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Biomedical subjects

N G Kim

Publications and source records attributed to N G Kim.

18 recordsLinked to original sources
PubMed2000

Angiopoietin-2 at high concentration can enhance endothelial cell survival through the phosphatidylinositol 3'-kinase/Akt signal transduction pathway.

The angiopoietin-Tie2 system in endothelial cells is an important regulator of vasculogenesis and vascular integrity. High levels of angiopoietin-2 (Ang2) mRNA are observed in vascular activation during tumorigenesis. Although Ang2 is known to be a naturally occurring antagonist of angiopoietin-1 (Ang1) in vivo, the exact function of Ang2 itself is not known. Here, we found that a high concentration of Ang2 (800 ng/ml) acts as an apoptosis survival factor for endothelial cells during serum deprivation apoptosis. The survival effect of high concentration Ang2 was blocked by pre-treatment with soluble Tie2 receptor and the PI 3'-kinase-specific inhibitors, wortmannin and LY294002. Accordingly, 800 ng/ml of Ang2 induced phosphorylation of Tie2, the p85 subunit of phosphatidylinositol 3'-kinase (PI 3'-kinase), and serine-threonine kinase Akt at Ser473 in the human umbilical vein endothelial cells; lower concentrations of Ang2 (50 - 400 ng/ml) did not produce notable effects. These findings indicate that at high concentrations, Ang2, like Ang1, can be an apoptosis survival factor for endothelial cells through the activation of the Tie2 receptor, PI 3'-kinase and Akt, and thus may be a positive regulator of tumor angiogenesis. Oncogene (2000) 19, 4549 - 4552.

Androstadienes↗
PubMed2000

p16 is a major inactivation target in hepatocellular carcinoma.

BACKGROUND: The p16(INK4A) gene encodes 2 cell cycle regulator proteins, p16 and p14(ARF), by alternative splicing. This genetic locus also contains another cell cycle regulator gene, p15(INK4B), which encodes p15. The inactivation of the p16 protein has been demonstrated in some hepatocellular carcinomas (HCCs); however, the inactivation of the other 2 cell regulator proteins and their inactivation patterns are not well characterized. METHODS: To characterize the role of the above 3 cell cycle regulator proteins in HCCs, the authors examined the genomic status of the p16(INK4A) and p15(INK4B) genes and their RNA products in 20 HCC tissues and 7 human HCC cell lines. Homozygous deletions in each exon of p16(INK4A) and p15(INK4B) were evaluated by comparative multiplex polymerase chain reaction (PCR), and the methylation status of the p16(INK4A) and p15(INK4B) promoter region was analyzed by methylation specific PCR. RESULTS: Homozygous deletions were found in 6 of 20 HCCs (30%) and 2 of 7 HCC cell lines (29%). In 20 HCCs, the frequency of homozygous deletions was 20% in exon 1 of p15(INK4B), 20% in exon 2 of p15(INK4B), 10% in exon 1beta of p16(INK4A), 25% in exon 1alpha of p16(INK4A), 15% in exon 2 of p16(INK4A), and 15% in exon 3 of p16(INK4A). The authors found hypermethylation of the p16(INK4A) promoter region in 7 HCCs (35%) and 3 HCC cell lines (43%). The overall frequency of p16 alterations in HCCs, including hypermethylation and homozygous deletions, was 60% (12 of 20 cases). According to reverse transcriptase-PCR analysis, the absence of RNA expression was most frequent in p16 (11 of 20 cases, 55%) and less frequent in p15 (7 of 20 cases, 35%) and p14(ARF) (5 of 20 cases, 25%). CONCLUSIONS: Among the 3 cell cycle regulator proteins encoded at the 9p21 genetic locus, inactivation of p16 is the most frequent event in HCCs in which promoter hypermethylation and homozygous deletions are the common mechanisms.

Carcinoma, Hepatocellular↗
PubMed2000

Reporter constructs showing proper globin gene switching in cultured erythroid cell lines.

Recent advances in the study of globin gene switching in the context of complete gene locus have contributed greatly to our understanding of developmental regulation mechanism of globin gene expression. However, it is not clear yet whether the cluster is sufficient in proper gene switching when the globin genes are replaced with conventional reporter genes. Furthermore, even though erythroid-specific and ubiquitous transcription factors involved in erythroid-specific globin gene expression have been characterized and some plausible globin gene switching models have been suggested, any specific factor directly involved in globin gene switching is not yet identified. In this study, as an effort to further understand globin switching mechanism and to identify globin switching factors, we constructed reporter vectors by juxtaposing several putative regulatory elements in human beta-globin locus to conventional reporter genes and analyzed their stage-specific expression in erythroid cell lines. At the end, we demonstrated that gammabeta-type constructs, in which both gamma-type and beta-type globin reporter genes were linked in cis below beta-globin locus control region (LCR), show proper stage-specific reporter gene expression in erythroid cell lines and also recapitulate globin switching in cell hybrids.

Animals↗
PubMed2000

Putative chromosomal deletions on 9P, 9Q and 22Q occur preferentially in malignant gastrointestinal stromal tumors.

To characterize the type of genetic alterations in gastrointestinal stromal tumors (GISTs), we performed a comprehensive allelotype study of 14 GISTs (2 benign, 7 borderline and 5 malignant) by polymerase-chain-reaction and loss-of-heterozygosity (PCR-LOH) analysis using 102 microsatellite markers, and compared the results with comparative-genomic-hybridization (CGH) analysis. Among the 38 evaluated chromosomal arms, 16 (42.1%) showed LOH in at least one patient. Most frequent LOH was observed at chromosome 14p and 14q (9/14, 64%) and this was demonstrated in all types of GISTs (50% in benign, 71% in borderline and 80% in malignant). Additional chromosomal deletions were found in several chromosomal arms. Among them, deletions on chromosomal arms of 22q (3/14, 21.4%), 9p (2/14, 14.3%) and 9q (2/14, 14.3%) were the most frequent, and were detected only in malignant GISTs both by PCR-LOH and by CGH analysis. Additionally, 2 malignant GISTs with LOH on 9p showed homozygous deletions in the restricted area of 9p by multiplex PCR-LOH analysis. Thus, several putative chromosomal changes were preferentially present in malignant GISTs but rare in benign and borderline GISTs. These findings suggest that accumulated chromosomal changes may contribute to the progression and/or malignant transformation of GISTs.

Chromosome Deletion↗
PubMed2000

Perceiving circular heading in noncanonical flow fields.

Five experiments examined circular heading perception with optical flows that departed from the canonical form. Noncanonicity was achieved through nonrigidity of the environment (Experiments 1 and 2), oscillations of the point of observation (Experiment 3), and the bending of light (Experiments 4 and 5). In Experiments 1 and 2, perception was impaired more by nonrigidity of the ground plane than by nonrigidity of the medium. In Experiment 3, perception was unimpaired by noncanonical flows induced by the bounce and sway of observer locomotion. In Experiments 4 and 5, perception was not impaired when light paths were distorted by a spherical projection, but perception was impaired when they were distorted by a sine function. Results are discussed in relation to the hypothesis that the information for perceiving heading is the ordinal pattern of optical flow.

Adult↗
PubMed1999

Molecular cloning, expression, and characterization of angiopoietin-related protein. angiopoietin-related protein induces endothelial cell sprouting.

Using degenerate polymerase chain reaction, we isolated a cDNA encoding a novel 493-amino acid protein from human and mouse adult heart cDNAs and have designated it angiopoietin-related protein-2 (ARP2). The NH(2)-terminal and COOH-terminal portions of ARP2 contain the characteristic coiled-coil domain and fibrinogen-like domain that are conserved in angiopoietins. ARP2 has two consensus glycosylation sites and a highly hydrophobic region at the NH(2) terminus that is typical of a secretory signal sequence. Recombinant ARP2 expressed in COS cells is secreted and glycosylated. In human adult tissues, ARP2 mRNA is most abundant in heart, small intestine, spleen, and stomach. In rat embryos, ARP2 mRNA is most abundant in the blood vessels and skeletal muscles. Endothelial and vascular smooth muscle cells also contain ARP2 mRNA. Recombinant ARP2 protein induces sprouting in vascular endothelial cells but does not bind to the Tie1 or Tie2 receptor. These results suggest that ARP2 may exert a function on endothelial cells through autocrine or paracrine action.

Amino Acid Sequence↗
PubMed1999

Deletion mapping on the short arm of chromosome 8 in hepatocellular carcinoma.

To define the commonly deleted region on chromosome 8p for further positional cloning of the putative tumor suppressor gene, we carried out allelic imbalance (AI) studies in 41 HCCs using a panel of 37 microsatellite markers. The overall AI on 8p was 87.8% (36 of 41). Among the 36 cases with AI, 13 cases showed AI in all of the loci, suggesting entire deletion on the short arm of chromosome 8, while the remaining 23 cases showed partial AI. Detailed deletion mapping identified two independent commonly deleted regions on chromosome 8p. These were as follows: (1) centered by the D8S1819 and D8S1706 loci between the D8S561 and D8S1825 loci, (2) centered by the D8S1733 locus between the D8S298 and D8S1739 loci. These results suggest that the two putative tumor suppressor genes may be present on chromosome 8p.

Carcinoma, Hepatocellular↗
PubMed1999

Differential regulation of MAP kinase cascade in human colorectal tumorigenesis.

Hyper-activation of mitogen-activated protein kinase (MAPK) has recently been reported in several human cancers and activation of MAPK in those cancers may be associated with carcinogenesis through aberrant cell proliferation. To understand the roles of the MAPK pathway in colorectal tumorigenesis, we examined the status of extracellular signal-regulated protein kinases (ERK1/2) in 21 colorectal tumour specimens and compared it with that of paired normals. The specific MAPK activities were two- to tenfold lower in 71% (15 out of 21 cases) of colorectal tumours compared to those in paired normals. The individual MAPK kinase (MEK) correlated with MAPK activities (P = 0.006). Reduction of the MAPK and MEK activities in colorectal tumours was also observed in adenomas. These results suggested that down-regulation of the MAPK cascade may be caused by early genetic event(s) and that it may be related to the loss of normal growth control. Although MAPK activities were down-regulated both in adenomas and carcinomas, activities of the MAPKs in carcinomas were higher than those of paired adenomas. These results suggested that MAPK activities may be increased in the adenoma-to-carcinoma sequence and that it may play a role in the tumour progression. Observation of the differential regulation of MAPK activities in colorectal tumorigeneis suggested roles for the MAPK pathway in both positive and negative controls of cell growth.

Adenoma↗
PubMed1999

A new rehabilitation training system for postural balance control using virtual reality technology.

A new rehabilitation training system, designated as a virtual cycling system, was developed to improve postural balance control by combining virtual reality (VR) technology with a bicycle. Several parameters including path deviation, path deviation velocity, cycling time, and head movement were extracted and evaluated to quantify the extent of control. The system was effective as a training device and, in addition, the technology might have a wider applicability to the rehabilitation field.

Adult↗
PubMed1999

Accumulated frameshift mutations at coding nucleotide repeats during the progression of gastric carcinoma with microsatellite instability.

Microsatellite instability (MSI) and frameshift mutations in genes containing nucleotide repeats have been reported in a subset of gastric carcinomas, but the mutational profiles in precancerous lesions have not been characterized. To characterize the genetic events during gastric carcinogenesis, we analyzed DNA from 56 gastric adenomas and 167 gastric carcinomas for MSI using five microsatellite markers and for frameshift mutations at coding nucleotide repeats of the type II transforming growth factor beta receptor, BAX, hMSH3, hMSH6, IGF II receptor, and E2F-4 genes. On the basis of the number of markers displaying instability per tumor, the tumors were divided into three groups: those with two or more of the five markers showing instability (high MSI [MSI-H]), those with one of the five markers showing instability (low MSI [MSI-L]), and those with no instability. MSI-H was found in 8 adenomas (14%) and 19 carcinomas (11%), and MSI-L was found in 8 adenomas (14%) and 9 carcinomas (5%). These groups were tested for correlations with several clinicopathologic parameters. MSI-H gastric adenomas were related to the high histologic grade of composing dysplastic glands (p = 0.004), and MSI-H gastric carcinomas were associated with exophytic tumor growth (p = 0.005). We found 48 frameshift mutations at coding nucleotide repeats of the six genes, and all mutations except one were found in MSI-H gastric tumors. Only one of the 17 MSI-L tumors showed frameshift mutations at coding nucleotide repeats of the transforming growth factor beta receptor II gene. Compared with MSI-H gastric carcinomas, MSI-H adenomas had no mutations in the hMSH6 and the IGF II receptor genes, less frequent mutations in the transforming growth factor beta receptor II (38% versus 63%), BAX (13% versus 37%), and hMSH3 (13% versus 37%) genes, and more frequent mutations in the E2F-4 (50% versus 37%) gene. Our findings suggest that MSI and E2F-4 mutations are early genetic events and that mutations of the other five genes are accumulated during the progression of gastric carcinomas with MSI.

Adenoma↗
PubMed1998

Visually perceiving heading on circular and elliptical paths.

Five experiments addressed the perception of curvilinear heading under various conditions of optical flow. Perception of heading was unaffected by optical noise (Experiment 1) and was successful and equally accurate for flows generated by circular and elliptical paths of locomotion (Experiment 2). In Experiment 3, random perturbations of vector magnitudes in general curvilinear fields did not reduce the accuracy of perceived heading. When vector directions were randomly perturbed in Experiments 4 and 5, curvilinear heading perception was impaired. Discussion focuses on the inappropriateness of the vector normal hypothesis to the general curvilinear case, the importance of the pattern of relative vector directions, and the practical and theoretical significance of investigating different forms of noncanonical optical flow.

Eye Movements↗
PubMed1998

Detection of epileptiform activities in the EEG using neural network and expert system.

This paper proposes a multichannel spike detection in long term EEG monitoring for epilepsy. It is achieved by wavelet transform(WT), artificial neural network(ANN) and the expert system. First, a small set of wavelet coefficients is used to represent the characteristics of a single channel epileptic spikes and normal activities. The purpose of this WT is to reduce the number of inputs to the ANN. Next, three layer feed-forward network employing the error back propagation algorithm is trained and tested using parameters obtained by the WT. Spikes are identified in individual EEG channels by 16 identical neural networks. Finally, 16-channel expert system based on the context information of adjacent channels is introduced to reject artifacts and produce reliable results. In this study, epileptic spikes and normal activities were selected from 32 patient's EEGs (the seizure disorder: 12, normal: 20) in consensus among experts. The result shows that the WT reduced data input size and the preprocessed ANN had 97% sensitivity and 89.5% selectivity, which were more accurate than that of ANN with the same input size of raw data. In clinical result, our expert rule system, which uses neighboring channel informations, was capable of rejecting artifacts commonly found in EEG recordings.

Adolescent↗
PubMed1997

Making the constraints visible: testing the ecological approach to interface design.

A haemodynamic monitoring and control task was used to evaluate the ecological approach to interface design for complex high-technology environments. Guidelines proposed by Bennett and Flach (1992) were used to design multilevel displays that made visible (a) anatomical constraints, and (b) causal constraints on haemodynamic systems. These displays were compared with a traditional display that showed pressure and flow values in five separate graphs. Simulations of clinical problems were generated by a computer model and presented in an interactive computer environment. Critical care nurses and nursing students observed changes in pressures and flow corresponding to certain disease states and corrected those states using simulated drugs. For both groups, speed and accuracy were progressively improved by the enhanced, multilevel displays.

Computer Simulation↗
PubMed1994

Making the relationships visible: testing alternative display design strategies for teaching principles of hemodynamic monitoring and treatment.

A hemodynamic monitoring and control task was used to explore the utility of perceptually based displays to teach basic hemodynamic principles. The baseline display showed discrete values of key hemodynamic data elements. Alternative displays showed (a) anatomical relationships between those elements, and (b) causal constraints. Critical care nurses and student nurses used simulated "drugs" to correct simple hemodynamic disturbances using the three displays. Showing the anatomic constraints on pressure and flow improved treatment coordination by novices. Showing how etiological factors related to symptoms shortened the time required to reach a criterion level of performance and improved treatment coordination for both novices and experts.

Computer Graphics↗
PubMed1993

Optical information about the severity of upcoming contacts.

The time derivative (tau) of the inverse of the relative rate of optical expansion (tau) may have critical values with potential implications for controlling activity. The present research addresses the particular hypothesis that tau < -0.5 specifies "unsafe" collision courses and tau > or = -0.5 specifies "safe" collision courses. Optical expansion patterns were simulated on a computer with -1.0 < or = tau < 0 and judged as suggesting a "hard" or "soft" collision. tau < -0.5 led to significantly different decisions from tau > or = -0.5, but the critical value of -0.5 was not perceived reliably as soft, a deviation possibly due to discretely approximating continuous functions. Additional experiments evaluated terminal rates of change and display duration and examined the effects of biasing the presented displays toward the soft or the hard end of the tau continuum. The results were consistent with the tau hypothesis.

Acceleration↗
PubMed1988

[Analysis of internal carotid-posterior communicating artery aneurysms with difficulty in clipping: with special reference to radiometry].

Although internal carotid-posterior communicating artery (ICPC) aneurysms seem to be one of the easiest to be operated on, some are known difficult to handle and could not be successfully clipped even with all sorts of preparations. It is, therefore, essential to analyze ICPC aneurysms with difficulty in clipping. Out of 106 cases with ICPC aneurysms admitted to Kyoto University Hospital since May 1977, 83 cases have been registered in this study to the exclusion of either non-operated cases or giant aneurysm cases. Cases with difficulty in clipping procedure are selected and classified depending on its causes, which were judged from operation records as well as operative photographs. Angiograms have been checked to discuss whether possible causes of difficulty in clipping could have been suspected preoperatively. Radiometry were also performed in the following items; distance between the anterior clinoid process (ACP) and proximal side of the aneurysmal neck (W) in AP view, distance of proximal side of the neck from ACP (D) and its height (H) from the baseline between the ACP and posterior clinoid process in lateral view. Causes of difficulty in clipping procedure can be grouped as follows: a) ventrally directed dome of the aneurysm (9 cases), b) incision of the plica petroclinoidea anterior (PPA) or removal of the anterior clinoid process (ACP) to identify proximal side of the neck (7 cases: b group), c) saucer-shaped dome with no apparent neck, d) branches of the internal carotid artery from dome.(ABSTRACT TRUNCATED AT 250 WORDS)

Carotid Artery Diseases↗