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Biomedical subjects

S Choi

Publications and source records attributed to S Choi.

At least 145 records · Page 8Linked to original sources
PubMed1999

Brain stem blood flow, pupillary response, and outcome in patients with severe head injuries.

OBJECTIVE: Acute pupillary dilation in a head-injured patient is a neurological emergency. Pupil dilation is thought to be the result of uncal herniation causing mechanical compression of the IIIrd cranial nerve and subsequent brain stem compromise. However, not all patients with herniation have fixed and dilated pupils, and not all patients with nonreactive, enlarged pupils have uncal herniation. Therefore, we have tested an alternative hypothesis that a decrease in brain stem blood flow (BBF) is a more frequent cause of mydriasis and brain stem symptomatology after severe head injury. We determined the relation of BBF to outcome and pupillary response in patients with severe head injuries. METHODS: One hundred sixty-two patients with a Glasgow Coma Scale score of 8 or less underwent stable xenon computed tomographic blood flow determination at the level of the superior colliculus, and this blood flow was correlated with pupillary features, intracranial pressure, computed tomographic scan pathology, and outcome. RESULTS: A BBF of less than 40 ml/100 g/min was significantly associated with poor outcome (P < 0.009). In patients with bilaterally nonreactive pupils, the BBF was 30.5+/-16.8 ml/100 g/min, and in those with normally reactive pupils, the BBF was 43.8+/-18.7 ml/100 g/min (P < 0.001). Intracranial pressure and the presence of a brain stem lesion observed on the computed tomographic scan did not correlate with BBF, pupillary size, or reactivity. Unfavorable outcome at 12 months was directly related to age (P = 0.062) and inversely related to pupillary responsiveness (P = 0.0006), pupil size (P = 0.005), and BBF of less than 40 ml/100 g/min (P = 0.009). CONCLUSION: These findings suggest that pupillary dilation is associated with decreased BBF and that ischemia, rather than mechanical compression of the IIIrd cranial nerve, is an important causal factor. More important, pupil dilation may be an indicator of ischemia of the brain stem. If cerebral blood flow and cerebral perfusion pressure can be rapidly restored in the patient with severe head injury who has dilated pupils, the prognosis may be good.

Adolescent↗
PubMed1999

Rats with hypothalamic obesity are insensitive to central leptin injections.

Genetically determined obesities, involving leptin- and melanocortin-signaling pathways, have focused attention on the four medial hypothalamic nuclei as primary sources of feeding- and metabolically-based obesity. All four medial cell groups contain leptin receptors. To determine which of these cell groups normally mediates the effects of leptin on food intake and body weight gain, we injected colchicine bilaterally into each nucleus and determined the pathophysiological effects of disruption and responsivity to leptin injected intracerebroventricularly. Intracerebroventricular injections of leptin in sham-lesioned rats decreased food intake during the dark period, but not during the light period. Lesions of the arcuate (ARC), paraventricular (PVN), and ventromedial (VMN) nuclei all resulted in leptin insensitivity; by contrast, lesions of the dorsomedial nuclei (DMN) augmented sensitivity to leptin on feeding and body weight gain. Although rats with ARC and PVN lesions were obese, they were still capable of reducing caloric efficiency over the 5 days of study and increasing uncoupling protein content in interscapular brown adipose tissue. Caloric efficiency and uncoupling protein content were unchanged in rats with VMN and DMN lesions. Finally, the slope of the relationship between leptin and mesenteric white adipose tissue was increased in rats with VMN lesions and abolished in rats with ARC lesions. Thus, lesions of the ARC, PVN, and VMN produced obesity via separate pathways. We conclude that the medial hypothalamic cell groups, each with a different role in energy balance, are all necessary for normal leptin responsiveness.

Animals↗
PubMed1999

Hypothalamic obesity: multiple routes mediated by loss of function in medial cell groups.

Cell groups of the medial hypothalamus are key to the regulation of energy balance. Functional disruption by colchicine injected in the hypothalamic arcuate (ARC), paraventricular (PVN), and ventromedial (VMN) cell groups produced increased food intake and obesity; disruption of the dorsomedial nuclei (DMN) produced decreased food intake. Colchicine in ARC or PVN increased food intake during both light and dark periods and increased cumulative food intake. By contrast, colchicine in VMN increased food intake only during the light, and cumulative food intake was not increased. Both leptin and insulin were elevated in the obese rats. Compared with sham, the slope of regression of leptin on insulin was increased by disruption of PVN and DMN but was not altered by disruption of VMN. ARC disruption abolished the relationship between leptin and insulin. Colchicine injected in the DMN did not cause obesity but altered feeding and the normal relationship between leptin, fat, and insulin, suggesting that blockade of signals, for example, from the lateral hypothalamus to DMN may disinhibit the normal medial hypothalamic drive to decrease energy stores. Changes in caloric efficiency with time after colchicine injections suggest that rats with both ARC and PVN disruption respond to signals of obesity, whereas rats with VMN disruption do not. These studies distinguish among functions in the four medial hypothalamic nuclei and suggest that interactions among them normally serve to regulate energy balance through alterations in food acquisition and storage.

Animals↗
PubMed1999

Starvation: early signals, sensors, and sequelae.

To identify the sequences of changes in putative signals, reception of these and responses to starvation, we sampled fed and starved rats at 2- to 6-h intervals after removal of food 2 h before dark. Metabolites, hormones, hypothalamic neuropeptide expression, fat depots, and leptin expression were measured. At 2 h, insulin decreased, and FFA and corticosterone (B) increased; by 4 h, leptin and glucose levels decreased. Neuropeptide Y messenger RNA (mRNA) increased 6 h after food removal and thereafter. Adrenal and plasma B did not follow ACTH and were elevated throughout, with a nadir at the dark-light transition. Leptin correlated inversely with adrenal B. Fat stores decreased during the last 12 h. Leptin mRNA in perirenal and sc fat peaked during the dark period, resembling plasma leptin in fed rats. We conclude that 1) within the first 4 h, hormonal and metabolic signals relay starvation-induced information to the hypothalamus; 2) hypothalamic neuropeptide synthesis responds rapidly to the altered metabolic signals; 3) catabolic activity quickly predominates, reinforced by elevated B, not driven by ACTH, but possibly to a minor extent by leptin, and more by adrenal neural activity; and 4) leptin secretion decreases before leptin mRNA or fat depot weight, showing synthesis-independent regulation.

Adipose Tissue↗
PubMed1999

Warning! Nearby construction can profoundly affect your experiments.

This is meant to alert people to potentially major effects of construction projects on research results. Because we study the effects of stress on regulation of ACTH and corticosterone secretion and of serotonin receptors and stress on energy balance, we serve as an early warning system when things go awry. Most of our experiments include taking daily, or twice daily, measurements of rat or mouse weights and food intake as well as stress hormone levels. We are highly sensitized to environmental disruption and we've shown previously the effects of construction on stress hormones (1). However, we did not anticipate the change and disruption in energy balance that may occur in response to environmental perturbation. We provide two examples of these, below.

Animals↗
PubMed1999

Power Doppler sonography of hepatocellular carcinoma treated by transcatheter arterial chemoembolization. Assessment of the therapeutic effect.

PURPOSE: To evaluate the usefulness of power Doppler sonography (PDS) in assessing the therapeutic effect of transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC). MATERIAL AND METHODS: TACE was performed in 43 patients (48 lesions) with HCC. All patients were examined with both PDS and color Doppler sonography (CDS) to assess the therapeutic results 1 week after TACE. Follow-up hepatic angiography was performed in 39 patients 3-4 months after TACE and then CT after iodized oil reinjection was also performed 3-4 weeks after a repeat TACE; in the remaining 4 patients, hepatectomy was performed within one month after chemoembolization and histologic study was undertaken to confirm the Doppler findings. RESULTS: Determination of therapeutic results with PDS and CDS were in agreement with those of follow-up findings in 37 and 29 of the 48 lesions, respectively. There was a significant difference in overall accuracy (p=0.038) between PDS and CDS results. CONCLUSION: PDS is more effective than CDS for evaluating changes in tumor vascularity after TACE. PDS may also replace angiography in assessing the therapeutic effects of TACE for HCCs, except in deep-seated areas.

Aged↗
PubMed1999

Anti-proliferating effects of ginsenoside Rh2 on MCF-7 human breast cancer cells.

Ginsenoside Rh2 (G-Rh2) isolated from the root of Panax ginseng has been shown to have anti-cancer proliferation, differentiation and chemopreventive effects in certain cancer cell types. We investigated the mechanism of G-Rh2-induced growth inhibition in MCF-7 human breast carcinoma cells. G-Rh2 significantly inhibited the cell growth in a concentration-dependent manner, which effect was reversible, and induced a G1 arrest in cell cycle progression. G-Rh2 treatment down-regulated the protein level of cyclin D3 but upregulated the expression of cyclin-dependent kinase (Cdk) inhibitor p21WAF1/CIP1. The increased levels of p21 were associated with increased binding of p21 and Cdk2 concomitant with marked decrease in Cdk2 and cyclin E-dependent kinase activities with no changes in Cdk2 and cyclin E expression. G-Rh2 markedly reduced the phosphorylated retinoblastoma protein (pRb) and enchanced association of unphosphorylated pRb and the transcription factor E2F-1. These data suggest that G-Rh2 inhibited the growth of MCF-7 cells, by inducing protein expression of p21 and reducing the protein levels of cyclin D which resulted in the down-regulation of cyclin/Cdk complex kinase activity, decreasing phosphorylation of pRb, and inhibiting E2F release.

Antineoplastic Agents↗
PubMed1998

Aberrant second branchial cleft fistula.

Second branchial cleft cysts and sinuses rarely present diagnostic problems to the pediatric otolaryngologist as their course is usually predictable based on consistent embryologic development. However, we evaluated two fistula tracts that did not fit the classic description of second branchial tract fistulas. Upon radiographic and intraoperative evaluation, their eventual course ending in the tonsillar fossa was identified. Realizing the potential for aberrancy and using preoperative radiographic evaluation will assist the surgeon in the excision of these developmental anomalies with little risk to underlying neurovascular structures.

Branchioma↗
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↗