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Biomedical subjects

J Choi

Publications and source records attributed to J Choi.

At least 127 records · Page 7Linked to original sources
PubMed2000

Intranuclear trafficking of transcription factors: implications for biological control.

The subnuclear organization of nucleic acids and cognate regulatory factors suggests that there are functional interrelationships between nuclear structure and gene expression. Nuclear proteins that are localized in discrete domains within the nucleus include the leukemia-associated acute myelogenous leukemia (AML) and promyelocytic leukemia (PML) factors, the SC-35 RNA-processing factors, nucleolar proteins and components of both transcriptional and DNA replication complexes. Mechanisms that control the spatial distribution of transcription factors within the three-dimensional context of the nucleus may involve the sorting of regulatory information, as well as contribute to the assembly and activity of sites that support gene expression. Molecular, cellular, genetic and biochemical approaches have identified distinct protein segments, termed intranuclear-targeting signals, that are responsible for directing regulatory factors to specific subnuclear sites. Gene rearrangements that remove or alter intranuclear-targeting signals are prevalent in leukemias and have been linked to altered localization of regulatory factors within the nucleus. These modifications in the intranuclear targeting of transcription factors might abrogate fidelity of gene expression in tumor cells by influencing the spatial organization and/or assembly of machineries involved in the synthesis and processing of gene transcripts.

Biological Transport↗
PubMed2000

A locus conferring resistance to diet-induced hypercholesterolemia and atherosclerosis on mouse chromosome 2.

Dietary cholesterol is known to raise total and low density lipoprotein cholesterol concentrations in humans and experimental animals, but the response among individuals varies greatly. Here we describe a mouse strain, C57BL/6ByJ (B6By), that is resistant to diet-induced hypercholesterolemia, in contrast to the phenotype seen in other common strains of mice including the closely related C57BL/6J (B6J) strain. Compared to B6J, B6By mice exhibit somewhat lower basal cholesterol levels on a chow diet, and show a relatively modest increase in absolute levels of total and LDL/VLDL cholesterol in response to an atherogenic diet containing 15% fat, 1.25% cholesterol, and 0.5% cholate. Correspondingly, B6By mice are also resistant to diet-induced aortic lesions, with less than 15% as many lesions as B6J. Food intake and cholesterol absorption are similar between B6By and B6J mice. To investigate the gene(s) underlying the resistant B6By phenotype, we performed genetic crosses with the unrelated mouse strain, A/J. A genome-wide scan revealed a locus, designated Diet1, on chromosome 2 near marker D2Mit117 showing highly significant linkage (lod = 9.6) between B6By alleles and hypo-response to diet. Examination of known genes in this region suggested that this locus represents a novel gene affecting plasma lipids and atherogenesis in response to diet.

Animals↗
PubMed1999

Effects of fasting and insulin-induced hypoglycemia on brain cell membrane function and energy metabolism during hypoxia-ischemia in newborn piglets.

This study was done to determine the effects of 12 h fasting-induced mild hypoglycemia (blood glucose 60 mg/dl) and insulin-induced moderate hypoglycemia (blood glucose 35 mg/dl) on brain cell membrane function and energy metabolism during hypoxia-ischemia in newborn piglets. Sixty-three ventilated piglets were divided into six groups; normoglycemic control (NC, n=8), fasting-induced mildly hypoglycemic control (FC, n=10), insulin-induced moderately hypoglycemic control (IC, n=10), normoglycemic/hypoxic-ischemic (NH, n=11), fasting-induced mildly hypoglycemic/hypoxic-ischemic (FH, n=12) and insulin-induced moderately hypoglycemic/hypoxic-ischemic (IH, n=12) group. Cerebral hypoxia-ischemia was induced by occlusion of bilateral common carotid arteries and simultaneous breathing with 8% oxygen for 30 min. The brain lactate level was elevated in NH group and this change was attenuated in FH and IH groups. The extent of cerebral lactic acidosis during hypoxic-ischemic insult showed significant positive correlation with blood glucose level (r=0.55, p<0.001). Cerebral Na+, K+-ATPase activity and concentrations of high-energy phosphate compounds were reduced in NH group and these changes were not ameliorated in FH or IH group. Cortical levels of conjugated dienes, measured as an index of lipid peroxidation of brain cell membrane, were significantly elevated in NH, FH and IH groups compared with NC, FC and IC groups and these increases were more profound in FH and IH with respect to NH. Blood glucose concentration showed significant inverse correlation with levels of conjugated dienes (r=-0.35, p<0.05). These findings suggest that, unlike in adults, mild or moderate hypoglycemia, regardless of methods of induction such as fasting or insulin-induced, during cerebral hypoxia-ischemia is not beneficial and may even be harmful in neonates.

Adenosine Triphosphate↗
PubMed1999

Influence of the antibody purification method on immunoassay performance: hapten-antibody binding in accordance with the structure of the affinity column ligand.

The effects of ligands for immunoaffinity chromatography on the immunoassay were investigated with three goat anti-methamphetamine (anti-MA) antibodies (Abs). An N-4-aminobutyl derivative of methamphetamine (4-ABMA) was conjugated with proteins and used as immunogens. All the antisera produced were purified by affinity chromatography with various ligands of 4-ABMA-proteins and of haptens as well as protein G: 4-ABMA-bovine serum albumin (4-ABMA-BSA), 4-ABMA-keyhole limpet hemocyanine (4-ABMA-KLH), 4-ABMA-ovalbumin (4-ABMA-OVA), MA, 4-ABMA, and amphetamine were used as ligands. Enzyme-linked immunosorbent assay (ELISA) was conducted to examine characteristics of the purified Abs with the 4-ABMA-OVA competitor coated. The results obtained revealed that characters of the purified Abs were closely related with chemical structures of ligands used. The Abs from the MA and the amphetamine columns showed better sensitivities than those from the others in each antiserum. Particularly, the Ab from the amphetamine column gave the best results in terms of sensitivity and specificity. The recognition or the affinity of the Ab selected was considered to be affected by the structure of the ligand concerned. These results suggest that the Ab purification method should be considered as an important parameter which has great influence on the performance of immunoassays with polyclonal Abs.

Animals↗
PubMed1999

Effect of C-terminal mutations of alfalfa mosaic virus coat protein on dimer formation and assembly in vitro.

The coat protein (CP) of alfalfa mosaic virus (AMV) strain 425 assembles to bacilliform or rod-shaped particles in the presence of nucleic acids or to T = 1 empty icosahedral particles in the absence of nucleic acids. To study the determinants of CP assembly, recombinant CPs (rCPs) that contained a (His)(6) region were expressed in Escherichia coli. Wt rCP and a mutant rCP, which lacked the last nine amino acids of the C terminus (amino acids 213-221), assembled to particles that were identical in electron micrographs. However, a mutant rCP, which lacked the last 18 amino acids of the C terminus (amino acids 204-221), did not assemble. Likewise, a mutant with alanine substitutions at W(191), F(197), and P(198) did not assemble. Furthermore rCP with a single alanine substitution at W(191) did not assemble, whereas the rCP, which had an arginine and an alanine substitution at A(196) and F(197), respectively, formed rod-shaped particles. The mutations that prevented assembly prevented dimer formation, which indicates that dimers are the minimal building blocks of particles. Our results indicate that two separate regions in the C terminus of AMV CP are critical for dimer formation and assembly and that changes in key amino acids in one of the regions affect both assembly and particle morphology.

Alfalfa mosaic virus↗
PubMed1999

Efficient and economical recovery of poly(3-hydroxybutyrate) from recombinant Escherichia coli by simple digestion with chemicals.

A simple method for the recovery of microbial poly(3-hydroxybutyrate) [P(3HB)] from recombinant Escherichia coli harboring the Ralstonia eutropha PHA biosynthesis genes was developed. Various acids (HCl, H2SO4), alkalies (NaOH, KOH, and NH4OH), and surfactants (dioctylsulfosuccinate sodium salt [AOT], hexadecyltrimethylammonium bromide [CTAB], sodium dodecylsulfate [SDS], polyoxyethylene-p-tert-octylphenol [Triton X-100], and polyoxyethylene(20)sorbitan monolaurate [Tween 20]) were examined for their ability to digest non-P(3HB) cellular materials (NPCM). Even though SDS was an efficient chemical for P(3HB) recovery from recombinant E. coli, it is expensive and has waste disposal problem. NaOH and KOH were also efficient and economical for the recovery of P(3HB), and therefore, were used to optimize digestion condition. When 50 g DCW/L of recombinant E. coli cells having the P(3HB) content of 77% was treated with 0.2 N NaOH at 30 degrees C for 1 h, P(3HB) was recovered with purity of 98.5%. Using this simple recovery method, the effect of recovery method on the final production cost of P(3HB) was examined. Processes for the production of P(3HB) by recombinant E. coli from glucose with two different recovery methods, surfactant-hypochlorite digestion and simple digestion with NaOH, were designed and analyzed. By employing the fermentation process that resulted in P(3HB) concentration, P(3HB) content and P(3HB) productivity of 157 g/L, 77%, and 3.2 P(3HB) g/L-h, respectively, coupled with the recovery method of NaOH digestion, the production cost of P(3HB) was US$ 3.66/kg P(3HB), which was 25% less than that obtained by employing the surfactant-hypochlorite digestion method.

Alkalies↗
PubMed1999

Increased tumor cell proliferation in murine tumors with decreasing dosage of wild-type p53.

A number of transgenic animal model systems have addressed the mechanistic role of p53 loss in tumor progression. However, many of these tumor models have analyzed p53 function in the context of other transgenes expressing activated oncogenes or defective tumor suppressor genes generated by gene targeting. To examine the role of p53 loss independent of other exogenous oncogenic influences, we analyzed some of the biological aspects of tumor formation and progression in p53-knockout mice containing a null germline p53 allele. We analyzed tumors from p53-/-, p53+/-, and p53+/+ littermates. Some of the p53+/- tumors had lost the remaining p53 allele (p53+/- loss of heterozygosity), whereas others retained the allele (p53+/-). In this report, we show that loss or absence of p53 conferred a tumor growth advantage by increasing the rate of cellular proliferation in a p53 dosage-dependent manner. The apoptotic levels in tumor tissue were found to be modest and not significantly dependent on p53 status. These results contrast with those from some other p53-deficient tumor models, in which p53 loss was associated with more rapid tumor progression through abrogated apoptosis. Finally, as p53 has been shown to regulate certain angiogenic factors, we examined the levels of angiogenesis in p53-containing and p53-deficient tumors. We found no p53-dependent differences in the levels of tumor angiogenesis measured by intratumoral microvessel density.

Alleles↗
PubMed1999

Lipopolysaccharide from Escherichia coli stimulates mucin secretion by cultured dog gallbladder epithelial cells.

Biliary infection is associated with mucin hypersecretion by the biliary epithelium. Mucins have been identified as potent pronucleators of cholesterol in bile. The aim of the present study was to determine whether lipopolysaccharides (LPS) from different bacteria are capable of stimulating mucin secretion by cultured dog gallbladder epithelial (DGBE) cells, and to investigate the mechanism by which LPS stimulate mucin secretion. Mucin secretion by confluent monolayers of DGBE cells was quantified by measuring the secretion of [3H]-N-acetyl-D-glucosamine-labeled glycoproteins. Cell viability was evaluated by measuring the leakage of the enzyme, lactate dehydrogenase (LDH), into the culture medium. LPS, derived from Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa (200 microg/mL), all caused an increase in mucin secretion by the DGBE cells, without causing concomitant cell lysis. LPS from E. coli was found to be the most potent stimulator of mucin secretion, and increased mucin secretion by the DGBE cells to 252% +/- 14% of control. LPS from E. coli had no effect on intracellular cyclic adenosine monophosphate (cAMP) levels in the DGBE cells. Addition of the nitric oxide (NO)-releasing compound, NOR-4 (0.125-1 mmol/L), to the cells did not result in increased mucin secretion, and the NO synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME) (4 or 10 mmol/L), did not inhibit the LPS-stimulated mucin secretion. Exogenous tumor necrosis factor alpha (TNF-alpha) (1-10 ng/mL) did cause a minor increase in mucin secretion by the DGBE cells, but the effect of LPS from E. coli on mucin secretion could not be inhibited by preincubation with a TNF-alpha antibody (10 microg/mL). We conclude that LPS stimulates mucin secretion by the gallbladder epithelium. Whether this stimulation is mediated by TNF-alpha remains to be determined.

Animals↗
PubMed1999

Expression of cyclin E in gynecologic malignancies.

OBJECTIVE: This study investigated the patterns of expression of cyclin E in clear cell carcinoma and other gynecological cancers. METHODS: Immunohistochemistry was performed on paraffin-embedded archival specimens of ovarian, endometrial, cervical, and renal carcinomas. RESULTS: Expression of cyclin E was evident in epithelial ovarian carcinomas utilizing immunohistochemistry. Immunohistochemistry revealed a high level of expression of cyclin E in a subset of gynecologic carcinomas, namely clear cell carcinomas, but not in clear cell carcinomas of renal origin. CONCLUSION: These data suggest that an elevated level of immunohistochemical activity of cyclin E is a property of clear cell carcinomas of Müllerian origin. Immunohistochemistry with anti-cyclin E antibodies may serve as a useful method for diagnosing gynecologic clear cell carcinomas. Future studies are needed to confirm a possible increased activity of cyclin E in clear cell tumors.

Adenocarcinoma, Clear Cell↗
PubMed1999

The effect of N-substituted alkyl groups on anticonvulsant activities of N-Cbz-alpha-amino-N-alkylglutarimides.

In order to examine the effects of N-substituted alkyl group on the anticonvulsant activities of N-Cbz-alpha-aminoglutarimides as novel anticonvulsants with broad spectrum, a series of (R) or (S) N-Cbz-alpha-amino-N-alkylglutarimides (1 and 2) were prepared from the corresponding (R) or (S) N-Cbz-glutamic acid and evaluated for the anticonvulsant activities in the maximal electroshock seizure (MES) test and pentylenetetrazol induced seizure (PTZ) test, including the neurotoxicity. The most potent compound in the MES test was (S) N-Cbz-alpha-amino-N-methylglutarimide (ED50=36.3 mg/kg, PI=1.7). This compound was also most potent in the PTZ test (ED50=12.5 mg/kg, PI=5.0). The order of anticonvulsant activities against the MES test as evaluated from ED50 values for (R) series was N-methyl > N-H > N-ethyl > N-allyl; for the (S) series N-methyl > N-H > N-ethyl > N-allyl > N-isobutyl compound. Against the PTZ tests, the order of anticonvulsant activities showed similar pattern; for the (R) series, N-methyl > N-H > N-ethyl > N-allyl; for the (S) series N-methyl > N-H > N-ethyl > N-allyl > N-isobutyl compound. From the above results, N-substituted alkyl groups were thought to play an important role for the anticonvulsant activities of N-Cbz-alpha-amino-N-alkylglutarimides.

Animals↗
PubMed1999

p53 in embryonic development: maintaining a fine balance.

In addition to its role as a tumour suppressor and cell-cycle checkpoint control protein, p53 has been implicated as an important protein in embryonic development. Despite the viability of most p53 null mice, evidence has accumulated that p53 may regulate differentiation and the response of embryonic cells to diverse environmental stresses. Moreover, it appears that maintenance of a fine balance of p53 protein levels within embryonic cells is important for optimal development. Inappropriate overexpression or underexpression of p53 can lead to embryonic lethality or increased risk of malformations. The p53 protein may utilize multiple functional activities in its regulation of developmental processes.

Animals↗
PubMed1999

Non-association of estrogen receptor genotypes with bone mineral density and bone turnover in Korean pre-, peri-, and postmenopausal women.

Estrogen is known to play a critical role in both skeletal maturity and the rate of bone loss. This suggests the possibility that the estrogen receptor (ER) gene is one of the candidate genes that determines peak bone density and/or bone turnover rate. We investigated two established restriction fragment length polymorphisms (RFLPs) in intron 1 at the ER gene, represented as PvuII and XbaI. In 598 healthy Korean women aged 20-74 years, we examined the association of these ER genotypes with bone mineral density (BMD) and bone turnover status. The distribution of the PvuII and XbaI RFLPs was as follows: pp 205 (34.3%), Pp 308 (51.5%), PP 85 (14.2%) and xx 384 (64.2%), Xx 180 (30.1%), XX 34 (5.7%), respectively (where capital letters signify the absence of, and lower-case letters signify the presence of, the restriction site of each RFLP). No significant genotypic differences were found in BMD and bone markers. We grouped the subjects into three categories according to their menstrual status: 104 premenopausal women with regular menstruation, 182 perimenopausal women who had amenorrhea of not less than 3 months and not more than 12 months' duration, and 312 postmenopausal women whose last menstruation was at least 12 months previously. No significant genotypic difference in either BMD or bone markers was found in any of these three groups. Furthermore we categorized women in peri- and postmenopause into a high loser group and a normal loser group according to the level of bone resorption markers. There was no difference in genotypic proportions between the high and normal loser groups. Our data suggest that these ER polymorphisms are not associated with BMD or bone turnover in Korean women.

Absorptiometry, Photon↗
PubMed1999

Visual input regulates the expression of basic fibroblast growth factor and its receptor.

Emerging evidence indicates that the expression of trophic factors in the brain is regulated in an activity-dependent manner, which suggests an involvement of trophic factors in events controlled by input activity. We have investigated the possibility that visual sensory input impacts the expression of basic fibroblast growth factor and its receptor in the brain. Rats were maintained for seven days in darkness and then re-exposed to normal illumination for 0, 1, 3 or 6 h. We assessed relative levels of basic fibroblast growth factor and fibroblast growth factor receptor messenger RNAs using nuclease protection assays, and examined possible changes in the phenotypic expression of basic fibroblast growth factor and its receptor using immunohistochemistry. There was a significant decrease in levels of basic fibroblast growth factor and fibroblast growth factor receptor messenger RNAs as a result of dark rearing, and levels of messenger RNAs increased progressively with light re-exposure. Changes in messenger RNAs were observed primarily in the cerebral cortex (caudal portion) and were accompanied by alterations in the staining intensity and density of cells exhibiting basic fibroblast growth factor and fibroblast growth factor receptor phenotypes. Regulation of the basic fibroblast growth factor system by sensory input suggests that basic fibroblast growth factor, and perhaps other trophic factors, are mediators of the effects of experience on the structure and function of the CNS.

Animals↗
PubMed1999

Testosterone levels and spatial ability in men.

Testosterone (T) levels were measured by salivary assays in 59 males at times of the day when T was expected to be highest and lowest. Relationships were evaluated for mean hormone levels across the two sessions and hormone level changes between sessions with performance on three-dimensional mental rotations, a spatial test which customarily favours males. An anagrams task and the digit symbol test were used as controls. Mental rotations scores showed a significant positive relationship with mean T levels but not with changes in T. There were no significant relationships between control test scores and mean T levels. Findings are discussed in terms of their contributions to the resolution of ambiguities in prior reported data.

Adult↗
PubMed1999

Characterization of superoxide dismutase activity in Chironomus riparius Mg. (Diptera, Chironomidae) larvae--a potential biomarker.

The activities of superoxide dismutase (SOD) isoenzymes were measured in fourth instar larvae of Chironomus riparius Mg. Three types of superoxide dismutase were identified: Cu,Zn-SOD in hemolymph and postmitochondrial fraction; Mn-SOD in mitochondrial fraction and presumably Fe-SOD in postmitochondrial fraction. The latter could have an endosymbiotic or a parasitic origin. Extracellular and cytosolic SOD activities, especially Cu,Zn-SOD, tended to increase in the last phase of larval development, independently of protein or hemoglobin contents. This supposes that SOD activity in Ch. riparius larvae is probably activated at the end of fourth instar stage. Cu,Zn-SOD and Mn-SOD activities showed a significant increase under severe hypoxia and slight hyperoxia. Oxygen radical scavengers such as SOD may play a role in the increased tolerance of Ch. riparius to oxidative stress. These results suggest that the specific induction of some SOD isoenzymes could be used as a biomarker of environmental disturbance such as oxidative stress initiated by xenobiotics.

Animals↗