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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 楊偉勛(Wei-Shiung Yang) | |
dc.contributor.author | Pei-Jung Lin | en |
dc.contributor.author | 林佩蓉 | zh_TW |
dc.date.accessioned | 2021-06-13T15:24:33Z | - |
dc.date.available | 2013-08-08 | |
dc.date.copyright | 2008-08-08 | |
dc.date.issued | 2008 | |
dc.date.submitted | 2008-07-21 | |
dc.identifier.citation | Adermann K, Wattler F, Wattler S, Heine G, Meyer M, Forssmann WG, Nehls M (1999) Structural and phylogenetic characterization of human SLURP-1, the first secreted mammalian member of the Ly-6/uPAR protein superfamily. Protein Sci 8(4):810-9
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(2001)The portrait and paper of a forgotten hero--Luca Stulli (1772-1828) and the Mal de Meleda of yesteryear: a 175-year anniversary. J Invest Dermatol 116:198-199. Favre B, Plantard L, Aeschbach L, Brakch N, Christen-Zaech S, de Viragh PA, Sergeant A, Huber M, Hohl D (2007) SLURP1 is a late marker of epidermal differentiation and is absent in Mal de Meleda. J Invest Dermatol 127:301-308 Fischer J, Bouadjar B, Heilig R, Fizames C, Prud'homme JF, Weissenbach J (1998) Genetic linkage of Meleda disease to chromosome 8qter. Eur J Hum Genet 6:542-547 Fischer J, Bouadjar B, Heilig R, Huber M, Lefevre C, Jobard F, Macari F, Bakija-Konsuo A, Ait-Belkacem F, Weissenbach J, Lathrop M, Hohl D, Prud'homme JF (2001) Mutations in the gene encoding SLURP-1 in Mal de Meleda. Hum Mol Genet 10:875-880 Robertson G, Bilenky M, Lin K, He A, Yuen W, Dagpinar M, Varhol R, Teague K, Griffith OL, Zhang X, Pan Y, Hassel M, Sleumer MC, Pan W, Pleasance ED, Chuang M, Hao H, Li YY, Robertson N, Fjell C, Li B, Montgomery SB, Astakhova T, Zhou J, Sander J, Siddiqui AS, Jones SJ.(2006) cisRED: a database system for genome-scale computational discovery of regulatory elements. Nucleic Acids Res 34:D68-73 Grando SA (1997) Biological functions of keratinocyte cholinergic receptors. J Investig Dermatol Symp Proc 2:41-48 Grando SA, Pittelkow MR, Schallreuter KU (2006) Adrenergic and cholinergic control in the biology of epidermis: physiological and clinical significance. J Invest Dermatol 126(9):1948-65 Grando SA (2008) Basic and clinical aspects of non-neuronal acetylcholine: biological and clinical significance of non-canonical ligands of epithelial nicotinic acetylcholine receptors. J Pharmacol Sci 106:174-179 Happle R, van de Kerkhof PC, Traupe H (1987) Retinoids in disorders of keratinization: their use in adults. Dermatologica 175 Suppl 1:107-124 Hu G, Yildirim M, Baysal V, Yerebakan O, Yilmaz E, Inaloz HS, Martinez-Mir A, Christiano AM, Celebi JT (2003) A recurrent mutation in the ARS (component B) gene encoding SLURP-1 in Turkish families with mal de Meleda: evidence of a founder effect. J Invest Dermatol 120:967-969 Jee SH, Lee YY, Wu YC, Lu YC, Pan CC (1985) Report of a family with mal de Meleda in Taiwan: a clinical, histopathological and immunological study. Dermatologica 171:30-37 Kabashima K, Sakabe J, Yamada Y, Tokura Y (2008) 'Nagashima-type' keratosis as a novel entity in the palmoplantar keratoderma category. Arch Dermatol 144:375-379 Kawashima K, Yoshikawa K, Fujii YX, Moriwaki Y, Misawa H (2007) Expression and function of genes encoding cholinergic components in murine immune cells. Life Sci 80:2314-2319 Krammer PH, Arnold R, Lavrik IN (2007) Life and death in peripheral T cells. Nat Rev Immunol 7: 532-542 Lestringant GG, Halawani NA, Zagzouk F (1989) Mal de Meleda. Int J Dermatol 28:277-278. Liu X, Fortin K, Mourelatos Z (2008) MicroRNAs: biogenesis and molecular functions. Brain Pathol 18(1):113-21 Lu PY, Woodle MC (2008) Delivering small interfering RNA for novel therapeutics. Methods Mol Biol 437:93-107 Marrakchi S, Audebert S, Bouadjar B, Has C, Lefevre C, Munro C, Cure S, Jobard F, Morlot S, Hohl D, Prud'homme JF, Zahaf A, Turki H, Fischer J (2003) Novel mutations in the gene encoding secreted lymphocyte antigen-6/urokinase-type plasminogen activator receptor-related protein-1 (SLURP-1) and description of five ancestral haplotypes in patients with Mal de Meleda. J Invest Dermatol 120:351-355 Mokni M, Charfeddine C, Ben Mously R, Baccouche D, Kaabi B, Ben Osman A, Dellagi K, Abdelhak S (2004) Heterozygous manifestations in female carriers of Mal de Meleda. Clin Genet 65:244-246 Moriwaki Y, Yoshikawa K, Fukuda H, Fujii YX, Misawa H, Kawashima K (2007) Immune system expression of SLURP-1 and SLURP-2, two endogenous nicotinic acetylcholine receptor ligands. Life Sci 80:2365-2368 Mozzillo N, Nunziata CA, Caraco C, Fazioli F, Botti G (2003) Malignant melanoma developing in an area of hereditary palmoplantar keratoderma (Mal de Meleda). J Surg Oncol 84:229-233 Muslumanoglu MH, Saracoglu N, Cilingir O, Basmaci T, Urer S, Sabuncu I, Demir S, Bademci G, Artan S (2006) A novel mutation in the ARS (component B) gene encoding SLURP-1 in a Turkish family with mal de Meleda. Br J Dermatol 155:467-469 Salamon T, Berberovic L, Topic B, Basic V (1988) Meleda disease (mal de Meleda). Data and considerations on an indigenous caseload. G Ital Dermatol Venereol 123:649-655 Salamon T (1985) Hairgrowth over the thenar and the sole in Mal de Meleda (Mljet disease). Acta Derm Venereol 65:352-353 Salamon T (1986) Sudan-IV-positive material in fingernails of patient affected with mal de Meleda. Dermatologica 173:199-200 Salamon T (1986) Various cutaneous and extracutaneous associations in Mljet disease (mal de Meleda). Dermato Monatsschr 172:528-534 Schnyder UW, Franceschetti A, Cezarovic B, Segedin J, Taugner M, Muller R (1970) Meleda disease (Mal de Meleda). Lije Vjes. 92:747-756 Sybert VP, Dale BA, Holbrook KA (1988) Palmar-plantar keratoderma. A clinical, ultrastructural, and biochemical study. J Am Acad Dermatol 18:75-86 Ward KM, Yerebakan O, Yilmaz E, Celebi JT (2003) Identification of recurrent mutations in the ARS (component B) gene encoding SLURP-1 in two families with mal de Meleda. J Invest Dermatol 120:96-98 Yerebakan O, Hu G, Yilmaz E, Celebi JT (2003) A novel mutation in the ARS (component B) gene encoding SLURP-1 in a family with Mal de Meleda. Clin Exp Dermatol 28:542-544 | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/37327 | - |
dc.description.abstract | Mal de Meleda(簡寫為MDM、或稱為Meleda島症,OMIM248300),係屬於一種罕見的體染色體隱性遺傳之皮膚疾病,主要特徵是患者的手掌與腳掌有襪子樣的角化性紅斑,基因異常為SLURP-1蛋白質之基因位點突變。
由於臺大皮膚部紀秀華醫師在1985年報導之Mal de Meleda (MDM)家族成員中,病患及非病患之免疫功能都有低下的情形。本研究中,我們著手進行此一臺灣Mal de Meleda (MDM)家族三代SLURP-1基因研究與表現型的相關聯性分析,並對於免疫功能進行探討。希望能進一步提供逐年增加家族成員的Mal de Meleda (MDM)家族一些遺傳諮詢的協助,以及期待能建立提供臨床診斷Mal de Meleda (MDM)的方法與治療的方向。 研究結果以PCR-sequencing檢測證實,此一臺灣的Mal de Meleda (MDM)家族其SLURP-1基因,在四位有皮膚異常之患者身上找到,其位在SLURP-1基因第三個exon上,核甘酸(X99977)位點上第1764號,由原來的核酸鳥糞嘌呤(Guanine, G),變成腺嘌呤(Adenine, A),造成第86號胺基酸由甘胺酸(Glycine)變成精氨酸(Arginine),簡寫為G86R。這種基因型A/A homozygous mutation與皮膚手套襪子樣角化紅斑表現有完全的一致性。反之,在沒有皮膚異常表現的15位家族成員中,有7 位其第1764位點上的基因型為G/G ,有8位為G/A基因型。 在這個Mal de Meleda (MDM)家族成員中,只要有遺傳到第1764位點上帶有A對偶基因的成員,其周邊血液細胞在α-CD3/CD28抗體刺激T細胞活化增生上,呈現出無法被活化的現象,而且無法誘發正常SLURP-1蛋白表現。這點,在過去Mal de Meleda (MDM)相關報導與研究上,從來沒有被提及與發現。 本研究以anti-CD3/28 抗體探討此一家族成員周邊血液細胞之T-cell活化反應,發現不具T-cell 活化反應與位點1764上帶有A/A基因型之homozygous mutation 或G/A基因型的heterozygous mutation 有一致性,利用卡方檢定與葉氏校正後,具有統計學上的意義(p=0.003)。此一特殊發現引領我們探討有發生突變的SLURP-1 蛋白質像是G86R ,其在T cell 活化反應所扮演的生物角色。 以anti-CD3/28 antibodies刺激正常人周邊血液細胞,SLURP-1 蛋白質會出現,且有T-cell 活化反應;反之,在1764位點上基因型為A/A的MDM病人及G/A基因型的家族成員,正常的SLURP-1 蛋白不會出現,並且沒有T-cell 活化反應,有半顯性(semi-dominant)的關連性。進一步,以合成的SLURP-1 蛋白加入A/A與G/A基因型之Mal de Meleda (MDM)病人與家族成員的周邊血液細胞中,則可使T-cell 活化,因而證實SLURP-1的在T-cell 活化功能上具有生物作用。 遺傳諮詢流程圖提供臨床診斷時,面對新的MDM家族或是其他隱性遺傳的手腳掌過度角化增生(PPK)家族一個簡單且直接的篩檢方式。 針對Meleda島症患者而言,進展式的病程,特別是足部的角化與反覆紅斑發炎症狀,會導致患者大約50歲後無法穿鞋與走路,偶爾也有在患部特別容易感染其他皮膚疾病的現象,都需要社會與醫療團隊提供諮商與協助。此外,面對如MDM家族成員中帶有位點1764上A對偶基因的家屬而言,我們目前提供其SLURP-1基因的產前診斷與Mal de Meleda (MDM)的遺傳諮詢,希望能對患者與家屬提供幫助。 | zh_TW |
dc.description.abstract | Mal de Meleda (MDM, OMIM 248300) is a rare autosomal recessive skin disorder characterized by glove- and sock-like erythrokeratosis on palms and soles with mutation of SLURP-1 gene. We reported a Taiwan MDM family and first found the association with impaired T cell activation in 1985. In the study, mutations of gene encoding SLURP-1 protein and lymphocytes proliferation tests were investigated in three generations of this family. We try to offer the genetic counseling to the members of MDM family and establish the ways for clinical diagnosis and therapy.
PCR-sequencing of SLURP-1 revealed 1764 (X99977) G to A mutation of exon 3 which changed the amino acid at number 86 from Glycine to Arginine (G86R). All of 4 affected members have homozygous mutation of 1764 A/A genotype On the other hand, among 15 members with normal skin phenotype were 7 of G/G genotype and 8 of G/A genotype. The T cell activation using anti-CD3/CD28 antibodies as stimulant is impaired in all 12 family members with heterozygous (G/A) or homozygous (A/A) 1764G>A mutation genotype. On the contrast, only 2 of 7 members with normal G/G genotype have impaired T-cell activation. (Chi-Square test with Yate’s correction, p=0.003) SLURP-1 was induced in PBMBs of normal subjects with normal proliferation response to anti-CD3/CD28 antibodies stimulation, while the MDM family members with A/A or G/A genotype exhibit low proliferation response. Treatment with 0.5ug/ml recombinant-human SLURP-1 protein recovered T cell activation in patient with A/A genotype. This finding supports that SLURP-1 protein play a crucial role in T cell activation. For clinical diagnosis, the genetic consulting flow chart is an easy and directed screen to facing the new Mal de Meleda (MDM) or other recessive palmar plantar erythyrokeratodermia (PPK) families. Regarding the MDM affected members, progressive of erythema and hyperkeratosis on feet and soles is led them incapable wear shoes and walk after 50 years old. Sometimes, other skin infections of MDM affected members have been reported. The conditions of MDM affected members indeed should be paid attention to the team of social and medical work cooperation. In addition, for the Mal de Meleda (MDM) family members, it is important to keep on going with heterozygous 1764G>A mutation members and provide them genetic consultations and prenatal diagnosis plan to pregnancy. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T15:24:33Z (GMT). No. of bitstreams: 1 ntu-97-P95448012-1.pdf: 1994801 bytes, checksum: e4ddce4ddd0d75a0c574507d54ccc77e (MD5) Previous issue date: 2008 | en |
dc.description.tableofcontents | 口試委員會審定書
誌謝………………………………………………………………………ii Abbreviations………………………………………………………… iv 中文摘要………………………………………………………………… v Abstract………………………………………………………………vii 1.Introduction………………………………………………………1 Background and aim 2. Materials and methods……………………………………………5 Samples collection and pedigree of Mal de Meleda (MDM) family members Isolation of whole mononuclear cells from peripheral blood and cord blood Genotyping and mutation analysis Proliferative responses of cultured lymphocytes RNA preparation, cDNA synthesis and RT-PCR analysis Cultured of primary kerationcytes Enzyme-Linked Immunosorbent Assay, ELISA Western blotting Statistic analysis UTR reference 3. Results………………………………………………………………17 Affected of MDM had 1764G>A homozygous mutations Proliferative responses of cultured lymphocytes Normal SLURP-1 did not detect in PBMCs of MDM A/A genotype stimulated by anti-CD3/CD28 antibodies. SLURP-1 played an important role in T-cell activation by anti-CD3/CD28 antibodies. 4.iscussion……………………………………………………………21 5.Conclusion…………………………………………………………25 6.Figures………………………………………………………………26 7.Tables………………………………………………………………40 8.References…………………………………………………………44 9.Appendixes……………………………………………………………49 | |
dc.language.iso | en | |
dc.title | 探討在台灣的Meleda島症家族其基因與SLURP-1蛋白質在免疫與其他功能之研究 | zh_TW |
dc.title | A study in Gene Encoding SLURP-1 Protein and Immunological Function in Taiwan Mal de Meleda Family | en |
dc.type | Thesis | |
dc.date.schoolyear | 96-2 | |
dc.description.degree | 碩士 | |
dc.contributor.coadvisor | 紀秀華(Shiou-Hwa Jee) | |
dc.contributor.oralexamcommittee | 李銘仁 | |
dc.subject.keyword | Mal de Meleda (MDM),Meleda島症,SLURP-1基因,T細胞活化與遺傳諮詢, | zh_TW |
dc.subject.keyword | Mal de Meleda (MDM),SLURP-1,G86A,anti-CD3/CD28,T cell activation,genetic consulting, | en |
dc.relation.page | 52 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2008-07-22 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 分子醫學研究所 | zh_TW |
顯示於系所單位: | 分子醫學研究所 |
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