• 제목/요약/키워드: disease cycle

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Clinical Manifestations of Inborn Errors of the Urea Cycle and Related Metabolic Disorders during Childhood

  • Endo, Fumio;Matsuura, Toshinobu;Yanagita, Kaede;Matsuda, Ichiro
    • 대한유전성대사질환학회지
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    • 제5권1호
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    • pp.76-87
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    • 2005
  • Various disorders cause hyperammonemia during childhood. Amongthem are those caused by inherited defects in urea synthesis and related metabolic pathways. These disorders can be grouped into two types: disorders of the enzymes that comprise the urea cycle, and disorders of the transporters or metabolites of theamino acids related to the urea cycle. Principal clinical features of these disorders are caused by elevated levels of blood ammonium. Additional disease-specific symptoms are related to the particular metabolic defect. These specific clinical manifestations are often due to an excess or lack of specific amino acids. Treatment of urea cycle disorders and related metabolic diseases consists of nutritional restriction of proteins, administration of specific amino acids, and use of alternative pathways for discarding excess nitrogen. Although combinations of these treatments are extensively employed, the prognosis of severe cases remains unsatisfactory. Liver transplantation is one alternative for which a better prognosis is reported.

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Oct4 resetting by Aurkb–PP1 cell cycle axis determines the identity of mouse embryonic stem cells

  • Shin, Jihoon;Youn, Hong-Duk
    • BMB Reports
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    • 제49권10호
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    • pp.527-528
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    • 2016
  • In embryonic stem cells (ESCs), cell cycle regulation is deeply connected to pluripotency. Especially, core transcription factors (CTFs) which are essential to maintaining the pluripotency transcription programs should be reset during M/G1 transition. However, it remains unknown about how CTFs are governed during cell cycle progression. Here, we describe that the regulation of Oct4 by Aurora kinase b (Aurkb)/protein phosphatase 1 (PP1) axis during the cell cycle is important for resetting Oct4 to pluripotency and cell cycle related target genes in determining the identity of ESCs. Aurkb starts to phosphorylate Oct4(S229) at the onset of G2/M phase, inducing the dissociation of Oct4 from chromatin, whereas PP1 binds Oct4 and dephosphorylates Oct4(S229) during M/G1 transition, which resets Oct4-driven transcription for pluripotency and the cell cycle. Furthermore, Aurkb phosphormimetic and PP1 binding-deficient mutations in Oct4 disrupt the pluripotent cell cycle, lead to the loss of pluripotency in ESCs, and decrease the efficiency of somatic cell reprogramming. Based on our findings, we suggest that the cell cycle is directly linked to pluripotency programs in ESCs.

PP2A function toward mitotic kinases and substrates during the cell cycle

  • Jeong, Ae Lee;Yang, Young
    • BMB Reports
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    • 제46권6호
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    • pp.289-294
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    • 2013
  • To maintain cellular homeostasis against the demands of the extracellular environment, a precise regulation of kinases and phosphatases is essential. In cell cycle regulation mechanisms, activation of the cyclin-dependent kinase (CDK1) and cyclin B complex (CDK1:cyclin B) causes a remarkable change in protein phosphorylation. Activation of CDK1:cyclin B is regulated by two auto-amplification loops-CDK1:cyclin B activates Cdc25, its own activating phosphatase, and inhibits Wee1, its own inhibiting kinase. Recent biological evidence has revealed that the inhibition of its counteracting phosphatase activity also occurs, and it is parallel to CDK1:cyclin B activation during mitosis. Phosphatase regulation of mitotic kinases and their substrates is essential to ensure that the progression of the cell cycle is ordered. Outlining how the mutual control of kinases and phosphatases governs the localization and timing of cell division will give us a new understanding about cell cycle regulation.

Cyclin-Dependent Kinase Inhibitor 2A is a Key Regulator of Cell Cycle Arrest and Senescence in Endothelial Colony-Forming Cells in Moyamoya Disease

  • Seung Ah Choi;Youn Joo Moon;Eun Jung Koh;Ji Hoon Phi;Ji Yeoun Lee;Kyung Hyun Kim;Seung-Ki Kim
    • Journal of Korean Neurosurgical Society
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    • 제66권6호
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    • pp.642-651
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    • 2023
  • Objective : Endothelial colony-forming cells (ECFCs) have been reported to play an important role in the pathogenesis of moyamoya disease (MMD). We have previously observed stagnant growth in MMD ECFCs with functional impairment of tubule formation. We aimed to verify the key regulators and related signaling pathways involved in the functional defects of MMD ECFCs. Methods : ECFCs were cultured from peripheral blood mononuclear cells of healthy volunteers (normal) and MMD patients. Low-density lipoproteins uptake, flow cytometry, high content screening, senescence-associated β-galactosidase, immunofluorescence, cell cycle, tubule formation, microarray, real-time quantitative polymerase chain reaction, small interfering RNA transfection, and western blot analyses were performed. Results : The acquisition of cells that can be cultured for a long time with the characteristics of late ECFCs was significantly lower in the MMD patients than the normal. Importantly, the MMD ECFCs showed decreased cellular proliferation with G1 cell cycle arrest and cellular senescence compared to the normal ECFCs. A pathway enrichment analysis demonstrated that the cell cycle pathway was the major enriched pathway, which is consistent with the results of the functional analysis of ECFCs. Among the genes associated with the cell cycle, cyclin-dependent kinase inhibitor 2A (CDKN2A) showed the highest expression in MMD ECFCs. Knockdown of CDKN2A in MMD ECFCs enhanced proliferation by reducing G1 cell cycle arrest and inhibiting senescence through the regulation of CDK4 and phospho retinoblastoma protein. Conclusion : Our study suggests that CDKN2A plays an important role in the growth retardation of MMD ECFCs by inducing cell cycle arrest and senescence.

『상한론(傷寒論)』 변병진단체계(辨病診斷體系)에 근거하여 마황행인감초석고탕(麻黃杏仁甘草石膏湯) 투여 후 호전된 증례 2례 고찰 (Two Case Reports treated by Mahwang-Haeangin-Gamcho-Seokgo-tang based on Shanghanlun Provisions)

  • 하현이;윤효중;이성준
    • 대한상한금궤의학회지
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    • 제8권1호
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    • pp.67-85
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    • 2016
  • Objectives: In this paper, two cases which showed the meaningful results on the patients' chief complaints were analyzed. The patients were treated with the Mahwang-Haengin-Gamcho-seokgo-tang herbal medication based on Shanghanlun disease pattern identification diagnostic system. Methods: The patients were diagnosed based on Shanghanlun, disease pattern identification diagnostic system. In case 1, the change of menstruation cycle was noted and pre-menstrual discomforts were measured with Menstrual Distress Questionnaire(MDQ). In case 2, Quality of life questionnaire for adult Korean asthmatics (QLQAKA) was used to estimate the quality of the patient's life. Results: All the symptoms were improved after the Mahwang-Haengin-Gamcho-seokgotang treatment. In case 1, the menstruation cycle decreased to 30 days average. MDQ score decreased 143 to 103. In case 2, the change of the QLQAKA score as 1.647 average point is considered as a meaningful improvement. Conclusion: With great difference to a 'Symptom-Medicine' diagnostic system, the disease pattern identification diagnostic system seeks the pathologic pattern through the patient's whole life. More studies and multiple cases based on the diagnostic system are needed to prove this possibility later.

한국신문에 게재된 식생활 전반에 관한 기사내용의 영양과학적 분석 -1960년 1월부터 1996년 6월까지- -제 2보: 특수영양, 건강 및 질병에 관한 영양정보의 분석 평가- (The Content Analysis of Food and Nutrition Articles in the Korean Newspapers -From January 1960 to June 1996- -II. Nutrition in Life Cycle, Health and Disease-)

  • 김은경;박태선;박영심;장미라;이기완
    • 한국식생활문화학회지
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    • 제11권4호
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    • pp.527-538
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    • 1996
  • The contents of articles on nutrition in life cycle, health and disease in the Korean daily newspapers were analyzed for the evaluation of the trends in nutrition information in mass media. Among 922 articles pressed from January 1960 to June 1996, articles on nutrition in life cycle were most frequently appeared, which is followed by articles on nutrition in disease, health foods and other related food and nutrition informations. There was a deep contrast in that the proportion of articles on nutrition in life clyle decreased from 58% in the 60's to 33% in the 90's, and those of nutrition in disease, and health foods increased from 23% and 5% in 60's to 34% and 18% in 90's, respectively.

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The Dynamics of Agricultural Commodities and Their Responses to Disruptions of Considerable Magnitude

  • Conrad Stephen H.
    • 한국시스템다이내믹스연구
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    • 제6권1호
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    • pp.17-32
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    • 2005
  • An agricultural commodity production cycle model consisting of corn, beef, and dairy sectors was constructed for the purpose of exploring the propagating effects of large-scale disruptive events. In an initial proof-of-concept exercise, we considered an agricultural disruption scenario in which foot-and-mouth disease (FMD) is introduced into the U.S., causing a large-scale outbreak of the disease in both beef and dairy cattle. The magnitude of disruption to the beef and dairy sectors are presented under the existing W response policy and then improvements under two alternative policies are shown.

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Gaucher병에서 resveratrol의 세포주기 조절자 p21을 통한 세포보호 효과 연구 (Resveratrol Upregulates p21, Cell Cycle Regulator, in Gaucher Disease Cells)

  • 김동현;허태회;김준범;김성조
    • 생명과학회지
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    • 제20권8호
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    • pp.1281-1286
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    • 2010
  • 고셔병은 세포내의 글루코세레브로시데이즈의 결핍으로 인하여 리소좀 내의 글루코세레브로사이드가 분해되지 못하고 축적되는 질환으로 알려져 있으며, 유형의 종류에 따라 신경퇴행성 질환으로 나타나는 것으로 보고되어 있으나 아직까지 정확한 기전이 밝혀져 있지 않다. 본 논문에서는 항산화 효과 및 신경보호 효과가 있는 것으로 알려진 레스베라트롤을 고셔병 환자의 fibroblast 세포에 투여하여 세포 생존율 변화 여부 및 세포주기 조절에 관하여 분자 생물학적 기전을 알아보고자 하였다. 고셔병 세포의 p21의 mRNA 발현 수준과 단백질 발현 양상을 확인한 결과 mRNA 상의 정량적 차이는 관찰되지 않았으나 단백질 발현수준은 레스베라트롤의 농도가 높아짐에 따라 증가 되는 것을 확인하였다. 또한 세포사멸의 표지 인자 단백질로 알려진 PARP의 변화양상을 확인한 결과 레스베라트롤의 농도가 높아짐에 따라 감소하는 것을 확인 할 수 있었다. 이를 통해 폴리페놀계 천연물인 레스베라트롤이 고셔병에서 세포 손상을 치유하며, 궁극적으로 세포사멸을 억제하는 효과를 가져올 것으로 생각할 수 있으며, 본 질환에서 병증을 완화 시킬 수 있을 것으로 사료된다.