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Biomedical subjects

B T Kim

Publications and source records attributed to B T Kim.

At least 19 recordsLinked to original sources
PubMed2002

Determination of the prognostic value of [(18)F]fluorodeoxyglucose uptake by using positron emission tomography in patients with non-small cell lung cancer.

The aim of this study was to determine whether quantitative information obtained from [(18)F]fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) has a prognostic significance for patients with non-small cell lung cancer (NSCLC). We investigated (18)F-FDG PET imaging of 73 patients with NSCLC. The maximum standardized uptake value (SUV(max)) was significantly different between the histopathological types of tumour (squamous cell carcinoma (n=37, 12.4+/-5.1), adenocarcinoma (n=30, 8.2+/-5.8), bronchioloalveolar carcinoma (n=4, 2.6+/-1.7), <0.01). In the univariate analysis of all patients, staging (P=0.0001), tumour cell type (P=0.013), and a SUV(max) greater than 7 (P=0.0011) was correlated with survival. However, a multivariate analysis identified staging and SUV(max) greater than 7 were affected survival adversely. The mortality rate of patients with group I disease (stage I to stage IIIA) was 5.8 times lower than that of patients with group II disease (stage IIIB to stage IV). Patients with a high SUV(max) (> or =7) had a 6.3 times higher mortality than those with a low SUV(max)(<7). By multivariate analysis of patients with squamous cell carcinoma, only grouping affected survival (P=0.008, relative risk=4.3). In the case of adenocarcinoma, the SUV(max) (>10) correlated exclusively with poorer survival (P=0.031, relative risk=11.152). (18)F-FDG uptake correlated with survival in NSCLC. Especially in adenocarcinomas, the SUV(max) was complementary to other known prognostic factors.

Adult↗
PubMed2001

Human tumor suppressor EXT gene family members EXTL1 and EXTL3 encode alpha 1,4- N-acetylglucosaminyltransferases that likely are involved in heparan sulfate/ heparin biosynthesis.

The tumor suppressors EXT1 and EXT2 are associated with hereditary multiple exostoses and encode bifunctional glycosyltransferases essential for chain polymerization of heparan sulfate (HS) and its analog, heparin (Hep). Three highly homologous EXT-like genes, EXTL1-EXTL3, have been cloned, and EXTL2 is an alpha1,4-GlcNAc transferase I, the key enzyme that initiates the HS/Hep synthesis. In the present study, truncated forms of EXTL1 and EXTL3, lacking the putative NH2-terminal transmembrane and cytoplasmic domains, were transiently expressed in COS-1 cells and found to harbor alpha-GlcNAc transferase activity. EXTL3 used not only N-acetylheparosan oligosaccharides that represent growing HS chains but also GlcAbeta1-3Galbeta1-O-C2H4NH-benzyloxycarbonyl (Cbz), a synthetic substrate for alpha-GlcNAc transferase I that determines and initiates HS/Hep synthesis. In contrast, EXTL1 used only the former acceptor. Neither EXTL1 nor EXTL3 showed any glucuronyltransferase activity as examined with N-acetylheparosan oligosaccharides. Heparitinase I digestion of each transferase-reaction product showed that GlcNAc had been transferred exclusively through an alpha1,4-configuration. Hence, EXTL3 most likely is involved in both chain initiation and elongation, whereas EXTL1 possibly is involved only in the chain elongation of HS and, maybe, Hep as well. Thus, their acceptor specificities of the five family members are overlapping but distinct from each other, except for EXT1 and EXT2 with the same specificity. It now has been clarified that all of the five cloned human EXT gene family proteins harbor glycosyltransferase activities, which probably contribute to the synthesis of HS and Hep.

Adult↗
PubMed2001

Antisense knockdown of the glial glutamate transporter GLT-1, but not the neuronal glutamate transporter EAAC1, exacerbates transient focal cerebral ischemia-induced neuronal damage in rat brain.

Transient focal cerebral ischemia leads to extensive neuronal damage in cerebral cortex and striatum. Normal functioning of glutamate transporters clears the synaptically released glutamate to prevent excitotoxic neuronal death. This study evaluated the functional role of the glial (GLT-1) and neuronal (EAAC1) glutamate transporters in mediating ischemic neuronal damage after transient middle cerebral artery occlusion (MCAO). Transient MCAO in rats infused with GLT-1 antisense oligodeoxynucleotides (ODNs) led to increased infarct volume (45 +/- 8%; p < 0.05), worsened neurological status, and increased mortality rate, compared with GLT-1 sense/random ODN-infused controls. Transient MCAO in rats infused with EAAC1 antisense ODNs had no significant effect on any of these parameters. This study suggests that GLT-1, but not EAAC1, knockdown exacerbates the neuronal death and thus neurological deficit after stroke.

ATP-Binding Cassette Transporters↗
PubMed2001

Usefulness of diabetic retinopathy as a marker of risk for thallium myocardial perfusion defects in non-insulin-dependent diabetes mellitus.

Among 236 non-insulin-dependent diabetics with clinically suspected coronary artery disease, the rate of thallium-201 myocardial perfusion defects was significantly higher in subjects with (40.6%) than without (22.1%) diabetic retinopathy. Retinopathy was associated with a higher risk of perfusion defects in subjects with cardiac and noncardiac chest pain, and may thus be a useful marker for selecting patients in whom thallium scintigraphy screening is warranted.

Chi-Square Distribution↗
PubMed2001

4-Hydroxy-6-oxo-6,7-dihydro-thieno[2,3-b] pyrimidine derivatives: synthesis and their biological evaluation for the glycine site acting on the N-methyl-D-aspartate (NMDA) receptor.

Bioisostere approach has been shown to be useful to augment potency or to modify certain physiological properties of a lead compound. Based upon well documented bioisosterism, an isosteric replacement of benzene ring of 4-hydroxy-2-quinolone compound (L-695902) with a thiophene moiety was carried out to prepare the title compounds, 4-hydroxy-6-oxo-6,7-dihydro-thieno[2,3-b] pyrimidines 15. The resulting bioisosteric compounds 15 were evaluated for their antagonistic activity (binding assay) for NMDA receptor glycine site.

Animals↗
PubMed2001

Evaluation of lymph node metastases in squamous cell carcinoma of the esophagus with positron emission tomography.

BACKGROUND: Previous studies suggest positron emission tomography (PET) may improve staging accuracy of esophageal cancer compared with conventional methods, especially in detecting occult distant metastases. We evaluated the accuracy of PET in the detection of lymph node metastasis prospectively with pathologic findings. METHODS: Fifty-three patients with squamous cell carcinoma underwent whole-body PET scan and chest computed tomography (CT). The findings of PET and chest CT of 50 patients who underwent curative esophagectomy with radical lymph node dissection were compared with the pathologic findings. RESULTS: Among 53 primary esophageal tumors, PET detected 51 (96.2%) and CT detected 49 (92.5%) tumors correctly. Nodal metastases were present in 108 of 436 dissected lymph node groups. PET detected 56 metastatic node groups (51.9% sensitivity, 94.2% specificity, 83.7% accuracy), compared with CT, which detected 16 (14.8% sensitivity, 96.7% specificity, 76.6% accuracy; sensitivity: p < 0.005). CONCLUSIONS: PET was more sensitive than CT in the detection of nodal metastases and may improve staging of squamous cell carcinoma of the esophagus.

Adult↗
PubMed2001

A simple and efficient in vitro method for metabolism studies of radiotracers.

In vitro metabolism of acetylcholinesterase inhibitors containing 3-[(18)F]fluoromethylbenzyl- ([(18)F]1) and 4-[(18)F]fluorobenzyl-piperidine moieties ([(18)F]2) was studied and compared with the in vivo metabolism. Defluorination of the [(18)F]1 mainly occurred to generate [(18)F]fluoride ion both in vitro and in vivo. In contrast, the [(18)F]2 was converted into an unknown polar metabolite in both metabolism methods and another metabolite, 4-[(18)F]fluorobenzoic acid in vitro. These results demonstrated that the in vitro method can be used to predict the in vivo metabolism of both radiotracers.

Animals↗
PubMed2001

Purification and characterization of acharan sulfate lyases, two novel heparinases, from Bacteroides stercoris HJ-15.

Two novel acharan sulfate lyases (ASL1 and ASL2: no EC number) have been purified from Bacteroides stercoris HJ-15 which was isolated from human intestinal bacteria with glycosaminoglycan (GAG) degrading enzymes. These enzymes were purified to apparent homogeneity by a combination of QAE-cellulose, DEAE-cellulose, carboxymethyl-Sephadex C-50, hydroxyapatite and HiTrap SP Sephadex C-25 column chromatography with the final specific activity of 50.5 and 76.7 micromol.min-1.mg-1, respectively. Both acharan sulfate lyases are single subunits of 83 kDa by SDS/PAGE and gel filtration. ASL1 showed optimal activity at pH 7.2 and 45 degrees C. ASL1 activity was inhibited by Cu2+, Ni2+ and Co2+, but ASL2 activity was inhibited by Cu2+, Ni2+and Pb2. Both enzymes were slightly inhibited by some agents that modify histidine and cysteine residues, but activated by reducing agents such as DL-dithiothreitol and 2-mercaptoethanol. Both purified bacteroidal acharan sulfate lyases acted to the greatest extent on acharan sulfate, and to a lesser extents on heparan sulfate and heparin. They did not act on de-O-sulfated acharan sulfate. These findings suggest that the biochemical properties of these purified acharan sulfate lyases are different from those of the previously purified heparin lyases, but these enzymes belong to heparinase II.

Amino Acid Sequence↗
PubMed2001

Comparison of intraoperative frozen section analysis of sentinel node with preoperative positron emission tomography in the diagnosis of axillary lymph node status in breast cancer patients.

BACKGROUND: Although axillary lymph node status is an important prognostic factor and axillary dissection is regarded as the gold standard for staging, it requires radical surgery which is accompanied by considerable postoperative problems such as lymphedema. This study was carried out to evaluate the diagnostic accuracy of preoperative positron emission tomography (PET) and intraoperative frozen biopsy of sentinel lymphadenectomy (SLND) in detecting axillary lymph node metastasis. METHODS: We studied 18 patients who had preoperative PET and SLND for breast cancer in the Department of Surgery at Samsung Medical Center. They all had preoperative PET with a radiolabeled glucose analogue ([18F]FDG) to visualize primary tumors and metastatic nodes. Isosulphan blue dye was used for intraoperative SLND. Frozen and permanent biopsies were then compared after full axillary dissection. RESULTS: In 18 cases, six had positive metastatic nodes in the permanent biopsy of full axillary dissection but were negative in three cases by preoperative PET. There was one false negative result by frozen biopsy of SLND which was later shown to be positive by permanent biopsy. The sensitivity and specificity of SLND and PET for detecting axillary node metastasis were 83, 100% and 50, 100%, respectively. CONCLUSION: Although both methods are good for axillary nodal status, the intraoperative frozen biopsy result of SLND was superior to preoperative PET in our preliminary study.

Adult↗
PubMed2001

Muc1 mucins on the cell surface are adhesion sites for Pseudomonas aeruginosa.

Recently, we cloned and characterized a full-length cDNA of the hamster Muc1 gene, the expression of which appears to be associated with secretory cell differentiation (Park HR, Hyun SW, and Kim KC. Am J Respir Cell Mol Biol 15: 237-244, 1996). The role of Muc1 mucins in the airway, however, is unknown. In this study, we investigated whether cell surface mucins are adhesion sites for Pseudomonas aeruginosa. Chinese hamster ovary (CHO) cells not normally expressing Muc1 mucin were stably transfected with the hamster Muc1 cDNA, and binding to P. aeruginosa was examined. Our results showed that 1) stably transfected CHO cells expressed both Muc1 mRNA and Muc1 mucins based on Northern and Western blot analyses, 2) Muc1 mucins present on the cell surface were degraded by neutrophil elastase, and 3) expression of Muc1 mucins on the cell surface resulted in a significant increase in adhesion of P. aeruginosa that was completely abolished by either proteolytic cleavage with neutrophil elastase or deletion of the extracellular domain by mutation. We conclude that Muc1 mucins expressed on the surface of CHO cells serve as adhesion sites for P. aeruginosa, suggesting a possible role for these glycoproteins in the early stage of airway infection and providing a model system for studying epithelial cell responses to bacterial adhesion that leads to airway inflammation in general and cystic fibrosis in particular.

Animals↗
PubMed2001

Sexual dimorphism in vertebral fragility is more the result of gender differences in age-related bone gain than bone loss.

Spine fractures usually occur less commonly in men than in women. To identify the structural basis for this gender difference in vertebral fragility, we studied 1013 healthy subjects (327 men and 686 women) and 76 patients with spine fractures (26 men and 50 women). Bone mineral content (BMC), cross-sectional area (CSA), and volumetric bone mineral density (vBMD) of the third lumbar vertebral body (L3) were measured by posteroanterior (PA) and lateral scanning using dual-energy X-ray absorptiometry (DXA). In this cross-sectional study, the diminution in peak vertebral body BMC from young adulthood to old age was less in men than in women (6% vs. 27%). This diminution was the net result of two opposing changes occurring concurrently throughout adult life: the removal of bone adjacent to marrow on the inner (endosteal) surface by bone resorption and the deposition of bone on the outer (periosteal) surface by bone formation. For L3, we estimated that men resorbed 3.7 g and deposited 3.1 g, producing a net loss of 0.6 g from young adulthood to old age and women resorbed 3.1 g and deposited only 1.2 g, producing a net loss of 1.9 g. Thus, based on our indirect estimates of periosteal gain and endosteal loss across life, the observed net diminution in BMC during aging was less in men than women because absolute periosteal bone formation was greater in men than women (3.1 g vs. 1.2 g) not because absolute bone resorption was less in men. On the contrary, the absolute amount of bone resorbed was greater in men than women (3.7 g vs. 3.1 g). Periosteal bone formation also increased vertebral body CSA 3-fold more in men than in women, distributing loads onto a larger CSA, so that the load imposed per unit CSA decreased twice as much in men than in women (13% vs. 5%). In men and women with spine fractures, CSA and vBMD were reduced relative to age-matched controls. However, vBMD was no different to the adjusted vBMD in age-matched controls derived assuming controls had no periosteal bone formation during aging. Thus, large amounts of bone are resorbed in men as well as in women, accounting for the age-related increase in spine fractures in both genders. Periosteal bone formation increases CSA and offsets bone loss in both genders but more greatly in men, accounting for the lower incidence of spine fractures in men than in women. We speculate that reduced periosteal bone formation, during growth or aging, may be in part responsible for both reduced vertebral size and reduced vBMD in men and women with spine fractures. Sexual dimorphism in vertebral fragility is more the result of gender differences in age-related bone gain than age-related bone loss.

Adult↗
PubMed2001

Protective effects of glial cell line-derived neurotrophic factor on hippocampal neurons after traumatic brain injury in rats.

OBJECT: The purpose of this study was to evaluate whether glial cell line-derived neurotrophic factor (GDNF) can protect against hippocampal neuronal death after traumatic brain injury (TBI). METHODS: Male Sprague-Dawley rats were subjected to moderate TBI with a controlled cortical impact device while in a state of halothane-induced anesthesia. Then, GDNF or artificial cerebrospinal fluid ([aCSF]; vehicle) was infused into the frontal horn of the left lateral ventricle. In eight brain-injured and eight sham-operated rats, GDNF was infused continuously for 7 days (200 ng/day intracerebroventricularly at a rate of 8.35 ng/0.5 microl/hour). An equal volume of vehicle was infused at the same rate into the remaining eight brain-injured and eight sham-operated rats. Seven days post-injury, all rats were killed. Their brains were sectioned and stained with cresyl violet, and the hippocampal neuronal loss was evaluated in the CA2 and CA3 regions with the aid of microscopy. A parallel set of sections from each brain was subjected to immunoreaction with antibodies against glial fibrillary acidic protein (GFAP; astroglia marker). In the aCSF-treated group, TBI resulted in a significant neuronal loss in the CA2 (60%, p < 0.05) and CA3 regions (68%, p < 0.05) compared with the sham-operated control animals. Compared with control rats infused with aCSF, GDNF infusion significantly decreased the TBI-induced neuronal loss in both the CA2 (58%, p < 0.05) and CA3 regions (51%, p < 0.05). There was no difference in the number of GFAP-positive astroglial cells in the GDNF-infused rats in the TBI and sham-operated groups compared with the respective vehicle-treated groups. CONCLUSIONS: The authors found that GDNF treatment following TBI is neuroprotective.

Animals↗
PubMed2001

Mucin secretion in the rat tracheal epithelial cells by epidermal growth factor and Pseudomonas aeruginosa extracts.

BACKGROUND: Hypersecretion of mucin due to goblet cell hyperplasia is frequently encountered in many chronic airway diseases, such as chronic bronchitis, bronchiectasis, bronchial asthma and cystic fibrosis. Even in normal individuals, viral infection or bacterial pneumonia frequently provoke huge amounts of bronchial secretions which may cause airway obstruction. The production of mucin was regulated by epidermal growth factor (EGF) in vitro. To know whether this EGF system regulates mucin secretion in vivo and Pseudomonas also stimulates the mucin secretion by the same pathway, we studied these relationships in the cultured rat tracheal epithelial cells. METHODS: Rat tracheal epithelial cells were obtained by pronase dissociation from the male Fisher 344 rats. When cells became confluent, they were divided into 6 groups and stimulated with either EGF for 24 hours or Pseudomonas extracts for 12 hours with or without selective EGF-R tyrosine kinase inhibitor tyrphostin AG1478. RESULTS: We found that both EGF and Pseudomonas extracts phosphorylated the tyrosine residue in the EGF receptor from the rat tracheal epithelial cells and this tyrosine phosphorylation was nearly completely blocked by selective EGF-R tyrosine kinase inhibitor tyrphostin AG1478. The mucin secretion was also stimulated by either EGF or Pseudomonas extracts but more strong secretion of mucin and MUC5AC gene expression in the rat tracheal epithelial cell was done by Pseudomonas extracts. CONCLUSION: These data suggest that Pseudomonas secretes the mucin by way of the EGF receptor and MUC5AC gene expression and the inhibitors of EGF receptor tyrosine phosphorylation would be useful to prevent the huge production of mucin due to Pseudomonas aeruginosa lung infection.

Animals↗
PubMed2000

Biotransformation of glycyrrhizin by human intestinal bacteria and its relation to biological activities.

The relationship between the metabolites of glycyrrhizin (18beta-glycyrrhetinic acid-3-O-beta-D-glucuronopyranosyl-(1-->2)-beta-D-glucuronide, GL) and their biological activities was investigated. By human intestinal microflora, GL was metabolized to 18beta-glycyrrhetinic acid (GA) as a main product and to 18beta-glycyrrhetinic acid-3-O-beta-D-glucuronide (GAMG) as a minor product. The former reaction was catalyzed by Eubacterium L-8 and the latter was by Streptococcus LJ-22. Among GL and its metabolites, GA and GAMG had more potent in vitro anti-platelet aggregation activity than GL. GA also showed the most potent cytotoxicity against tumor cell lines and the potent inhibitory activity on rotavirus infection as well as growth of Helicobacter pylori. GAMG, the minor metabolite of GL, was the sweetest.

Anti-Bacterial Agents↗
PubMed2000

Radiolabeling of paclitaxel with electrophilic 123I.

123I-Labeled paclitaxel, [123I]-1 was prepared by electrophilic aromatic radioiodination of 3'-N-(p-trimethylstannylbenzoyl)-3'-debenzoylpaclitaxel 2 with 123I- in the presence of peracetic acid.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Brain tumor imaging with 99mTc-tetrofosmin: comparison with 201Tl, 99mTc-MIBI, and 18F-fluorodeoxyglucose.

The purpose of the present study was to assess the ability of technetium-99m-tetrofosmin (99mTc-TF) to predict tumor malignancy and to compare its uptake with that of thallium-201 (201Tl), technetium-99m-hexakis-2-methoxyisobutyl isonitrile (99mTc-MIBI) and fluorine-18-fluorodeoxyglucose (18F-FDG) in brain tumors. 99mTc-TF single-photon emission computed tomography (SPECT) imaging was performed in 22 patients with brain tumors and 3 healthy controls. Some of the patients underwent 201Tl (n = 12) and 99mTc-MIBI SPECT (n = 14) and 18F-FDG positron emission tomography (PET) (n = 12). The radioactivity ratio of tumor to contralateral normal tissue (T/N) and the ratio of tumor to contralateral white matter (T/WM) were calculated in SPECT and PET images, respectively. In healthy controls, 99mTc-TF uptake was seen only in scalp, in the choroid plexus and pituitary gland, but not in normal cerebral parenchyma. TF T/N in low grade gliomas (2.8+/-0.4) was significantly lower than that in high grade gliomas (22.5+/-29.8) and malignant non-gliomas (8.3+/-2.8) without overlap of values (p = 0.003 and p = 0.014, respectively). TF T/N was significantly correlated with MIBI T/N (p = 0.92, p = 0.001), Tl T/N (p = 0.72, p = 0.017), and FDG T/WM (p = 0.65. p = 0.031). There was an excellent agreement between TF T/N and MIBI T/N values on linear regression analysis (MIBI T/N = -0.63+/-0.97 x TF T/N). These preliminary results indicate that SPECT imaging with 99mTc-TF may be useful for the non-invasive grading of brain tumors. They also suggest that 99mTc-TF and 99mTc-MIBI may accumulate in brain tumors by a similar mechanism or in relation to a similar process of tumor cell proliferation.

Adolescent↗
PubMed2000

Development of a miniature scintillation camera using an NaI(Tl) scintillator and PSPMT for scintimammography.

We have developed a small scintillation camera dedicated to breast imaging and have evaluated the performance of the system. In order to increase the limited field of view (FOV) determined by the size of a position-sensitive photomultiplier tube (PSPMT), the imaging characteristics of a diverging hole collimator (DHC) were also investigated. The small scintillation camera system consists of an NaI(Tl) crystal (60 mm x 60 mm x 6 mm) coupled to a Hamamatsu R3941 PSPMT, a resistor chain circuit, preamplifiers, nuclear instrument modules, an analogue to digital converter and a PC for control and display. The intrinsic energy resolution of the system was 12.9% FWHM at 140 keV. The spatial resolution was measured using a line-slit mask and 99mTc point sources and was 3.1 mm FWHM. The intrinsic sensitivity of the system was approximately 162 counts/s kBq(-1). The DHC made it possible to image a larger FOV (75 x 75 mm2 at the surface of collimator) than a parallel-hole collimator (60 x 60 mm2). The system sensitivity obtained using the DHC gradually decreased with distance (3% at 1 cm, 6% at 2 cm and 9% at 3 cm). The results demonstrate that the system developed in this study could be utilized clinically to image malignant breast tumours. A DHC can be employed to expand the FOV of the system confined by the size of PSPMT with a modest compromise in the performance of the system.

Breast Neoplasms↗