Biomedical subjects

K T Lu

Publications and source records attributed to K T Lu.

At least 19 recordsLinked to original sources

PubMed2006

Dissociation dynamics of positive-ion and negative-ion fragments of gaseous and condensed Si(CH(3))(2)Cl(2) via Si 2p, Cl 2p, and Cl 1s core-level excitations.

The state-selective positive-ion and negative-ion dissociation pathways of gaseous and condensed Si(CH(3))(2)Cl(2) following Cl 2p, Cl 1s, and Si 2p core-level excitations have been characterized. The excitations to a specific antibonding state (15a(1) (*) state) of gaseous Si(CH(3))(2)Cl(2) at the Cl 2p, Cl 1s, and Si 2p edges produce significant enhancement of fragment ions. This ion enhancement at specific core-excited states correlates closely with the ion kinetic energy distribution. The results deduced from ion kinetic energy distribution are consistent with results of quantum-chemical calculations on Si(CH(3))(2)Cl(2) using the ADF package. The Cl(-) desorption yields for Si(CH(3))(2)Cl(2)Si(100) at approximately 90 K are notably enhanced at the 15a(1) (*) resonance at both Cl 2p and Si 2p edges. The resonant enhancement of Cl(-) yield occurs through the formation of highly excited states of the adsorbed molecules. These results provide insight into the state-selective ionic fragmentation of molecules via core-level excitation.

Chlorine↗

PubMed2005

Facilitation of conditioned fear extinction by d-cycloserine is mediated by mitogen-activated protein kinase and phosphatidylinositol 3-kinase cascades and requires de novo protein synthesis in basolateral nucleus of amygdala.

Recent results showed that either systemic or intra-amygdala administration of d-cycloserine, a partial agonist at the glycine modulatory site on the glutamate N-methyl-d-aspartate receptor facilitates the extinction of conditioned fear. Here we evaluated the role of mitogen-activated protein kinase and phosphatidylinositol 3-kinase in the basolateral nucleus of amygdala on the effect of d-cycloserine. The facilitation effect of d-cycloserine on fear extinction and mitogen-activated protein kinase activation was completely blocked by intra-amygdala administration of mitogen-activated protein kinase inhibitor PD98059 (500 ng/side, bilaterally) or U0-126 (20 microM/side, bilaterally). Furthermore, phosphatidylinositol 3-kinase inhibitor (wortmannin, 5.0 microg/side, bilaterally) infused into the basolateral nucleus of amygdala significantly reduced both facilitation effect of d-cycloserine and phosphatidylinositol 3-kinase activation. Intra-amygdala administration of a transcription inhibitor (actinomycin D, 10 microg dissolved in 1.6 microl vehicle; 0.8 microl per side) and a translation inhibitor (anisomycin, 125 microg dissolved in 1.6 microl vehicle; 0.8 microl per side) completely blocked the facilitation effect of d-cycloserine. Control experiments indicated the blockage by actinomycin D or anisomycin were not due to lasting damage to the basolateral nucleus of amygdala or state dependency. In addition, none of the active drugs used here altered the expression of conditioned fear. These results suggested that phosphatidylinositol 3-kinase and mitogen-activated protein kinase-dependent signaling cascades and new protein synthesis within the basolateral nucleus of amygdala played important roles in the d-cycloserine facilitation of the extinction of conditioned fear.

Amygdala↗

PubMed2004

State selective enhanced production of excited fragments and ionic fragments of gaseous Si(CH3)2Cl2 and solid-state analogs following core-level excitation.

State-selective fragmentation dynamics for excited fragments and ionic fragments of gaseous and condensed Si(CH3)2Cl2 following Cl 2p and Si 2p core-level excitations have been characterized. The Cl 2p-->15a1* excitation of Si(CH3)2Cl2 induces significant enhancement of the Cl+ desorption yield in the condensed phase and the Si(CH3)+2 and SiCH+3 yields in the gaseous phase. The core-to-Rydberg excitations at both Si 2p and Cl 2p edges lead to enhanced production of the excited fragments. These complementary results provide deeper insight into the origin of state-selective fragmentation of molecules via core-level excitation.

Journal Article↗

PubMed2004

Genetic testing in spinocerebellar ataxia in Taiwan: expansions of trinucleotide repeats in SCA8 and SCA17 are associated with typical Parkinson's disease.

DNA tests in normal subjects and patients with ataxia and Parkinson's disease (PD) were carried out to assess the frequency of spinocerebellar ataxia (SCA) and to document the distribution of SCA mutations underlying ethnic Chinese in Taiwan. MJD/SCA3 (46%) was the most common autosomal dominant SCA in the Taiwanese cohort, followed by SCA6 (18%) and SCA1 (3%). No expansions of SCA types 2, 10, 12, or dentatorubropallidoluysian atrophy (DRPLA) were detected. The clinical phenotypes of these affected SCA patients were very heterogeneous. All of them showed clinical symptoms of cerebellar ataxia, with or without other associated features. The frequencies of large normal alleles are closely associated with the prevalence of SCA1, SCA2, MJD/SCA3, SCA6, and DRPLA among Taiwanese, Japanese, and Caucasians. Interestingly, abnormal expansions of SCA8 and SCA17 genes were detected in patients with PD. The clinical presentation for these patients is typical of idiopathic PD with the following characteristics: late onset of disease, resting tremor in the limbs, rigidity, bradykinesia, and a good response to levodopa. This study appears to be the first report describing the PD phenotype in association with an expanded allele in the TATA-binding protein gene and suggests that SCA8 may also be a cause of typical PD.

Age of Onset↗

PubMed2001

A role for the PI-3 kinase signaling pathway in fear conditioning and synaptic plasticity in the amygdala.

Western blot analysis of neuronal tissues taken from fear-conditioned rats showed a selective activation of phosphatidylinositol 3-kinase (PI-3 kinase) in the amygdala. PI-3 kinase was also activated in response to long-term potentiation (LTP)-inducing tetanic stimulation. PI-3 kinase inhibitors blocked tetanus-induced LTP as well as PI-3 kinase activation. In parallel, these inhibitors interfered with long-term fear memory while leaving short-term memory intact. Tetanus and forskolin-induced activation of mitogen-activated protein kinase (MAPK) was blocked by PI-3 kinase inhibitors, which also inhibited cAMP response element binding protein (CREB) phosphorylation. These results provide novel evidence of a requirement of PI-3 kinase activation in the amygdala for synaptic plasticity and memory consolidation, and this activation may occur at a point upstream of MAPK activation.

Afferent Pathways↗

PubMed2001

Mitogen-activated protein kinase cascade in the basolateral nucleus of amygdala is involved in extinction of fear-potentiated startle.

Previous results indicate that intra-amygdala infusions of NMDA receptor antagonists block the extinction of conditioned fear. Mitogen-activated protein kinase (MAPK) can be activated by NMDA receptor stimulation and is involved in excitatory fear conditioning. Here, we evaluate the role of MAPK within the basolateral amygdala in the extinction of conditioned fear. Rats received 10 light-shock pairings. After 24 hr, fear was assessed by eliciting the acoustic startle reflex in the presence of the conditioned stimulus (CS) (CS-noise trials) and also in its absence (noise-alone trials). Rats subsequently received an intra-amygdala or intrahippocampal infusion of either 20% DMSO or the MAPK inhibitor PD98059 (500 ng/side) followed 10 min later by 30 presentations of the light CS without shock (extinction training). After 24 hr, they were again tested for fear-potentiated startle. PD98059 infusions into the basolateral amygdala but not the hippocampus significantly reduced extinction, which was otherwise evident in DMSO-infused rats. Control experiments indicated that the effect of intra-amygdala PD98059 could not be attributed to lasting damage to the amygdala or to state dependency. These results suggest that a MAPK-dependent signaling cascade within or very near the basolateral amygdala plays an important role in the extinction of conditioned fear.

Amygdala↗

PubMed2001

State-specific enhancement of Cl+ and Cl- desorption for SiCl4 adsorbed on a Si(100) surface following Cl 2 p and Si 2 p core-level excitations.

State-specific desorption for SiCl4 adsorbed on a Si(100) surface at approximately 90 K with variable coverage following the Cl 2p and Si 2p core-level excitations has been investigated using synchrotron radiation. The Cl+ yields show a significant enhancement following the Cl 2p-->8a*1 excitation. The Cl- yields are notably enhanced at the 8a*1 resonance at both Cl 2p and Si 2p edges. The enhancement of the Cl- yield occurs through the formation of highly excited states of the adsorbed molecules. These results provide some new dissociation processes from adsorbates on surfaces via core-level excitation.

Journal Article↗

PubMed2001

Protective effects of anti-C5a peptide antibodies in experimental sepsis.

We evaluated antibodies to different peptide regions of rat C5a in the sepsis model of cecal ligation and puncture (CLP) for their protective effects in rats. Rabbit polyclonal antibodies were developed to the following peptide regions of rat C5a: amino-terminal region (A), residues 1-16; middle region (M), residues 17-36; and the carboxyl-terminal region (C), residues 58-77. With rat neutrophils, the chemotactic activity of rat C5a was significantly inhibited by antibodies with the following rank order: anti-C > anti-M >> anti-A. In vivo, antibodies to the M and C (but not A) regions of C5a were protective in experimental sepsis, as determined by survival over a 10-day period, in a dose-dependent manner. The relative protective efficacies of anti-C5a preparations (in descending order of efficacy) were anti-C > anti-M >> anti-A. In CLP rats, a delay in infusion of antibodies, which were injected at 6 or 12 h after CLP, still resulted in significant improvement in survival rates. These in vivo and in vitro data suggest that there are optimal targets on C5a for blockade during sepsis and that delayed infusion of anti-C5a antibody until after onset of clinical evidence of sepsis still provides protective effects.

Animals↗

PubMed2001

Role of C5a in multiorgan failure during sepsis.

In humans with sepsis, the onset of multiorgan failure (MOF), especially involving liver, lungs, and kidneys, is a well known complication that is associated with a high mortality rate. Our previous studies with the cecal ligation/puncture (CLP) model of sepsis in rats have revealed a C5a-induced defect in the respiratory burst of neutrophils. In the current CLP studies, MOF occurred during the first 48 h with development of liver dysfunction and pulmonary dysfunction (falling arterial partial pressure of O(2), rising partial pressure of CO(2)). In this model an early respiratory alkalosis developed, followed by a metabolic acidosis with increased levels of blood lactate. During these events, blood neutrophils lost their chemotactic responsiveness both to C5a and to the bacterial chemotaxin, fMLP. Neutrophil dysfunction was associated with virtually complete loss in binding of C5a, but binding of fMLP remained normal. If CLP animals were treated with anti-C5a, indicators of MOF and lactate acidosis were greatly attenuated. Under the same conditions, C5a binding to blood neutrophils remained intact; in tandem, in vitro chemotactic responses to C5a and fMLP were retained. These data suggest that, in the CLP model of sepsis, treatment with anti-C5a prevents development of MOF and the accompanying onset of blood neutrophil dysfunction. This may explain the protective effects of anti-C5a in the CLP model of sepsis.

Acidosis↗

PubMed2000

Quantitative measurement on three-dimensional computed tomography: an experimental validation using phantom objects.

BACKGROUND: The use of 3-dimensional computed tomography (CT) imaging has been applied to the craniofacial region as well as to many other parts of the human body. Quantitative measurements have frequently been performed on the 3-dimensional images. However, critical validation of the measurement has been insufficient in the literature. This study was designed to evaluate the errors of the 3-dimensional measurements. METHODS: Four phantom objects, a cube, a sphere, a cylinder, and a life-size adult skull model, were scanned using standard CT acquisition protocol. The data were transferred, reformatted, and displayed on an IBM-compatible personal computer running AnalyzePC 2.5 software. Linear, area, and volume measurements were obtained using one of the two methods. The first was physical measurement of the phantom objects using a caliper for linear measurement and mathematical calculations for area and volume measurements. The second was done by computer measurement on 3-dimensional images using the AnalyzePC 2.5 program. Each measurement was performed twice. The differences were compared between the repeated measurements and between the two methods. RESULTS: The images were displayed according to standard 3-dimensional CT protocol. The differences between the measurements were insignificant and ranged from 0.00 to 2.57%. CONCLUSION: This study validated the accuracy of the quantitative measurements on 3-dimensional CT images.

Humans↗

PubMed1999

Promotion of forskolin-induced long-term potentiation of synaptic transmission by caffeine in area CA1 of the rat hippocampus.

Caffeine which is present in soft drinks has been shown to increase alertness and allays drowsiness and fatigue. The aim of this study is to investigate whether caffeine could produce a long-term effect on the synaptic transmission using extracellular recording technique in the hippocampal slices. Bath application of caffeine (100 microM) reversibly increased the slope of field excitatory postsynaptic potential (fEPSP). Forskolin (25 microM) by its own did not affect the fEPSP significantly. However, in the presence of caffeine, forskolin induced a long-term potentiation (LTP) of fEPSP. Enprofylline which has been shown to exhibit some actions like caffeine but with a low adenosine antagonistic potency did not affect the normal synaptic transmission or the effect of forskolin at a lower concentration (10 microM). However, when the concentrations were increased to 20 and 50 microM, enprofylline significantly enhanced the fEPSP slope and promoted forskolin-induced LTP. The parallel increase of fEPSP and promotion of LTP observed with enprofylline suggests that adenosine A1 antagonism is the primary mechanism behind caffeine's effect. This hypothesis was further strengthened by the finding that promotion of forskolin-induced LTP was mimicked by the non-xanthine adenosine antagonist 9-chloro-2-(furyl)[1,2,4]triazolo [1,5-c]quinazolin-5-amine (CGS 15943). The promotion of forskolin-induced LTP provides a cellular basis behind caffeine's increase in capacity for sustained intellectual performance.

Adenosine↗

PubMed1999

Masking of forskolin-induced long-term potentiation by adenosine accumulation in area CA1 of the rat hippocampus.

At hippocampal Schaffer collateral-CA1 synapses, activation of beta-adrenergic receptors and adenylyl cyclase increases transmitter release. However, this effect is transient, which is in contrast to that seen at mossy fiber-CA3 synapses, where activation of cyclic-AMP-dependent protein kinase results in long-lasting facilitation of transmitter release, a phenomenon known as a presynaptic form of long-term potentiation. The present study was aimed at investigating whether forskolin, an adenylyl cyclase activator, could produce long-term effects at the Schaffer collateral-CA1 synapses using extracellular recording techniques. As has been reported previously, forskolin persistently increased the amplitude of evoked population spikes without having a long-term effect on the field excitatory postsynaptic potentials. However, under the conditions where adenosine A1 receptors are inhibited, cyclic-AMP metabolism is disrupted or the transport of cyclic-AMP is blocked, forskolin induces long-term potentiation. Forskolin-induced potentiation is associated with a decrease in paired-pulse facilitation and is blocked by the cyclic-AMP-dependent protein kinase inhibitor Rp-adenosine-3',5'-cyclic monophosphorothioate. Activation of N-methyl-D-aspartate receptors is not required for forskolin-induced long-term potentiation, because pretreatment of slices with the N-methyl-D-aspartate receptor antagonist D-2-amino-5-phosphonovalerate did not prevent forskolin-induced potentiation. These results suggest that blockade of adenosine A1 receptors unmasks forskolin-induced long-term potentiation, and activation of cyclic-AMP-dependent protein kinase induces a form of long-term potentiation which is different from that induced by tetanic stimulation.

2-Amino-5-phosphonovalerate↗

PubMed1998

Heat shock protein expression protects against death following exposure to heatstroke in rats.

Rats 0, 16, or 48 h after heat shock (42 degrees C core temperature for 15 min) or chemical stress (5 mg/kg sodium arsenite, i.p.) were exposed to a high ambient temperature (43 degrees C) to induce heatstroke onset. The moment in which the mean arterial pressure and cerebral blood flow began to decrease from their peak values was taken as the onset of heatstroke. Prior heat shock or chemical stress conferred significant protection against heatstroke-induced arterial hypotension, cerebral ischemia, cerebral neuronal damage and death, and correlated with expression of HSP72 in brain, heart, liver and kidney at 16 h. However, at 48 h, when HSP72 expression returned to basal values, the above responses that occurred after the onset of heatstroke of two groups (0 h group VS 48 h group) were indistinguishable. The data suggest that HSP72 presence increases survival in rat heatstroke by attenuating arterial hypotension, cerebral ischemia and neuronal damage.

Animals↗

PubMed1998

Endogenous serotonin inhibits epileptiform activity in rat hippocampal CA1 neurons via 5-hydroxytryptamine1A receptor activation.

The modulatory effects of endogenous serotonin on the synaptic transmission and epileptiform activity were studied in the rat hippocampus with the use of extracellular and intracellular recording techniques. Field excitatory postsynaptic potential was reversibly depressed by serotonin in a concentration-dependent manner. Intracellular recordings revealed that serotonin-mediated synaptic depression was unaffected by extracellular Ba2+ or intracellular application of Cs+ while the postsynaptic hyperpolarizing effect was completely blocked. Epileptiform activity induced by picrotoxin (50 microM), a GABA(A) receptor antagonist, was also dose-dependently suppressed by serotonin. The antiepileptic effect was mimicked by 5-hydroxytryptamine1A agonist and was blocked by 5-hydroxytryptamine1A antagonists. 5-Hydroxytryptamine2 antagonist had no effect on the modulation. Similarly, fluoxetine, a selective serotonin re-uptake blocker, potently inhibited the epileptiform activity and this effect was blocked by 5-hydroxytryptamine1A receptor antagonist. Depletion of endogenous serotonin by pretreating the slices with p-chloroamphetamine completely prevented the antiepileptic action of fluoxetine, without modifying the action of serotonin in the same cells. These results suggest that the antiepileptic action of fluoxetine is due to an enhancement of endogenous serotonin which in turn is mediated by 5-hydroxytryptamine1A receptor. Endogenous serotonin transmission in the hippocampus is therefore capable of limiting the development and propagation of seizure activity.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1997

Effect of glucose concentration on swimming motility in enterobacteria.

Since the observation that glucose prevents the synthesis of flagella in Escherichia coli was first reported in 1967, many studies have addressed the underlying mechanism. Currently, it is thought that an increase in glucose concentration decreases the intracellular CRP/cAMP concentration. This leads to an inhibitory effect on the expression of the flhD operon, the master operon for flagella synthesis. In our study on defining factors influencing the cell differentiation of Serratia marcescens, glucose catabolite repression of hag expression and swimming/swarming motility was not observed. Further experiments using a simple swimming motility assay extended this observation to other members of Enterobacteriaceae. Although the underlying mechanism is still uncharacterised, our results suggest that glucose catabolite repression of swimming motility may not be a common phenomenon in Enterobacteriaceae.

DNA-Binding Proteins↗

PubMed1997

Inhibition of synaptic transmission and epileptiform activity in central neurones by fluspirilene.

1. Recent studies have shown that fluspirilene, a dopamine D2 receptor antagonist which is a long-acting neuroleptic useful in the maintenance therapy of schizophrenic patients, also displays Ca2+ channel blocking activity. In the present study, we have investigated the effect of fluspirilene on synaptic transmission and epileptiform activity induced in slices of hippocampus and amygdala. 2. Fluspirilene reversibly suppressed the field excitatory postsynaptic potential (f-e.p.s.p) in a concentration-dependent manner in the area CA1 of the hippocampus without affecting the size and shape of fibre volley. Fluspirilene also inhibited the intracellularly recorded e.p.s.p. in amygdala neurones without affecting the resting membrane potential or neuronal input resistance. 3. Fluspirilene increased the ratio of paired-pulse facilitation suggesting a presynaptic mode of action. 4. Epileptiform activity induced in the disinhibited slices was suppessed by fluspirilene in a concentration-dependent manner. This antiepileptic effect was occluded in slices pretreated with the adenosine A1 receptor agonist, N6-cyclopentyladenosine (CPA). 5. It is concluded that fluspirilene-induced synaptic inhibition is probably due to a reduction in presynaptic Ca2+ currents. In clinical trials, the low incidence of seizures provoked by fluspirilene might be related to its intrinsic ability to inhibit synaptic transmission and epileptiform activity.

Adenosine↗

PubMed1997

Population cell differentiation of Serratia marcescens on agar surface and in broth culture.

The bacterium Serratia marcescens shows population surface migration (swarming) phenomenum on an LB swarming plate, and differentiated cells can be observed at the swarming front. How the cell population differentiates during swarming on the agar surface is not known, neither is it clear whether cells with differentiated characteristics can be observed in broth culture. To monitor the population cell differentiation in a highly sensitive way without cell destruction, experiments were designed using bacterial luciferase genes luxAB as the reporter genes to allow direct monitoring of the differentiating cells through bioluminescence. An isogenic S. marcescens strain was constructed with luxAB under the control of the promoter of flagellin gene hag (phag::luxAB). Patterns of cell differentiation were monitored either by direct X-ray film exposure and/or by Autolumat luminometer detection. Results show that population cell differentiation on the agar surface occurs first in a temporal and then spatial way during colonial growth. It was also found that cells harvested from both the spreading agar plate and broth culture showed differentiation patterns similar to those from swarming cells, suggesting that the agar surface culture may not be essential for the formation of differentiated cells.

Culture Media↗

PubMed1996

Subspecies typing of Vibrio parahaemolyticus by pulsed-field gel electrophoresis.

Vibrio parahaemolyticus is one of the most important food-borne pathogens in Taiwan, Japan, and other costal regions. We report on the development of a pulsed-field gel electrophoresis (PFGE) method for the molecular typing of this pathogen. Genomic DNA was digested with SfiI, and the fragments were resolved on 1% agarose with a contour-clamped homogeneous electric field apparatus set at 190 V and a pulse time of 3 to 80 s. A total of 130 selected isolates obtained from outbreaks during 1993 and 1994 on Taiwan were also characterized by this PFGE method. These isolates were grouped into 14 PFGE types which consisted on one to six patterns, and a total of 39 patterns were identified. Most of these domestic clinical isolates could be clustered into several major types (types A, B, C, and G). These major types showed relatively low degrees of similarity to several foreign strains and other domestic but environmental strains. Strain CCRC12863, which originated from Japan, was close to the group consisting of F, G, and H PFGE types, suggesting a clonal relationship between this Japanese strain and other domestic isolates.

Bacterial Typing Techniques↗