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Biomedical subjects

J K Kim

Publications and source records attributed to J K Kim.

At least 19 recordsLinked to original sources

Portal, mesenteric, and splenic vein thromboses after splenectomy in a patient with chronic myeloid leukemia variant with thrombocythemic onset.

Portal, mesenteric, or splenic vein thrombosis is a very uncommon complication with significant mortality in the patients undergoing splenectomy for hematologic disorders. We report a 49-year-old woman who developed portal, superior mesenteric, and splenic vein thromboses after splenectomy. Four years before the event, she presented with a marked thrombocytosis and was diagnosed to have chronic myeloid leukemia variant with thrombocythemic onset as evidence by Philadelphia (Ph1) chromosome and a b3a2 BCR/ABL transcript. Six weeks after splenectomy, she developed severe epigastric pain. The diagnosis of thromboses of portal, mesenteric, and splenic veins was made by computed tomography scan and Doppler sonogram. She was successfully treated with antegrade intraarterial urokinase therapy via superior mesenteric artery and long-term anticoagulant therapies. To our knowledge, our patient is the first case of portal, mesenteric, and splenic vein thromboses after splenectomy in a patient with CML variant with thrombocythemic onset successfully treated with antegrade intraarterial thrombolytic therapy followed by anticoagulant therapies.

Female

Tracking oxygen effects on MR signal in blood and skeletal muscle during hyperoxia exposure.

Blood and muscle T1 and T2 relaxivity was examined under normoxic (air; 20.8% O2) and hyperoxic (100% O2) conditions to determine whether the oxygenation state of blood in the large vessels and in the microcirculation can be monitored in vivo. The femoral artery/vein and the soleus and gastrocnemius muscles were examined in healthy human male volunteers. Arterial blood T1 decreased with hyperoxia, while venous blood T2 increased, due to increased dissolved O2 and decreased deoxyhemoglobin, respectively. A biexponential T2 model of muscle is proposed, where the short T2 component reflects primarily the intracellular and interstitial compartments (in fast exchange), and the long T2 reflects blood. In this model, the long T2 component increased with hyperoxia exposure. This was more evident in slow twitch (soleus) than in fast twitch (gastrocnemius) muscle. It is concluded that changes in the long T2 component reflect change in the microcirculation oxygenation state.

Adult

Animal model of bile duct dilatation created with minimally invasive surgery.

RATIONALE AND OBJECTIVES: The purpose of the study was to evaluate a method of producing obstruction of the common bile duct and concomitant biliary duct dilatation in an animal model. MATERIALS AND METHODS: Laparoscopic placement of a double-balloon occlusion device was used to produce common bile duct obstruction and bile duct dilatation in pigs. RESULTS: One week after the procedure, common bile duct obstruction and dilatation of the biliary tree were demonstrated with either percutaneous transhepatic cholangiography or percutaneous cholecystography. CONCLUSION: The use of this method is technically feasible and provides a useful subacute and chronic animal model of common bile duct obstruction and dilatation of the biliary tree for percutaneous interventional training and research purposes.

Animals

Management of foreign bodies in the gastrointestinal tract: an analysis of 104 cases in children.

BACKGROUND AND STUDY AIMS: Ingested foreign bodies may be managed by endoscopy, observation, or surgery. The aim of the study was to investigate the methods of removal of foreign bodies according to type and location, success rates, and complications. PATIENTS AND METHODS: The charts of 104 children who had ingested foreign bodies were retrospectively reviewed. RESULTS: Of the patients, 80 (76.9%) were managed endoscopically. The overall success rate for endoscopic management was 98.8%. There were no complications during endoscopic interventions. In 23 cases the foreign bodies spontaneously passed through the gastrointestinal tract (22.1%). Surgical removal of a foreign body was done in only one case (0.96%). The majority of the foreign bodies which were located in the upper gastrointestinal tract could be removed endoscopically regardless of the nature of the material. Foreign bodies in the small and large intestine tended to pass through spontaneously without complications. CONCLUSIONS: It appears that the endoscopic approach is the preferable method for the extraction of upper gastrointestinal foreign bodies in child patients because of its high success rate, and that foreign bodies in the small and large intestine tend to be passed spontaneously without complications.

Adolescent

Statistical textural features for detection of microcalcifications in digitized mammograms.

Clustered microcalcifications on X-ray mammograms are an important sign for early detection of breast cancer. Texture-analysis methods can be applied to detect clustered microcalcifications in digitized mammograms. In this paper, a comparative study of texture-analysis methods is performed for the surrounding region-dependence method, which has been proposed by the authors, and conventional texture-analysis methods, such as the spatial gray-level dependence method, the gray-level run-length method, and the gray-level difference method. Textural features extracted by these methods are exploited to classify regions of interest (ROI's) into positive ROI's containing clustered microcalcifications and negative ROI's containing normal tissues. A three-layer backpropagation neural network is used as a classifier. The results of the neural network for the texture-analysis methods are evaluated by using a receiver operating-characteristics (ROC) analysis. The surrounding region-dependence method is shown to be superior to the conventional texture-analysis methods with respect to classification accuracy and computational complexity.

Breast Diseases

The metabolic effects of estriol in female rat liver.

The effects of estriol on oxygen uptake, glucose release, lactate and pyruvate production, beta-hydroxybutyrate and acetoacetate production in perfused rat liver as well as, carbon uptake in rat liver and intracellular calcium in isolated Kupffer cells were investigated. Basal oxygen consumption of perfused liver increased significantly in estriol or ethanol-treated rats. But these increased effects were blocked by gadolinium chloride pretreatment. In a metabolic study, pretreatment with estriol resulted in a decrease in glucose production and in glycolysis while an increase in ketogenesis. A more oxidized redox state of the mitochondria was indicated by increased ratios of perfusate [lactate]/[pyruvate] and decreased ratios of perfusate [beta-hydroxybutyrate]/[acetoacetate]. Carbon uptake of Kupffer-cell increased significantly in estriol-treated rats. But these increased uptake were not shown in rats pre-treated by gadolinium chloride blocking phagocytosis. In isolated Kupffer cells from estriol-treated rats, intracellular calcium was more significantly increased after addition of lipopolysaccharide (LPS) than in controls. These findings suggest that the metabolic effects of estriol (two mg per 100 mg body wt) can be summarized to be highly toxic in rat liver, and these findings suggest that oral administration of estrogens may induce hepatic dysfunctions and play a role in the development of liver disease.

3-Hydroxybutyric Acid

Early homogeneously enhancing hemangioma versus hepatocellular carcinoma: differentiation using quantitative analysis of multiphasic dynamic magnetic resonance imaging.

The aim of this study was to determine the usefulness of quantitative analysis of multiphasic dynamic contrast-enhanced magnetic resonance (MR) imaging in differentiating early homogeneously enhancing hemangiomas from hepatocellular carcinomas (HCCs). Four-phased dynamic MR imaging at 10 sec (first phase of dynamic contrast-enhanced imaging, P1), 35 sec (second phase, P2), 60 sec (third phase, P3) and 300 sec (delay phase, P4) immediately after intravenous administration of 0.1 mmol/kg Gadolinium-DTPA was obtained with 1.5-T unit with breath-hold multisection FLASH (fast low angle-shot) sequence (TR/TE, 113-130 msec/4.1 msec; flip angle, 80 degrees). Thirty-three HCCs and 18 hemangiomas, homogeneously enhanced on P1, were included in the study. The images were evaluated quantitatively (SNR, signal-to-noise ratio; and CNR, contrast- to- noise ratio of lesions). Quantitatively, mean CNR was higher for hemangiomas than for HCCs on all phases, and the difference in CNRs between hemangioma and HCCs was statistically significant on P3 and P4 (p < 0.0001). When the cutoff for CNR was set at a value of 7.00 on P3 and 1.00 on P4, sensitivity, specificity and accuracy were 94.4%, 93.9%, and 94.1% on P3, and 94.4%, 81.8%, and 86.3% on P4, respectively. There was no statistically significant difference in SNRs between HCC and hemangioma. The differential diagnosis between early, homogeneously enhancing hemangiomas and HCCs was more confidently made with CNRs of lesions on P3 and P4 in dynamic contrast-enhanced MR imaging.

Adult

Up-regulation of the expression of major histocompatibility complex class I antigens by plasmid DNA transfection in non-hematopoietic cells.

The effect of DNA on the surface expression of major histocompatibility (MHC) class I antigens was examined in non-hematopoietic tumor cell lines. Transfection with plasmid DNA via liposome or electroporation significantly increased the surface expression of MHC class I molecules in a transient manner. Northern blot analysis showed that levels of MHC class I mRNA were increased by DNA transfection, probably via transcriptional activation. In contrast, the expression of the MHC class II and beta-actin genes was not affected, suggesting that the up-regulation of MHC class I expression by plasmid DNA works in a gene-specific manner.

Actins

The solution structure of DNA decamer duplex containing the Dewar product of thymidylyl(3-->5')thymidine by NMR and full relaxation matrix refinement.

The (6-4) adducts and their Dewar isomers play an important role in cytotoxicity and mutation in skin cells exposed to sunlight. Structural study of the DNA duplex containing a site-specific photoproduct is an essential step toward understanding the molecular mechanism of the mutagenesis and the repair activity of UV-irradiated DNA. Here we use 1H NMR spectroscopy and full relaxation matrix refinement to investigate the solution structure of the duplex Dewar decamer. We find that the isomerization of the (6-4) adduct to its Dewar form induces a substantial change in overall structure of the oligonucleotide duplex. Contrasting base stacking of two lesion sites results in a large difference in the structural impacts induced by the two photoproducts, such as differential disruption of hydrogen bonding at the lesion sites and overall helical bending of 44 degrees by the (6-4) lesion and 21 degrees by the Dewar lesion.

Base Composition

Sequencing and chromosomal localization of the RA138 gene encoding a rice allergenic protein.

A cDNA clone (RA138) encoding a rice allergenic (RA) protein has been isolated during a large-scale random sequencing of a cDNA library prepared from developing seeds. The nucleotide sequence of the RA138 gene contained an open reading frame (ORF, 477 bp) encoding a 17 kDa protein. The amino acid sequence deduced from the ORF was composed of 159 amino acid residues and was highly homologous to those from RA genes previously isolated, such as RA5 (92% identity), RA14 (73%), and RA17 (68%). The protein contained 10 cysteine residues that were conserved in the alpha-amylase/trypsin inhibitor family including RA proteins. Excluding a putative signal peptide consisting of 26 amino acid residues, the mature protein would be 14.4 kDa in size and have a pI of 7.0. DNA gel blot analysis under high stringency conditions indicated that multiple copies of the RA138 gene were present in the rice genome. The chromosomal location of the RA138 gene has been identified on chromosome 7 in a segregation analysis using a population of 164 recombinant inbred lines derived from a cross between Milyang 23 and Gihobyeo. The locus that may contain multiple copies of the RA138 was located between RFLP markers RG477A and C492 with genetic distances of 10.7 cM and 6.7 cM, respectively.

Allergens

Upregulation of aquaporin 2 water channel expression in pregnant rats.

Water retention is characteristic of pregnancy but the mechanism(s) of the altered water metabolism has yet to be elucidated. The collecting duct water channel, aquaporin 2 (AQP2), plays a pivotal role in the renal water regulation, and we hypothesized that AQP2 expression could be modified during pregnancy. Sprague-Dawley female rats were studied on days 7 (P7), 14 (P14), and 20 (P20) of pregnancy, and expression of AQP2 in papillae was examined. Nonpregnant (NP) littermates were used as controls. Plasma osmolalities were significantly lower in pregnant rats by day 7 of gestation (P7 283.8+/-1.82, P14 284.3+/-1.64, P < 0.001, P20 282. 4+/-1.32, P < 0.0001, vs. NP 291.8+/-1.06 mosmol/kgH2O). However, plasma vasopressin concentrations in pregnant rats were not significantly different than in nonpregnant rats (NP 1.03+/-0.14, P7 1.11+/-0.21, P14 1.15+/-0.21, P20 1.36+/-0.24 pg/ml, NS). The mRNA of AQP2 was increased early during pregnancy: AQP2/beta actin: P7 196+/-17.9, P14 200+/-6.8, and P20 208+/-15.5%, P < 0.005 vs. NP (100+/-11.1%). AQP2 protein was also increased during pregnancy: AQP2 protein: P7 269+/-10.0, P14 251+/-12.0, P < 0.0001, and P20 250+/-13.6%, P < 0.001 vs. NP (100+/-12.5%). The effect of V2 vasopressin receptor antagonist, OPC-31260, was then investigated. AQP2 mRNA was suppressed significantly by OPC-31260 administration to P14 rats (AQP2/beta actin: P14 with OPC-31260 39.6+/-1.7%, P < 0.001 vs. P14 with vehicle) and was decreased to the same level of expression as NP rats receiving OPC-31260. Similar findings were found with the analysis of AQP2 protein. The decreased plasma osmolality of P14 rats was not modified by OPC-31260. The results of the study indicate that upregulation of AQP2 contributes to the water retention in pregnancy through a V2 receptor-mediated effect. In addition to vasopressin, other factors may be involved in this upregulation.

Actins

Triprimer-PCR method: rapid and reliable detection of transgenes in transgenic rice plants.

We designed a triprimer-PCR system for detection of transgenes and applied for analysis of two different kinds of transgenic rice plants, which were previously transformed with the plasmids pBY605RR or pARP7 containing a maize ribosome-inactivating protein gene, Zmcrip3a, and a herbicide-resistant gene, bar. Genomic Southern-blot analysis demonstrated that the transgenes were stably inherited to their R1 progenies without changes in configuration. The resulting data were used as a reference for triprimer-PCR analysis. The triprimer-PCR system uses an endogenous gene as an internal standard which shares an identical priming site for one primer with a transgene while each of the other two primers is specific to either the transgene or the endogenous gene. Triprimer-PCR analysis was carried out on genomic DNA isolated from 24 different progenies of the pBY605RR- and the pARP7-transformed lines that contain different copy numbers of transgenes. The RbcS:Zmcrip3a junction region of the pBY605RR integrated in rice chromosomes, together with the endogenous RbcS, was efficiently amplified, producing 440 and 250 bp expected PCR products. Also, the Act1:Zmcrip3a junction region of the transgene pARP7 with the endogenous Act1 was similarly amplified, producing 540 and 340 bp expected PCR products. The two PCR products in each set of experiments were observed consistently and independently of copy numbers or rearrangements of the transgene. Thus, the triprimer-PCR strategy may provide a rapid and reliable method for confirming transformation or analyzing segregation of transgenes at the molecular level.

Blotting, Southern

Control of initiation of viral plus strand DNA synthesis by HIV reverse transcriptase.

Human immunodeficiency virus reverse transcribes its single-stranded RNA genome making a DNA copy. As synthesis proceeds, the RNA is simultaneously degraded to oligomers; one of these, the polypurine tract, primes synthesis of a plus strand DNA. The viral reverse transcriptase (RT) degrades all of the non-polypurine tract oligomers. We show that unlike other DNA polymerases the retroviral RT can bind either end of an annealed RNA primer, the 5'-end for degradation and the 3'-end for synthesis. The competition between the two binding modes at any primer determines whether it will be extended or degraded. The 5'-end binding can be suppressed in at least two ways. The sequence of the primer can be such that a region at the 5'-end is unannealed or a DNA primer can be annealed just adjacent to the 5'-end of the RNA primer. This promotes binding of RT to the RNA 3'-end, allowing a primer that would normally be degraded to be extended. Implications for human immunodeficiency virus replication and antiviral therapy are discussed.

Binding Sites

Involvement of hydrogen peroxide in the differentiation of clonal HD-11EM cells into osteoclast-like cells.

The present study uses the osteoclast precursor clonal line, HD-11EM, to study the potential of hydrogen peroxide (H2O2) in mediating the differentiation of HD-11EM into osteoclast-like cells. HD-11EM cells are a newly established clonal cell line that, in response to 1alpha,25-(OH)2D3, differentiate into osteoclast-like cells that are multinucleated (more than three nuclei), express tartrate-resistant acid phosphatase (TRAP), and excavate resorption pits when cultured on dentin slices in the presence of osteoblasts (Hsia et al., 1995, J. Bone Miner. Res., 10(Suppl 1):S424; Hsia, and Hauschka, 1997, unpublished data). Here we demonstrate that HD-11EM express the reduced nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase specific cytochrome b558 subunits, and that stimulation of HD-11EM with 1 or 10 nM 1alpha,25-(OH)2D3 increases the extracellular release of H2O2 within 5-10 min. Ours is the first report that stimulation of a cell with 1alpha,25-(OH)2D3 enhances the activation of NADPH-oxidase and increases the basal release of superoxide and the formation of its dismutation product, H2O2. To determine the possible involvement of H2O2 in the differentiation of HD-11EM, these cells were exposed to glucose/glucose oxidase. This enzyme system was used to deliver a pure and continuous source of H2O2 in nanomole amounts consistent with quantities produced by HD-11EM in response to 1alpha,25-(OH)2D3. Both 1alpha,25-(OH)2D3 and the exogenously generated H2O2 stimulated a dose- and time-dependent increase in TRAP activity/cell and the number of multinucleated cells 24-48 hr after treatment. Northern analysis confirmed an increase in expression of TRAP mRNA in response to either 1alpha,25-(OH)2D3 or H2O2. Decreases in cell proliferation and v-myc mRNA were also observed in response to these agents. Taken together, our findings indicate that production of H2O2 by HD-11EM is an important local factor involved in differentiation of HD-11EM into osteoclast-like cells, and suggest that H2O2 may play a role in native osteoclast differentiation.

Acid Phosphatase

Changes in brain-derived neurotrophic factor immunoreactivity in rat dorsal root ganglia, spinal cord, and gracile nuclei following cut or crush injuries.

In the present study, we evaluated changes in brain-derived neurotrophic factor (BDNF) immunoreactivity in the rat lumbar (L) 5 dorsal root ganglion (DRG) and areas where afferents from the DRG terminate, the L5 spinal cord and gracile nuclei, following unilateral sciatic nerve transection or crush. From 3 days to 4 weeks following cut or crush injury, the percentage of medium and large BDNF-immunoreactive neurons in the ipsilateral DRG increased significantly compared with those on the contralateral side. Following cut injury, there was no significant change in the percentage of small BDNF-immunoreactive neurons in the ipsilateral DRG; however, the intensity of immunoreactivity of these cells decreased. Following crush injury, however, both the percentage and intensity of small BDNF-immunoreactive neurons in the ipsilateral DRG significantly increased. Following cut injury, the expression of BDNF-immunoreactive axonal fibers decreased markedly in the ipsilateral superficial laminae of the L5 spinal cord and increased significantly in the ipsilateral deeper laminae of the spinal cord and gracile nuclei. Crush injury induced a marked increase in the expression of BDNF-immunoreactive axonal fibers in the superficial laminae of the spinal cord and gracile nuclei. These differences in BDNF response in the DRG and spinal cord after cut or crush injuries may reflect differences in trophic support to the injured DRG neurons and altered neuronal activity in the spinal cord and gracile nuclei following different types of peripheral nerve injury.

Animals

Antitumor activity of the aqueous-alcoholic extracts from unripe cotton ball of Gossypium indicum.

The present study investigated the antitumor activity of the aqueous-alcoholic extracts from unripe cotton balls of Gossypium indicum. An Exposure of murine B16 melanoma and L1210 lymphoma cells to the extracts resulted in their severe deaths in time- and concentration-dependent manners. Of the extracts, hydrophilic fractions were most efficacious for the antitumor activity and found to contain certain amounts of catechin and its derivatives. The hydrophilic extract fraction C36B2-8 had approximately 10 times more cytotoxic effects on B12 and L1210 cells than on isolated murine thymocytes. High concentrations (> 150 micrograms/ml) of C 36B3-8 mainly induced necrotic cell death. At low concentrations (< 100 micrograms/ml), however, C 36B3-8 induced not only necrosis but also apoptosis of the two tumor cell lines, which was proved by the TUNEL staining and DNA fragmentation techniques. The data indicate that certain ingredients of the cotton ball extract of G. indicum have an antitumor activity.

Animals

Antitumor activity of 7-[2-(N-isopropylamino)ethyl]-(20S)-camptothecin, CKD602, as a potent DNA topoisomerase I inhibitor.

We developed a novel water-soluble camptothecin analogue, CKD602, and evaluated the inhibition of topoisomerase I and the antitumor activities against mammalian tumor cells and human tumor xenografts. CKD602 was a nanomolar inhibitor of the topoisomerase I enzyme in the cleavable complex assay. CKD602 was found to be 3 times and slightly more potent than topotecan and camptothecin as inhibitors of topoisomerase, respectively. In tumor cell cytotoxicity, CKD602 was more potent than topotecan in 14 out of 26 human cancer cell lines tested, while it was comparable to camptothecin. CKD602 was tested for the in vivo antitumor activity against the human tumor xenograft models. CKD602 was able to induce regression of established HT-29, WIDR and CX-1 colon tumors, LX-1 lung tumor, MX-1 breast tumor and SKOV-3 ovarian tumor as much as 80, 94, 76, 67, 87% and 88%, respectively, with comparable body weight changes to those of topotecan. Also the therapeutic margin (R/Emax: maximum tolerance dose/ED58) of CKD602 was significantly higher than that of topotecan by 4 times. Efficacy was determined at the maximal tolerated dose levels using schedule dependent i.p. administration in mice bearing L1210 leukemia. On a Q4dx4 (every 4 day for 4 doses) schedule, the maximum tolerated dose (MTD) was 25 mg/kg per administration, which caused great weight loss and lethality in < 5% tumor bearing mouse. This schedule brought significant increase in life span (ILS), 212%, with 33% of long-term survivals. The ex vivo antitumor activity of CKD602 was compared with that of topotecan and the mean antitumor index (ATI) values recorded for CKD602 were significantly higher than that noted for topotecan. From these results, CKD602 warrants further clinical investigations as a potent inhibitor of topoisomerase I.

Animals