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Enhanced Efficacy of Human Brain-Derived Neural Stem Cells by Transplantation of Cell Aggregates in a Rat Model of Parkinson's Disease

  • Shin, Eun Sil;Hwang, Onyou;Hwang, Yu-Shik;Suh, Jun-Kyo Francis;Chun, Young Il;Jeon, Sang Ryong
    • Journal of Korean Neurosurgical Society
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    • v.56 no.5
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    • pp.383-389
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    • 2014
  • Objective : Neural tissue transplantation has been a promising strategy for the treatment of Parkinson's disease (PD). However, transplantation has the disadvantages of low-cell survival and/or development of dyskinesia. Transplantation of cell aggregates has the potential to overcome these problems, because the cells can extend their axons into the host brain and establish synaptic connections with host neurons. In this present study, aggregates of human brain-derived neural stem cells (HB-NSC) were transplanted into a PD animal model and compared to previous report on transplantation of single-cell suspensions. Methods : Rats received an injection of 6-OHDA into the right medial forebrain bundle to generate the PD model and followed by injections of PBS only, or HB-NSC aggregates in PBS into the ipsilateral striatum. Behavioral tests, multitracer (2-deoxy-2-[$^{18}F$]-fluoro-D-glucose ([$^{18}F$]-FDG) and [$^{18}F$]-N-(3-fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl)nortropane ([$^{18}F$]-FP-CIT) microPET scans, as well as immunohistochemical (IHC) and immunofluorescent (IF) staining were conducted to evaluate the results. Results : The stepping test showed significant improvement of contralateral forelimb control in the HB-NSC group from 6-10 weeks compared to the control group (p<0.05). [$^{18}F$]-FP-CIT microPET at 10 weeks posttransplantation demonstrated a significant increase in uptake in the HB-NSC group compared to pretransplantation (p<0.05). In IHC and IF staining, tyrosine hydroxylase and human ${\beta}2$ microglobulin (a human cell marker) positive cells were visualized at the transplant site. Conclusion : These results suggest that the HB-NSC aggregates can survive in the striatum and exert therapeutic effects in a PD model by secreting dopamine.

Post-marketing Surveillance Study of an Inactivated Split-Virion Influenza Vaccine in Korea (불활화 분할 인플루엔자 백신의 국내 시판 후 조사 연구)

  • Huh, Jae-Won;Ma, Sang-Hyuk;Kim, Hyun-Kyun;Gunapalaiah, Bhavyashree;Bock, Hans L.;on behalf of the Fluarix-054 Study Group,
    • Pediatric Infection and Vaccine
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    • v.18 no.1
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    • pp.68-79
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    • 2011
  • Purpose : This post-marketing surveillance study (NCT00750360) assessed the safety and reactogenicity of an inactivated, trivalent split-virion influenza vaccine licensed for use in the Korea since 2002. Methods : Eight hundred and eighty three subjects aged 6 months received a single dose of the ${\geq}$ vaccine; an additional dose was administered to those aged <9 years and unprimed with an influenza vaccine. Four hundred and eleven subjects used diary cards to record safety information; this report presents data from these subjects. Incidence of solicited local, general and unsolicited adverse events (4-days and 21-days post-vaccination follow-up periods, respectively) were recorded. Serious adverse events (SAEs) were recorded throughout the study period. Results : Injection site pain (subjects aged <6 years: 12.6% of subjects, ${\geq}$6 years: 34.7%), fever (<6 years: 1.3%) and myalgia (${\geq}$6 years: 13.9%) were the most frequently recorded solicited local and general adverse events. Grade 3 solicited adverse events were reported by ${\leq}$4.0% subjects. No vaccine-related SAEs were recorded (KFDA criteria). Conclusion : Considering the vaccine's well-established immunogenicity and its favourable safety and reactogenicity profile across all age groups and its high coverage rate in Korea, it may be recommended as a candidate to facilitate annual seasonal influenza vaccination for all ages as part of the Korean National Immunization Program.

The Police's Public Safety Infra Construction Plans for the Protection of Victims of Sexual Violence (경찰의 성폭력 범죄피해자 보호를 위한 치안인프라 구축방안)

  • Kim, Hyun-Dong;Jo, Hyun-Bin
    • The Journal of the Korea Contents Association
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    • v.13 no.12
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    • pp.715-723
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    • 2013
  • Following the social consensus for the need to stop sexual violence, the government has amended juvenile sex protection laws to impose fees on education practitioners who do not report sexual crimes against women, and amended the 'domestic violence prevention and victim protection laws' (2012. 2) so that the police can investigate on site. However, regardless of these wide efforts, the reality is that sexual crimes against the socially weak do not seem to be dwindling, raising concerns of the effectiveness of such amendments. Generally sexual crimes are hard to prove, and even if reports are filed, most cases are dropped with non-prosecution disposition. Victims are usually limited to women and children and this leads to secondary victims. As this thesis states, developed countries have a more systematic protection methods than our country. Therefore, the purpose of this thesis lies on the construction of public safety infrastructure for the protection of sexual abuse victims (enhancing safety protocols with related organizations, implementing a bill of rights for the victims, prevention-centered police education, amendments to current law) to limit human rights violations and criminal injuries.

Novel Low-Temperature-Active Phytase from Erwinia carotovora var. carotovota ACCC 10276

  • Huang, Huoqing;Luo, Huiying;Wang, Yaru;Fu, Dawei;Shao, Na;Yang, Peilong;Meng, Kun;Yao, Bin
    • Journal of Microbiology and Biotechnology
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    • v.19 no.10
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    • pp.1085-1091
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    • 2009
  • A phytase with high activity at low temperatures has great potential for feed applications, especially in aquaculture. Therefore, this study used a degenerate PCR and TAIL PCR to clone a phytase gene from Erwinia carotovora var. carotovota, the cause of soft rot of vegetables in the ground or during cold storage. The full-length 2.5-kb fragment included an open reading frame of 1,302 bp and encoded a putative phytase of 45.3 kDa with a 50% amino acid identity to the Klebsiella pneumoniae phytase. The phytase contained the active site RHGXRXP and HD sequence motifs that are typical of histidine acid phosphatases. The enzyme was expressed in Escherichia coli, purified, and displayed the following characteristics: a high catalytic activity at low temperatures (retaining over 24% activity at $5^{\circ}C$) and remarkably thermal lability (losing >96% activity after incubation at $60^{\circ}C$ for 2 min). The optimal phytase activity occurred at pH 5.5 and ${\sim}49^{\circ}C$, and the enzyme activity rapidly decreased above $40^{\circ}C$. When compared with mesophilic counterparts, the phytase not only exhibited a high activity at a low temperature, but also had a low $K_m$ and high $k_{cat}$. These temperature characteristics and kinetic parameters are consistent with low-temperature-active enzymes. To our knowledge, this would appear to be the first report of a low-temperature-active phytase and its heterogeneous expression.

Effect of a Phospholamban Peptide on the Skeletal Sarcoplasmic Reticulum $Ca^{2+}$ Transport (골격근 근장그물 칼슘이동에 대한 Phospholamban 펩타이드의 조절)

  • Kim, Hae-Won;Lee, Hee-Ran
    • The Korean Journal of Pharmacology
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    • v.30 no.1
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    • pp.117-124
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    • 1994
  • Phospholamban is the regulator of $Ca^{2+}-ATPase$ in cardiac sarcoplasmic reticulum(SR). The mechanism of regulation appears to involve inhibition by dephosphorylated phospholamban. Phosphorylation of phospholamban relieves this inhibition. Recently, there has been a report that the cytoplasmic domain (amino acids 1-25) of phospholamban is insufficient to inhibit the $Ca^{2+}$ pump. To explore the domains of phospholamban responsible for $Ca^{2+}-ATPase$ inhibitory activity, we examined the effect of a synthetic phospholamban peptide consisting of amino acid residues 1-25 on $Ca^{2+}$ uptake by reconstituted skeletal SR $Ca^{2+}-ATPase$. The $Ca^{2+}-ATPase$ of skeletal SR was purified and reconstituted in proteoliposomes containing phosphatidylcholine (PC) or phosphatidylcholine: phosphatidylserine (PC:PS). Inclusion of a phospholamban peptide in PC proteoliposomes was associated with significant inhibition of the initial rates of $Ca^{2+}$ uptake at pCa 6.0, and phosphorylation of this peptide by the catalytic subunit of cAMP-dependent protein kinase reversed the inhibitory effect on the $Ca^{2+}$ pump. Similar effects of phospholamban peptide were also observed using PC:PS proteoliposomes. Based on these results, we could conclude that the cytoplasmic domain of phospholamban, containing the phosphorylation sites, by itself is sufficient to inhibit the $Ca^{2+}$ pump of SR.

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Interseeding Substitution Ratio Assessment by Using of Molecular Tool (분자생물학적 기법을 이용한 Interseeding률 평가)

  • Jung, Seung-Ho;Lim, Deuk-Jong;Jang, Duk-Hwan
    • Asian Journal of Turfgrass Science
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    • v.24 no.2
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    • pp.131-137
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    • 2010
  • Recently, many domestic golf course have showed interest in introducing new cultivars into existing putting greens without reconstruction. But, any report and survey method for interseeding substitute ratio haven't been published. Therefore, this study was conducted to evaluate the effectiveness for interseeding by investigating how many interseeding plants were introduced into existing putting green by using molecular biologic tool. The Woo Jung Hills Country Club was one time introduced penn A4 into penncross putting green. The Lake Side Country Club was three times introduced CY-2 into penncross putting green. The interseeding substitute ratio using SCAR markers was 20% in the Woo Jung Hills Country Club and 35.5% in Lake Side Country Club. The interseeding putting green in Lake Side Country Club was investigated to three site, strong pressure, middle pressure and weak pressure. These substitute ratios were strong pressure 27.1%, middle pressure 37.3%, and weak pressure 47.2%. The data indicated that an interseeding substitute ratio was more increased three times than one time to introducing new cultivar into existing putting green. A long-term program should be made in order to exchange existing cultivar in putting green without reconstruction.

Assessment of Discoidal Polymeric Nanoconstructs as a Drug Carrier (약물 운반체로서의 폴리머 디스크 나노 입자에 대한 평가)

  • BAE, J.Y.;OH, E.S.;AHN, H.J.;KEY, Jaehong
    • Journal of Biomedical Engineering Research
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    • v.38 no.1
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    • pp.43-48
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    • 2017
  • Chemotherapy, radiation therapy, and surgery are major methods to treat cancer. However, current cancer treatments report severe side effects and high recurrences. Recent studies about engineering nanoparticles as a drug carrier suggest possibilities in terms of specific targeting and spatiotemporal release of drugs. While many nanoparticles demonstrate lower toxicity and better targeting results than free drugs, they still need to improve their performance dramatically in terms of targeting accuracy, immune responses, and non-specific accumulation at organs. One possible way to overcome the challenges is to make precisely controlled nanoparticles with respect to size, shape, surface properties, and mechanical stiffness. Here, we demonstrate $500{\times}200nm$ discoidal polymeric nanoconstructs (DPNs) as a drug delivery carrier. DPNs were prepared by using a top-down fabrication method that we previously reported to control shape as well as size. Moreover, DPNs have multiple payloads, poly lactic-co-glycolic acid (PLGA), polyethylene glycol (PEG), lipid-Rhodamine B dye (RhB) and Salinomycin. In this study, we demonstrated a potential of DPNs as a drug carrier to treat cancer.

Relative Frequency of Oral Malignancies and Oral Precancer in the Biopsy Service of Jazan Province, 2009-2014

  • Idris, AM;Vani, NV;Saleh, Sanna;Tubaigy, Faisal;Alharbi, Fahd;Sharwani, Abubkr;Tadrus, Nabil;Warnakulasuriya, Saman
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.2
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    • pp.519-525
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    • 2016
  • Background: The objective of this study was to report the types and relative frequency of oral malignancies and precancer in the Jazan region of Saudi Arabia during the period 2009-2014. Materials and Methods: Pathology reports were retrieved from the archives of Histopathology Department, King Fahd hospital in Jazan. Demographic data on tobacco habits, clinical presentation and histologic grading of oral precancer and cancer cases were transcribed from the files. Results: 303 (42.7%) oral pre-malignant and malignant cases were found out of 714 oral biopsy lesions. A pathology diagnosis of squamous cell carcinoma (85.1%) was most frequent, followed by premalignant lesions/epithelial dysplasia (8.6%), verrucous carcinoma (3.3%) and malignancy of other histological types (3%) such as ameloblastic carcinoma, salivary gland malignancy and sarcomas. Oral squamous cell carcinoma was predominant in females with a male to female ratio of 1:1.9. Patient age ranged from 22 to 100 years with a mean of $65{\pm}13.9$. Almost 44.6% of oral cancer had occurred after 65 years of age. Only 16.3% cases were reported in patients younger than 50 years, predominantly females. The majority of female patients had the habit of using shammah with a long duration of usage for more than 45 years. Buccoalveolar mucosa (52.3%) was the common site of involvement followed by tongue/floor of the mouth (47.7%) and clinically presented mostly as ulceration/swelling clinically. Moderately differentiated tumours (53.9%) were common followed by well differentiated (32.2%) and poorly differentiated tumours (5.8%). The prevalence of oral verrucous carcinoma (3.3%) was comparatively low with an equal distribution in both males and females. Both bucco-alveolar mucosa and tongue were predominantly affected. Oral precancer/epithelial dysplasia (8.6%) was common in females with a shammah habit. Bucco-alveolar mucosa was commonly involved and clinically presented mostly as white/red patches. Most cases were mild followed by moderate and severe dysplasia. Tumours of other histological types (3%) include 1 ameloblastic carcinoma, 3 malignant salivary gland tumours and 5 sarcomas. Conclusions: In this study, it was found that oral cancers reported in the pathology service to be a common occurrence. This study reconfirms previous reports of the high burden of oral cancer in this population This indicates that conventional preventive programs focused on oral cancer are in need of revision. In addition, further research into identifying new risk factors and molecular markers for oral cancer are needed for screening high risk individuals.

Clonig of CM-cellulase Gene of Rhizobium meliloti TAL1372 in Escherichia coli (Rhizobium meliloti TAL1372에서 섬유소분해효소 유전자 클로닝)

  • Park, Yong-Woo;Lim, Sun-Teak;Kang, Kyu-Young;Yun, Han-Dae
    • Applied Biological Chemistry
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    • v.38 no.4
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    • pp.313-319
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    • 1995
  • The involvement of the cell-wall degrading enzymes in Rhizobium has long been an unsolved question about the infection process in the formation of root nodule. To assess the contribution of the cellulase to the nodulation of rhzobia, here we report the production of cellulase from R. meliloti TAL1372 which degrade carboxymethylcellulose (CMC) model substrate with CMC-plate method. We constructed a genomic library by cloning Sau3A-digested genomic DNA from R. meliloti TAL1372 into the BamHI site of the cosmid vector pLAFR3. Out of more than one thousand transductants of E. coli, one clone (pRC8-71) had CM-cellulase activity and contained pLAFR3 cosmid with 30 kb insert of R. meliloti DNA The product of CM-cellulase gene was analyzed by native PAGE. About 45 kD protein was considered to be a product of the gene. Tn5 mutagenesis reveals that the structural gene located in a ca. 3 kb KpnI fragment. The cellulase-minus mutants of R. meliloti TAL1372 were obtained by Tn5 mutagenesis of pRC8-71 and marker exchange techniques. Analyses of the nodulation ability of these Tn5 mutants showed that the CM-cellulase gene of R. meliloti TAL1372 may be involved in early nodulation development on alfalfa (Medicago satiua).

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Cardiac Pharmacology of Anesthetics (마취제(痲醉劑)의 심장약리학적(心臟藥理學的) 연구(硏究) 제2보(第2報) 각종대사기질(各種代謝基質)에 대(對)한 Halothane 저하유이심방(低下遊離心房)의 수축반응(收縮反應))

  • Ko, Kye-Chang;Jung, Jee-Chang;Han, Dae-Sup
    • The Korean Journal of Pharmacology
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    • v.10 no.1 s.15
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    • pp.55-59
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    • 1974
  • Further elucidation of the mechanism of halothane's negative inotropic action has resulted from a study of the effect of various substrates on halothane-depressed rat atria. Approximately 6 mg% halothane was required to maintain a 50% depression of the contractility of rat atria suspended in a modified Krebs-Ringer bicarbonate glucose medium, pH 7.4, $30^{\circ}C$ for 2hr. Both lactate and acetate were found to restore partially the contractility of halothane-depressed atria. The maximally effective concentration of lactate was 5 mM; for acetate it was 2.5mM. Neither 5 nor 20 mM of additional glucose was effective in restoring the force of contraction of halothane-depressed atria. The results are consistent with the hypothesis that halothane exerts at least a part of its negative inotropic effect on rat atria by inhibiting either the uptake or utilization of glucose by the myocardium. The site of blockade must be prior to the conversion of pyruvate to acetyl CoA. In our previous report dealing with the mechanism of cardiac depressant action of inhalation anesthetic halothane, it has been demonstrated that: 1) approximately 6 mg/100 ml halothane is required to maintain 50% depression of the force of contraction of isolated rat atria in Krebs-Ringer bicarbonate glucose medium; 2) pyruvate partially restores the contractility of halothane-depressed atria, but has no effect on normal atria; the partial recovery of depressed atria by the addition of sodium pyruvate is due to the effect of the pyruvate ion itself, not to the sodium ion; 4) addition of pyruvate, to atria depressed with hypertonic medium, produced only further depression. From these findings we concluded that the cardiac depressant action of halothane on rat atria is a manifestation of inhibition of glucose uptake or utilization. The present studies were undertaken to observe the effect of other substrates on halothane-depressed atria in order to substantiate our conclusion. As with the case of pyruvate, lactate and acetate also partially restored the force of contraction of halothane-depressed atria. These data are consistent with the hypothesis that halothane inhibits glucose uptake or utilization in the glycolytic cycle of the myocardium.

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