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K Chen

Publications and source records attributed to K Chen.

At least 199 records · Page 11Linked to original sources
PubMed1999

Glutamergic transmission of neuronal responses to carbachol in rat dorsal cochlear nucleus slices.

This study found that glutamate receptor antagonists block the excitatory effects of carbachol, a cholinergic agonist, on bursting neurons in the dorsal cochlear nucleus of rat brain slices. Among antagonists for glutamate receptor subtypes, those for non-N-methyl-D-aspartate ionotropic glutamate receptors were more potent than those for N-methyl-D-aspartate receptors. The glutamate receptor antagonists did not block the effects of carbachol on regularly firing neurons in the dorsal cochlear nucleus of the same slices. Antagonists for GABA or glycine receptors did not alter the effects of carbachol on bursting neurons. Effects of carbachol on bursting activity could be mimicked by application of glutamate or its agonist, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate, whose effects were not blocked by synaptic blockade. During carbachol application, increased release of glutamate and glycine from the dorsal cochlear nucleus part of brain slices was measured using high-performance liquid chromatography. Release of other amino acids showed no significant change. The results suggest that, in rat dorsal cochlear nucleus, cholinergic effects on regular and bursting spontaneous firing occur through different mechanisms. Cholinergic effects on regular neurons (which include fusiform cells) are direct, through muscarinic receptors. Cholinergic effects on bursting neurons (which include cartwheel cells) are indirect and involve glutamatergic neurotransmission, mostly via non-N-methyl-D-aspartate ionotropic receptors. The granule cell-parallel fiber pathway may be involved in this glutamatergic transmission.

Amino Acids↗
PubMed1999

Inhibition of copper-induced LDL oxidation by vitamin C is associated with decreased copper-binding to LDL and 2-oxo-histidine formation.

Oxidatively modified low-density lipoprotein (LDL) has numerous atherogenic properties, and antioxidants that can prevent LDL oxidation may act as antiatherogens. We have previously shown that vitamin C (L-ascorbic acid, AA) and its two-electron oxidation product dehydro-L-ascorbic acid (DHA) strongly inhibit copper (Cu)-induced LDL oxidation. These findings are unusual, as AA is known to act not only as an antioxidant, but also a pro-oxidant in the presence of transition metal ions in vitro, and DHA has no known reducing capacity. Here we report that human LDL (0.4 mg protein/ml) incubated with 40 microM Cu2+ binds 28.0 +/- 3.3 Cu ions per LDL particle (mean +/- SD, n = 10). Co-incubation of LDL with AA or DHA led to the time- and concentration-dependent release of up to 70% of bound Cu, which was associated with the inhibition of LDL oxidation. Incubation of LDL with Cu and AA or DHA also led to the time-dependent formation of 2-oxo-histidine, an oxidized derivative of histidine with a low affinity for Cu. Addition of free histidine prevented the formation of the LDL-Cu complexes and inhibited LDL oxidation, despite the fact that Cu remained redox-active. Interestingly, histidine was more effective than AA or DHA at limiting Cu binding to LDL, but at low concentrations AA and DHA were more effective than histidine at inhibiting LDL oxidation. These data suggest that there are at least two types of Cu binding sites on LDL: those that bind Cu in a redox-active form critical for initiation of LDL oxidation, and those that bind Cu in a redox-inactive form not contributing to LDL oxidation. The former sites may be primarily histidine residues of apolipoprotein B-100 that are oxidized to 2-oxo-histidine in the presence of Cu and AA or DHA, thus explaining, at least in part, the unusual inhibitory effect of vitamin C on Cu-induced LDL oxidation.

Antioxidants↗
PubMed1999

Schizophrenia, monoamine oxidase activity, and cigarette smoking.

Reduced monoamine oxidase activity has been proposed as a marker for vulnerability to schizophrenia. Reduced monamine oxidase activity has also been shown to occur in cigarette smokers. This study compared monamine oxidase activity level in a matched group of patients with schizophrenia who smoked with a group who did not. Lower levels of monoamine oxidase activity were found in the smokers and this is the likely explanation for the low levels hypothesized as a marker for schizophrenia.

Adult↗
PubMed1999

Improved learning algorithms for mixture of experts in multiclass classification.

Mixture of experts (ME) is a modular neural network architecture for supervised learning. A double-loop Expectation-Maximization (EM) algorithm has been introduced to the ME architecture for adjusting the parameters and the iteratively reweighted least squares (IRLS) algorithm is used to perform maximization in the inner loop [Jordan, M.I., Jacobs, R.A. (1994). Hierarchical mixture of experts and the EM algorithm, Neural Computation, 6(2), 181-214]. However, it is reported in literature that the IRLS algorithm is of instability and the ME architecture trained by the EM algorithm, where IRLS algorithm is used in the inner loop, often produces the poor performance in multiclass classification. In this paper, the reason of this instability is explored. We find out that due to an implicitly imposed incorrect assumption on parameter independence in multiclass classification, an incomplete Hessian matrix is used in that IRLS algorithm. Based on this finding, we apply the Newton-Raphson method to the inner loop of the EM algorithm in the case of multiclass classification, where the exact Hessian matrix is adopted. To tackle the expensive computation of the Hessian matrix and its inverse, we propose an approximation to the Newton-Raphson algorithm based on a so-called generalized Bernoulli density. The Newton-Raphson algorithm and its approximation have been applied to synthetic data, benchmark, and real-world multiclass classification tasks. For comparison, the IRLS algorithm and a quasi-Newton algorithm called BFGS have also been applied to the same tasks. Simulation results have shown that the use of the proposed learning algorithms avoids the instability problem and makes the ME architecture produce good performance in multiclass classification. In particular, our approximation algorithm leads to fast learning. In addition, the limitation of our approximation algorithm is also empirically investigated in this paper.

Journal Article↗
PubMed1999

A simple new model of physiologically working heterotopic rat heart transplantation provides hemodynamic performance equivalent to that of an orthotopic heart.

BACKGROUND: The widely used non-volume-loaded abdominal heterotopic heart transplant (NL) in rats undergoes atrophy after transplantation. Various techniques have been designed to load the transplanted heart because of its potential immunological impact. Our aim was to create a volume-loaded heterotopic heart transplantation model (VL) capable of ejection and practical for routine studies. Using this model, we tested the hypothesis that VL isografts would retain myocardial performance comparable to native hearts (NH). METHODS: Heterotopic hearts were transplanted using and end-to-side anastomosis between the donor's superior vena cava and the recipient's abdominal inferior vena cava. The right ventricle loads the left ventricle (LV) via a direct anastomosis of the pulmonary artery to the left atrium. The LV ejects volume through an end-to-side anastomosis of the donor's aorta to the recipient's abdominal aorta. Hemodynamic data (systolic and diastolic LV pressures, dP/dt max and min, tau) were studied in-situ (at baseline and after adding volume) and in a Langendorff perfusion system (at baseline and after stimulation with isoproterenol) 2 weeks after transplantation. RESULTS: In situ systolic pressure and diastolic function of VL was superior to NL, and beta-adrenergic stimulated performance in the Langendorff perfusion of VL showed hemodynamic performance equivalent to NH, unlike NL which had a diminished response. CONCLUSION: This technique results in a volume-loaded ejecting heart transplant model that preserves anatomical structures. The VL can be evaluated in situ and after explantation in Langendorff perfusion system and may offer advantages if workload of the graft is of significance to the study performed.

Abdomen↗
PubMed1999

Febrile seizures in the developing brain result in persistent modification of neuronal excitability in limbic circuits.

Febrile (fever-induced) seizures affect 3-5% of infants and young children. Despite the high incidence of febrile seizures, their contribution to the development of epilepsy later in life has remained controversial. Combining a new rat model of complex febrile seizures and patch clamp techniques, we determined that hyperthermia-induced seizures in the immature rat cause a selective presynaptic increase in inhibitory synaptic transmission in the hippocampus that lasts into adulthood. The long-lasting nature of these potent alterations in synaptic communication after febrile seizures does not support the prevalent view of the 'benign' nature of early-life febrile convulsions.

Animals↗
PubMed1999

Striatal dopamine metabolism in monoamine oxidase B-deficient mice: a brain dialysis study.

We have studied striatal dopamine (DA) metabolism in monoamine oxidase (MAO) B-deficient mice using brain microdialysis. Baseline DA levels were similar in wild-type and knock-out (KO) mice. Administration of a selective MAO A inhibitor, clorgyline (2 mg/kg), increased DA levels and decreased levels of its metabolites in all mice, but a selective MAO B inhibitor, l-deprenyl (1 mg/ kg), had no effect. Administration of 10 and 50 mg/kg L-DOPA, the precursor of DA, increased the levels of DA similarly in wild-type and KO mice. The highest dose of L-DOPA (100 mg/kg) produced a larger increase in DA in KO than wild-type mice. This difference was abolished by pretreating wild-type mice with l-deprenyl. These results suggest that in mice, DA is only metabolized by MAO A under basal conditions and by both MAO A and B at high concentrations. This is in contrast to the rat, where DA is always metabolized by MAO A regardless of concentration.

Animals↗
PubMed1999

Regions of the human brain affected during a liquid-meal taste perception in the fasting state: a positron emission tomography study.

BACKGROUND: The sensation of taste provides reinforcement for eating and is of possible relevance to the clinical problem of obesity. OBJECTIVE: Positron emission tomography (PET) was used to explore regions of the brain that were preferentially affected during the taste perception of a liquid meal by 11 right-handed, lean men in the fasting state. DESIGN: After subjects had fasted for 36 h, 2 measurements of regional cerebral blood flow (rCBF) obtained immediately after subjects retained and swallowed 2 mL of a flavored liquid meal (the taste condition) were compared with 2 measurements of rCBF obtained immediately after subjects retained and swallowed 2 mL of water (the baseline condition). RESULTS: Compared with the baseline condition, taste was associated with increased rCBF (P < 0.005) in the left dorsolateral prefrontal cortex and superior temporal gyrus; the right ventrolateral prefrontal cortex, supramarginal gyrus, and anterior thalamus; and bilaterally in the hippocampal formation, posterior cingulate, midbrain, occipital cortex, and cerebellum. Taste was also associated with decreased rCBF (P < 0.005) in the right dorsolateral prefrontal cortex, superior temporal gyrus, and supplementary motor area, and bilaterally in the medial prefrontal cortex and inferior parietal lobule. CONCLUSIONS: This exploratory study provides additional evidence that the temporal cortex, thalamus, cingulate cortex, caudate, and hippocampal formation are preferentially affected by taste stimulation. The asymmetric pattern of activity in the dorsolateral prefrontal cortex and superior temporal gyrus may contribute to the taste perception of a liquid meal perceived as pleasant. Additional studies are required to determine how these regions are affected in patients with obesity or anorexia.

Adult↗
PubMed1999

A modular neural network architecture for pattern classification based on different feature sets.

We propose a novel connectionist method for the use of different feature sets in pattern classification. Unlike traditional methods, e.g., combination of multiple classifiers and use of a composite feature set, our method copes with the problem based on an idea of soft competition on different feature sets developed in our earlier work. An alternative modular neural network architecture is proposed to provide a more effective implementation of soft competition on different feature sets. The proposed architecture is interpreted as a generalized finite mixture model and, therefore, parameter estimation is treated as a maximum likelihood problem. An EM algorithm is derived for parameter estimation and, moreover, a model selection method is proposed to fit the proposed architecture to a specific problem. Comparative results are presented for the real world problem of speaker identification.

Humans↗
PubMed1999

Monoamine oxidase: from genes to behavior.

Cloning of MAO (monoamine oxidase) A and B has demonstrated unequivocally that these enzymes are made up of different polypeptides, and our understanding of MAO structure, regulation, and function has been significantly advanced by studies using their cDNA. MAO A and B genes are located on the X-chromosome (Xp11.23) and comprise 15 exons with identical intron-exon organization, which suggests that they are derived from the same ancestral gene. MAO A and B knock-out mice exhibit distinct differences in neurotransmitter metabolism and behavior. MAO A knock-out mice have elevated brain levels of serotonin, norephinephrine, and dopamine and manifest aggressive behavior similar to human males with a deletion of MAO A. In contrast, MAO B knock-out mice do not exhibit aggression and only levels of phenylethylamine are increased. Mice lacking MAO B are resistant to the Parkinsongenic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine. Both MAO A and B knock-out mice show increased reactivity to stress. These knock-out mice are valuable models for investigating the role of monoamines in psychoses and neurodegenerative and stress-related disorders.

Alcoholism↗
PubMed1999

Genetic mapping of the rat Lcn2 gene to chromosome 3.

The expression of rat 24p3, encoded by the Lcn2 gene, has been associated with rat mammary carcinomas initiated by the neu oncogene (Stoesz and Gould, 1995). In this study, we assign the Lcn2 gene to rat chromosome band 3q12 by genetic linkage analysis.

Acute-Phase Proteins↗
PubMed1999

Functional brain mapping using positron emission tomography scanning in preoperative neurosurgical planning for pediatric brain tumors.

OBJECT: The purpose of this report is to demonstrate the value of functional brain mapping using the positron emission tomography (PET) method for preoperative neurosurgical planning in children with brain tumors. Brain maps were used to characterize the relationship between potentially resectable tumors and functionally eloquent brain areas. METHODS: Five children, ranging in age from 3 to 13 years, with hemispheric brain tumors adjacent to eloquent cortex were studied. Magnetic resonance (MR) imaging was used to identify the brain tumors; PET imaging after injection of [18F] fluorodeoxyglucose (FDG), [11C]L-methionine (CMET), or a combination of the two was performed to grade the tumors; and a [15O] H2O uptake study was used to characterize the anatomical relationships of the tumors to functional cortex. The cortical activation maps were obtained during control periods and during behavioral tasks and were used to document motor, visual, and speech and language organizational areas. Wada tests were performed in two patients. Language and speech activation was concordant with the results of Wada testing. CONCLUSIONS: Functional brain mapping using PET scans and coregistered MR images provided the neurosurgeon with precise definitions of structural and functional cortical areas; this altered surgical management in some cases and/or was used to predict outcome. The combination of PET imaging with FDG and/or CMET and measurements of [15O] water uptake was useful in characterizing and grading tumors and instrumental in achieving effective neurosurgical planning. Postoperative results in the five cases suggest that preoperative functional brain mapping has the potential to improve outcome by defining a surgical plan to maximize resection and minimize the risk of neurological sequelae.

Adolescent↗
PubMed1999

Acute effect of ephedrine on 24-h energy balance.

Ephedrine is used to help achieve weight control. Data on its true efficacy and mechanisms in altering energy balance in human subjects are limited. We aimed to determine the acute effect of ephedrine on 24-h energy expenditure, mechanical work and urinary catecholamines in a double-blind, randomized, placebo-controlled, two-period crossover study. Ten healthy volunteers were given ephedrine (50 mg) or placebo thrice daily during each of two 24-h periods (ephedrine and placebo) in a whole-room indirect calorimeter, which accurately measures minute-by-minute energy expenditure and mechanical work. Measurements were taken of 24-h energy expenditure, mechanical work, urinary catecholamines and binding of (+/-)ephedrine in vitro to human beta1-, beta2- and beta3-adrenoreceptors. Twenty-four-hour energy expenditure was 3.6% greater (8965+/-1301 versus 8648+/-1347 kJ, P<0.05) with ephedrine than with placebo, but mechanical work was not different between the ephedrine and placebo periods. Noradrenaline excretion was lower with ephedrine (0.032+/-0.011 microg/mg creatinine) compared with placebo (0.044+/-0.012 microg/mg creatinine) (P<0.05). (+/-)Ephedrine is a relatively weak partial agonist of human beta1- and beta2-adrenoreceptors, and had no detectable activity at human beta3-adrenoreceptors. Ephedrine (50 mg thrice daily) modestly increases energy expenditure in normal human subjects. A lack of binding of ephedrine to beta3-adrenoreceptors and the observed decrease in urinary noradrenaline during ephedrine treatment suggest that the thermogenic effect of ephedrine results from direct beta1-/beta2-adrenoreceptor agonism. An indirect beta3-adrenergic effect through the release of noradrenaline seems unlikely as urinary noradrenaline decreased significantly with ephedrine.

Adrenergic alpha-Agonists↗
PubMed1999

Quantification of myocardial blood flow using 13N-ammonia and PET: comparison of tracer models.

UNLABELLED: Several tracer kinetic methods have been proposed for quantification of regional myocardial blood flow (MBF) with 13N-ammonia and PET. Merits and limitations specific to each approach, however, generally are not clear, because they have not been evaluated in the same experimental environment. Therefore, we compared six different commonly used methods (11 modifications) to characterize the accuracy of each approach. The methods included the two-parameter model (method 1), the modified two-parameter model (method 2), the four-parameter model (method 3), the graphical analysis (method 4), the first-pass extraction method (method 5) and the dose uptake index (DUI; method 6). METHODS: Eleven studies in four dogs, 16 studies in eight healthy human volunteers and 14 studies in seven patients were performed using 13N-ammonia and PET. MBF in dogs was varied with dipyridamole and coronary occlusions and was measured independently and simultaneously with microspheres. Volunteers and patients were studied at baseline and after dipyridamole. MBF and DUI were estimated using a time-activity curve (Qi[t]) derived from dynamic images and regions of interest (ROls) and using the six methods. DUI was defined as Qi(t = 2 min) x weight/dose. RESULTS: MBF estimated by methods 1-5 correlated well with microsphere MBF in dogs. MBF estimates by method 1 correlated well with those by methods 2, 4 and 5 and to a lesser degree with those by method 3 in both dog and human studies. DUI correlated poorly with MBF by microspheres and by methods 1-5 in both dog and human studies. MBF estimates by method 3 showed larger dispersion (SD/mean flow) and higher sensitivity to metabolites correction in arterial blood than those by methods 1, 2, 4 and 5. CONCLUSION: MBF can be measured accurately using 13N-ammonia PET and tracer kinetic methods. DUI is a poor indicator of MBF values. The results indicate that preference should be given to the two-parameter model, incorporating geometrical ROI representation (method 2) among the compartment models, and to the graphical analysis (method 4) among the noncompartmental approaches.

Adult↗
PubMed1999

Expression of NOS II and its role in experimental small bowel ulceration in rats.

BACKGROUND: Overproduction of nitric oxide (NO) has been implicated in the pathogenesis of experimental and clinical inflammatory bowel disease (IBD). METHODS: We observed the expression and localization of inducible NO synthase (NOS-II) in small intestinal ulceration induced by indomethacin in rats. The role of NO was investigated by using NO synthase inhibitors. RESULTS: The small intestine was affected by longitudinal ulcers after indomethacin administration and ulceration was associated with distinctive expression of NOS-II protein and mRNA. The amount of its expression was found to correlate with the extent of inflammation. Histologically, both immunohistochemistry and in situ hybridization revealed a similar localization of NOS-II to inflammatory and epithelial cells. The possible amelioration of the inflammation was modulated by aminoguanidine (AG) and NG-nitro-L-arginine methyl ester (L-NAME) treatment for 10 days. Both AG and L-NAME attenuated intestinal myeloperoxidase activity and gross inflammation, only AG was found to decrease intestinal permeability with a significant amelioration of body weight loss. CONCLUSION: These findings indicate that NO derived mainly from inflammatory cells may play an important role in the pathophysiology of intestinal ulceration and offer the potential for future treatment directed at blocking neutrophils recruitment and NO overproduction in IBD.

Animals↗
PubMed1999

Extent and appropriateness of emergency department services usage by foreign workers in Singapore.

The objective of this study was to determine the extent and appropriateness of emergency department services usage by foreign workers. A prospective questionnaire survey of foreign workers who attended the Emergency Department (ED) of Tan Tock Seng Hospital was conducted from 30 December 1996 to 29 January 1997. A foreign worker was defined as a non-citizen, non-permanent resident working in Singapore, excluding students and tourists. Demographic and clinical data were collected. During the study period, 7409 patients above the age of 15 attended the ED of which 1174 (15.8%) were foreign workers. Forty-seven per cent of these foreign workers could not speak English, of whom 48.2% did not come with any English-speaking companion. Most of their ED visits were on weekdays and during office hours. Of the foreign workers, 43.1% were classified as non-emergency by ED doctors compared to 6.7% of other ED patients (P < 0.01). Trauma-related complaints accounted for 43.4% while febrile and minor infectious illnesses accounted for 26.7% of foreign workers' complaints. Admissions from ED into the hospital were 17.1% for foreign workers and 28.3% (P < 0.01) for other patients. Language barrier and lack of information on types of health care services available could have led to the high proportion of inappropriate use of ED services by foreign workers. Most of their complaints were minor injuries and illnesses which could be managed by non-ED health care providers. Care provided across a language barrier raises ethical and medico-legal questions. A multi-agency approach involving the Manpower and Health Ministries, employer and foreign worker representatives is needed to eliminate language barrier and help these workers to use health care services appropriately.

Adolescent↗