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Biomedical subjects

K S Kim

Publications and source records attributed to K S Kim.

At least 127 records · Page 7Linked to original sources

Traversal of Candida albicans across human blood-brain barrier in vitro.

Candida albicans is an opportunistic pathogen, which primarily affects neonates and immunocompromised individuals. The pathogen can invade the central nervous system, resulting in meningitis. At present, the pathogenesis of C. albicans meningitis is unclear. We used an in vitro model of the human blood-brain barrier to investigate the interaction(s) of C. albicans with human brain microvascular endothelial cells (BMEC). Binding of C. albicans to human BMEC was time and inoculum dependent. Invasion of C. albicans into human BMEC was demonstrated by using an enzyme-linked immunosorbent assay based on fluorescent staining of C. albicans with calcoflour. In contrast, avirulent Candida mutant strains and nonpathogenic yeast Saccharomyces cerevisiae were not able to bind and invade human BMEC. Morphological studies revealed that on association with human BMEC, C. albicans formed germ tubes and was able to bud intracellularly. Transmission electron microscopy showed various stages of C. albicans interactions with human BMEC, e.g., pseudopod-like structures on human BMEC membrane and intracellular vacuole-like structures retaining C. albicans. Of interest, C. albicans was able to bud and develop pseudohyphae inside human BMEC without apparent morphological changes of the host cells. In addition, C. albicans penetrates through human BMEC monolayers without a detectable change in transendothelial electrical resistance and inulin permeability. This is the first demonstration that C. albicans is able to adhere, invade, and transcytose across human BMEC without affecting monolayer integrity. A complete understanding of the interaction(s) of C. albicans with human BMEC should contribute to the understanding of the pathogenic mechanism(s) of C. albicans meningitis.

Blood-Brain Barrier↗

Role of skin prick test and serological measurement of specific IgE in the diagnosis of occupational asthma resulting from exposure to vinyl sulphone reactive dyes.

OBJECTIVES: Some patients with occupational asthma resulting from exposure to reactive dyes have skin reactivity to the causative dyes and specific IgE to reactive dyes have been found in these patients. However, the usefulness of skin prick tests (SPTs) and serological measurement of specific IgE in screening, diagnosis, and monitoring the occupational asthma resulting from exposure to reactive dyes have not yet been assessed. In this study, the clinical validation of SPTs and measurement of specific IgE to vinyl sulphone reactive dyes by enzyme linked immunosorbent assay (ELISA) was evaluated. METHODS: 42 Patients with occupational asthma from reactive dyes (true positive group) were enrolled. In these the causative reactive dye was confirmed by bronchial challenge test. 93 Asymptomatic factory workers with negative challenge to the reactive dye (true negative group) and 16 unexposed controls with negative challenge to the reactive dye were also enrolled. Skin prick tests were done with 10 mg/ml reactive dye in 0.4% phenol/0.9% saline. IgE specific to reactive dye conjugated to human serum albumin (HSA) was measured with enzyme linked immunosorbent assays (ELISAs). RESULTS: None of the unexposed controls had a positive response to SPTs. The sensitivity (76.2% v 53.7%), specificity (91.4% v 86.0%), positive predictive value (80.0% v 62.9%), and negative predictive value (89.5% v 80.8%) of SPTs were higher than those of ELISAs. The mean weal size of reaction to reactive dye was weakly correlated with the ELISA optical density of IgE to reactive dye conjugate in patients with occupational asthma from reactive dyes (n=41, r=0.337, p<0.05). In four patients with occupational asthma from reactive dyes and eight control subjects exposed to reactive dye, IgE specific to reactive dye conjugated to HSA was detected with ELISA even though they showed negative skin reactivity. Six patients completely avoided the reactive dye for a mean (SD) 27.8 (10.3) months, IgE specific to reactive dyes decreased in all six patients (p<0.05) during this time. CONCLUSIONS: Both SPTs and detection of IgE specific to reactive dye in serum samples could be valuable for screening, diagnosis, and monitoring occupational asthma resulting from exposure to reactive dyes. These two tests would complement each other.

Adult↗

Spatio-temporal pattern of EEG in young brain respiration-training children.

We have evaluated the effect of 'Brain Respiration' training on brain activity using Karhunen-Loeve (KL) decomposition as a method for spatio-temporal analysis of the electroencephalogram (EEG). BR training is a form of breath-work to optimize the function of the brain by concentrating Qi energy in the brain. Recently, BR-training has been reported to improve emotional maturity (i.e., EQ), short-term memory and intuition (Yoo et al., 1998). EEG data were taken during BR-training from 12 young BR-trainees (average age: 9.4 years) who had trained for 4 to 14 months, and during relaxation from age matched non-trained children. Spatio-temporal analysis showed a significant difference of EEG dynamics in right prefrontal, right inferior frontal, posterior temporal, parietal and occipital areas between BR-trainees and the control group. Amplitude of eigenvector components of BR-trainees in the areas of frontal, temporal and occipital cortex was larger than that of non-trained children (values were smaller in parietal cortex), with remarkably high amplitude alpha coherence all over the scalp. These results suggest that BR-training possibly activates brain function through changes in the activity of the frontal association area where higher mental integration and creative activities are mediated.

Brain↗

Natural history of refluxing distal ureteral stumps following upper tract surgery in children with ectopic ureter or ureterocele.

BACKGROUND: It is a difficult problem to manage refluxing distal ureteral stumps after an upper tract approach in the ectopic ureter and ureterocele. We evaluated the natural history of the remaining refluxing distal ureteral stumps through a close follow-up. PATIENTS AND METHODS: From 1991 to 1998, nine patients with the ectopic ureter or ureterocele, whose age ranged from one to 20 (median 5.0) months, had undergone an upper tract surgery for ectopic ureter (2) or ectopic ureterocele (7). The upper tract surgery for ureterocele or ectopic ureter included a total nephrectomy (2), a partial nephrectomy (6) or a proximal ureteroureterostomy (1), leaving distal ureteral stump. We evaluated the clinical results of the remaining ureteral stumps every 6 or 12 months. The postoperative follow-up period was 51 (median; range 21-96) months. RESULTS: Among the 9 patients, 5 showed disappearance of the reflux and a markedly reduced stump size in the follow-up study. Improvement was noted in 4 patients within 6 months and in 1 by 20 months postoperatively. Two patients subsequently underwent a bladder level surgery due to problems not associated with the ureteral stump itself. Two patients have been followed up for 30 and 39 months, but without any improvement. An intermittent asymptomatic bacteriuria was noted in all patients during the follow-up, but no patient suffered from symptomatic urinary tract infection requiring an additional surgery. CONCLUSIONS: Since refluxing distal ureteral stumps were spontaneously resolved in more than half of the cases and did not cause significant problems during the follow-up, it is not necessary to remove the refluxing ureter simultaneously at the time of the upper tract surgery.

Female↗

Suitability of AFLP markers for the study of genetic relationships among Korean native dogs.

To determine the genetic relationships among domestic dog breeds, we performed both a sequence comparison of mitochondrial DNA (mtDNA) and an amplified fragment length polymorphisms (AFLP) analysis. Three of four regions of mtDNA, cytochrome b, cytochrome oxidase subunit II, and 16S rRNA genes were highly homogeneous among dog breeds, whereas the other region, the control region, showed relatively high polymorphisms with a maximum percentage difference of 3.18%. However, the control region showed extensive polymorphism even within breeds, and the relationship tree derived from the data could not clearly delimit distinct breeds. 19 EcoRI/MseI primer combinations were used to generate AFLP markers among 25 dogs from 11 breeds including three Korean native dogs. These amplification reactions allowed the detection of more than 1900 amplification products of which 408 were identified as polymorphic bands. Unrooted neighbor-joining tree based on dissimilarity values showed that the Korean native dogs were clustered together with the Asian dogs and that the Asian originated dogs were clustered separately from Western originated dogs. A consensus tree using parsimony method also showed Korean native dogs were grouped separately from the other dogs with moderate bootstrap values. Taken together, it is concluded that AFLP analysis is a more informative tool for revealing genetic relationships among dog breeds than mtDNA sequence comparison.

Animals↗

Using edge enhancement to identify subtle findings on soft-copy neonatal chest radiographs.

OBJECTIVE: The purpose of this study was to evaluate whether edge enhancement could improve the visibility of subtle findings on soft copies of neonatal chest radiographs. MATERIALS AND METHODS: Two radiologists reviewed 82 soft-copy neonatal chest radiographs before and after the application of edge enhancement on our picture archiving and communication system (PACS). The visibility of a pneumothorax (n = 22), central venous catheter (n = 32), umbilical arterial catheter (n = 36), endotracheal tube (n = 40), and normal anatomic structures (the minor fissure, anterior segmental bronchus of the right upper lobe, and aortic arch, n = 57) was evaluated. Six of 22 soft-copy images depicting a pneumothorax were excluded from the evaluation of image quality either because of the large size of the pneumothorax itself (n = 7) or because of the lack of confirmatory evidence that would have been provided by an additional lateral decubitus (n = 6) or cross-table lateral radiograph (n = 3). Image quality was evaluated by visual grading analysis. RESULTS: The visibility of a pneumothorax (p < 0.01), vascular catheters (p < 0.001), the minor fissure (p < 0.001), and the anterior segmental bronchus of the right upper lobe (p < 0.001) improved significantly after applying edge enhancement to soft copies of neonatal chest radiographs, whereas the visibility of the aortic arch did not improve. Evaluations of the improvements in the visibility of the endotracheal tube were inconsistent. CONCLUSION: Application of edge enhancement to soft copies of neonatal chest radiographs helps radiologists to identify small pneumothoraces, vascular catheters, and delicate normal structures, thereby improving the detection of subtle chest findings in the neonatal intensive care unit.

Catheterization, Central Venous↗

The effect of total sleep deprivation on cognitive functions in normal adult male subjects.

This study was conducted to evaluate the effect of acute sleep deprivation on cognitive functions. A total of 18 healthy right handed males were deprived of sleep for 24 hours. Luria-Nebraska Neuropsychological Battery and calculation & digit-span subtest of K-WAIS were administered before and after sleep deprivation in order to examine the changes of cognitive functions. There were no differences in freedom from distractibility, tacile function, visual function, reading, writing, arithmetic and intellectual process function. However, the cognitive functions such as motor, rhythm, receptive & expressive speech, memory and complex verbal arithmetic function were decreased after sleep deprivation. All of these functions are known to be related to the right anterior hemisphere. For localization scales, the scores of right frontal and right temporal dysfunction scale were increased after sleep deprivation. These results indicate that sleep deprivation has a negative effect on cognitive functions, especially those associated with right anterior hemisphere or subcortical areas.

Adult↗

Meta-analysis of hypertension as a risk factor of cerebrovascular disorders in Koreans.

This study was conducted to integrate the results of previous studies which evaluated hypertension as a risk factor for cerebrovascular disorders (CVD) in Koreans. We retrieved the Korean literature using a manual search and the English literature using the MEDLINE database concerning the relationship between hypertension and CVD in Koreans from 1980 to 1997. The overall effect size of hypertension as a risk factor of CVD was represented by common odds ratio (OR). Before the integration of each effect size, a heterogeneity test and a sensitivity test was conducted. The materials were nine published epidemiologic studies with a total of 2,271 cases of CVD. The common ORs (95% confidence interval) of overall CVD, hemorrhagic CVD and ischemic CVD associated with hypertension were 4.10 (3.56-4.71), 6.56 (4.92-8.80) and 3.28 (2.77-3.90), respectively. Thus, the common OR of hemorrhagic CVD associated with hypertension was significantly higher than that of overall or ischemic CVD. This suggests that hypertension is an important risk factor for overall CVD and its subtypes in Koreans. Due to the lack of reliable prospective studies, however, longitudinal study is required in this area.

Humans↗

The relationship between microvessel count and the expression of vascular endothelial growth factor, p53, and K-ras in non-small cell lung cancer.

Using immunohistochemical staining, we studied the relationship between the microvessel count (MC) and the expression of K-ras, mutant p53 protein, and vascular endothelial growth factor (VEGF) in 61 surgically resected non-small cell lung cancers (NSCLC) (42 squamous cell carcinoma, 14 adenocarcinoma, 2 large cell carcinoma, 2 adenosquamous carcinoma, and 1 mucoepidermoid carcinoma). MC of the tumors with lymph node (LN) metastasis was significantly higher than that of tumors without LN metastasis (66.1+/-23.1 vs. 33.8+/-13.1, p<0.05). VEGF was positive in 54 patients (88.5%). MC was 58.1+/-25.2 (mean+/-S.D.) in a x200 field, and it was significantly higher in VEGF(+) tumors than in VEGF(-) tumors (61.4+/-23.7 vs. 32.9+/-23.8, p<0.05). VEGF expression was higher in K-ras-positive or mutant p53-positive tumors than in negative tumors (p<0.05). MC was significantly higher in K-ras(+) tumors than in K-ras(-) tumors, although it did not differ according to the level of mutant p53 protein expression. Survival did not differ with VEGF, mutant p53, or K-ras expression, or the level of MC. In conclusion, there is a flow of molecular alterations from K-ras and p53, to VEGF expression, leading to angiogenesis and ultimately lymph node metastasis. Correlations between variables in close approximation and the lack of prognostic significance of individual molecular alterations suggest that tumorigenesis and metastasis are multifactorial processes.

Adult↗

Is body mass index the prognostic factor in breast cancer?: a meta-analysis.

This study was performed to integrate the results of previous studies that investigated the relationship between body mass index (BMI) and prognosis in breast cancer. We reviewed the English literatures using the MEDLINE database from 1966 to 1999. The materials included 12 published articles with a total of 8,029 cases of breast cancer. The effect size was obtained from hazard ratio in each study. Homogeneity test was conducted before the integration of each effect size and the result demonstrated that the studies were heterogeneous. A random effect model was used to integrate the overall effect size. The integrated effect size was 1.56 (95% confidence interval, 1.22-2.00). In addition, publication bias should be accounted for because each published study was asymmetric in shape revealed by funnel plot. These results suggest that BMI have a prognostic significance in breast cancer. We believe that well-designed longitudinal studies, involving a large number of samples are required to resolve these issues.

Body Mass Index↗

Inhibition of rac1 reduces PDGF-induced reactive oxygen species and proliferation in vascular smooth muscle cells.

In vascular smooth muscle cells, reactive oxygen species (ROS) were known to mediate platelet-derived growth factor (PDGF)-induced cell proliferation and NADH/NADPH oxidase is the major source of ROS. NADH/NADPH oxidase is controlled by rac1 in non-phagocytic cells. In this study, we examined whether the inhibition of rac1 by adenoviral-mediated gene transfer of a dominant negative rac1 gene product (Ad.N17rac1) could reduce the proliferation of rat aortic vascular smooth muscle cells (RASMC) stimulated by PDGF via decreasing intracellular ROS. RASMC were stimulated by PDGF (80 ng/mL) with or without N-acetylcysteine 1 mM or infected with 100 mutiplicity of infection of Ad.N17rac1. Intracellular ROS levels were measured at 12 hr using carboxyl-2', 7'-dichlorodihydrofluorescein diacetate confocal microscopy. At 72 hr, cellular proliferation was evaluated by cell number counting and XTT assay. Compared with control, ROS levels were increased by 2-folds by PDGF. NAC and Ad.N17rac1 inhibited PDGF-induced increase of ROS by 77% and 65%, respectively. Cell number was increased by PDGF by 1.6-folds compared with control. NAC and Ad.N17rac1 inhibited PDGF-induced cellular growth by 45% and 87%, respectively. XTT assay also showed similar results. We concluded that inhibition of rac1 in RASMCs could reduce intracellular ROS levels and cellular proliferation induced by PDGF.

Adenoviridae↗

Thermovisual evaluation of acupuncture points.

The aim of our study is to evaluate the temperature distributions around the acupuncture points and channels by visualizing the infrared emissions emanated from the human skin. Our thermal imaging system that is the most sensitive to 10um long infrared wavelength allows us to recognize the actual location of acupuncture point and analyze its functional condition by examining the temperature gradient between the point and its surrounding skin area. The temperature perception of acupuncture point on extremities is especially important since its location and functional condition have a tendency to be altered if one contract disease such as immunodeficiency, arterial hypertension, and dyskinesia of biliary ducts. Also, thermovisual examinations over the acupuncture points allow us to perform the objective medical treatments by observing the transition of temperature gradients.

Acquired Immunodeficiency Syndrome↗

Cyclooxygenase inhibitors regulate the expression of a TGF-beta superfamily member that has proapoptotic and antitumorigenic activities.

The antitumorigenic activity of nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase (COX) inhibitors, is well established, but responsible molecular mechanisms are not fully understood. NSAIDs stimulate apoptosis by COX dependent and independent mechanisms in colorectal cells in culture. Identification of genes regulated by COX inhibitors could lead to a better understanding of their proapoptotic and anti-neoplastic activities. Using subtractive hybridization, a cDNA which was designated as NSAID activated gene (NAG-1) was identified from NSAID-treated HCT-116, human colorectal cells. NAG-1 has an identical sequence with a novel member of the TGF-beta superfamily that has 5 different names. In the HCT-116 cells, NAG-1 expression is increased and apoptosis is induced by treatment with some NSAIDs in a concentration and time-dependent manner. NAG-1 transfected cells exhibited increased basal apoptosis, increased response to NSAIDs and reduced soft agar cloning efficiency. Furthermore, transplantable tumors derived from NAG-1 transfected HCT-116 cells showed reduced tumorigenicity in athymic nude mice compared with vector-transfected HCT-116 cells. The increased NAG-1 expression by NSAIDs provides a suitable explanation for COX-independent apoptotic effects of NSAIDs in cultured cells. These data demonstrate that NAG-1 is an antitumorigenic and proapoptotic protein, and its regulation by COX inhibitors may provide new clues for explaining their proapoptotic and antitumorigenic activities.

Animals↗

Oxidation of polycyclic aromatic hydrocarbons by ozone in the presence of sand.

A series of soil slurry experiments was performed to investigate the characteristics of PAHs removal by ozone in various conditions. Gaseous ozone was bottled into the aqueous phase in the presence of soil contaminated by PAHs. The effects of soil media, OH radical scavengers, ozone dosage, and humic acid were examined at the given experimental conditions. There exists a substantial difference in the removal of PAH according to the types of soil media tested. Baked sand showed the highest removal efficiency compared to the others. The descending order of removal rate was: BS > S > GB. This is considered to be due to the OH radical effect produced by catalytic reactions of ozone with the reactive site on the and. This is qualitatively proved by the experiment of scavenging OH radicals using tert-butanol. The comparison of half-lives of ozone in sand and glass bead columns further supports this hypothesis. It was found that about 22% of enhancement of phenanthrene destruction was accomplished by OH radicals produced by the catalytic ozone decomposition. The rate of ozone consumption for the phenanthrene oxidation was obtained as 1.88 mg/mgO3/min.

Catalysis↗

Structural analysis of multifunctional peptide motifs in human bifunctional tRNA synthetase: identification of RNA-binding residues and functional implications for tandem repeats.

Human bifunctional glutamyl-prolyl-tRNA synthetase (EPRS) contains three tandem repeats linking the two catalytic domains. These repeated motifs have been shown to be involved in protein-protein and protein-nucleic acid interactions. The single copy of the homologous motifs has also been found in several different aminoacyl-tRNA synthetases. The solution structure of repeat 1 (EPRS-R1) and the secondary structure of the whole appended domain containing three repeated motifs in EPRS (EPRS-R123) was determined by nuclear magnetic resonance (NMR) spectroscopy. EPRS-R1 consists of two helices (residues 679-699 and 702-721) arranged in a helix-turn-helix, which is similar to other RNA binding proteins and the j-domain of DnaJ, and EPRS-R123 is composed of three helix-turn-helix motifs linked by an unstructured loop. When tRNA is bound to the appended domain, chemical shifts of several residues in each repeat are perturbed. However, the perturbed residues in each repeat are not the same although they are in the same binding surface, suggesting that each repeat in the appended domain is dynamically arranged to maximize contacts with tRNA. The affinity of tRNA to the three-repeated motif was much higher than to the single motif. These results indicate that each of the repeated motifs has a weak intrinsic affinity for tRNA, but the repetition of the motifs may be required to enhance binding affinity. Thus, the results of this work gave information on the RNA-binding mode of the multifunctional peptide motif attached to different ARSs and the functional reason for the repetition of this motif.

Amino Acid Motifs↗

Phosphatidylinositol 3-kinase activation and interaction with focal adhesion kinase in Escherichia coli K1 invasion of human brain microvascular endothelial cells.

Invasion of brain microvascular endothelial cells (BMEC) is a prerequisite for successful crossing of the blood-brain barrier by Escherichia coli K1. We have previously demonstrated the requirement of cytoskeletal rearrangements and activation of focal adhesion kinase (FAK) in E. coli K1 invasion of human BMEC (HBMEC). The current study investigated the role of phosphatidylinositol 3-kinase (PI3K) activation and PI3K interaction with FAK in E. coli invasion of HBMEC. PI3K inhibitor LY294002 blocked E. coli K1 invasion of HBMEC in a dose-dependent manner, whereas an inactive analogue LY303511 had no such effect. In HBMEC, E. coli K1 increased phosphorylation of Akt, a downstream effector of PI3K, which was completely blocked by LY294002. In contrast, non-invasive E. coli failed to activate PI3K. Overexpression of PI3K mutants Deltap85 and catalytically inactive p110 in HBMEC significantly inhibited both PI3K/Akt activation and E. coli K1 invasion of HBMEC. Stimulation of HBMEC with E. coli K1 increased PI3K association with FAK. Furthermore, PI3K/Akt activation was blocked in HBMEC-overexpressing FAK dominant-negative mutants (FRNK and Phe397FAK). These results demonstrated the involvement of PI3K signaling in E. coli K1 invasion of HBMEC and identified a novel role for PI3K interaction with FAK in the pathogenesis of E. coli meningitis.

Blood-Brain Barrier↗

Remission in models of type 1 diabetes by gene therapy using a single-chain insulin analogue.

A cure for diabetes has long been sought using several different approaches, including islet transplantation, regeneration of beta cells and insulin gene therapy. However, permanent remission of type 1 diabetes has not yet been satisfactorily achieved. The development of type 1 diabetes results from the almost total destruction of insulin-producing pancreatic beta cells by autoimmune responses specific to beta cells. Standard insulin therapy may not maintain blood glucose concentrations within the relatively narrow range that occurs in the presence of normal pancreatic beta cells. We used a recombinant adeno-associated virus (rAAV) that expresses a single-chain insulin analogue (SIA), which possesses biologically active insulin activity without enzymatic conversion, under the control of hepatocyte-specific L-type pyruvate kinase (LPK) promoter, which regulates SIA expression in response to blood glucose levels. Here we show that SIA produced from the gene construct rAAV-LPK-SIA caused remission of diabetes in streptozotocin-induced diabetic rats and autoimmune diabetic mice for a prolonged time without any apparent side effects. This new SIA gene therapy may have potential therapeutic value for the cure of autoimmune diabetes in humans.

Animals↗