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만성 자발성 두드러기의 병인기전에서 TCTP의 역할
No full textBACKGROUND AND OBJECTIVES: Translationally controlled tumor protein (TCTP) is widely expressed as housekeeping protein that has various intracellular and extracellular functions including its ability to activate mast cells. Extracellular TCTP has been found in nasal, bronchoalveolar lavage and skin blister fluids and exhibits the capacity to induce histamine release from basophils, suggesting that TCTP plays a role in allergic diseases including asthma, atopic dermatitis and urticaria. Dimerization of TCTP is important for its cytokine-like activity, therefore, we hypothesized that the dimerized TCTP may have an important role by inducing histamine and other mediator release, which may drive development of chronic spontaneous urticaria (CSU) symptoms.
MATERIALS AND METHODS: One hundred sixteen CSU patients and 70 healthy normal controls (NCs) were enrolled at Ajou University Medical Center, Suwon, South Korea. Serum TCTP levels of study subjects were measured by ELISA and compared according to other CSU-related clinical parameters. Basophil activation test (BAT) was performed by measuring CD203c expression on peripheral basophils from CSU patients. In vitro, β-hexosaminidase release from human mast cell line, monomeric and dimeric TCTP stimulated LAD-2 mast cells was evaluated. Western blot (WB) analysis was performed to detect dimeric TCTP from sera of CSU patients and NCs in non-reducing condition. Rapid dot-blot immunoassay was used for measuring the level of IgG to high affinity Fc epsilon receptor I alpha subunit (FcεRIα) level in serum of CSU patients and NCs.
RESULTS: There was no difference between serum levels of TCTP in CSU patients and NCs. The intensity of dimeric TCTP on WB was visually stronger in CSU patients than in NCs. Severe CSU patients had higher serum TCTP levels (P=0.049) and those having IgG positivity to FcɛRIα (P=0.038). Serum TCTP was significantly positive correlated with eosinophil cationic protein levels (Spearman’s rho 0.341, P=0.001). Both basophil and mast cell degranulation were significantly increased after the stimulation with dimeric TCTP, but, not with monomic TCTP.
CONCLUSION: The capability of TCTP to activate basophils and mast cells is dependent on its dimerization process, suggesting that the inhibition of TCTP dimerization might have therapeutic benefit for CSU. Association of TCTP levels with the presence of IgG to FcεRIα autoantibody indicating that autoimmune mechanisms of CSU which may related to its dimerization.배경 및 목적: TCTP는 히스타민 분비인자로도 알려진 물질로서 비만세포의 활성화를 포함한 다양한 기능을 가진 단백질이다. 세포외 TCTP는 비강 및 폐포 세척액, 피부 수포액에서 발견되었고 이는 호염기구로부터 히스타민을 분비하게 함으로써 TCTP가 알레르기 질환의 병인기전에 관여함을 알 수 있었다. TCTP의 이량체화(dimerization)는 사이토카인과 같은 활성을 나타낸다는 보고가 있어, 이량체화된 TCTP가 만성 자발성 두드러기 증상을 일으키는 히스타민과 그 외의 매개물질의 분비를 유도하는데 중요한 역할을 할 것이라 가정하였다.
방법: 116명의 만성 자발성 두드러기 환자 및 70명의 건강한 정상 대조군의 혈청 내 TCTP를 ELISA를 이용하여 측정하여, 만성 자발성 두드러기의 임상지표들과 비교 분석하였다. 만성 자발성 두드러기 환자군의 말초 호염기구에서 발현되는 CD203c를 측정하여 호염기구 활성화를 평가하였다. 단량체 및 이량체 TCTP를 자극하여 비만 세포주로부터 분비되는 β-hexosaminidase를 측정하였다. Non-reducing Western blot 분석을 통해 만성 자발성 두드러기 환자군 및 정상 대조군의 혈청에서 이량체 TCTP를 측정하였다. 또한, Rapid dotblot immunoassay 를 이용하여 만성 자발성 두드러기 환자 및 정상 대조군의 혈청에서 고친화성 FcεRIα에 결합된 면역글로불린 G를 측정하였다.
결과: 만성 자발성 두드러기 환자 및 정상 대조군에서 혈청 TCTP 수치의 유의한 차이는 관찰되지 않았다. 그러나, Western blot에서 이량체 TCTP의 강도는 정상 대조군에 비해 만성 자발성 두드러기 환자군에서 더 강하게 나타났다. 혈청 TCTP 수치는 중증 만성 자발성 두드러기 환자 (51.1 ± 31.6 vs 44.6 ± 45.6 ng/ml, P=0.049)와 FcɛRIα에 대한 면역글로불린 G 양성을 나타내는 환자 (60.4 ± 49.8 vs 42.5 ± 37.6 ng/ml, P=0.038)에서 더 높게 측정되었다. TCTP는 혈청 eosinophil cationic protein 와 유의한 양의 상관관계를 보였다 (Spearman’s rho 0.341, P=0.001). 이량체 TCTP로 자극하였을 때 호염기구의 활성 및 비만 세포주의 탈과립이 모두 증가하였으나, 단량체 TCTP를 자극하였을 때는 이러한 결과가 관찰되지 않았다.
결론: TCTP가 호염기구와 비만세포를 활성화시킬 수 있는 것은 그것의 이량 체화 여부에 달려있음을 확인하였다. 따라서, TCTP의 이량체화를 억제하면, 만성 자발성 두드러기의 새로운 치료방법이 될 수 있음을 제시하였다.I.INTRODUCTION 1
II.MATERIALS AND METHODS 4
A.Clinical characteristics of the study subjects 4
B.Evaluation of clinical parameters of CSU patients 5
C.Measurement of TCTP in sera of study subjects 6
D.Purification of recombinant TCTP protein 7
E.Western blotting for detecting the dimerized TCTP in sera from CSU patients and NCs 8
F.Basophil activation test 8
G.Measurement of ß-hexosaminidase release from LAD-2 cells 9
H.Statistical analysis 10
III.RESULTS 12
A.Clinical characteristics of study subjects 12
B.Serum TCTP levels in CSU patients and NCs 12
C.Correlation of serum TCTP levels with clinical characteristics of chronic spontaneous urticaria 14
D.Effects of TCTP on basophil activation 21
E.β-hexosaminidase release from LAD2 cells upon the stimulation with TCTP 22
IV.DISCUSSION 24
V.CONCLUSION 28
REFERENCES 29Maste
Translationally Controlled Tumor Protein in Chronic Spontaneous Urticaria
No full text학위논문(석사)--아주대학교 일반대학원 :의학과,2019. 2I. INTRODUCTION 1
II. MATERIALS AND METHODS 4
A. Clinical characteristics of the study subjects 4
B. Evaluation of clinical parameters of CSU patients 5
C. Measurement of TCTP in sera of study subjects 6
D. Purification of recombinant TCTP protein 7
E. Western blotting for detecting the dimerized TCTP in sera from CSU patients and NCs 8
F. Basophil activation test 8
G. Measurement of ß-hexosaminidase release from LAD-2 cells 9
H. Statistical analysis 10
III. RESULTS 12
A. Clinical characteristics of study subjects 12
B. Serum TCTP levels in CSU patients and NCs 12
C. Correlation of serum TCTP levels with clinical characteristics of chronic spontaneous urticaria 14
D. Effects of TCTP on basophil activation 21
E. β-hexosaminidase release from LAD2 cells upon the stimulation with TCTP 22
IV. DISCUSSION 24
V. CONCLUSION 28
REFERENCES 29MasterBackground and objectives: Translationally controlled tumor protein (TCTP) is widely expressed as housekeeping protein that has various intracellular and extracellular functions including its ability to activate mast cells. Extracellular TCTP has been found in nasal, bronchoalveolar lavage and skin blister fluids and exhibits the capacity to induce histamine release from basophils, suggesting that TCTP plays a role in allergic diseases including asthma, atopic dermatitis and urticaria. Dimerization of TCTP is important for its cytokine-like activity, therefore, we hypothesized that the dimerized TCTP may have an important role by inducing histamine and other mediator release, which may drive development of chronic spontaneous urticaria (CSU) symptoms.
Materials and Methods: One hundred sixteen CSU patients and 70 healthy normal controls (NCs) were enrolled at Ajou University Medical Center, Suwon, South Korea. Serum TCTP levels of study subjects were measured by ELISA and compared according to other CSU-related clinical parameters. Basophil activation test (BAT) was performed by measuring CD203c expression on peripheral basophils from CSU patients. In vitro, β-hexosaminidase release from human mast cell line, monomeric and dimeric TCTP stimulated LAD-2 mast cells was evaluated. Western blot (WB) analysis was performed to detect dimeric TCTP from sera of CSU patients and NCs in non-reducing condition. Rapid dot-blot immunoassay was used for measuring the level of IgG to high affinity Fc epsilon receptor I alpha subunit (FcεRIα) level in serum of CSU patients and NCs.
Results: There was no difference between serum levels of TCTP in CSU patients and NCs. The intensity of dimeric TCTP on WB was visually stronger in CSU patients than in NCs. Severe CSU patients had higher serum TCTP levels (P=0.049) and those having IgG positivity to FcɛRIα (P=0.038). Serum TCTP was significantly positive correlated with eosinophil cationic protein levels (Spearman’s rho 0.341, P=0.001). Both basophil and mast cell degranulation were significantly increased after the stimulation with dimeric TCTP, but, not with monomic TCTP.
Conclusion: The capability of TCTP to activate basophils and mast cells is dependent on its dimerization process, suggesting that the inhibition of TCTP dimerization might have therapeutic benefit for CSU. Association of TCTP levels with the presence of IgG to FcεRIα autoantibody indicating that autoimmune mechanisms of CSU which may related to its dimerization
Going Beyond Counting First Authors in Author Co-citation Analysis
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counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
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Appropriate Similarity Measures for Author Cocitation Analysis
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Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
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koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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