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Biomedical subjects

H J Choi

Publications and source records attributed to H J Choi.

At least 73 records · Page 4Linked to original sources

Proliferating cell nuclear antigen expression and its relationship to malignancy potential in invasive colorectal carcinomas.

PURPOSE: Cellular proliferative activity is a useful indicator of biologic aggressiveness in colorectal carcinoma. Immunohistochemical analysis of proliferating cell nuclear antigen (PCNA) has important advantages of maintaining tissue architecture and technical simplicity. The aim of this study was to investigate the correlation between proliferative activity and malignancy potential in colorectal carcinomas to determine whether proliferative index of cancer cells has prognostic significance using immunohistochemical technique. METHODS: Proliferation index at the invasive tumor margin of 86 paraffin sections of advanced colorectal carcinomas was assessed by immunohistochemical study using a mouse monoclonal antibody to PCNA (PC-10) and was compared with conventional clinicopathologic factors and other possible prognostic parameters, including p53 overexpression, tissue carcinoembryonic antigen immunoreactivity pattern, and flow cytometric DNA ploidy. In addition, recurrence and survival were analyzed in accordance with degree of PCNA expression. RESULTS: PCNA labeling index (PCNA-LI) increased significantly as the Astler-Coller stage advanced (P = 0.0001). Strong correlations were observed between PCNA-LI and various pathologic parameters, including histologic differentiation (P = 0.0027), lymphatic invasion (P = 0.0001), vascular invasion (P = 0.0001), lymph node metastasis (P = 0.0001), and liver metastasis (P = 0.0036). Mean PCNA-LI was also significantly higher in tumors with DNA aneuploidy (P = 0.0006) and negative and cytoplasmic patterns of carcinoembryonic antigen immunoreactivity (P = 0.01). Linear relationships were demonstrated between PCNA-LI and clinical outcomes; recurrence rate was significantly greater in the group with higher than the mean PCNA-LI, who underwent curative resection (P < 0.01), and four-year survival rates for both overall and curative cases with higher than the mean PCNA-LI were significantly poorer than those with lower than mean PCNA-LI (P < 0.005 and P < 0.01, respectively). CONCLUSION: Evaluation of PCNA-LI at the invasive tumor margin in colorectal carcinomas is suggested to be valuable in predicting those people with a higher potential for metastasis and recurrence after surgery; thus, the evaluation is helpful in planning reasonable adjuvant therapy, even in the earlier stages.

Cell Division↗

The native strains in the hydrophobic core and flexible reactive loop of a serine protease inhibitor: crystal structure of an uncleaved alpha1-antitrypsin at 2.7 A.

BACKGROUND: The protein alpha1-antitrypsin is a prototype member of the serpin (serine protease inhibitor) family and is known to inhibit the activity of neutrophil elastase in the lower respiratory tract. Members of this family undergo a large structural rearrangement upon binding to a target protease, involving cleavage of the reactive-site loop. This loop is then inserted into the main body of the enzyme following the opening of a central beta sheet, leading to stabilization of the structure. Random mutageneses of alpha1-antitrypsin identified various mutations that stabilize the native structure and retard the insertion of the reactive-site loop. Structural studies of these mutations may reveal the mechanism of the conformational change. RESULTS: We have determined the three-dimensional structure of an uncleaved alpha1-antitrypsin with seven such stabilizing mutations (hepta alpha1-antitrypsin) at 2.7 A resolution. From the comparison of the structure with other serpin structures, we found that hepta alpha1-antitrypsin is stabilized due to the release of various strains that exist in native wild type alpha1-antitrypsin, including unfavorable hydrophobic interactions in the central hydrophobic core. The reactive-site loop of hepta alpha1-antitrypsin is an extended strand, different from that of the previously determined structure of another uncleaved alpha1-antitrypsin, and indicates the inherent flexibility of the loop. CONCLUSIONS: The present structural study suggests that the uncleaved alpha1-antitrypsin has many folding defects which can be improved by mutations. These folding defects seem to be utilized in a coordinated fashion in the regulation of the conformational switch of alpha1-antitrypsin. Some of the defects, represented by the Phe51 region and possibly the Met374 and the Thr59 regions, are part of the sheet-opening mechanism.

Computer Simulation↗

Effect of omental pedicle hammock in protection against radiation-induced enteropathy in patients with rectal cancer.

PURPOSE: The aim of this nonrandomized study was to assess effects against radiation-induced enteropathy by constructing an omental pedicle hammock, thus isolating the small bowel outside the pelvis. METHODS: Since 1991, 32 patients received the omental pedicle hammock procedure as an adjunct to definitive cancer surgery, and the perioperative experiences and toxic effects of radiation therapy were evaluated and compared with 25 patients who received pelvic floor reperitonealization only. RESULTS: There were no surgical complications related to the omental hammock procedure. Contrary to control cases that showed the bowel to adhere deeply in the pelvis, exclusion of the small bowel from the pelvic cavity demonstrated by contrast study was successful in all except four cases of a segment of bowel loop descent within the radiation portals. According to acute and late radiation morbidity scoring criteria, 26 patients (81 percent) scored Grade 0 in the treatment group, whereas only 3 patients (12 percent) scored Grade 0 in the control group (P < 0.01) in the acute phase, and 28 patients (88 percent) of Grade 0 in the former group and 15 (60 percent) in the latter (P < 0.025) in late phase. There has been no case of radiation-induced enteropathy requiring surgical treatment. CONCLUSION: The technique of bowel exclusion by pedicle omental hammock would make it possible to use higher doses of postoperative pelvic radiation therapy without fear of complications from radiation-induced enteropathy.

Adult↗

Induction of gene expression of the catecholamine-synthesizing enzymes by insulin-like growth factor-I.

The effects of insulin-like growth factor-I (IGF-I) on gene expression and the activities of the three enzymes specific for catecholamine biosynthesis, tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), and phenylethanolamine N-methyltransferase (PNMT), were determined in bovine adrenomedullary chromaffin cells primary cultured in serum-free medium. The mRNA level of TH was maximally elevated in the presence of IGF-I by 3.1 +/- 0.4-fold after 48 h, DBH by 5.1 +/- 0.3-fold in 24 h, and PNMT by 2.8 +/- 0.5-fold in 72 h. In addition, the activity of TH was increased by 77%, DBH by 70%, and PNMT by 23% in IGF-I-exposed cultures. In the absence of the growth factor, the mRNA levels of TH and DBH were decreased to 45 +/- 10% and 35 +/- 12% of the time-zero control within 48 h while PNMT mRNA was decreased to 82 +/- 5% only after 72 h. When the cells were cotreated with the protein tyrosine kinase inhibitor genistein, DBH induction by IGF-I was suppressed, confirming that the effect is mediated by tyrosine kinase. Cotreatment with the protein kinase A (PKA) inhibitor H89 caused complete reversal of the IGF-I-induced DBH increase and the effects of IGF-I treatment and PKA activation by forskolin were not additive, suggesting that PKA is involved in the signaling initiated by IGF-I in these cells.

Adrenal Medulla↗

Doppler sonography in experimentally induced acute renal failure in rabbits. Resistive index versus serum creatinine levels.

RATIONALE AND OBJECTIVES: The purpose of this study is to investigate the temporal relation between the change in the resistive index (RI) from renal Doppler sonography and that of serum creatinine values in the course of experimentally induced reversible acute renal failure (ARF) in rabbits. METHODS: Reversible ARF was induced in 10 New Zealand white rabbits by injecting a glycerol solution (6.0 mL/kg) into the thigh muscle. Doppler sonography was performed before injection, and 6, 12, and 24 hours, and 3, 5, 7, and 14 days after injection of glycerol. Blood samples for measuring serum creatinine levels were obtained in the same time sequence. Three rabbits, which died during the course of the experiment, were excluded from the study group. RESULTS: The RI elevated rapidly after glycerol injection, peaked at 12 hours, and then decreased to normal values by 7 days. Conversely, serum creatinine values were elevated and peaked at 1 day and then decreased to normal by 14 days. The change in the RI preceded the change in serum creatinine levels in the course of reversible ARF. There was a weak linear correlation between RI and serum creatinine levels, with a correlation coefficient of 0.33. CONCLUSION: Doppler sonography with measurement of resistive index may be useful in predicting the course of ARF.

Acute Kidney Injury↗

Origin of muscle action potentials evoked by transcranial magnetic stimulation in cats.

We studied the effects of transcranial magnetic stimulation on ipsilateral and contralateral forelimb extensor muscles in anesthetized cats. A magnetic stimulator, operating at 100% intensity, was used through a circular coil, which was placed tangentially over the midline scalp. Bilateral activation of extensor muscles was readily obtained in all animals. The onset latencies were 7.3 +/- 1.1 and 7.07 +/- 0.8 msec for the contralateral and ipsilateral muscles, respectively. The amplitude of muscle response was unstable in magnitude, nevertheless, it did not show any significant difference between the two sides. The latency of response for ipsilateral and contralateral muscles was similar, which suggests simultaneous activation of motor pathways servicing forelimb muscles. Lesioning or ablation of the motor cortex and decerebration at mid-colliculi level did not abolish the evoked responses elicited at high intensity magnetic stimulation. Stereotactic electrical stimulation of the vestibular nuclei complex was performed, and satisfactory ipsilateral motor responses were obtained. Subsequently, a stereotactic radiofrequency lesion was made at the vestibular nuclei complex, with morphological confirmation. After this lesion, the motor evoked potentials (MEPs) were significantly diminished in amplitude. This finding strongly suggests that the generator of the MEPs resides in the brainstem, mainly at the vestibular nuclei complex.

Animals↗

Small hepatocellular carcinoma: high dose internal radiation therapy with superselective intra-arterial injection of I-131-labeled Lipiodol.

The aim of the present study was to deliver a high internal radiation dose to small hepatocellular carcinoma (HCC) lesions in an attempt to treat this disease. A total of 18 patients with HCC lesions measuring less than 4.5 cm in diameter (25 lesions) were treated with superselective intra-arterial injection of I-131-labeled Lipiodol (370-1,100 MBq in 3-5 ml) using a 5-F or coaxial catheter. All the lesions were nodular, multinodular, or hypervascular on pretreatment angiography. In all, 15 lesions that received over 180 Gy of cumulative radiation decreased in size in proportion to the Lipiodol retention on CT, and no pericapsular recurrence was found on angiography after 14-54 months of follow-up. In five patients who subsequently underwent surgery, 65% to 100% tumor necrosis was detected. No abnormal change in liver function tests or untoward clinical symptom of the lung, thyroid, or bone marrow was detected in patients who survived for more than 3 years after the treatment. Superselective high-dose internal radiation therapy of small HCC offers hope of treatment and long-term local control without complications.

Adult↗

Effect of anticancer drugs and desferrioxamine in combination with radiation on hepatoma cell lines.

Several anticancer chemotherapeutic agents (5-fluorouracil, adriamycin and cisplatinum) and desferrioxamine, an iron chelator, were tested with regard to cytotoxicity and to the combined effect on radiation induced cell killing using two human hepatoma cell lines (HepG2 and PLC/PRF/5). Survival fractions were measured by quantitative colorimetric assay (MTT assay) and dose-response curves were plotted. MTT assay could be successfully used in the assessment of radiosensitivity in addition to chemosensitivity, because a good linear relationship between optical densities and cell numbers was observed and cells approached exponential growth for the first 7 days of culture when 5 x 10(3) or less cells were inoculated per well in our study. Steepness of the final slope (D0), width of the shoulder (D0) and the extrapolation number (n) of radiation survival curves were 1061.72 rad, 226.43 rad and 1.25 respectively in HepG2 and 1091.38 rad, 268.42 rad and 1.29 respectively in PLC/PRF/5. After combining anticancer chemotherapeutic agents and desferrioxamine with radiation, the widths of the shoulders were decreased whereas sensitizer enhancement ratios were increased as the concentration of drugs increased in both cell lines. These results suggest that neither anticancer chemotherapeutic agents nor desferrioxamine enhance cell killing induced by radiation alone, but suggested the possibility that they inhibit the repair of radiation damage.

Antineoplastic Agents↗

Liver involvement in multiple myeloma proven by peritoneoscopy--a case report.

Liver involvement in multiple myeloma has been known to be common in autopsied series. However, since its clinical significance is uncertain yet, invasive procedure confirming plasma cell infiltration of the liver has been rarely performed. We report a case with multiple myeloma which had plasma cell infiltration of a liver. A peritoneoscopic biopsy of the liver for the purpose of disclosing the nature of the aggravating liver function in a carrier of the hepatitis B virus showed infiltration of lymphoreticular cell which were identified later as lambda-light chain producing primitive plasma cells by immunohistochemical stain.

Adult↗

Effect of polyadenylic.polyuridylic acid on cellular responses of peripheral blood mononuclear cells from patients with chronic active hepatitis B.

We have investigated in vitro proliferative responses of peripheral blood mononuclear cells and productions of interferon-gamma and soluble interleukin-2 receptors by these cells from 6 patients with chronic active hepatitis B immediately before and 24 hours after a single intravenous injection of 100 mg of polyadenylic.polyuridylic acid. Cell proliferations were assessed by the technique of tritiated-thymidine incorporation and productions of interferon-gamma and soluble interleukin-2 receptors were measured by enzyme-linked immunosorbent assay. The administration of polyadenylic.polyuridylic acid to the patients has resulted in significant increases of in vitro proliferations of their peripheral blood mononuclear cells as well as productions of interferon-gamma by these cells. However, in vitro productions of soluble interleukin-2 receptors were not changed significantly. These results suggest that the enhanced cellular responses by polyadenylic.polyuridylic acid might be due to the increased sensitivity rather than the increased expression of cellular interleukin-2 receptor.

Adult↗

Gastric varices: diagnosis with duplex Doppler ultrasonography--a case report.

The diagnosis of gastric varices may be difficult due to their anatomic location and morphology. In this abstract we describe a case of gastric varices, of which a duplex Doppler sonography was useful in the diagnosis, that was initially suggested as submucosal tumor of the stomach by barium studies and endoscopy.

Aged↗

Histologic study of chronic active hepatitis C; comparison with chronic active hepatitis B.

Reports on the histologic findings of chronic active hepatitis C (CAH-C) have been rare, and the characteristic histologic findings of CAH-C have been not yet determined. To compare the differences in the histologic findings between CAH-C and chronic active hepatitis B (CAH-B) group, we analyzed the histologic findings of 19 patients with CAH-C, who had positive tests for HCV-antibody by EIA, and 19 patients with CAH-B who had negative tests for HCV-antibody but positive tests for HBsAg by RIA. Histologic features were analyzed between the CAH-C and CAH-B groups using a scoring system which is modified from Knodell's histologic activity index-looking at portal inflammation, periportal necroinflammation, portal fibrosis, focal necrosis, regeneration, polyploid nuclear change, sinusoidal lymphocytic reaction and fatty change. Portal inflammatory cell infiltrations with prominent lymphocytes and follicular arrangement were more frequent in the CAH-C group (10 of 19 cases) than in the CAH-B group (5 of 19 cases). Severe sinusoidal lymphocytic reactions were also more prominent in the CAH-C group (11 of 19 cases) than in the CAH-B group (6 of 19 cases). However, periportal necroinflammation, portal fibrosis, focal hepatic necrosis, regeneration and polyploid nuclear changes were more prominent in the CAH-B group than in the CAH-C group. In conclusion, follicular portal inflammation and severe sinusoidal lymphocytic reactions were common histologic findings in serologically proven CAH-C when compared to CAH-B.

Adult↗

Nodular hepatocellular carcinoma. Treatment with subsegmental intraarterial injection of iodine 131-labeled iodized oil.

Internal radiation therapy with subsegmental arterial injection of iodine 131(131I)-labeled iodized oil (Lipiodol; Laboratorie, Guerbet, France) was evaluated in 24 patients with nodular hepatocellular carcinoma (HCC) ranging from 2.5 to 8.0 cm in size. 131I Lipiodol (555 to 2220 MBq in 3 to 8 ml) was injected depending on the tumor size. Tumor reduction was seen in 88.9% of tumors smaller than 4.0 cm in diameter, 65.5% of tumors between 4.1 to 6.0 cm, and 25.0% of tumors larger than 5.1 cm. The tumor size reduction corresponded to the gradual drop of serum alpha-fetoprotein (AFP) levels and devascularization on follow-up angiography. Adverse reactions from treatment included fever, mild abdominal pain, nausea, and elevation of transaminases. These were mild and well tolerated by patients. This method provided long-term local control without complications related to the thyroid, lung, gastrointestinal tract, and bone marrow.

Adult↗

Development of epidemiological method for the Helicobacter pylori by polymerase chain reaction.

The polymerase chain reaction was used to develop a method for the detection of Helicobacter pylori, a causative agent of gastritis, as well as for the elucidation of its mode of transmission. A genomic library of Helicobacter pylori DNA in Escherichia coli JM109 was constructed by cloning Hind III-digested DNA fragments into plasmid vector pUC18. The nucleotide sequences from seven recombinant clones were determined and five sets of oligonucleotide primers were synthesized on the basis of the sequences from five clones (B4, B9, B10, C15 and I22). The PCR amplifications with these primers were performed using DNA samples from five strains of Helicobacter pylori, two Campylobacter spp. and eleven species of enteric bacteria. Amplifications of the target DNA fragments in all of 5 strains of Helicobacter pylori were observed from the PCR with primers derived from clone B4, B9, C15 and I22. When the specificity was checked with the DNA samples from 13 other bacteria as template DNA for the PCR, specific amplification that produced the correct size of the target DNA of Helicobacter pylori was shown only in the PCR with primers derived from clone B9 and C15. The detection limit in the PCR amplification, determined by the heat-lysis method, was 500 cells of Helicobacter pylori.

Base Sequence↗

Histological studies of surgically resected hepatocellular carcinoma following combined radiotherapy and hyperthermia.

Four cases of hepatocellular carcinoma (HCC) were surgically resected following combined radiotherapy (RT) and hyperthermia (HT). Complete necrosis of the tumor without viable tumor cell was found in one case and extensive tumor necrosis was observed in the other three cases; the percentage of necrosis in the specimens were 40%, 70%, and 80%, respectively. Histologic assessment showed mainly coagulative necrosis in the tumor with focal liquefactive necrosis. Cystic dilatation of sinusoids was observed in both tumor and nontumorous normal liver tissue. Other changes in normal liver tissue were unremarkable except for infiltration of inflammatory cells, fatty change, and proliferation of the bile ducts which can usually be seen beyond the area where any space occupying lesions are present. It is concluded that combined radiotherapy and hyperthermia can significantly induce coagulative necrosis of hepatocellular carcinoma with nonsignificant minimal histologic changes in adjacent nontumorous liver tissue.

Carcinoma, Hepatocellular↗

Adjuvant treatment of operable stomach cancer with polyadenylic.polyuridylic acid in addition to chemotherapeutic agents: a preliminary report.

A randomized trial of polyadenylic.polyuridylic acid [poly(A).poly(U)] in addition to chemotherapy was undertaken in patients with stomach cancer following curative gastrectomy. They were randomized into a group of 108 patients receiving chemotherapy plus poly(A).poly(U) and a control group of 116 patients receiving chemotherapy alone. Chemotherapy consisted of injections of 5-fluorouracil, 12 mg/kg once weekly and adriamycin, 40 mg/m2 once every 3 weeks, continuously after operation. Poly(A).poly(U) was infused in a 100 mg dose, once a week six times from 5 days after the first injection of chemotherapeutic agents and 6 months later in a half dose similarly. At 55 months after initiation of the trial, the mean follow-up periods were 24 months for both groups. It has been revealed that patients who received the combined treatment postoperatively showed a lesser mortality and lower rate of recurrence, both reflecting significant increases in overall (P less than 0.05) and relapse-free (P less than 0.02) survivals as compared to those who received chemotherapy alone. This effect is more pronounced in patients having moderately advanced lymphnode involvement (N1) than in patients without (N0) or more advanced (N2) involvement. Thus, poly(A).poly(U) appears to be an effective agent when used postoperatively with chemotherapy in stomach cancers.

Aged↗

A case of idiopathic fibrosing pancreatitis.

We experienced a case of chronic fibrosing pancreatitis in an 18/12-year-old girl, which was idiopathic because there were no familial back ground, no cystic fibrosis of pancrease, no ductal anomalies and obstruction. The patient presented intermittent colicky abdominal pain and progressive obstructive jaundice, but T-tube drainage and removal of the lymph nodes around the common bile duct relieved her symptoms and disease process. This seems to be the first case reported in a Korean child. Idiopathic fibrosing pancreatitis should be considered in the differential diagnosis of abdominal pain with obstructive jaundice in children.

Abdominal Pain↗

Nodular hepatocellular carcinoma--treatment with intraarterial injection of I-131 Lipiodol.

Twenty four patients with hepatocellular carcinoma who refused surgery or had unresectable tumor ranging 2.5 to 8.0 cm in size were treated with intrahepatic arterial injection of iodine-131-labeled iodized oil (I-131 Lipodol) in an attempt to achieve internal radiation of tumor. 555-2,220 MBq in 3-8 ml of I-131 Lipiodol was injected into the hepatic artery or proximal to the tumor feeding vessel depending on the tumor size. Tumor size reduction was observed in 88.9% of tumor smaller than 4.0 cm in diameter, 65.5% between 4.1 to 6.0 cm, and 25.0% of larger than 6.1cm, respectively. The tumor size reduction was corresponded to the gradual drop of serum AFP levels, decreased uptake on gallium-67 scintigraphy, and devascularization on follow-up angiography. Tumors having significant A-V shunts revealed further tumor growth. Adverse reactions from the treatment include fever, mild abdominal pain, nausea and elevation of transaminases. These have been mild and well-tolerated by the patients. This method was able to provide long term local control without complications related to thyroid, lung, GI tract and bone marrow.

Adult↗