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Biomedical subjects

C Kim

Publications and source records attributed to C Kim.

At least 55 records · Page 3Linked to original sources
PubMed2001

Drosophila phosphoinositide-dependent kinase-1 regulates apoptosis and growth via the phosphoinositide 3-kinase-dependent signaling pathway.

Phosphoinositide-dependent kinase-1 (PDK-1) is a central mediator of the cell signaling between phosphoinositide 3-kinase (PI3K) and various intracellular serine/threonine kinases including Akt/protein kinase B (PKB), p70 S6 kinases, and protein kinase C. Recent studies with cell transfection experiments have implied that PDK-1 may be involved in various cell functions including cell growth and apoptosis. However, despite its pivotal role in cellular signalings, the in vivo functions of PDK-1 in a multicellular system have rarely been investigated. Here, we have isolated Drosophila PDK-1 (dPDK-1) mutants and characterized the in vivo roles of the kinase. Drosophila deficient in the dPDK-1 gene exhibited lethality and an apoptotic phenotype in the embryonic stage. Conversely, overexpression of dPDK-1 increased cell and organ size in a Drosophila PI3K-dependent manner. dPDK-1 not only could activate Drosophila Akt/PKB (Dakt1), but also substitute the in vivo functions of its mammalian ortholog to activate Akt/PKB. This functional interaction between dPDK-1 and Dakt1 was further confirmed through genetic analyses in Drosophila. On the other hand, cAMP-dependent protein kinase, which has been proposed as a possible target of dPDK-1, did not interact with dPDK-1. In conclusion, our findings provide direct evidence that dPDK-1 regulates cell growth and apoptosis during Drosophila development via the PI3K-dependent signaling pathway and demonstrate our Drosophila system to be a powerful tool for elucidating the in vivo functions and targets of PDK-1.

3-Phosphoinositide-Dependent Protein Kinases↗
PubMed2001

Solvent-free enzymatic synthesis of alitame precursor using eutectic substrate mixtures.

N-benzyloxycarbonyl-L-aspartic acid ethyl ester-D-alanine amide, a derivative of alitame, was synthesized from a eutectic mixture of the substrates N-benzyloxycarbonyl-L-aspartic acid diethyl ester and D-alanine amide using alpha-chymotrypsin. The hydrophilic solvents DMSO and MEA were found to be the best adjuvants for formation of a eutectic substrate mixture. A low eutectic temperature of 27 degrees C was obtained for the substrate mixture containing 9% DMSO, 18% MEA, and 12% water. Under these conditions a conversion yield of 70.3% (mol/mol) was obtained at 37 degrees C. The optimum molar ratio of the acyl acceptor D-alanine amide and the acyl donor N-benzyloxycarbonyl-L-aspartic acid diethyl ester was 1:1.

Journal Article↗
PubMed2001

Superconducting gap and strong in-plane anisotropy in untwinned YBa2Cu3O(7-delta).

With significantly improved sample quality and instrumental resolution, we clearly identify in the ( pi,0) photoemission spectra from YBa(2)Cu(3)O(6.993), in the superconducting state, the long-sought "peak-dip-hump" structure. This advance allows us to investigate the large a-b anisotropy of the in-plane electronic structure including, in particular, a 50% difference in the magnitude of the superconducting gap that scales with the energy position of the hump feature. This anisotropy, likely induced by the presence of the CuO chains, raises serious questions about attempts to quantitatively explain the YBa(2)Cu(3)O(7-delta) data from various experiments using models based on a perfectly square lattice.

Journal Article↗
PubMed2001

Isolation of novel human fetal brain cDNAs mapped to human chromosome bands, 1q25 and 8q24.1.

We isolated chromosome band-specific human fetal brain cDNAs by the microdissection mediated cDNA capture method, and localized these cDNA using in situ hybridization histochemistry with developing rat brain sections. Uni-Amp cDNAs were prepared from an 18-week old human fetal brain, and hybridized to human metaphase chromosomes. Eight Uni-Amp cDNAs, hybridized to chromosome band 1q25 or 8q24.1, were recovered by microdissection and PCR amplification with Uni-Amp primers. Among these cDNAs, two novel genes (FB113 of 8q24.1 and FB134 of 1q25) showed a temporospatially interesting expression pattern in the developing rat brains. The expression of FB113 was under dynamic regulation in the developing granule cells of cerebellum and dentate gyrus. FB134 showed a nervous tissue specific expression pattern and an exclusively prominent expression in the developing presubiculum and parasubiculum. By the fluorescence in situ hybridization using human genomic DNAs, FB113 and FB134 were mapped back to the human chromosome bands 8q24.1 and 1q25, respectively. These results indicate that combined application of the microdissection mediated cDNA capture method and in situ hybridization histochemistry can be used for the isolation of chromosomal band-specific genes related to brain development or human genetic diseases.

Animals↗
PubMed2001

Determinants of chemotactic signal amplification in Escherichia coli.

A well-characterized protein phosphorelay mediates Escherichia coli chemotaxis towards the amino acid attractant aspartate. The protein CheY shuttles between flagellar motors and methyl-accepting chemoreceptor (MCP) complexes containing the linker CheW and the kinase CheA. CheA-CheY phosphotransfer generates phospho-CheY, CheY-P. Aspartate triggers smooth swim responses by inactivation of the CheA bound to the target MCP, Tar; but this mechanism alone cannot explain the observed response sensitivity. Here, we used behavioral analysis of mutants deleted for CheZ, a catalyst of CheY-P dephosphorylation, or the methyltransferase CheR and/or the methylesterase CheB to examine the roles of accelerated CheY-P dephosphorylation and MCP methylation in enhancement of the chemotactic response. The extreme motile bias of the mutants was adjusted towards wild-type values, while preserving much of the aspartate response sensitivity by expressing fragments of the MCP, Tsr, that either activate or inhibit CheA. We then measured responses to small jumps of aspartate, generated by flash photolysis of photo-labile precursors. The stimulus-response relation for Delta cheZ mutants overlapped that for the host strains. Delta cheZ excitation response times increased with stimulus size consistent with formation of an occluded CheA state. Thus, neither CheZ-dependent or independent increases in CheY-P dephosphorylation contribute to the excitation response. In Delta cheB Delta cheR or Delta cheR mutants, the dose for a half-maximal response, [Asp](50), was ca 10 microM; but was elevated to 100 microM in Delta cheB mutants. In addition, the stimulus-response relation for these mutants was linear, consistent with stoichiometric inactivation, in contrast to the non-linear relation for wild-type E. coli. These data suggest that response sensitivity is controlled by differential binding of CheR and/or CheB to distinct MCP signaling conformations.

Bacterial Proteins↗
PubMed2001

Long-term delivery of all-trans-retinoic acid using biodegradable PLLA/PEG-PLLA blended microspheres.

All-trans-retinoic acid (atRA) has been proved to be effective against several malignancies in human clinical trials. However, in many patients who were treated with atRA, the cancer relapsed after a brief remission. One reason for such relapse is that atRA is metabolized by specific P450s that are induced in the liver during prolonged atRA treatments. In order to overcome such a drawback of atRA, we prepared biodegradable microspheres to provide continuous release of atRA for a long period of time. These biodegradable microspheres were prepared by poly(L-lactide) (PLLA) and polyethylene glycol (PEG)-PLLA diblock copolymers (PLE) in various blending ratios to control the release rate of atRA. As the PLE content in microsphere was increased, the density of the hydrophilic PEG block of PLE on microsphere surfaces increased and the microspheres were dispersed well in PBS without any surfactants. Various release patterns of atRA were obtained according to PLE and atRA contents in the microspheres. Especially, the pseudo-zero-order release profiles were observed for 5 weeks when the contents of PLE and atRA in the microspheres were above 4 wt.%.

Excipients↗
PubMed2001

Superconducting gap anisotropy in Nd1.85Ce0.15CuO4: results from photoemission.

We have performed angle resolved photoelectron spectroscopy on the electron doped cuprate superconductor Nd1.85Ce0.15CuO4. A comparison of the leading edge midpoints between the superconducting and normal states reveals a small, but finite shift of 1.5-2 meV near the ( pi,0) position, but no observable shift along the zone diagonal near ( pi/2, pi/2). This is interpreted as evidence for an anisotropic superconducting gap in the electron doped materials, which is consistent with the presence of d-wave superconducting order in this cuprate superconductor.

Journal Article↗
PubMed2001

Is the cancer protective effect correlated with growth inhibitions by green tea (-)-epigallocatechin gallate mediated through an antioxidant mechanism?

The preferential inhibition by (-)-epigallocatechin gallate (EGCg) of growth of cancer cells (e.g. HeLa) in culture correlates with the ability of EGCg to inhibit a growth-related, cell surface hydroquinone oxidase with protein disulfide-thiol interchange activity (tNOX) measured as an NADH oxidase and specifically associated with tumorigenically-transformed cells and tissues. tNOX is reduced or absent from the surface of non-cancer cells. Various oxidizing conditions known to render other antioxidants such as thiols, ascorbate and vitamin E ineffective did not reduce the effectiveness of EGCg in inhibiting either the tNOX activity or the growth of HeLa cells. Only after Fenton reaction with iron catalysis in the presence of hydrogen peroxide was the effectiveness of the EGCg reduced. We conclude that it is unlikely that the anticancer action of green tea EGCg on the tNOX protein is mediated through antioxidant properties of EGCg.

Anticarcinogenic Agents↗
PubMed2001

Rac2 is an essential regulator of neutrophil nicotinamide adenine dinucleotide phosphate oxidase activation in response to specific signaling pathways.

Rac2 is a hematopoietic-specific Rho family GTPase implicated as an important constituent of the NADPH oxidase complex and shares 92% amino acid identity with the ubiquitously expressed Rac1. In bone marrow (BM) neutrophils isolated from rac2(-/-) mice generated by gene targeting, we previously reported that PMA-induced superoxide production was reduced by about 4-fold, which was partially corrected in TNF-alpha-primed BM neutrophils and in peritoneal exudate neutrophils. We investigated receptor-mediated activation of the NADPH oxidase in the current study, finding that superoxide production in rac2(-/-) BM and peritoneal exudate neutrophils was normal in response to opsonized zymosan, reduced to 22% of wild type in response to IgG-coated SRBC, and almost absent in response to fMLP. In wild-type murine BM neutrophils, phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, and Akt was induced by PMA or fMLP, which was decreased in rac2(-/-) neutrophils for ERK1/2 and p38. Activation of p38 by either opsonized zymosan or IgG-coated SRBC was similar in wild-type and rac2(-/-) cells. Inhibition of ERK1/2 or p38 activation using either PD98059 or SB203580, respectively, had only a modest effect on fMLP-elicited superoxide production and no effect on the PMA-induced response. These data provide genetic evidence supporting an important role for Rac2 in regulating neutrophil NADPH oxidase activation downstream of chemoattractant and Fcgamma receptors. The effect of Rac2 deficiency on superoxide production is probably exerted through multiple pathways, including those independent of mitogen-activated protein kinase activation.

Animals↗
PubMed2001

Bi-directional activation between human airway smooth muscle cells and T lymphocytes: role in induction of altered airway responsiveness.

Because both T lymphocyte and airway smooth muscle (ASM) cell activation are events fundamentally implicated in the pathobiology of asthma, this study tested the hypothesis that cooperative intercellular signaling between activated T cells and ASM cells mediates proasthmatic changes in ASM responsiveness. Contrasting the lack of effect of resting human T cells, anti-CD3-activated T cells were found to adhere to the surface of naive human ASM cells, increase ASM CD25 cell surface expression, and induce increased constrictor responsiveness to acetylcholine and impaired relaxation responsiveness to isoproterenol in isolated rabbit ASM tissues. Comparably, exposure of resting T cells to ASM cells prestimulated with IgE immune complexes reciprocally elicited T cell adhesion to ASM cells and up-regulated T cell expression of CD25. Extended studies demonstrated that: 1) ASM cells express mRNAs and proteins for the cell adhesion molecules (CAMs)/costimulatory molecules, CD40, CD40L, CD80, CD86, ICAM-1 (CD54), and LFA-1 (CD11a/CD18); 2) apart from LFA-1, ASM cell surface expression of the latter molecules is up-regulated in the presence of activated T cells; and 3) pretreatment of ASM cells and tissues with mAbs directed either against CD11a or the combination of CD40 and CD86 completely abrogated both the activated T cell-induced changes in expression of the above CAMs/costimulatory molecules in ASM cells and altered ASM tissue responsiveness. Collectively, these observations identify the presence of bi-directional cross-talk between activated T cells and ASM cells that involves coligation of specific CAMs/costimulatory molecules, and this cooperative intercellular signaling mediates the induction of proasthmatic-like changes in ASM responsiveness.

Adolescent↗
PubMed2001

Altered nociceptive response in mice deficient in the alpha(1B) subunit of the voltage-dependent calcium channel.

Calcium influx through N-type calcium channels mediates synaptic transmission at numerous central synapses and transduces nociceptive information in the spinal dorsal horn. However, the precise role of N-type calcium channels in pain perception is not fully elucidated. To address this issue, we generated and analyzed knockout mice for alpha(1B,) the pore-forming subunit of the N-type calcium channel. Homozygous mutants are viable, fertile, and show normal motor coordination. In small-diameter dorsal root ganglion neurons from mutants the density of calcium channel currents is significantly reduced, which can be accounted for by the abolition of N-type currents. We performed several pain-related behavioral tests using the mutant mice. alpha(1B)-Deficient mice show reduced response to mechanical stimuli in the von Frey test and increased tail flick latency in response to radiant heat, indicating altered spinal reflexes. However, pain response in the hot plate test is normal. In the formalin paw test, the mutant mice exhibit significantly attenuated response in Phase 2, but normal pain behaviors in Phase 1. The response to visceral inflammatory pain caused by acetic acid is also reduced in alpha(1B) knockout mice. These results suggest that the alpha(1B) subunit of N-type calcium channel plays a major role in pain perception by acting at the spinal level, but not at the supraspinal level.

Animals↗
PubMed2001

Skeletal and dental effects of maxillary protraction in patients with angle class III malocclusion. A meta-analysis.

The aim of this study was a quantitative review of the published results concerning the treatment effects of maxillary protraction in patients with Angle Class III using the meta-analysis method. 85 articles published between 1966 and 1998 were reviewed under strict, pre-defined criteria. Of these, 12 studies presenting results of cephalometric measurements were selected for further analysis. The results of different cephalometric measurements were reviewed with Dstat 1.10 software in order to calculate a standardized treatment effect variable. The homogeneity of the variances of the different effect variables as well as a composite effect were calculated. For the latter, each individual effect variable was weighted by the reciprocal of its variance, with predefined study characteristics being used for categorical model calculations. Our results showed a significant composite effect of the therapy on the skeletal components (SNA: 1.4 degrees, composite effect = 1.11; SNB: -1.3 degrees, composite effect = -0.94; ANB: 2.6 degrees, composite effect = 1.73; lower anterior face height: 1.6 mm, composite effect = 0.85) as well as on the dental components of the face (inclination of upper incisors: 1.6 degrees, composite effect = 0.37; inclination of lower incisors: -3.7 degrees, composite effect = -0.87). However, several of the individual effect variables demonstrated a significant lack of homogeneity. Study characteristics which might possibly account for this variability were the patients' ages at the start of treatment and the combination of maxillary protraction with rapid maxillary expansion. In summary, maxillary protraction was shown to have a significant treatment effect. The meta-analysis method proved to be a valuable tool in judging the current status of a given clinical therapeutic concept.

Cephalometry↗
PubMed2001

Medical therapy or coronary artery bypass graft surgery for chronic stable angina: an update using decision analysis.

PURPOSE: Randomized trials comparing medical and surgical therapies for the treatment of chronic stable angina were completed in the early 1980s. Therapies developed since then have decreased mortality and myocardial infarction rates from coronary artery disease. Using decision analysis and incorporating current recommendations for treatment, we simulated a trial comparing coronary artery bypass graft surgery and medical therapy. METHODS: A Markov decision analysis model was constructed to compare the 5-year and 10-year outcomes of a simulated trial of medical therapy versus bypass surgery for stable chronic angina. Baseline data were obtained from a meta-analysis of trials comparing the two treatments. Data on risk reduction from contemporary therapies were obtained from randomized trials and meta-analyses. RESULTS: All subgroups experienced modest gains in survival with current therapies. At 5 years, the survival rate was 90% in the medical group (an absolute gain of 6%) and 94% in the surgical group (an absolute gain of 4%). Similar results were obtained for patients with triple-vessel disease. Among patients with a low ejection fraction, the 5-year survival rate was 85% for medical patients and 92% for surgical patients. Sensitivity analyses did not substantially affect the conclusions. CONCLUSION: Advances in the treatment of chronic stable angina have improved the outcome both for patients treated initially with surgery and for those treated initially with medical therapy. The improvements were of similar magnitude in both groups, so the fundamental conclusions of the bypass trials are unchanged.

Adult↗
PubMed2001

Effect of cataract extraction on blue-on-yellow visual field.

PURPOSE: It is assumed that cataract can influence the results of blue-on-yellow perimetry. However, actual sensitivity change in blue-on-yellow perimetry before and after cataract surgery has not been fully demonstrated. METHODS: Prospective. SETTING: Institutional. STUDY POPULATION: Twenty-two eyes of 22 consecutive patients without ocular pathology, other than cataract, known to influence visual field undergoing cataract surgery. OBSERVATION PROCEDURES: Both white-on-white (W-W) and blue-on-yellow (B-Y) perimetries. MAIN OUTCOME MEASURES: Global indexes including mean deviation and other pertinent data of white-on-white and blue-on-yellow perimetries were compared before and after cataract surgery. RESULTS: Mean deviation was improved after cataract surgery in both white-on-white perimetry (from -6.88 dB to -3.36 dB, P <.0001) and blue-on-yellow perimetry (from -12.22 dB to -3.64 dB, P <.0001, paired t test). However, the mean difference between preoperative and postoperative mean deviation in blue-on-yellow perimetry (8.58 +/- 3.96 dB) was significantly higher than that of white-on-white perimetry (3.52 +/- 2.69 dB; P <.0001, unpaired t test). That is, the change in mean deviation was greater in blue-on-yellow perimetry than in white-on-white perimetry by a factor of 2.4 times. CONCLUSION: Cataract causes predominantly a general reduction of sensitivity in both blue-on-yellow and white-on-white perimetries, and the general reduction of blue-on-yellow sensitivity is far greater than that of white-on-white sensitivity.

Adult↗
PubMed2001

Transscleral suture fixation of posterior chamber lenses combined with trabeculectomy.

OBJECTIVE: To evaluate the outcome of transscleral suture-fixated posterior chamber intraocular lens (PCIOL) implantation in glaucoma patients when combined with a trabeculectomy. DESIGN: A retrospective study of 56 consecutive glaucoma patients with a minimum follow-up of 6 months after transscleral suture-fixated PCIOL implantation combined with trabeculectomy. SETTING: Patients were drawn from the clinical glaucoma practice of the Kresge Eye Institute, Detroit, MICHIGAN: PATIENTS: Fifty-six eyes of 56 consecutive chronic glaucoma patients who had undergone transscleral suture-fixated PCIOL implantation in combination with a trabeculectomy were included in the analysis. RESULTS: The mean follow-up time was 38.5 +/- 19.1 months. Mean intraocular pressure (IOP) was significantly reduced, from 22.9 +/- 10.9 mmHg before surgery to 16.7 +/- 6.7 mmHg at the last follow-up visit (P = 0.0005), with the mean number of medications used also significantly decreased, from 2.3 +/- 0.9 to 1.9 +/- 0.9 (P = 0.0002). Postoperative IOP control to 21 mmHg or less was achieved or maintained in 84% of patients. Visual acuity improved or remained stable within two Snellen lines of the preoperative level in 39 eyes (70%) and within three Snellen lines in 45 eyes (80%) at the last follow-up visit. Overall, 46% to 68% of the patients had both stable visual acuity and satisfactory pressure control at the last postoperative visit, depending on criteria of varying stringency. However, 19 eyes (34%) required one or more additional surgical interventions for pressure control. Patients with anterior chamber intraocular lens (ACIOL) complications, diabetes mellitus, or a preoperative IOP level of more than 21 mmHg on maximum tolerated medications were especially prone to requiring additional surgical interventions. CONCLUSIONS: We conclude that transscleral suture-fixated PCIOL implantation can be combined successfully with a trabeculectomy and can be useful in glaucoma patients in need of both visual rehabilitation and IOP control. However, patients with ACIOL complications, diabetes, or preoperative IOP of more than 21 mmHg on maximum tolerated medications were prone to requiring additional surgical interventions.

Aged↗
PubMed2001

Effect of ginsenosides on voltage-dependent Ca(2+) channel subtypes in bovine chromaffin cells.

In previous reports we have shown that ginsenosides inhibit high threshold voltage-dependent Ca(2+) channels in neuronal cells. However, these studies did not show whether ginsenosides-induced inhibition of Ca(2+) currents discriminates among the various Ca(2+) channel subtypes, although it is known that there are at least five different Ca(2+) channel subtypes in neuronal cells. In this study we investigated the effect of ginsenosides on high threshold voltage-dependent Ca(2+) channel subtypes using their selective Ca(2+) channel blockers nimodipine (L-type), omega-conotoxin GVIA (N-type), or omega-agatoxin IVA (P-type) in bovine chromaffin cells. We could observe that ginsenosides inhibited high threshold voltage-dependent Ca(2+) currents in a dose-dependent manner. The IC(50) was about 120 microgram/ml. Nimodipine had no effect on ginsenosides response. However, the effect of ginsenosides on Ca(2+) currents was reduced by omega-conotoxin GVIA, omega-agatoxin IVA, and mixture of nimodipine, omega-conotoxin GVIA, and omega-agatoxin IVA. These data suggest that ginsenosides are negatively coupled to three types of calcium channels in bovine chromaffin cell, including an omega-conotoxin GVIA-sensitive (N-type) channel, an omega-agatoxin IVA-sensitive (P-type) channel and nimodipine/omega-conotoxin GVIA/omega-agatoxin VIA-resistant (presumptive Q-type) channel. Thus, the selective regulation of voltage-dependent Ca(2+) subtypes by ginsenosides in bovine chromaffin cell could be the cellular basis of antistress effects induced by ginseng.

Animals↗
PubMed2001

The transcriptional regulator Yin Yang 1 activates the myelin PLP gene.

Inauguration of the myelin program in developing oligodendrocytes requires the activation of those genes that encode the myelin proteins and the enzymes responsible for the synthesis and degradation of myelin lipids. An activator of the most abundantly expressed myelin protein, proteolipid protein (PLP), has been identified in a yeast one-hybrid system. The ubiquitously expressed zinc finger protein Yin Yang 1 (YY1) recognizes the myelin PLP promoter in vitro and in vivo. When overexpressed in an oligodendrocyte cell line, YY1 enhances transcription of the PLP promoter. A truncated version of YY1 that includes only the four zinc finger domains has little effect. The binding site for YY1 in the PLP promoter (site 3) fits the YY1 consensus site and DNA-protein complexes containing site 3 can be supershifted with an antibody directed against YY1 protein. Moreover, oligonucleotides with a mutated version of the PLP promoter site 3 are unable to bind to nuclear proteins or to compete for binding in a gel shift system. Finally, mutation of this site greatly reduces the activity of a 1-kb PLP promoter region in transfected glial cells. Our results suggest that PLP is a target gene for the transcriptional regulator YY1. This versatile transcription factor and nuclear matrix protein may boost transcription of the PLP gene to meet the demands of actively myelinating oligodendrocytes.

Animals↗