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Biomedical subjects

J K Chung

Publications and source records attributed to J K Chung.

At least 19 recordsLinked to original sources

Sequence analysis of hemagglutinin and nucleoprotein genes of measles viruses isolated in Korea during the 2000 epidemic.

To characterize the genetic properties of currently circulating measles viruses in Korea, the complete nucleotide sequences of hemagglutinin (H) protein and nucleoprotein (N) genes of Korean viruses were analyzed. The entire genes of H and N were directly amplified by RT-PCR from each clinical specimen and sequenced. Sequence analyses of H and N genes indicated that all Korean viruses had a high degree of homology (>99.8%) when compared with each other. The Korean viruses differed from other wild-type viruses by as much as 6.8% in the H gene and 6.5% in the N gene at the nucleotide level. The deduced amino acid variability was up to 6.4% for the H protein and up to 6.5% for the N protein. Phylogenetic analyses of nucleotide sequences and deduced amino acid sequences of the H and N genes revealed that all Korean viruses were grouped into the clade H1.

Disease Outbreaks↗

Anti-JL1 antibody-conjugated poly (L-lysine) for targeted gene delivery to leukemia T cells.

We have designed the gene delivery carrier targeted to Molt 4 cells, human leukemia T cells, using monoclonal antibody against leukemia-specific JL1 antigen, anti-JL1 antibody, as a targeting moiety. Anti-JL1 antibody has been proven to bind to JL1 antigen and subsequently be internalized into Molt 4 cells, demonstrating that anti-JL1 antibody has the potential as a targeting ligand for leukemia-specific gene transfer. Anti-JL1 antibody was modified with the heterobifunctional crosslinker, PDPH, at carbohydrate sites and conjugated to thiolated poly-L-lysine (PLL) via disulfide bridges. The composition and antigen binding affinity of antibody-PLL conjugates were analyzed by the amino acid analysis and the flow cytometry, respectively. Antibody-PLL conjugates neutralized pSV-beta-galactosidase plasmid DNA at 5:1 weight ratio and condensed into about 200--300-nm complexes. DNA/antibody-PLL complexes were effectively internalized into Molt 4 cells after 4 h incubation at 37 degrees C and showed significantly higher in vitro transfection efficiency than DNA/PLL complexes and DNA/Lipofectin formulation due to the targeting effect of receptor-mediated endocytosis induced by anti-JL1 antibody.

Amino Acids↗

CDNA for an immune response gene encoding low molecular weight polypeptide from flounder, Paralichthys olivaceus.

The cDNA for an immune response gene encoding the low molecular weight polypeptide (LMP7) was cloned and sequenced from a flounder (Paralichthys olivaceus) leukocyte cDNA library. The cDNA clone was 1,160 bp, and composed of an open reading frame of 822 bp that corresponded to a protein of 273 amino acid residues with a calculated mass of 30.5 kDa. The ScanProsite search indicated that the deduced amino acid sequence from the flounder LMP7 contains a proteasome beta-type subunit signature, which is well conserved during evolution. The sequence shares a high degree of identity with other LMP7 sequences varying from a 66% identity with zebra fish (Danio renio) to a 57% identity with the African clawed frog (Xenopus laevis), which was confirmed from a phylogenetic tree. A reverse transcription-polymerase chain reaction (RT-PCR) was used to determine tissue specificity, and the expression of LMP7 was detected from the liver, kidney, leukocyte, and spleen of the flounder.

Amino Acid Sequence↗

F-18-fluorodeoxyglucose positron emission tomography as a presurgical evaluation modality for I-131 scan-negative thyroid carcinoma patients with local recurrence in cervical lymph nodes.

BACKGROUND: F-18-labeled fluorodeoxyglucose-positron emission tomography (FDG-PET) has a supplementary role in localizing recurrent sites of differentiated thyroid carcinoma. We evaluated whether FDG-PET is feasible as a presurgical evaluation modality for I-131 scan-negative thyroid carcinoma patients. METHODS: Preoperative FDG-PET results were compared with the pathologic findings of lymph nodes specimens of 22 papillary thyroid patients. All patients had thyroidectomy and I-131 ablation therapy beforehand and showed negative I-131 scans on follow-up studies. RESULTS: In 85 cervical lymph node groups dissected, 56 lymph node groups revealed metastasis. The sensitivity and specificity of FDG PET for metastasis were 80% (45 of 56) and 83% (24 of 29), respectively. Among the pathologically positive 33 lymph nodes with normal size(< or =1 cm), FDG-PET detected 23 nodes. Serum thyroglobulin levels were elevated in 12 patients (sensitivity, 55%). CONCLUSION: FDG-PET accurately detected the recurred cervical lymph nodes of differentiated thyroid carcinoma patients who showed negative I-131 scan. FDG-PET is suitable for the presurgical evaluation of these patients.

Adult↗

Quantification of F-18 FDG PET images in temporal lobe epilepsy patients using probabilistic brain atlas.

A probabilistic atlas of the human brain (Statistical Probabilistic Anatomical Maps: SPAM) was developed by the international consortium for brain mapping (ICBM). It is a good frame for calculating volume of interest (VOI) in many fields of brain images. After calculating the counts in VOI using the product of probability of SPAM images and counts in FDG images, asymmetric indices (AI) were calculated and used for finding epileptogenic zones in mesial temporal lobe epilepsy (mTLE). FDG PET images from 18 surgically confirmed mTLE patients and 22 age-matched controls were spatially normalized to the average brain MRI template of ICBM. Counts from normalized PET images were multiplied with the probability of 12 VOIs from SPAM images in both temporal lobes. Finally AI were calculated on each pair of VOIs, and compared with visual assessment. If AI of mTLE patients were not within 2.9 standard deviation from those of normal control group (P < 0.008; Bonferroni correction for P < 0.05), epileptogenic zones were considered to be found successfully. The counts of VOIs in the normal control group were symmetric (AI < 4.3%, paired t test P > 0.05) except for those of the inferior temporal gyrus (P < 0.001). By AIs in six pairs of VOIs, PET in mTLE had deficit on one side (P < 0.05). Lateralization was correct in only 14/18 of patients by AI, but 17/18 were consistent with visual inspection. In three patients with normal AI, PET images were symmetric on visual inspection. The asymmetric indices obtained by taking the product of the statistical probability anatomical map and FDG PET, correlated well with visual assessment in mTLE patients. SPAM is useful for the quantification of VOIs in functional images.

Adult↗

Fluorodeoxyglucose positron emission tomography for detection of recurrent or metastatic breast cancer.

Fluorodeoxyglucose-positron emission tomography (FDG-PET) is a noninvasive imaging technique capable of identifying primary tumors and metastases with high sensitivity and accuracy. The aim of this study was to evaluate the diagnostic accuracy of whole-body FDG-PET imaging for the detection of recurrent or metastatic breast cancer after surgery. Whole-body FDG-PET imaging was performed on 27 patients with suspected recurrent breast carcinoma. PET images were evaluated qualitatively for each patient and lesion. FDG-PET scans showed that there were 61 reference sites of malignant or benign lesions in 27 patients. In a patient-based analysis, FDG-PET scans correctly identified 16 of 17 patients with recurrent or metastatic disease and 8 of 10 without recurrence, resulting in a sensitivity, specificity, and accuracy of 94%, 80%, and 89%, respectively. In a lesion-based analysis, FDG-PET scans correctly identified 46 of 48 lesion sites with recurrent or metastatic disease and 11 of 13 without recurrence. The overall sensitivity, specificity, and accuracy for all lesion sites were 96%, 85%, and 93%, respectively. FDG-PET scans revealed unsuspected recurrent or metastatic diseases in 8 of 27 (30%) of patients and 11 of 20 (55%) distant metastatic lesions. In 13 patients treatment was altered by the outcome of the PET scan. We concluded that whole-body FDG-PET scan is a useful diagnostic imaging modality for detecting recurrent or metastatic breast carcinoma in patients suspected of having recurrent disease after primary surgery.

Adult↗

Plasma ascorbic acid: measurement, stability and clinical utility revisited.

AIMS: To compare plasma ascorbic acid results by the colorimetric FRASC (Ferric Reducing/Antioxidant and Ascorbic Acid) assay and a reference HPLC method; to re-examine plasma ascorbic acid stability, and anticoagulant effect. DESIGN AND METHODS: For method comparison, 31 plasma samples were tested by both methods. For stability, matching EDTA, heparin, citrate and fluoride/oxalate plasma, stored under different conditions of time and temperature, was measured. RESULTS: FRASC is an acceptable alternative to HPLC for plasma ascorbic acid: precision, limit of detection and recovery were similar, and results by the two methods were indistinguishable: mean (95% CI) difference:1.8 (-1.1-4.6; n = 31) micromol/L. Ascorbic acid was most stable in heparinized plasma. Marked loss (p < 0.05) in EDTA plasma occurred within 30 min of blood collection. CONCLUSIONS: FRASC offers a speedy and reliable alternative to HPLC for plasma ascorbic acid. Heparin is proposed as the anticoagulant of choice; loss of ascorbic acid is rapid in EDTA plasma ex vivo.

Adult↗

Lipiodol solution of a lipophilic agent, (188)Re-TDD, for the treatment of liver cancer.

Radiolabeled lipiodol has been used for targeting liver cancer. We developed a lipiodol solution of (188)Re-TDD (2,2,9,9-tetramethyl-4,7-diaza-1,10-decanedithiol) and investigated its feasibility for the treatment of liver cancer. The lipiodol solution of (188)Re-TDD was well-retained in the lipiodol phase in vitro. After injection through the tail veins of mice, high lung-uptake was investigated which is evidence of embolizing activity. We also found high accumulation in hepatoma after injection through the hepatic arteries of hepatoma-bearing rats. In conclusion, the lipiodol solution of (188)Re-TDD is a promising agent for liver cancer therapy.

Animals↗

Disparity of perfusion and glucose metabolism of epileptogenic zones in temporal lobe epilepsy demonstrated by SPM/SPAM analysis on 15O water PET, [18F]FDG-PET, and [99mTc]-HMPAO SPECT.

PURPOSE: To elucidate uncoupling of perfusion and metabolism and its significance in epilepsy, 15O water and 18F fluorodeoxyglucose (FDG) positron emission tomography (PET) and Tc-99m hexamethyl-propyleneamine-oxime (HMPAO) single-photon emission computed tomography (SPECT) were examined by SPM (statistical parametric mapping) and quantitation by using SPAM (statistical probabilistic anatomic map). METHODS: [15O]water and [18F]FDG-PET, and [99mTc]-HMPAO SPECT were performed in 25 patients (SPECT in 17 of 25) with medial temporal lobe epilepsy. For volume of interest (VOI) count analysis, the normalized counts using VOI based on SPAM templates of PET and SPECT were compared with those of the normal controls. Perfusion or metabolism was found abnormal if the Z score was >2 for each VOI. For SPM analysis, the differences between each patient's image and a group of normal control images (t statistic for p < 0.01) on a voxel-by-voxel basis were examined to find significant decreases in perfusion or metabolism. RESULTS: With SPAM VOI count analysis, areas of hypoperfusion were found in 13 patients in the epileptogenic temporal lobes by [15O]water PET and areas of hypometabolism in 21 patients by [18F]FDG-PET. With voxel-based SPM analysis, the epileptogenic zones were localized in 15 by [15O]water PET and in 23 patients by [18F]FDG-PET. The localization by [15O]water PET was concordant with that of [18F]FDG-PET. The areas of hypoperfusion on [15O]water PET were absent or smaller than the areas of hypometabolism on [18F]FDG-PET. Interictal [99mTc]-HMPAO SPECT revealed the hypoperfused zones in seven of 17 patients on visual assessment. CONCLUSIONS: SPAM VOI count and SPM analysis of [15O]water and [18F]FDG-PET and [99mTc]-HMPAO SPECT revealed that in the same patients, the areas of hypoperfusion were concordant with but smaller than the areas of hypometabolism. Discordance of perfusion and metabolic abnormalities represents an uncoupling of perfusion and metabolism in the epileptogenic zones, and this might explain the lower diagnostic accuracy of perfusion imaging in temporal lobe epilepsy.

Adolescent↗

Diagnostic performance of [18F]FDG-PET and ictal [99mTc]-HMPAO SPECT in occipital lobe epilepsy.

PURPOSE: We investigated whether interictal F-18 fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) or ictal [99mTc]-HMPAO single-photon emission computed tomography (SPECT) was useful to find epileptogenic zones in occipital lobe epilepsy (OLE). METHODS: We reviewed visually and quantified patterns of hypometabolism in interictal [18F]FDG-PET and those of hyperperfusion in ictal SPECT in 17 OLE patients (27 plus minus 6.8 years old; M/F, 10/7; injection time, 30 plus minus 17 s). OLE was diagnosed based on invasive electroencephalography, surgery, and postsurgical outcome (Engel class I in all at an average of 26 months after surgery). RESULTS: Epileptogenic zones were correctly localized in nine (60%) of 15 patients by interictal [18F]FDG-PET, and asymmetric indices corroborated visual diagnosis. Epileptogenic hemispheres were correctly lateralized in 14 (93%) of 15 patients on [18F]FDG-PET. Epileptogenic hemispheres were correctly lateralized in 13 (76%) of 17 patients using ictal SPECT, but localization was possible in only five (29%) patients. Interictal [18F]FDG-PET was helpful in two of the patients who showed no abnormality on magnetic resonance imaging (MRI) and no possible localization with ictal SPECT. CONCLUSIONS: In OLE, ictal SPECT was helpful in lateralization, but less helpful in localization. Interictal [18F]FDG-PET was helpful in localization or lateralization of epileptogenic zones, even in patients with ambiguous MRI or ictal SPECT findings.

Adolescent↗

Different patterns of lymphoscintigraphic findings in patients with intestinal lymphangiectasia.

Technetium-99m antimony sulfide colloid lymphoscintigraphy conveniently demonstrates intestinal leakage of lymph in patients with intestinal lymphangiectasia. However, we found no intestinal radioactivity in some patients. We evaluated lymphoscintigraphic findings and compared them with clinical data. Technetium-99m antimony colloid lymphoscintigraphy was performed in 12 patients (age, 8.9+/-6.4 years; male:female=8:4) with histologically proven intestinal lymphangiectasia. After subcutaneous injection of 103.6 MBq of technetium-99m antimony colloid into the webs of both feet, sequential abdominal images were obtained up to 24 h post-injection. Four patients underwent technetium-99m methylene diphosphonate bone scintigraphy. Patients were divided into two groups according to the presence or absence of intestinal radioactivity. Five showed intestinal activity (Group 1), but seven did not (Group 2). No Group 1 patient had a history of ascites, while all Group 2 patients had ascites as the initial manifestation. Serum total protein and albumin levels were significantly lower in Group 1 patients than in Group 2 patients. In three Group 1 patients, technetium-99m methylene diphosphonate bone scintigraphy revealed intestinal radioactivity, while in one Group 2 patient this was not found. We observed two types of lymphoscintigraphic pattern in patients with intestinal lymphangiectasia. To clarify the exact pathophysiology, further study is required.

Adolescent↗

Reproducibility of an automatic quantitation of regional myocardial wall motion and systolic thickening on gated 99mTc-sestamibi myocardial SPECT.

UNLABELLED: We investigated the reproducibility of an automatic quantitative algorithm for measuring regional myocardial wall motion and systolic thickening. METHODS: 99mTc-sestamibi gated myocardial SPECT with dipyridamole stress was performed twice consecutively on 31 patients with known or suspected coronary artery disease, with the patients in the same position for each scan. With AutoQUANT software, segmental wall motion and systolic thickening were quantified automatically and expressed in millimeters and percentage increase, respectively, for 20 segments. Afterward, the correlation and agreement between repeated measurements were investigated, and the influences of wall location, perfusion grade, and partitioning of the myocardium on reproducibility were evaluated by ANOVA and t testing. RESULTS: High correlations (r = 0.95 for wall motion and 0.88 for systolic thickening) and good agreements (weighted kappa = 0.81 and 0.71, respectively) were obtained from repeated measurements on consecutive gated SPECT. Changes in wall location and perfusion grade did not cause significant differences between repeated measurements (P > 0.05 in ANOVA and t testing), but a change in partitioning did. On Bland-Altman analysis, 2 SDs for repeated wall motion and for systolic thickening were 2.0 mm and 20%, respectively. CONCLUSION: The automatic quantitative algorithm for myocardial SPECT provided by AutoQUANT software has good reproducibility under diverse conditions. A change of motion > 2.0 mm or a change of systolic thickening > 20% can be regarded as significant during a follow-up study using this software.

Adult↗

Quantification of regional myocardial blood flow using dynamic H2(15)O PET and factor analysis.

UNLABELLED: Because the use of factor analysis has been proposed for extracting pure physiologic temporal or spatial information from dynamic nuclear medicine images, factor analysis should be capable of robustly estimating regional myocardial blood flow (rMBF) using H2(15)O PET without additional C15O PET, which is a cumbersome procedure for patients. Therefore, we measured rMBF using time-activity curves (TACs) obtained from factor analysis of dynamic myocardial H2(15)O PET images without the aid of C15O PET. METHODS: H2(15)O PET of six healthy dogs at rest and during stress was performed simultaneously with microsphere studies using 85Sr, 46Sc, and 113SN: We performed factor analysis in two steps after reorienting and masking the images to include only the cardiac region. The first step discriminated each factor in the spatial distribution and acquired the input functions, and the second step extracted regional-tissue TACS: Image-derived input functions obtained by factor analysis were compared with those obtained by the sampling method. rMBF calculated using a compartmental model with tissue TACs from the second step of the factor analysis was compared with rMBF measured by microsphere studies. RESULTS: Factor analysis was successful for all the dynamic H2(15)O PET images. The input functions obtained by factor analysis were nearly equal to those obtained by arterial blood sampling, except for the expected delay. The correlation between rMBF obtained by factor analysis and rMBF obtained by microsphere studies was good (r = 0.95). The correlation between rMBF obtained by the region-of-interest method and rMBF obtained by microsphere studies was also good (r = 0.93). CONCLUSION: rMBF can be measured robustly by factor analysis using dynamic myocardial H2(15)O PET images without additional C15O blood-pool PET.

Animals↗

Relationship between expression of the sodium/iodide symporter and 131I uptake in recurrent lesions of differentiated thyroid carcinoma.

The sodium/iodide symporter (NIS) is known to be responsible for the active accumulation of iodide within the thyroid gland. We evaluated the relationship between the expression of NIS in primary or lymph node lesions and iodine-131 uptake in recurrent lesions of differentiated thyroid cancer. In 67 patients with differentiated thyroid cancer (5 follicular and 62 papillary carcinomas), the expression of NIS was analysed by immunohistochemical staining using polyclonal antibodies against human NIS. We used paraffin block tissues of primary tumours or metastatic lesions, and also assessed 131I uptake in recurrent lesions of thyroid cancer on post-operative 131I whole-body scan. Immunohistochemical staining was positive in 22 patients (32.8%), including 2 of 5 follicular and 20 of 62 papillary carcinomas. Recurrence was confirmed in 40 patients pathologically or clinically by serum thyroglobulin, 131I scan, fluorine-18 fluorodeoxyglucose positron emission tomography and/or computed tomography. Among these 40 patients, 28 showed positive uptake on 131I scan. Fourteen tumour specimens out of 28 (50%) were positive by NIS immunohistochemical staining. The remaining 12 patients with recurrent cancer showed negative 131I scans, and all specimens were negative by NIS immunohistochemical staining. Thus, NIS immunohistochemical staining predicted 131I uptake in recurrent cancer with a 100% positive predictive value and a 46.2% negative predictive value. There was no difference in the positivity of NIS according to the site of recurrence on 131I scan. Outcome of 131I therapy could be assessed in 22 of the 28 patients who showed 131I uptake in recurrent lesions. Patients with positive NIS immunostaining responded to 131I therapy better than did patients with negative immunostaining (P<0.05). In conclusion, NIS immunohistochemical staining showed a high positive predictive value in predicting iodine uptake. Positive immunohistochemical staining of human NIS in primary or lymph node lesions may predict 131I accumulation and effectiveness of 131I therapy in recurrent lesions.

Adenocarcinoma, Follicular↗

Blind separation of cardiac components and extraction of input function from H(2)(15)O dynamic myocardial PET using independent component analysis.

UNLABELLED: The independent component analysis (ICA) method is suggested to be useful for separation of the ventricles and the myocardium and for extraction of the left ventricular input function from the dynamic H(2)(15)O myocardial PET. The ICA-generated input function was validated with the sampling method, and the myocardial blood flow (MBF) calculated with this input function was compared with the microsphere results. METHODS: We assumed that the elementary activities of the ventricular pools and the myocardium were spatially independent and that the mixture of them composed dynamic PET image frames. The independent components were estimated by recursively minimizing the mutual information (measure of dependence) between the components. The ICA-generated input functions were compared with invasively derived arterial blood samples. Moreover, the regional MBF calculated using the ICA-generated input functions and single-compartment model was correlated with the results obtained from the radiolabeled microspheres. RESULTS: The ventricles and the myocardium were successfully separated in all cases within a short computation time (<15 s). The ICA-generated input functions displayed shapes similar to those obtained by arterial sampling except that they had a smoother tail than those obtained by sampling, which meant that ICA removed the statistical noise from the time--activity curves. The ICA-generated input function showed a longer time delay of peaks than those obtained by arterial sampling. MBFs estimated using the ICA-generated input functions ranged from 1.10 to approximately 2.52 mL/min/g at rest and from 1.69 to approximately 8.00 mL/min/g after stress and correlated well with those calculated with microspheres (y = 0.45 + 0.98x; r = 0.95, P < 0.000). CONCLUSION: ICA, a rapid and reliable method for extraction of the pure physiologic components, was a valid and useful method for quantification of the regional MBF using H(2)(15)O PET.

Animals↗

Hypoglycemia-induced cerebellar dysfunction and quantitative positron emission tomography study.

OBJECTIVE: To describe an unusual case of hypoglycemia-induced bilateral cerebellar dysfunction. BACKGROUND: The cerebellum is known to be resistant to hypoglycemia, and selective cerebellar dysfunction caused by hypoglycemia has not been reported. Previous studies showed that the ratio between the rate constants for glucose uptake and phosphorylation (K1 and k3) is reversed in the cerebellum compared with the cerebral cortex; higher K1 in the cerebellum and higher k3 in the cerebral cortex. METHODS: Quantitative dynamic PET scanning with labeled fluorodeoxyglucose (18F-FDG) was performed to prove altered glucose kinetics in the cerebellum of a patient who presented with episodic cerebellar dysfunction associated with hypoglycemia. Four control subjects underwent the same study. RESULTS: The ratio between K1 and k3 was not reversed in the cerebellum of our patient (K1 = 0.082, k3 = 0.192). On the contrary, the ratio was reversed in the control subjects (mean K1 = 0.109, mean k3 = 0.080). In addition, the patient's cerebellar metabolic rate of glucose (rCMRglu = 27.9 micromol/100 g/minute) and the rate constant of glucose egress (k2 = 0.543) were relatively increased compared with those of control subjects (mean rCMRglu = 21.9 micromol/100 g/minute, mean k2 = 0.352). CONCLUSIONS: In a case of episodic bilateral cerebellar dysfunction caused by hypoglycemia, quantitative dynamic PET study demonstrated decreased glucose uptake-to-utilization ratio and increased leak of glucose in the cerebellum. The cerebellum is not invariably resistant to hypoglycemia.

Blood Glucose↗

Inhibition of phospholipase D by amphiphysins.

Two distinct proteins inhibiting phospholipase D (PLD) activity in rat brain cytosol were previously purified and identified as synaptojanin and AP180, which are specific to nerve terminals and associate with the clathrin coat. Two additional PLD-inhibitory proteins have now been purified and identified as the amphiphysins I and II, which forms a heterodimer that also associates with the clathrin coat. Bacterially expressed recombinant amphiphysins inhibited both PLD1 and PLD2 isozymes in vitro with a potency similar to that of brain amphiphysin (median inhibitory concentration of approximately 15 nm). Expressions of either amphiphysin in COS-7 cells reduced activity of endogenous PLD as well as exogenously expressed PLD1 and PLD2. Coprecipitation experiments suggested that the inhibitory effect of amphiphysins results from their direct interaction with PLDs. The NH(2) terminus of amphiphysin I was critical for both inhibition of and binding to PLD. Phosphatidic acid formed by signal-induced PLD is thought to be required for the assembly of clathrin-coated vesicles during endocytosis. Thus, the inhibition of PLD by amphiphysins, synaptojanin, and AP180 might play an important role in synaptic vesicle trafficking.

Amino Acid Sequence↗