounds 20b and 28b warrant further evaluation.

Adrenergic alpha-Antagonists↗

Excitatory and inhibitory amino acid levels in the cerebrospinal fluids of children with neurological disorders.

Measurement of amino acid levels in the cerebrospinal fluid (CSF) of children with various neurological disorders was performed with high performance liquid chromatography (HPLC). Glutamate increased in patients with bacterial meningitis, aseptic meningitis and encephalitis. Aspartate increased in bacterial meningitis and seizure disorders. Glycine increased in both bacterial and aseptic meningitis. Taurine increased in bacterial meningitis and encephalitis. GABA, the main inhibitory amino acid, increased in encephalitis. Excitatory and inhibitory amino acids are richly distributed in brain tissue and are related to neuron activity. Changes in amino acid levels in the CSF may reflect the pathologic state and severity of brain insults, and may be useful in monitoring disease processes. Further study is necessary to determine whether CSF aminos acid levels have a role in practical clinical application.

Amino Acids↗