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Biomedical subjects

J L Kim

Publications and source records attributed to J L Kim.

At least 19 recordsLinked to original sources
PubMed2001

5-HT2A receptor gene promoter polymorphism -1438A/G and bipolar disorder.

Genetic factors, such as the genes involved in the serotonin pathway, probably play an important role in the pathogenesis of bipolar disorder, and serotonin type 2A (5-HT2A) receptor gene promoter polymorphism -1438A/G has been reported. This study investigated the association between -1438A/G polymorphism of 5-HT2A receptor gene promoter and bipolar disorder in a Korean population. Using the polymerase chain reaction, -1438A/G polymorphism typed in 142 patients with bipolar disorder and in 148 normal control subjects. Differences in genotype distributions and allele frequencies of -1438A/G between patients with bipolar disorder and normal control subjects were tested for significance using the chi-squared test. There were significant differences in genotype distributions [chi2 = 9.697, degrees of freedom (df) = 2, P = 0.008] and allele frequencies (chi2 = 7.284, df = 1, P = 0.007) of -1438A/G between patients with bipolar disorder and normal control subjects. Although further studies are necessary, these results in a Korean population suggest that -1438A/G polymorphism of 5-HT2A receptor gene promoter may be causally related to the development of bipolar disorder.

Adenine↗
PubMed2001

A nationwide survey of the prevalence of human Gymnophalloides seoi infection on western and southern coastal islands in the Republic of Korea.

A nationwide survey was performed to know the distribution and prevalence of human Gymnophalloides seoi infection on western and southern coastal islands in the Republic of Korea. A total of 4,178 fecal specimens were collected from residents on 45 (24 western and 21 southern) islands, and examined by Kato-Katz and formalin-ether sedimentation techniques. Eggs of G. seoi were detected from 160 (3.8%) people living on 22 (13 western and 9 southern) islands. The prevalence varied by the location of islands; higher on western islands than on southern islands. The highest prevalence was found on Amtaedo (25.3%), followed by Cheungdo (25.0%), and Anchwado (20.9%) (Shinan-gun). A little lower prevalence was observed on Munyodo (13.3%), Shinshido (12.9%), and Sonyudo (10.3%) (Kunsan-shi). Of the remaining islands, the regions showing the prevalence greater than 5% included Kohado, Dallido (Mokpo-shi), Pyeongildo, Kogumdo (Wando-gun), and Keogumdo (Kohung-gun). A strong age predilection was noted (p < 0.05); 95% of the infected people were over 40 years old. Females showed a little higher prevalence than males. The results indicate that human G. seoi infection is more widely distributed than previously considered. Nine of 11 islands (excluding the 2 known areas Munyodo and Sunyudo) that showed greater prevalence than 5% are regarded as new endemic foci of G. seoi.

Adolescent↗
PubMed2000

Structure and function of hepatitis C virus NS3 helicase.

Hepatitis C Virus helicase activity has been mapped to the COOH-terminal 450 residues of the NS3 protein. Due to its complexity and presumed essentiality for viral replication, the helicase is an attractive target for drug discovery. The elucidation of the atomic structure of the HCV NS3 helicase in complex with oligonucleotide and with ADP has helped clarify our understanding of potential sites for inhibitor binding. Molecular details of the mechanism of this enzyme, and in particular, a better understanding of the mechanism by which ATP hydrolysis is coupled to unwinding of double-stranded substrate may facilitate more efficient structure-based drug design.

Amino Acid Sequence↗
PubMed2000

High endemicity of Metagonimus yokogawai infection among residents of Samchok-shi, Kangwon-do.

A small-scale epidemiological survey was undertaken during 1997-1998 on the residents along the Osib-chon (Stream), Samchok-shi (City), Kangwon-do (Province), to evaluate the status of Metagonimus yokogawai infection. A total of 165 fecal samples was collected and examined by cellophane thick smear and formalin-ether sedimentation techniques. The egg positive rate of M. yokogawai was 29.7%, showing a remarkable difference between males (46.6%) and females (16.3%). To obtain the adult flukes of M. yokogawai, 11 egg positive persons were treated with praziquantel and purged with magnesium sulfate. A total of 242,119 adult flukes (average 22,010 per person, 367-119,650 in range) was collected from diarrheic stools, all of which were identified as M. yokogawai. The results show that M. yokogawai is still highly endemic in this area.

Adolescent↗
PubMed1999

TATA element recognition by the TATA box-binding protein has been conserved throughout evolution.

Cocrystal structures of wild-type TATA box-binding protein (TBP) recognizing 10 naturally occurring TATA elements have been determined at 2.3-1.8 A resolution, and compared with our 1.9 A resolution structure of TBP bound to the Adenovirus major late promoter (AdMLP) TATA box (5'-TATAAAAG-3'). Minor-groove recognition by the saddle-shaped protein induces the same conformational change in each of these oligonucleotides, despite variations in promoter sequence that reduce the efficiency of transcription initiation. Three molecular mechanisms explain assembly of diverse TBP-TATA element complexes. (1) T --> A and A --> T transversions leave the minor-groove face unchanged, permitting formation of TBP-DNA complexes on many A/T-rich core promoter sequences. (2) Cavities in the interface between TBP and the minor-groove face of the AdMLP TATA box accommodate the exocyclic NH(2) groups of G in a TACA box and in a TATAAG box. (3) Formation of a C:G Hoogsteen basepair in a TATAAAC box eliminates steric clashes that would be produced by the Watson-Crick base pair. We conclude that the structure of the TBP-TATA box complex found at the heart of the polymerase II (pol II) transcription machinery has remained constant over the course of evolution, despite variations in TBP and its DNA targets.

Amino Acid Sequence↗
PubMed1999

New hydrolysis method for extremely small amount of lipids and capillary gas chromatographic analysis as n(O)-tert.-butyldimethylsilyl fatty acid derivatives compared with methyl ester derivatives.

The organic basic solution, 1 M tetramethylammonium hydroxide (TMAH) in methanol, was employed for the hydrolysis of extremely small amounts of lipids compared to the classical inorganic basic solution, 1 M KOH in ethanol. The hydrolysed fatty acids were derivatized as N(O)-tert.-butyldimethylsilyl (tBDMSi) esters with N-methyl-N-(tert.-butyldimethylsilyl) trifluoroacetamide (MTBSTFA) and compared with the classical derivatives, the methyl esters, made by the BF3-methanol method. Recoveries of fatty acids determined on the standard fatty acids and soybean oil hydrolysed with TMAH were high: about 1.1-2.1- and 2.0-5.4-times, respectively, in all fatty acids compared with the hydrolysis by KOH regardless of derivatization method. The relative standard deviations (RSDs) on the recoveries of standard fatty acids were less than 5% when hydrolysed with TMAH, regardless of derivatives, but when hydrolysed with KOH, RSDs were more than 5% for most fatty acids, especially for long-chain fatty acids. The RSDs on the recoveries of fatty acids on the soybean oil were also very high in the KOH hydrolysis. Fatty acid compositions of soybean oil were similar in the main fatty acids regardless of hydrolysis methods, but showed slightly different values, depending on the methods of derivatization. RSDs were also very high in the KOH hydrolysis. In view of these results, precision of analysis by KOH hydrolysis was very poor, so we could not rely on the data. On the other hand, the reliability of data by TMAH hydrolysis method was very high, so it is a useful new hydrolysis method for extremely small amounts of lipid samples. Both derivatives of 35 standard fatty acids were successfully separated on a HP-1 nonpolar capillary column. tBDMSi derivatives were completely resolved in 70 min by 295 degrees C. In the methyl ester derivatives it took about 80 min to get satisfying resolution, but these derivatives were completely resolved by 250 degrees C. The sensitivity of tBDMSi derivatives was about 1.5-6.3-times higher than that with methyl ester derivatives. The stability of tBDMSi derivatives was constant for about 144 h except arachidic, docosahexanoic, behenic and heneicosanoic acids, which were stable for only 86 h.

Acetamides↗
PubMed1999

Structural analysis of the lymphocyte-specific kinase Lck in complex with non-selective and Src family selective kinase inhibitors.

BACKGROUND: The lymphocyte-specific kinase Lck is a member of the Src family of non-receptor tyrosine kinases. Lck catalyzes the initial phosphorylation of T-cell receptor components that is necessary for signal transduction and T-cell activation. On the basis of both biochemical and genetic studies, Lck is considered an attractive cell-specific target for the design of novel T-cell immunosuppressants. To date, the lack of detailed structural information on the mode of inhibitor binding to Lck has limited the discovery of novel Lck inhibitors. RESULTS: We report here the high-resolution crystal structures of an activated Lck kinase domain in complex with three structurally distinct ATP-competitive inhibitors: AMP-PNP (a non-selective, non-hydrolyzable ATP analog); staurosporine (a potent but non-selective protein kinase inhibitor); and PP2 (a potent Src family selective protein tyrosine kinase inhibitor). Comparison of these structures reveals subtle but important structural changes at the ATP-binding site. Furthermore, PP2 is found to access a deep, hydrophobic pocket near the ATP-binding cleft of the enzyme; this binding pocket is not occupied by either AMP-PNP or staurosporine. CONCLUSIONS: The potency of staurosporine against Lck derives in part from an induced movement of the glycine-rich loop of the enzyme upon binding of this ligand, which maximizes the van der Waals interactions present in the complex. In contrast, PP2 binds tightly and selectively to Lck and other Src family kinases by making additional contacts in a deep, hydrophobic pocket adjacent to the ATP-binding site; the amino acid composition of this pocket is unique to Src family kinases. The structures of these Lck complexes offer useful structural insights as they demonstrate that kinase selectivity can be achieved with small-molecule inhibitors that exploit subtle topological differences among protein kinases.

Adenosine Triphosphate↗
PubMed1999

Structure-based mutagenesis study of hepatitis C virus NS3 helicase.

The NS3 protein of hepatitis C virus (HCV) is a bifunctional protein containing a serine protease in the N-terminal one-third, which is stimulated upon binding of the NS4A cofactor, and an RNA helicase in the C-terminal two-thirds. In this study, a C-terminal hexahistidine-tagged helicase domain of the HCV NS3 protein was expressed in Escherichia coli and purified to homogeneity by conventional chromatography. The purified HCV helicase domain has a basal ATPase activity, a polynucleotide-stimulated ATPase activity, and a nucleic acid unwinding activity and binds efficiently to single-stranded polynucleotide. Detailed characterization of the purified HCV helicase domain with regard to all four activities is presented. Recently, we published an X-ray crystallographic structure of a binary complex of the HCV helicase with a (dU)(8) oligonucleotide, in which several conserved residues of the HCV helicase were shown to be involved in interactions between the HCV helicase and oligonucleotide. Here, site-directed mutagenesis was used to elucidate the roles of these residues in helicase function. Four individual mutations, Thr to Ala at position 269, Thr to Ala at position 411, Trp to Leu at position 501, and Trp to Ala at position 501, produced a severe reduction of RNA binding and completely abolished unwinding activity and stimulation of ATPase activity by poly(U), although the basal ATPase activity (activity in the absence of polynucleotide) of these mutants remained intact. Alanine substitution at Ser-231 or Ser-370 resulted in enzymes that were indistinguishable from wild-type HCV helicase with regard to all four activities. A mutant bearing Phe at Trp-501 showed wild-type levels of basal ATPase, unwinding activity, and single-stranded RNA binding activity. Interestingly, ATPase activity of this mutant became less responsive to stimulation by poly(U) but not to stimulation by other polynucleotides, such as poly(C). Given the conservation of some of these residues in other DNA and RNA helicases, their role in the mechanism of unwinding of double-stranded nucleic acid is discussed.

Amino Acid Sequence↗
PubMed1999

Hepatitis C virus NS3/4A protease.

Despite an urgent medical need, a broadly effective anti-viral therapy for the treatment of infections with hepatitis C viruses (HCVs) has yet to be developed. One of the approaches to anti-HCV drug discovery is the design and development of specific small molecule drugs to inhibit the proteolytic processing of the HCV polyprotein. This proteolytic processing is catalyzed by a chymotrypsin-like serine protease which is located in the N-terminal region of non-structural protein 3 (NS3). This protease domain forms a tight, non-covalent complex with NS4A, a 54 amino acid activator of NS3 protease. The C-terminal two-thirds of the NS3 protein contain a helicase and a nucleic acid-stimulated nucleoside triphosphatase (NTPase) activities which are probably involved in viral replication. This review will focus on the structure and function of the serine protease activity of NS3/4A and the development of inhibitors of this activity.

Antiviral Agents↗
PubMed1999

Macrophage depletion alters vein graft intimal hyperplasia.

BACKGROUND: The principal cause of vein graft failure is intimal hyperplasia (IH); however, its etiology remains unclear. In a rat model of vein graft IH we have observed prolonged transmural macrophage infiltration, leading us to hypothesize that these cells regulate IH. To test this, we used liposome-encapsulated dichloromethylene bisphosphonate (L-Cl2MBP) to deplete rat macrophages and observed the effects on IH. METHODS: Epigastric vein-to-femoral artery grafts were microsurgically placed in male Lewis rats that had been intravenously injected with L-Cl2MBP, phosphate-buffered saline solution liposomes, or phosphate-buffered saline solution alone 2 days before surgery. Several animals in each group received a second equivalent dose at 2 weeks. Grafts, contralateral epigastric veins, spleens, and livers were harvested at 1, 2, and 4 weeks for histologic examination, immunohistochemistry, and transmission electron microscopy. RESULTS: In the L-Cl2MBP-treated animals splenic and hepatic macrophages were greatly reduced, confirming the efficacy of the agent. At 1 to 2 weeks graft macrophages were significantly decreased, and there was a trend toward decreased IH. At 4 weeks macrophage numbers were normal and IH development had resumed. In contrast, the 4-week grafts treated with 2 doses of L-Cl2MBP had fewer macrophages and displayed severely attenuated IH. CONCLUSIONS: The results indicate a suppression of IH as macrophages are depleted, with a resumption of the process as macrophages repopulate the graft.

Animals↗
PubMed1998

Hepatitis C virus NS3 RNA helicase domain with a bound oligonucleotide: the crystal structure provides insights into the mode of unwinding.

BACKGROUND: Hepatitis C virus (HCV) represents a major health concern as it is responsible for a significant number of hepatitis cases worldwide. Much research has focused on the replicative enzymes of HCV as possible targets for more effective therapeutic agents. HCV NS3 helicase may provide one such suitable target. Helicases are enzymes which can unwind double-stranded regions of DNA or RNA in an ATP-dependent reaction. The structures of several helicases have been published but the structural details as to how ATP binding and hydrolysis are coupled to RNA unwinding are unknown. RESULTS: The structure of the HCV NS3 RNA helicase domain complexed with a single-stranded DNA oligonucleotide has been solved to 2.2 A resolution. The protein consists of three structural domains with the oligonucleotide lying in a groove between the first two domains and the third. The first two domains have an adenylate kinase like fold, including a phosphate-binding loop in the first domain. CONCLUSIONS: HCV NS3 helicase is a member of a superfamily of helicases, termed superfamily II. Residues of NS3 helicase which are conserved among superfamily II helicases line an interdomain cleft between the first two domains. The oligonucleotide binds in an orthogonal binding site and contacts relatively few conserved residues. There are no strong sequence-specific interactions with the oligonucleotide bases.

Amino Acid Sequence↗
PubMed1998

Hepatitis C virus NS3/4A protease.

Despite an urgent medical need, a broadly effective anti-viral therapy for the treatment of infections with hepatitis C viruses (HCVs) has yet to be developed. One of the approaches to anti-HCV drug discovery is the design and development of specific small molecule drugs to inhibit the proteolytic processing of the HCV polyprotein. This proteolytic processing is catalyzed by a chymotrypsin-like serine protease which is located in the N-terminal region of non-structural protein 3 (NS3). This protease domain forms a tight, non-covalent complex with NS4A, a 54 amino acid activator of NS3 protease. The C-terminal two-thirds of the NS3 protein contain a helicase and a nucleic acid-stimulated nucleoside triphosphatase (NTPase) activities which are probably involved in viral replication. This review will focus on the structure and function of the serine protease activity of NS3/4A and the development of inhibitors of this activity.

Amino Acid Sequence↗
PubMed1998

Does low dose dopamine attenuate the decrease of renal function in the treatment of patients under controlled mechanical ventilation with positive end expiratory pressure?

Controlled mechanical ventilation (CMV) with positive and expiratory pressure (PEEP) is often used to improve the pulmonary gas exchange in patients with acute respiratory distress syndrome. However, this ventilatory technique may induce hemodynamic and hormonal changes which may lead to vital organ dysfunction, such as oliguria. Low dose dopamine, acting as a dopaminergic receptor agonist, may improve vital organ perfusions, i.e. renal, mesenteric and coronary perfusions. The purpose of this current study was to evaluate the effects of low dose dopamine on renal function and hemodynamic change during controlled mechanical ventilation with PEEP. The study was performed on 10 patients treated with PEEP in the surgical intensive care unit. Starting with 0 cmH2O of PEEP and adding 4 cmH2O of PEEP at 4-hour intervals until it reached 12 cmH2O of PEEP, dopamine, 2 ug/kg/min, was selectively, administered, intravenously during the last two hours of each four hour intervals. Following each procedure, hemodynamic parameters, urine output, creatinine clearance and fractional excretion of sodium were measured. The cardiac index and mean arterial pressure had both decreased, but the mean pulmonary arterial pressure was increased at 12 cmH2O of PEEP compared with 0 cmH2O of PEEP in both groups with and without low dose dopamine. The main result of this study was that low dose dopamine attenuated the decrease of the cardiac index, urine output and creatinine clearance induced by mechanical ventilation with PEEP at 12 cmH2O.

Adult↗
PubMed1997

Establishment of ANSI N13.11 X-ray radiation fields for personal dosimetry performance test by computation and experiment.

This paper describes establishment by computational and experimental methods of the American National Standard Institute (ANSI) N13.11 X-ray radiation fields by the Korea Atomic Energy Research Institute (KAERI). These fields were used in the standard irradiations of various personal dosimeters for the personal dosimetry performance test program performed by the Ministry of Science and Technology of Korea in the autumn of 1995. Theoretical X-ray spectra produced from two KAERI X-ray generators were estimated using a modified Kramers' theory with target attenuation and backscatter correction and their spectral distributions experimentally measured by a high-purity germanium semiconductor detector through proper corrections for measured pulse height distributions with photopeak efficiency, Compton fraction, and K-escape fraction. The average energies and conversion coefficients obtained from the computation and experimental methods, when compared with ANSI N13.11 and the recently published National Institute of Standards and Technology X-ray beams, appeared to be in good agreement--(+/-)3% between corresponding values--and thus, could be satisfactorily applied in the performance test of personal dosimeters.

Korea↗
PubMed1997

An unusual over-gravid female of Enterobius vermicularis recovered from a child.

An unusual over-gravid female of Enterobius vermicularis was recovered from a 15-month old child by cello-tape anal swab. The patient resided in Inchon and complained of severe anal itching. The worm measured 7.8 mm in length and 0.5 mm in width, and retained typical morphologic features of E. vermicularis such as cephalic alae and a sharply pointed posterior end. In this gravid female, peculiarly, the uterus was tremendously distended, and about 99% of the whole body length was completely packed with a great number of eggs. Other internal organs were difficult to observe. This paper describes a peculiar over-gravid female of E. vermicularis.

Animals↗
PubMed1997

A new endemic focus of Heterophyes nocens, Pygidiopsis summa, and other intestinal flukes in a coastal area of Muan-gun, Chollanam-do.

A small coastal village of Muan-gun, Chollanam-do, was surveyed for intestinal fluke infections, especially heterophyids such as Heterophyes nocens and Pygidiopsis summa by fecal examination on 108 inhabitants. The egg positive rate of heterophyids was very high, 75.0%, and that of other parasites was comparatively low, 0.9-3.7% by parasite species. After treatment of 20 patients showing high E.P.G. with praziquantel and purging with MgSO4, total 3,864 specimens of H. nocens were collected from the diarrheic stools of all the patients treated (3-1,338 individually) and total 703 P. summa were harvested from 18 patients (1-170 individually), together with several other species of flukes. Other flukes included Stictodora fuscata (164 specimens from 4 patients), Heterophyopsis continua (2 from 2 patients), and Gymnophalloides seoi (4 from 3 patients). From this study, the surveyed coastal area of Muan-gun, Chollanam-do was proven to be a new endemic focus of H. nocens and P. summa. The occurrence of a few infected cases suggests that this area should also be a low-grade endemic area of S. fuscata, H. continua, and G. seoi.

Animals↗
PubMed1997

Heparin attenuated neutrophil infiltration but did not affect renal injury induced by ischemia reperfusion.

Although heparin is better known as an anticoagulant, it also has several anti-inflammatory effects. Heparin is known to inhibit neutrophil adhesion, chemotaxis and oxygen free radical production. In addition, heparin is also known to act as an oxygen radical scavenger. Our hypothesis was that heparin would attenuate renal ischemia reperfusion injury. In this study, we investigated whether heparin had a protective effect on renal ischemia reperfusion injury. Sheep (n = 12) were prepared for the chronic study with venous, arterial and urinary catheters inserted. In addition, pneumatic occluders and ultrasonic flow probes were placed on renal arteries. After a 5-day recovery period, the sheep were randomized to either a heparin treatment group (400 IU/kg i.v. bolus 10 minutes before renal artery occlusion, followed by a continuous effusion 25,000 IU in 250 ml of 0.9% NaCl at 10 ml/hr, n = 6) or a control group (n = 6), which received an equivalent volume of 0.9% NaCl. All the sheep then underwent 90 minutes of bilateral renal ischemia followed by 24 hours of reperfusion. Blood urea nitrogen (BUN), serum creatinine (Scr), and creatinine clearance (CrCl) were determined at various intervals during both the ischemic and reperfusion periods. Kidney tissue samples were obtained at autopsy for histologic examination. As a result, there were significant differences in the degree of inflammation (1.50 +/- 1.24 Vs 0.50 +/- 0.79, P < 0.05) between the control and heparin treatment groups, but not in the degree of injury (2.83 +/- 0.44 Vs 2.33 +/- 0.28). In this study, heparin significantly attenuated polymorphonuclear leukocytes (PMNs) infiltration within the interstitium, but it did not affect the degree of renal damage as measured by urinary chemistries or renal tubular damage as assessed by histopathologic evaluation.

Animals↗