• Title/Summary/Keyword: ALS

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Inhibition of Barley Acetolactate Synthase by Triazolopyrimidine Derivative (트리아졸로피리미딘계 유도체에 의한 보리 Acetolactate Synthase의 저해)

  • Kim, Sung Ho;NamGoong, Sung Keon;Shin, Jung Hyu;Chang, Soo Ik;Choi, Jung Do
    • Journal of the Korean Chemical Society
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    • v.43 no.4
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    • pp.461-468
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    • 1999
  • Acetolactate synthase (ALS) catalyzes the first common reaction in the biosynthesis of branched-chain amino acids, valine, leucine, and isoleucine. ALS is the common target of several classes of structurally diverse herbicides, the triazolopyrimidines, the imidazolinones, the sulfonylureas, and pyrimidyl-oxy-benzoates. We examined ihibitory activities of newly synthesized triazolopyrimidine sulfonamide derivatives using partially purified ALS from barley. $IC_{50}$ values for the active derivatives are 0.5nM∼8$\mu$M. Among them TP1 and TP2 are the most potent ALS inhibitors with $IC_{50}$ values of 0.5nM and 1.6nM, respectively. These inhibitors are more potent in the inhibition of barley ALS than commercial herbicides, Metosulam ($IC_{50}$;3.6 nM), Flumetsulam ($IC_{50}$;126 nM), and Cadre ($IC_{50};4 {\mu}M$). The progress curves for inhibition of ALS by TP2 showed that the amount of inhibition increases with time. The inhibition of ALS by TP2 was mixed-type inhibition with respect to pyruvate. Dual inhibition analyses of TP2 versus an imidazolinone, Cadre, and Leu showed parallel and intercepting kinetic pattern, respectively. The results suggest that TP2 binds to ALS competively with Cadre but not with Leu. Chemical modification of cysteinly residues in ALS decreased the sensitivity of ALS to Leu, while the modification did not affect the sensitivity of ALS to TP2 and Cadre.

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High Throughput Screening for Searching a New Inhibitors of Acetolactate Synthase (Acetolactate synthase에 대한 고효율 활성 측정방법 및 신규 저해제 탐색)

  • Park, S.H.;Lee, K.H.;Choi, J.S.;Pyon, J.Y.;Cho, K.Y.;Hwang, I.T.
    • The Korean Journal of Pesticide Science
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    • v.5 no.3
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    • pp.41-46
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    • 2001
  • This study was conducted to develop a high throughput system for screening acetolactate synthase(ALS) inhibitors, and to detect basic mother molecules for developing new novel herbicide candidates. The high throughput screening (HTS) method using 96-well plate and microplate reader was developed. This method is 8 times more effective than basic technique in one cycle per person. Futhermore, considering for less than 1/10 volume of materials required for ALS test and enzyme kinetics with 16 times faster speed compared to those of former procedure, this HTS method has more than 100 times higher efficacy than basic system in a consecutive procedure. We discovered 11 new ALS inhibitors such as 2-oxoglutaric acid, aminooxyacetic acid, azelaic acid, citric acid, cyanuric fluoride, itaconic acid, malonic acid, niclosamide, oxalic acid, glyoxylic acid, and suramin from 107 commercial plant-specific inhibitors using this technique. We hope these results might be useful to discover lead compounds for developing new novel herbicide candidate.

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Three Cases of Amyotrophic Lateral Sclerosis Treated With Oriental Medical Therapy (근위축성 측삭 경화증의 한방적 치료에 대한 증례 3례)

  • Byun, Mi-Kwon;Kim, Jin-Young;Sim, Sung-Heum;Kim, Ki-Tak;Kim, Jong-Deuk;Park, Dong-Il;Kam, Cheol-Woo
    • The Journal of Internal Korean Medicine
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    • v.28 no.4
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    • pp.937-947
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    • 2007
  • Amyotrophic lateral sclerosis (ALS) is a progressive disorder that causes degeneration of motor neurons of the brain and spinal cord. ALS is a progressive, fatal neuromuscular disease characterized by loss of motor neurons leading to muscle weakness. Sensation and mental function stay intact during the course of the disease. ALS is characterized by both upper and lower motor neuron damage. Diagnosis includes magnetic response imaging (MRI) electromyogram (EMG), muscle biopsy, and blood test. There is no cure for ALS. We recently observed three cases of ALS. The patients were diagnosis with ALS by EMG and symptoms. This report was conducted to evaluate how oriental medical treatment can affect ALS. We report the change of their symptoms through oriental medical treatment compared with taking riluzole.

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Sasang Constitutional Characteristic of Amyotrophic Lateral Sclerosis (근위축성측삭경화증 환자의 사상체질 특성)

  • Park, Soo-Jung;Jeong, Ho-Hyun;Jang, Eun-Su;Kim, Sang-Hyuk;Kim, Sung-Chul;Joo, Jong-Cheon
    • Journal of Sasang Constitutional Medicine
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    • v.26 no.2
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    • pp.156-164
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    • 2014
  • Objectives The purpose of this study was to analyze the Sasang constitution and psychological traits of amyotrophic lateral sclerosis (ALS) patients and to utilize the results in treatment and management. Methods The differences of Sasang Constitution distribution, psychological characteristics, comorbid disorders between ALS group of 26 patients and general group of 1132 persons were investigated and analyzed. Results There was no significant different distribution of Sasang Constitution between ALS group and general group but there was Yang-like personality tendency in ALS group than general group. In overall constitution, ALS group had the high prevalence rate of musculoskeletal disorders and diabetes than general group. In Soyangin constitution, ALS group had a high prevalence rate of musculoskeletal disorders than genral group. In Taeeumin constitution, ALS group had a high prevalence rate of diabetes and hypertension than general group. Conclusion ALS patients have the Yang-like personality. It is due to the adaptation of personality on the environmental change or coping strategy on diseases rather than the characteristics of congenital Sasang Constitution.

Functional Amino Acid Residues of Recombinant Tobacco Acetolactate Synthase

  • Chong, Chom-Kyu;Chang, Soo-Ik;Choi, Jung-Do
    • BMB Reports
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    • v.31 no.3
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    • pp.258-263
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    • 1998
  • Acetolactate synthase (ALS) is the common enzyme in the biosynthetic pathways leading to leucine, valine, and isoleucine. Tobacco ALS was expressed in E. coli and purified to homogeneity. The recombinant tobacco ALS was inactivated by thiol-specific reagents, N-ethylmaleimide (NEM) and 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB). Inactivation of the ALS by NEM followed pseudo-first order kinetics and was first order with respect to the modifier. The substrate pyruvate protected the enzyme against the inactivation by NEM and DTNB. Extrapolation to complete inactivation of the enzyme by DTNB showed modification of approximately 2 out of 4 total cysteinyl residues (or 2 cysteinyl and 1 cysteinyl residues), with approximately 1 residue protected by pyruvate. The tobacco ALS was also inactivated by the tryptophanspecific reagent, N-bromosuccinimide (NBS), and was similarly protected by pyruvate. The kinetics of the inactivation was first-order with respect to NBS. The present data suggest that cysteinyl and tryptophanyl residues play a key role in the catalytic function of the enzyme.

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Update of Therapeutic Clinical Trials for Amyotrophic Lateral Sclerosis (근위축측삭경화증에 대한 치료약물 임상시험 현황)

  • Kim, Nam-Hee;Lee, Min Oh
    • Annals of Clinical Neurophysiology
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    • v.17 no.1
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    • pp.1-16
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    • 2015
  • Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is characterized by progressive death of motor neurons in the cortex, brainstem, and spinal cord. Until now, many treatment strategies have been tested in ALS, but so far only Riluzole has shown efficacy of slightly slowing disease progression. The pathophysiological mechanisms underlying ALS are multifactorial, with a complex interaction between genetic factors and molecular pathways. Other motor neuron disease such as spinal muscular atrophy (SMA) and spinobulbar muscular atrophy (SBMA) are also progressive neurodegenerative disease with loss of motor neuron as ALS. This common thread of motor neuron loss has provided a target for the development of therapies for these motor neuron diseases. A better understanding of these pathogenic mechanisms and the potential pathological relationship between the various cellular processes have suggested novel therapeutic approaches, including stem cell and genetics-based strategies, providing hope for feasible treatment of ALS.

The Endocrine Regulation of Chicken Growth

  • Kim, Jin-Wook
    • Asian-Australasian Journal of Animal Sciences
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    • v.23 no.12
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    • pp.1668-1676
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    • 2010
  • The somatotropic axis plays a key role in proliferation and differentiation of avian organs during both pre- and posthatching periods. This review discusses the complexity of regulation of the endocrine system for chicken development and growth by growth hormone (GH), insulin-like growth factor (IGF), and IGF binding protein (IGFBP). In addition, the thyrotropic axis, including thyrotropin-releasing hormone (TRH) and thyroid hormones ($T_4$ and $T_3$), is also involved in the GH-secreting pattern. In mammals, IGFI and -II are always sequestered in a 150 kDa non-covalent ternary complex. This complex consists of one molecule each of IGF-I or IGF-II, IGFBP-3 or IGFBP-5 and an acid labile subunit (ALS). Chick ALS is identified in different strains for the first time, and further investigation of the expression of ALS on developmental stage and ALS effect on IGF bioavailability may be addressed in the future.

Clinical Studies of Amyotrophic Lateral Sclerosis(ALS) through Korean Medicine (한방치료를 통한 근위축성 측삭경화증(ALS)의 임상적 연구)

  • Kwon, Ki-rok
    • Journal of Acupuncture Research
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    • v.20 no.3
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    • pp.209-216
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    • 2003
  • 목적 : 대표적인 motor neuron disease(MND)이면서 가장 치명적인 신경퇴행성 질환인 ALS의 발생 양상과 한방치료효과에 대하여 연구하였다. 방법: 상지대학교 부속 한방병원에 래원한 ALS 환자들의 성별, 연령, 발병일, 발병양상, 래원 당시의 병태양상 등을 분석하였고, 이 중 3개월 이상 입원치료를 통하여 치료과정 평가가 가능하였던 18명의 환자들의 치료 전과 치료 후의 변화양상을 평가하였다. 결과 : 외국의 보고에 비하여 여성 환자가 많았고 발병 연령도 유의하게 낮았으며 상지에서 최초의 증상이 발현되는 비율이 상대적으로 높았다. Bulbar From의 비율도 높았고, 대부분의 환자가 여성인 것도 특이하였다. 환자들이 생각하는 질병의 발생원인 중 약 80%가 stress나 정신적 충격 등을 지적하여 정신적 불안상태가 유관함을 추정할 수 있었다. 한방치료가 ALS를 호전시키지는 못하였으나 진행을 억제하였고, 국소적인 주소증을 완화시키며 심리적 안정 상태를 유지하는데 도움이 된다고 평가되었다.

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Likely pathogenic FIG4 related amyotrophic lateral sclerosis patient who correlated with clinical, imaging and neuropsychological studies

  • Ko, Pan-Woo;Min, Yu-Sun;Park, Jin-Sung
    • Annals of Clinical Neurophysiology
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    • v.22 no.1
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    • pp.33-36
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    • 2020
  • Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with numerous causes that include genetic factors. Efforts to reveal the genetics of ALS have identified several candidate genes that are associated with familial and sporadic ALS. Here we report a Korean ALS patient who showed prominent upper motor-neuron-related symptoms with marked brain atrophy and neuropsychological deficits. The findings were highly suggestive of ALS in a patient with a likely pathogenic FIG4 variant.

The Adjustment Process of Patients with Amyotrophic Lateral Sclerosis (근위축성측삭경화증 환자의 적응과정)

  • Lee, Yoon-Kyoung;Lim, Nan-Young;Kim, Seung-Hyun
    • Journal of muscle and joint health
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    • v.15 no.2
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    • pp.140-154
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    • 2008
  • Purpose: The purpose of this study was to describe the adjustment process of patients with Amyotrophic Lateral Sclerosis(ALS). Method: The data were collected from May 2007 to February 2008 through individual in-depth interviews with 4 ALS patients. The data collection and analysis were performed according to grounded theory methodology, as suggested by Strauss and Corbin. Results: 'Accepting the sick role' was the central phenomenon, which was derived from 'perceiving an intial symptom'. Therefore, the adjustment pattern was represented by using the different strategies, which were 'raising hope' and 'hoping to dye comfortably'. For taking a view of the future, ALS patients adopted the strategies of 'living positively', 'being treated hardly', 'joining in the experience', 'depending on the absolute being', 'recognizing the dying process'. Conclusion: This study provides guidance for the development of nursing interventions for patients with ALS.

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