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Biomedical subjects

J K Chung

Publications and source records attributed to J K Chung.

At least 55 records · Page 3Linked to original sources
PubMed1999

Myocardial oxygenation during high work states in hearts with postinfarction remodeling.

BACKGROUND: Postinfarction left ventricular remodeling (LVR) is associated with reductions in myocardial high-energy phosphate (HEP) levels, which are more severe in animals that develop overt congestive heart failure (CHF). During high work states, further HEP loss occurs, which suggests demand-induced ischemia. This study tested the hypothesis that inadequate myocyte oxygen availability is the basis for these HEP abnormalities. METHODS AND RESULTS: Myocardial infarction was produced by left circumflex coronary artery ligation in swine. Studies were performed in 20 normal animals, 14 animals with compensated LVR, and 9 animals with CHF. Phosphocreatine (PCr)/ATP was determined with 31P NMR and deoxymyoglobin (Mb-delta) with 1H NMR in myocardium remote from the infarct. Basal PCr/ATP tended to be decreased in postinfarct hearts, and this was significant in animals with CHF. Infusion of dobutamine (20 microg x kg-1 x min-1 IV) caused doubling of the rate-pressure product in both normal and LVR hearts and resulted in comparable significant decreases of PCr/ATP in both groups. This decrease in PCr/ATP was not associated with detectable Mb-delta. In CHF hearts, rate-pressure product increased only 40% in response to dobutamine; this attenuated response also was not associated with detectable Mb-delta. CONCLUSIONS: Thus, the decrease of PCr/ATP during dobutamine infusion is not the result of insufficient myocardial oxygen availability. Furthermore, in CHF hearts, the low basal PCr/ATP and the attenuated response to dobutamine occurred in the absence of myocardial hypoxia, indicating that the HEP and contractile abnormalities were not the result of insufficient oxygen availability.

Adenosine Triphosphate↗
PubMed1999

The effect of tumor size on F-18-labeled fluorodeoxyglucose and fluoroerythronitroimidazole uptake in a murine sarcoma model.

The purpose of this study was to evaluate the effect of tumor size on the uptake of 18F-fluorodeoxyglucose (FDG) and fluoroerythronitroimidazole (FETNIM) in a murine sarcoma model. ICR mice were xenografted with sarcoma 180 cell line and tumors were allowed to grow to a weight of 0.26-5.82 grams. 18F-FDG and 18F-FETNIM were injected intravenously in separate groups of mice, and after 1 hr, the tumors were excised and radiotracer uptake was measured. In another group of mice tumors were autoradiographically analyzed and subjected to H & E staining. In both the FDG and FETNIM group, per-gram radiotracer uptake by a tumor was inversely proportional to tumor weight. 18F-FETNIM correlated more (r = -0.593, p < 0.05) than 18F-FDG (r = -0.447, p < 0.05). Autoradiographic studies revealed that FDG accumulated in viable tumor areas, whereas FETNIM accumulated in both viable and partially necrotic areas. In the case of 18F-FETNIM, a direct correlation between tumor weight and the no-uptake-area to total-tumor-area was demonstrated. We concluded that increased tumor size is associated with decreased uptake of 18F-FDG and FETNIM, though this depends on the type of radiotracers and distribution of necrosis.

Animals↗
PubMed1999

Detection of cancer in augmented breasts by positron emission tomography.

OBJECTIVE: To assess the diagnostic efficiency of positron emission tomography with 18-fluorine fluorodeoxyglucose in detecting breast cancer in augmented breasts. DESIGN: Retrospective study. SETTING: University hospital, Korea. SUBJECT: 9 cases or 8 patients with breasts augmented with paraffin or silicone. INTERVENTION: FDG-PET, mammography, and ultrasonography RESULTS: The mammogram detected the breast cancer in only 1 of 3 patients, and ultrasonography gave a false positive result in 1 patient with an augmented breast. In contrast, PET predicted all the cancers and 5/6 benign lesions. 2/3 breast cancers had axillary FDG uptake interpreted as showing metastatic involvement, and in 1 case with cancer with no axillary lymph node involvement there was no FDG uptake in the axilla, which correlated with the pathological finding. CONCLUSIONS: Although the high cost of PET makes its use as a screening test for all patients with augmented breasts unrealistic, it would be the best diagnostic choice if other methods failed.

Axilla↗
PubMed1999

Mechanisms related to [18F]fluorodeoxyglucose uptake of human colon cancers transplanted in nude mice.

UNLABELLED: [18F]Fluorodeoxyglucose ([18F]FDG), a glucose analogue, has been widely used for tumor imaging. To investigate the mechanisms related to [18F]FDG uptake by tumors, an experiment involving nude mice was performed. METHODS: Human colon cancer cell lines SNU-C2A, SNU-C4 and SNU-C5 were transplanted to nude mice. Using immunohistochemical staining and Western blot, the expression of glucose transporter (Glut) isoforms (Glut-1 through -5) in xenografted tumors was analyzed. For the analysis of messenger ribonucleic acid (mRNA) expression, reverse-transcription polymerase chain reaction and Northern blot were used and the enzyme activity of hexokinase in cancer tissues was measured by continuous spectrophotometric rate determination. RESULTS: [18F]FDG uptake in SNU-C4 and SNU-C5 cells was higher than in normal colon cells. Among these cells and xenografted tumors, SNU-C5 showed the highest level of [18F]FDG uptake, followed by SNU-C4 and SNU-C2A. An immunostaining experiment showed intense staining of Glut-1 in SNU-C5 tumors but somewhat faint staining in SNU-C4. SNU-C5 tumors also showed positive staining with Glut-3, although this was not the case with SNU-C2A and SNU-C4. Western blot analysis showed the expression of Glut-1 and Glut-3 in all tumors. Experiments involving Northern blot analysis and reverse-transcription polymerase chain reaction confirmed the overexpression of Glut-1 mRNA in all tumors, with the highest level in SNU-C5. The level of Glut-3 mRNA was also elevated in SNU-C5 tumors but not in SNU-C2A and SNU-C4. The enzyme activity of hexokinase did not vary among different tumors. CONCLUSION: Gluts, especially Glut-1, are responsible for [18F]FDG uptake in a nude mouse model of colon cancer rather than hexokinase activity. Increased numbers of glucose transporters at the plasma membrane of cancer cells is attributed to an increased level of transcripts of glucose transporter genes and may be a cause of increased [18F]FDG uptake, at least in colon cancer tumors.

Animals↗
PubMed1999

Value of FDG PET in papillary thyroid carcinoma with negative 131I whole-body scan.

UNLABELLED: The management of metastatic thyroid carcinoma patients with a negative 131I scan presents considerable problems. Fifty-four athyrotic papillary thyroid carcinoma patients whose 1311 whole-body scans were negative underwent 18F-fluorodeoxyglucose (FDG) PET; the purpose was to determine whether this procedure could localize metastatic sites. We also assessed its usefulness in the management of these patients. METHODS: Whole-body emission scan was performed 60 min after the injection of 370-555 MBq 18F-FDG, and additional regional attenuation-corrected scans were obtained. Metastasis was pathologically confirmed in 12 patients and was confirmed in other patients by overall clinical evaluation of the findings of other imaging studies and of the subsequent clinical course. RESULTS: In 33 patients, tumor had metastasized, whereas 21 patients were in remission. FDG PET revealed metastases in 31 patients (sensitivity 93.9%), whereas thyroglobulin levels were elevated in 18 patients (sensitivity 54.5%). FDG PET was positive in 14 of 15 metastatic cancer patients with normal thyroglobulin levels. In 20 of 21 patients in remission, FDG PET was negative (specificity 95.2%), whereas thyroglobulin levels were normal in 16 patients (specificity 76.1%). The sensitivity and specificity of FDG PET were significantly higher than those of serum thyroglobulin. In patients with negative 1311 scans, FDG PET detected cervical lymph node metastasis in 87.9%, lung metastasis in 27.3%, mediastinal metastasis in 33.3% and bone metastasis in 9.1%. In contrast, among 117 patients with 131I scan-positive functional metastases, 131I scan detected cervical lymph node metastasis in 61.5%, lung metastasis in 56.4%, mediastinal metastasis in 22.2% and bone metastasis in 16.2%. In all 5 patients in whom thyroglobulin was false-negative with negative antithyroglobulin antibody, PET showed increased 18F-FDG uptake in cervical lymph nodes, mediastinal lymph nodes, or both. Among patients with increased 18F-FDG uptake only in the cervical lymph nodes, the nodes were dissected in 11. Metastasis was confirmed in all, even in normal-sized lymph nodes. CONCLUSION: FDG PET scan localized metastatic sites in 131I scan-negative thyroid carcinoma patients with high accuracy. In particular, it was superior to 131I whole-body scan and serum thyroglobulin measurement for detecting metastases to cervical lymph nodes. FDG PET was helpful for determining the surgical management of these patients.

Adult↗
PubMed1998

Interaction of phospholipase C gamma 1 via its COOH-terminal SRC homology 2 domain with synaptojanin.

The role of the phospholipase C gamma 1 (PLC gamma 1) in signal transduction was investigated by characterizing its interactions with proteins that may represent components of a novel signalling pathway. A 145-kDa protein that binds SH2 domain of PLC gamma 1 was purified from rat brain. The sequence of peptide derived from the purified binding protein now identify it as synaptojanin, a nerve terminal protein that has been implicated in the endocytosis of fused synaptic vesicles and shown to be a member of the inositol polyphosphate 5-phosphatase family. We demonstrate here stable association of PLC gamma 1 with synaptojanin, a protein that not only binds carboxyl terminal SH2 domain of PLC gamma 1, but also inhibits PLC gamma 1 activity.

Amino Acid Sequence↗
PubMed1998

Induction of differentiation of the cultured rat mammary epithelial cells by triterpene acids.

We investigated the effects of triterpene acids (TAs), ursolic acid (UA) and oleanolic acid (OA), on the induction of proliferation and differentiation of normal rat mammary epithelial cells (RMEC) or organoids cultured in Matrigel or primary culture system. To elucidate the effects, we tested their differentiation inducing activities with intercellular communication ability, cell cycle patterns, induction of apoptosis, and morphological differentiation in the three dimensional extracellular culture system. To study the changes of RMEC subpopulation in culture, the cultured cells were isolated, immunostained with peanut lectin (PNA) and anti-Thy-1.1 antibody and then analyzed with flow cytometry. Four different subpopulations, such as PNA and Thy-1.1 negative cells (B-), PNA positive cells (PNA+), Thy-1.1 positive cells (Thy-1.1+), PNA and Thy-1.1 positive cells (B+), were obtained and the size of each subpopulation was changed in culture with time in the presence of TAs. Intercellular communication was observed in culture for 7 days in TAs-treated cells, but not in culture for 4 days with scrape-loading dye transfer technique. G2/M phase cells and the number of apoptotic population were increased in TAs-treated groups in cell cycle analyses. S phase fractions were reduced and the change of G1 phase cells was not observed. The colonies with distinct multicellular structures, such as stellate, ductal, webbed, squamous, lobulo-ductal colonies, were observed in Matrigel culture and the frequencies of each colony were changed in the presence of TAs. These results suggest that UA and OA have differentiation inducing effects on rat mammary epithelial cells in primary or in Matrigel culture.

Animals↗
PubMed1998

Diagnostic value of positron emission tomography for detecting breast cancer.

Positron emission tomography (PET) is an imaging method that employs radionuclide and tomography techniques. PET has high sensitivity for detecting breast cancer, both the primary tumor and axillary node metastasis. From June 1995 to November 1996 a total of 27 patients underwent breast operations based on PET results at Seoul National University Hospital. Whole-body PET images were obtained beginning 60 minutes after injection of 370 MBq (10 mCi) 18F-fluorodeoxyglucose. Regional scans were also obtained with transmission images. We compared the PET results with those from the physical examination and mammography. All cases were histologically confirmed. The diagnostic accuracy of PET was excellent for the primary tumor mass (97%) compared with that of the physical examination (78%) and mammography (67%). For axillary lymph node metastasis, PET had outstanding detection accuracy (96%) compared with the physical examination and mammography (74% and 60%, respectively). Whole-body PET scans made it possible to see all of the metastatic lesions at a glance in cases of metastatic or recurrent breast cancer. There was a probable correlation between the standard uptake value (SUV) and the number of axillary lymph node metastases, but in this study statistical significance was not proved because of the small number of cases. PET also could detect breast cancer in paraffin-augmented breasts. We concluded that PET is a highly sensitive, accurate diagnostic tool for breast cancer and that SUV, after more studies, could be used as an important prognostic factor.

Breast Neoplasms↗
PubMed1998

Whole-body [18F]FDG PET in the management of metastatic brain tumours.

BACKGROUND: To determine its roles in the diagnosis and the systemic evaluation of metastatic brain tumours, whole-body positron emission tomography (PET) using [18F]FDG was performed in 20 consecutive patients. METHODS: All patients were thought to be suffering or needing to be differentiated from metastatic brain tumours. Nine patients had multiple brain lesions; six were older and showed a rim-enhancing lesion with surrounding oedema; seven had homogeneously enhancing periventricular lesion(s) on computed tomography (CT) and/or magnetic resonance (MR) imaging, thought to be central nervous system lymphomas. Two patients had skull mass(es) and two patients had a solid mass suspected to be, respectively, a haemorrhagic metastasis and a metastatic malignant melanoma. All of them received whole-body [18F]FDG PET and conventional systemic work-up for metastasis in order to compare the results of the two methods. RESULTS: Metastatic brain tumours were diagnosed on whole-body [18F]FDG PET in eleven patients who had extracranial and intracranial hypermetabolic lesions. In nine of these, a conventional work-up also detected primary lesions which on whole-body [18F]FDG PET were seen to be hypermetabolic foci. Systemic lymph node metastases were detected by whole-body [18F]FDG PET only in two patients and histological diagnosis was possible by biopsy of lymph nodes rather than of brain lesions. In the remaining nine patients who had only intracranial hypermetabolic foci, histological diagnosis was made by craniotomy or stereotactic biopsy. It was confirmed that seven of nine patients were suffering from a primary brain tumour and two from metastatic carcinoma. None of the nine showed evidence of systemic cancer on conventional work-up. Histological diagnoses of the primary brain tumours were four cases of primary central nervous system lymphoma and one each of multifocal glioblastoma, Ewing's sarcoma, and cavernous angioma. Patients felt no discomfort during the whole-body [18F]FDG PET procedure and there were no complications. The false negative rate in [18F]FDG PET and in conventional work-up was 15.4% and 30.7% respectively. There were no false positives on either [18F]FDG PET or conventional work-up. CONCLUSION: It is suggested that whole-body [18F]FDG PET is a safe, reliable, and convenient method for the diagnosis and systemic evaluation of patients thought to be suffering or needing to be differentiated from a metastatic brain tumour.

Adult↗
PubMed1998

A cell surface molecule, JL1; a specific target for diagnosis and treatment of leukemias.

We previously reported a novel differentiation antigen, which is specifically expressed in stage II double positive (CD4+CD8+) human cortical thymocytes (Park et al, J Exp Med 1993; 178: 1447-1451). This study was designed to investigate the expression pattern of JL1 in various types of leukemic cells from patients and normal hematopoietic cells to evaluate the possibility as a tool for diagnosis and treatment of leukemia. The expression of JL1 antigen was observed in 75.6% of leukemic cases (117 out of 154 leukemic patients tested) on flow cytometric analysis. The percentage of JL1-positive cases of T lineage acute lymphoblastic leukemia (T-ALL) (92.6%) was higher than that of other types of leukemias (75%). The presence of JL1 antigen was also confirmed by immunoblotting and immunoprecipitation. Since the JL1 antigen is selectively expressed on the surface of human leukemic cells but not on the mature human peripheral blood cells, normal bone marrow cells and various types of normal tissues, JL1 could be an excellent candidate for an immunodiagnostic and immunotherapeutic tool for hematopoietic malignancies such as leukemia.

Antibodies, Monoclonal↗
PubMed1998

The potential role for CDC42 protein from rat brain cytosol in phospholipase D activation.

Phospholipase D (PLD) has been extracted from rat brain membranes and chromatographically enriched 70-fold. From the rat brain cytosol, Cdc42 with a Mr of about 24,000 and ADP-ribosylation Factor (Arf) with a Mr of about 18,000 have been purified to near homogeneity. PLD was activated better by purified cytosolic Arf than by the other small G proteins tested. Cdc42 purified from rat brain cytosol showed 70% of PLD activation activity exerted by cytosolic Arf, suggesting that Cdc42 may be one of the major G proteins involved in the activation of membrane-associated PLD. While Cdc42 or RhoA exhibited synergistic activation of PLD when administered in conjunction with Arf, Cdc42 and RhoA showed an additive effect when used together. It is possible that Arf and Rho family proteins may have different interaction sites on PLD. These findings support a role for GTP-binding proteins of the Rho family as well as Arf in the activation of membrane-associated PLD and further suggest that Cdc42 may be a major G protein involved in the PLD activation in rat brain.

Amino Acid Sequence↗
PubMed1998

99Tcm-labelled chimeric human/mouse anti-granulocyte antibody bone marrow scintigraphy: a preliminary clinical study.

Bone marrow scintigraphy using 99Tcm-labelled chimeric anti-granulocyte antibody (anti-NCA-95) was performed in 17 patients with haematological disorders and skeletal metastases. Chimeric anti-NCA-95 antibody (chNCA95 Ab, 0.2 mg) labelled with 444 MBq 99Tcm was administered to obtain bone marrow images 4 h post-injection. One week later, an 111In-chloride bone marrow scan was performed on nine patients with haematological disorders. Lumbar bone marrow-to-background (L/B) and ilium-to-background (I/B) uptake ratios were calculated for each scan. In six patients with suspected skeletal metastases, 99Tcm-HMDP bone scans were performed. No patient had any adverse reaction or any immune reaction over 20 weeks. In the patients with haematological disorders, the L/B and I/B ratios of the 99Tcm-chNCA95 Ab scan were 3.41 +/- 0.90 and 1.23 +/- 0.31, whereas those of the 111In-chloride scan were 1.58 +/- 0.32 and 1.00 +/- 0.32, respectively. In assessing findings of irregular central bone marrow uptake and peripheral expansion of the bone marrow, the 99Tcm-chNCA95 Ab scan was much better than the 111In-chloride scan. In the six patients with suspected skeletal bone metastases, three true-positive and two true-negative results were observed. This preliminary study has revealed that 99Tcm-chNCA95 Ab scanning is safe and useful in the diagnosis of haematological disorders and skeletal metastases.

Adult↗
PubMed1998

Epidemiology and time trends of gestational trophoblastic disease in Korea.

OBJECTIVES: For the purpose of determining the annual incidence and time trends of gestational trophoblastic disease (GTD), the medical records from 24 university hospitals, 13 private general hospitals and the Korean Research Institute of Gestational Trophoblastic Disease (KRI-TRD) were analyzed from 1971 to 1995. MATERIALS & RESULTS: From a total of 7198 GTD cases (H-mole=3831, Invasive mole=2163, Choriocarcinoma=1177, PSTr=27) among 838659 deliveries between 1971 and 1995, the hospital-based incidence of H-mole per 1000 deliveries declined from 40.2 during 1971-975, to 2.3 during 1991-995. The population-based incidence of H-mole, however, revealed an average of 2.05 per 1000 deliveries during 1991-995. Old age and gravidities as factors in GTD patients both decreased significantly during the study period. Time trends for the incidence of GTD in Korea revealed significant changes, not only a decrease in the incidence of GTD, but also an improvement in the annual remission rate. Korea's socio-eonomic improvement in recent decades also contributed to the decreased incidence of GTD and the increased survival rates.

Choriocarcinoma↗
PubMed1997

Synaptojanin inhibition of phospholipase D activity by hydrolysis of phosphatidylinositol 4,5-bisphosphate.

A 150-kDa protein that inhibits phospholipase D (PLD) activity stimulated by ADP-ribosylation factor and phosphatidylinositol 4, 5-bisphosphate (PI(4,5)P2) was previously purified from rat brain. The sequences of peptides derived from the purified PLD inhibitor now identify it as synaptojanin, a nerve terminal protein that has been implicated in the endocytosis of fused synaptic vesicles and shown to be a member of the inositol polyphosphate 5-phosphatase family. Further characterization of the enzymatic properties of synaptojanin now shows that it hydrolyzes only the 5-phosphate from inositol 1,4,5-trisphosphate (I(1,4,5)P3) and that it does not catalyze the dephosphorylation of either I(1,3,4)P3 or inositol 1, 4-bisphosphate. However, synaptojanin hydrolyzes both the 4- and 5-phosphates of PI(4,5)P2 and the 4-phosphate of phosphatidylinositol 4-phosphate, converting both compounds to phosphatidylinositol. Magnesium is required for the hydrolysis of I(1,4,5)P3, but not for that of phosphoinositides, by synaptojanin. The inhibition of PLD by synaptojanin is attributable to its ability to hydrolyze PI(4,5)P2. Synaptojanin did not inhibit PLD in the absence of PI(4,5)P2, and the extent of PLD inhibition was related to the extent of PI(4,5)P2 hydrolysis in substrate vesicles. It has been proposed that the biosynthesis of PI(4,5)P2 and the activation of PLD by ADP-ribosylation factor constitute a positive loop to increase rapidly the concentrations of PI(4,5)P2 and phosphatidic acid (PA) during membrane vesiculation. The PA thus produced, probably together with PI(4,5)P2, facilitates vesicle coat assembly. The hydrolysis of PI(4,5)P2, and consequent inhibition of PLD, by synaptojanin might therefore constitute a mechanism to halt the positive loop connecting PI(4,5)P2 and PA during the endocytotic cycle of synaptic vesicles and serve as a signal for uncoating.

Amino Acid Sequence↗
PubMed1997

Inhibition of phospholipase D by clathrin assembly protein 3 (AP3).

In the accompanying paper (Chung, J.-K., Sekiya, F., Kang, H.-S., Lee, C., Han, J.-S., Kim, S. R., Bae, Y. S., Morris, A. J., and Rhee, S. G. (1997) J. Biol. Chem. 272, 15980-15985), synaptojanin is identified as a protein that inhibits phospholipase D (PLD) activity stimulated by ADP-ribosylation factor and phosphatidylinositol 4, 5-bisphosphate (PI(4,5)P2). Here, the purification from rat brain cytosol of another PLD-inhibitory protein that is immunologically distinct from synaptojanin is described, and this protein is identified as clathrin assembly protein 3 (AP3) by peptide sequencing and immunoblot analysis. AP3 binds both inositol hexakisphosphate and preassembled clathrin cages with high affinity. However, neither inositol hexakisphosphate binding nor clathrin cage binding affected the ability of AP3 to inhibit PLD. AP3 also binds to PI(4,5)P2 with low affinity. But the PI(4,5)P2 binding was not responsible for PLD inhibition, because the potency and efficacy of AP3 as an inhibitor of PLD were similar in the absence and presence of PI(4,5)P2. A bacterially expressed fusion protein, glutathione S-transferase-AP3 (GST-AP3), also inhibited PLD with a potency equal to that of brain AP3. The inhibitory effect of AP3 appeared to be the result of direct interaction between AP3 and PLD because PLD bound GST-AP3 in an in vitro binding assay. Using GST fusion proteins containing various AP3 sequences, we found that the sequence extending from residues Pro-290 to Lys-320 of AP3 is critical for both inhibition of and binding to PLD. The fact that AP3 is a synapse-specific protein indicates that the AP3-dependent inhibition of PLD might play a regulatory role that is restricted to the rapid cycling of synaptic vesicles.

Adaptor Protein Complex 3↗