Biomedical subjects

S H Kim

Publications and source records attributed to S H Kim.

At least 163 records · Page 9Linked to original sources

PubMed2002

Receptor mechanisms and circuitry underlying NMDA antagonist neurotoxicity.

NMDA glutamate receptor antagonists are used in clinical anesthesia, and are being developed as therapeutic agents for preventing neurodegeneration in stroke, epilepsy, and brain trauma. However, the ability of these agents to produce neurotoxicity in adult rats and psychosis in adult humans compromises their clinical usefulness. In addition, an NMDA receptor hypofunction (NRHypo) state might play a role in neurodegenerative and psychotic disorders, like Alzheimer's disease and schizophrenia. Thus, understanding the mechanism underlying NRHypo-induced neurotoxicity and psychosis could have significant clinically relevant benefits. NRHypo neurotoxicity can be prevented by several classes of agents (e.g. antimuscarinics, non-NMDA glutamate antagonists, and alpha(2) adrenergic agonists) suggesting that the mechanism of neurotoxicity is complex. In the present study a series of experiments was undertaken to more definitively define the receptors and complex neural circuitry underlying NRHypo neurotoxicity. Injection of either the muscarinic antagonist scopolamine or the non-NMDA antagonist NBQX directly into the cortex prevented NRHypo neurotoxicity. Clonidine, an alpha(2) adrenergic agonist, protected against the neurotoxicity when injected into the basal forebrain. The combined injection of muscarinic and non-NMDA Glu agonists reproduced the neurotoxic reaction. Based on these and other results, we conclude that the mechanism is indirect, and involves a complex network disturbance, whereby blockade of NMDA receptors on inhibitory neurons in multiple subcortical brain regions, disinhibits glutamatergic and cholinergic projections to the cerebral cortex. Simultaneous excitotoxic stimulation of muscarinic (m(3)) and glutamate (AMPA/kainate) receptors on cerebrocortical neurons appears to be the proximal mechanism by which the neurotoxic and psychotomimetic effects of NRHypo are mediated.

Adrenergic alpha-Agonists↗

PubMed2002

High prevalence of current asthma and active smoking effect among the elderly.

BACKGROUND: Although asthma is a common cause of morbidity in adults, relatively few objectively measured population studies of asthma prevalence in adult populations have been conducted. OBJECTIVE: To evaluate the prevalence of asthma, based on both a questionnaire and methacholine bronchial provocation test, and to determine the risk factors of asthma prevalence in an adult population. METHODS: A total of 2,467 adults, who were randomly selected from metropolitan urban, non-metropolitan urban and rural areas, responded to the modified ISAAC questionnaire, and underwent methacholine bronchial provocation tests and skin prick tests to locally common aeroallergens. RESULTS: The prevalence of current asthma based on the questionnaire and the methacholine challenge was 2.0% in adults younger than 40, 3.8% in 40- to 54-year-olds, 7.7% in 55- to 64-year-olds and 12.7% in those aged 65 or higher. For subjects of 55-64 years, active smoking was found to be significantly related with the prevalence of current asthma and bronchial hyper-responsiveness, although smoking was positively associated with percentage predictive value of forced expiratory volume of 1 s (FEV1). CONCLUSION: The prevalence of current asthma is common among the elderly, and active smoking may play an important role in the development of asthma and bronchial hyper-responsiveness among the elderly.

Adult↗

PubMed2002

Interferon-alpha induces interleukin-18 binding protein in chronic hepatitis C patients.

Interleukin-18 (IL-18), derived from macrophages and Kupffer cells, is the central pro-inflammatory cytokine leading to experimental liver failure. IL-18 binding protein (IL-18BP) is a circulating protein that binds IL-18 and neutralizes its activity. Since IL-18 production is increased in chronic HCV infection, we asked whether IFN-alpha might act on the IL-18/IL-18BP system in HCV patients. IL-18BP, total and free IL-18 plasma levels were determined in 13 HCV patients receiving 1 x 107 IU IFN-alpha subcutaneously daily for 28 days. The in vitro effects of IFN-alpha on macrophage IL-18BP and IL-18 were studied by enzyme-linked immunosorbent assays and Northern analysis. IFN-alpha administration increased IL-18BP plasma levels 3.24 fold 24 h after institution of therapy, resulting in a 67.4% reduction of free IL-18. Total IL-18 levels decreased from day +24 on. In vitro, IFN-alpha diminished IL-18 release from macrophages of healthy volunteers and chronic HCV patients. On top of its inhibitory effects on IL-1 and TNF-alpha release, IFN-alpha also exerts its anti-inflammatory action in vivo by induction of IL-18BP. These anti-inflammatory properties might account - together with its antiviral action - for its clinical efficacy in chronic hepatitis C.

Down-Regulation↗

PubMed2002

Typing of clinical isolates of Mycobacterium leprae and their distribution in Korea.

Although there is no genetic diversity in isolates of Mycobacterium leprae, the variance of tandem repeats in the rpoT gene was recently demonstrated. We have typed clinical isolates of M. leprae in Korea using difference of the tandem repeats in the rpoT gene. Among 69 patients, 65 Korean isolates (94.2%) demonstrated four copies of the 6 bp tandem repeat (GACATC) in the rpoT gene, and incidences of three copies were found in only two Koreans and two foreigners (2.9%, respectively).

Base Sequence↗

PubMed2002

Novel anaerobic process for the recovery of methane and compost from food waste.

Multi-step sequential batch two-phase anaerobic composting (MUSTAC) process was used to recover methane and composted material from food waste. The MUSTAC process consists of five leaching beds for hydrolysis, acidification and post-treatment, and an upflow anaerobic sludge blanket (UASB) reactor for methane recovery. This process involves the combined methods of sequential batch operation and two-phase anaerobic digestion for simple operation and high efficiency. Rumen microorganisms are inoculated due to their enhanced cellulolytic activity. Each leaching bed is operated in a sequential batch mode. Five leaching beds are operated in a multi-step mode with a two-day interval between degradation stages. Acidified products in the leachate from the leaching beds are converted to methane in the UASB reactor. The MUSTAC process demonstrated that it was capable of removing 84.9% of volatile solids (VS) and converting 85.6% of biochemical methane potential (BMP) into methane at 10.9 kg VS/m3 x d in 10 days. Methane gas production rate was 2.31 m3/m3 x d. The output from the post-treatment of residues in the same leaching bed without troublesome moving met the Korean regulation on compost, indicating that it could be used for soil amendment.

Bacteria, Anaerobic↗

PubMed2002

Development of rapid in vitro assay for oxidative liver injury and its application to 230 chemicals.

Water environments are thought to be polluted with thousands of synthetic chemicals and biproducts involving persistent organic pollutants and endocrine disrupters, and their human and ecological impacts are causing serious anxiety. Many bioassays have been undertaken to evaluate the hazardous impacts of toxic chemicals dissolved in water. Reactive Oxygen Species (ROS) are well known to be involved in the toxicity of various chemicals. ROS are mostly generated in liver and cause oxidative damage to DNA, lipids and proteins, resulting in the failure of cellular functions. In order to develop an in vitro bioassay system to estimate ROS induced liver toxicity by chemicals, we investigated the lipid peroxidation, liver cell injury, and genotoxicity using the human hepatocellular carcinoma cell line, Hep-G2 (ATCC HB 8065), and applied it to 230 chemicals.

Biological Assay↗

PubMed2001

Tandem translocation of chromosomes 22 and 15 with two preserved satellite stalk regions and deletion 22q13.3-qter.

We describe here a case of a tandem 22/15 translocation with deletion of the 22q13.3-qter region and retention of the NOR of chromosome 15. A 2(1/2)-year-old Korean girl was referred for chromosome analysis after a clinical evaluation for developmental delay. Physical examination revealed hypotonia, developmental delay, delay of gross motor milestones and speech delay. No dysmorphic features of face, hands or feet were evident in the patient. G-banded peripheral blood lymphocyte chromosomes showed a tandem translocation between chromosomes 22 and 15, with the satellite stalks of chromosome 15 apparently being retained. All-telomere FISH analysis using a TTAGGG repeat probe showed absent signals at the junction of the translocation. Sequential G-banding and FISH analysis using a beta satellite probe showed positive signals close to the junction of the translocation, an indication that the short arms of the chromosome 15 involved in the translocation are retained. FISH with a probe for arylsulfatase, mapped to 22q13.3 region, was negative on the translocation chromosome. Therefore, the 22q13.3 region is deleted.

Abnormalities, Multiple↗

PubMed2001

Deficient neurogenesis in forebrain-specific presenilin-1 knockout mice is associated with reduced clearance of hippocampal memory traces.

To examine the in vivo function of presenilin-1 (PS1), we selectively deleted the PS1 gene in excitatory neurons of the adult mouse forebrain. These conditional knockout mice were viable and grew normally, but they exhibited a pronounced deficiency in enrichment-induced neurogenesis in the dentate gyrus. This reduction in neurogenesis did not result in appreciable learning deficits, indicating that addition of new neurons is not required for memory formation. However, our postlearning enrichment experiments lead us to postulate that adult dentate neurogenesis may play a role in the periodic clearance of outdated hippocampal memory traces after cortical memory consolidation, thereby ensuring that the hippocampus is continuously available to process new memories. A chronic, abnormal clearance process in the hippocampus may conceivably lead to memory disorders in the mammalian brain.

Alzheimer Disease↗

PubMed2001

Tracheal compression by elongated aortic arch in patients with congenitally corrected transposition of the great arteries.

We investigate the tracheal compression by aortic arch in patients with congenitally corrected transposition of the great arteries. Fourteen patients whose ascending aorta was connected to descending aorta on the contralateral side were divided into two groups according to the severity of tracheal compression on lateral angiogram: group 1 (stenosis > or = 50%, eight patients) and group 2 (stenosis < 50%, six patients). We compared the following variables between the groups: aortic size, lateral displacement of ascending aorta, retrosternal space, and contour of aortic arch. Spiral computed tomography (CT) was done in five patients of group 1. The ratio between measured and normal diameters of ascending aorta of group 1 was significantly larger than that of group 2 (1.57 +/- 0.14 compared to 1.19 +/- 0.26, p = 0.014). There was linear correlation between the tracheal compression and aortic size (r = 0.69, p = 0.001). The ascending aorta was positioned more laterally and the aortic arch was located more posteriorly in group 1. In four patients with decreased tracheal compression after surgery, aortic size decreased and the ascending aorta restored its anterior position. Spiral CT showed transversely oriented aortic arch and severe tracheal compression in the anteroposterior direction by aortic arch. The tracheal compression by aortic arch in corrected transposition is common when the descending aorta is located on the contralateral side of the ascending aorta. Aortic size, posterior position, elongation, and end-on appearance of the aortic arch are the useful predictors of tracheal compression.

Adolescent↗

PubMed2001

Enhanced IL-18 expression in common skin tumors.

Interleukin-18 (IL-18) has been found to have multiple effects upon various cells involved in inflammatory response. Recently we reported that B16 murine melanoma cells are able to produce IL-18, which is involved in the regulation of intracellular reactive oxygen intermediates (ROI) and Fas-ligand expression, indicating that IL-18 plays key role in the tumor activity of melanoma. In this study, we investigated the pattern of IL-18 expression in the human system. IL-18 production was tested by enzyme linked immunosorbent assay (ELISA) assay in various tumor cell lines, including Raji (Burkitt's lymphoma), IM-9 (B lymphoblast), Jurkat (acute T cell leukemia), SK-MES-1 (squamous cell carcinoma (SCC) cell line), SK-MEL-2, G-361, DM-4, and DX-3 (melanoma cell lines). ELISA tests showed that IL-18 was highly expressed in malignant skin tumors such as SK-MES-1, SK-MEL-2, G-361, DM-4, and DX-3 cell lines, thus suggesting that IL-18 production may be associated with the malignancy of skin tumors. Here, we report that enhanced IL-18 expression is positively correlated with malignant skin tumors such as SCC and melanoma, suggesting the importance role of IL-18 in malignancy of skin tumors. Taken together, expression of IL-18 by tumor cells in human skin tissue may provide an important clue to understand the pathogenesis of malignant skin tumors.

Basal Cell Carcinoma↗

PubMed2001

Increased frequencies of glutathione S-transferase (GSTM1 and GSTT1) gene deletions in Korean patients with acquired aplastic anemia.

Patients with reduced ability to metabolize environmental carcinogens or toxins may be at risk of developing aplastic anemia. Glutathione S-transferase (GST) has been implicated in detoxifying mutagenic electrophilic compounds. This study asked whether the homozygous gene deletions of GSTM1 and GSTT1 affect the likelihood of developing aplastic anemia. The incidence of GSTM1 and GSTT1 gene deletions was significantly higher for aplastic anemia patients (odds ratio [OR]: 3.1, P =.01 and OR: 3.1, P =.004, respectively) than for healthy controls. Among the aplastic anemia patients, 17.5% (10:57) had chromosomal abnormalities at the time of diagnosis, and all aplastic anemia patients with chromosomal abnormalities showed GSTT1 gene deletions (P =.048). Individuals with GSTM1 and GSTT1 gene deletions may have greater susceptibility to aplastic anemia. It is possible that genetic instability or chromosomal damage due to abnormal detoxification of environmental toxins might have worked as an important pathophysiologic mechanism of aplastic anemia for patients with GSTT1 gene deletions.

Adolescent↗

PubMed2001

Crystal structure and mechanism of catalysis of a pyrazinamidase from Pyrococcus horikoshii.

Bacterial pyrazinamidase (PZAase)/nicotinamidase converts pyrazinamide (PZA) to ammonia and pyrazinoic acid, which is active against Mycobacterium tuberculosis. Loss of PZAase activity is the major mechanism of pyrazinamide-resistance by M. tuberculosis. We have determined the crystal structure of the gene product of Pyrococcus horikoshii 999 (PH999), a PZAase, and its complex with zinc ion by X-ray crystallography. The overall fold of PH999 is similar to that of N-carbamoylsarcosine amidohydrolase (CSHase) of Arthrobacter sp. and YcaC of Escherichia coli, a protein with unknown physiological function. The active site of PH999 was identified by structural features that are also present in the active sites of CSHase and YcaC: a triad (D10, K94, and C133) and a cis-peptide (between V128 and A129). Surprisingly, a metal ion-binding site was revealed in the active site and subsequently confirmed by crystal structure of PH999 in complex with Zn(2+). The roles of the triad, cis-peptide, and metal ion in the catalysis are proposed. Because of extensive homology between PH999 and PZAase of M. tuberculosis (37% sequence identity), the structure of PH999 provides a structural basis for understanding PZA-resistance by M. tuberculosis harboring PZAase mutations.

Amidohydrolases↗

PubMed2001

Destabilization of CHK2 by a missense mutation associated with Li-Fraumeni Syndrome.

Li Fraumeni Syndrome (LFS) is a multicancer phenotype, most commonly associated with germ-line mutations in TP53. In a kindred with LFS without an inherited TP53 mutation, we have previously reported a truncating mutation (1100delC) in CHK2, encoding a kinase that phosphorylates p53 on Ser(20). Here, we describe a CHK2 missense mutation (R145W) in another LFS family. This mutation destabilizes the encoded protein, reducing its half-life from >120 min to 30 min. This effect is abrogated by treatment of cells with a proteosome inhibitor, suggesting that CHK2(R145W) is targeted through this degradation pathway. Both 1100delC and R145W germ-line mutations in CHK2 are associated with loss of the wild-type allele in the corresponding tumor specimens, and neither tumor harbors a somatic TP53 mutation. Our observations support the functional significance of CHK2 mutations in rare cases of LFS and suggest that such mutations may substitute for inactivation of TP53.

Adult↗

PubMed2001

Receptor-mediated delivery of all trans-retinoic acid to hepatocyte using poly(L-lactic acid) nanoparticles coated with galactose-carrying polystyrene.

All trans-retinoic acid (RA)-loaded poly(L-lactic acid) (PLA) nanoparticles coated with galactose-carrying polymer, as hepatocyte-specific targeting material using galactose ligands as recognition signals to asialoglycoprotein receptors were prepared by the diafiltration method. Effects of released RA from its loaded nanoparticles on morphology and DNA synthesis of hepatocytes were studied. Receptor-mediated endocytosis of the nanoparticles was checked by fluorescence and confocal laser microscopy. It was found that the shapes of most hepatocytes attached onto polystyrene dish precoated with collagen solution were flat and spreading at low concentration of RA for the RA-loaded nanoparticles, whereas their shapes were round at even low concentration of RA when RA was mixed with the nanoparticles. From the fluorescence and confocal laser microscopic studies, it was suggested that the nanoparticles coated with galactose-carrying polymers were internalized by the hepatocytes through the receptor-mediated mechanism. The RA-loaded nanoparticles were more potent stimulators of hepatocyte DNA synthesis than the free RA system in the presence of epidermal growth factor (EGF) owing to the controlled release of RA from the RA-loaded nanoparticles.

Animals↗

PubMed2001

Observation of a (6)(LambdaLambda)He double hypernucleus.

A double-hyperfragment event has been found in a hybrid-emulsion experiment. It is identified uniquely as the sequential decay of ( 6)(LambdaLambda)He emitted from a Xi(-) hyperon nuclear capture at rest. The mass of ( 6)(LambdaLambda)He and the Lambda-Lambda interaction energy DeltaB(LambdaLambda) have been measured for the first time devoid of the ambiguities due to the possibilities of excited states. The value of DeltaB(LambdaLambda) is 1.01+/-0.20(+0.18)(-0.11) MeV. This demonstrates that the Lambda-Lambda interaction is weakly attractive.

Journal Article↗

PubMed2001

Structure-motion-performance relationship of flux-enhanced reverse osmosis (RO) membranes composed of aromatic polyamide thin films.

The present paper explores the role of dimethyl sulfoxide (DMSO) used as an additive to modify the morphological as well as the molecular nature of aromatic polyamide during the formation of thin-film-composite (TFC) membranes. In addition, it elucidates the mechanism of enhancing the reverse osmosis (RO) permeation of the resulting membranes in proportion to the addition of DMSO. Morphological studies by atomic force microscopy (AFM) observed that as the concentration of DMSO increased, the surface roughness and the surface area of the aromatic polyamide TFC membranes became higher and larger, compared to FT-30 membrane for which DMSO was not added during interfacial reaction. Such morphological changes were brought about from fluctuating interface through reducing the immiscibility between aqueous/organic phases by DMSO and provided more opportunities to have contact with water molecules on the surface, participating in the enhancement of the water permeability. Chemical composition studies by X-ray photoelectron spectroscopy (XPS) revealed that there was a considerable increase of the cross-linked amide linkages relative to the linear pendant carboxylic acid groups in the TFC membranes of more DMSO addition. The increase of such amide linkages as hydrogen bonding sites facilitated the diffusion of water molecules through the thin films and played a favorable role in elevating water flux without considerable loss of salt rejection. Relaxation and motion analyses by 1H solid-state nuclear magnetic resonance (NMR) spectroscopy also confirmed the XPS revelation on the basis of measurements of the spin-lattice relaxation time in the rotating frame, T1rho, and determination of the correlation time, tau(c), for the aromatic polyamides forming thin films. The trend of longer tau(c)'s with the increase of DMSO concentration reflected the thin-film aromatic polyamides of less locally mobile chains, accompanied by the higher degree of cross-linking and, hence, the greater number of amide groups. The combined results of AFM, XPS, and solid-state NMR provided a robust explanation for the mechanism of flux enhancement of the aromatic polyamide TFC membranes with the addition of DMSO, which would contribute to not only a fundamental understanding of the process but also an advanced designing of the so-called "tailor-fit" TFC membranes.

Dimethyl Sulfoxide↗

PubMed2001

A proapoptotic peptide for the treatment of solid tumors.

We have designed a novel peptide, DP1, which is able to mediate significant induction of apoptosis in solid tumors by local injection. This peptide, comprised of a protein transduction domain (PTD), PTD-5, fused to an antimicrobial peptide, (KLAKLAK)2, was able to trigger rapid apoptosis in a variety of cell lines in vitro, including MCA205 murine fibrosarcomas and human head and neck tumors. Furthermore, direct injection of DP1 into day 7 established MCA205 tumors in C57BL/6 mice resulted in the induction of tumor apoptosis and subsequent reduction in tumor volume. These results suggest that DP1 may be used clinically to treat accessible solid tumors or as an adjuvant therapy in conjunction with radiotherapy, standard chemotherapy, immunotherapy, or surgical debulking.

Amino Acid Sequence↗

PubMed2001

Efficient intracellular delivery of an exogenous protein GFP with genetically fused basic oligopeptides.

Several oligopeptides, derived from certain proteins, translocate as a form fused to small molecules or exogenous proteins across the plasma membrane into cells. Some of these oligopeptides, the so-called protein-transduction domains (PTDs), contain a high proportion of basic residues. The translocation of some of these basic PTDs, such as oligoarginines, has been studied as chemically fused forms to other organic compounds. In this study, we also tested to determine whether or not oligoarginines, when fused genetically to an exogenous protein such as GFP, are also able to translocate efficiently across the plasma membrane. The oligoarginine Rn (n = 5,6,7,8,9)-GFP fusion proteins were translocated quite efficiently, and the transduction efficiency increased in proportion to the number of arginine residues. However, the cellular uptake of the oligolysine-GFP fusion proteins was less efficient than that of the corresponding oligoarginine-GFP fusion proteins. When fused to GFP, the translocation efficiency of R5 was similar to that of Tat(49-57)(RKKRRQRRR). This finding suggests that the arginine homo-oligopeptide is more efficient than other PTDs which contain a mixture of basic residues. On the other hand, both the K9- and Tat(49-57)-GFP fusion proteins were transduced with similar efficiencies. It appears that basic oligopeptides may be useful for the efficient translocation of diverse exogenous proteins as genetically fused forms.

Amino Acid Sequence↗