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A Case Study of Botulinum Toxin A Treatment in Cerebral Palsy (뇌 생 마비 환아의 Botulinum Toxin A 주사 후 보행양상의 변화)

  • Lee, Jae-Ho;Hong, Do-Sun;Kim, Young-Hee
    • Physical Therapy Korea
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    • v.5 no.1
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    • pp.44-50
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    • 1998
  • The purpose of this case study was to introduce botulinum toxin A injection in cerebral palsy. Spasticity can be managed using a variety of methods. Eliminating aggravating sources, promoting stretching and bracing, and positioning are the least invasive methods of treatment. Botulinum toxin A injection is a relatively recent method of spasticity management in children with cerebral palsy. A 3-year old boy was evaluated for possible botulinum toxin injection to promote left side function. The patient had left hemiparetic cerebral palsy. He walked with bilateral intoning, much worse on the left than on the right and with excessive plantar flexion on the left. Botulinum toxin A was injected into the left medial gastrocnemius, with the goals of improving quality of gait. Finally, botulinum toxin treatment of would improve the motor function and ambulatory status in cerebral palsy by hypertonicity, spasticity, dynamic contracture and athetoid movement.

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Antiproliferative Effect of Trichostatin A and HC-Toxin in T47D Human Breast Cancer Cells

  • Joung, Ki-Eun;Kim, Dae-Kee;Sheen, Yhun-Yhong
    • Archives of Pharmacal Research
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    • v.27 no.6
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    • pp.640-645
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    • 2004
  • Histone deacetylase inhibitors are new class of chemotherapeutic drugs able to induce tumor cell apoptosis and/or cell cycle arrest. Trichostatin A, an antifungal antibiotic, and HC-toxin are potent and specific inhibitors of histone deacetylase activity. In this study, we have examined the antiproliferative activities of trichostatin A and HC-toxin in estrogen receptor positive human breast cancer, T47D cells. Both trichostatin A and HC-toxin showed potent antiprolifer-ative efficacy and cell cycle arrest at $G_2/M$ in T47D human breast cancer cells in a dose-dependent manner. Trichostatin A caused potent apoptosis of T47D human breast cancer cells and trichostatin A-induced apoptosis might be involved in an increase of caspase-3/7 activity. HC-toxin evoked apoptosis of T47D cells and HC-toxin induced apoptosis might not be medi-ated through direct increase in caspase-3/7 activity. We have identified potent activities of anti-proliferation, apoptosis, and cell cycle arrest of trichostatin A and HC-toxin in estrogen receptor positive human breast cancer cell line T47D.

Isolation and Identification of Cytotoxic and Biological Active Toxin from the Puffer Fish Arothron stellatus

  • Veeruraj, Anguchamy;Pugazhvendan, Sampath Renuga;Ajithkumar, Thipramalai Thankappan;Arumugam, Muthuvel
    • Toxicological Research
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    • v.32 no.3
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    • pp.215-223
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    • 2016
  • This study is to investigate the biological, biochemical and cytotoxic effects of puffer fish (Arothron stellatus) toxin extracts under in-vitro condition. Extracted toxins from various organs of puffer fish were purified by using active charcoal column, and Bio-gel-P2 column chromatography. The lethality of toxin was tested in crabs, which consists of neurotoxic compounds. The degree of the brine shrimp lethality assay was found directly proportional to the concentration of the toxin extracts, which was well supported by hemolytic assay. The experimental results suggested that the gonad was found higher toxins than the liver and muscles. The mortality rate of brine shrimp nauplii was increased with the raise of concentrations of toxin level. Among the different doses and time dependent cytotoxic effect of human cervical carcinoma (HeLa) cells were showed $4.0{\mu}g/mL$ of toxin, which was effectively inhibited cancer cell proliferation. HPLC and TLC analysis was revealed that the A. stellatus toxin contains tetrodotoxin (TTX), related compounds 4-epi TTX and anhydro-TTX. The present results suggested that the A. stellatus contain TTX as a major and anh-TTX as a minor toxin. It could be the potential candidate in the field of anticancer drug discovery against human cervical cancer cells. The present data is confirming that the puffer fish toxin as an interesting source of novel bioactive natural compounds with potent applications in pharmacology.

Increased Refolding Yield of Disulfide Bond Bridged Fab-Toxin Homodimers by the Insertion of CH3 Domains

  • Song Jeong-Wha;Won Jae-Seon;Lee Yong-Chan;Choe Mu-Hyeon
    • Journal of Microbiology and Biotechnology
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    • v.16 no.7
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    • pp.1104-1110
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    • 2006
  • Recombinant antibody-toxin is a bifunctional protein that binds and kills a target cell expressing a specific antigen on the surface of the cell, and its structure is chimeric, in which a toxin is fused to an antigen-binding domain such as scFv or Fab. Divalent antibody-toxin molecules showed higher cytotoxicities against cancer cell lines than monovalent molecules. However, the yields of the divalent molecules were very low. In this study, we introduced the CH2, CH3, or CH2-CH3 (=Fc) domain of antibody in the middle of the Fab-toxin between the hinge region of human IgG1 and the toxin domain to increase the yield. The covalently bonded dimer could be formed by three disulfide bridges from cysteine residues in the hinge region. The molecule with the CH3 domain showed about 3-fold higher dimerization yield than previously constructed Fab-toxin molecules, while maintaining the cytotoxic activity comparable to that of scFv-toxin. However, the introduction of CH2 or Fc domain to the same position showed little effect on the dimerization yield. We also observed that the introduction of the CH3 region made it possible to form noncovalently associated dimer molecules.

Characteristics of Pichia anomala K15 Producing Killer Toxin Isolated from Traditional Nuruk (전통 누룩으로부터 분리된 Killer Toxin 생산 균주 Pichia anomala K15의 특성)

  • Jung, Hee-Kyoung;Park, Chi-Duck;Lee, Gee-Dong;Park, Seung-Chun;Park, Hwan-Hee;Hong, Joo-Heon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.36 no.8
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    • pp.1077-1082
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    • 2007
  • In this study, killer yeasts were isolated from traditional Nuruk to improve storage and suppress contaminant in food industry. Among killer yeasts, yeast K15 showed strong killer toxin activity and inhibited growth of Salmonella Typhimurium and Vibrio parahaemolyticus. Killer yeast K15 was identified with Pichia anomala by the Microlog TM 4.0 identification system and homology of the ITS sequence. Killer toxin generated from P. anomala K15 was inactivated by pronase E and suggested to be a protein. Therefore killer toxin of P. anomala K15 was thought to be safe in human such as bacteriocin. P. anomala K15 was sufficient for growth in 50% glucose and could be used to prevent contaminant in initial stages of alcohol beverage fermentation.

Modulation of Interleukin Production in Anthrax Lethal Toxin-treated Macrophages by Melatonin and Dehydroepiandrosterone

  • Shin, Sung-Ho;Hur, Gyeung-Haeng;Yeon, Kyu-Baek;Kim, Yun-Bae;Park, Kyung-Jin;Park, Young-Min;Lee, Woo-Sung;Cho, Bong-Huey;Kim, Won-Yong;Chung, Sang-In;Choi, Chul-Soon
    • BMB Reports
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    • v.33 no.6
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    • pp.463-468
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    • 2000
  • Anthrax lethal toxin, which consists of two separate protein, protective antigen (83 KDa) and lethal factor (85 KDa) is responsible for major symptoms and death from systemic infection of Bacillus anthracis. High concentrations of this toxin are cytolytic to macrophages, whereas sublytic concentrations of lethal toxin induce these cells to produce interleukin $1{\beta}$ ($IL-1{\beta}$). It is proposed that melatonin and dehydroepiandrosterone (DHEA) may play an important role in modifying immune dysfunction. In this study, we investigated whether or not melatonin and DHEA could prevent $IL-1{\beta}$ production that is induced by anthrax lethal toxin in mouse peritoneal macrophages. Treatment of melatonin or DHEA alone, as well as together, prevented the production of $IL-1{\beta}$ caused by anthrax lethal toxin. We found that melatonin at a concentration of $10^{-6}-10^{-7}$ M inhibits $IL-1{\beta}$ production induced by anthrax lethal toxin. As expect, treatment of DHEA at a concentration $10^{-6}-10^{-7}$ M also suppressed production of $IL-1{\beta}$ by lethal toxin stimulated macrophages. The results of these studies suggest that melatonin and DHEA, immunomodulators, may have an important role in reducing the increase of cytokine production in anthrax lethal toxin-treated macrophages.

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Clostridium difficile Toxin A Inhibits the Kinase Activity of Extracellular Signal-Related Kinases 1 and 2 Through Direct Binding

  • Seok, Heon;Nam, Hyo-Jung;Nam, Seung-Taek;Kang, Jin-Ku;Kim, Sung-Kuk;Chang, Jong-Soo;Ha, Eun-Mi;Park, Young-Joo;Kim, Ho
    • Journal of Microbiology and Biotechnology
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    • v.22 no.2
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    • pp.170-175
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    • 2012
  • Clostridium difficile toxin A glucosylates Rho family proteins, resulting in actin filament disaggregation and cell rounding in cultured colonocytes. Given that the cellular toxicity of toxin A is dependent on its receptor binding and subsequent entry into the cell, we herein sought to identify additional colonocyte proteins that might bind to toxin A following its internalization. Our results revealed that toxin A interacted with ERK1 and ERK2 in two human colonocyte cell lines (NCM460 and HT29). A GST-pulldown assay also showed that toxin A can directly bind to ERK1 and ERK2. In NCM460 cells exposed to PMA (an ERK1/2 activator), the phosphorylation of ERK1/2 did not affect the interaction between toxin A and ERK1/2. However, an in vitro kinase assay showed that the direct binding of toxin A to ERK1 or ERK2 inhibited their kinase activities. These results suggest a new molecular mechanism for the cellular toxicity seen in cells exposed to toxin A.

The Correlation between Toxin Genotype and Antibiotic Resistance in Methicillin Resistant Staphylococcus aureus Isolated from Clinical Specimen of Intensive Care Unit (중환자실의 임상검체로부터 분리된 Methicillin 내성 Staphylococcus aureus의 독소유전자형과 항생제내성의 상관관계)

  • Park, Chul;Seong, Chi Nam
    • Korean Journal of Clinical Laboratory Science
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    • v.48 no.3
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    • pp.202-209
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    • 2016
  • This study is aimed to determine the correlation between the toxin gene types and antibiotic resistance from MRSA (methicillin-resistant Staphylococcus aureus). Fifty-two strains of MRSA, between January 2014, and December 2014, were isolated from clinical specimens obtained from 2,664 cases in the intensive care unit of a hospital in Suncheon, Jeonnam, Korea. Genes encoding mecA, enterotoxin (SE), toxic shock syndrome toxin-1 (TSST-1), exfoliative toxin (ET), and Panton-Valentine leukocidin (PVL) were detected by multiplex PCR-mediated amplification using specific primers. Toxin genes (seg and sei) were present in 40 strains (76.9%), followed by tst in 34 strains (65.4%). Other genes (eta, etb, sea, sed, see, seh, sej, and pvl) were not detected. Forty strains (76.9%) of MRSA had 2 or more toxin genes simultaneously; 5 coexistent toxin-genes (seb, sec, seg, sei, tst) were the most common in 28 strains (53.8%), and 6 strains (11.5%) had seg and sei genes. The coexistence of genes were 72.5~100%, showing a high correlation among genes (seb, sec, seg, sei and tst). As strains (seb, sec, tst) that had particular toxin genes (seb, sec, seg, sei, tst) in multiple showed 100% resistance to ciprofloxacin, clindamycin, erythromycin, we were able to find that seb, sec, and tst genes have a close relationship to the aforementioned antibiotics. It showed a higher resistance to ciprofloxacin, clindamycin, erythromycin, and tetracycline compared with strains that had toxin genes independent from multiple toxin genes.

The Use of AM-toxin in Monitoring the Numbers of Air-borne Spores of Alternaria mali Causing Leaf Spot in Apple Orchards (AM-toxin을 이용(利用)한 사과점무늬낙엽병균(Alternaria mali)의 공기중(空氣中) 밀도(密度) 조사(調査))

  • Yu, Seung-Hun;Shim, Hyeong-Kwon;Park, Jong-Seong
    • Korean journal of applied entomology
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    • v.26 no.4 s.73
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    • pp.273-275
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    • 1987
  • Changes in the numbers of air-borne spores of Alternaria mali causing the Alternaria leaf spot of apple were investigated in apple orchards, by monitoring their AM- toxin(host-specific toxin) producing ability. Most of the air-borne Alternaria in apple orchards were not AM-toxin producers. In culture, only about 2% of Alternaria isolates from a commercially managed apple orchards produced the toxin that was highly toxic only to susceptible leaves.

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Effect of Botulinum Toxin A on Proliferation and Apoptosis in the T47D Breast Cancer Cell Line

  • Bandala, Cindy;Perez-Santos, Jose Luis Martin;Lara-Padilla, Eleazar;Delgado Lopez, Ma. Guadalupe;Anaya-Ruiz, Maricruz
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.2
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    • pp.891-894
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    • 2013
  • The present study was performed to assess the activity of the botulinum toxin A on breast cancer cells. The T47D cell line was exposed to diverse concentrations of the botulinum toxin A and cell viability and apoptosis were estimated using MTT and propidium iodine/annexin V methods, respectively. Botulinum toxin A exerted greater cytotoxic activity in T47D cells in comparison with MCF10A normal cells; this appeared to be via apoptotic processes caspase-3 and -7. In conclusion, botulinum toxin A induces caspase-3 and -7 dependent apoptotic processes in the T47D breast cancer cell line.