• 제목/요약/키워드: ALS

검색결과 527건 처리시간 0.023초

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

  • 김성호;남궁성건;신정휴;장수익;최정도
    • 대한화학회지
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    • 제43권4호
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    • pp.461-468
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    • 1999
  • Acetolactate synthase (ALS)는 가지를 가진 필수아미노산 Val, Leu, Ile의 생합성 과정에서 공통적으로 작용하는 효소이다. ALS는 서로 구조적 유사성이 없는triazolopyrimidine, imidazolinone,sulfonylurea, 그리고 pyrimidyl-oxy-benzoate 제초제들의 공통적인 작용 표적이다. 보리로부터 부분 정제한 ALS를 이용하여 새로이 합성한 triazolopyrimidine sulfonamide 유도체들의 저해 활성을 측정하였다. 활성을 가진 유도체들의 $IC_{50}$ 값은 0.5nM∼8${\mu}M$ 범위였으며, 그 중에서 탁월한 저해 활성을 갖는 것은 TP1과TP2 유도체로 $IC_{50}$ 값은 각각 0.5 nM과 1.6 nM이였다. 이 저해제들은 기존의 상품화된 제초제인 Metosulam ($IC_{50}$;3.6 nM), Flumetsulam ($IC_{50}$;126 nM), 그리고 Cadre ($IC_{50};4 {\mu}M$)에 비해 보리 ALS에 대한 저해 활성이 보다 우수하였다. 보리 ALS에 대한 TP2의 저해 활성은 반응시간이 증가함에 따라 증가하였고, 혼합형 저해 유형을 보였다. TP2와 imidazolinone 계열의 제초제인 Cadre, 그리고 되먹임(feedback) 저해제인 Leu에 대한 이중저해 (dual inhibition) 실험 결과 TP2와 Cadre의 경우는 평행한 반응속도론적 형태가 그러나 TP2와 Leu의 경우는 한 점에서 만나는 반응속도론적 헝태가 얻어졌다. 이는 TP2와 Cadre의 결합 부위가 최소한 부분적으로 중복되고 있음을 시사한다. Cys 잔기에 대한 화학적 변형은 TP2와 Cadre의 결합에는 영향을 미치지 않으나, Leu의 결합에는 영향을 미쳤다.

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

  • 박상희;이관휘;최정섭;변종영;조광연;황인택
    • 농약과학회지
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    • 제5권3호
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    • pp.41-46
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    • 2001
  • 분지아미노산 생합성 과정에 관여하는 첫 번째 효소인 acetolactate synthase (ALS)를 대상으로 수행할 수 있도록 고효율 검색방법(High Throughput Screening, HTS)을 개발하였고, 이를 이용하여 식물특이적 효소 저해제로 알려진 107개의 기존 화합물 중에서 새로운 ALS 저해 화합물을 선발하였다. 기존의 방법과 비교할 경우 한사람이 1회 수행한다고 하면 8 배 효율이지만 연속적으로 수행한다고 할 경우 1/10 이하의 양, 동일한 재료의 적용, 측정 결과의 계산, enzyme kinetics 등을 감안하면 최소 100 배 이상의 효과를 얻을 수 있다. 새로운 ALS 저해제로 탐색된 화학물질은, ammooxyacetic acid, azelaic acid, citric acid, cyanuric fluoride, glyoxylic acid, itaconic acid, malonic acid, niclosamid, oxalic acid, 2-oxoglutaric acid, suramin 등이었다. 앞으로 이들을 기본 구조로 하여 신규 ALS 저해 제초제의 개발을 위한 유도체의 합성에 이용되었으면 한다.

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

  • 변미권;김진영;심성흠;김기탁;김종득;박동일;감철우
    • 대한한방내과학회지
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    • 제28권4호
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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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근위축성측삭경화증 환자의 사상체질 특성 (Sasang Constitutional Characteristic of Amyotrophic Lateral Sclerosis)

  • 박수정;정호현;장은수;김상혁;김성철;주종천
    • 사상체질의학회지
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    • 제26권2호
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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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    • 제31권3호
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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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근위축측삭경화증에 대한 치료약물 임상시험 현황 (Update of Therapeutic Clinical Trials for Amyotrophic Lateral Sclerosis)

  • 김남희;이민오
    • Annals of Clinical Neurophysiology
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    • 제17권1호
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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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    • 제23권12호
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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.

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

  • 권기록
    • Journal of Acupuncture Research
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    • 제20권3호
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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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    • 제22권1호
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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.

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

  • 이윤경;임난영;김승현
    • 근관절건강학회지
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    • 제15권2호
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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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