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Biomedical subjects

K I Kim

Publications and source records attributed to K I Kim.

At least 19 recordsLinked to original sources

Antitumor, genotoxicity and anticlastogenic activities of polysaccharide from Curcuma zedoaria.

The antitumor effect of the partially purified polysaccharide from Curcuma zedoaria was studied in mice transplanted with sarcoma 180 cells. The polysaccharide fraction, CZ-1-III, at dose of 6.25 mg/kg/d showed 50% inhibition in solid tumor growth. When mice were injected with fractions, CZ-1 and CZ-1-III, at the dose of 100.0 mg/kg, 91.6% and 97.1% of tumor growth were inhibited, respectively, indicating that the cytotoxic effect of polysaccharide on sarcoma 180 cells increases upon increasing the amount of polysaccharide administered. To assess the genotoxicity of CZ-1-III fraction, several classical toxicological tests were performed. In Ames test, CZ-1-III did not show any transformation of revertant with or without S-9 metabolic activating system, indicating the lack of mutagenic effect of the compound. To assess clastogenic effect, micronucleus and chromosomal aberration assays were performed using Chinese hamster lung (CHL) fibroblast cells. However, up to 259.0 microg/ml concentration of CZ-1-III, neither micronucleus formation nor chromosomal aberration was induced regardless of the presence of S-9 metabolic activating system. Inhibition of CZ-1-III on micronucleus formation induced by mitomycin C was exhibited in a dose-dependent manner, maximally up to 52.0%. These results strongly suggest that CZ-1-III, the polysaccharide fraction from C. Zedoaria, decreases tumor size of mouse and prevents chromosomal mutation.

Animals↗

A new SUMO-1-specific protease, SUSP1, that is highly expressed in reproductive organs.

A full-length cDNA encoding a SUMO-1-specific protease, named SUSP1, was identified and cloned for the first time from the human brain. Nucleotide sequence analysis of the cDNA containing an open reading frame of 3336 base pairs revealed that the protease consists of 1112 amino acids with a calculated molecular mass of 126,116 Da. Like yeast Ulp1, SUSP1 is a cysteine protease containing the well conserved His/Asp/Cys catalytic triad. SUSP1 expressed in Escherichia coli cells efficiently released SUMO-1 from SUMO-1. beta-galactosidase fusion but not from other ubiquitin-like protein fusions, including Smt3.beta-galactosidase, suggesting its role in the generation of matured SUMO-1 specifically from its precursors. Interestingly, reproductive organs, such as testis, ovary, and prostate, contained much higher amounts of SUSP1 mRNA than colon and peripheral blood leukocyte, whereas other tissues, such as heart and spleen, had little or none. In addition, confocal microscopy using green fluorescent protein.SUSP1 fusion showed that SUSP1 is exclusively localized to the cytoplasm of NIH3T3 and HeLa cells. These results suggest that SUSP1 may play a role in the regulation of SUMO-1-mediated cellular processes particularly related to reproduction.

Amino Acid Sequence↗

Synergistic effect of angiotensin-converting enzyme and angiotensinogen gene on cardiac hypertrophy.

AIMS: There are controversies concerning the association of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism with left ventricular hypertrophy (LVH), and the unclear association between angiotensinogen (ATG) M235T polymorphism and LVH. We investigated both the separate and interactive effects of these two genes on LVH in patients (N=396) with cardiovascular disease and normal healthy volunteers (N=133). RESULTS: Frequency of DD genotype of ACE gene was significantly (P<0.05) higher in patients with LVH than patients without LVH or normal controls. Frequency of IT genotype of ATG gene in patients with LVH was significantly (P<0.01) greater than that in normal controls or marginally (P=0.1) higher than that in patients without LVH. These findings were also observed in normotensive patients and normal controls after excluding hypertensive patients. Only in patient group, the frequency of DD genotype in the highest quartile of LVMI was significantly greater than that in the lowest quartile (P<0.05). The higher tendency of TT genotype in the highest quartile patients compared with that in the lowest, did not reach statistical significance. In combined genotype analysis, there was a remarkable difference in LVMI between the two extreme double homozygotes only in patient group (156+/-25 versus 109+/-25 g/m2 for TT+DD versus MM+II) (P<0.01). In ANCOVA, the interaction term composed of ACE and ATG genotype was a significant independent variable for LVMI only in the male patient group (P<0.01). CONCLUSION: The D-allele of ACE and T-allele of ATG gene exert a synergistic effect on cardiac hypertrophy in male patients with cardiovascular diseases, but not in normal healthy population.

Adult↗

Ruptured giant intrathoracic lipoblastoma in a 4-month-old infant: CT and MR findings.

BACKGROUND: We describe a 4-month-old infant with a ruptured intrathoracic lipoblastoma arising from the parietal pleura and associated with a pleural effusion. OBJECTIVE: The clinical presentation was rapidly evolving respiratory distress. The chest radiograph showed a large mass and a pleural effusion in the right thoracic cavity. CT demonstrated an inhomogeneous low-attenuation mass which was 7 cm in diameter and which showed areas of enhancement after intravenous contrast medium. MRI showed a fatty intrathoracic mass with intratumoral streaks and whorls, which were attributed to loose fibrovascular connective tissue on pathological examination. RESULTS: Thoracotomy and pathological examination revealed a ruptured intrathoracic lipoblastoma arising from the parietal pleura. CONCLUSION: The pleural effusion might have suggested rupture of the tumour.

Female↗

beta-catenin expression and mutational analysis in renal cell carcinomas.

beta-Catenin acts as a downstream transcriptional activator of the Wingless-Wnt signaling pathway. The beta-catenin-Tcf complex transactivates the downstream genes that regulate cell proliferation or inhibit apoptosis. The activation of this pathway through stabilization of beta-catenin is caused either by inactivating mutations of adenomatous polyposis coli (APC) tumor suppressor gene or by activating mutations in beta-catenin exon 3. To determine whether the abnormal expression and activating mutations in exon 3 of the beta-catenin gene are implicated in renal cell carcinogenesis, 52 renal cell carcinomas (RCC) were analyzed by immunohistochemistry, polymerase chain reaction-single-strand conformational polymorphism analysis (PCR-SSCP), and direct DNA sequencing. Immunohistochemically, all cases, as well as normal kidneys, showed membranous and/or cytoplasmic staining patterns without nuclear localization. However, the cytoplasmic accumulations of beta-catenin were observed in five (22.7%) of 22 cases of conventional (clear cell) renal carcinoma, but not in papillary or chromophobe renal carcinomas. The beta-catenin mutation was identified in only one case of conventional renal carcinoma and was a single-base missense mutation on codon 61, leading to substitution of glutamine by arginine. In conclusion, this study demonstrates that beta-catenin mutations are a relatively rare event in RCC and that cytoplasmic accumulations of beta-catenin protein are found only in conventional (clear cell) renal carcinomas. These data suggest that the activation of the beta-catenin signaling pathway may partly play a role in the development of conventional RCC.

Adenocarcinoma↗

TTV positivity and transfusion history in non-B, non-C hepatocellular carcinoma compared with HBV- and HCV-positive cases.

The prevalence of TT virus (TTV) and its rate of transmission through transfusion were investigated to determine its possible hepatocarcinogenic role in non-B, non-C hepatocellular carcinoma (HCC) as compared with that in hepatitis B virus (HBV)- and hepatitis C virus (HCV)-positive HCC. Its transfection route in TTV-positive cases was also studied. Serum was positive for TTV in 77.8% (7/9) of HBV-positive, 36.4% (12/33) of HCV-positive, and 63. 6% (7/11) of non-B, non-C cases of HCC. The rate of transmission through transfusion was 52.4% (11/21) in HBV-positive, 40.1% (61/152) in HCV-positive, 33.3% (2/6) in HBV+HCV-positive, and 40% (8/20) in non-B, non-C HCCs, while it was 48.3% (14/29) in TTV-positive and 39.3% (11/28) in TTV-negative cases. The association between TTV and HCC was limited, and the main route of infection of TTV was not through transfusion.

Adult↗

Selective degradation of unfolded proteins by the self-compartmentalizing HtrA protease, a periplasmic heat shock protein in Escherichia coli.

HtrA, which has a high molecular mass of about 500 kDa, is a periplasmic heat shock protein whose proteolytic activity is essential for the survival of Escherichia coli at high temperatures. To determine the structural organization of HtrA, we have used electron microscopy and chemical cross-linking analysis. The averaged image of HtrA with end-on orientation revealed a six-membered, ring-shaped structure with a central cavity, and its side-on view showed a two-layered structure. Thus, HtrA behaves as a dodecamer consisting of two stacks of hexameric ring. HtrA can degrade thermally unfolded citrate synthase and malate dehydrogenase but cannot when in their native form. HtrA degraded partially unfolded casein more rapidly upon increasing the incubation temperature. However, it hydrolyzed oxidized insulin B-chain, which is fully unfolded, at nearly the same rate at all of the temperatures tested. HtrA also rapidly degraded reduced insulin B-chain generated by treatment of insulin with dithiothreitol but not A-chain or intact insulin. Moreover, HtrA degraded fully unfolded alpha-lactalbumin, of which all four disulfide bonds were reduced, but not the native alpha-lactalbumin and its unfolded intermediates containing two or three disulfide bonds. These results indicate that unfolding of the protein substrates, such as by exposure to high temperatures or reduction of disulfide bonds, is essential for their access into the inner chamber of the double ring-shaped HtrA, where cleavage of peptide bonds may occur. Thus, HtrA with a self-compartmentalizing structure may play an important role in elimination of unfolded proteins in the periplasm of Escherichia coli.

Amino Acid Sequence↗

The detection of Epstein-Barr virus in the lesions of salivary glands.

Epstein-Barr virus (EBV) is known in association with lymphoid and epithelial lesion. Because the salivary gland is an organ close to the oropharynx, it has a higher incidence of EBV infection and is a possible route of EBV infection. Formalin-fixed, paraffin embedded tissue sections of 87 cases of salivary gland diseases were used for the study of EBV with PCR, in situ PCR for EBNA-1 (EBV nuclear antigen-1), and immunohistochemistry for LMP-1 (latent membrane protein-1). EBV was detected in 12 cases (13.8%): 7 of nonspecific chronic sialadenitis (21.2%), 4 of Warthin's tumors (30.8%), and one lymphoepithelial carcinoma. EBNA-1 was negative in all the other lesions. EBV DNA was detected in the nucleus of epithelial cells and the surrounding lymphocytes. LMP-1 positivity was found in the cytoplasm of epithelial cells. The results of the present study showed that EBV is implicated in some of the inflammatory and neoplastic lesions of the salivary gland in which the lymphocytes are abundant. However, the pathogenesis and mechanism of immortalization and tumorigenesis of the epithelial cells in the salivary glands remain to be determined.

Epstein-Barr Virus Nuclear Antigens↗

Effect of site and rate of contrast material injection on pulmonary vascular distention.

RATIONALE AND OBJECTIVES: The authors performed this study to determine if there were differences in vascular caliber measured on angiograms obtained with the injection protocol used for spiral computed tomography (CT) versus that used for pulmonary angiography. MATERIALS AND METHODS: The authors studied seven juvenile anesthetized pigs by using a prospective repeated measures experimental design. All pigs received injections of nonionic contrast material via catheters in the brachial vein, superior vena cava, main pulmonary artery, and left pulmonary artery. Weight-adjusted injection rates and volumes ranged from 0.05 mL/kg/sec (3.5 mL/sec, spiral CT protocol) to 0.56 mL/kg/sec (40 mL/sec, pulmonary angiography protocol). Heart rate and pulmonary artery and systemic artery pressures were recorded. During each injection, identically positioned pulmonary angiograms were obtained at full inspiration. Vessel diameters were measured at identical locations after each injection by two observers. The relationship between vessel diameter and hemodynamic parameters and injection site and rate was assessed with analysis of variance. RESULTS: At suspended full inspiration, no statistically significant difference (P > .05) in vessel diameter or hemodynamic parameters was found between the different injection sites or rates. There was no difference in vascular caliber between systole and diastole. CONCLUSION: The improved detection of subsegmental pulmonary emboli at pulmonary angiography compared with contrast material-enhanced spiral CT is not due to differences in vascular distention.

Angiography↗

Phylogenetic relationships of Cheju horses to other horse breeds as determined by mtDNA D-loop sequence polymorphism.

Historical records suggest that horses inhabiting the island of Cheju in Korea are descendants of Mongolian horses introduced in 1276. Other studies, however, suggest that horses may have been present on the island prior to the Mongolian introduction. To determine the origin of the Cheju horses we used a phylogenetic analysis of sequences of the mitochondrial DNA (mtDNA) D-loop region, including tRNA Pro and parts of tRNA thr and tRNA Phe sequences (1102-bp excluding the tandem repeat region). Maximum parsimony and neighbor-joining trees were constructed using sequences determined for seven Cheju, four Mongolian, one Przewalskii and two Chinese Yunnan horses, and published sequences for one Swedish and three Thoroughbred horses. Donkey mtDNA was used as an outgroup. We found that the mtDNA D-loop sequence varies considerably within Mongolian, Cheju and Thoroughbred horse breeds, and that Cheju horses clustered with Mongolian horses as well as with horses from other distantly related breeds. On the basis of these findings we propose that horses on Cheju Island are of mixed origin in their maternal lineage, and that horses may have existed and been traded on the island before the Mongolian introduction.

Animals↗

Inflammatory pseudotumor of the liver in a patient with chronic hepatitis C: difficulty in differentiating it from hepatocellular carcinoma.

A case of an inflammatory pseudotumor of the liver in a 75-year-old female with chronic hepatitis C whose radiologic features simulated that of hepatocellular carcinoma (HCC) is presented. On imaging studies, hypervascularity by CO2 ultrasound (US) angiography, enhancement at an early phase and isodensity at a late phase by incremental dynamic computed tomography (CT), perfusion defect by CT during arteriography (CTAP), and clinical background of hepatitis C virus (HCV) infection strongly suggested HCC. A US-guided needle biopsy revealed a mainly diffuse and polyclonal proliferation of lymphocytes positive for leukocyte common antigen (pan-lymphocyte cells), L-26 (B cell lymphocytes), and UCHL-1 (T cell lymphocytes), negative for both kappa and lambda light chains and sparsely distributed neutrophils and histiocytes. No lymphoid follicles were observed. The liver tissue around this tumor showed chronic hepatitis with mild activity and mild fibrosis. These histopathologic findings suggested that the diagnosis of inflammatory pseudotumor of the liver was tenable. As it is difficult to differentiate between inflammatory pseudotumor of the liver and HCC by imaging studies alone, supplemental biopsy, where possible, should be obtained when diagnostic imaging of tumors suggesting HCC is carried out. We emphasize that histopathology is a true gold standard in the diagnosis of this disease.

Aged↗

Clinically suspected pulmonary embolism: utility of spiral CT.

PURPOSE: To prospectively determine the utility of contrast material-enhanced spiral computed tomography (CT) in the examination of patients clinically suspected of having pulmonary embolism (PE). MATERIALS AND METHODS: One hundred ten patients clinically suspected of having PE were examined with contrast-enhanced spinal CT and at least one other imaging modality: ventilation-perfusion scintigraphy, Doppler ultrasonography of deep leg veins, or pulmonary angiography. Chart review or telephone contact with the referring clinician was used to evaluate the contribution of spiral CT to the final clinical diagnosis. RESULTS: Spiral CT helped correctly identify 23 of 25 patients with PE (sensitivity, 92%). In 57 (67%) of the 85 patients without PE, spiral CT provided additional information that suggested or confirmed the alternate clinical diagnosis: pneumonia (n = 14), cardiovascular disease (n = 10), pulmonary fibrosis (n = 7), trauma (n = 6), malignancy (n = 5), pleural disease (n = 4), postoperative changes (n = 4), and other (n = 7). In the remaining 28 patients, spiral CT scans were normal (n = 12), failed to produce findings supportive of the final clinical diagnosis (n = 13), or were false-positive for PE (n = 3; specificity, 96%). CONCLUSION: Spiral CT has good sensitivity and specificity for the diagnosis of PE. In the majority of patients who do not have PE, it also provides important ancillary information for the final diagnosis.

Adolescent↗

A novel family of ubiquitin-specific proteases in chick skeletal muscle with distinct N- and C-terminal extensions.

We have recently identified a cDNA for a ubiquitin-specific protease (UBP), UBP41, that encodes the smallest functional UBP identified to date, using an Escherichia coli-based in vivo screening method. In the present study we isolated highly related cDNAs encoding a new family of UBP enzymes, named UBP46, UBP52 and UBP66. These UBPs have virtually identical catalytic domains spanning the sequence of UBP41 between the active-site Cys and the His box (95% identity). However, they possess distinct N- and/or C-terminal extensions. Moreover, they are more closely related to each other than to any other members of the UBP family. Thus these chick UBPs must define a novel family of de-ubiquitinating enzymes and should represent the first example among the UBP family enzymes, whose multiplicity is achieved by variation in their N- and C-terminal extensions. The chick UBPs were expressed in E. coli, and purified from the cells to apparent homogeneity using 125I-labelled ubiquitin-alphaNH-MHISPPEPESEEEEEHYC as a substrate. Each of the purified UBP46, UBP52 and UBP66 enzymes behaved as proteins of similar sizes under both denaturing and non-denaturing conditions, suggesting that all of them consist of a single polypeptide chain. The UBP enzymes cleaved the C-terminus of the ubiquitin moiety in natural and engineered fusions irrespective of their sizes and thus are active against ubiquitin-beta-galactosidase as well as a ubiquitin C-terminal extension protein of 80 amino acids. All UBPs except UBP66 released free ubiquitin from poly-His-tagged di-ubiquitin. However, the isopeptidase activity for hydrolysing polyubiquitinated lysozyme conjugates was not detected from these UBPs, which makes these UBPs distinct from UBP41. These results suggest that the chick UBPs may play an important role in production of free ubiquitin from linear polyubiquitin chains and of certain ribosomal proteins from ubiquitin fusion proteins.

Amino Acid Sequence↗

Mutational analysis of the two ATP-binding sites in ClpB, a heat shock protein with protein-activated ATPase activity in Escherichia coli.

The 93 kDa ClpB (ClpB93) is a heat shock protein and has a protein-activated ATPase activity. To define the role of the two ATP-binding sites in ClpB93, site-directed mutagenesis was performed to replace Lys212 or Lys611 with Thr or Glu. All of the mutant proteins hydrolysed ATP at a higher rate than that seen with ClpB93 at ATP concentrations up to 2 mM. However, ClpB93 carrying mutations in both of the ATP-binding sites could not cleave ATP. Thus any of the two ATP-binding sites seems to be capable of supporting the ATPase activity of ClpB93. The ATPase activities of both ClpB93/K212T and ClpB93/K212E were gradually decreased when ATP concentrations were increased above 2 mM, unlike those of ClpB93, ClpB93/K611T and ClpB93/K611E, which showed a typical saturation curve. Furthermore ADP inhibited ATP hydrolysis by ClpB93/K212T and ClpB93/K212E more effectively than that by the latter proteins, suggesting that the mutations in the first ATP-binding site result in an increase in the affinity of ADP for the second site in ClpB93. In addition, all of the purified ClpB93 and its mutant forms behaved as an oligomer of 400-450 kDa on a Sephacryl S-300 gel-filtration column, whether or not ATP was present. Thus the binding of ATP to either of the two sites seems not to be essential for oligomerization of ClpB93. Although a low-copy plasmid carrying clpB93 could rescue the sensitivity of a clpB-null mutant cell at 52 degreesC, none of the plasmids carrying the mutations in the ATP-binding sites could. Furthermore, incubation at 52 degreesC resulted in a gradual loss of the ATPase activity of ClpB93 carrying the mutations in either of the two ATP-binding sites, but not of the parental ClpB93, indicating that the mutant proteins have a greater tendency to denature at this temperature than the parental ClpB93. These results suggest that both of the ATP-binding sites in ClpB have an important role in maintaining the thermotolerance of the protein and hence in the survival of Escherichia coli at high temperatures.

Adenosine Triphosphatases↗

Pulmonary tuberculosis in five young infants with nursery exposure: clinical, radiographic and CT findings.

Clinical, radiographic (n = 5) and CT findings (n = 4) of five Korean infants ranging in age from 2 to 3 months with confirmed tuberculosis were retrospectively analysed. All of the patients were symptomatic, anergic to tuberculin, and had a positive culture of Mycobacterium tuberculosis in gastric aspirates. The probable source of infection was the hospital in which they were born. CT scans demonstrated hilar and mediastinal lymph node enlargement with central low attenuation and peripheral enhancement in all cases. CT may be useful in diagnosis by demonstrating characteristic adenopathy and disseminated disease in young infants.

Cross Infection↗

Feeding diets containing high levels of milk products or cellulose decrease urease activity and ammonia production in rat intestine.

Three studies were done to determine the effect of feeding diets containing high levels of a readily fermentable carbohydrate (lactose in milk or yogurt, or pure lactose) or an undigestible, unfermentable diluent (alpha-cellulose) on urease (EC 3.5.1.5) activity and net ammonia production in the rat gastrointestinal (GI) contents. Rats (170-200 g) were fed a control diet or diets containing 55% dried milk or 55% dried yogurt, 25% lactose or 10% alpha-cellulose. Feeding diets containing milk or yogurt decreased urease activity to approximately 11% of the control value in the small intestine (on the basis of grams of collected contents or total contents), and to 50% in the large intestine (only on the basis of grams of collected contents). Feeding the diet containing 25% lactose also decreased urease activity (on the basis of grams of collected contents or total contents) to about 20% of the control value in the small intestine, but not (P > 0.05) in the large intestine. Net ammonia production rate was correlated (r2 = 0.98) with urease activity in the large intestinal contents, and the rate of ammonia production from ureolysis represented about two thirds of the total. Feeding the cellulose diet decreased (P < 0.05) both urease activity and net ammonia production in the large intestine to approximately 30% of the control value. Weights of tissue and contents of the large intestine were much higher (P < 0.01) in rats fed diets containing milk products or lactose than in the control rats, but were not affected by consumption of the cellulose diet. Results of our studies indicate that feeding diets containing high levels of milk products (lactose) or cellulose reduces urease activity and net ammonia production in the rat intestine, and thus may be beneficial for improving animal and human health.

Ammonia↗

A case of well-differentiated minute hepatocellular carcinoma with extrahepatic metastasis.

A rare case of well-differentiated minute hepatocellular carcinoma (HCC) metastasizing to distant sites in a 77-year-old man with hepatitis C virus (HCV)-related cirrhosis is presented. Ultrasonography (US) disclosed a 9 mm hypoechoic lesion in segment seven (S7) of the liver, although computed tomography (CT), magnetic resonance imaging (MRI) and angiography did not reveal any space-occupying lesion. Ultrasound-guided biopsy showed the histological features of well-differentiated HCC. A plain film of the abdomen and CT revealed osteolytic changes in the sacrum and the lumbar vertebra. Ultrasound-guided biopsy of the sacrum revealed well-to-moderately differentiated HCC metastasizing from the liver. Percutaneous ethanol injection therapy (PEIT) effected complete response and completely eliminated the abnormal findings on US. Three months after PEIT, metastasis to the thoracic vertebra was revealed by CT, despite negative alpha-fetoprotein-mRNA in serum. This is the first report describing a well-differentiated HCC with metastatic potential. Further studies may provide insights into metastasis of well-differentiated HCC.

Aged↗