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Biomedical subjects

J K Chung

Publications and source records attributed to J K Chung.

At least 73 records · Page 4Linked to original sources

Establishment and characterization of human gastric carcinoma cell lines.

We report 8 newly established gastric-carcinoma cell lines (SNU-216, 484, 520, 601, 620, 638, 668, 719) from Korean patients. Morphologic study was carried out using light and electron microscopes. CEA, alpha FP, and CA 19-9 and TPA in supernatant and in cell lysate were measured by radioimmunoassay. p53 and c-Ki-ras gene mutations were screened and confirmed by sequencing. The cell lines, derived from tumors with moderate differentiation, grew as a diffuse monolayer, and those from tumors with poor differentiation and minimal desmoplasia grew exclusively as non-adherent. Out of the 8 gastric-cancer cell lines, 5 had detectable levels of CEA both in supernatant and in cell lysate; there was no expression or secretion of alpha FP in these cells; 4 cell lines showed high levels of CA 19-9 in cell pellets. All cell lines except SNU-484 had high concentrations of TPA both in cell lysate and in supernatants. p53 mutation was found in 6 cell lines (75%): 2 (SNU-216 and SNU-668) had mutations in exon 6, and other 3 in exon 8. The c-Ki-ras mutation was found in 2 cell lines (25%), SNU-601 and SNU-668. The former showed GGT-to-GAT transition mutation at codon 12, while the latter showed CAA-to-AAA transversion mutation at codon 61. DNA profiles using restriction endonuclease HinfI and polymorphic DNA probes ChdTC-15 and ChdTC-114 showed different unique patterns; which suggests that these cell lines are unique and not cross-contaminated. We believe that the newly characterized gastric-cancer cell lines presented in this paper will provide a useful in vitro model for studies related to human gastric cancer.

Adult↗

Establishment and characterization of human ovarian carcinoma cell lines.

Five human ovarian carcinoma cell lines cultured from primary and metastatic tumors of Korean patients were characterized. These lines were isolated from two papillary serous cystadenocarcinomas, two endometrioid carcinomas, and one malignant Brenner tumor. It was shown that the growth of these cell lines was stable when cultured after at least 20 passages. Population doubling times varied from 40 to 67 hr. All lines showed high viability and were proven by DNA fingerprinting analysis to be unique. Contamination by mycoplasma or bacteria was excluded. In two lines, SNU-8 and SNU-840, an elevated level of CA125 antigen secretion could be detected, whereas CEA was undetectable in all five lines. Four different mutations in functional and highly conserved regions of the p53 gene were identified in three of our five lines (60%), namely in SNU-119, SNU-251, and SNU-563. Included were two missense mutations, one in-frame 3-base-pair deletion, and one out-of-frame 1-base-pair deletion. It is interesting to note that one of these three lines, SNU-251, presented an additional simultaneous nonsense mutation of the BRCA1 gene and missense mutation of the hMLH1 gene. In its lacking both wild-type alleles of the BRCA1 gene, SNU-251 might serve as an unusual and important in vitro model for studies related to ovarian carcinoma and the BRCA1 gene. It is thus likely that the establishment and characterization of these permanent human ovarian carcinoma cell lines in continuous cultures can provide useful tools for in vitro studies related to human ovarian carcinomas.

Antigens, Neoplasm↗

Establishment and characterization of cell lines derived from uterine malignant mixed Müllerian tumor.

OBJECTIVE: We report the establishment and characterization of three new cell lines derived from uterine malignant mixed müllerian tumor (MMMT). METHODS: Three uterine MMMT cell lines from primary tumors of Korean patients were cultured and the involved cell morphology, growth properties, DNA profiles, immunohistochemical properties, tumor-associated antigen secretion, and genetic alterations of related oncogenes and tumor suppressor genes were studied as well. RESULTS: Three MMMT cell lines were successfully established including one homologous tumor SNU-539 and two heterologous tumors SNU-685 and SNU-1077. All lines showed substrate adherence and high viability and were proven by DNA fingerprinting analysis to be unique. Contamination by mycoplasma and bacteria was excluded. SNU-539 and SNU-1077 cells stained positively for both epithelial and mesenchymal antigens, while SNU-685 cells only stained positively for mesenchymal antigens. The level of secretion of tumor-associated antigens, CA125 and CEA, was shown to be undetectable in all three lines. One missense mutation from AAC to GAC at codon 239 of exon 7 in the p53 gene was identified in SNU-539. CONCLUSIONS: These newly established and characterized permanent uterine MMMT cell lines might be regarded as valuable resources for a multitude of in vitro investigations, which should be used for clarifying the obscure histogenetic origin and understanding the biological behavior of this aggressive tumor.

Aged↗

In vitro and in vivo properties of murine monoclonal antibody for a novel immature thymocyte-differentiated antigen, JL1.

JL1 is a novel thymocyte-differentiated antigen strictly confined to stage II immature cortical thymocytes. It is expressed in several types of leukemias and lymphomas. Murine anti-JL1 monoclonal antibody labeled with 131I and 99mTc showed 60-70% of immunoreactivity and 1.4-1.9 x 10(9) L/mol of affinity constant. The incubation of the radiolabeled antibody with Molt-4 cells showed no evidence of modulation or shedding. Localization indices increased from day 3 to day 5 in SCID mice bearing Molt-4 cells.

Animals↗

Crossed-cerebellar diaschisis in cerebral infarction: technetium-99m-HMPAO SPECT and MRI.

UNLABELLED: We studied 26 patients with a single supratentorial infarction using 99mTc-HMPAO SPECT and MRI to investigate the phenomenon of crossed-cerebellar diaschisis (CCD). METHODS: From the total single-photon emission counts obtained from each cerebellar hemisphere, the percent difference between the contralateral (CCH) and ipsilateral (ICH) cerebellar hemispheres [delta %cbll = (CCH-ICH)/ ICH x 100] was calculated. Both SPECT (SVD) and MRI volume deficit (MVD) were measured to examine their relationship with CCD. RESULTS: A CCD was observed in 12 of the 26 patients (46%) with cerebral infarction. There was no significant correlation between SVD and delta %cbll or MVD and delta %cbll in the patients with cerebral infarction. There were no significant differences in SVD and MVD between the patients with and without CCD. The frequency of CCD was significantly higher in the patients whose infarctions were in the frontoparietal lobes or the deep middle cerebral artery territory, including the basal ganglia and internal capsule (11/19) than in the patients whose infarctions were in other regions (1/7) (p = 0.048). The severely hemiparetic patients had a higher frequency of CCD and lower delta %cbll than the patients with milder or no hemiparesis (frequency, 5/5 compared with 6/18, p = 0.008; delta %cbll, -21.4% +/- 3.8% compared with -8.3% +/- 11.1%, p = 0.018). However, CCD also occurred in 5 of the 14 patients without hemiparesis and was not seen in 5 of the 12 hemiparetic patients. None of the patients with CCD demonstrated the apparent clinical signs of cerebellar dysfunction. CONCLUSION: The location rather than the extent and severity of the lesion may be the major determinant for the occurrence and magnitude of CCD in patients with cerebral infarction. Our results also support the notion that CCD is a consequence of the interruption of the corticopontocerebellar pathway at the supratentorial level.

Adult↗

Clinical significance of hepatic visualization on iodine-131 whole-body scan in patients with thyroid carcinoma.

UNLABELLED: The purpose of this study was to evaluate the frequency and clinical significance of diffuse hepatic uptake on 131I whole-body scan in 399 patients (53 males, 348 females) with well-differentiated adenocarcinomas of the thyroid. METHODS: Two hundred and ninety-one diagnostic scans were performed 2 days after the administration of 74-370 MBq (2-10 mCI) 131I, and 824 post-therapy scans were done 3-5 days after the administration of 1.11-7.4 GBq (30-200 mCI) 131I. There was no evidence of liver metastasis in these patients. Liver and thyroid visualization on each 131I scan were graded from 0-4. To evaluate the incorporation of radioiodine to thyroglobulin and thyroid hormones, a patient's serum was extracted by 80% ethanol/20% trichloroacetic acid solution and analyzed by silica gel thin-layer chromatography. RESULTS: Diffuse hepatic uptake (> Grade 2) was definitely seen in 239 of 399 (59.9%) of the patients and 397 of 1115 (35.6%) of the studies. In the diagnostic scans, 36 (12.0%) showed uptake in the liver. In post-therapy scans, however, the incidence of liver uptake increased according to increased doses of 131I (39.1% with 1.11 GBq, 61.5% with 2.775-3.7 GBq and 71.3% with 5.55-7.4 GBq). The more that uptake appeared in the residual thyroid, the more it appeared in the liver. There were 13 patients whose scans showed metastatic and liver uptake without any thyroid uptake. Fifteen patients showed diffuse liver uptake without uptake by the thyroid or metastasis. Follow-up studies of seven of these patients revealed metastatic lesions. Liver uptake on scan related to the fraction of 131I-labeled thyroglobulin in the serum. CONCLUSION: Diffuse liver uptake indicated functioning thyroid remnant or metastasis. In a few cases, liver uptake without uptake by the thyroid or metastasis on whole-body scans suggests hidden metastases.

Adenocarcinoma↗

Multiple forms of phospholipase D inhibitor from rat brain cytosol. Purification and characterization of heat-labile form.

Rat brain cytosol contains proteins that markedly inhibit the activity of partially purified brain membrane phospholipase D (PLD) stimulated by ADP-ribosylation factor (Arf) and phosphatidylinositol 4,5-bisphosphate (PIP2). Sequential chromatography of the brain cytosol yielded four inhibitor fractions, which exhibited different kinetics to heat treatment at 70 degrees C. Purification of the most heat-labile inhibitor to homogeneity yielded two preparations, which displayed apparent molecular masses of 150 kDa and 135 kDa, respectively, on SDS-polyacrylamide gels. Tryptic digests of the 150- and 135-kDa proteins yielded similar elution profiles on a C18 reverse-phase column, suggesting that the 135-kDa form is a truncated form of the 150-kDa form. Sequences of two tryptic peptides were determined. A data base search revealed no proteins with these sequences. The purified 150-kDa inhibitor negated the PLD activity stimulated by Arf, RhoA, or Cdc42. The concentration required for half-maximal inhibition was 0.4 nM. Concentration dependence on the 150-kDa inhibitor was not affected by changes in the concentrations of Arf, PIP2, or phosphatidylcholine used in the assays, suggesting that the inhibition is not due to competition with the activators or substrate for PLD. The purified inhibitor did not affect the PIP2-hydrolyzing activity of a phospholipase C isozyme that was measured with substrate vesicles of lipid composition identical with that used for the PLD assay. Thus, the mechanism of inhibition appears to be a specific allosteric modification of PLD rather than disruption of substrate vesicles.

ADP-Ribosylation Factors↗

Quantitative lung perfusion scintigraphy in postoperative evaluation of congenital right ventricular outflow tract obstructive lesions.

Improved methods to relieve pulmonary artery stenosis have emphasized the need for an accurate noninvasive method to quantify the pulmonary blood flow. The aim of this study was to compare the roles of Tc-99m MAA perfusion lung imaging, chest x-ray, MRI, and cine-angiography for postoperative evaluation of pulmonary blood flow in patients with congenital right ventricular outflow tract (RVOT) obstructive lesions. Eleven patients underwent chest x-ray, MRI, perfusion lung imaging, and cine-angiography after corrective surgery of RVOT obstruction. The perfusion ratio on lung scans was calculated on the posterior views. The correlation coefficient of the left to right perfusion ratio measured by lung scans obtained with that by visual assessment of chest x-rays, with the most stenotic diameter ratio on MRI and on angiography being 0.57, 0.88 (P < 0.001), and 0.87 (P < 0.001), respectively. Follow-up perfusion lung scans in seven patients, before and after pulmonary artery intervention showed significantly improved perfusion ratios (0.30 +/- 0.11 to 0.70 +/- 0.22; P < 0.001), which were concordant with the clinical findings. The authors conclude that the quantitative perfusion lung scan is the noninvasive method of choice for postoperative evaluation of the pulmonary artery in congenital RVOT obstruction.

Adolescent↗

Bone marrow scintigraphy using technetium-99m-antigranulocyte antibody in hematologic disorders.

UNLABELLED: Bone marrow is the primary site for many hematologic disorders. To date, however, no suitable bone marrow imaging method has been found. The present study investigates the usefulness of bone marrow immunoscintigraphy using 99mTc-labeled antigranulocyte antibody (anti-NCA-95) in 31 patients with hematologic disorders. METHODS: One milligram of antibody labeled with 259-370 MBq 99mTc was injected intravenously, and bone marrow images were taken 4 hr later. We also calculated the uptake ratios of lumbar bone marrow-to-background (L/B) and ilium-to-background (I/B). RESULTS: Of 15 patients with aplastic anemia, 7 showed diffusely decreased antibody uptake (L/B = 2.3 +/- 0.8, I/B = 3.0 +/- 0.8) compared to control patients (n = 21, L/B = 8.2 +/- 2.5, I/B = 10.3 +/- 3.1) Six patients had both decreased and increased uptake areas and two had normal to slightly increased uptake. Of those patients receiving various types of therapy for aplastic anemia, all but one showed increased or irregular uptake. The degree of antibody uptake in the bone marrow correlated with peripheral blood analyses (hemoglobin, white blood cells, platelets). Of six patients with myelodysplastic syndrome, four had irregular uptake and two diffusely decreased uptake. Four patients with myelogenous leukemia showed normal uptake, whereas two with lymphocytic leukemia had decreased uptake. Patients with iron deficiency anemia, pure red cell aplasia or thalassemia minor exhibited normal uptake with bone marrow expansion. CONCLUSION: Immunoscintigraphy with antigranulocyte antibody is a useful method for evaluating the bone marrow status of patients with various hematologic disorders.

Adolescent↗

Intestinal leakage of technetium-99m-MDP in primary intestinal lymphangiectasia.

We present a case in which a patient with primary intestinal lymphangiectasia demonstrated abnormal intestinal accumulation of tracer during 99mTc-methylene diphosphonate (MDP) skeletal scintigraphy. Early intestinal leakage with gradual colonic migration and concentration was confirmed by repeat bone scan with serial acquisitions. The mechanism for the intestinal localization of 99mTc-MDP seen in this patient is not clear. Thus, intestinal lymphangiectasia can be a cause for extra-osseous localization of bone scan agents in the intestine.

Adult↗

Effect of hypocapnia on extracellular glutamate and glycine concentrations during the periischemic period in rabbit hippocampus.

Glutamate (GLU) is a neurotransmitter. Massive release of GLU and glycine (GLY) into the brain's extracellular space may be triggered by ischemia, and may result in acute neuronal lysis or delayed neuronal death. The aim of this study was to evaluate the possible relationship between hyperventilation and the level of GLU and GLY during brain ischemia. Rabbits were anesthetized with halothane and oxygen. Group 1 was allowed to hyperventilate (PaCO2 25-35 mmHg). PaCO2 was maintained throughout the study. Group 2 was a normal control group that maintained normocapnia. Two global cerebral ischemic episodes were produced. Microdialysate was collected during the periischemic and reperfusion periods from the dorsal hippocampus. GLU and GLY concentrations were determined using high-performance liquid chromatography. In the control group, GLU and GLY were significantly elevated during each episode of ischemia; these levels returned to baseline within 10 minutes after reperfusion. In contrast, in the hyperventilation group GLU and GLY concentrations increased during ischemia, but they were not statistically significant. Two way ANOVA for the periischemic periods (t = 15,80; p = 0.06) revealed lower GLU values for the hyperventilated animals. A similar analysis for periischemic GLY concentrations revealed significantly lower values in the hyperventilated group (t = 10,15,75,80: p = 0.03) as compared to normal controls. We were able to demonstrate that hypocapnia during periischemic period lowered extracellular GLU and GLY concentrations. These results can explain a part of the protective action of hypocapnia during cerebral ischemia.

Analysis of Variance↗

Concentration and distribution of tumor associated antigens TAG-72 and CEA in stomach cancer.

We measured the concentration and distribution of tumor associated antigens, TAG-72 and CEA, in stomach cancer by in vitro quantitative autoradiography (IV-QAR). Frozen sections of 33 specimens were incubated with varying concentrations of 125I-labeled CEA-79.1 and B72.3 antibodies specific for carcinoembryonic antigen (CEA) and tumor-associated glycoprotein-72 (TAG-72), respectively. Computer analysis of specific antibody binding gave maximal binding values which were equal to the concentrations of the antigen or epitope. TAG-72 was detected in 25 specimens, at a concentration ranging from 8.4 to 562.9 pmol/g. CEA was detected in 32 of the 33 specimens and its concentration ranged from 8.8 to 525.3 pmol/g. The distribution of TAG-72 by IV-QAR coincided with that of the tumor cells in 41.4% of the pathologic lesions. The distribution of CEA coincided with the tumor cells in 80.5% of pathologic lesions, nearly twice the TAG-72. The concentration of TAG-72 was significantly higher in mucinous adenocarcinoma and mucin containing adenocarcinomas than other types of adenocarcinomas. There was no significant difference in the concentration of CEA among the pathologic types of stomach cancer. In summary, stomach cancer exhibited wide variations in TAG-72 and CEA expression. CEA expression was more frequent and homogeneous than TAG-72.

Adenocarcinoma↗

Does prevalence of migraine and Raynaud's phenomenon also increase in Korean patients with proven variant angina?

BACKGROUND: The incidence of coronary artery spasm in oriental patients is higher than that in western patients. Oriental patients with variant angina (VA) frequently show normal or insignificant coronary artery stenosis by angiogram, compared with western patients. The prevalence of migraine and Raynaud's phenomenon in oriental patients with VA has not yet reported. OBJECTIVE: We did a prospective study on the prevalence of migraine and Raynaud's phenomenon in patients with proven VA compared with those in two control groups using a radioisotope technique following ice water exposure. Simultaneously, we studied lipid profiles of each group. METHODS AND RESULTS: migraine was diagnosed if the score in part A totalled 7 or more of 26, and Raynaud's phenomenon was diagnosed if the score in part B totalled 4 or more of 11 by Miller et al. Technetium-99m-labeled red blood cells (99mTc-RBC) radionuclide angiography was performed in all patients. Patients were included in a prospective protocol. Patients were grouped as follows: Group I: 20 patients with proven VA; Group II: 30 patients with coronary artery disease; Group III: 31 patients without heart disease. Age and sex of patients were not statistically different among the three groups. Migraine was diagnosed in 8 patients (40.0%) of group I and in 6 patients (20.0%) of group II and in 12 patients (38.7%) of group III. Raynaud's phenomenon was reported in 2 (10.0%) of the patients in group I and in 5 (16.1%) of the patients of group III. The mean index ratio of the digital blood flow of right over left hand on static image was 0.85 +/- 0.07 (mean +/- S.E.M.) of the patients of group I, 0.73 +/- 0.03 of the patients of group II and 0.74 +/- 0.04 of the patients of group III. The mean flow index ratio of right over left hand of the digital blood flow on dynamic study was 0.51 of the patients of group I, 0.43 of the patients of group II and 0.43 of the patients of group III. The score of migraine did not differ significantly among the three groups. The score of Raynaud's phenomenon of patients with variant angina did not differ significantly from that of patients in the non-coronary control group, although it differed significantly from that of patients in the coronary control group. But, the prevalence of migraine and Raynaud's phenomenon (questionnaire and radionuclide angiography) in patients of group I did not differ significantly from that in groups II and III. In the end, more patients with variant angina than coronary or non-coronary control group did not reach the predetermined point level for the diagnosis of migraine and Raynaud's phenomenon. Lipid profiles were not significantly different among three groups. CONCLUSIONS: This result suggests that variant angina may not be a manifestation of a generalized vasospastic disorder in Korean patients.

Adult↗

Development of bone marrow immunoscintigraphy using a Tc-99m labeled anti-NCA-95 monoclonal antibody.

We evaluated the monoclonal antibody CEA-79.4 against carcinoembryonic antigen as an immunoscintigraphic agent for assessing the state of the bone marrow. Western blotting of human granulocyte extracts with the antibody could confirm that the binding was with the epitope of NCA-95. Immunocytochemical staining of bone marrow aspirates revealed specific uptake of this antibody by granulopoietic cells. The affinity constant was 2-9 x 10(9) L/mol. Immunoscintigraphy using 99mTc-labeled CEA-79.4 in a normal volunteer revealed high uptake in the bone marrow as compared to other organs.

Antibodies, Monoclonal↗

Poor renal uptake of Tc-99m DMSA and Tc-99m MDP in a patient with Fanconi syndrome and near normal glomerular filtration rate.

The authors present a patient with Fanconi syndrome who demonstrated poor renal uptake of Tc-99m DMSA and high urinary concentration of the tracer. Tc-99m DTPA imaging was normal and the creatinine clearance was only minimally decreased. These findings suggest that Tc-99m DMSA may be accumulated in the kidney by glomerular filtration and subsequent tubular reabsorption. A Tc-99m MDP bone scan showed faint renal uptake, as well as diffuse high skeletal uptake, particularly in the spine, demonstrating that the metabolic bone disease associated with Fanconi syndrome can be one of the causes of poor renal visualization on a bone scan.

Bone and Bones↗

Evaluation of bone metastases by Tc-99m MDP imaging in patients with stomach cancer.

The authors conducted a retrospective review of 234 bone scans of stomach cancer patients who had been diagnosed at the Seoul National University Hospital. In 106 of the 234 cases (45.3%), there were abnormal bone scan results, suggestive of bone metastases. The most common site of bone metastases was the spine, followed by the ribs, pelvis, femur, and skull. These sites were similar to those known for other malignant diseases. The incidence of bone metastases increased according to the duration of disease, especially within 12 months after diagnosis in patients with stage III gastric cancer. The incidence of bone metastases increased as the clinical stage increased. However, the incidence of metastases did not relate to gastric cancer pathologic type. The authors found 6 cases of "superscan" in the 234 bone scans (2.6%). The bone scan findings correlated positively with the level of serum alkaline phosphatase.

Bone Neoplasms↗

Comparison of nuclear bone and gallium scans in the therapeutic evaluation of bone lymphoma.

The objective of this study was to compare Tc-99m MDP bone and Ga-67 scans for the therapeutic response to bone lymphoma in 40 patients. The authors retrospectively compared 40 Tc-99m MDP bone scans and 20 Ga-67 scans before therapy, 29 bone scans and 13 Ga-67 scans during the therapy, and 33 bone scans and 15 Ga-67 scans after therapy. Tc-99m MDP and Ga-67 whole body scans were obtained within 2 weeks of each study and were graded visually (grades 1-4) in which grade 3 means similar count density to that of normal iliac alar activity on bone scans and normal liver activity on Ga-67 scans, respectively. The findings of lesion improvement during and after therapy were found in 66.0% (19 of 29) and 72.7% (24 of 33) with Tc-99m MDP bone scans, 84.6% (11 of 13) and 86.7% (13 of 15) with Ga-67 scans, respectively. The mean grades of Tc-99m MDP uptake were 3.06 before, 2.34 during, and 1.75 after therapy. The mean grades of Ga-67 uptake were 3.22 before, 1.42 during, and 1.30 after therapy. Ga-67 scans appear to be more reliable than Tc-99m MDP bone scans in evaluating the therapeutic response of bone lymphoma.

Adult↗

Technetium-99m-labeled antigranulocyte antibody bone marrow scintigraphy.

UNLABELLED: Although bone scintigraphy is a sensitive method for detecting skeletal metastases, it is often equivocal for metastases due to poor specificity. This study evaluates 99mTc-antigranulocyte antibody (AGA) bone marrow scintigraphy in differentiating malignant from benign lesions, in 42 patients with skeletal tumors who had equivocal bone scans. METHODS: AGA scans performed approximately 1 wk after 99mTc-MDP bone imaging were visually assessed for the presence of concordant marrow defects. Final diagnoses were made from radiological results, follow-up bone scans or clinical evaluation for 12 mo or longer. RESULTS: The final diagnoses were: skeletal metastasis (19 patients), no metastasis (20 patients) and unconfirmed (3 patients). AGA scans could not determine the presence of a concordant defect in three patients because of overlying liver activity or previous irradiation of the region. Seventeen patients had bone marrow defects concordant with bone scan lesions, whereas 15/19 patients without metastasis had normal AGA scans. The sensitivity and specificity of AGA for detecting skeletal metastases were 100% and 79%, respectively. CONCLUSION: AGA scans had a low incidence of skeletal metastases in patients who had equivocal bone scans. Although a concordant marrow defect increases the possibility of metastasis, further radiological investigation to exclude benign disease is warranted.

Antibodies, Monoclonal↗