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Biomedical subjects

H K Kim

Publications and source records attributed to H K Kim.

At least 127 records · Page 7Linked to original sources
PubMed2000

Changes of plasma tissue factor and tissue factor pathway inhibitor antigen levels and induction of tissue factor expression on the monocytes in coronary artery disease.

BACKGROUND: Several studies have shown that thrombosis and inflammation play an important role in the pathogenesis of coronary artery disease (CAD). Tissue factor (TF) is responsible for the thrombogenicity of the atherosclerotic plaque and plays a key in triggering thrombin generation. The aim of this study was to assess the levels of TF and tissue factor pathway inhibitor (TFPI) in patients with angiographically documented CAD and also to evaluate TF induction on monocytes in vitro in the presence of these plasmas from patients with CAD. METHODS: Plasma antigen levels of soluble TF and TFPI were measured in 65 CAD patients and 22 healthy controls. Surface TF expression on monocytes from a healthy donor treated with plasma samples was evaluated by flow cytometry with a direct double-color immunofluorescence technique. RESULTS: Significantly elevated levels of both TF and TFPI were found in CAD patients compared with healthy controls (303.6 +/- 134.1 vs. 187.3 +/- 108.7 pg/ml, p < 0.05; 85.2 +/- 48.6 vs. 65.0 +/- 29.0 ng/ml, p < 0.05). By flow cytometry, monocytes from a healthy donor displayed higher TF antigen expression when incubated in the presence of CAD plasmas than in control plasmas (34.6 +/- 10.7 vs. 23.2 +/- 10.2%, p < 0.05). CONCLUSIONS: The high levels of circulating TF are present in CAD, which were not sufficiently inhibited by the elevated TFPI plasma levels. Although the source of circulating TF is unclear, TF induction of monocytes by plasma from CAD patients may contribute to the hypercoagulable state.

Adult↗
PubMed2000

Expression of functional markers in acute nonlymphoblastic leukemia.

Multidrug resistance parameters, tissue infiltration parameters, receptors for colony-stimulating factors (CSFr) and cell cycle parameters were analyzed using flow cytometry in 145, 109 initial and 36 relapsed or refractory, acute nonlymphoblastic leukemia (ANLL) patients to find out clinically more reliable functional parameters. Lung resistance-associated protein (LRP) was most frequently expressed in ANLL (44.1%) followed by P-glycoprotein (PGP) (35.9%) and multidrug resistance-associated protein (MRP) (8.3%). LRP and PGP were expressed more frequently in relapsed or refractory ANLL than initial ANLL cases. Complete remission rate after standard chemotherapy falls in PGP-positive cases (p = 0.001). CD44-positive ANLL cases relapsed more frequently. The organ tropism is different depending on the infiltration parameters, vascular cell adhesion molecule to splenomegaly, matrix metalloprotease-2 to hepatomegaly and to extramedullary infiltration other than spleen, liver or lymph node. The percentage of the granulocyte-macrophage-CSFr expression was high in M4 and M5, and granulocyte-CSFr-positive ANLL showed less extramedullary infiltration (p = 0.007) and more PGP expression. Ki-67 was expressed significantly less in refractory ANLL than initial ANLL and DNA topisomerase IIalpha was expressed significantly more in the surviving patients group. In conclusion, analysis of these new functional parameters could help to predict and overcome the clinical behavior of each ANLL at the time of diagnosis.

Adolescent↗
PubMed2000

Allium sativum potentiates suicide gene therapy for murine transitional cell carcinoma.

This study evaluated the synergistic effect of Allium sativum (AS) with suicide gene therapy for transitional cell carcinoma (TCC) of the bladder. Subcutaneous TCCs were established in syngeneic C3H/He mice with 1 x 10(5) MBT-2 cells. AS liquid extract was injected at the site of tumor transplantation on Day 1 for three weeks (Experiment I) and into the established tumors weekly for five weeks (Experiment II) in combination with or without gene therapy using a replication-defective adenoviral vector containing a herpes simplex virus thymidine kinase (HSV-TK) gene under the transcriptional control of Rous sarcoma virus (RSV) promoter (Ad-RSV-TK, 5 x 10(8) plaque-forming units) plus ganciclovir (20 mg/kg/day i.p.). AS demonstrated a statistically significant reduction in incidence of TCC (cumulative dose 25 mg of AS). Combination AS-suicide gene therapy significantly inhibited the tumor growth compared with the controls, which was evidenced by apoptosis on histomorphological and immunohistochemical studies. These results suggest that AS had a definite antitumor effect in inhibiting tumorigenesis and growth of TCC in a murine model. AS treatment combined with suicide gene therapy had significant additive antitumor effects on TCC and may provide a novel and effective treatment modality for TCC of the bladder.

Adenoviridae↗
PubMed2000

Cloning and expression of the ccpA gene encoding catabolite control protein from Thermoactinomyces sp. E79.

The gene ccpA encoding the catabolite control protein A (CcpA) of Thermoactinomyces sp. E79 has been cloned and characterized. Nucleotide sequence analysis of the CcpA clone showed that the cloned fragment contained the full structural gene for a protein of 346 amino acids. The predicted amino acid sequence shows similarity to the transcriptional regulators of the Lacl-GalR family; a highly conserved helix-turn-helix motif, which might bind to DNA, was identified through comparison with regulator proteins in this family. The highest sequence identity was obtained when it was compared with the CcpA of Bacillus subtilis (60%) or Bacillus megaterium (60%). The expression of ccpA in Thermoactinomyces sp. E79 was dependent on glucose, which is contrast to the cases of B. subtilis, B. megaterium and S. xylosus. The complementation experiment with the B. megaterium ccpA mutant indicated that the cloned gene was a ccpA.

Amino Acid Sequence↗
PubMed2000

Thermostable lipase of Bacillus Stearothermophilus: high-level production, purification, and calcium-dependent thermostability.

An efficient expression system was developed for the production of the thermostable lipase from Bacillus stearothermophilus L1 in an Escherichia coli system. A structural gene corresponding to mature lipase was subcloned in the pET-22b(+) expression vector and its expression was induced by IPTG at 30 degrees C in E. coli cells. The lipase activity in a cell-free extract was as high as 448,000 units/g protein, which corresponds to as much as 26% of the total cellular protein and is 77 times higher than that of E. coli RR1/pLIP1. Based on its pI (7.4) and pH stability data reported previously, the L1 lipase was efficiently purified to homogeneity with CM (at pH 6.0) and DEAE (at pH 8.8) column chromatographies with a recovery yield of 62%. The specific activity of the purified enzyme was 1700 units/mg protein when olive oil emulsion was used as a substrate. Its optimum temperature for the hydrolysis of olive oil was 68 degrees C and it was stable up to 55 degrees C for 30 min-incubation. The thermostability increased by about 8-10 degrees in the presence of calcium ions. This calcium-dependent thermostability was confirmed by the tryptophan fluorescence emission kinetics showing that the enzyme starts to unfold at 66 degrees C in the presence of calcium ions but at 58 degrees C in the absence of calcium ions, implying that the calcium ions bind to the thermostable enzyme and stabilize the protein tertiary structure even at such high temperatures.

Base Sequence↗
PubMed2000

Proteoglycan synthesis in porcine nasal cartilage grafts following Nd:YAG (lambda = 1.32 microns) laser-mediated reshaping.

Mechanically deformed morphologic cartilage grafts undergo temperature-dependent stress relaxation during sustained laser irradiation resulting in stable shape changes. In this study, porcine nasal septal cartilage specimens were evaluated for viability by measuring the incorporation of Na2(35)SO4 into proteoglycan (PTG) macromolecules in whole tissue culture following laser-mediated reshaping. Synthesis rates of PTG were determined by scintillation counting lyophilized specimens and normalizing these values by total protein content. Positive controls were established by inducing chondrocyte apoptosis using prolonged exposure to nitric oxide (NO). In chondrocytes, apoptosis induced using NO resulted in significantly lower PTG synthesis rates compared to untreated native specimens. Cartilage specimens were irradiated with light emitted from a Nd:YAG laser (25 W/cm2, lambda = 1.32 microns) while recording simultaneously radiometric surface temperature, internal stress and back-scattered light intensity from a probe laser. Each specimen received one, two or three sequential laser exposures. The duration of each exposure was determined from real-time measurements of characteristic changes in back-scattered light intensity that correlate with accelerated stress relaxation. A 5 min time interval between each laser exposures allowed the cartilage specimen to return to thermal equilibrium. Average PTG synthesis rates decreased with successive laser exposures, though these were always higher than baseline rates established for NO-treated tissues, suggesting that laser-mediated cartilage reshaping acutely does not eliminate the entire population of viable chondrocytes. The reduction in PTG synthesis is correlated with the time-temperature-dependent heating profile created during laser irradiation, supporting our hypothesis that careful monitoring of laser dosimetry is required to ensure chondrocyte viability.

Animals↗
PubMed2000

Feeder vessel laser photocoagulation of subfoveal choroidal neovascularization.

We performed laser photocoagulation for extrafoveal feeder vessels in a series of 10 eyes with subfoveal choroidal neovascular membranes (CNVMs) in which feeder vessels could be detected by means of indocyanine green angiography using scanning laser ophthalmoscope. On the follow up indocyanine green angiograms performed within one week after treatment, successful occlusion of the feeder vessels with nonperfusion of the corresponding CNVMs was observed in 8 eyes (80%). Four eyes showed improved visual acuities with resolution of the exudative manifestation. But within 3 months, recanalization of the feeder vessels or further proliferation of the CNVMs developed in 7 eyes. We confirmed the possibility of infarction and regression of the CNVM by feeder vessel photocoagulation, which could improve the visual acuity. But it was rarely possible to maintain them.

Aged↗
PubMed2000

Potentials and limitations of adenovirus-p53 gene therapy for brain tumors.

We investigated the antineoplastic potentials of recombinant adenovirus containing wild-type p53 cDNA (Ad5CMV-p53) for malignant gliomas. In four human glioma cell lines (U-251 and LG expressing endogenous mutant p53, and U-87 and EFC-2 expressing wild-type p53) and two rat glioma cell lines (9L and C6, each expressing mutant and wild-type p53), gene transfer efficiency determined by X-gal staining and Western blotting was varied (10-99% at 10-500 multiplicity of infection, MOI). Growth inhibitory effect was drastic (>90% at 100 MOI) in U-251 cells and only moderate or minimal in other cell lines harboring wild-type p53 or low gene transfer efficiency. Ex vivo transduction of U-251 cells with Ad5CMV-p53 suppressed the in vivo tumorigenicity of the cells. Histopathologic examination for Ad5CMV-p53 toxicity to rat brains showed inflammatory reactions in half of the tested brains at 10(8) MOI. U-251 cells were inoculated intracerebrally in nude mice and injected Ad5CMV-p53 into the tumor, in which neither the tumor suppression nor the survival benefit was observed. In conclusion, heterogeneity of the cellular subpopulations of malignant glioma in p53 status, variable and insufficient gene delivery to tumor, and adenoviral toxicity to brain at higher doses may be limiting factors to be solved in developing adenovirus-p53 gene therapy for malignant gliomas.

Adenoviruses, Human↗
PubMed2000

Expression of osteopontin in calcified coronary atherosclerotic plaques.

Advanced atherosclerosis is often associated with dystrophic calcification and remodeling of extracellular matrix of vascular wall. Recently many studies have documented a general relationship between calcification and severity of coronary disease, and discussed the feasibility of electron beam computed tomography for detecting and quantifying the coronary artery calcification in the patients. The present study investigated the expression and the localization of osteopontin, one of noncollagenous bone matrix protein, within the calcified coronary arteries. Autopsy-derived coronary artery specimens were scanned and reconstructed to visualize the pattern of coronary calcification using a novel microscopic computed tomography technique. The localization of the osteopontin were evaluated by immunohistochemial stain with LF7. The present study showed that the pattern of coronary calcification is variable and the expression of osteopontin is localized mainly to calcified lesion. The smooth muscle cells in addition to macrophage expressed osteopontin protein in human coronary atherosclerotic plaques. Soluble osteopontin released near to the sites of vascular calcification may represent an adaptive mechanism aimed at regulating the process of vascular calcification.

Aged↗
PubMed2000

Intraoperative radiation therapy as an adjunctive therapy for huge and highly vascular parasagittal meningiomas.

This case presents a 34-year-old man who had a huge parasagittal meningioma. Initial treatment consisted of preoperative external carotid artery embolization and partial tumor resection. During the resection, we found that the tumor invaded the adjacent calvarium, and due to massive hemorrhage, total removal of the tumor was impossible. The patient was treated with intraoperative radiation therapy (IORT) (25 Gy via 16 MeV) as an adjunctive therapy. Eight months after IORT, we were able to remove the tumor completely without surgical difficulties. IORT can be considered an useful adjunctive therapy for the superficially located, huge, and highly vascular meningioma.

Adult↗
PubMed2000

Coexpression of cyclooxygenase-2 and matrix metalloproteinases in human aortic atherosclerotic lesions.

Inflammation appears to have a major role in the development of atherosclerosis. Cyclooxygenase-2 (COX-2) is involved in the inflammatory response via the generation of prostanoids that, in turn, are involved in the production of matrix metalloproteinases (MMPs). This study aimed to investigate atherosclerosis in human aortas for in situ tissue distribution of COX-2, MMPs including MMP-9 and membrane type 1 MMP (MT1-MMP), and tissue inhibitor of metalloproteinase-2 (TIMP-2). Immunohistochemical studies were performed on atherosclerotic lesions of aortas from patients with aortic aneurysms (n = 4) and dissections (n = 3) by using antibodies to COX-2, MMP-9, MT1-MMP, and TIMP-2. Control tissues were obtained from traumatically dissected aortas (n = 2). All specimens from diseased aortas had atherosclerotic lesions ranging from fatty streak to atheromatous plaques. In control, there was no expression of COX-2, MMP-9, and MT1-MMP in all aortic layers. Immunoreactivity for COX-2 was predominantly noted in macrophages and smooth muscle cells (SMCs) of the intima including atherosclerotic plaque itself and the medial layer of the plaque base, as well as in SMCs and endothelial lining of the vasa vasorum in the adventitia. Immunoreactivity for MMP-9 and MT1-MMP was found in the same distribution as that of COX-2. Additionally, the expression of TIMP-2 increased in relation to MMP-9 expression. This study demonstrates that COX-2 is coexpressed with MMP-9 and MT1-MMP, not only by macrophages and SMCs in atherosclerotic lesions, but also in endothelial lining of the vasa vasorum of human aortas. Thus, vascular inflammatory reactions may influence extracellular matrix remodeling by coactivation of MMPs in the development of atherosclerosis and, in turn, the progression of disease.

Animals↗
PubMed2000

Mesenchymal hamartomas of the chest wall in infancy: radiologic and pathologic correlation.

Mesenchymal hamartoma of the chest wall is a rare tumor with about 53 reported cases in the English literature. We reviewed six chest wall mesenchymal hamartomas in four patients, including two cases with multiple lesions, with specific focus on the radiologic and pathologic correlation. All cases occurred in neonates or infants with ages ranging from seven hours to seven months. They were diagnosed with plain chest radiographs (n=6), ultrasonography (n=2), chest CT scan (n=6), whole body bone scan (n=2) and MRI (n=3). All cases except a small one without cystic change showed the typical features of mesenchymal hamartoma radiographically and pathologically. Radiologically they were well-circumscribed masses with solid and cystic components with multiple fluid-fluid levels in association with single or multiple rib destruction or change. The CT scan showed the typical findings of chest wall hamartoma, and the MR showed heterogeneous signal intensities of the mass on T1- and T2-weighted images. The MR also revealed more concisely a secondary aneurysmal bone cyst formation with multiple fluid-fluid levels on the T2-weighted image. Microscopically, they showed alternating areas of cartilaginous islands and primitive appearing mesenchymal proliferation, which corresponded well with the solid component on the radiologic findings. The areas of bone formation and blood-filled cystic spaces matched the calcified or ossified densities and the cystic components, respectively. A small case without cystic change showed peculiar radiological and pathological findings resembling an osteochondroma. In conclusion, mesenchymal hamartoma of the chest wall in infancy is quite rare and sometimes can be misdiagnosed as malignancy due to the bone-destroying radiographic appearance and the highly cellular and mitotically active microscopic features, unless the radiologists and pathologists are aware of the characteristic clinical, radiological, and pathological findings. Imaging studies can usually make a correct diagnosis with good correlation to the pathologic findings.

Female↗
PubMed2000

ACE gene polymorphism and renal responsiveness to ACE inhibitors in IgA nephropathy patients.

We examined the renal responsiveness to ACE inhibitor in IgA nephropathy (IgAN) patients according to the grouping of ACE gene polymorphism. Sixty one patients diagnosed as IgAN by renal biopsy and prescribed with ACE inhibitors were enrolled. Genomic DNA was extracted from whole blood and PCR was performed. The I/D polymorphism was determined by the presence of the 287 bp fragment in intron 16 of chromosome 17. During the follow-up period (mean; 44.6 months, median: 44.5 months, 5 to 113 months), the blood pressure of 61 patients was controlled below 130/80 mmHg. The renal responsiveness was determined by the degree of changes of proteinuria at 12 months after initiation of ACE inhibitors and by the slope of reciprocal variation of the serum creatinine against follow-up duration ¿(1/Cr2-1/Cr1)/durations¿. The distribution of the II, ID and DD genotype among 61 patients was 21, 16 and 24 patients, respectively. There were no differences among three genotypes in age, sex, the number of patients with initial blood pressure over 140/90 mmHg, initial serum creatinine level, the number of patients with initial azotemia (> 1.4 mg/dL) and with initial 24-hr proteinuria amount over 2.0 g. Significant anti-proteinuric effect of ACE inhibitor was found in IgAN (p = 0.001), but no significant difference was found among genotypes. Significant difference (p = 0.011) was noticed between II type and DD type in the slope of reciprocal variation of the serum creatinine against follow-up duration. In conclusion, efficacy of ACE inhibitors on renal function preservation in IgAN was more pronounced in DD genotype than II genotype.

Adolescent↗
PubMed2000

Dermatomyositis without elevation of creatine kinase presented as bronchiolitis obliterans organizing pneumonia.

A case of dermatomyositis presented as bronchiolitis obliterans organizing pneumonia has been rarely reported. We describe a 46-year-old female patient with dermatomyositis without elevation of creatine kinase presented as bronchiolitis obliterans organizing pneumonia. She was treated with prednisolone and azathioprine. Over a 2-year follow-up she has had no elevation of creatine kinase. The patient remains asymptomatic and has no medication for dermatomyositis and bronchiolitis obliterans organizing pneumonia two years after initial treatment. It has been suggested that the prognosis of dermatomyositis without creatine kinase elevation may be poor. Because the prognosis of bronchiolitis obliterans organizing pneumonia is generally believed to be good, we tentatively suggest that the normal value of creatine kinase in dermatomyositis does not always seem to herald a poor prognosis, an associated malignancy or severe interstitial lung disease.

Azathioprine↗
PubMed2000

Fas (APO-1/CD95) ligand and Fas expression in renal cell carcinomas: correlation with the prognostic factors.

BACKGROUND AND OBJECTIVE: Fas ligand (FasL, CD95L) is a type II transmembrane protein of the tumor necrosis factor family that induces cells to send an apoptotic signal to cells expressing Fas (CD95, APO-1). It has been shown that cancers have a dysregulated expression of Fas and FasL system, conferring a survival advantage. It is important to understand FasL and Fas expression in tumors, because the growth of cancer might be controlled by Fas-mediated apoptosis. METHODS: The expressions of FasL and Fas were studied by immunohistochemical analyses in 51 cases of renal cell carcinomas and the adjacent normal renal tissues, respectively. In addition, their expressions were compared with prognostic factors, such as tumor size, nuclear grade, TNM stage, and histologic types. RESULTS: In nonneoplastic renal tissues, FasL was expressed in all nephron segments, whereas Fas also expressed in all tubules, except for glomeruli. In renal cell carcinomas, FasL protein was detected in 50 (98.0%) of 51 cases, whereas Fas expressed in 38 (74.5%) of 51 cases. In fact, the immunostaining of Fas was less intense than that in the adjacent normal segments of all cases. The staining pattern showing both high expression of FasL and low expression of Fas was found in 36 (70.6%) (P = .04) of 51 cases, most of which were Fuhrman grade 2 or 3 tumors. However, the expression pattern did not correlate statistically with the tumor size, histologic type, or clinical stage. On the other hand, most grade 4 tumors displayed high expression of both FasL and Fas (P<.001). CONCLUSION: These data indicate that high expression of FasL and low expression of Fas protein in renal cell carcinomas may play a role in evading surveillance of the immune system. In addition, the FasL and Fas expressions appear to have a therapeutic implication for high-grade tumors rather than a prognostic one.

Adult↗
PubMed2000

cis-fumagillin, a new methionine aminopeptidase (type 2) inhibitor produced by Penicillium sp. F2757.

Selective inhibition against the yeast MetAP2 (methionine aminopeptidase type 2) was detected in the fermentation broth of a fungus F2757 that was later identified as Penicillium janczewskii. A new compound cis-fumagillin methyl ester (1) was isolated from the diazomethane treated fermentation extracts together with the known compound fumagillin methyl ester (2). The cis-fumagillin methyl ester, a stereoisomer of fumagillin methyl ester at the C2'-C3' position of the aliphatic side chain, selectively inhibited growth of the map1 mutant yeast strain (MetAP1 deletion strain) at a concentration as low as 1 ng. However, the wild type yeast w303 and the mutant map2 (MetAP2 deleted) strains were resistant up to 10 microg of the compound. In enzyme experiments, compound 1 inhibited the MetAP2 with an IC50 value of 6.3 nM, but it did not inhibit the MetAP1 (IC50 >200 microM). Compound 2 also inhibited the MetAP2 with an IC50 value of 9.2 nM and 105 microM against MetAP1.

Aminopeptidases↗