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Biomedical subjects

S W Choi

Publications and source records attributed to S W Choi.

At least 73 records · Page 4Linked to original sources

A case of primary leiomyosarcoma of the lesser omentum.

Leiomyosarcoma is a rare tumor that originates in the smooth muscle, usually in the gastrointestinal tract, the retroperitoneum and the genitourinary tract. The omentum has been rarely reported as a primary site of occurrence with leiomyosarcoma. A 72 year-old woman, with palpable mass on the left upper quadrant of abdomen and weight loss, was admitted to St. Paul's Hospital. Abdominal CT scan showed a 12 x 8 x 8 cm-sized cystic mass in the left upper quadrant of the abdomen. Endoscopic ultrasonography showed a large cystic mass between the stomach and the liver, which was 1.6 cm length in wall thickness. Laparotomy and resection of the mass was performed. A 12 x 8 x 8 cm-sized mass, originated from the lesser omentum, was discovered near the lesser curvature of the stomach. Microscopic examination revealed spindle-shaped cells with 7-8 mitoses per high power field. She was diagnosed as primary leiomyosarcoma originated from the lesser omentum.

Aged↗

Fractional allelic loss in gastric carcinoma correlates with growth patterns.

To gain an insight into the genetic events underlying morphological phenotypes, we analysed 58 gastric carcinoma tissues for the genome-wide allelotype study using microsatellite markers. Based on a binomial distribution, loss of heterozygosity (LOH) that was significantly more frequent than expected (P<0.05) thus interpreted as nonrandom LOH selected during tumorigenesis. The overall extent of chromosomes undergoing LOH i.e. fractional allelic loss (FAL, the ratio of LOH-positive markers to the total number of informative markers) was measured in each tumor patient. Nonrandom LOH was found on 17p (48.0%), 18q (38.4%), 13q (38.1%) and 9p (36.4%). Overall, there were no significant phenotypes correlated with allelic loss on specific chromosome regions. Based on a bimodal distribution of FAL values with two peaks bordered by a mean of 0.233, tumors were classified into LOH-related (>0.233) and LOH-unrelated (<0.233) types. Among 24 patients with LOH-related tumors, increase in the infiltrative type of growth pattern was found to correspond with a significant trend of increasing FAL values. This study shows that the growth pattern of gastric carcinoma is correlated with FAL, suggesting that a malignant phenotype is influenced by LOH event.

Adenocarcinoma↗

Protein kinase C-alpha levels are inversely associated with growth rate in cultured human dermal fibroblasts.

Human dermal fibroblasts are known to express the alpha, delta, epsilon, and zeta isoforms of protein kinase C (PKC). We asked whether the growth of human dermal fibroblasts correlates with expression of a particular PKC isoform. Of total PKC activity measured in the presence of calcium, a condition permissive for activation of all PKC isoforms, 75%) was contributed by PKC-alpha, suggesting that PKC-alpha is the dominant isoform in human dermal fibroblasts. We then further studied PKC-alpha under different culture conditions and in cultures derived from different aged donors. In both subconfluent and confluent cultures, total PKC activity and the level of PKC-alpha protein were consistently higher in slowly proliferating adult cells than in more rapidly proliferating newborn cells. Moreover, in newborn fibroblasts density strongly influenced these parameters. At subconfluent density, when cells were dividing exponentially, total PKC activity was 345+/-63 cpm/,ug protein; whereas at confluent density, when cells were growth arrested, it was 6-7 fold higher, 2334+/-50 cpm/ug protein. Immunoblot analysis using a specific monoclonal antibody against PKC-alpha exhibited a similar 6-7 fold increase in the level of PKC-alpha protein at confluent density. However, in adult cells, density had no influence on the already high total activity or level of PKC-alpha. To further determine whether the increases in the levels of total PKC activity and the alpha isoform correlate with the decreased growth rate, a characteristic of both adult donor-derived and confluent cells, total PKC activity and the level of PKC-alpha in subconfluent quiescent cells was compared to that in paired exponentially growing cells at the same density. Total PKC activity was 8836+/-71 cpm/microg protein in subconfluent quiescent cells versus 4415+/-175 cpm/microg protein in dividing cells. The level of PKC-alpha protein was also 2-3 fold higher in quiescent than in growing cultures. However, the amount of PKC-alpha mRNA in these two conditions was identical as determined by northern blot analysis. Taken together, these results suggest an inverse relationship between the levels of total PKC activity and PKC-alpha protein and fibroblast growth rate that is regulated at the post-transcriptional level.

Adult↗

Implantable control, telemetry, and solar energy system in the moving actuator type total artificial heart.

The moving actuator type total artificial heart (TAH) developed in the Seoul National University has numerous design improvements based upon the digital signal processor (DSP). These improvements include the implantability of all electronics, an automatic control algorithm, and extension of the battery run-time in connection with an amorphous silicon solar system (SS). The implantable electronics consist of the motor drive, main processor, intelligent Li ion battery management (LIBM) based upon the DSP, telemetry system, and transcutaneous energy transmission (TET) system. Major changes in the implantable electronics include decreasing the temperature rise by over 21 degrees C on the motor drive, volume reduction (40 x 55 x 33 mm, 7 cell assembly) of the battery pack using a Li ion (3.6 V/cell, 900 mA.h), and improvement of the battery run-time (over 40 min) while providing the cardiac output (CO) of 5 L/min at 100 mm Hg afterload when the external battery for testing is connected with the SS (2.5 W, 192.192, 1 kg) for the external battery recharge or the partial TAH drive. The phase locked loop (PLL) based telemetry system was implemented to improve stability and the error correction DSP algorithm programmed to achieve high accuracy. A field focused light emitting diode (LED) was used to obtain low light scattering along the propagation path, similar to the optical property of the laser and miniature sized, mounted on the pancake type TET coils. The TET operating resonance frequency was self tuned in a range of 360 to 410 kHz to provide enough power even at high afterloads. An automatic cardiac output regulation algorithm was developed based on interventricular pressure analysis and carried out in several animal experiments successfully. All electronics have been evaluated in vitro and in vivo and prepared for implantation of the TAH. Substantial progress has been made in designing a completely implantable TAH at the preclinical stage.

Algorithms↗

Folate depletion impairs DNA excision repair in the colon of the rat.

BACKGROUND/AIMS: Diminished folate status appears to promote colonic carcinogenesis by, as of yet, undefined mechanisms. Impaired DNA repair plays a significant role in the evolution of many colon cancers. Since folate is essential for the de novo synthesis of nucleotides and since folate depletion has previously been associated with excessive DNA strand breaks, it was hypothesised that folate depletion may impair DNA repair. Studies were therefore performed to examine whether folate depletion affects the two major categories of DNA repair. METHODS: Study 1: eight weanling male Sprague-Dawley rats were fed on diets containing either 0 or 8 mg folate/kg diet with 1% succinylsulphathiazole for four weeks. After viable colonocytes had been harvested, DNA excision repair was evaluated by a single cell gel electrophoresis assay. Study 2: eighteen animals were fed on similar diets for five weeks. Also in study 2, 18 additional rats were fed on the same defined diet without succinylsulphathiazole for 15 weeks. Weekly injections with the procarcinogen, 1,2-dimethylhydrazine (20 mg base/kg), were administered to the latter group of animals. Five microsatellite loci from different chromosomes were investigated for instability in hepatic and colonic DNA. RESULTS: In study 1, a significantly retarded rate of DNA excision repair was observed in the folate deficient colonocytes compared with controls (p < 0.05). In study 2, there was no evidence of instability at the five microsatellite loci associated with either short or long term folate depletion. CONCLUSIONS: Folate deficiency impairs DNA excision repair in rat colonic mucosa; a similar degree of deficiency, even when administered in conjunction with a colonic carcinogen, did not produce evidence of a widespread defect in mismatch repair.

1,2-Dimethylhydrazine↗

Effects of prostaglandins on ethanol damage in primary cultured rat hepatocytes.

OBJECTIVES: Several reports demonstrated that ethanol administration impairs the DNA synthesis in rat hepatocytes. Also, it has been demonstrated that prostaglandin (PG) helps prevent membrane damage by hepatotoxic chemicals. In this study, the authors examined PG's effects on the toxicity of ethanol in the primary culture of rat regenerations. METHODS: We examined two kinds of parameters, i.e., DNA synthesis and lipid peroxidation in the primary culture of rat hepatocytes. Hepatocytes were isolated by the collagenase perfusion method. The rate of DNA synthesis was determined by pulse-labelling cultured cells with [3H]-thymidine. Incorporation of (3H)-thymidine was determined by liquid scintillation spectrophotometer. DNA content was measured by the fluorescence spectrophotometer. The lipid peroxidation was assayed with spectrophotometer. RESULTS: The results were as follows: 1) PG family (PGA1, PGD2, PGE1, PGE2, PGG2a, PGI2 & Thromboxane B2) stimulated the DNA synthesis of hepatocytes (especially PGD2 and PGE1), 2) ethanol decreased DNA synthesis by clear dose-dependent manner, 3) the combined treatment of PGD2 or PGE1, prevents the decreasing of DNA synthesis, which was induced by ethanol, 4) in ethanol treatment, lipid peroxidation was decreased significantly, but PGD2, PGE1 and PGA1 were not affected, and 5) PGD2, PGE1 and PGA1 decreased lipid peroxidation with ethanol, significantly. CONCLUSIONS: From these results, we concluded that PG could be useful for the treatment of degenerative liver disease and alcohol-induced liver disease in the assumption that further studies on the action mechanisms of PG will continue.

Animals↗

Evidence of genetic progression in human gastric carcinomas with microsatellite instability.

Mutator phenotype tumors provide unique opportunities to unravel malignant progression because of various gene alterations acquired during clonal tumor evolution. Gastric carcinomas, which have been known to show frequent genetic instability, would be composed of initial gene alterations shared by most tumor areas and subsequent alterations restricted to particular tumor sites. To analyse the timing of genetic events, we examined separate sites of tumor tissue obtained from a given gastric carcinoma patient with microsatellite instability (MSI). Our study included 95 normal/tumor area pairs from 25 patients. Six of the 25 patients (24%) demonstrated various levels of MSI ranging from 7% (two of 30) to 97% (28 of 29) of markers tested in multiple tumor sites. Of the six patients, five manifested frameshift mutations in a tract of ten deoxyadenosines within transforming growth factor beta receptor type II and four demonstrated frameshift mutations in a tract of eight deoxyguanosines within BAX. These mutations were common to all tumor sites regardless of the various level of MSI phenotype, indicating initial events. Two of the six patients exhibited frameshift mutations in mononucleotide repeats of mismatch repair genes, hMSH3 and hMSH6, and the insulin-like growth factor II receptor in restricted tumor areas, indicating additional alterations. Insulin-like growth factor II receptor mutations appear to be caused by hMSH3 and hMSH6 mutations because the former mutations were confined to tumor portions with the latter two mismatch repair lesions. These results provide genetic progression evidence for gastric carcinomas of the mutator pathway. In this pathway, mismatch repair insufficiency initially targets mononucleotide tracts of transforming growth factor beta receptor type II and BAX. During tumorigenesis, primary mismatch repair failure may give rise to the secondary mismatch repair lesions, frameshift mutations of hMSH3 and hMSH6, which result in another tumorigenic mutation in the insulin-like growth factor II receptor.

Adult↗

Parameter recovery for the partial credit model using MULTILOG.

This study investigated parameter recovery for the partial credit model using the MULTILOG computer program. Factors studied were the sample size and the number of item parameters, which were manipulated by systematically varying the number of steps per item and the number of items. The findings suggest that the ratio of sample size to number of item parameters being estimated as a "rule of thumb" can be a more complete guideline when the number of steps per item is taken into account. Accurate estimation of ability can be obtained across all conditions, even with sample sizes as small as 250. With regard to estimation of step values, however, more caution is warranted. Accurate estimation of the step values of items which have more categories requires larger sample sizes for a given number of total parameters to be estimated.

Humans↗

Microsatellite instability-associated mutations associate preferentially with the intestinal type of primary gastric carcinomas in a high-risk population.

Most colon cancers exhibiting microsatellite instability (MI), a mutator phenotype of mismatch repair failure, are associated with mutations of the transforming growth factor-beta receptor type II genes (TGF-beta RII). Of intestinal- and diffuse-type gastric carcinomas, the former have been thought to arise from intestinal metaplasia in which gastric mucosa resembles intestinal mucosa. To evaluate the preferential histological type of MI-associated mutations in the development of gastric carcinoma, mutations of TGF-beta RII, p53, and p16 were analyzed for the two types of primary gastric carcinomas showing MI. Of 50 primary gastric carcinomas, including 33 intestinal types and 17 diffuse types, 15 cases (30%) demonstrated MI at 1 or more of the 11 microsatellite markers tested. The 15 MI cases were classified into two groups, widespread MI and low-level MI, based on the number of markers exhibiting the instability. Eleven were widespread MIs, and the remaining four cases were low-level MIs. Ten of the 11 (91%) widespread MIs were of the intestinal type, and 1 case (9%) was of the diffuse type. Of the 11 widespread MIs, 10 cases (91%) demonstrated frameshift mutations within the polyadenylate tract of the TGF-beta RII. The frameshift mutation was rarely detected at p53 and p16 (1 of 11, 9%). In contrast, the four low-level MI cases had no frameshift mutations within the repeat sequences of TGF-beta RII, p53, and p16, but two of the four cases demonstrated base substitution mutations within p53. Our results suggest that mismatch repair failure can mutate the TGF-beta RII and may provide one of the pathways for the development of the intestinal-type gastric carcinoma in high-risk populations.

Adenocarcinoma↗

To culture or not to culture: fecal lactoferrin screening for inflammatory bacterial diarrhea.

Because of its low yield in unselected specimens, stool culture is often cost ineffective. We tested 55 fecal samples from Fairfax Hospital (46 patients with diarrhea and 9 from controls without diarrhea) for lactoferrin by latex agglutination (LFLA) with the Leukotest (Techlab, Blacksburg, Va.) as a marker for inflammatory diarrhea. Of the 28 samples with Salmonella, Shigella, or Campylobacter infection, 93% had detectable fecal lactoferrin at > or = 1:50 (61% had LFLA titers of > or = 1:400), while 83% of 18 samples with rotavirus or no detectable pathogen were LFLA negative at a titer of 1:50 (100% were negative at 1:400). All 9 controls without diarrhea were LFLA negative at 1:50. The use of fecal lactoferrin to screen for inflammatory diarrhea selects specimens for which stool culture is fivefold more likely to yield an invasive bacterial pathogen (reducing the cost per positive result by over $800) and thus may greatly enhance a cost-effective approach to evaluating diarrheal illness.

Adolescent↗

Dietary folate protects against the development of macroscopic colonic neoplasia in a dose responsive manner in rats.

BACKGROUND AND AIMS: Diminished folate status is associated with enhanced colorectal carcinogenesis. This study investigated the potential chemopreventive role of dietary folate in the dimethylhydrazine colorectal cancer model. SUBJECTS AND METHODS: Sprague-Dawley rats were fed diets containing either 0, 2 (daily dietary requirement), 8 or 40 mg folate/kg diet for 20 weeks. After five weeks of diet, rats were injected with dimethyl-hydrazine (44 mg/kg) weekly for 15 weeks. Fifteen weeks after the first injection of dimethylhydrazine, all rats were killed. Folate status was determined, and the entire colorectum from each rat was analysed for macroscopic and microscopic neoplasms. RESULTS: Plasma and colonic folate concentrations correlated directly with dietary folate levels (p < 0.005). The incidence of microscopic neoplasms was similar among the four groups. However, the incidence and the average number of macroscopic tumours per rat decreased progressively with increasing dietary folate levels up to 8 mg/kg diet (p < 0.05). In the strongly procarcinogenic milieu used in this study, folate supplementation at 20 times the basal requirement was associated with rates of macroscopic tumour development that were intermediate, and not statistically distinct, from rates observed at either 0 or 8 mg/kg diet. CONCLUSIONS: These data indicate that in this rat model, (a) increasing dietary folate up to four times the basal requirement leads to a progressive reduction in the evolution of macroscopic neoplasms from microscopic foci; and (b) folate supplementation beyond four times the requirement does not convey further benefit.

Analysis of Variance↗

A case of combined gastrojejunal and gastrocolic fistula secondary to gastric cancer.

A rare case of gastric cancer associated with gastrojejunal and gastrocolic fistula is presented. A 56-year-old man who had been diagnosed with advanced gastric cancer(Borrmann's type III) 5 months previously was admitted due to watery diarrhea and frequent vomiting for 2 weeks. Fluoroscopic examination was visualized two abnormal passage of contrast medium from the stomach, one to the colon, and the other to the jejunum. Gastrofiberscopy revealed that the tumor on the great curvature of the body appeared to penetrate into the colon, while the other one on the antrum directly invaded into the jejunum. The patient was treated conservatively with total parenteral nutrition and pain control.

Colonic Diseases↗

A case of polyarteritis nodosa with bilateral ureteral obstruction.

We report a case of bilateral ureteral obstruction most likely caused by polyarteritis nodosa. The diagnosis was based upon muscle biopsy which showed typical necrotizing vasculitis in medium size artery in conjunction with microaneurysms in renal angiography. Ureteral obstruction is a rare manifestation of polyarteritis nodosa. This condition is thought to result from vasculitis of periureteral vessels. The patient was managed with prednisolone alone, which resulted in complete resolution of ureteral obstruction on both sides.

Female↗

Exon-specific DNA hypomethylation of the p53 gene of rat colon induced by dimethylhydrazine. Modulation by dietary folate.

Folate deficiency enhances colorectal carcinogenesis in dimethylhydrazine-treated rats. Folate is an important mediator of DNA methylation, an epigenetic modification of DNA that is known to be dysregulated in the early stages of colorectal cancer. This study investigated the effect of dimethylhydrazine on DNA methylation of the colonic p53 gene and the modulation of this effect by dietary folate. Sprague-Dawley rats were fed diets containing 0, 2, 8, or 40 mg of folate/kg of diet. Five weeks after diet initiation, dimethylhydrazine was injected weekly for fifteen weeks. Folate-depleted and folate-replete control animals did not receive dimethylhydrazine and were fed the 0- and 8-mg folate diets, respectively. The extent of p53 methylation was determined by a quantitative HpaII-polymerase chain reaction. In exons 6 and 7, significant p53 hypomethylation was observed in all dimethylhydrazine-treated rats relative to controls (P < 0.01), independent of dietary folate. In exon 8, significant p53 hypomethylation was observed only in the dimethylhydrazine-treated folate-depleted rats compared with controls (P = 0.038) and was effectively overcome by increasing levels of dietary folate (P = 0.008). In this model, dimethylhydrazine induces exon-specific p53 hypomethylation. In some exons, this occurs independent of dietary folate, and in others, increasing levels of dietary folate effectively override the induction of hypomethylation in a dose-responsive manner. This may be a mechanism by which increasing levels of dietary folate inhibit colorectal carcinogenesis.

Animals↗

Short-course doxycycline treatment versus conventional tetracycline therapy for scrub typhus: a multicenter randomized trial.

To assess the clinical efficacy of short-course doxycycline in the treatment of scrub typhus, we compared conventional 7-day tetracycline therapy with 3-day doxycycline therapy in 116 patients. Patients were randomized to receive either tetracycline (500 mg four times daily; n = 50) or doxycycline (100 mg twice daily; n = 66) and were followed for 4 weeks after the completion of treatment. The cure rate was 100% in the tetracycline group and 93.9% in the doxycycline group (P > .05). The two groups did not differ significantly in terms of the interval required for defervescence or for the alleviation of symptoms. There were no relapses in either group. These data suggest that 3-day doxycycline therapy is as effective as conventional 7-day tetracycline therapy for the cure of scrub typhus and the prevention of relapses.

Adult↗

Systemic plasmacytosis: a case which improved with melphalan.

Plasmacytosis, a distinctive proliferative disorder of plasma cells, is characterized by peculiar multiple skin eruptions, lymphadenopathy and polyclonal hypergammaglobulinemia. To date there has been no report of such cases showing remarkable responses to therapeutic agents. We herein report a case of plasmacytosis which developed in a 52-year-old Korean man and showed remarkable improvement with melphalan.

Humans↗