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Biomedical subjects

J Choi

Publications and source records attributed to J Choi.

At least 109 records · Page 6Linked to original sources
PubMed2000

Evolved mechanisms underlying wayfinding. further studies on the hunter-gatherer theory of spatial sex differences.

Based on Silverman and Eals' hunter-gatherer theory of the origin of sex-specific spatial attributes, the present research sought to identify the evolved mechanisms involved in hunting that contribute to the dimorphism. The focus of these studies was the relationship between three-dimensional mental rotations, the spatial test showing the largest and most reliable sex difference favoring males, and wayfinding in the woods. Space constancy was presumed to be the evolved mechanism fundamental to both of these abilities. Measures of wayfinding were derived by leading subjects individually on a circuitous route through a wooded area, during which they were stopped at prescribed places and required to set an arrow pointing in the direction the walk began. As well, subjects were eventually required to lead the experimenters back to the starting point by the most direct route. In support of the hypotheses, males excelled on the various measures of wayfinding, and wayfinding was significantly related across sexes to mental rotations scores but not to nonrotational spatial abilities or general intelligence.

Journal Article↗
PubMed2000

Design and synthesis of anticonvulsive agents as gamma-vinyl GABA-based potential dual acting prodrugs and their biological activities.

For the development of new anticonvulsive agents, gamma-vinyl GABA (vigabatrin) and GABA mimetics derivatives were covalently coupled as potential dual acting prodrugs and evaluated for their anticonvulsive activities. Among the prepared compounds, 11 showed the most potent anticonvulsive activity, a shorter onset time and a broader spectrum compared to vigabatrin.

Animals↗
PubMed2000

The structure and expression of the murine wildtype p53-induced phosphatase 1 (Wip1) gene.

The human wildtype p53-induced phosphatase 1 (Wip1; GenBank symbol Ppm1d) gene encodes a type 2C protein phosphatase (PP2C) that is induced by ionizing radiation in a p53-dependent manner. We have cloned and sequenced the mouse Wip1 gene and its encoded mRNA. The mouse Wip1 gene is composed of six exons and spans over 36 kb of DNA. The mouse cDNA sequence predicts a 598-amino-acid protein with a molecular mass of roughly 66 kDa. Comparison of human and mouse Wip1 sequences revealed 83% overall identity at the amino acid level. The 5'-flanking region of exon 1 had promoter elements characteristic of a housekeeping gene. The Wip1 coding sequences share conserved functional regions with other PP2Cs from a diverse array of species. Expression of Wip1 mRNA was detected ubiquitously in adult and embryonic tissues, though expression in the testis was much higher than in other tissues. Wip1 has been mapped near the p53 gene on mouse chromosome 11.

Amino Acid Sequence↗
PubMed2000

Modulation of glutathione synthetic enzymes by acidic fibroblast growth factor.

Increasing evidence suggests that glutathione (GSH) synthesis is a regulated process. Documented increases in gamma-glutamylcysteine synthetase (GCS) occur in response to oxidants, in tumors, on plating cells at a low cell density, and with nerve growth factor stimulation, suggesting that GSH synthesis may be related to the cell growth and transformation. Previously, extracellular acidic fibroblast growth factor (FGF-1) has been demonstrated to cause transformation and aggressive cell growth in murine embryonic fibroblasts. In the present investigation, we sought to determine whether FGF-1, with its growth inducing properties, resulted in the modulation of GSH biosynthetic enzymes, GCS and GSH synthetase. Murine fibroblasts transduced with (hst/KS)FGF-1, a chimeric human FGF-1 gene containing a signal peptide sequence for secretion, displayed elevated gene expression of both heavy and light subunits of GCS. Activity of GSH synthetase was also elevated in these cells compared with control cells. Nonetheless, GSH was decreased in the FGF-1-transduced cells along with high energy phosphates, adenine nucleotides, NADH, and the redox poise. However, GSSG was not elevated in these cells. Fibroblasts stably expressing human immunodeficiency virus type 1 Tat, which induces intrinsic FGF-1 secretion, resulted in similar changes in GCS, GS, and GSH. The results suggest that although increases in the enzymes of GSH synthesis are a common response to growth factors, an increase in GSH content per se is not required for altered cell growth.

Adenosine Triphosphate↗
PubMed2000

Dominant-negative Jun N-terminal protein kinase (JNK-1) inhibits metabolic oxidative stress during glucose deprivation in a human breast carcinoma cell line.

Signal transduction pathway involved in glucose deprivation-induced oxidative stress were investigated in human breast carcinoma cells (MCF-7/ADR). In MCF-7/ADR, glucose deprivation-induced prolonged activation of c-Jun N-terminal kinase (JNK1) as well as cytoxicity and the accumulation of oxidized glutathione. Glucose deprivation also caused significant increases in total glutathione, cysteine, gamma-glutamylcysteine, and immunoreactive proteins corresponding to the catalytic as well as regulatory subunits of gamma-glutamylcysteine, and immunoreactive proteins corresponding to the catalytic as well as regulatory subunits of gamma-glutamylcysteine synthetase, suggesting that the synthesis of glutathione increased as an adaptive response. Expression of a catalytically inactive dominant negative JNK1 in MCF-7/ADR inhibited glucose deprivation- induced cell death and the accumulation of oxidized glutathione as well as altered the duration of JNK activation from persistent (> 2 h) to transient (30 min). In addition, stimulation of glutathione synthesis during glucose deprivation was not observed in cells expressing the highest levels of dominant negative protein. Finally, a linear dose response suppression of oxidized glutathione accumulation was noted for clones expressing increasing levels of dominant negative JNK1 during glucose deprivation. These results show that expression of a dominant negative JNK1 protein was capable of suppressing persistent JNK activation as well as oxidative stress and cytotoxicity caused by glucose deprivation in MCF-7/ADR. These findings support the hypothesis that JNK signaling pathways may control the expression of proteins contributing to cell death mediated by metabolic oxidative stress during glucose deprivation. Finally, these results support the concept that JNK signaling-induced shifts in oxidative metabolism may provide a general mechanism for understanding the diverse biological effects seen during the activation of JNK signaling cascades.

Breast Neoplasms↗
PubMed2000

Age-associated decline in gamma-glutamylcysteine synthetase gene expression in rats.

Although glutathione (GSH) concentration has been reported to diminish with age, the mechanism underlying such age-associated decline in the GSH content is not well understood. In this study, we compared the gene expression of both subunits of gamma-glutamylcysteine synthetase (GCS), the rate-limiting enzyme in de novo GSH synthesis, in young, adult, and old Fisher 344 rats. It was found that GCS activity was significantly decreased with increased age in liver, kidney, lung, and red blood cells (RBC). Parallel with the decreased enzyme activity, the protein and mRNA contents of both GCS subunits also changed inversely with age in liver, kidney, and lung, implying a decreased GCS gene expression during aging. Such a reduced GCS gene expression was accompanied by a decline in total GSH content without any change in cysteine concentration. Furthermore, the decreased GCS gene expression in old rats was not associated with a decline in the plasma insulin or cortisol level. This study showed, for the first time, that the expression of both GCS subunit genes was decreased in some organs of old rats, which would result in a reduced rate of GSH biosynthesis. Such decline in GSH synthetic capacity may underlie the observed decrease in GSH content during aging.

Aging↗
PubMed2000

Molecular mechanism of decreased glutathione content in human immunodeficiency virus type 1 Tat-transgenic mice.

Human immunodeficiency virus (HIV) progressively depletes GSH content in humans. Although the accumulated evidence suggests a role of decreased GSH in the pathogenesis of HIV, significant controversy remains concerning the mechanism of GSH depletion, especially in regard to envisioning appropriate therapeutic strategies to help compensate for such decreased antioxidant capacity. Tat, a transactivator encoded by HIV, is sufficient to cause GSH depletion in vitro and is implicated in AIDS-associated Kaposi's sarcoma and B cell lymphoma. In this study, we report a decrease in GSH biosynthesis with Tat, using HIV-1 Tat transgenic (Tat+) mice. A significant decline in the total intracellular GSH content in liver and erythrocytes of Tat+ mice was accompanied by decreased gamma-glutamylcysteine synthetase regulatory subunit mRNA and protein content, which resulted in an increased sensitivity of gamma-glutamylcysteine synthetase to feedback inhibition by GSH. Further study revealed a significant reduction in the activity of GSH synthetase in liver of Tat+ mice, which was linearly associated with their GSH content. Therefore, Tat appears to decrease GSH in vivo, at least partially, through modulation of GSH biosynthetic enzymes.

Animals↗
PubMed2000

Effects of acetylbergenin against D -galactosamine-induced hepatotoxicity in rats.

The hepatoprotective effects of acetylbergenin were examined against D -galactosamine (GalN)-induced liver damage in rats, compared with that of bergenin reported previously. Acetylbergenin was synthesized from acetylation of bergenin, isolated from Mallotus japonicus, to increase lipophilic and physiological activities. Acetylbergenin was administered orally once daily for 7 days and then GalN (400 mg kg(-1), i.p.) was injected at 24 h and 96 h after the final administration of acetylbergenin. Acetylbergenin reduced the elevated serum enzyme activities of alanine/aspartate aminotransferase, sorbitol dehydrogenase and gamma -glutamyltransferase and the formation of hepatic malondialdehyde induced by GalN. Acetylbergenin also significantly restored towards normalization the decreased levels of glutathione and the decreased activities of glutathione S-transferase and glutathione reductase induced by GalN. Therefore, these results suggest that acetylbergenin has hepatoprotective effects against GalN-induced hepatotoxicity by inhibiting lipid peroxidation and maintaining an adequate level of GSH for the detoxification of xenobiotics as underlying hepatoprotective mechanisms. In addition, lipophilic acetylbergenin showed more activity in the hepatoprotection than that of the much less lipophilic bergenin reported previously.

Analysis of Variance↗
PubMed2000

Economic considerations in the production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) by bacterial fermentation.

The process for the production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB/V)] by bacterial fermentation and its recovery was analysed. The effects of various factors such as P(3HB/V) content, P(3HB/V) productivity, P(3HB/V) yield and 3-hydroxyvalerate (3HV) fraction in P(3HB/V) on the production cost of P(3HB/V) were examined. The increase in the 3HV yield on a carbon source did not significantly decrease the production cost when the 3HV fraction was 10 mol%, because the cost of the carbon substrate for 3HV was relatively small in terms of the total cost. However, at a 3HV fraction of 30 mol%, the 3HV yield on a carbon source had a significant effect on the total P(3HB/V) production cost. The production cost of P(3HB/V) increased linearly with the increase in the 3HV fraction in P(3HB/V).

Alcaligenes↗
PubMed2000

Melanoma lymphoscintigraphy and lymphatic mapping.

Lymphoscintigraphy in melanoma has proven to be a reliable method to identify regional lymph nodes at risk for metastases. The first lymph node to drain a cutaneous lesion, the sentinel lymph node (SLN), is predictive of the metastatic status of the regional lymph node group. Lymphatic mapping allows for the identification of the SLN and for selective lymph node sampling. Selective lymph node sampling is less invasive and because only a small quantity of high-risk tissue is submitted for pathological examination, it allows for a more complete and comprehensive pathological examination, which identifies melanoma with up to 100 times the sensitivity of conventional examinations.

Humans↗
PubMed2000

Expression of senescence-associated beta-galactosidase in enlarged prostates from men with benign prostatic hyperplasia.

OBJECTIVES: Cellular senescence is a unique cellular response pathway thought to be closely associated with the aging process. The senescent phenotype is characterized by the loss of a cell's ability to respond to proliferative and apoptotic stimuli even while normal metabolic activity and vitality is maintained. Recently, a novel biomarker, senescent-associated beta-galactosidase (SA-beta-gal), was found to identify cells with the senescent phenotype. In the present study, we examined whether human prostatic epithelial cells adopt a senescence-associated phenotype after prolonged culture and analyzed a series of human benign prostatic hyperplasia (BPH) specimens to determine whether the cellular senescence process might be a factor in the development of BPH. METHODS: A primary culture of epithelial cells was established from the normal tissue of the peripheral zone of a radical prostatectomy specimen and was serially passaged until senescence. Forty-three human prostate specimens were obtained subsequent to radical prostatectomy or transrectal ultrasound-guided biopsy. The cultured cells and tissue specimens were histochemically stained to reveal the expression of SA-beta-gal, the cellular senescence biomarker. RESULTS: As has been reported for other types of cultured cells, human prostatic epithelial cells demonstrated widespread expression of the cellular senescence marker, SA-beta-gal, on prolonged culture. In our survey of hypertrophied human prostate tissues, 17 specimens (40%) of the 43 analyzed demonstrated positive staining for SA-beta-gal. In these tissues, SA-beta-gal expression was noted only in the epithelial cells. No statistical correlation (P = 0.42) between the chronologic age of the patient donor and SA-beta-gal expression was found. However, a high prostate weight (greater than 55 g) was found to correlate strongly with the expression of the SA-beta-gal biomarker (P = 0. 0001). CONCLUSIONS: Cultured prostatic epithelial cells expressed SA-beta-gal on reaching replicative senescence in vitro. The survey of human BPH specimens for the senescent marker showed that prostatic epithelial cells in patients with BPH with more advanced enlargement of the prostate (greater than 55 g prostate weight) expressed SA-beta-gal, and the prostates from patients with BPH that weighed less than 55 g tended to lack senescent epithelial cells. On the basis of these results, we propose that the accumulation of senescent epithelial cells may play a role in the development of the prostatic enlargement associated with BPH.

Aged↗
PubMed2000

Nitric oxide reduces Ca(2+) and Zn(2+) influx through voltage-gated Ca(2+) channels and reduces Zn(2+) neurotoxicity.

The translocation of synaptic Zn(2+) from nerve terminals into selectively vulnerable neurons may contribute to the death of these neurons after global ischemia. We hypothesized that cellular Zn(2+) overload might be lethal for reasons similar to cellular Ca(2+) overload and tested the hypothesis that Zn(2+) neurotoxicity might be mediated by the activation of nitric oxide synthase. Although Zn(2+) (30-300microM) altered nitric oxide synthase activity in cerebellar extracts in solution, it did not affect nitric oxide synthase activity in cultured murine neocortical neurons. Cultured neurons exposed to 300-500microM Zn(2+) for 5min under depolarizing conditions developed widespread degeneration over the next 24h that was unaffected by the concurrent addition of the nitric oxide synthase inhibitor N(G)-nitro-L-arginine. Furthermore, Zn(2+) neurotoxicity was attenuated when nitric oxide synthase activity in the cultures was induced by exposure to cytokines, exogenous nitric oxide was added or nitric oxide production was pharmacologically enhanced. The unexpected protective effect of nitric oxide against Zn(2+) toxicity may be explained, at least in part, by reduction of toxic Zn(2+) entry. Exposure to nitric oxide donors reduced Ba(2+) current through high-voltage activated calcium channels, as well as K(+)-stimulated neuronal uptake of 45Ca(2+) or 65Zn(2+). The oxidizing agents thimerosal and 2,2'-dithiodipyridine also reduced K(+)-stimulated cellular 45Ca(2+) uptake, while akylation of thiols by pretreatment with N-ethylmaleimide blocked the reduction of 45Ca(2+) uptake by a nitric oxide donor.The results suggest that Zn(2+)-induced neuronal death is not mediated by the activation of nitric oxide synthase; rather, available nitric oxide may attenuate Zn(2+) neurotoxicity by reducing Zn(2+) entry through voltage-gated Ca(2+) channels, perhaps by oxidizing key thiol groups.

Animals↗
PubMed2000

Diazepam induces FGF-2 mRNA in the hippocampus and striatum.

starting by 6 h following diazepam injection and returning to approximately control values by 24 h. In situ hybridization showed elevated FGF-2 mRNA labeling in the hippocampal formation, mostly in the pyramidal layer of the CA1 and CA2 subfields and in the dentate gyrus hilar region. These results indicate that diazepam treatment up-regulates FGF-2 expression in select regions of the brain and suggest that GABA may promote neuroplasticity in concert with FGF-2.

Animals↗
PubMed2000

Hepatoprotective effects of bergenin, a major constituent of Mallotus japonicus, on carbon tetrachloride-intoxicated rats.

The hepatoprotective effects of bergenin, a major constituent of Mallotus japonicus, were evaluated against carbon tetrachloride (CCl(4))-induced liver damage in rats. Bergenin at a dose of 50, 100 or 200 mg/kg was administered orally once daily for successive 7 days and then a mixture of 0.5 ml/kg (ip) of CCl(4) in olive oil (1:1) was injected two times each at 12 and 36 h after the final administration of bergenin. The substantially elevated serum enzymatic activities of alanine/aspartate aminotransferase, sorbitol dehydrogenase and gamma-glutamyltransferase due to CCl(4) treatment were dose dependently restored towards normalization. Meanwhile, the decreased activities of glutathione S-transferase and glutathione reductase were restored towards normalization. In addition, bergenin also significantly prevented the elevation of hepatic malondialdehyde formation and depletion of reduced glutathione content in the liver of CCl(4)-intoxicated rats in a dose dependent fashion. The results of this study clearly indicate that bergenin has a potent hepatoprotective action against CCl(4)-induced hepatic damage in rats.

Animals↗
PubMed2000

Specific cell targeting for delivery of toxins into small-cell lung cancer using a streptavidin fusion protein complex.

New modalities of treatment for small-cell lung cancer (SCLC) are needed, because the majority of patients continue to die of disseminated disease despite an initial response to conventional chemotherapy. Abnormal surface expression of the neural-cell adhesion molecule (NCAM) has been noted to be highly associated with SCLC. We examined the ability and efficiency of a streptavidin-Protein A (ST-PA) fusion protein complexed with an anti-NCAM monoclonal antibody (Mab) to transfer biotinylated beta-galactosidase into human SCLC cell lines NCI-H69, NCI-H526, and NCI-H446. When the surface molecule NCAM was targeted with this system, more than 99% of the targeted cells internalized and exhibited beta-galactosidase activity. In addition, we evaluated cytotoxic activity against SCLC lines NCI-H69 and NCI-H526 by efficient delivery of biotinylated glucose oxidase using the same ST-PA/anti-NCAM Mab complex. Cytotoxicity of the transduced cells (SCLC) was 10-fold and 100-fold greater, respectively, than the glucose oxidase control. This system could be widely applied for specific therapy of cancer cells by targeting unique surface molecules (antigens) using the corresponding Mab/ST-PA complex to transfer a variety of effector molecules; e.g., immunotoxic compounds, into target cells with a high degree of efficiency and specificity.

Animals↗
PubMed2000

Deep venous thrombosis: detection by using indirect CT venography. The Pulmonary Angiography-Indirect CT Venography Cooperative Group.

PURPOSE: To assess the clinical benefits of performing indirect computed tomographic (CT) venography after pulmonary CT angiography to detect deep venous thrombosis (DVT) in patients suspected of having a pulmonary embolism. MATERIALS AND METHODS: The authors prospectively enrolled 541 consecutive patients who underwent pulmonary CT angiography for suspected pulmonary embolism at seven institutions. Using a protocol that optimizes venous enhancement without additional contrast material injection, the authors obtained contiguous images from the pelvis to the popliteal fossa. Ultrasonography (US) also was performed in 116 patients. RESULTS: DVT was found at indirect CT venography in 45 (8%), and pulmonary embolism was found at pulmonary CT angiography in 91 (17%) of 541 patients. Among the 45 patients with DVT, DVT occurred in 16 patients who had no pulmonary embolism at pulmonary CT angiography, which increased the diagnosis of thromboembolic disease by 18%. Among 116 patients who underwent US and indirect CT venography, 15 had DVT at US, and in all 15, DVT also was seen at indirect CT venography. In four additional cases, DVT was seen at only indirect CT venography. CONCLUSION: Among patients suspected to have pulmonary embolism, a substantial number had DVT in the absence of pulmonary embolism. Combined pulmonary CT angiography-indirect CT venography can depict these cases with accuracy comparable to that of US and thus could have a significant effect on patient care.

Adolescent↗
PubMed2000

Pharmacological properties of the gastric H(+)/K(+) ATPase inhibitor, AU-461.

AU-461 (1-(2-methyl-4-methoxyphenyl)-4-[(2-hydroxyethyl)amino]-6-beta,beta, beta-trifluoroethoxy-2,3-dihydropyrrolo[3,2-c]quinoline) was tested for its ability to act as an anti-ulcer agent. AU-461 inhibited gastric H(+)/K(+) ATPase activities with IC(50) values of 12.15 and 4.20 micromol/l for rabbit and pig enzymes, respectively. The inhibition was reversible, and competitive with respect to the activating cation K(+). When AU-461 was examined for the in vivo antisecretory activity, we found that AU-461 reduced the histamine-stimulated acid secretion as well as the basal secretion in rat stomach. Duration of the antisecretory effect was about 6 h upon oral administration. AU-461 prevented dose-dependently the ulcer formation produced by either ethanol or NaOH. This protective effect was not altered by indomethacin pretreatment. In addition, the elevated plasma gastrin by the oral administration of AU-461 was returned to control by 12 h. Taken together, these results suggest that AU-461 could be developed as a new therapeutic agent for peptic ulcer disease.

Animals↗