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Biomedical subjects

D W Choi

Publications and source records attributed to D W Choi.

At least 181 records · Page 10Linked to original sources
PubMed1990

Paragonimus and paragonimiasis in Korea.

The lung fluke, Paragonimus, and lung fluke disease, were reviewed, especially on the works performed in Korea. Among 43 species of Paragonimus recorded in the world literature, P. westermani, P. pulmonalis, and P. iloktsuenensis are known to distribute in Korea. Biological studies on P. westermani have revealed that its snail intermediate host is Semisulcospira spp. and major second intermediate hosts are crabs such as Eriocheir japonicus and E. sinensis or crayfish such as Cambaroides similis and C. dauricus. The final hosts other than man are dogs, cats, pigs, and wild animals. Paragonimiasis has been known to distribute widely over the south Korea, however, the prevalence among people and intermediate hosts is gradually decreasing in recent years. In Korean people, the lung fluke have caused pulmonary infections in a great many of cases but as well extrapulmonary ones including cerebral, spinal, subcutaneous, hepatic, splenic, abdominal, urinary, gynecologic, and other types. The definite diagnosis of paragonimiasis can be executed by the recovery of eggs from sputum or feces of patients, however, immunological methods such as intradermal test, complement-fixation test, precipitin reactions, immunofluorescent techniques, enzyme-linked immunosorbent assay (ELISA) are greatly helpful for egg-negative or extrapulmonary cases. Various drugs have been introduced for the treatment of paragonimiasis, and among them, bithionol, niclofolan and praziquantel have shown high therapeutic efficacy. The most recommendable one is considered praziquantel. For control of this disease, mass chemotherapy of patients seems to be the most efficient and feasible measure.

Animals↗
PubMed1990

Effect of zinc on NMDA receptor-mediated channel currents in cortical neurons.

Recent data have indicated that the divalent cation Zn2+ can selectively block central neuronal excitation mediated by N-methyl-D-aspartate (NMDA) receptors. The present experiments were conducted to determine the action of Zn2+ at the single-channel level. Outside-out membrane patches were prepared from cultured murine cortical neurons. Glutamate, 3 microM, in the presence of 5 microM glycine activated channels with a main conductance state of about 50 pS which were blocked in a voltage-dependent manner by Mg2+. Zn2+ appeared to have 2 effects on these NMDA receptor-activated channels. First, at concentrations as low as 1-10 microM, Zn2+ produced a concentration-dependent reduction in channel open probability, insensitive to membrane voltage between -60 and +40 mV; about 50% reduction in open probability was produced by 3 microM Zn2+. This reduction was mostly due to a decrease in opening frequency and only weakly mimicked by Mg2+. Second, at higher concentrations (10-100 microM) and negative membrane voltages, Zn2+ additionally produced an apparent reduction in single-channel amplitude, associated with an increase in channel noise, suggestive of a fast channel block. The amplitude reduction was voltage-dependent, with a delta of 0.51; amplitude distribution analysis suggested that this voltage dependence was primarily contributed by the "on" blocking rate constant, with little contribution from the "off" rate constant. The channel block produced by Zn2+ was faster than that of Mg2+, which at 100 microM and negative membrane voltages induces flickering of the NMDA receptor-activated channel without changing apparent channel amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Possible mechanisms limiting N-methyl-D-aspartate receptor overactivation and the therapeutic efficacy of N-methyl-D-aspartate antagonists.

Cytotoxic overactivation of neuronal N-methyl-D-aspartate receptors is postulated to contribute to the pathogenesis of neuronal loss in hypoxia-ischemia. However, several events associated with hypoxia-ischemia may limit N-methyl-D-aspartate receptor-mediated injury. Perhaps the most important of these events is the development of extracellular acidosis. These limiting events may help explain why N-methyl-D-aspartate receptors contribute to injury more in focal ischemia or hypoxia in vitro than in global ischemia.

Adenosine↗
PubMed1990

Methods for antagonizing glutamate neurotoxicity.

Recent evidence suggests that glutamate-induced neuronal damage may contribute importantly to neuronal death in several neurological diseases, including cerebral hypoxia-ischemia. This review outlines a range of measures that might be used to protect neurons from such excitotoxic damage. The organizing thesis is a speculative consideration of glutamate neurotoxicity as a sequential three-stage process--induction, amplification, and expression--each perhaps specifically amenable to therapeutic interference. Overstimulation of glutamate receptors likely induces the intracellular accumulation of several substances, including Ca2+, Na+, inositol-1,4,5-trisphosphate, and diacylglycerol. Blockade of this induction might be accomplished most easily by antagonizing postsynaptic glutamate receptors, but also might be accomplished by reducing glutamate release from presynaptic terminals, or improving glutamate clearance from synaptic clefts. Following induction, several steps may importantly amplify the resultant rise in intracellular free Ca2+, and promote the spread of excessive excitation to other circuit neurons. Protective strategies operative at this level might include blockade of additional Ca2+ influx, blockade of Ca2+ release from intracellular stores, and interference with the mechanisms coupling glutamate receptor stimulation to lasting enhancements of excitatory synaptic efficacy. Following amplification, toxic levels of intracellular free Ca2+ might trigger destructive cascades bearing direct responsibility for resultant neuronal degeneration--the expression of excitotoxicity. The most important cascades to block may be those related to the activation of catabolic enzymes, and the generation of free radicals. Broad consideration of possible methods for antagonizing glutamate neurotoxicity may be needed to develop therapies with the greatest efficacy, and least adverse consequences for brain function.

Cell Survival↗
PubMed1990

Intracellular free calcium increases in cultured cortical neurons deprived of oxygen and glucose.

Dissociated neocortical cultures from fetal mice exposed transiently to a medium lacking both glucose and oxygen developed neuronal degeneration without glial degeneration. We have found that this injury depends on extracellular calcium and is associated with uptake of calcium from the culture medium. We measured free cytoplasmic calcium in individual neurons using the fluorescent calcium indicator fluo-3 and provide evidence that oxygen and glucose deprivation injury increases the intracellular calcium signal. Both intracellular calcium elevation and subsequent neuronal loss could be blocked by the N-methyl-D-aspartate receptor antagonist dextrorphan.

Aniline Compounds↗
PubMed1990

Carcinosarcoma of the stomach. A case report with light microscopic, immunohistochemical, and electron microscopic study.

A carcinosarcoma of the stomach in a 66-year-old man is reported. The tumor which had a diameter of 4 cm was an ulcerofungating mass in the posterior wall of the antrum. Histologically it was composed of well-differentiated adenocarcinoma admixed with sarcomatous elements which showed chondrocytic differentiation on light and electron microscopy. The sarcomatous areas were multifocally scattered in the central portion of the tumor and intimately blended with adenocarcinoma cells. CEA immunoreactivity was found not only in the adenocarcinoma but also in the transitional sarcomatous cells, supporting the hypothesis that this tumor might derive from mesenchymal metaplasia of a primarily epithelial neoplasm.

Adenocarcinoma↗
PubMed1990

Non-NMDA receptor-mediated neurotoxicity in cortical culture.

The neurotoxicity of 3 non-NMDA glutamate receptor agonists--kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA), and quisqualate--was investigated quantitatively in dissociated murine cortical cultures. Five minute exposure to 500 microM kainate, but not AMPA, produced widespread acute neuronal swelling. Kainate-induced swelling was resistant to 2-amino-5-phosphonovalerate (APV) or replacement of extracellular sodium with choline but attenuated by either kynurenate or low concentrations of quisqualate. Unlike NMDA agonists, kainate or AMPA did not produce much late neuronal loss after a 5 min exposure. In contrast, 5 min exposure to 500 microM quisqualate produced both acute neuronal swelling and widespread late neuronal degeneration. This acute swelling was blocked by APV or by replacement of extracellular sodium by choline, consistent with mediation by NMDA receptors; we speculate that high concentrations of quisqualate may directly activate NMDA receptors or induce the release of endogenous glutamate. Quisqualate-induced late neuronal degeneration may be due to another unexpected process: cellular quisqualate uptake and delayed release, converting brief addition into prolonged exposure. Hours after thorough washout of exogenously added quisqualate, micromolar concentrations could be detected in the bathing medium by high performance liquid chromatography. With lengthy exposure (20-24 hr), all 3 non-NMDA agonists were potent neurotoxins, able to destroy neurons with EC50's of about 20 microM for kainate, 4 microM for AMPA, and 1 microM for quisqualate. Kynurenate and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), but not APV or L-glutamate diethyl ester, were effective in attenuating the neuronal degeneration induced by these agonists. CNQX was about 3 times more selective than kynurenate against kainate-induced neuronal injury, but CNQX was still nearly equipotent with APV against NMDA-induced injury. Gamma-D-glutamylaminomethyl sulfonate exhibited partial antagonist specificity for AMPA-induced toxicity.

Amino Acids↗
PubMed1989

Neurotoxicity of beta-N-methylamino-L-alanine (BMAA) and beta-N-oxalylamino-L-alanine (BOAA) on cultured cortical neurons.

Recent studies have implicated the ingestion of the structurally related plant excitotoxins, beta-N-methylamino-L-alanine (BMAA), and beta-N-oxalylamino-L-alanine (BOAA), in the pathogenesis of two human motor system diseases, the amyotrophic lateral sclerosis-Parkinsonism-dementia complex of Guam (Guam ALS-PD), and lathyrism, respectively. We have investigated the toxicity of these amino acids on cultured mouse cortical neurons in the presence of physiological concentrations of bicarbonate (a required toxic cofactor for BMAA neurotoxicity). A 24 h exposure to 10 microM - 3 mM BMAA, or to 300 nM - 100 microM BOAA, induced, concentration-dependent neuronal degeneration without glial damage; the neurotoxic EC50 for BMAA was about 1 mM, and the EC50 for BOAA was about 20 microM. At high concentrations, both compounds destroyed essentially the entire neuronal population. Neurotoxicity also depended on exposure duration, with reduced injury at an exposure time of 1 h, and increased injury at an exposure time of 3 days. Despite the fact that ingestion of BMAA and BOAA both lead to motor system damage, previous studies have suggested that the two excitotoxins act primarily on different glutamate receptor subtypes: BMAA on N-methyl-D-aspartate (NMDA) receptors, and BOAA on non-NMDA receptors. Consistent with these studies, the neurotoxicity of high concentrations of BMAA was substantially attenuated by 1 mM D-amino-5-phosphonovalerate (D-APV), whereas BOAA neurotoxicity was less sensitive to D-APV but was attenuated by 2 mM kynurenate.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids, Diamino↗
PubMed1989

Selective vulnerability of the brain: new insights into the pathophysiology of stroke.

Stroke is a major cause of morbidity and mortality in the United States with 250,000 cases per year. Cerebral ischemia is the largest category of stroke with cardiac arrest, profound hypotension, and vascular occlusion the principal causes. Traditional approaches to the treatment of ischemic stroke focus on maintaining cardiac output, blood pressure, cerebral blood flow, and on preventing thrombosis. Recently, attention has been focused on developing new therapies that are directed toward abnormal biochemical events at excitatory synapses. Ischemia causes impairment of brain energy metabolism and the release of excessive amounts of glutamate into the extracellular space. This process secondarily excites neurons and further depletes energy stores. The excitotoxic hypothesis of brain injury proposes that glutamate is a principal cause of damage in ischemia. Three components of this hypothesis have been tested and largely proved in experimental studies in tissue culture and in animal models of stroke. First, elevated concentrations of glutamate cause excessive excitation at a subset of glutamate receptors, the N-methyl-D-aspartate (NMDA) receptor. Second, excitation at this receptor leads to excessive influx of sodium chloride and water which causes acute neuronal damage, and calcium which causes delayed and more permanent damage. Third, pharmacologic blockade at the NMDA receptor-ion channel complex prevents ischemic neuronal damage. Studies using specific pharmacologic compounds that block glutamate's action hold particular promise for treating stroke in humans, including competitive antagonists at the NMDA glutamate binding site (for example, 2-amino-5-phosphonovalerate, AP5), noncompetitive antagonists at the calcium channel (for example, MK-801, dextromethorphan, ketamine), and agents that might be directed at the glycine, zinc, and magnesium sites.

Animals↗
PubMed1989

Glucose deprivation neuronal injury in cortical culture.

Murine cortical cell cultures deprived of glucose for 6-8 h developed extensive neuronal degeneration, apparent both morphologically and by efflux of lactate dehydrogenase to the bathing medium. This neuronal damage could be substantially reduced by addition of D-2-amino-5-phosphonovalerate (D-APV), in a concentration-dependent (IC50 about 2 microM) and stereospecific (D-APV more potent than L-APV) fashion. A similar neuron-protective effect could also be obtained with several other NMDA antagonists, 2-amino-7-phosphonoheptanoate, phencyclidine, MK-801, ketamine, and (+)-SKF 10,047, as well as with the broad spectrum glutamine antagonist kynurenate. In contrast, little protection could be obtained with gamma-D-glutamylaminomethyl sulfonate and L-glutamate diethyl ester, compounds which have been reported to act primarily at non-NMDA receptors. These observations support the hypothesis that glucose deprivation-induced cortical neuronal injury is largely mediated by NMDA receptors, and suggest that cell culture methodology can be useful in the quantitative characterization of that injury.

2-Amino-5-phosphonovalerate↗
PubMed1989

Zinc and LTP.

Explore the source record for details and available documents.

Action Potentials↗
PubMed1989

N-methyl-D-aspartate antagonists: ready for clinical trial in brain ischemia?

Antagonists of the N-methyl-D-aspartate (NMDA) subclass of glutamate receptors may offer a new approach for the treatment of ischemic brain injury. This strategy is supported by a well-developed scientific foundation and encouraging results in a variety of in vivo and in vitro experimental models. Several specific antagonists, including MK-801, dextrorphan, dextromethorphan, and ketamine, have already been used at low doses in humans for other indications and are potential candidates for Phase I clinical trials.

Aspartic Acid↗
PubMed1989

Aspartate neurotoxicity on cultured cortical neurons.

L-aspartate neurotoxicity was quantitatively characterized in murine cortical cell cultures. Five-minute exposure to 30 microM-3 mM L-aspartate resulted in concentration-dependent (ED50 about 190 microM) neuronal destruction over the next 10 hr; glia were not injured. D-aspartate and L-aspartate were roughly equipotent neurotoxins. Ion substitution experiments suggested that L-aspartate neurotoxicity is comprised of both acute, sodium-dependent "excitotoxicity" and delayed, calcium-dependent degeneration, with the latter predominant under conditions of brief exposure. Aspartate neurotoxicity could be attenuated by D-2-amino-5-phosphonovalerate (D-APV), dextrorphan, ketamine, and kynurenate, but not by L-glutamate diethyl ester or gamma-D-glutamylaminomethyl sulfonate, consistent with principal involvement of N-methyl-D-aspartate receptors. D-APV and dextrorphan produced different effects on the aspartate concentration-toxicity relation; the former drug was consistent with a competitive and the latter with a noncompetitive mechanism of antagonism.

Animals↗
PubMed1989

Traumatic neuronal injury in vitro is attenuated by NMDA antagonists.

Pure traumatic neuronal injury was modeled in dispersed neocortical cell cultures derived from fetal mice. A plastic stylet was used to tear the neuronal and glial cell layer; medium oxygen content, pH, and glucose remained unchanged. Adjacent to this local disruption, many neurons developed acute swelling and went on to degenerate over the next day, but glia were relatively spared. If the same mechanical insult was delivered in the presence of the N-methyl-D-aspartate (NMDA) antagonists dextrorphan or D-2-amino-5-phosphonovalerate, resultant neuronal degeneration was markedly reduced. The protective effect of these NMDA antagonists was concentration-dependent between 1 and 100 microM, with EC50 near 10 microM for both compounds. Present findings suggest that endogenous excitatory amino acids may participate significantly in the propagation of central neuronal cell loss in response to a purely mechanical insult.

2-Amino-5-phosphonovalerate↗
PubMed1989

Bicarbonate dependence of glutamate receptor activation by beta-N-methylamino-L-alanine: channel recording and study with related compounds.

beta-N-methylamino-L-alanine (BMAA) is a neurotoxic glutamate agonist possibly responsible for the neuronal degeneration found in the Guam amyotrophic lateral sclerosis-Parkinsonism-dementia complex. The basis for glutamate receptor activation by BMAA has been unclear, as BMAA lacks the omega electronegative moiety characteristic of other excitatory amino acids. We recently reported that the neuroexcitatory and neurotoxic effects of BMAA depend strongly on the presence of bicarbonate ions and proposed that an interaction between bicarbonate and the beta amino group of BMAA produces a molecular configuration appropriate for activating glutamate receptors. We now report that bicarbonate potentiates the ability of BMAA to open NMDA receptor-activated channels in isolated membrane patches. Furthermore, the neurotoxic and neuroexcitatory effects of two structural analogs of BMAA, DL-2,4-diaminobutyrate and DL-2,3-diaminopropionate, were also potentiated by bicarbonate. These findings support the bicarbonate cofactor hypothesis for BMAA action and provide direct evidence that it may be generalizable to certain other compounds.

Amino Acids, Diamino↗