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Biomedical subjects

S Choi

Publications and source records attributed to S Choi.

At least 19 recordsLinked to original sources
PubMed1999

Variability of neurotransmitter concentration and nonsaturation of postsynaptic AMPA receptors at synapses in hippocampal cultures and slices.

To understand the elementary unit of synaptic communication between CNS neurons, one must know what causes the variability of quantal postsynaptic currents and whether unitary packets of transmitter saturate postsynaptic receptors. We studied single excitatory synapses between hippocampal neurons in culture. Focal glutamate application at individual postsynaptic sites evoked currents (I(glu)) with little variability compared with quantal excitatory postsynaptic currents (EPSCs). The maximal I(glu) was >2-fold larger than the median EPSC. Thus, variations in [glu]cleft are the main source of variability in EPSC size, and glutamate receptors are generally far from saturation during quantal transmission. This conclusion was verified by molecular antagonism experiments in hippocampal cultures and slices. The general lack of glutamate receptor saturation leaves room for increases in [glu]cleft as a mechanism for synaptic plasticity.

Animals↗
PubMed1998

Hypothalamic ventromedial nuclei amplify circadian rhythms: do they contain a food-entrained endogenous oscillator?

Several endogenous oscillators determine circadian rhythms. One, light-entrained, is in the suprachiasmatic nuclei (SCN), the others, food-entrained, are in unknown sites. To determine how the hypothalamic ventromedial nuclei (VMN) and feeding affect rhythms, we compared nocturnally active rats fed either ad libitum or for 2 hr/d during light [restricted feeding (RF)] and either with or without colchicine-induced disruption of VMN. We measured rhythms in temperature, locomotor activity, feeding, drinking, corticosterone, and the numbers of cells expressing c-Fos in light/dark in hypothalamic nuclei, the suprachiasmatic nuclei, and two major SCN targets, the subparaventricular zone (sPVNz) and paraventricular thalamus (pvTHAL). c-Fos cells were always light > dark in SCN, whereas the VMN and sPVNz lacked light/dark differences except after RF and RF plus VMN disruption, respectively. Controls fed ad libitum had high-amplitude rhythms and, generally, c-Fos cells dark > light. In RF controls, a c-Fos pattern dark > light occurred in VMN; generally, c-Fos cell numbers increased elsewhere maintaining dark > light. By contrast, levels of corticosterone peaked before food. In rats fed ad libitum, VMN with colchicine markedly reduced rhythm amplitudes, not phase. c-Fos patterns were abolished except in pvTHAL and SCN. In RF, VMN disruption blocked corticosterone and light/dark c-Fos patterns in all nuclei but produced a pattern in the sPVNz like SCN. We conclude that VMN amplify rhythmic output from the SCN, and the RF-induced rhythm in VMN enhances c-Fos activity driven by the SCN. The VMN may contain a food-entrained oscillator, and the sPVNz may integrate output from several oscillators.

Animals↗
PubMed1998

Relationship between excitatory amino acid release and outcome after severe human head injury.

In previous studies, Katayama and our group have documented a massive increase in excitatory amino acid release following traumatic brain injury, in both rat fluid percussion, and humans [2,5]. To test the hypothesis that the magnitude of this "Excitotoxic Surge" plays a significant role in determining 6-month patient outcome. We have studied 83 consecutive severely head injured patients at the Medical College of Virginia for inclusion into this study. A microdialysis probe was placed within the cortex to continuously measure dialysate excitatory amino acids (Glutamate and Aspartate), along with several other analytes for approximately 5 days after injury. ICP, CPP, and MABP measurements were also time linked with each analyte measurement to create a neurochemical, clinical, and physiological "profile" for each patient. Outcome was determined by follow up using the Glasgow 6-Month outcome scale. A very strong correlation existed between the release of the EAA's glutamate and aspartate after TBI (p < 0.0001). Patients with significantly elevated mean glutamate values for the entire monitoring period were most likely to exhibit elevated levels of ICP. The magnitude of glutamate released significantly correlates with 6-month patient outcome (p = 0.0234). When patients were subdivided by the CT diagnosis of lesion type, we found that those patients with contusions displayed the highest overall of EAA's.

Animals↗
PubMed1998

Syntheses and cytotoxicities of four stereoisomers of muricatacin from D-glucose.

Four stereoisomers of muricatacin 1a-d were prepared by the reaction of corresponding aldehydes 4a-d, which in turn were prepared from D-glucose, with the anion of triethylphosphonoacetate followed by reduction and cyclization under acidic conditions. Cytotoxicities of four stereoisomers were tested against in vitro A-549 cell line as well as MCF-7 cell line. Stereochemistry at C4 and C5 position of muricatacin did not affect the cytotoxicities significantly.

Antineoplastic Agents↗
PubMed1998

Endovascular coil occlusion of a traumatic basilar-cavernous fistula: technical report.

OBJECTIVE AND IMPORTANCE: We describe an unusual case of an 8-year-old male patient presenting with a traumatic basilar artery aneurysm associated with a basilar-cavernous fistula. CLINICAL PRESENTATION: The fistula occurred as the result of an accident involving a vehicle and a pedestrian. The patient originally presented in a coma and with a dense left hemiparesis. INTERVENTION: The traumatic basilar aneurysm and basilar-cavernous fistula were successfully occluded by endovascular coil embolization in two sessions. By 6 months after injury, the patient had made an excellent neurological recovery, requiring only a left leg brace for walking. CONCLUSION: Endovascular coil embolization provided an effective treatment option in the case of this complex and unusual arteriovenous fistula. We discuss the radiological and clinical features of related traumatic neurovascular lesions.

Arteriovenous Fistula↗
PubMed1998

The design, synthesis and activity of pentapeptide pp60c-src inhibitors containing L-phosphotyrosine mimics.

Efficient syntheses of 4-(R,S-hydroxyphosphonomethyl)-L-phenylalanine and 4-carboxy-L-phenylalanine within the context of the pentapeptide Ac-Ile-X-Gly-Glu-Phe-NH2 (wherein X = the unnatural amino acid) illustrate the use of a divergent synthetic strategy from an advanced common peptide intermediate to more readily access peptide-based tyrosine kinase inhibitors. The key intermediate, Ac-Ile-Phe(4-formyl)-Gly-Glu(O-tBu)-Phe-NH2, was synthesized by a facile palladium-catalyzed carbonylation of Ac-Ile-Phe(4-iodo)-Gly-Glu(O-tBu)-Phe-NH2. Oxidation of Ac-Ile-Phe(4-formyl)-Gly-Glu(O-tBu)-Phe-NH2 with tetrabutylammonium permanganate or addition of di-t-butylphosphite, both followed by trifluoroacetic acid deprotection, gave the target pentapeptide inhibitors wherein X = 4-carboxy-L-phenylalanine or 4-(R,S-hydroxyphosphonomethyl)-L-phenylalanine, respectively. These two peptides gave somewhat more potent inhibition of the tyrosine kinase pp60c-src than the corresponding pentapeptide wherein X = L-phenylalanine, demonstrating that appended functionalities at the 4-position are accepted and can enhance binding through added interactions within the catalytic region of the active site.

Animals↗
PubMed1998

Accelerated lipoprotein uptake by transplantable hepatomas that express hepatic lipase.

To test the hypothesis that hepatic lipase plays a key role in lipoprotein removal in vivo, a novel system was used. Hepatoma cells (HTC 7288c) were transfected with a cDNA encoding hepatic lipase in culture and grown as solid tumors in vivo. In culture, transfected cells degraded chylomicron remnants and low density lipoprotein (LDL) somewhat more efficiently than untransfected cells. Tumors from the transplanted cells produced hepatic lipase localized to the surface of tumors from transfected cells but not tumors from non-transfected cells, grown in the same rat. The tumors from transfected cells removed, per gm of tissue, 34% (P < 0.001) more 125I-labeled LDL than tumors from non-transfected cells in the same animal. The uptake of chylomicron remnants (by tumors from transfected cells) was also modestly enhanced (15 +/- 6%, P < 0.005). There were no differences in the uptake of 125I-labeled albumin or 125I-labeled asialoglycoprotein. Compared to the liver, the untransfected tumors took up 12%, and the transfected tumors took up about 18% as much LDL per gram of tissue. The uptake of chylomicron remnants compared to liver was far lower. Both types of tumors had about twice as much LDL receptor related protein as the liver. Wild-type tumors had the highest level of LDL receptor, twice hepatic lipase-secreting tumors, and six times that of the liver. Using the novel approach of transfecting transplantable tumor cells with hepatic lipase, the ability of hepatic lipase to facilitate the removal of apoB-containing lipoproteins was demonstrated. The liver still removes low density lipoprotein and especially chylomicron remnants more rapidly than the tumors, suggesting factors in addition to hepatic lipase and LDL receptor level play a major role in hepatic lipoprotein removal.

Animals↗
PubMed1997

Decreased frequency but not amplitude of quantal synaptic responses associated with expression of corticostriatal long-term depression.

We have investigated the site of expression of striatal long-term synaptic depression (LTD) using analysis of Sr2+-induced asynchronous release of quanta from stimulated synapses. The cumulative amplitude distribution of Sr2+-induced asynchronous synaptic responses overlaps with that of miniature EPSCs (mEPSCs), suggesting that Sr2+-induced asynchronous responses are quantal. Quantal amplitude at stimulated synapses is not significantly altered after LTD induction, whereas quantal frequency decreases after LTD induction. The decrease in quantal frequency is prevented when LTD expression is blocked by dialyzing 10 mM EGTA into the postsynaptic neuron. Our findings are most consistent with the idea that expression of striatal LTD involves decreased neurotransmitter release with no change in quantal amplitude, despite the fact that induction of striatal LTD involves postsynaptic mechanisms.

Animals↗
PubMed1997

Translocation of autophosphorylated calcium/calmodulin-dependent protein kinase II to the postsynaptic density.

Calcium/calmodulin-dependent protein kinase II (CaMKII) undergoes calcium-dependent autophosphorylation, generating a calcium-independent form that may serve as a molecular substrate for memory. Here we show that calcium-independent CaMKII specifically binds to isolated postsynaptic densities (PSDs), leading to enhanced phosphorylation of many PSD proteins including the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)-type glutamate receptor. Furthermore, binding to PSDs changes CaMKII from a substrate for protein phosphatase 2A to a protein phosphatase 1 substrate. Translocation of CaMKII to PSDs occurs in hippocampal slices following treatments that induce CaMKII autophosphorylation and a form of long term potentiation. Thus, synaptic activation leads to accumulation of autophosphorylated, activated CaMKII in the PSD. This increases substrate phosphorylation and affects regulation of the kinase by protein phosphatases, which may contribute to enhancement of synaptic strength.

Animals↗
PubMed1997

Decreased probability of neurotransmitter release underlies striatal long-term depression and postnatal development of corticostriatal synapses.

Changes in synaptic efficacy are crucial for the development of appropriate neural circuits and brain information storage. We have investigated mechanisms underlying long-term depression (LTD) at glutamatergic synapses in the striatum, a brain region important in motor performance and cognition, and a target for Huntington and Parkinson diseases. Induction of striatal LTD is dependent on postsynaptic depolarization and calcium influx through L-type channels. Surprisingly, LTD maintenance appears to involve a decrease in the probability of neurotransmitter release from presynaptic terminals as evidenced by increases in paired-pulse facilitation and the coefficient of variation of synaptic responses that are tightly associated with LTD expression. Furthermore, both the apparent probability of neurotransmitter release and the magnitude of LTD decrease concomitantly during postnatal development, consistent with the idea that striatal LTD is involved in a developmental decrease in the probability of neurotransmitter release at corticostriatal synapses. The presynaptic changes that underlie striatal LTD may also be important for motor performance and certain forms of learning and memory.

Aging↗
PubMed1997

Control of endogenous norepinephrine release in the hypothalamus of male rats changes over adolescent development.

In order to evaluate mechanisms that could contribute to the effect of adolescent development on the in vivo utilization of norepinephrine (NE) in the hypothalamus, the depolarized release of endogenous norepinephrine (using 50 mM potassium) was measured in vitro in hypothalamic explants from male rats over late juvenile (28 days) to young adult (70 days) ages. Depolarized release, expressed as a percent of the total endogenous pool, was significantly greater in juveniles than in either adolescents (42 days) or young adults. Incubation in the presence of idazoxan, an alpha 2-adrenoceptor antagonists, increased the depolarized fractional NE release in adolescent and young adult rats; however, the same drug decreased depolarized release in juveniles. Inhibition of norepinephrine reuptake by incubation in the presence of nisoxetine (1 microM) significantly increased depolarized release (fractional and absolute) in young adults only. A higher concentration of nisoxetine (5 microM) significantly increased depolarized release in juveniles, but significantly reduced release in adults. Nisoxetine did not influence release in adolescents at either concentration. The possibilities that adolescents development brings about a change in alpha 2-adrenoceptor subtype and that juveniles may have a greater NE reuptake capacity than adults are discussed. Hypothalamic NE projections are important to several regulatory functions, and changes that take place in this system over adolescence may be important for the emergence of adult-typical responses as well as render adolescents vulnerable to specific dysfunctions.

Adrenergic alpha-Antagonists↗
PubMed1997

A large-insert (130 kbp) bacterial artificial chromosome library of the rice blast fungus Magnaporthe grisea: genome analysis, contig assembly, and gene cloning.

Magnaporthe grisea (Hebert) Barr causes rice blast, one of the most devastating diseases of rice (Oryza sativa) worldwide. This fungus is an ideal organism for studying a number of aspects of plant-pathogen interactions, including infection-related morphogenesis, avirulence, and pathogen evolution. To facilitate M. grisea genome analysis, physical mapping, and positional cloning, we have constructed a bacterial artificial chromosome (BAC) library from the rice infecting strain 70-15. A new method was developed for separation of partially digested large-molecular-weight DNA fragments that facilitated library construction with large inserts. The library contains 9216 clones, with an average insert size of 130 kbp (> 25 genome equivalents) stored in 384-well microtiter plates that can be double spotted robotically on to a single nylon membrane. Several unlinked single-copy DNA probes were used to screen 4608 clones in the library and an average of 13 (minimum of 6) overlapping BAC clones was found in each case. Hybridization of total genomic DNA to the library and analysis of individual clones indicated that approximately 26% of the clones contain single-copy DNA. Approximately 35% of BAC clones contained the retrotransposon MAGGY. The library was used to identify BAC clones containing a adenylate cyclase gene (mac1). In addition, a 550-kbp contig composed of 6 BAC clones was constructed that encompassed two adjacent RFLP markers on chromosome 2. These data show that the BAC library is suitable for genome analysis of M. grisea. Copies of colony hybridization membranes are available upon request.

Ascomycota↗
PubMed1997

Scheduling processes in working memory: instructions control the order of memory search and mental arithmetic.

Humans must often use working memory to execute processes one at a time because of its limited capacity. Two experiments tested where limits in access to working memory occur. Subjects searched a short-term memory set for one stimulus digit and performed mental arithmetic with another stimulus digit. In one experiment, they were told to carry out the mental arithmetic before the memory search and to make the arithmetic response first. In the other, they were instructed to perform the tasks in the opposite order. The overt responses were executed in the prescribed order. Moreover, the covert working memory processes were executed in the prescribed order, as revealed by a critical path network analysis of reaction times. Results are explained in terms of a double-bottleneck model in which central processes and responses are constrained to be carried out for one task at a time.

Adult↗
PubMed1997

Spinal extradural leiomyoma in a pediatric patient with acquired immunodeficiency syndrome: case report.

OBJECTIVE AND IMPORTANCE: We report a case of two separate cervicothoracic, extradural leiomyomas occurring in a male pediatric patient with acquired immunodeficiency syndrome (AIDS). To our knowledge, such a case has never been reported in the literature. CLINICAL PRESENTATION: A 9-year-old male patient with AIDS presented with progressive leg weakness. At examination, he was myelopathic with paraparesis and a T4 sensory level to pinprick. A magnetic resonance image revealed two separate cervicothoracic lesions causing cord compression. INTERVENTION: The patient underwent resection of both lesions. Postoperatively, he regained normal strength in his legs and was discharged home after 2 weeks. CONCLUSION: With the ever-growing number of pediatric patients with AIDS, the entity will likely be encountered with increasing frequency in the future. Because of the potential for neurological recovery and cure, the neurosurgeon should be cognizant of this entity.

Acquired Immunodeficiency Syndrome↗
PubMed1996

The hypothalamic ventromedial nuclei couple activity in the hypothalamo-pituitary-adrenal axis to the morning fed or fasted state.

Function in the adrenocortical system is markedly altered by availability of food. Basal activity is lowest and stress responsivity highest in the morning when nocturnal rats eat approximately 90% of their daily calories during the dark. After an overnight fast, basal corticotrophin and corticosteroid levels are elevated, and responsivity to stressors is decreased. Central neural sites that control these changes are unidentified. The hypothalamic ventromedial nuclei (VMN) appear to signal satiety; lesions result in increased food intake, obesity, and elevated basal insulin and corticosteroids. Thus, the VMN are good candidates for calorically mediated control of adrenocortical system function in satiated rats. We injected colchicine into the VMN to cause reversible inhibition of activity (Avrith and Mogenson, 1978) and tested the effects on basal and stimulated function in the adrenocortical system. Colchicine-injected rats that fed ad libitum exhibited increased basal but reduced corticotrophin and corticosterone responses to restraint in the morning compared with controls. By contrast, after an overnight fast, control rats had increased basal adrenocortical hormones and decreased stress responses that did not differ from colchicine-injected rats. Colchicine was visualized within cells in the VMN for up to 5 d using fluorescein/colchicine, and the treatment did not cause increased gliosis; moreover, the functional effects of the injections were reversed within 15 d. We conclude that (1) the VMN serve to couple activity in the adrenocortical system to energy intake and (2) discrete colchicine injections provide a behaviorally and neuroendocrinologically useful period of inhibition without causing permanent functional damage.

Animals↗