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Biomedical subjects

H Park

Publications and source records attributed to H Park.

At least 73 records · Page 4Linked to original sources
PubMed2001

Inhibition of TPA-induced cyclooxygenase-2 expression and skin inflammation in mice by wogonin, a plant flavone from Scutellaria radix.

Wogonin (5,7-dihydroxy-8-methoxyflavone), isolated from Scutellaria radix, was previously reported to inhibit the expression and activity of the enzyme cyclooxygenase-2 in lipopolysaccharide (LPS)-stimulated cells of a mouse macrophage cell line, RAW 264.7. Here, in order to find in vivo effects, inhibition by wogonin of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cyclooxygenase-2 expression and anti-inflammatory activity in vivo were investigated. When applied topically to the dorsal skin of mice, wogonin at doses of 50-200 microg/site/treatment (total of five treatments in 3 days) inhibited cyclooxygenase-2 expression and prostaglandin E2 production induced by multiple treatments with TPA. At 200 microg/site/treatment, wogonin caused a 55.3% reduction of prostaglandin E2 production on the dorsal skin compared with an increased production in the TPA-treated control group. The same compound significantly inhibited mouse ear edema induced by TPA in both preventive (58.1% inhibition) as well as curative treatment (31.3% inhibition) schedules at 200 microg/ear/treatment. Inhibition of neutrophil infiltration was also observed. Therefore, wogonin may be beneficial for cyclooxygenase-2-related skin disorders.

Animals↗
PubMed2001

E3 ligase activity of RING finger proteins that interact with Hip-2, a human ubiquitin-conjugating enzyme.

To identify proteins that interact with Huntingtin-interacting protein-2 (Hip-2), a ubiquitin-conjugating enzyme, a yeast two-hybrid screen system was used to isolate five positive clones. Sequence analyses showed that, with one exception, all Hip-2-interacting proteins contained the RING finger motifs. The interaction of Hip-2 with RNF2, one of the clones, was further confirmed through in vitro and in vivo experiments. Mutations in the RING domain of RNF2 prevented the clone from binding to Hip-2, an indication that the RING domain is the binding determinant. RNF2 showed a ubiquitin ligase (E3) activity in the presence of Hip-2, suggesting that a subset of RING finger proteins may have roles as E3s.

Amino Acid Sequence↗
PubMed2001

Apoptosis signal-regulating kinase 1 controls the proapoptotic function of death-associated protein (Daxx) in the cytoplasm.

Although Daxx (death-associated protein) was first reported to mediate the apoptotic signal from Fas to JNK in the cytoplasm, other data suggested that Daxx is mainly located in the nucleus as a transcriptional regulator. Here, we demonstrated that cellular localization of Daxx could be determined by the relative concentration of a proapoptotic kinase, apoptosis signal-regulating kinase 1 (ASK1) by using immunofluorescence and transcriptional reporter assay. ASK1 sequestered Daxx in the cytoplasm and inhibited the repressive activity of Daxx in transcription. In addition, Daxx was bound to the activated Fas only in the presence of ASK1, accelerating the Fas-mediated apoptosis. These results suggest that Daxx requires ASK1 for its cytoplasmic localization and Fas-mediated signaling. Taken together, we could conclude that ASK1 controls the dual function of Daxx as a transcriptional repressor in the nucleus and as a proapoptotic signal mediator in the cytoplasm.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Distinct characteristic of Galpha(h) (transglutaminase II) by compartment: GTPase and transglutaminase activities.

Galpha(h) (transglutaminase II) is a bifunctional enzyme possessing transglutaminase and GTPase activities. To better understand the factors affecting these two functions of Galpha(h), we have examined the characteristics of purified Galpha(h) from membrane and cytosol. GTP binding activity of mouse heart Galpha(h) was higher in membrane than that from cytosol. Furthermore, phospholipase C-delta1 (PLC-delta1) activity and coimmunoprecipitation of Galpha(h)-coupled PLC-delta1 in the alpha(1)-adrenoceptor-Galpha(h)-PLC-delta1 complex preparations were increased by phenylephrine in the presence of membranous Galpha(h). On the other hand, transglutaminase activity of cytosolic Galpha(h) was higher than that from membrane Galpha(h). These results demonstrate that bifunctions of Galpha(h) are regulated by its localization that can reflect the cellular functions of Galpha(h).

Animals↗
PubMed2001

Fabry - Perot interference in a nanotube electron waveguide.

The behaviour of traditional electronic devices can be understood in terms of the classical diffusive motion of electrons. As the size of a device becomes comparable to the electron coherence length, however, quantum interference between electron waves becomes increasingly important, leading to dramatic changes in device properties. This classical-to-quantum transition in device behaviour suggests the possibility for nanometer-sized electronic elements that make use of quantum coherence. Molecular electronic devices are promising candidates for realizing such device elements because the electronic motion in molecules is inherently quantum mechanical and it can be modified by well defined chemistry. Here we describe an example of a coherent molecular electronic device whose behaviour is explicitly dependent on quantum interference between propagating electron waves-a Fabry-Perot electron resonator based on individual single-walled carbon nanotubes with near-perfect ohmic contacts to electrodes. In these devices, the nanotubes act as coherent electron waveguides, with the resonant cavity formed between the two nanotube-electrode interfaces. We use a theoretical model based on the multichannel Landauer-Büttiker formalism to analyse the device characteristics and find that coupling between the two propagating modes of the nanotubes caused by electron scattering at the nanotube-electrode interfaces is important.

Electronics↗
PubMed2001

A cofactor of tRNA synthetase, p43, is secreted to up-regulate proinflammatory genes.

An auxiliary factor of mammalian multi-aminoacyl-tRNA synthetases, p43, is thought to be a precursor of endothelial monocyte-activating polypeptide II (EMAP II) that triggers proinflammation in leukocytes and macrophages. In the present work, however, we have shown that p43 itself is specifically secreted from intact mammalian cells, while EMAP II is released only when the cells are disrupted. Secretion of p43 was also observed when its expression was increased. These results suggest that p43 itself should be a real cytokine secreted by an active mechanism. To determine the cytokine activity and active domain of p43, we investigated tumor necrosis factor (TNF) and interleukin-8 (IL-8) production from human monocytic THP-1 cells treated with various p43 deletion mutants. The full length of p43 showed higher cytokine activity than EMAP II, further supporting p43 as the active cytokine. p43 was also shown to activate MAPKs and NFkappaB, and to induce cytokines and chemokines such as TNF, IL-8, MCP-1, MIP-1alpha, MIP-1beta, MIP-2alpha, IL-1beta, and RANTES. Interestingly, the high level of p43 was observed in the foam cells of atherosclerotic lesions. Therefore, p43 could be a novel mediator of atherosclerosis development as well as other inflammation-related diseases.

Amino Acyl-tRNA Synthetases↗
PubMed2001

Study of the decay D0 --> K+pi-.

Using a large sample of photoproduced charm mesons from the FOCUS experiment at Fermilab (FNAL-E831), we observe the decay D0-->K+pi- with a signal yield of 149+/-31 events compared to a similarly cut sample consisting of 36 760+/-195 D0-->K-pi+ events. We use the observed ratio of D0-->K+pi- to D0-->K-pi+ (0.404+/-0.085+/-0.025)% to obtain a relationship between the D0 mixing and doubly Cabibbo suppressed decay parameters.

Journal Article↗
PubMed2001

Fas-induced expression of chemokines in human glioma cells: involvement of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase.

Fas transduces not only apoptotic signals through various pathways but also angiogenic and proinflammatory responses in vivo. Human glioma cells express Fas although sensitivity to Fas-mediated cell death is variable, suggesting that Fas may have functions other than apoptosis in these cells. In this study, we addressed alternative functions of Fas expressed on human gliomas by Fas ligation in three human glioma cell lines, CRT-MG, U373-MG, and U87-MG, and the in vivo expression of Fas and chemokines in human glioblastoma multiforme (GBM). Herein, we demonstrate that: (a) stimulation with agonistic anti-Fas monoclonal antibody CH-11 and human recombinant soluble Fas ligand induces expression of the CC chemokine MCP-1 and the CXC chemokine interleukin-8 by human glioma cell lines at the mRNA and protein levels in a dose- and time-dependent manner; (b) selective pharmacological inhibitors of MEK1 (U0126 and PD98059) and p38 mitogen-activated protein kinase (MAPK) (SB202190) suppress Fas-mediated chemokine expression in a dose-dependent manner; (c) Fas ligation on human glioma cells leads to activation of both extracellular signal-regulated kinases ERK1/ERK2 and p38 MAPK; and (d) GBM samples express higher levels of Fas compared with normal control brain, which correlates with increased interleukin 8 expression. These findings indicate that Fas ligation on human glioma cells leads to the selective induction of chemokine expression, which involves the ERK1/ERK2 and p38 MAPK signaling pathways. Therefore, the Fas-Fas ligand system in human brain tumors may be involved not only in apoptotic processes but also in the provocation of angiogenic and proinflammatory responses.

Adult↗
PubMed2001

Rad23 provides a link between the Png1 deglycosylating enzyme and the 26 S proteasome in yeast.

In addition to a role in DNA repair events in yeast, several lines of evidence indicate that the Rad23 protein (Rad23p) may regulate the activity of the 26 S proteasome. We report evidence that a de-N-glycosylating enzyme, Png1p, may be involved in the proteasomal degradation pathway via its binding to Rad23p. Interaction of Rad23p and Png1p was first detected by two-hybrid screening, and this interaction in vivo was confirmed by biochemical analyses. The Png1p-Rad23p complex was shown to be distinct from the well established DNA repair complex, Rad4p-Rad23p. We propose a model in which Rad23p functions as an escort protein to link the 26 S proteasome with proteins such as Rad4p or Png1p to regulate their cellular activities.

Amidohydrolases↗
PubMed2001

Green's function approach to nonclassical reaction kinetics in fractal media.

We present an accurate description for the mean field kinetics of the reversible recombination reaction occurring in fractal media, which is in good agreement with Monte Carlo simulation results from an intermediate to a long time region. The central dynamic quantity is the Green's function for the generalized diffusion equation that is defined in a hypothetical space whose dimensionality is given by the fracton dimension d. An exact expression for the Green's function that is valid for arbitrary values of d is presented.

Journal Article↗
PubMed2001

Real-time measurement of glutamate release from the ischemic penumbra of the rat cerebral cortex using a focal middle cerebral artery occlusion model.

Following permanent middle cerebral artery occlusion, extracellular penumbral glutamate levels, measured by a real-time glutamate electrode, increased in two different patterns. In 7/11 rats, glutamate increased from baseline levels of 19+/-4 (mean+/-SEM) to 208+/-29 microM and then declined towards baseline levels. Blood flow in the penumbral area declined to 30% of pre-ischemic levels with recovery to 60 and 70% of baseline values by 3 and 6 h, respectively. Four of 11 rats in the study also exhibited late peaks of glutamate release (120+/-40 microM ) 2 h after the onset of ischemia. There were no changes in the EEG recordings or cerebral blood flow during these late glutamate peaks.

Animals↗
PubMed2001

The role of peripheral N-methyl-D-aspartate receptors in Freund's complete adjuvant induced mechanical hyperalgesia in rats.

We investigated the role of excitatory amino acid receptors in mechanical hyperalgesia induced by subcutaneous injection of Freund's complete adjuvant (FCA) into the rat hind paw. In normal rats, an intraplantar (i.pl.) injection of L-glutamate, but not of D-glutamate (3 pmol/0.1 ml each) produced a mechanical hyperalgesia in the hind paw with a lowered paw-withdrawal threshold to pressure. In rats that developed mechanical hyperalgesia associated with inflammation in the hind paw following i.pl. injection of FCA (0.15 ml), the injection of N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 (1 pmol/0.1 ml) into the inflamed paw increased the paw pressure threshold. On the other hand, the injection of non-NMDA receptor antagonist, 6-cyano-7-nitroqiunoxaline-2,3-dione (CNQX, 10 pmol/0.1 ml) into the inflamed paw had no effect on FCA-induced lowering of the paw pressure threshold. The results suggest that NMDA, but not non-NMDA receptors play a substantial role in mediating the development of mechanical hyperalgesia induced in the inflamed paw following i.pl. FCA injection.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2001

Resonant electron scattering by defects in single-walled carbon nanotubes.

We report the characterization of defects in individual metallic single-walled carbon nanotubes by transport measurements and scanned gate microscopy. A sizable fraction of metallic nanotubes grown by chemical vapor deposition exhibits strongly gate voltage-dependent resistance at room temperature. Scanned gate measurements reveal that this behavior originates from resonant electron scattering by defects in the nanotube as the Fermi level is varied by the gate voltage. The reflection coefficient at the peak of a scattering resonance was determined to be about 0.5 at room temperature. An intratube quantum dot device formed by two defects is demonstrated by low-temperature transport measurements.

Carbon↗
PubMed2001

Correlation between Abetax-40-, Abetax-42-, and Abetax-43-containing amyloid plaques and cognitive decline.

CONTEXT: Accumulation of senile plaques containing amyloid beta (Abeta)-protein is a pathologic hallmark of Alzheimer disease. Amyloid beta-peptide is heterogeneous, with carboxyterminal variants ending at residues Val40 (Abetax-40), Ala42 (Abetax-42), or Thr43 (Abetax-43). The relative importance of each of these variants in dementia or cognitive decline remains unclear. OBJECTIVE: To study whether Abeta deposition correlates with dementia and occurs at the earliest signs of cognitive decline. DESIGN, SETTING, AND PATIENTS: Postmortem cross-sectional study comparing the deposition of Abeta variants in the prefrontal cortex of 79 nursing home residents having no, questionable, mild, moderate, or severe dementia. MAIN OUTCOME MEASURES: Levels of staining of Abeta-peptides ending at amino acid 40, 42, or 43 in the frontal cortex, as a function of Clinical Dementia Rating score. RESULTS: There were significant deposits of all 3 Abeta species that strongly correlated with cognitive decline. Furthermore, deposition of Abetax-42 and Abetax-43 occurred very early in the disease process before there could be a diagnosis of Alzheimer disease. Levels of deposited Abetax-43 appeared surprisingly high given the low amounts synthesized. CONCLUSIONS: These data indicate that Abetax-42 and Abetax-43 are important species associated with early disease progression and suggest that the physiochemical properties of the Abeta species may be a major determinant in amyloid deposition. The results support an important role for Abeta in mediating initial pathogenic events in Alzheimer disease dementia and reinforce that treatment strategies targeting the formation, accumulation, or cytotoxic effects of Abeta should be pursued.

Aged↗
PubMed2001

Effect of compression on fast swelling of poly(acrylamide-co-acrylic acid) superporous hydrogels.

Superporous hydrogels (SPHs) swell to a large size in a very short time. In many applications it is preferred to compress SPHs to reduce the overall dimension in the dried state. The effects of compression on the swelling property of SPHs were examined. The swelling property of the compressed SPHs was dependent on the orientation of the SPHs during compression. If SPHs were compressed in an orientated manner so that they retained interconnected porous structure, they were able to swell to near equilibrium within 10 min of immersion in aqueous fluids. If SPHs were compressed in a manner that did not retain the open pore structure, the swelling rate was greatly reduced. The results showed that the SPHs could be compressed without significant sacrifice of the fast swelling property if compressed in a proper orientation. Because pores were formed owing to the generation of gas which rose from bottom to the top of the container, the compression parallel to the pore formation resulted in preservation of the pore structure, and thus fast swelling property. The ability to compress SPHs, maintaining the fast swelling property, is expected to be useful in various applications including development of gastric retention devices for oral drug delivery.

Acrylamides↗
PubMed2001

1,4-dioxane-fused 4-anilinoquinazoline as inhibitors of epidermal growth factor receptor kinase.

The 4-anilinoquinazoline PD 153035 (1) is a potential antitumor agent which acts by inhibiting tyrosine kinase activity of epidermal growth factor receptor (EFGR) via competitive binding at the ATP site of enzyme. A series of cyclic analogues of PD 153035 bearing the 1,4-dioxane ring was prepared by reaction of 6-chloro derivative 5 with several aniline nucleophiles. These were evaluated for their ability to inhibit the EGFR kinase and the growth of primary human tumor cell cultures. All of the new 4-anilinoquinazolines exhibited less potency than PD 153035 against EGFR kinase. However, compounds 2b, 2c, 2e, 2g, and 2h showed higher inhibitory activities than PD 153035 against the growth of A431 tumor cell line. The compound 2b containing 3-chloroaniline ring was as potent as PD 153035 against EGFR kinase and showed about 5.4-fold better potency than PD153035 in the inhibition of growth of A431 cell line with good selectivity.

Antineoplastic Agents↗
PubMed2001

Risk factors for back pain among male farmers: analysis of Iowa Farm Family Health and Hazard Surveillance Study.

BACKGROUND: Back pain causes considerable morbidity, disability, and economic loss among workers. Farmers handle heavy objects, often in awkward postures. However, the prevalence of back pain among farmers and the risk factors associated with back pain are not well known. METHODS: In this study, we assess the frequency of risk factors for back pain among 287 Iowa male farmers. From 1992 to 1994, using a mail questionnaire, we collected data on potential risk factors for back pain. Eighteen months later, we surveyed occurrence of back pain as the outcome measure. RESULTS: Thirty-one percent of farmers reported having daily back pain for a week or more during the past 12 months compared to 18.5% in the general working population. Using a multiple logistic regression model, we found two factors associated with back pain: 45-59 years of age (OR = 2.13, 95% CI 1.02-4.43) and having a non-agricultural job as the major occupation (OR = 2.02, 95% CI 0.98-4.17, P = 0.055). CONCLUSIONS: Farmers had a significantly higher prevalence of back pain than the general working population. Middle-aged farmers and those with additional non-agricultural jobs had the highest risk for back pain.

Adult↗