PubMed Health⌕ Search

Biomedical subjects

K C Chung

Publications and source records attributed to K C Chung.

At least 19 recordsLinked to original sources
PubMed2001

Protein kinase Dyrk1 activates cAMP response element-binding protein during neuronal differentiation in hippocampal progenitor cells.

Dyrk is a dual specific protein kinase thought to be involved in normal embryo neurogenesis and brain development. Defects/imperfections in this kinase have been suggested to play an important role in the mental retardation of patients with Down's syndrome. The transcriptional factor cAMP response element-binding protein (CREB) has been implicated in the formation of many types of synaptic plasticity, such as learning and memory. In the present study we show that Dyrk1 activity is markedly induced during the differentiation of immortalized hippocampal progenitor (H19-7) cells. The addition of a neurogenic factor, basic fibroblast growth factor, to the H19-7 cells results in an increased specific binding of Dyrk1 to active CREB. In addition, Dyrk1 directly phosphorylates CREB, leading to the stimulation of subsequent CRE-mediated gene transcription during the neuronal differentiation in H19-7 cells. Blockade of Dyrk1 activation significantly inhibits the neurite outgrowth as well as CREB phosphorylation induced by basic fibroblast growth factor. These findings suggest that Dyrk1 activation and subsequent CREB phosphorylation is important in the neuronal differentiation of central nervous system hippocampal cells.

Animals↗
PubMed2001

Multiple ligand interaction of alpha-synuclein produced various forms of protein aggregates in the presence of Abeta25-35, copper, and eosin.

Various protein aggregates of alpha-synuclein developed by way of the common protein self-oligomerization in the presence of Abeta25-35, copper, and eosin were examined. All the aggregates exhibited congo red birefringence although the actual amounts of the aggregates were varied as determined by thioflavin T binding fluorescence. When their morphologies were analyzed in relation to in vitro cytotoxicity, the smallest granular aggregates obtained with copper exhibited the highest cytotoxicity, while the fibrous structures by eosin did not affect the cell.

Amyloid beta-Peptides↗
PubMed2001

Induction of neuronal cell death by Rab5A-dependent endocytosis of alpha-synuclein.

The presynaptic alpha-synuclein is a prime suspect for contributing to Lewy pathology and clinical aspects of diseases, including Parkinson's disease, dementia with Lewy bodies, and a Lewy body variant of Alzheimer's disease. Here we examined the pathogenic mechanism of neuronal cell death induced by alpha-synuclein. The exogenous addition of alpha-synuclein caused a marked decrease of cell viability in primary and immortalized neuronal cells. The neuronal cell death appeared to be correlated with the Rab5A-specific endocytosis of alpha-synuclein that subsequently caused the formation of Lewy body-like intracytoplasmic inclusions. This was further supported by the fact that the expression of GTPase-deficient Rab5A resulted in a significant decrease of its cytotoxicity as a result of incomplete endocytosis of alpha-synuclein.

Animals↗
PubMed2001

Basic fibroblast growth factor-induced activation of novel CREB kinase during the differentiation of immortalized hippocampal cells.

Growth factors bind to their specific receptors on the responsive cell surface and thereby initiate dramatic changes in the proliferation, differentiation, and survival of their target cells. In the present study we have examined the mechanism by which growth factor-induced signals are propagated to the nucleus, leading to the activation of transcription factor, cis-acting cAMP response element (CRE)-binding protein (CREB), in immortalized hippocampal progenitor cells (H19-7). During the differentiation of H19-7 cells by basic fibroblast growth factor (bFGF) a critical regulatory Ser(133) residue of CREB was phosphorylated followed by an increase of CRE-mediated gene transcription. Expression of S133A CREB mutants blocked the differentiation of H19-7 cells by bFGF. Although the kinetics of CREB phosphorylation by EGF was transient, bFGF induced a prolonged pattern of CREB phosphorylation. Interestingly, bFGF-induced CREB phosphorylation and subsequent CRE-mediated gene transcription is not likely to be mediated by any of previously known signaling pathways that lead to phosphorylation of CREB, such as mitogen-activated protein kinases, protein kinase A, protein kinase C, phosphatidylinositol 3-kinase-p70(S6K), calcium/calmodulin dependent protein kinase, and casein kinase 2. By using in vitro in gel kinase assay the presence of a novel 120-kDa bFGF-inducible CREB kinase was identified. These findings identify a new growth factor-activated signaling pathway that regulates gene expression at the CRE.

Animals↗
PubMed2001

Zn2+-induced ERK activation mediated by reactive oxygen species causes cell death in differentiated PC12 cells.

Recent studies have provided evidence that Zn2+ plays a crucial role in ischemia- and seizure-induced neuronal death. However, the intracellular signaling pathways involved in Zn2+-induced cell death are largely unknown. In the present study, we investigated the roles of mitogen-activated protein kinases (MAPKs), such as c-Jun N-terminal kinase (JNK), p38 MAPK and extracellular signal-regulated kinase (ERK), and of reactive oxygen species (ROS) in Zn2+-induced cell death using differentiated PC12 cells. Intracellular accumulation of Zn2+ induced by the combined application of pyrithione (5 microM), a Zn2+ ionophore, and Zn2+ (10 microM) caused cell death and activated JNK and ERK, but not p38 MAPK. Preventing JNK activation by the expression of dominant negative SEK1 (SEKAL) did not attenuate Zn2+-induced cell death, whereas the inhibition of ERK with PD98059 and the expression of dominant negative Ras mutant (RasN17) significantly prevented cell death. Inhibition of protein kinase C (PKC) and phosphatidylinositol-3 kinase had little effect on Zn2+-induced ERK activation. Intracellular Zn2+ accumulation resulted in the generation of ROS, and antioxidants prevented both the ERK activation and the cell death induced by Zn2+. Therefore, we conclude that although Zn2+ activates JNK and ERK, only ERK contributes to Zn2+-induced cell death, and that ERK activation is mediated by ROS via the Ras/Raf/MEK/ERK signaling pathway.

Animals↗
PubMed2001

Differential activation of phospholipases by mitogenic EGF and neurogenic PDGF in immortalized hippocampal stem cell lines.

In several neuronal systems, nerve growth factor (NGF) and platelet-derived growth factor (PDGF) act as neurogenic agents, whereas epidermal growth factor (EGF) acts as a mitogenic agent. Hippocampal stem cell lines (HiB5) immortalized by the expression of a temperature-sensitive SV40 large T antigen also respond differentially to EGF and PDGF. While EGF treatment at the permissive temperature induces proliferation, the addition of PDGF induces differentiation at the non-permissive temperature. However, the mechanism responsible for these different cellular fates has not been clearly elucidated. In order to clarify possible critical signaling events leading to these distinct cellular outcomes, we examined whether either EGF or PDGF differentially induces the activation of phospholipases, such as phospholipase A(2) (PLA(2)), C (PLC), or D (PLD). Although EGF stimulation did not induce phospholipases, PDGF caused a rapid and transient activation of PLC and PLD, but not PLA(2). When the activation of PLC or PLD was blocked, the neurite outgrowth induced by PDGF was significantly inhibited. Although the activation of PLD occurred faster than PLC, blocking of PLD activity by transient expression of lipase-inactive mutants did not inhibit the induction of PLC activity by PDGF. These results suggest that the differential activation of phospholipases may play an important role in signal transduction by mitogenic EGF and neurotrophic PDGF in HiB5 neuronal hippocampal stem cells. In particular, the activation of phospholipase C and D may contribute to neuronal differentiation by neurogenic PDGF in the HiB5 cells.

Animals↗
PubMed2001

Use of three free flaps based on a single vascular pedicle for complex hand reconstruction in an electrical burn injury: a case report.

The use of conjoint flaps based on the dorsalis pedis artery enabled a transfer of 3 free flaps-dorsalis pedis flap, fillet flap of the second toe, and trimmed large toe-to reconstruct a severely traumatized hand in a 12-year-old girl. High-voltage electrical burn injury had caused a large wound over the volar wrist and exposed the flexor tendons and median/ulnar nerves. In addition, she suffered a partial loss of the thumb and had an open wound at the base of the index finger. The application of the conjoint flaps restored hand function in a one-stage procedure.

Burns, Electric↗
PubMed2001

The frequency and epidemiology of hand and forearm fractures in the United States.

The purpose of this study was to estimate the frequency and describe the epidemiology of hand and forearm fractures in the United States. We extracted cases with ICD-9-CM diagnostic codes of 813.0 to 817.1 from the 1998 National Hospital Ambulatory Medical Care Survey. In 1998 there were 1,465,874 estimated cases of hand/forearm fractures, accounting for 1.5% of all emergency department cases. Radius and/or ulna fractures comprised the largest proportion of fractures (44%). The most affected age group was 5 to 14 years of age (26%). Private insurance paid for 49% of the cases. Most of the fractures occurred at home (30%); the street/highway was the second most likely fracture location (14%). Accidental falls caused the majority (47%) of fractures. Large database analysis provides important information that can be used to target interventions toward vulnerable populations and to allocate adequate resources for treating upper extremity fractures.

Adolescent↗
PubMed2001

Inhibitory effect of dry needling on the spontaneous electrical activity recorded from myofascial trigger spots of rabbit skeletal muscle.

OBJECTIVE: Dry needling of myofascial trigger points can relieve myofascial pain if local twitch responses are elicited during needling. Spontaneous electrical activity (SEA) recorded from an active locus in a myofascial trigger point region has been used to assess the myofascial trigger point sensitivity. This study was to investigate the effect of dry needling on SEA. DESIGN: Nine adult New Zealand rabbits were studied. Dry needling with rapid insertion into multiple sites within the myofascial trigger spot region was performed to the biceps femoris muscle to elicit sufficient local twitch responses. Very slow needle insertion with minimal local twitch response elicitation was conducted to the other biceps femoris muscle for the control study. SEA was recorded from 15 different active loci of the myofascial trigger spot before and immediately after treatment for both sides. The raw data of 1-sec SEA were rectified and integrated to calculate the average integrated value of SEA. RESULTS: Seven of nine rabbits demonstrated significantly lower normalized average integrated value of SEA in the treatment side compared with the control side (P < 0.05). The results of two-way analysis of variance show that the mean of the normalized average integrated value of SEA in the treatment group (0.565 +/- 0.113) is significantly (P < 0.05) lower than that of the control (0.983 +/- 0.121). CONCLUSIONS: Dry needling of the myofascial trigger spot is effective in diminishing SEA if local twitch responses are elicited. The local twitch response elicitation, other than trauma effects of needling, seems to be the primary inhibitory factor on SEA during dry needling.

Animals↗
PubMed2000

Intracellular calcium mobilization induces immediate early gene pip92 via Src and mitogen-activated protein kinase in immortalized hippocampal cells.

Regulation of intracellular calcium levels plays a central role in cell survival, proliferation, and differentiation. A cell-permeable, tumor-promoting thapsigargin elevates the intracellular calcium levels by inhibiting endoplasmic reticulum Ca(2+)-ATPase. The Src-tyrosine kinase family is involved in a broad range of cellular responses ranging from cell growth and cytoskeletal rearrangement to differentiation. The immediate early gene pip92 is induced in neuronal cell death as well as cell growth and differentiation. To resolve the molecular mechanism of cell growth by intracellular calcium mobilization, we have examined the effect of thapsigargin and subsequent intracellular calcium influx on pip92 expression in immortalized rat hippocampal H19-7 cells. An increase of intracellular calcium ion levels induced by thapsigargin stimulated the expression of pip92 in H19-7 cells. Transient transfection of the cells with kinase-inactive mitogen-activated protein kinase kinase (MEK) and Src kinase or pretreatment with the chemical MEK inhibitor PD98059 significantly inhibited pip92 expression induced by thapsigargin. When constitutively active v-Src or MEK was overexpressed, the transcriptional activity of the pip92 gene was markedly increased. Dominant inhibitory Raf-1 blocked the transcriptional activity of pip92 induced by thapsigargin. The transcription factor Elk1 is activated during thapsigargin-induced pip92 expression. Taken together, these results suggest that an increase of intracellular calcium ion levels by thapsigargin stimulates the pip92 expression via Raf-MEK-extracellular signal-regulated protein kinase- as well as Src kinase-dependent signaling pathways.

Animals↗
PubMed2000

Novel biphasic effect of pyrrolidine dithiocarbamate on neuronal cell viability is mediated by the differential regulation of intracellular zinc and copper ion levels, NF-kappaB, and MAP kinases.

Nuclear factor kappaB (NF-kappaB) is a transcription factor involved in the expression of a wide range of genes, most of which code for proteins that play a role in immunity and inflammation. Pyrrolidine dithiocarbamate (PDTC) is a well-known inhibitor of NF-kappaB. Although its mechanism of action is conferred by its antioxidant property, other mechanisms by which PDTC can act as a prooxidant, metal chelator, and free thiol group modulator have recently been suggested. Here we report that PDTC caused a dual effect on cell viability in neuronal rat pheochromocytoma (PC12) cells, depending on its concentration. Increase of intracellular zinc and copper ion levels selectively potentiated the cytotoxic PDTC effect in a dose-dependent manner, and thiol reagents, such as glutathione and N-acetylcysteine, as well as divalent metal-chelating reagents, such as EDTA and bathocuproline disulfonic acid, blocked its cell death effect. The differential effect of PDTC on cell viability correlates well with the inhibition of NF-kappaB activities. In addition, PDTC differentially activated microtubule-associated protein (MAP) kinases, such as extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), but not p38, depending on its dose, and the coaddition of glutathione (GSH), other antioxidants, and metal ions also modulated their activities. Furthermore, stable Bcl-2 expression blocked the PDTC-induced cell death. These results suggest that the thiol groups and free zinc and copper ion levels are important for the novel biphasic PDTC effect on cell viability, which is associated with the differential activation of NF-kappaB and MAP kinases.

Animals↗
PubMed2000

Reliability of physical examination of the upper extremity among keyboard operators.

BACKGROUND: Physical examination is a traditional outcome measure in epidemiological research. Its value as a reliable measure depends, in part, on the prevalence of positive findings. The purpose of this paper is to determine the empirical reliability of physical examination and anthropometry in a field study of upper extremity disorders among keyboard operators. METHODS: Two experienced examiners independently performed common provocative tests and procedures in physical examinations of the neck and upper extremity among 160 keyboard operators. Two additional examiners conducted anthropometric surveys among 137 workers. Inter-examiner reliability was assessed with observed agreement, kappa statistics, and intra-class correlations (ICC). RESULTS: Observed agreement was between 96% and 100% for neck and upper extremity signs, muscle stretch reflexes, and muscle strength, however, with the exception of provocative tests, reliability statistics were unstable. Among the provocative tests, Phalen and Tinel tests had modest agreement after adjusting for chance (kappa range: 0.20-0.43). The carpal compression test had the best reliability (kappa=0.60 and kappa=0.67, left and right side, respectively). The ICCs for anthropometry ranged from 0.36-0.91. CONCLUSIONS: Results from the study showed that statistically, except for the carpal compression test, physical examination contributed minimal reliable information. This was attributed mainly to the low prevalence of positive findings, and generally mild nature of upper extremity disorders in this population. The results are the best estimate of what would be found in a field study with experienced examiners. While it may reduce bias, separating physical examination from medical history may contribute to the poor reliability of findings. With a shift toward reliable measures, resources can be allocated to more effective tools, like questionnaires, in epidemiological research of upper extremity disorders among keyboard operators.

Adult↗
PubMed2000

Expression of immediate early gene pip92 during anisomycin-induced cell death is mediated by the JNK- and p38-dependent activation of Elk1.

We report here that immediate early gene pip92 is expressed during anisomycin-induced cell death in fibroblast NIH3T3 cells. To determine the mechanism by which this occurs and to identify downstream signaling pathways, we investigated the induction of the pip92 promoter. The activation of pip92 by anisomycin is mediated by the activation of MAP kinases, such as JNK and p38 kinase, but not ERK. Deletion analysis of the pip92 promoter indicated that pip92 activation occurs primarily within the region containing a serum response element (SRE). Further analysis of the SRE using a heterologous thymidine kinase promoter showed that both an Ets and CArG-like site are required for anisomycin-induced pip92 expression. Elk1, which binds to the Ets site, was phosphorylated by the JNK- and p38-dependent pathways and the phosphorylation of Elk1-GAL4 fusion proteins by these pathways was sufficient for the transactivation. Overall, this study suggested that different MAPK pathways are involved in the expression of immediate early gene pip92 by growth factors and environmental stresses.

3T3 Cells↗
PubMed2000

A systemic administration of NMDA induces immediate early gene pip92 in the hippocampus.

In the mammalian CNS, aspartate and glutamate are major excitatory amino acids, and their receptors are believed to mediate a wide range of physiological and pathological processes, including neurotransmission, plasticity, excitotoxicity, and various forms of neurodegeneration. The immediate early gene pip92 has been identified in serum-stimulated BALB/c 3T3 fibroblasts, activated T lymphocytes treated with cycloheximide, and fibroblast growth factor-stimulated hippocampal cells during neuronal differentiation. In this study we have demonstrated that pip92 is expressed in the mouse brain after a single intraperitoneal injection of NMDA. The distribution of pip92 mRNA levels in the NMDA-treated mouse brain was investigated using in situ RT-PCR. The region-specific activation of pip92 in the CNS was observed 3 h after NMDA injection, and high levels of pip92 mRNA were detected in the hippocampal dentate gyrus and piriform cortex regions. In addition, the activation of pip92 by NMDA was mediated by activation of mitogen-activated protein kinases (MAPKs), such as c-Jun N-terminal kinase (JNK) and p38 kinase, but not extracellular signal-regulated kinase (ERK) in the mouse hippocampus and immortalized rat hippocampal progenitor cells. This study suggests that pip92 is likely to play an important role in neuronal cell death induced by excitotoxic NMDA injury in the CNS.

Animals↗
PubMed2000

Finger replantation in the United States: rates and resource use from the 1996 Healthcare Cost and Utilization Project.

Although finger replantation has been performed by hand surgeons in the United States for over 30 years the epidemiology of this procedure has not been studied. We used a national sampling database from the Agency for Health Care Policy and Research to summarize descriptive statistics surrounding finger replantation in the United States. This sample contained 304 cases of finger replantation performed in 1996. Mean hospital length of stay was 5.5 days and mean total charges were $20,330. Of the 906 hospitals included in this database, only 136 performed finger replantation during 1996. Of those, 60% performed only one case and 2% performed 10 or more cases. This descriptive analysis provides an examination of the largest sample size to date of finger replantation in the United States. Epidemiologic studies using national databases can provide researchers and policy makers with the analyses needed to examine treatment options and appropriately allocate future health care resources.

Adult↗
PubMed2000

Lymphangiosarcoma (Stewart-Treves syndrome) in postmastectomy patients.

Stewart-Treves syndrome (STS) is a rare but aggressive upper extremity lymphangiosarcoma in postmastectomy patients. Unfamiliarity with this disease and the innocuous appearance of the tumor often lead to delayed diagnosis. A comprehensive search of the databases at a single tertiary-care academic institution revealed only 3 cases of STS in the last 63 years. The latency time between breast cancer treatment and diagnosis of STS was 11 to 21 years. Survival after diagnosis of STS ranged from 8 to 15 months. One patient underwent radical surgery. The extensive lymphangiosarcoma in the other 2 patients precluded surgical resection and they underwent chemotherapy. All patients had adjuvant radiation therapy at the time of the original breast cancer resection. This report includes a discussion of the epidemiology, etiology, presentation, treatment, and prognosis of STS.

Aged↗