• Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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• v.12 no.2
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• pp.126-132
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• 2001

Background and Objectives : Signal traduction through phospholipase C(PLC) participate in the regulation of cell growth and differentiation. Growth factors bind to their receptors and thereby induce tyrosine phophorylation of the phospholipase C-${\gamma}$1(PLC-${\gamma}$1). PLC-${\gamma}$1 is a substrate for several receptor tyrosine kinases and its catalytic activity is increased by tyrosine phosphorylation. Tyrosine kinase phosphorylation of PLC-${\gamma}$1 stimulates PLC activation and cell proliferation. However the signal transduction pathway and the significance of PLC in injured recurrent laryngeal nerve regeneration is unknown. Therefore after we obtained fuctionally recovered rats using PEMF in this study, we attempt to provide some evidence that PLC plays a role in nerve regeneration itself and regeneration related to PEMF through the analysis of the difference between fucntional recovery group and non-recovery group in the recurrent laryngeal nerve. Materials and Method : Using 32 healthy male Sprague-Dawley rats, transections and primary anastomosis were performed on their left recurrent laryngeal nerves. Rats were then randomly assigned to 2 groups. The experimental group(n=16) received PEMS by placing them in custom cages equipped with Helm-holz coils(3hr/day, 5days/wk, for 12wk). The control group(n=16) were handled the same way as the experimental group, except that they did not receive PEMS. Laryngo-videoendoscopy was performed before and after surgery and followed up weekly. Laryngeal EMG was obtained in both PCA and TA muscles. Immunohistochemisty staining and Western blotting analysis using monoclonal antibody was performed to detect PLC-${\gamma}$1 in recurrent laryngeal nerve and nodose ganglion. Results : 10 rats(71%) in experimental group and 4 rats(38%) in the control group showed recovery of vocal fold motion. Functionally-recoverd rats show PLC-${\gamma}$1 positive cells in neuron and ganglion cells after 12 weeks from nerve injury. Conclusion : This study shows that PLC1-${\gamma}$ involved in singnal trasduction pathway in functinal recovery of injured recurrent laryngeal nerve and PEMF enhance the functional recovery by effect on this molecule.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4933-4938
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• 2014

Background: Although various tumor markers have been utilized in management of stomach cancer (SC), only a few reports have described relevance of examples such as CYFRA 21-1 and neuron-specific enolase (NSE). The purpose of this study was to evaluate the potential diagnostic performance of carcinoembryonic antigen (CEA), CA 19-9, CA72-4, CYFRA 21-1 and NSE in patients with SC. Materials and Methods: Ninety-six SC patients with pathologic confirmation between 2012 and 2013 were enrolled. Serum levels of five tumor markers were analyzed using a solid-phase immunoradiometric assay. Receiver operating characteristic (ROC) curves were plotted for the five tumor markers to investigate their diagnostic powers and adjusted cutoff values derived from analysis of ROC curves were evaluated to calculate the sensitivity of each for SC with recommended cutoff values. Results: Based on two different cutoff values (recommended and adjusted), CYFRA 21-1 (${\geq}2.0$ and 1.2 ng/ml) had a respective sensitivity of 50% and 78.1%, compared with 8.3% and 18.8% for CEA (${\geq}7.0$ and 3.9 ng/ml), 15.6% and 18.8% for CA 19-9 (${\geq}37$ and 26.7 ng/ml), 28.1% and 9.6% for CA 72-4 (${\geq}4.0$ and 13 ng/ml) and 7.3% and 7.3% for NSE (${\geq}14.7$ and 15.0 ng/ml) in the initial staging of primary SC. The area under the curve (AUC) for CYFRA 21-1, with a value of 0.978 (95% confidence interval, 0.964-0.991) was comparatively the highest. Univariate analysis revealed significant relationships between tumor marker level and lymph node involvement, metastasis and staging with CYFRA 21-1, CA 72-4 and NSE. Conclusions: CYFRA 21-1 was the most sensitive tumor marker and showed the most powerful diagnostic performance among the five SC tumor markers. NSE and CA 72-4 are significantly related to lymph node involvement, metastasis or stage. Further evaluations are warranted to clarify the clinical usefulness and prognostic prediction of these markers in SC.

• Journal of Sericultural and Entomological Science
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• v.46 no.1
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• pp.23-27
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• 2004

We were investigated the cognitive ability enhancement in rats using B. mori fibroin molecular controlled hydrolysate by preparative recycle HPLC system. Also, some of its physicochemical properties and free amino acid components were investigated, too. Nuclear magnetic resonance (NMR) spectrum are measured different pattern between high (HF) and low (LF) molecular controlled B. mori fibroin samples, respectively. The in vitro test by neuron primary cell culture are showed dependent on molecular weight (Mw) of B. mori fibroin in the order of LF > MF > HF, too. However, the memorial effects in rats by in vivo test are large dependent molecular weight on that maximum 50% than control. Also, the memorial effect was higher than the enzymatic relative and acid hydrolysate, which was 50.0$\pm$2.1 and 25.9$\pm$0.32%, respectively.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.5
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• pp.539-546
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• 2018

Botulinum toxin type A (BoNT/A) has been used therapeutically for various conditions including dystonia, cerebral palsy, wrinkle, hyperhidrosis and pain control. The substantia gelatinosa (SG) neurons of the trigeminal subnucleus caudalis (Vc) receive orofacial nociceptive information from primary afferents and transmit the information to higher brain center. Although many studies have shown the analgesic effects of BoNT/A, the effects of BoNT/A at the central nervous system and the action mechanism are not well understood. Therefore, the effects of BoNT/A on the spontaneous postsynaptic currents (sPSCs) in the SG neurons were investigated. In whole cell voltage clamp mode, the frequency of sPSCs was increased in 18 (37.5%) neurons, decreased in 5 (10.4%) neurons and not affected in 25 (52.1%) of 48 neurons tested by BoNT/A (3 nM). Similar proportions of frequency variation of sPSCs were observed in 1 and 10 nM BoNT/A and no significant differences were observed in the relative mean frequencies of sPSCs among 1-10 nM BoNT/A. BoNT/A-induced frequency increase of sPSCs was not affected by pretreated tetrodotoxin ($0.5{\mu}M$). In addition, the frequency of sIPSCs in the presence of CNQX ($10{\mu}M$) and AP5 ($20{\mu}M$) was increased in 10 (53%) neurons, decreased in 1 (5%) neuron and not affected in 8 (42%) of 19 neurons tested by BoNT/A (3 nM). These results demonstrate that BoNT/A increases the frequency of sIPSCs on SG neurons of the Vc at least partly and can provide an evidence for rapid action of BoNT/A at the central nervous system.

• Journal of Life Science
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• v.28 no.5
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• pp.597-604
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• 2018

Although the core mechanisms of Attention Deficit/Hyperactivity Disorder (ADHD) are unknown, several ADHD-associated proteins have been studied. G-protein - coupled receptor kinase interacting protein-1 (GIT1) is a multifunctional adapter protein that affects neuron growth and dendrite formation. GIT1-deficient mice have shown ADHD-like behavior and also recovered through amphetamine treatment. In this study, gliotransmitters were investigated in both intracellular and extracellular space from GIT1-deficient mice. To measure the amount of gliotransmitters, primary astrocyte cultures were taken from the cerebral and cerebellar cortices of wild (WT), hetero (HE), and knock-out (KO) mice. Major gliotransmitters were analyzed using high-performance liquid chromatography. It was observed that the amount of excitatory and inhibitory gliotransmitters were dependent on genotype and showed a change in excitation/inhibition ratios. Interestingly, the major excitatory gliotransmitter, glutamate, existed at the lowest level in WT mice, but the amount of inhibitory gliotransmitters, gamma-aminobutyric acid (GABA) and glycine, varied depending on brain region. Remarkably, an increased amount of GABA was measured at the intracellular cerebrum in WT mice compared with KO mice. It was presumed that KO mice would secrete more inhibitory gliotransmitters to compensate for GIT1 depletion or else acquire a defect to reuptake-secreted GABA. This may be a possible mechanism for ADHD pathology.

• International Journal of Oral Biology
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• v.31 no.4
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• pp.113-118
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• 2006

In the primary sensory neuron of the mesencephalic trigeminal nucleus (MTN), the peripheral axon supplies a large number of annulospiral endings surrounding intrafusal fibers encapsulated in single muscle spindles while the central axon sends only a few number of synapses onto single ${\alpha}-motoneurons({\alpha}-MNs)$. Therefore, the ${\alpha}-{\gamma}$ linkage is thought to be very crucial in the jaw-closing movement. Spike activity in a ${\gamma}-motoneuron\;({\gamma}-MN)$ would induce a large number of impulses in single peripheral axons by activating many intrafusal fibers simultaneously, subsequently causing an activation of ${\alpha}-MNs$ in spite of the small number of synapses. Thus, the activity of ${\gamma}-MNs$ may be vital for modulation of jaw-closing movements. Independently of such a spindle activity modulated by ${\gamma}-MNs$, somatic depolarization in MTN neurons is known to trigger the oscillatory spike activity. Nevertheless, the trafficking of these spikes arising from the two distinct sources of MTN neurons is not well understood. In this short review, switching among multiple functional modes of MTN neurons is discussed. Subsequently, it will be discussed which mode can support the ${\alpha}-{\gamma}$ linkage. In our most recent study, simultaneous patch-clamp recordings from the soma and axon hillock revealed a spike-back-propagation from the spike-initiation site in the stem axon to the soma in response to a somatic current pulse. The persistent $Na^+$ current was found to be responsible for the spike-initiation in the stem axon, the activation threshold of which was lower than those of soma spikes. Somatic inputs or impulses arising from the sensory ending, whichever trigger spikes in the stem axon first, would be forwarded through the central axon to the target synapse. We also demonstrated that at hyperpolarized membrane potentials, 4-AP-sensitive $K^+$ current ($IK_{4-AP}$) exerts two opposing effects on spikes depending on their origins; the suppression of spike initiation by increasing the apparent electrotonic distance between the soma and the spike-initiation site, and the facilitation of axonal spike invasion at higher frequencies by decreasing the spike duration and the refractory period. Through this mechanism, the spindle activity caused by ${\gamma}-MNs$ would be safely forwarded to ${\alpha}-MNs$. Thus, soma spikes shaped differentially by this $IK_{4-AP}$ depending on their origins would reflect which one of the two inputs was forwarded to the target synapses.

• Clinical and Experimental Reproductive Medicine
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• v.32 no.2
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• pp.133-147
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• 2005

Objectives: This study was carried out to establish human embryonic stem cells derived from frozen-thawed embryos using mouse embryonic fibroblasts (mEFs), human fetal skin and muscle fibroblasts as feeder cells, and to identify the characteristic of embryonic stem cells. Methods: When primary mEFs, human fetal skin and muscle fibroblasts were prepared, passaging on 4 days from replating could have effective trypsinization and clear feeder layers. Eight of 23 frozenthawed 4~8 cell stage embryos donated from consenting couples developed to blastocysts. Inner cell mass (ICM) was isolated by immunosurgery. ICM was co-cultured on mEFs, human fetal skin or muscle fibroblasts. The ICM colonies grown on mEFs, human fetal skin or muscle fibroblasts were tested the expression of stage specific embryonic antigen-3, -4 (SSEA-3, -4), octamer binding transcription factor-4 mRNA (Oct-4) and alkaline phosphatase surface marker. Results: We obtained 1 ICM colony from 2 ICM co-cultured on mEFs as feeder cells and did not obtain any ICM colony from 6 ICM clumps co-cultured on human fetal skin or muscle fibroblasts. The colony formed on mEFs could be passaged 30 times every 5 days with sustaining undifferentiated colony appearance. When the colonies cultured on mEFs were grown on human fetal skin or muscle fibroblasts, the colonies could be passaged 15 times every 9 days with sustaining undifferentiated colony appearance. The colonies grown on mEFs and human fetal fibroblasts expressed SSEA-4 and alkaline phosphatase surface markers and positive for the expression of Oct-4 by reverse transcription-polymerase chain reaction (RT-PCR). The produced embryoid body differentiated spontaneously to neural progenitorlike cells, neuron-like cells and beating cardiomyocyte-like cells, and frozen-thawed embryonic stem cells displayed normal 46,XX karyotype. Conclusions: The human embryonic stem cells can be established by using mEFs and human fetal fibroblasts produced in laboratory as feeder cells.

• Tuberculosis and Respiratory Diseases
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• v.42 no.3
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• pp.322-331
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• 1995

Introduction: This study was performed to evaluate the diagnostic usefulness of simultaneous determination of 3 tumor markers {serum carcinoembryonic antigen(CEA), squamous cell carcinoma antigen (SCC Ag) and neuron specific enolase(NSE)} in lung cancer patients. Method: In 113 patients with primary lung cancer(70 with squamous cell carcinoma, 30 with adenocarcinoma, 13 with small cell carcinoma) and 103 patients with benign lung diseases, serum CEA and NSE were measured by enzyme immunoassay, and SCC Ag was measured by microparticle enzyme immunoassay. Results: 1) The mean serum levels of 3 tumor markers were significantly higher in lung cancer groups than benign lung disease groups respectively(p=0.001). 2) In squamous cell carcinoma, the SCC Ag was elevated in 67%, in adenocarcinoma CEA was elevated in 77% and in small cell carcinoma NSE was elevated in 77%, but there were no significant differences according to the stage of each cancer cell types. 3) CEA was the most sensitive marker, but nonspecific to cancer types. SCC Ag was less sensitive than other markers, but more specific toward squamous cell carcinoma, and NSE was more specific to primary lung cancer. 4) As the number of positive tumor markers was increased, the relative possibility of lung cancer was also increased. If two markers were positive, it increased to 77%, and if three markers were positive it increased to 90%. Conclusion: The simultaneous measurement of serum CEA, SCC Ag and NSE would provide additional information for the diagnosis of lung cancer.

• Journal of Life Science
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• v.21 no.5
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• pp.647-655
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• 2011

The neurotoxicity of aggregated amyloid ${\beta}$ ($A{\beta}$) has been implicated as a critical cause in the pathogenesis of Alzheimer's disease (AD). It can cause neurotoxicity in AD by evoking a cascade of apoptosis to neuron. Here, we investigated the neuroprotective effects of cilostazol, which acts as a phosphodiesterase III inhibitor, on $A{\beta}_{25-35}$-induced cytotoxicity in mouse neuronal cells and cognitive decline in the C57BL/6J AD mouse model via peroxisome proliferator-activated receptor (PPAR)-${\gamma}$ activation. $A{\beta}_{25-35}$ significantly reduced cell viability and increased the number of apoptotic-like cells. Cilostazol treatment recovered cells from $A{\beta}$-induced cell death as well as rosiglitazone, a PPAR-${\gamma}$ activator. These effects were suppressed by GW9662, an antagonist of PPAR-${\gamma}$ activity, indicative of a PPAR-${\gamma}$-mediated signaling. In addition, cilostazol and rosiglitazone also restored PPAR-${\gamma}$ activity levels that had been altered as a result of $A{\beta}_{25-35}$ treatment, which were antagonized by GW9662. Furthermore, cilostazol also markedly decreased the number of apoptotic-like cells and decreased the Bax/Bcl-2 ratio. Intracerebroventricular injection of $A{\beta}_{25-35}$ in C57BL/6J mice resulted in impaired cognitive function. Oral administration of cilostazol (20 mg/kg) for 2 weeks before $A{\beta}_{25-35}$ injection and once a day for 4 weeks post-surgery almost completely prevented the $A{\beta}_{25-35}$-induced cognitive deficits, as did rosiglitazone. Taken together, our findings suggest that cilostazol could attenuate $A{\beta}_{25-35}$-induced neuronal cell injury and apoptosis as well as promote the survival of neuronal cells, subsequently improving cognitive decline in AD, partly because of PPAR-${\gamma}$ activation. The phosphodiesterase III inhibitor cilostazol may be the basis of a novel strategy for the therapy of AD.

• Tuberculosis and Respiratory Diseases
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• v.58 no.6
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• pp.582-589
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• 2005

Background : The incidence of lung adenocarcinoma, which is more prevalent in women and nonsmokers, is increasing. The aim of this study was to determine the prognostic factors of an adenocarcinoma of the lung. Material and method : The clinical information of patients diagnosed with an adenocarcinoma of the lung at the Kosin University Gospel Hospital from January 1994 to July 2004 was reviewed retrospectively. The survival time of these patients was analyzed by the patient's age, gender, performance status, weight loss, smoking history, location of the primary tumor, clinical stage, serologic tumor markers, and treatment modality. Results : For all 422 patients with an adenocarcinoma of the lung, 247 (58.5%) were male, and their mean age was 59.8 years the. The majority of patients were smokers (58.3%), and the tumors were located in the periphery (59.7%). In the smokers, the tumor was located more in the central airway compared to the non-smokers (42.8% vs. 31.9%, p=0.12). The overall median survival time was 390 days (95% CI;304-436 days). Univariate survival analysis revealed that an older age (${\geq}65$ years old), male, weight loss, smoker, central type, advanced clinical stage, elevated serum carcinoembryonic antigen (CEA, >5 ng/ml) and neuron specific enolase (NSE, >15 ng/ml), and the supportive care only were significantly poor prognostic factors. The median survival time was shorter in the smokers than nonsmokers (289 days vs. 533 days, p<0.001). In addition, it was also shorter in the elevated NSE group than in the normal range group (207 days vs. 469 days, p<0.001). Multivariate analysis showed that age, clinical stage, serum NSE, smoking status, and treatment modality were independent predictors of survival (hazard ratios: 1.68, 1.94, 1.92, 2.39 and 1.57, respectively). Conclusions : Smoking is an important prognostic factor in an adenocarcinoma of the lung, but not gender. This suggests that the better prognosis of women is more related with the lower rate of smoking. In addition, the elevated serum NSE is also an important prognostic in an adenocarcinoma of the lung.