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S W Choi

Publications and source records attributed to S W Choi.

At least 55 records · Page 3Linked to original sources
PubMed2000

Effects of dietary folate on DNA strand breaks within mutation-prone exons of the p53 gene in rat colon.

BACKGROUND & AIMS: Diminished folate status has been observed to increase colorectal cancer risk. Folate plays an important role in DNA synthesis and repair. This study investigated the effects of dietary folate on DNA strand breaks in the p53 and Apc genes, and how these changes are related to steady-state levels of the corresponding transcripts. METHODS: Three groups of rats were fed diets containing 0, 2 (basal requirement), or 8 mg folate/kg for 5 weeks. At each weekly time point, plasma and colonic mucosal folate concentrations were determined. Site-specific DNA strand breaks were assessed by semiquantitative PCR. Steady-state levels of messenger RNA were measured by semiquantitative RT-PCR. RESULTS: Dietary folate deficiency produced progressive DNA strand breaks within exons 5-8 of the p53 gene in rat colon (P<0.02). Accumulation of strand breaks was not observed in other exons of the p53 gene, in the Apc and beta-actin genes, or at the genomic level. Folate supplementation at 4 times the basal requirement significantly increased p53 integrity compared with the basal and deficient diets (P<0.05). p53 integrity in exons 5-8 was significantly correlated with folate status (P<0.03). Dietary folate deprivation progressively decreased, whereas supplementation increased, steady-state levels of p53 transcript over 5 weeks (P<0.05). No such changes were observed for the Apc gene. Steady-state levels of p53 transcript were significantly correlated with folate status and p53 integrity in exons 5-8 (P<0.002). CONCLUSIONS: These data provide a plausible mechanism by which folate deficiency promotes, and folate supplementation suppresses, colorectal carcinogenesis.

Adenomatous Polyposis Coli↗
PubMed2000

A case of extragenital lichen sclerosus following Blaschko's lines.

Extragenital lichen sclerosus is most common on the neck, shoulders, and upper portion of the trunk. A 20-year-old Korean man had asymptomatic, well-demarcated, linear violaceous plaques on the left lateral chest, in a pattern corresponding to the lines of Blaschko. We describe a case with a pattern of extragenital lichen sclerosus following Blaschko's lines.

Adult↗
PubMed2000

Folate and carcinogenesis: an integrated scheme.

Collectively, the evidence from epidemiologic, animal and human studies strongly suggests that folate status modulates the risk of developing cancers in selected tissues, the most notable of which is the colorectum. Folate depletion appears to enhance carcinogenesis whereas folate supplementation above what is presently considered to be the basal requirement appears to convey a protective effect. The means by which this modulation of cancer risk is mediated is not known with certainty, but there are several plausible mechanisms which have been described. Folate plays a major role in the formation of S-adenosylmethionine, the universal methyl donor, as well as in the formation of purine and thymidine synthesis for DNA and RNA. Therefore, most mechanistic studies performed to date have focused on alterations in DNA methylation, disruption of DNA integrity and disruption of DNA repair, all of which have been observed with folate depletion. These aberrations in DNA are believed to enhance carcinogenesis by altering the expression of critical tumor suppressor genes and proto-oncogenes. Recently, the role of a common polymorphism of the methylenetetrahydrofolate reductase gene has been highlighted as well. This review presents those mechanisms which are the most likely candidates to explain folate's effects and it proposes an integrated scheme to explain how these mechanisms might interact.

Animals↗
PubMed2000

Effect of wearing clothes on oxygen uptake and ratings of perceived exertion while swimming.

For a comparative study between swimming in swimwear (control-sw) and swimming in clothes (clothes-sw), oxygen uptake (VO2) and ratings of perceived exertion (RPE) were measured. The subjects were six male members of a university swimming team. Three swimming strokes--the breaststroke, the front crawl stroke and the elementary backstroke--were applied. With regards to clothes-sw, swimmers wore T-shirts, sportswear (shirt and pants) over swimwear and running shoes. In both cases of control-sw and clothes-sw, the VO2 was increased exponentially with increased swimming speed. The VO2 of the subjects during the clothed tests did not exceed 1.4 times of that in the case of control-sw at swimming speeds below 0.3 m/s. As swimming speeds increased, VO2 difference in both cases increased. Consequently, VO2 in the clothed tests was equal to 1.5-1.6 times and 1.5-1.8 times of that in the swimwear tests at speeds of 0.5 and 0.7 m/s, respectively. At speeds below 0.6 m/s in clothes-sw, the breaststroke showed lower VO2 than the front crawl stroke, and the elementary backstroke showed higher VO2 than the other two swimming strokes. RPE increased linearly with %peak VO2. In addition, any RPE differences among the three swimming strokes were not shown in the control-sw tests. At an exercise intensity above 60 %peak VO2, clothed swimmers showed slightly higher RPE in the front crawl stroke compared to that in the two other swimming strokes.

Adult↗
PubMed2000

Churg-Strauss syndrome with perforating ulcers of the colon.

We report a case of a 72-year-old woman with Churg-Strauss syndrome, who presented with intestinal perforation. She has had bronchial asthma with peripheral blood eosinophilia for 30 years. Gross findings of a resected colon showed multiple ulcers with perforation. Histologic findings demonstrated transmural inflammation infiltrated with large numbers of eosionophils, neutrophils and lymphoplasma cells, and characteristic extravascular granuloma in the subserosa. There were multifocally-distributed transmural vasculitis showing all stages of activity in medium and small-sized arteries and veins located in the submucosa, and proper muscle and subserosal layers of the colon, some of which revealed granulomatous inflammation. Histologic finding of liver showed chronic viral hepatitis B with mild inflammatory activity and macronodular cirrhosis. Immunohistochemical findings, acid fuschin orange G staining and electromicroscope found no evidence of hepatitis B virus infection contributing to the pathogenesis of this lesion.

Aged↗
PubMed2000

A case of chronic cerebral paragonimiasis westermani.

We report a chronic cerebral paragonimiasis from a 41-year-old Korean man who complains a headache and weakness of left motor neuron components. Magnetic resonance images of the brain revealed conglomerates of multiple ring-like enhancements in temporo-occipital and frontal lobes of the right hemisphere. An intradermal test for paragonimiasis westermani was positive. The patient was born near an endemic area of paragonimiasis and used to eat boiled or grilled freshwater crayfish in his childhood. Nodules in the brain were resected through craniotomies. The eggs of P. westermani were identified pathologically and parasitologically in the calcified necrotic lesions. Examinations on sputum and fecal specimens for the eggs of P. westermani were shown to be negative and a chest radiograph was normal. It is presumed that the brain lesions were formed by P. westermani approximately 30 years ago.

Adult↗
PubMed2000

Effect of chronic alcohol consumption on total plasma homocysteine level in rats.

BACKGROUND: Chronic alcoholism in humans is associated with the development of hyperhomocysteinemia, the mechanism of which remains unclear. Among the causes of hyperhomocysteinemia is depletion of folate, vitamin B12, or vitamin B6. Population-based studies indicate that folate is the strongest vitamin determinant of hyperhomocysteinemia and, in most settings, folate supplementation effectively lowers elevated homocysteine levels. However, it is not clear whether folate deficiency is the cause of alcohol-related hyperhomocysteinemia. METHODS: In the present study, 10 male Sprague Dawley rats were fed ethanol-containing Lieber-DeCarli diets with 13 mg of folic acid per kilogram of diet. This represents a folate intake more than 20 times the basal requirement. Ethanol represented 36% of total energy, which yielded a concentration of 6.2% (vol/vol). The same number of rats were pair-fed with isocaloric control diets that contained an identical level of folate in which ethanol was entirely replaced by maltodextrin. RESULTS: At the end of 4 weeks, alcohol-fed rats did not show any significant reduction in plasma or hepatic folate concentrations, plasma pyridoxal-5'-phosphate concentration, or plasma vitamin B12 concentration. On the other hand, alcohol-fed rats were significantly hyperhomocysteinemic (17.24 +/- 4.63 micromol/liter,p < 0.01) compared to the nonalcohol group (10.73 +/- 2.76 micromol/liter). Alcohol-fed rats also had a significantly lower hepatic S-adenosylmethionine and higher hepatic S-adenosylhomocysteine levels. CONCLUSIONS: Chronic alcohol consumption produces hyperhomocysteinemia by a mechanism that is related to interference with one-carbon metabolism, and not through vitamin depletion.

Alcohol Drinking↗
PubMed2000

Genomic DNA hypomethylation, a characteristic of most cancers, is present in peripheral leukocytes of individuals who are homozygous for the C677T polymorphism in the methylenetetrahydrofolate reductase gene.

DNA methylation is an epigenetic feature of DNA that influences cellular development and function, and aberrations of DNA methylation are a candidate mechanism for the development of cancer. Methylenetetrahydrofolate reductase (MTHFR) catalyzes the synthesis of 5-methyltetrahydrofolate, the methyl donor for methionine synthesis and the precursor of S-adenosylmethionine. S-adenosylmethionine is the universal methyl donor for methylation reactions, including that of DNA methylation. In the present study, we investigated whether a common C677T mutation in the MTHFR gene, which results in reduced enzyme activity in vitro, affects genomic DNA methylation. We selected 9 subjects homozygous for the wild-type MTHFR and 10 subjects homozygous for the mutation (T/T). Genomic DNA methylation was determined by an established enzymatic assay that measures the capacity of DNA to accept methyl groups in vitro, which is inversely related to endogenous methylation. DNA from subjects with the T/T MTHFR genotype had a significantly higher methyl group acceptance capacity (12,615 +/- 1836 dpm/2 microg of DNA) compared with wild-type MTHFR (7843 +/- 1043 dpm/2 microg of DNA; P < 0.05), indicating DNA hypomethylation in the T/T genotype. Furthermore, DNA methylation was directly and significantly related to RBC folate concentrations in persons with the T/T genotype, but not in those with wild-type MTHFR. These data are consistent with prior observations, which suggest that the T/T genotype is associated with impaired MTHFR activity in vivo and that the cellular impact of this impairment is determined, in part, by folate status. The relationship of genomic DNA hypomethylation in persons with the T/T MTHFR genotype to the development of cancer remains to be defined.

Adult↗
PubMed1999

Relationship between intratumor histological heterogeneity and genetic abnormalities in gastric carcinoma with microsatellite instability.

Microsatellite instability (MSI)-mutator phenotype variably targets microsatellite-like sequences in coding regions of cancer-related genes. Intratumor histological heterogeneity of gastric carcinoma with MSI was evaluated and found to be linked with the topographical distribution of MSI-associated mutations. One hundred fifty tumor sites derived from 51 gastric cancer patients were microdissected with respect to histological and topographical clonality. We found 11 gastric carcinomas with a high frequency of MSI, which were characterized by marked intratumor genetic heterogeneity arising from the progressive MSI-phenotype that was associated with frameshift mutations on multiple cancer-related genes. The 11 MSI-tumor cases manifested the MSI-phenotype in 34 of 36 tumor sites tested, but not in the remaining 2 sites. Most (88.2%, 30 of 34) MSI-positive sites and most (96.2%, 25 of 26) tumor sites harboring the frameshift mutations in transforming growth factor-beta receptor type II gene exhibited intestinal-type histology, whereas the 2 MSI-negative sites were found to be of diffuse-type histology without accompanying frameshift mutations. In 2 of 5 cases harboring E2F-4 frameshift mutations, glandular structures of intestinal-type tumor were likely to be variably differentiated in relation to the extent of the mutation, i.e., the number of mutated alleles and the size of deleted or inserted base pairs. Overall, the intratumor histological heterogeneity of gastric carcinoma with MSI was associated with the progressive frameshift mutations in transforming growth factor-beta receptor type II and E2F-4 genes.

Base Pair Mismatch↗
PubMed1999

Design, synthesis, and biological evaluation of novel non-piperazine analogues of 1-[2-(diphenylmethoxy)ethyl]- and 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazines as dopamine transporter inhibitors.

A series of novel diamine, amine-amide, and piperazinone analogues of N-[2-(bisarylmethoxy)ethyl]-N'-(phenylpropyl)piperazines, GBR 12909 and 12935, were synthesized and evaluated as inhibitors of presynaptic monoamine neurotransmitter transporters. The primary objective of the study was to determine the structural requirements for selectivity of ligand binding and potency for neurotransmitter reuptake inhibition. In general, the target compounds retained transporter affinity; however, structural variations produced significant effects on reuptake inhibition and transporter selectivity. For example, analogues prepared by replacing the piperazine ring in the GBR structure with an N, N'-dimethylpropyldiamine moiety displayed enhanced selectivity for binding and reuptake inhibition at the norepinephrine (NE) transporter site (e.g. 4 and 5). Congeners in which the amide nitrogen atom was attached to the aralkyl moiety of the GBR molecule showed moderate affinity (K(i) = 51-61 nM) and selectivity for the dopamine transporter (DAT) site. In contrast, introduction of a carbonyl group adjacent to either nitrogen atom of the piperazine ring (e.g. 25 and 27) was not well tolerated. From the compounds prepared, analogue 16 was selected for further evaluation. With this congener, locomotor activity induced by cocaine at a dose of 20 mg/kg was attenuated with an AD(50) (dose attenuating cocaine-induced stimulation by 50%) of 60.0 +/- 3.6 mg/kg.

Amides↗
PubMed1999

Cloning and sequencing of beta-1,4-endoglucanase gene (celA) from Pseudomonas sp. YD-15.

A beta-1,4-endoglucanase gene (celA) from Pseudomonas sp. YD-15 was cloned in Escherichia coli DH5 alpha and its nucleotide sequence determined. The open reading frame of celA was 1830 base pairs and the enzyme was composed of 609 amino acids with a molecular weight of 63,617 Da. The deduced amino acid sequence and putative active site of CelA had high amino acid homology with family E cellulases. By dot blot analysis, the induction of celA according to carbon sources was determined. The transcripts hybridizing to the internal fragment of celA were detected in total RNA isolated from Pseudomonas sp. YD-15 cells grown on avicel and glycerol, but not from cells grown on glucose and cellobiose.

Amino Acid Sequence↗
PubMed1999

The effect of dietary folate on Apc and p53 mutations in the dimethylhydrazine rat model of colorectal cancer.

Dietary inadequacy of folate enhances and folate supplementation suppresses colorectal carcinogenesis in the dimethylhydrazine rat model. Folate is an essential factor for DNA methylation and the de novo biosynthesis of nucleotides, aberrations of which play important roles in mutagenesis. This study investigated whether the mutational hot spots of the Apc and p53 genes for human colorectal cancer are mutated in dimethylhydrazine-induced colorectal neoplasms and whether dietary folate can modulate mutations in these regions. Rats were fed diets containing 0, 2 (basal requirement), 8 or 40 mg folate/kg diet. Five weeks after diet initiation, dimethylhydrazine was injected weekly for 15 weeks. Mutations were determined by direct sequencing in 11 low and seven high grade dysplasias and 13 invasive adenocarcinomas. A total of six Apc mutations were found in four dysplastic and carcinomatous lesions: two in two low grade dysplasias, two in one high grade dysplasia and two in one adenocarcinoma. All mutations were single base substitutions, four of which were A:T-->G:C transitions. Five of the six mutations were located upstream from the region corresponding to the human APC mutation cluster region. Dietary folate had no effect on the frequency and type of Apc mutations. No mutations were detected in exons 5-9 of the p53 gene in neoplastic lesions. These data suggest that in the dimethylhydrazine rat model of colorectal cancer, the Apc gene is mutated in early stages, albeit to a lesser degree than observed in human colorectal cancer, whereas the mutational hot spot of the p53 gene for human colorectal cancer is not commonly mutated. Although the low frequency of Apc mutations and the small number of neoplasms studied in this study might have precluded our ability to observe modulatory effects of folate, dietary folate appears to have no significant effect on Apc and p53 mutations.

Animals↗
PubMed1999

Chronic alcohol consumption induces genomic but not p53-specific DNA hypomethylation in rat colon.

Alcohol consumption has been implicated as an etiologic agent in colorectal carcinogenesis, but the mechanism by which alcohol enhances the development of colorectal cancer is not yet known. Recent reports indicate that alcohol consumption can diminish cellular S-adenosylmethionine levels, thus possibly altering normal patterns of DNA methylation, a phenomenon that is mediated by S-adenosylmethionine and whose abnormalities are observed in colonic neoplasia. This study investigated the effect of chronic alcohol consumption on genomic DNA methylation of rat colonic epithelium and methylation of the p53 tumor suppressor gene, abnormalities of which have been implicated in colonic carcinogenesis. Two groups of rats (n = 10/group) were pair-fed either an alcohol-containing or an isocaloric control Lieber-DeCarli diet for 4 wk. The extent of genomic DNA methylation was assessed by incubating the extracted DNA with [(3)H]S-adenosylmethionine and Sss1 methyltransferase. Gene-specific methylation was assessed by using semiquantitative polymerase chain reaction (PCR). Tritiated methyl uptake by colonic DNA (which is inversely correlated with genomic methylation) from alcohol-fed rats was 57% less than that in control DNA (P < 0.05). However, gene-specific DNA methylation, both in the p53 gene (exons 5-8) and in the beta-actin gene, a control gene, did not differ between the two groups. In conclusion, this study indicates that chronic alcohol consumption produces genomic DNA hypomethylation in the colonic mucosa. This may constitute a means by which carcinogenesis is enhanced, although further studies are required to establish causality.

Animals↗
PubMed1999

Vitamin B12 deficiency: a new risk factor for breast cancer?

A prospective epidemiologic study found a threshold level for serum vitamin B12, below which an increased risk of breast cancer among postmeno-pausal women was observed. This is the first observation to suggest that B12 status may influence breast carcinogenesis and therefore may be a modifiable risk factor for breast cancer prevention.

Animals↗
PubMed1999

The metabolic effects of estriol in female rat liver.

The effects of estriol on oxygen uptake, glucose release, lactate and pyruvate production, beta-hydroxybutyrate and acetoacetate production in perfused rat liver as well as, carbon uptake in rat liver and intracellular calcium in isolated Kupffer cells were investigated. Basal oxygen consumption of perfused liver increased significantly in estriol or ethanol-treated rats. But these increased effects were blocked by gadolinium chloride pretreatment. In a metabolic study, pretreatment with estriol resulted in a decrease in glucose production and in glycolysis while an increase in ketogenesis. A more oxidized redox state of the mitochondria was indicated by increased ratios of perfusate [lactate]/[pyruvate] and decreased ratios of perfusate [beta-hydroxybutyrate]/[acetoacetate]. Carbon uptake of Kupffer-cell increased significantly in estriol-treated rats. But these increased uptake were not shown in rats pre-treated by gadolinium chloride blocking phagocytosis. In isolated Kupffer cells from estriol-treated rats, intracellular calcium was more significantly increased after addition of lipopolysaccharide (LPS) than in controls. These findings suggest that the metabolic effects of estriol (two mg per 100 mg body wt) can be summarized to be highly toxic in rat liver, and these findings suggest that oral administration of estrogens may induce hepatic dysfunctions and play a role in the development of liver disease.

3-Hydroxybutyric Acid↗