Biomedical subjects

T K Kim

Publications and source records attributed to T K Kim.

At least 37 records · Page 2Linked to original sources

PubMed2001

Synthesis and phosphodiesterase inhibitory activity of new sildenafil analogues containing a carboxylic acid group in the 5'-sulfonamide moiety of a phenyl ring.

New sildenafil analogues possessing a carboxylic acid group in the 5'-sulfonamide of the phenyl ring, 9a-l, were prepared from the readily available starting compounds 6a-b and cyclic amines 3-5 in a three-step sequence. In the enzyme assays, it has been shown that all the target compounds 9a-l proved to be more potent in inhibiting phosphodiesterase type 5 (PDE5) than sildenafil by 4-38-fold. The effects on the IC(50) values were investigated by varying the alkoxy group (R) of the phenyl ring, the sulfonamide type (X), and the length of the methylene chain linking the carboxylic acid, and the results were discussed in detail. From this study, we have clearly demonstrated that introduction of a carboxylic acid group to the 5'-sulfonamide moiety of the phenyl ring greatly enhanced PDE5 inhibitory activity, probably by mimicking the phosphate group of cGMP. The piperidinyl propionic acid derivative 9i, which showed the highest PDE5 inhibitory activity and comparable to better selectivity over PDE isozymes in comparison with sildenafil, has been selected for more detailed biological investigations.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2001

Comparison of contrast-enhanced fundamental imaging, second-harmonic imaging, and pulse-inversion harmonic imaging.

RATIONALE AND OBJECTIVES: To investigate the feasibility of recent contrast-specific ultrasound techniques in depicting vascular flow and the effects of changing the output power of the transducer and insonation mode on contrast enhancement, the authors performed an experimental study with a flow phantom. METHODS: While changing the mechanical index and the sound insonation mode (continuous and intermittent), images were obtained with three contrast-enhanced ultrasound techniques: fundamental, second-harmonic, and pulse-inversion harmonic imaging (PIHI) after a bolus injection of microbubble contrast agent. The images were compared on a time-intensity curve. RESULTS: In assessing fixed flow (10 cm/s), PIHI showed the best depiction of flow signal. In intermittent scanning, increases in the mechanical index caused stronger flow signals and longer enhancement duration in all techniques. However, continuous scanning revealed poor depiction of flow signal regardless of the technique or changes in the mechanical index because of significant bubble destruction. CONCLUSIONS: Microbubble-enhanced PIHI with intermittent scanning at a high mechanical index can depict vascular flow highly effectively without shortening the duration of enhancement.

Blood Flow Velocity↗

PubMed2001

Peripheral T-cell lymphoma of the colon: double-contrast barium enema examination findings in six patients.

PURPOSE: To evaluate radiologic findings of peripheral T-cell lymphoma (PTCL) of the colon at double-contrast barium enema examination. MATERIALS AND METHODS: Double-contrast barium enema findings in six patients with pathologically proved PTCL of the colon were retrospectively evaluated and compared with colonoscopic and histopathologic findings. RESULTS: There was a diffuse involvement of almost all segments of the colon in four patients and a focal segmental involvement in two. Frequent findings at double-contrast barium enema examination included geographic ulcerations (n = 6), aphthous ulcerations (n = 4), pseudopolyps (n = 4), circumferential luminal narrowing (n = 4), and ileocecal deformity (n = 4). CONCLUSION: PTCL of the colon manifested as either a diffuse or a focal segmental lesion and showed extensive mucosal ulceration at double-contrast barium enema examination. These findings are similar to those of inflammatory bowel disease and are different from those of colorectal lymphoma with the B-cell phenotype.

Adult↗

PubMed2001

Hepatic hemangiomas with arterioportal shunt: findings at two-phase CT.

PURPOSE: To determine the prevalence of arterioportal shunt associated with hepatic hemangiomas, describe the two-phase spiral computed tomographic (CT) findings, and correlate the presence of arterioportal shunt with the size and rapidity of enhancement of hemangiomas. MATERIALS AND METHODS: The study group consisted of 109 hepatic hemangiomas in 69 patients who underwent two-phase spiral CT during 1 year. CT scans were obtained during the hepatic arterial (30-second delay) and portal venous (65-second delay) phases after injection of 120 mL of contrast material (3 mL/sec). Arterioportal shunts were diagnosed when hepatic arterial phase CT scans showed a wedge-shaped or irregularly shaped homogeneous enhancement in the liver parenchyma adjacent to the tumor and when portal venous phase CT scans showed isoattenuation or slight hyperattenuation, compared with normal liver in that area, and when there was no demonstrable cause of these attenuation differences. The presence of arterioportal shunt in hemangioma was correlated with the size of the tumor and the rapidity of intratumoral enhancement. RESULTS: Arterioportal shunt was found in 28 (25.7%) of 109 hemangiomas. There was no statistically significant relationship between lesion size and presence of the arterioportal shunt (P =.653). Arterioportal shunt was more frequently found in hemangiomas with rapid enhancement (P <.01). CONCLUSION: Arterioportal shunts are not uncommonly seen in hepatic hemangiomas at two-phase spiral CT. Hemangiomas with arterioportal shunts tend to show rapid enhancement.

Arteriovenous Fistula↗

PubMed2001

Abdominopelvic actinomycosis involving the gastrointestinal tract: CT features.

PURPOSE: To assess the computed tomographic (CT) features of abdominopelvic actinomycosis involving the gastrointestinal tract. MATERIALS AND METHODS: CT scans were analyzed in 18 patients with pathologically proved abdominopelvic actinomycosis involving the gastrointestinal tract. Eight patients had a history of using intrauterine contraceptive devices. Bowel site, wall thickness, length, bowel involvement patterns, inflammatory infiltration, and features of peritoneal or pelvic mass, if present, were evaluated at CT. RESULTS: Of the gastrointestinal tract, the sigmoid colon was most commonly involved (50%). All patients showed concentric (n = 15) or eccentric (n = 3) bowel wall thickening, with a mean thickness of 1.2 cm and a mean length of 8.3 cm. The thickened bowel enhanced homogeneously in nine patients and heterogeneously in the other nine. Inflammatory infiltration was mostly diffuse and severe. In 17 patients, a peritoneal or pelvic mass (mean maximum diameter, 3.2 cm) was seen adjacent to the involved bowel and appeared to be heterogeneously enhanced in most cases; infiltration into the abdominal wall was seen in four patients. CONCLUSION: Actinomycosis should be included in the differential diagnosis when CT scans show bowel wall thickening and regional pelvic or peritoneal mass with extensive infiltration, especially in patients with abdominal pain, fever, leukocytosis, or long-term use of intrauterine contraceptive devices.

Actinomycosis↗

PubMed2001

Formulation and release characteristics of poly(lactic-co-glycolic acid) microspheres containing chemically modified protein.

Chemical modification of proteins may influence their formulation into and release from polymeric microspheres. Three chemical modifications of rat serum albumin (RSA) were effected on the amine groups of this protein: conjugation with a polyanion using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide, intermolecular cross-linking using glutaraldehyde, and reductive alkylation using propyl aldehyde. The modified proteins had different physicochemical properties as well as improved encapsulation efficiencies compared with native RSA microspheres. The microspheres were incubated at 37 degrees C for over one month to investigate the influence of protein modification on the release profiles. Microsphere degradation accelerated from the ninth day of the release studies and this coincided with an increase in the release rates. The degradation rates of poly(lactic-co-glycolic acid) microspheres containing either native or cross-linked RSA were more rapid than those containing either heparin conjugated or propylated RSA. This was in agreement with the release data, since the release of the native and cross-linked RSA were more rapid than those of the other modified proteins. The release profiles of the RSA-heparin conjugates and the propylated RSA were approximately zero rather than first order between the tenth and thirtieth day of study. Chemical modification of protein may be a useful method to increase encapsulation efficiency and to decrease release rates of proteins that are to be used in microsphere formulations of potent therapeutic proteins.

Animals↗

PubMed2001

Ultrasonographic evaluation of the gallbladder: comparison of fundamental, tissue harmonic, and pulse inversion harmonic imaging.

The purpose of our study was to compare pulse inversion harmonic imaging, tissue harmonic imaging, and fundamental imaging in the evaluation of normal and diseased gallbladder. Gallbladders in 170 patients were examined with fundamental imaging, tissue harmonic imaging, and pulse inversion harmonic imaging using a 2- to 5-MHz curved array transducer. Images were divided into normal and abnormal groups. The sharpness of the wall and degree of internal artifact were evaluated in normal groups, and lesion conspicuity and internal artifact were evaluated in abnormal groups. In images of both normal and abnormal gallbladder, significant differences were demonstrated among the 3 imaging methods (P < .001), and pulse inversion harmonic imaging provided the best image quality and the least artifact. Tissue harmonic imaging was the next best, providing better image quality and less artifact than fundamental imaging. In conclusion, pulse inversion harmonic imaging provided the best image quality and the least artifact among the 3 ultrasonographic methods in the evaluation of both normal and abnormal gallbladder.

Aged↗

PubMed2001

Pharmacokinetic studies of 2-amino-9-(3-acetoxymethyl-4-isopropoxycarbonyl-oxybut-1-yl)purine, an oral prodrug for the antiviral agent penciclovir.

2-Amino-9-(3-acetoxymethyl-4-isopropoxycarbonyloxybut-1-yl)- purine (SK1899) was tested as an oral prodrug for penciclovir. SK1899 was administered orally to rats and dogs at doses up to 2 and 0.68 mmol/kg, respectively. SK1899 was well absorbed, and the major metabolites detected in plasma and urine were penciclovir, the active antiviral compound, and 6-deoxypenciclovir (M4) in both species. In rats, SK1899 was rapidly and extensively metabolized to penciclovir, which reached the peak plasma concentration (C(max)) of 39.5 microM at 0.5 h after 0.2-mmol/kg dosing. The area under the plasma concentration-time curve (AUC) for penciclovir was 57.5 microM x h. After an oral dose of 0.034 mmol/kg to dogs, extensive conversion of SK1899 to penciclovir also occurred with slower rate of formation of penciclovir from M4 than in rats. The mean C(max) and AUC for penciclovir were 4.5 microM at 2.7 h and 28.2 microM x h, respectively. The 0- to 24-h urinary recovery of penciclovir represented 36.1 and 36.3% of dose to rats and dogs, respectively. Radioactivity was found in fetuses following an oral administration of [(14)C]SK1899 to pregnant rats, but no significant accumulation was observed. Although substantial milk transfer of [(14)C]SK1899 occurred in rats, the radioactivity in milk was rapidly cleared. The values of C(max), AUC, and urinary recovery of penciclovir after dosing with SK1899 to rats and dogs were similar or slightly higher than those from famciclovir. These data indicate that introduction of an isopropoxy carbonate group into one of the two hydroxyl groups of M4 did not significantly alter the oral bioavailability of penciclovir compared with famciclovir.

Acyclovir↗

PubMed2000

Osmoprotective effect of glycine betaine on foreign protein production in hyperosmotic recombinant chinese hamster ovary cell cultures differs among cell lines.

When three recombinant Chinese hamster ovary (rCHO) cell lines, CHO/dhfr-B22-4, CS13-1.00*, and CS13-0.02*, were cultivated in hyperosmolar media resulting from NaCl addition, their specific foreign protein productivity increased with medium osmolality. However, due to a simultaneous suppression of cell growth at elevated osmolality, no enhancement in the maximum foreign protein titer was made in batch cultures. To test the feasibility of using glycine betaine, known as a strong osmoprotective compound, for improved foreign protein production in hyperosmotic rCHO cell cultures, hyperosmotic batch cultures were carried out in the presence of 15 mM glycine betaine. Glycine betaine was found to have a strong osmoprotective effect on all three rCHO cell lines. Inclusion of 15 mM glycine betaine in hyperosmolar medium enabled rCHO cell lines to grow at 557 to 573 mOsm/kg, whereas they could not grow in the absence of glycine betaine. However, effect of glycine betaine inclusion in hyperosmolar medium on foreign protein production differed among rCHO cell lines. CHO/dhfr-B22-4 cells retained enhanced specific human thrombopoietin (hTPO) productivity in the presence of glycine betaine, and thereby the maximum hTPO titer obtained at 573 mOsm/kg was increased by 72% over that obtained in the control culture with physiological osmolality (292 mOsm/kg). On the other hand, enhanced specific antibody productivity of CS13-1.00* and CS13-0.02* at elevated osmolality was decreased significantly in the presence of glycine betaine. As a result, the maximum antibody titer at 557 mOsm/kg was similar to that obtained in the control culture with physiological osmolality. The mRNA contents per cell determined by northern blot hybridization correlated with q in all three rCHO cell lines, indicating that transcriptional regulation is responsible in part for q enhancement at hyperosmolality in the absence as well as the presence of glycine betaine. Taken together, efficacy of the simultaneous use of hyperosmotic pressure and glycine betaine as a means to improve foreign protein production was variable among different rCHO cell lines.

Animals↗

PubMed2000

A downstream element in the human beta-globin promoter: evidence of extended sequence-specific transcription factor IID contacts.

We describe here the identification and characterization of a functional downstream element in the human adult beta-globin promoter. The existence of this element was indicated by two mutations at +22 and +33 downstream of the beta-globin transcriptional start site in humans with beta-thalassemia. In vitro transcriptional analysis of these mutants, plus a third at +13, indicates that all three decrease transcription from the beta-globin promoter. Scanning mutagenesis from +10 to +45 indicates that this region contains a functional cis element(s) in vitro, and we designated this element the DCE (downstream core element). The DCE functions in concert with the beta-globin CATA box and initiator element, as well as in a heterologous, TATA-less context. A second set of mutants indicates that a particular geometry of the DCE and core promoter is necessary for promoter function. Lastly, DCE mutants show reduced affinity for transcription factor IID (TFIID). These data indicate that TFIID makes sequence-specific contacts to the DCE and that TFIID binding is necessary for DCE function.

Globins↗

PubMed2000

Signaling pathways to the assembly of an interferon-beta enhanceosome. Chemical genetic studies with a small molecule.

Small molecules that modulate specific protein functions are valuable tools for dissecting complex signaling pathways. Here, we identified a small molecule that induces the assembly of the interferon-beta (IFN-beta) enhanceosome by stimulating all the enhancer-binding activator proteins: ATF2/c-JUN, IRF3, and p50/p65 of NF-kappaB. This compound stimulates mitogen-activated protein kinase kinase kinase 1 (MEKK1), which is a member of a family of proteins involved in stress-mediated signaling pathways. Consistent with this, MEKK1 activates IRF3 in addition to ATF2/c-JUN and NF-kappaB for the assembly of the IFN-beta enhanceosome. MEKK1 activates IRF3 through the c-JUN amino-terminal kinase (JNK) pathway but not the p38 and IkappaB kinase (IKK) pathway. Taken together with previous observations, these results implicate that, for the assembly of an IFN-beta enhanceosome, MEKK1 can induce IRF3 and ATF2/c-JUN through the JNK pathway, whereas it can induce NF-kappaB through the IKK pathway. Thus, specific MEKK family proteins may be able to integrate some of multiple signal transduction pathways leading to the specific activation of the IFN-beta enhanceosome.

Enhancer Elements, Genetic↗

PubMed2000

Mechanism of ATP-dependent promoter melting by transcription factor IIH.

We show that transcription factor IIH ERCC3 subunit, the DNA helicase responsible for adenosine triphosphate (ATP)-dependent promoter melting during transcription initiation, does not interact with the promoter region that undergoes melting but instead interacts with DNA downstream of this region. We show further that promoter melting does not change protein-DNA interactions upstream of the region that undergoes melting but does change interactions within and downstream of this region. Our results rule out the proposal that IIH functions in promoter melting through a conventional DNA-helicase mechanism. We propose that IIH functions as a molecular wrench: rotating downstream DNA relative to fixed upstream protein-DNA interactions, thereby generating torque on, and melting, the intervening DNA.

Adenosine Triphosphate↗

PubMed2000

Identification of Mad as a repressor of the human telomerase (hTERT) gene.

Activation of telomerase, which has been frequently associated with cellular immortality, may constitute a key step in the development of human cancer. De-repression in the expression of its catalytic subunit hTERT gene has been proposed to directly link to the telomerase activation in tumor cells. Little is known about the mechanism how the hTERT gene is repressed in telomerase-negative mortal cells. This study was conducted, using an expression cloning approach, with the aim of identifying the gene(s) responsible for repressing the hTERT gene expression. Using this genetic screen, we isolated the transcription factor Mad as a repressor. Mutation of its DNA binding sites caused significant de-repression of hTERT promoter activity in mortal cells. This Mad-mediated repression of the hTERT promoter in mortal cells was counteracted by ectopic expression of Myc. The antagonism between Mad and Myc was also observed with an endogenous hTERT promoter. Their potential roles in differential hTERT promoter activities were further supported by the relative amounts of Mad and Myc proteins detected in immortal and mortal cells. Thus, Mad may be a direct negative regulator of hTERT in mortal cells and this repression mechanism can be inhibited by induction of Myc in immortal cells.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗

PubMed2000

Chemotherapeutic DNA-damaging drugs activate interferon regulatory factor-7 by the mitogen-activated protein kinase kinase-4-cJun NH2-terminal kinase pathway.

Chemotherapeutic drugs and energy-rich radiation cause DNA damage, inducing signaling pathways for apoptotic cell death or cell growth arrest. The tumor suppressor gene p53 plays the critical role in the regulation of these DNA damage responses. Human tumor cells can become resistant to chemotherapy through functional inactivation of p53. Thus, it is important to identify p53-independent DNA damage signaling pathways. Here, treatment of cells with chemotherapeutic drugs or UV irradiation potentiated the transcriptional activity of IFN regulatory factor-7 (IRF7), inducing its phosphorylation and its nuclear translocation. Furthermore, IRF7 was activated by the c-Jun NH2-terminal kinase (JNK) in response to DNA-damaging agents. Activation of JNK by mitogen-activated protein kinase kinase-4 stimulated the transcriptional activity of IRF7 and induced its translocation into the nucleus. Thus, activation of IRF7 through the JNK signaling pathway may play a role in the transcriptional regulation of genes in response to DNA-damaging agents.

Antineoplastic Agents↗

PubMed2000

Involvement of retinoblastoma protein in p27Kip1-induced apoptosis.

p27Kip1, a cyclin-dependent kinase (CDK) inhibitor, plays a critical role in cell cycle regulation. Expression of p27Kip1 is shown to increase during apoptosis in mammalian cells. Here, to directly address the role of p27Kip1 in apoptosis, p27Kip1 is overexpressed in human SK-Hep1 hepatoma cells. This leads to apoptotic cell death and this reduces protein, but not mRNA, levels of the retinoblastoma (Rb). Consistently, accumulation of Rb protein blocks p27Kip1-mediated apoptosis. These studies demonstrate an involvement of Rb in the apoptotic cell death which is induced by overexpression of p27Kip1.

Apoptosis↗

PubMed2000

Improved imaging of hepatic metastases with delayed pulse inversion harmonic imaging using a contrast agent SH U 508A: preliminary study.

To investigate the feasibility of delayed pulse-inversion harmonic imaging (PIHI) with the SH U 508A to improve imaging of hepatic metastases, we evaluated 20 patients with known hepatic metastases. Conventional ultrasound (US) was performed before administration, and PIHI was performed 5 min after a bolus injection of 4 G of microbubble contrast agent (300 mg/mL of SH U 508A). Intense, homogeneous enhancement in the liver parenchyma was seen in all patients on delayed PIHI. In 10 patients (50%), 1 or more focal liver lesions that were not seen on unenhanced imaging were detected on delayed PIHI. When comparing 55 lesions that were seen on both techniques, delayed PIHI was superior to unenhanced imaging in terms of lesion conspicuity and lesion-to-liver contrast (p < 0.001, respectively). Delayed PIHI with SH U 508A can improve conspicuity of hepatic metastases and reveal focal liver lesions that are not detected on unenhanced imaging.

Adult↗

PubMed2000

Comparison of harmonic and conventional power Doppler ultrasonography for assessment of slow flow in hyperechoic tissue: experimental study using a Doppler phantom.

RATIONALE AND OBJECTIVES: Despite the advantages of depicting slow flow in small vessels, conventional power Doppler ultrasound (US) has a basic limitation, specifically that artifactual power Doppler signals mimic blood flow, especially in hyperechoic tissue. The purpose of this study was to compare harmonic power Doppler US with power Doppler US using a Doppler phantom under various parameter settings, focusing on the assessment of slow flow in the hyperechoic tissue. METHODS: While controlling the flow velocity (5 and 10 cm/s), pulse repetition frequency (500, 700, and 1,000 Hz), wall filter (low and medium), and Doppler gain (90%, 96%, and 100%), the authors performed both harmonic Doppler US and power Doppler US by using a Doppler phantom/flow control system. We measured and compared the relative intensities of the Doppler signals (0-250 scale) in both the vessels and hyperechoic tissue-mimicking materials with the two different imaging modalities. RESULTS: Power Doppler US with any combination of the four parameters evaluated depicted strong flow signals (mean, 213) that were superior to harmonic Doppler US (mean, 61). Relatively strong artifactual signals within the hyperechoic tissue-mimicking materials were noted on all power Doppler US studies (mean, 106) but nearly none on harmonic Doppler US (mean, 3). The contrast-to-noise ratio of harmonic Doppler US was significantly greater than that of power Doppler US. CONCLUSIONS: Harmonic Doppler US is more useful in assessing slow flow in hyperechoic tissue than power Doppler US because it produces fewer artifactual Doppler signals originating from stationary hyperechoic tissues, which can be misjudged as true signals on power Doppler US.

Blood Flow Velocity↗

PubMed2000

Lactobacillus kimchii sp. nov., a new species from kimchi.

A bacteriocin-producing lactic acid bacterium, which was isolated from the Korean fermented-vegetable food kimchi, was subjected to a polyphasic taxonomic study using phenotypic characterization and phylogenetic and genetic methods. This organism (MT-1077T) has phenotypic properties that are consistent with the description characterizing the genus Lactobacillus. Phylogenetic analysis based on 16S rDNA sequences showed clearly that strain MT-1077T is a member of the genus Lactobacillus. The closest phylogenetic relatives are Lactobacillus alimentarius KCTC 3593T and Lactobacillus farciminis LMG 9200T, with levels of 16S rDNA similarity of 98.4 and 98.2%, respectively. Levels of 16S rDNA similarity between strain MT-1077T and other Lactobacillus species were less than 93.0%. Differences in some phenotypic characteristics and DNA-DNA relatedness data indicated that strain MT-1077T should be distinguished from L. alimentarius KCTC 3593T and L. farciminis LMG 9200T. On the basis of the data presented, it is proposed that strain MT-1077T should be placed in the genus Lactobacillus as a new species, Lactobacillus kimchii sp. nov. The type strain of the new species is strain MT-1077T (= KCTC 8903PT = JCM 10707T).

Bacterial Typing Techniques↗