• Title/Summary/Keyword: NF1

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The production and characterization of anti-Naegleria fowleri monoclonal antibodies (Naegleyiu fowleri에 대한 단세포군 항체의 생산과 그 특성에 관한 연구)

  • 류재숙;임경일
    • Parasites, Hosts and Diseases
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    • v.30 no.1
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    • pp.33-42
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    • 1992
  • Naegleria fowleri, a free-living amoeba commonly found in moist soil and fresh water, enters the body via the nasal mucosa and migrates along the olfactory nerve to t he brain, where it causes acute amoebic meningoencephalitis. In the present study 7 clones secreting monoclonal antibodies (McAbs) against N. fowleri were produced and the effector function of them was investigated. Their isotopes were IgGl (Nf 1, Nf 154), 19G3 (Nf 137) and 19A (Nf 1, Nf 2, Nf 256, Nf 279). Five McAbs (McAb Nf 2, Nf 279, Nf 27, Nf 154, Nf 137) were specific for N. fowleri by ELISA and recognized the antigenic determinants located on the trophoBoite surface by IFAT and immunoperoxidase stain. These aye McAbs had capacity to agglutinate N. fowleri trophozoites and inhibited the growth of the amoeba in culture medium. McAb Nf 2 inhibited proliferation of trophozoites in vitro significantly. Also the cytotoxicity of JV. fowleri against CHO cell was reduced in the presence of McAb Nf 2 and McAb Nf 154. From these results McAb Nf 2 was confirmed to weaken the virulence of the amoeba among 7 screened McAbs.

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Mutation spectrum of NF1 gene in Korean unrelated patients with neurofibromatosis 1: Six novel pathogenic variants

  • Sung Hee Han;Eun Joo Kang;Mina Yang;Suekyeung Kim;Sang Gon Lee;Eun Hee Lee
    • Journal of Genetic Medicine
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    • v.21 no.1
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    • pp.22-30
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    • 2024
  • Purpose: Neurofibromatosis 1 (NF1) is one of the most common autosomal dominant diseases caused by heterozygous mutation in the NF1 gene. Mutation detection is complex owing to the large size of the NF1 gene, the presence of a high number of partial pseudogenes, and the great variety of mutations. We aimed to study the mutation spectrum of NF1 gene in Korean patients with NF1. Materials and Methods: We have analyzed total 69 unrelated patients who were clinically diagnosed with NF1. PCR and sequencing of the NF1 gene was performed in all unrelated index patients. Additionally, multiplex ligation-dependent probe amplification (MLPA) test of the NF1 and SPRED1 gene analysis (sequencing and MLPA test) were performed in patients with negative results from NF1 gene sequencing analysis. Results: Fifty-five different variants were identified in 60 individuals, including six novel variants. The mutations included 36 single base substitutions (15 missense and 21 nonsense), eight splicing mutations, 13 small insertion or deletions, and three gross deletions. Most pathogenic variants were unique. The mutations were evenly distributed across exon one through 58 of NF1, and no mutational hot spots were found. When fulfilling the National Institutes of Health criterion for the clinical diagnosis of NF1, the detection rate was 84.1%. Cafe-au-lait macules were observed in all patients with NF1 mutations. There is no clear relationship between specific mutations and clinical features. Conclusion: This study revealed a wide spectrum and genetic basis of patients with NF1 in Korea. Our results aim to contribute genetic management and counseling.

Kinematics of the Northern Filament in Orion Molecular Clouds Complex Using 12CO Molecular Observation Data (12CO 분자선 관측 자료를 이용한 오리온 분자운 복합체내 북쪽 필라멘트의 운동학 연구)

  • Jo, Hoon;Sohn, Jungjoo;Kim, ShinYoung;Lee, JeeWon;Kim, Sungsoo S.;Morris, Mark
    • Journal of the Korean earth science society
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    • v.39 no.6
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    • pp.519-532
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    • 2018
  • We investigated the effect of galactic plane toward molecular motion and kinematics in the northern filament (NF) of Orion Molecular Clouds Complex (OMC) using $^{12}CO$ (J=1-0) line. Observed data were from three areas including NF1, NF2, and NF3 in far-out order from galactic plane, for a total 270 hours by Seoul National University Radio Astronomy Observatory (SRAO) 6m telescope, with 2arcmin spatial resolution. galactic plane and OMC NF were connected to each other along the magnetic field at a density of 3% for $^{12}CO$ (J=2-1) and 9% for the case of dust. $^{12}CO$ (J=1-0), $^{12}CO$ (J=2-1), and interstellar dusts were distributed uniformly in NF3, but only in certain regions with relatively high density in NF1 and NF2. NF showed a single structure, partial shrinking motion in NF1, and rotational motion at the bottom of NF2, and spiral rotation associated with magnetic field only in NF3. The position-velocity analysis showed that the materials including $^{12}CO$ (J=1-0) could flow toward galactic plane along NF2 and NF3. However, there was no clear cause for the material to flow toward galactic plane in this result. Further detailed observation for rotational motion at the top of NF1 and NF2 might help to confirm it.

Kinematic Study of Northern Filament in Orion Molecular Clouds Complex By 12CO Radio Observation

  • Jo, Hoon;Sohn, Jungjoo;Kim, ShinYoung;Lee, Jee Won;Kim, Sungsoo;Morris, Mark
    • The Bulletin of The Korean Astronomical Society
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    • v.43 no.2
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    • pp.52.1-52.1
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    • 2018
  • Orion Molecular Clouds Complex(OMC) 분자운에는 별 생성은 없으면서 은하면 방향으로 누워있는 큰 규모($10^{\circ}{\times}0.5^{\circ}$)의 필라멘트 구조가 있다. 본 연구는 북쪽 필라멘트(이하 NF)를 대상으로 12CO (J = 1-0) 선 관측 데이터를 이용하여 필라멘트의 운동학적 연구를 수행함으로서 은하면과의 상관관계를 알아보고자 하였다. 관측은 공간분해능은 2 arcmin인 SRAO(Seoul Radio Astronomy Observatory)의 6m 밀리미터 망원경이 사용되었고 큰 규모로 인해 은하면으로부터 먼 순서로 NF1, NF2, NF3 세 곳으로 관측 지역이 정해졌다. 연구결과 필라멘트는 매우 낮은 수준의 12CO (J = 2-1)과 티끌 분포에서 자기장을 따라 은하면 방향으로 연계되어 보였다. 밀도 분포에서는 SRAO 12CO (J = 1-0) 적분강도와 Planck 위성의 12CO (J = 2-1)과 티끌 자료를 이용했을 때, 12CO와 성간 티끌은 주로 은하면에 수직인 방향에서 밀도가 높았다. 속도 분포와 위치 속도 분석을 통해 NF는 단일 구조의 분자운 형태이고 NF2 하단에서는 회전 운동의 가능성이 확인되었다. NF3는 자기장에 의해 생성된 나선형 회전을 하고 있으며, NF2와 NF3를 따라 은하면을 향하여 12CO (J = 1-0)를 비롯한 물질이 흐르고 있음도 확인되었다. 하지만 은하면을 향하여 물질이 흐르는 원인을 제공하는 천체가 무엇인지와 NF1과 NF2 상단의 회전 운동은 확인 할 수 없었으며 이들 지역에 대한 상세한 관측이 요구된다.

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PI3-Kinase and PDK-1 Regulate HDAC1-mediated Transcriptional Repression of Transcription Factor NF-κB

  • Choi, Yong Seok;Jeong, Sunjoo
    • Molecules and Cells
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    • v.20 no.2
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    • pp.241-246
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    • 2005
  • PDK-1 activates PI3-kinase/Akt signaling and regulates fundamental cellular functions, such as growth and survival. NF-${\kappa}B$ is involved in the induction of a variety of cellular genes affecting immunity, inflammation and the resistance to apoptosis induced by some anti-cancer drugs. Even though the crucial involvement of the PI3-kinase/Akt pathway in the anti-apoptotic activation of NF-${\kappa}B$ is well known, the exact role of PDK-1 as well as PI3-kinase/Akt in NF-vactivation is not understood. Here we demonstrate that PDK-1 plays a pivotal role in transcriptional activation of NF-${\kappa}B$ by dissociating the transcriptional co-repressor HDAC1 from the p65 subunit of NF-${\kappa}B$. The association of CBP with p65 was not directly modulated by PDK-1 or by PI3-kinase. Etoposide activated NF-${\kappa}B$ through PI3-kinase/Akt, and the transcription activation domain (TAD) of p65 was further activated by wild-type PDK-1. Overexpression of a dominant negative PDK-1 mutant decreased etoposide-induced NF-${\kappa}B$ transcription and further down-regulated the ectopic HDAC1-mediated decrease in NF-${\kappa}B$ transcriptional activity. Thus activation of PDK-1 relieves the HDAC1-mediated repression of NF-${\kappa}B$ that may be related to basal as well as activated transcription by NF-${\kappa}B$. This effect may also explain the role of the PI3-kinase/PDK-1 pathway in the anti-apoptotic function of NF-${\kappa}B$ associated with the chemoresistance of cancer cells.

A case of neurofibromatosis(NF-I) (신경섬유종증(Neurofibromatosis) 환아(患兒) 1예(例)에 대한 증례보고(症例報告))

  • Min Sang-Yeon;Jang Gyu-Tae;Kim Jang-Hyun
    • The Journal of Pediatrics of Korean Medicine
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    • v.15 no.2
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    • pp.69-73
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    • 2001
  • The neurofibromatosis (NF) are a set of genetic disorders which cause tumors to grow along various types of nerves and, in addition, can affect the development of non-nervous tissues such as bones and skin. NF causes tumors to grow anywhere on or in the body. It also leads to developmental abnormalities. For example, individuals with NF have a higher incidence of learning disabilities. Neurofibromatosis(NF) has been classified into two distinct types: NF-I and NF-II. neurofibromatosis 1(NF-I), also known as von Recklinghausen NF or Peripheral NF, occurring in 1:4,000 births, is characterized by multiple cafe-au-lait spots and neurofibromas on or under the skin. Enlargement and deformation of bones and curvature of the spine (scoliosis) may also occur. Occasionally, tumors may develop in the brain, on cranial nerves, or on the spinal cord. About 50% of people with NF also have learning disabilities. Neurofibromatosis 2(NF-II), also known as Bilateral Acoustic NF(BAN), is much rarer occurring in 1:50,000 births. NF-II is characterized by multiple tumors on the cranial and spinal nerves, and by other lesions of the brain and spinal cord. Tumors affecting both of the auditory nerves are the hallmark. Hearing loss beginning in the teens or early twenties is generally the first symptom. We reported a 10-year-old female patient with NF-I, she has pain and edema in left leg, no symptoms of NF.

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Effects of the Heptasequence SPTSPTY of Rat Nuclear Factor 1-A on Interactions between the C-Terminal Regions of Mammalian Nuclear Factor 1 Proteins

  • Hwang, Jung-Su;Kim, Ji-Young
    • BMB Reports
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    • v.33 no.6
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    • pp.519-524
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    • 2000
  • NF1 proteins are a family of DNA binding proteins which consist of two separate domains, N-terminal DNA binding domain and C-terminal transcription activation domain. The N-terminal 220 amino acids are highly conserved and are also known to mediate dimerization of NF1 proteins. The C-terminal regions of different type of NF1 proteins are heterogeneous and responsible for transcriptional activation. In this study, we tested the interaction between different domains of rat NF1-A protein by yeast two hybrid analysis and observed the interaction between C-terminal regions of NF1-A which do not contain the N-terminal dimerization domain. Our results showed that the C-terminal region of rat NF1-A between residues 231 and 509 strongly interacted not only with itself, but also with human NF1/CTF1 which is a different type of NF1. When the C-terminal region was divided into two fragments, one from residue 231 to 447 and the other from 448 to 509, the two fragments were able to interact with the C-terminal region of NF1-A significantly. This indicates that both fragments contain independent interaction domains. Analysis of the interactions with alanine substituted fragments showed that substitutions of the heptasequence, SPTSPTY of NF1-A, affected interaction between NF1 proteins. Our results strongly suggest that C-terminal regions may also be important for the formation of homo- and heterodimers in addition to the N-terminal dimerization domain. Also, the heptasequence motif may play some roles in dimer formation.

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Inhibition of NF-IL6 Activity by Manassantin B, a Dilignan Isolated from Saururus chinensis, in Phorbol Myristate Acetate-stimulated U937 Promonocytic Cells

  • Son, Kyung-No;Song, In-Sung;Shin, Yong-Hyun;Pai, Tong-Kun;Chung, Dae-Kyun;Baek, Nam-In;Lee, Jung Joon;Kim, Jiyoung
    • Molecules and Cells
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    • v.20 no.1
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    • pp.105-111
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    • 2005
  • Mannasantin B, a dilignan structurally related to manssantin A, is an inhibitor of NF-${\kappa}B$ transactivation. In the present study, we found that it inhibited PMA-induced expression of IL-$1{\beta}$, IL-$1{\beta}$ mRNA, and IL-$1{\beta}$ promoter activity in U937 cells with $IC_{50}$ values of about 50 nM. It also inhibited NF-IL6- and NF-${\kappa}B$-induced activation of IL-$1{\beta}$, with $IC_{50}$ values of 78 nM and $1.6{\mu}M$, respectively, revealing a potent inhibitory effect on NF-IL6. Electrophoretic mobility shift assays showed that manassantin B had an inhibitory effect on DNA binding by NF-IL6, but not by NF-${\kappa}B$. Further analysis revealed that transactivation by NF-IL6 was also inhibited. Our results indicate that manassantin B suppresses expression of IL-$1{\beta}$ in promonocytic cells by inhibiting not only NF-${\kappa}B$ but also NF-IL6 activity. Furthermore, our observations suggest that manassantin B may be clinically useful as a potent inhibitor of NF-IL6 activity.

Nypa fruticans wurmb regulates the secretion level of inflammatory cytokines in vitro models.

  • Jin, Yu-Mi;Kim, Seong-Seon;Lee, Jong-Hyun;Jeon, Yong-Deok;Jin, Jong-Sik
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2018.10a
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    • pp.128-128
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    • 2018
  • Nypa fruticans wurmb (NF) has been used as traditional medicinal food in Asian countries. Especially, NF has been used for conventional medicine to treat inflammatory periodontal diseases. Previous studies have been shown that NF has large amount of useful constituents such as phenolic acids, polyphenols and flavonoids. Also, NF is known as having medicinal effects such as anti-oxidant, anti-inflammatory and cholesterol-lowering effects. NF has recently been attracted to use complementary medicinal food on inflammatory diseases in Korea. However, there are no obvious effects in inflammatory and metabolic diseases also mechanisms has been studied yet. The purpose of this study was to investigate the anti-inflammatory effects of NF and steamed-NF (SNF), which recently has been used as health food, using Human keratinocyte cell line (HaCaT) and Human mast cell line (HMC-1). The cytotoxicities of NF and SNF were measured by using MTT assays in HaCaT cells and HMC-1 cell. To evaluate anti-inflammatory effects of NF and SNF, HaCaT cells were stimulated with tumor necrosis factor $(TNF)-{\alpha}$ and Interferon $(IFN)-{\gamma}$. Also, HMC-1 cells were stimulated with phorbol-12-myristate-13-acetate (PMA) and A23187 calcium ionophore (A23187) to induce allergic inflammation. Inflammatory cytokine were measured by enzyme-linked immunosorbent assay (ELISA). In this result, the extract of NF and SNF (0.01 - 1mg/ml) did not show cytotoxicity in HaCaT cells and HMC-1 cells. In addition, the NF and SNF suppressed the production of interleukin (IL)-6 and IL-8 in HaCaT cells at highest concentration. Furthermore, the treatment of SNF significantly inhibited the secretion level of IL-8 in PMA plus A23187-stimulated HMC-1 cells compared with NF treatment group. These results suggest that the extract of NF and SNF may serve as a potential therapy for skin inflammatory diseases.

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NF-Y binds to both G1- and G2-specific cyclin promoters; a possible role in linking CDK2/Cyclin A to CDK1/Cyclin B

  • Chae, Hee-Don;Kim, Jung-Bin;Shin, Deug-Y.
    • BMB Reports
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    • v.44 no.8
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    • pp.553-557
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    • 2011
  • We previously reported that CDK2/Cyclin A can phosphorylate and activate the transcription factor NF-Y. In this study, we investigated a potential regulatory role for NF-Y in the transcription of Cyclin A and other cell cycle regulatory genes. Gel-shift assays demonstrate that NF-Y binds to CCAAT sequences in the Cyclin A promoter, as well as to those in the promoters of cell cycle G2 regulators such as CDC2, Cyclin B and CDC25C. Furthermore, expression of Cyclin A increases NF-Y's affinity for CCAAT sequences in the CDC2 promoter; however, Cyclin A's induction of CDC2 transcription is antagonized by p21, an inhibitor of CDK2/Cyclin A. These results suggest a model wherein NF-Y binds to and activates transcription from the Cyclin A promoter, increasing cellular levels of Cyclin A/CDK2 and potentiating NF-Y's capacity for transcriptional transactivation, and imply a positive feedback loop between NF-Y and Cyclin A/CDK2. Our findings are additionally indicative of a role for Cyclin A in activating Cyclin B/CDK1 through promoting NF-Y dependent transcription of Cyclin B and CDC2; NF-Y mediated crosstalk may therefore help to orchestrate cell-cycle progression.