{"id":10910,"date":"2021-11-18T12:28:06","date_gmt":"2021-11-18T09:28:06","guid":{"rendered":"http:\/\/blog.ulubat.org\/?p=10910"},"modified":"2022-01-30T22:00:25","modified_gmt":"2022-01-30T19:00:25","slug":"sam-bernsun-felsefesi-progeriaya-yaklasim","status":"publish","type":"post","link":"https:\/\/blog.ulubat.org\/index.php\/genel\/sam-bernsun-felsefesi-progeriaya-yaklasim\/","title":{"rendered":"Sam Berns&#8217;\u00fcn Felsefesi: Progeria&#8217;ya Yakla\u015f\u0131m"},"content":{"rendered":"\n<p><em>&#8220;<strong>Bana \u00fcz\u00fclmeniz i\u00e7in kendimi sizin \u00f6n\u00fcn\u00fcze koymad\u0131m. Benim i\u00e7in \u00fcz\u00fclmenize gerek yok. \u00c7\u00fcnk\u00fc beni tan\u0131man\u0131z\u0131 istiyorum. Bu benim hayat\u0131m.<\/strong><\/em>&#8220;<\/p>\n\n\n\n<p><strong><em>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; -Sampson Gordon Berns&nbsp;<\/em><\/strong><\/p>\n\n\n\n<figure class=\"wp-block-audio\"><audio controls src=\"https:\/\/blog.ulubat.org\/wp-content\/uploads\/2022\/01\/Sam-Berns.mp3\"><\/audio><figcaption><strong><em>Yaz\u0131m\u0131z\u0131 yukar\u0131daki oynat\u0131c\u0131y\u0131 kullanarak sesli olarak dinleyebilirsiniz.<\/em><\/strong><\/figcaption><\/figure>\n\n\n\n<p>Sam Berns, 23 Ekim 1996 tarihinde Amerika\u2019n\u0131n Providence \u015fehrinde do\u011fdu. Sam\u2019e 22 ayl\u0131kken erken ya\u015flanma ile kendisini g\u00f6steren ve nadir bir genetik hastal\u0131k olan <strong>progeria <\/strong>te\u015fhisi konuldu. Progeria, 8 milyonda bir g\u00f6r\u00fcl\u00fcyordu. Bu hastal\u0131\u011fa sahip insanlar ortalama 13 ya\u015f\u0131nda kardiyovask\u00fcler hastal\u0131k veya fel\u00e7 ile ilgili komplikasyonlardan dolay\u0131 \u00f6l\u00fcyordu. \u00c7ocuk doktoru olan ebeveyni (Dr. Leslie Gordon ve Dr. Scott Berns) bu te\u015fhisin ard\u0131ndan 1999 y\u0131l\u0131nda, hastal\u0131\u011f\u0131 incelemek ve bir tedavi bulabilmek i\u00e7in Progeria Ara\u015ft\u0131rma Vakf\u0131&#8217;n\u0131&nbsp; (PRF: Progeria Research Foundation) kurdu. Sam ve ailesi, sonraki 15 y\u0131l boyunca hastal\u0131\u011fa \u00e7are bulabilmek i\u00e7in multidisipliner bir \u00e7aba sarf etti. Progeria hastalar\u0131n\u0131n bilgilerini ve g\u00f6r\u00fcnt\u00fclerini yayarak, PRF\u2019yi tan\u0131mayan veya hen\u00fcz te\u015fhis edilmemi\u015f ki\u015filerin ortaya \u00e7\u0131kmas\u0131n\u0131 ama\u00e7layan PRF, g\u00fcn\u00fcm\u00fczde yaln\u0131zca progeria\u2019n\u0131n ara\u015ft\u0131r\u0131lmas\u0131na ve tedavisinin ke\u015ffine adanm\u0131\u015f d\u00fcnyadaki tek organizasyondur.<\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img src=\"https:\/\/els-jbs-prod-cdn.jbs.elsevierhealth.com\/cms\/attachment\/57b78b0b-5454-4a62-933c-408846be2de6\/fx1_lrg.jpg\" alt=\"\"\/><figcaption><strong>Sampson Gordon Berns <br>Kaynak: <\/strong><a href=\"http:\/\/The Lancet\">The Lancet<\/a><\/figcaption><\/figure>\n\n\n\n<h2>Progeria&#8217;ya Genel Bak\u0131\u015f<\/h2>\n\n\n\n<p>Hutchinson-Gilford Progeria Sendromu (HGPS) olarak da bilinen <em>Progeria<\/em>, ilk olarak Johnathan Hutchinson taraf\u0131ndan 1886\u2019da bildirilen ve daha sonra Hastings Gilford taraf\u0131ndan 1904\u2019te a\u00e7\u0131klanan, \u00e7ocuklarda h\u0131zla ya\u015flanmaya sebep olan ve son derece nadir g\u00f6r\u00fclen \u00f6l\u00fcmc\u00fcl genetik bir hastal\u0131kt\u0131r. Progerial\u0131 \u00e7ocuklar genellikle do\u011fumda normal g\u00f6r\u00fcn\u00fcmdedir.&nbsp;\u0130lk y\u0131l i\u00e7inde b\u00fcy\u00fcme gerili\u011fi ve sa\u00e7 d\u00f6k\u00fclmesi gibi belirti ve semptomlar ortaya \u00e7\u0131kar.<\/p>\n\n\n\n<p>Kalp sorunlar\u0131 veya fel\u00e7, progerial\u0131 \u00e7o\u011fu \u00e7ocukta nihai \u00f6l\u00fcm nedenidir. Yeti\u015fkin insanlar\u0131 etkileyen kalp hastal\u0131klar\u0131 60 &#8211; 70 ya\u015flar\u0131nda g\u00f6r\u00fcl\u00fcrken,&nbsp; progeria hastas\u0131 \u00e7ocuklar 5-6 ya\u015flar\u0131ndan itibaren kalp krizi ve fel\u00e7lere maruz kalabilirler. Progeria olan bir \u00e7ocuk i\u00e7in ortalama ya\u015fam beklentisi yakla\u015f\u0131k 13 y\u0131ld\u0131r. Progeria, \u00e7ocuklar\u0131n zekalar\u0131n\u0131 etkilemez. Bu \u00e7ocuklar gen\u00e7 bedenlerindeki \u015fa\u015f\u0131rt\u0131c\u0131 fiziksel de\u011fi\u015fikliklere ra\u011fmen zeki, cesur ve hayat doludur.<\/p>\n\n\n\n<p>Bu sendromdan sorumlu olan mutasyon de\u015fifre edilmi\u015f olsa da, etki mekanizmas\u0131 belirsizli\u011fini korumaktad\u0131r. Progeria ara\u015ft\u0131rmas\u0131, normal ve di\u011fer patofizyolojik ko\u015fullarda ya\u015flanma s\u00fcrecine ili\u015fkin kan\u0131tlar\u0131n ortaya \u00e7\u0131kma olas\u0131l\u0131\u011f\u0131 nedeniyle \u00f6zellikle son yirmi y\u0131lda h\u0131z kazanm\u0131\u015ft\u0131r.<\/p>\n\n\n\n<p>Progeria i\u00e7in kesin bir tedavi yoktur, ancak devam eden ara\u015ft\u0131rmalar tedavi i\u00e7in baz\u0131 umutlar vadetmektedir. En son klinik ara\u015ft\u0131rma raporlar\u0131na g\u00f6re, bir farnesil transferaz inhibit\u00f6r\u00fc olan Lonafarnib, Hutchinson-Gilford Progeria Sendromu (HGPS) i\u00e7in g\u00fc\u00e7l\u00fc bir \u2018umut ilac\u0131d\u0131r\u2019 ve progeroid \u00e7ocuklarda kilo al\u0131m\u0131n\u0131 kolayla\u015ft\u0131rmada, kardiyovask\u00fcler ve iskelet patolojilerini iyile\u015ftirmede ba\u015far\u0131l\u0131 olmu\u015ftur. Bu, progeria ara\u015ft\u0131rmas\u0131nda yeni bir \u00e7a\u011f\u0131n \u015fafa\u011f\u0131 olarak g\u00f6r\u00fclebilir.<\/p>\n\n\n\n<figure class=\"wp-block-image size-large is-resized\"><img loading=\"lazy\" src=\"https:\/\/nihrecord.nih.gov\/sites\/recordNIH\/files\/styles\/float_medium\/public\/2020\/December-11\/digest-121120-progeria.jpg?itok=kmxdMsII&amp;timestamp=1607370280\" alt=\"\" width=\"579\" height=\"496\"\/><figcaption><strong>Hutchinson- Gilford Progeria sendromlu iki \u00e7ocuk <br>Kaynak: <\/strong><a href=\"http:\/\/USA.gov\">http:\/\/USA.gov<\/a><\/figcaption><\/figure>\n\n\n\n<h3>Epidemiyoloji, Belirtiler ve Semptomlar <\/h3>\n\n\n\n<p>Progeria sendromu, 8 milyon \u00e7ocukta bir g\u00f6r\u00fcl\u00fcr. \u0130nsidans\u0131; cinsiyete, co\u011frafi ve etnik \u00f6zelliklere g\u00f6re farkl\u0131l\u0131k g\u00f6stermez. \u00c7o\u011funlukla sporadik olarak kabul edilir. Genellikle ya\u015fam\u0131n ilk y\u0131l\u0131nda progerial\u0131 bir \u00e7ocu\u011fun b\u00fcy\u00fcmesi belirgin \u015fekilde yava\u015flar; ancak motor geli\u015fimi ve zeka normal kal\u0131r. Bu ilerleyici bozuklu\u011fun belirti ve semptomlar\u0131 farkl\u0131 bir g\u00f6r\u00fcn\u00fcm\u00fc i\u00e7erir:<\/p>\n\n\n\n<ul><li>Boyu ve a\u011f\u0131rl\u0131\u011f\u0131 ortalaman\u0131n alt\u0131nda olan yava\u015f b\u00fcy\u00fcme<\/li><li>Dar y\u00fcz, k\u00fc\u00e7\u00fck alt \u00e7ene, ince dudaklar ve gaga burun<\/li><li>Ba\u015f\u0131n y\u00fcze g\u00f6re orant\u0131s\u0131z \u015fekilde b\u00fcy\u00fcmesi<\/li><li>Belirgin g\u00f6zler ve g\u00f6z kapaklar\u0131n\u0131n kusurlu kapanmas\u0131<\/li><li>Kirpik, ka\u015f ve sa\u00e7 d\u00f6k\u00fclmesi<\/li><li>Ciltte incelme<\/li><li>Sivilceli ve k\u0131r\u0131\u015f\u0131k cilt <\/li><li>G\u00f6r\u00fcn\u00fcr damarlar<\/li><li>Tiz ses<\/li><\/ul>\n\n\n\n<p>Belirtiler ve semptomlar ayr\u0131ca a\u015fa\u011f\u0131da belirtilen sa\u011fl\u0131k sorunlar\u0131n\u0131n g\u00f6stergesi olabilir:<\/p>\n\n\n\n<ul><li>\u015eiddetli ilerleyen kardiyovask\u00fcler hastal\u0131k<\/li><li>G\u00f6vde ve ekstremitelerde; deride sertle\u015fme ve s\u0131k\u0131la\u015fma (sklerodermaya benzer)<\/li><li>Gecikmi\u015f ve anormal di\u015f olu\u015fumu<\/li><li>Hafif i\u015fitme kayb\u0131<\/li><li>Deri alt\u0131nda ya\u011f kayb\u0131 ve kas k\u00fctlesi kayb\u0131<\/li><li>\u0130skelet anormallikleri ve k\u0131r\u0131lgan kemikler<\/li><li>Sert eklemler<\/li><li>Kal\u00e7a \u00e7\u0131k\u0131\u011f\u0131<\/li><li>\u0130ns\u00fclin direnci<\/li><\/ul>\n\n\n\n<p>Klinik bulgular, bu hastalar\u0131n normal fizyolojik ya\u015flanmada g\u00f6r\u00fclmeyen uzam\u0131\u015f protrombin zaman\u0131na ve y\u00fcksek trombosit say\u0131s\u0131na sahip oldu\u011funu g\u00f6sterir. Biyokimyasal analizler, bu hastalarda serumda artm\u0131\u015f d\u00fc\u015f\u00fck yo\u011funluklu lipoproteinler, kolesterol seviyeleri ve artm\u0131\u015f hyaluronik asit at\u0131l\u0131m\u0131 d\u0131\u015f\u0131nda normal sonu\u00e7lar g\u00f6stermektedir.<\/p>\n\n\n\n<p>Progeria sendromuna sahip \u00e7ocuklarda ortalama ya\u015fam beklentisi yakla\u015f\u0131k 8-21 y\u0131ld\u0131r. \u00d6l\u00fcm; fel\u00e7, miyokardial enfarkt\u00fcs, kalp yetmezli\u011fi veya ateroskleroz nedeniyle meydana gelir.<\/p>\n\n\n\n<p>Progeria sendromunu \u2018klasik progeria\u2019 ve \u2018klasik olmayan progeria\u2019 olmak \u00fczere iki tipte g\u00f6rebiliriz. Klasik progeria\u2019ya genellikle sporadik otozomal dominant mutasyon neden olur. Klasik olmayan progeria ise otozomal resesif kal\u0131t\u0131m modelini izler. Klasik olmayan progeriada b\u00fcy\u00fcme daha az gecikir, sa\u00e7lar yava\u015f d\u00f6k\u00fcl\u00fcr, lipodistrofi ilerlemesi gecikir, osteoliz daha belirgin olur ve hayatta kalma \u00e7o\u011funlukla yeti\u015fkinli\u011fe kadar g\u00f6zlenir.<\/p>\n\n\n\n<figure class=\"wp-block-image size-large is-resized\"><img loading=\"lazy\" src=\"https:\/\/ccr.cancer.gov\/sites\/default\/files\/MilestonesTiles\/accelerated-aging-1.png\" alt=\"\" width=\"580\" height=\"434\"\/><figcaption><strong>Hutchinson- Gilford Progeria sendromlu bir k\u0131z \u00e7ocu\u011fu <br>Kaynak: <\/strong><a href=\"http:\/\/USA.gov\">http:\/\/USA.gov<\/a><\/figcaption><\/figure>\n\n\n\n<h3>Etken Fakt\u00f6rler ve Patofizyoloji <\/h3>\n\n\n\n<p>Progeria\u2019dan tek bir gen mutasyonu sorumludur. Lamin A( LMNA) olarak bilinen gen, bir h\u00fccrenin \u00e7ekirde\u011fini bir arada tutmak i\u00e7in gerekli bir proteini yapar.&nbsp;Bu genin bir kusuru oldu\u011funda, progerin ad\u0131 verilen lamin A proteininin anormal bir formu \u00fcretilir ve h\u00fccreleri karars\u0131z hale getirir. DNA onar\u0131m\u0131 h\u00fccresel ya\u015flanmay\u0131 ind\u00fckler. Progeria&#8217;da onar\u0131lamayan DNA hasar\u0131n\u0131n birikmesine, mitokondriyal reaktif oksijen t\u00fcrleri (ROS) arac\u0131l\u0131 h\u00fccre hasar\u0131na ve antioksidan kapasite kayb\u0131na neden olur. Gen mutasyonunun etkisi, vask\u00fcler d\u00fcz kas h\u00fccrelerinin kayb\u0131na ve adventif fibroblast disfonksiyonuna neden olur. N\u00fckleer morfolojik \u00f6zellikler ve i\u015flevdeki anormallikler h\u00fccresel sertle\u015fmeye neden olur. Progeria&#8217;da bulunan a\u015f\u0131r\u0131 vask\u00fcler kalsifikasyon, esas olarak ROS ile ind\u00fcklenen mitokondriyal disfonksiyona ba\u011fl\u0131 pirofosfat sentezi kayb\u0131ndan kaynaklan\u0131r. Vask\u00fcler kalsifikasyon, vask\u00fcler d\u00fcz kas h\u00fccrelerinin osteojenik farkl\u0131la\u015fmas\u0131n\u0131 destekler. Kardiyovask\u00fcler problemler aras\u0131nda interstisyel miyokardiyal fibrozis, miyokardiyal enfarkt\u00fcs, hipertansiyon ve mitral ve aort kapaklar\u0131n\u0131n kal\u0131nla\u015fmas\u0131 ve kalsifikasyonu yer al\u0131r. Bu hastal\u0131\u011f\u0131n nadir olmas\u0131 nedeniyle, ilgili kardiyovask\u00fcler bozukluklar\u0131n do\u011fal seyri hakk\u0131nda s\u0131n\u0131rl\u0131 bilgi mevcuttur.<\/p>\n\n\n\n<p>Progeria\u2019n\u0131n h\u0131zlanm\u0131\u015f ya\u015flanma s\u00fcrecini a\u00e7\u0131klamak i\u00e7in \u00e7e\u015fitli hipotezler \u00f6ne s\u00fcr\u00fclm\u00fc\u015ft\u00fcr. Telomerlerin progeria\u2019da rol oynad\u0131\u011f\u0131 g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. Fibroblastlarda telomer uzunlu\u011funun ya\u015fa uygun kontrollere g\u00f6re daha k\u0131sa oldu\u011fu bildirilmi\u015ftir. Yap\u0131lan ba\u015fka bir \u00e7al\u0131\u015fmada, mutant lamin A\u2019n\u0131n do\u011frudan bir etki yoluyla telomer uzunlu\u011funu azaltt\u0131\u011f\u0131 ileri s\u00fcr\u00fclm\u00fc\u015ft\u00fcr. Bir organizmada artan h\u00fccre \u00f6l\u00fcm\u00fc, DNA onar\u0131m mekanizmas\u0131ndaki baz\u0131 aksakl\u0131klara, telomerin k\u0131salmas\u0131na veya telomerik DNA\u2019daki kusurlara ba\u011fl\u0131 olabilir.<\/p>\n\n\n\n<p>Pek \u00e7ok genetik mutasyonun aksine, progeria ailelerde nadiren aktar\u0131l\u0131r.&nbsp;Gen mutasyonu, vakalar\u0131n \u00e7o\u011funda nadir g\u00f6r\u00fclen, tesad\u00fcfi bir olayd\u0131r.<\/p>\n\n\n\n<h3>Te\u015fhis ve Umut Vadeden Tedaviler <\/h3>\n\n\n\n<p>Progeria i\u00e7in etkili bir tedavi bulma aray\u0131\u015f\u0131 hala devam etse de, yine de erken te\u015fhisi i\u00e7in mevcut bir te\u015fhis kiti yoktur. Genellikle pratikte, sendromun karakteristik belirti ve semptomlar\u0131na dayanarak progeria&#8217;dan \u015f\u00fcphelenebilir.&nbsp;Bunu takiben, LMNA mutasyonlar\u0131 i\u00e7in genetik bir test, progeria tan\u0131s\u0131n\u0131 do\u011frulamak i\u00e7in yayg\u0131n olarak yap\u0131l\u0131r. Progeria ile ilgili bir vaka raporu, klinik tan\u0131n\u0131n radyolojik bulgularla da (kafatas\u0131nda birka\u00e7 wormian kemik bulunan sagital s\u00fct\u00fcr\u00fcn diyastaz\u0131, infantil a\u00e7\u0131l\u0131 hipoplastik \u00e7ene, bal\u0131k a\u011f\u0131zl\u0131 omurlar\u0131n varl\u0131\u011f\u0131, iki tarafl\u0131 coxa valga deformitesinin ortaya \u00e7\u0131k\u0131\u015f\u0131, terminal falankslar\u0131n rezorbsiyonu vb.)&nbsp; konulabilece\u011fini bildirmi\u015ftir.<\/p>\n\n\n\n<p>Farnesil transferaz inhibit\u00f6rleri (FTI) olarak bilinen bir kanser ilac\u0131 s\u0131n\u0131f\u0131n\u0131n, progerial\u0131 \u00e7ocuklardaki h\u00fccrelerin \u00f6zelliklerinden biri olan \u00e7ekirde\u011fin yap\u0131sal anormalliklerini (prelamin A olu\u015fumuyla ili\u015fkili) tersine \u00e7evirdi\u011fi g\u00f6sterilmi\u015ftir. Ad\u0131ndan da anla\u015f\u0131laca\u011f\u0131 gibi bu ila\u00e7lar, farnesil gruplar\u0131 ve progerin proteinleri aras\u0131nda bir ba\u011flant\u0131 kurmak i\u00e7in gerekli olan farnesil transferaz aktivitesini k\u0131s\u0131tlar. FTI\u2019ler progeria benzeri fare modelinin bir\u00e7ok \u00f6zelli\u011finde geli\u015fme g\u00f6stermi\u015ftir. Spesifik olarak FTI\u2019ler, progerial\u0131 hastalardan al\u0131nan fibroblastlardaki n\u00fckleer \u015fekli iyile\u015ftirir. Yap\u0131lan bir \u00e7al\u0131\u015fmada, progeria benzeri fare modelinde bir FTI ile kardiyovask\u00fcler hastal\u0131\u011f\u0131n hem ba\u015flang\u0131c\u0131n\u0131n hem de ge\u00e7 ilerlemesinin \u00f6nlendi\u011fi g\u00f6sterilmi\u015ftir.<\/p>\n\n\n\n<p>Progeria Ara\u015ft\u0131rma Vakf\u0131, Ulusal Sa\u011fl\u0131k Enstit\u00fcleri, Boston \u00c7ocuk Hastanesi ve Dana-Farber Kanser Enstit\u00fcs\u00fc ortakl\u0131\u011f\u0131 alt\u0131nda, Pravastatin adl\u0131 bir statin ilac\u0131, Zoledronik asit adl\u0131 bir bifosfonat ilac\u0131 ve Lonafarnib adl\u0131 bir farnetil transferaz inhibit\u00f6r\u00fc olan \u00fc\u00e7 \u201c<strong>umut ilac\u0131<\/strong>\u201d n\u0131n etkinli\u011fini test etmek i\u00e7in 2010 y\u0131l\u0131nda progeria klinik ila\u00e7 denemesi ba\u015flat\u0131lm\u0131\u015ft\u0131r. 25 progeroid \u00e7ocukta y\u00fcr\u00fct\u00fclen klinik bir ara\u015ft\u0131rmada, bir FTI ilac\u0131 olan Lonafarnib\u2019in kilo al\u0131m\u0131n\u0131 kolayla\u015ft\u0131rmada, kardiyovask\u00fcler ve iskelet patolojilerini iyile\u015ftirmede ba\u015far\u0131l\u0131 oldu\u011fu bildirilmi\u015ftir. Bu, progeria ara\u015ft\u0131rmas\u0131n\u0131n ilerlemesinde muazzam bir ba\u015far\u0131d\u0131r ve belki de bu nadir ve karma\u015f\u0131k sendrom i\u00e7in kesin bir tedavinin ke\u015ffedilmesine giden yolu a\u00e7acakt\u0131r.<\/p>\n\n\n\n<h2>Sam Berns&#8217;\u00fcn Felsefesi <\/h2>\n\n\n\n<p>Sam, zeki ve cesur bir \u00e7ocuktu. Di\u011fer insanlardan farkl\u0131 oldu\u011funu biliyordu. Yapmak istedi\u011fi bir\u00e7ok \u015feyi fiziksel \u00f6zelliklerinden dolay\u0131 yapam\u0131yordu. \u00c7o\u011fu zaman bocalam\u0131\u015f ve elbette k\u00f6t\u00fc g\u00fcnler de ya\u015fam\u0131\u015ft\u0131. Ama nihayetinde cesur olman\u0131n kolay olmas\u0131 gerekmiyordu. \u00c7ok iyi bildi\u011fi bir \u015fey daha vard\u0131. Ailesi onu \u00e7ok seviyordu ve onun hayallerinin ger\u00e7ekle\u015fmesi i\u00e7in daima arkas\u0131ndayd\u0131lar. Sam, \u00e7ok \u015fansl\u0131 bir \u00e7ocuktu. Bu fark\u0131ndal\u0131kla kar\u015f\u0131la\u015ft\u0131\u011f\u0131 engelleri s\u00fcrekli d\u00fc\u015f\u00fcnmek yerine yapabildi\u011fi ve merakl\u0131 oldu\u011fu etkinliklere odaklanmay\u0131 tercih etti. \u0130zcilikle, \u00e7izgi romanlarla, m\u00fczikle ilgileniyordu. En b\u00fcy\u00fck hayallerinden biri ise \u00f6\u011frencisi oldu\u011fu Foxborough Lisesi\u2019nde okulun bando tak\u0131m\u0131nda trampet \u00e7almakt\u0131. Ama \u00e7ok zay\u0131f olan v\u00fccudu trampet d\u00fczene\u011fini ta\u015f\u0131yamazd\u0131. Bu duruma bir \u00e7\u00f6z\u00fcm bulmas\u0131 gerekiyordu. Ailesiyle birlikte daha hafif ve ta\u015f\u0131mas\u0131 kolay bir trampet d\u00fczene\u011fi tasarlamak i\u00e7in bir m\u00fchendisle birlikte \u00e7al\u0131\u015ft\u0131lar. Sam, \u00f6zel olarak tasarlanm\u0131\u015f bir ko\u015fum tak\u0131m\u0131 yard\u0131m\u0131yla hayalini ger\u00e7ekle\u015ftirdi.<\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img src=\"https:\/\/i1.wp.com\/directorsblog.nih.gov\/wp-content\/uploads\/2021\/01\/Sam-Berns-Quote.jpg?w=720&amp;ssl=1\" alt=\"\"\/><figcaption><strong>Sam Berns trampet \u00e7alarken <br>Kaynak:<\/strong> <a href=\"http:\/\/USA.gov\">http:\/\/USA.gov<\/a><\/figcaption><\/figure>\n\n\n\n<p>Sam, progeria hakk\u0131nda fark\u0131ndal\u0131\u011f\u0131 art\u0131rmak ve nadir bir hastal\u0131kla ya\u015fama deneyimini d\u00fcnyayla payla\u015fmak istiyordu. Sam ile 3 ya\u015f\u0131ndayken tan\u0131\u015fan ve progeria\u2019n\u0131n genetik nedeni ile ilgili temel ara\u015ft\u0131rmada annesiyle i\u015f birli\u011fi yapan Ulusal Sa\u011fl\u0131k Enstit\u00fcleri Direkt\u00f6r\u00fc Francis Collins, Sam\u2019i TED MED\u2019de sahnede kendisine kat\u0131lmaya davet etti. 1980\u2019lerin ba\u015f\u0131nda Yale \u00dcniversitesinde bir \u00f6\u011fretim g\u00f6revlisiyken progeria hastas\u0131na bakan, bu durumdan etkilenen ve bu konuda \u00e7ok az \u015fey bilindi\u011finden dolay\u0131 hayal k\u0131r\u0131kl\u0131\u011f\u0131na u\u011frayan Collins, Sam\u2019in s\u00f6zlerinin unutulmaz olaca\u011f\u0131ndan emindi.<\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img src=\"https:\/\/i0.wp.com\/directorsblog.nih.gov\/wp-content\/uploads\/2014\/01\/tedmed20121.jpg?resize=800%2C671\" alt=\"\"\/><figcaption><strong>Berns ve Francis Collins- 2012 TED MED <br>Kaynak: <\/strong><a href=\"http:\/\/USA.gov\">http:\/\/USA.gov<\/a><\/figcaption><\/figure>\n\n\n\n<p>Ayr\u0131ca Sam\u2019in \u201c<em>Mutlu Ya\u015fam Felsefem<\/em> (<em>My Philosophy for A Happy Life<\/em>)\u201d ba\u015fl\u0131kl\u0131 bir TEDx konu\u015fmas\u0131 da mevcut. Sam, bu konu\u015fmas\u0131nda mutlu bir ya\u015fam i\u00e7in olan felsefesini dinleyicilerle payla\u015ft\u0131:<\/p>\n\n\n\n<p>\u201c Denesem de en sonunda yapamad\u0131\u011f\u0131m \u015feyler benim i\u00e7in sorun de\u011fil, \u00e7\u00fcnk\u00fc yapabildi\u011fin \u00e7ok \u015fey var. \u00c7evremde birlikte olmak istedi\u011fim insanlara yer veriyorum. \u0130lerlemeye devam ediyorum.\u201d&nbsp;<\/p>\n\n\n\n<p>Sam\u2019in mutlulukla ilerleyebilmesinin esas sebebi b\u00f6yle bir felsefesinin olmas\u0131yd\u0131. Ekim 2013\u2019te HBO, Sam ve ailesi ile ilgili bir belgesel olan \u201c<em>Sam\u2019e G\u00f6re Ya\u015fam<\/em>\u201d (<em>Life According to Sam<\/em>) belgeselini yay\u0131nlad\u0131. \u201cBana \u00fcz\u00fclmeniz i\u00e7in kendimi sizin \u00f6n\u00fcn\u00fcze koymad\u0131m. Benim i\u00e7in \u00fcz\u00fclmenize gerek yok. \u00c7\u00fcnk\u00fc beni tan\u0131man\u0131z\u0131 istiyorum. Bu benim hayat\u0131m.\u201d diyen Sam\u2019e insanlar\u0131n kendisiyle ilgili bilmesi gereken en \u00f6nemli \u015feyin ne oldu\u011fu soruldu\u011funda onun tek yan\u0131t\u0131, \u00e7ok mutlu bir ya\u015fam\u0131 oldu\u011fuydu. Sam 10 Ocak 2014 y\u0131l\u0131nda, 17 ya\u015f\u0131nda, hayal etti\u011fi \u00e7o\u011fu \u015feyi ba\u015farm\u0131\u015f ve mutlu bir gen\u00e7 olarak &nbsp;hayata g\u00f6zlerini yumdu. Sam, herkese nas\u0131l ya\u015flanmalar\u0131 gerekti\u011fini g\u00f6steren gen\u00e7 bir \u00e7ocuktu.<\/p>\n\n\n\n<p>Sam Berns\u2019\u00fcn &nbsp;\u201c<em>Mutlu Ya\u015fam Felsefem<\/em> (<em>My Philosophy for A Happy Life<\/em>)\u201d ba\u015fl\u0131kl\u0131 TED konu\u015fmas\u0131n\u0131 izleminizi tavsiye ederim.<\/p>\n\n\n\n<figure class=\"wp-block-embed is-type-video is-provider-youtube wp-block-embed-youtube wp-embed-aspect-16-9 wp-has-aspect-ratio\"><div class=\"wp-block-embed__wrapper\">\n<iframe loading=\"lazy\" title=\"My philosophy for a happy life | Sam Berns | TEDxMidAtlantic\" width=\"800\" height=\"450\" src=\"https:\/\/www.youtube.com\/embed\/36m1o-tM05g?feature=oembed\" frameborder=\"0\" allow=\"accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture\" allowfullscreen><\/iframe>\n<\/div><figcaption><strong>Sam Berns- TEDxMidAtlantic <\/strong><\/figcaption><\/figure>\n\n\n\n<h2>Kaynaklar<\/h2>\n\n\n\n<ul><li>Alison Snyder, Sampson Gordon Berns, The Lancet, 2014; 383(9921): 948<\/li><\/ul>\n\n\n\n<p><a href=\"https:\/\/www.thelancet.com\/journals\/lancet\/article\/PIIS0140-6736(14)60472-4\/fulltext\">https:\/\/www.thelancet.com\/journals\/lancet\/article\/PIIS0140-6736(14)60472-4\/fulltext<\/a><\/p>\n\n\n\n<ul><li>Eurordis. Global Campaign To Find All Children With Progeria. (24 Ekim 2010)<\/li><\/ul>\n\n\n\n<p><a href=\"https:\/\/stars.eurordis.org\/content\/global-campaign-find-all-children-progeria\">https:\/\/stars.eurordis.org\/content\/global-campaign-find-all-children-progeria<\/a><\/p>\n\n\n\n<ul><li>&nbsp;<a href=\"http:\/\/www.progeriaresearch.org\/assets\/files\/Turkey%20-%20PRF%20Quick%20Facts.pdf\">http:\/\/www.progeriaresearch.org\/assets\/files\/Turkey%20-%20PRF%20Quick%20Facts.pdf<\/a><\/li><\/ul>\n\n\n\n<ul><li>Mayo Clinic. Progeria. (01 \u015eubat 2018)<\/li><\/ul>\n\n\n\n<p><a href=\"https:\/\/www.mayoclinic.org\/diseases-conditions\/progeria\/diagnosis-treatment\/drc-20356043\">https:\/\/www.mayoclinic.org\/diseases-conditions\/progeria\/diagnosis-treatment\/drc-20356043<\/a><\/p>\n\n\n\n<p><a href=\"https:\/\/www.mayoclinic.org\/diseases-conditions\/progeria\/symptoms-%20%20%20causes\/syc-20356038\">https:\/\/www.mayoclinic.org\/diseases-conditions\/progeria\/symptoms-&nbsp;&nbsp;&nbsp; HYPERLINK &#8220;https:\/\/www.mayoclinic.org\/diseases-conditions\/progeria\/symptoms-%20%20%20causes\/syc-20356038&#8243;causes HYPERLINK &#8220;https:\/\/www.mayoclinic.org\/diseases-conditions\/progeria\/symptoms-%20%20%20causes\/syc-20356038&#8243;\/ HYPERLINK &#8220;https:\/\/www.mayoclinic.org\/diseases-conditions\/progeria\/symptoms-%20%20%20causes\/syc-20356038&#8243;syc HYPERLINK &#8220;https:\/\/www.mayoclinic.org\/diseases-conditions\/progeria\/symptoms-%20%20%20causes\/syc-20356038&#8221;-20356038<\/a><\/p>\n\n\n\n<ul><li>Prakash A, Gordon LB, Kleinman ME, et al. Cardiac abnormalities in patients with Hutchinson-Gilford progeria syndrome.&nbsp;<em>JAMA Cardiol.&nbsp;<\/em>2018;3(4):326\u201334.<\/li><li>Olive M, Harten I, Mitchell R, et al. Cardiovascular pathology in Hutchinson-Gilford progeria: Correlation with the vascular pathology of aging.&nbsp;<em>Arterioscler Thromb Vasc Biol.&nbsp;<\/em>2010;30(11):2301\u20139.<\/li><li>Kubben N, Zhang W, Wang L, vd.&nbsp;Erken ya\u015flanmada antioksidan NRF2 yolunun bask\u0131lanmas\u0131.&nbsp;<em>H\u00fccre.&nbsp;<\/em>2016;&nbsp;165&nbsp;(6): 1361\u201374.<\/li><li>Yan T, Li S, Jiang X, Oberley LW.&nbsp;Progeria deri fibroblastlar\u0131nda de\u011fi\u015fen birincil antioksidan enzim seviyeleri.&nbsp;<em>Biochem Biophys Res Commun.&nbsp;<\/em>1999;&nbsp;257&nbsp;(1): 163\u201367.<\/li><li>Osorio FG, Navarro CL, Cadi\u00f1anos J, vd.&nbsp;\u0130nsan\u0131n ya\u015flanmas\u0131n\u0131 h\u0131zland\u0131ran yeni bir fare modelinde eklemeye y\u00f6nelik tedavi.&nbsp;<em>Sci Transl Med.&nbsp;<\/em>2011;&nbsp;3&nbsp;(106): 106r.&nbsp;a107.<\/li><li>Marji J, O&#8217;Donoghue SI, McClintock D, vd.&nbsp;Hutchinson-Gilford progeria sendromunda kusurlu lamin A-Rb sinyali ve farnesiltransferaz inhibisyonu ile tersine \u00e7evirme.&nbsp;<em>PLoS One.&nbsp;<\/em>2010;&nbsp;5&nbsp;(6): e11132.<\/li><li>Musich PR, Zou Y. Hutchinson-Gilford progeria sendromunda DNA hasar\u0131 birikimi ve replikatif tutuklama.&nbsp;<em>Biochem Soc Trans.&nbsp;<\/em>2011;&nbsp;39&nbsp;(6): 1764\u201369.<\/li><li>Villa-Bellosta R, Rivera-Torres J, Osorio FG, vd.&nbsp;H\u00fccre d\u0131\u015f\u0131 pirofosfat metabolizmas\u0131 bozuk, Hutchinson-Gilford progeria sendromunun bir fare modelinde piro-fosfat tedavisi ile iyile\u015ftirilen vask\u00fcler kalsifikasyonu destekler.&nbsp;<em>Dola\u015f\u0131m.&nbsp;<\/em>2013;&nbsp;127&nbsp;(24): 2442\u201351.<\/li><\/ul>\n\n\n\n<p><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7805248\/\">https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7805248\/<\/a><\/p>\n\n\n\n<ul><li>Pereira S, Bourgeois P, Navarro C, Esteves-Vieira V, Cau P, De Sandre-Giovannoli A, vd.&nbsp;HGPS ve ilgili erken ya\u015flanma bozukluklar\u0131: genomik tan\u0131mlamadan ilk terap\u00f6tik yakla\u015f\u0131mlara.&nbsp;<em>Mech Aging Dev.&nbsp;<\/em>2008;&nbsp;129&nbsp;: 449\u201359.<\/li><\/ul>\n\n\n\n<ul><li>Hennekam RC.&nbsp;Hutchinson-Gilford progeria sendromu: fenotipin g\u00f6zden ge\u00e7irilmesi.&nbsp;<em>Am J Med Genet A.<\/em>&nbsp;2006;&nbsp;140&nbsp;: 2603\u201324.<\/li><\/ul>\n\n\n\n<ul><li>Yu CE, Oshima J, Fu YH, Wijsman EM, Hisama F, Alisch R, vd.&nbsp;Werner sendromu geninin konumsal klonlanmas\u0131.&nbsp;<em>Bilim.&nbsp;<\/em>1996;&nbsp;272&nbsp;: 258\u201362.<\/li><\/ul>\n\n\n\n<ul><li>Allsopp RC, Vaziri H, Patterson C, Goldstein S, Younglai EV, Futcher AB, et al.&nbsp;Telomer uzunlu\u011fu, insan fibroblastlar\u0131n\u0131n replikatif kapasitesini \u00f6ng\u00f6r\u00fcr.&nbsp;<em>Proc Natl Acad Sci ABD.&nbsp;<\/em>1992;&nbsp;89&nbsp;: 10114\u20138.<\/li><\/ul>\n\n\n\n<ul><li>Decker ML, Chavez E, Vulto I, Lansdorp PM.&nbsp;Hutchinson-Gilford progeria sendromunda telomer uzunlu\u011fu.&nbsp;<em>Mech Aging Dev.&nbsp;<\/em>2009;&nbsp;130&nbsp;: 377\u201383.&nbsp;<\/li><\/ul>\n\n\n\n<ul><li>Aubert G, Lansdorp PM.&nbsp;Telomerler ve ya\u015flanma.&nbsp;<em>Physiol Rev.<\/em>&nbsp;2008;&nbsp;88&nbsp;: 557\u201379.&nbsp;<\/li><\/ul>\n\n\n\n<ul><li>Rastogi R, Chander Mohan SM.&nbsp;Progeria sendromu: bir vaka raporu.&nbsp;<em>Hintli J Orthop.&nbsp;<\/em>2008;&nbsp;42&nbsp;: 97\u20139.<\/li><\/ul>\n\n\n\n<ul><li>Yang SH, Bergo MO, Toth JI, Qiao X, Hu Y, Sandoval S, vd.&nbsp;Protein farnesiltransferaz\u0131n bloke edilmesi, hedeflenen Hutchinson-Gilford progeria sendromu mutasyonu ile fare fibroblastlar\u0131nda n\u00fckleer kabarc\u0131klanmay\u0131 iyile\u015ftirir.&nbsp;<em>Proc Natl Acad Sci ABD.&nbsp;<\/em>2005;&nbsp;102&nbsp;: 10291\u20136.&nbsp;<\/li><\/ul>\n\n\n\n<ul><li>Yang SH, Qiao X, Fong LG, Young SG.&nbsp;Bir farnesiltransferaz inhibit\u00f6r\u00fc ile tedavi, Hutchinson-Gilford progeria sendromu mutasyonu olan farelerde hayatta kalmay\u0131 iyile\u015ftirir.&nbsp;<em>Biochim Biophys A\u00e7ta.&nbsp;<\/em>2008;&nbsp;1781&nbsp;: 36\u20139.&nbsp;<\/li><\/ul>\n\n\n\n<ul><li>Verstraeten VL, Ji JY, Cummings KS, Lee RT, Lammerding J. Hutchinson-Gilfordprogeria h\u00fccrelerinde artan mekanosensitivite ve n\u00fckleer sertlik: farnesil transferaz inhibit\u00f6rlerinin etkileri.&nbsp;<em>Ya\u015flanma H\u00fccresi.&nbsp;<\/em>2008;&nbsp;7&nbsp;: 383\u201393.&nbsp;<\/li><\/ul>\n\n\n\n<ul><li>Toth JI, Yang SH, Qiao X, Beigneux AP, Gelb MH, Moulson CL, vd.&nbsp;Protein farnesiltransferaz\u0131n bloke edilmesi, progeroid sendromlu insanlardan al\u0131nan fibroblastlarda n\u00fckleer \u015fekli iyile\u015ftirir.&nbsp;<em>Proc Natl Acad Sci ABD.&nbsp;<\/em>2005;&nbsp;102&nbsp;: 12873\u20138.<\/li><\/ul>\n\n\n\n<ul><li>Capell BC, Olive M, Erdos MR, Cao K, Faddah DA, Tavarez UL, vd.&nbsp;Bir farnesiltransferaz inhibit\u00f6r\u00fc, bir progeria fare modelinde kardiyovask\u00fcler hastal\u0131\u011f\u0131n hem ba\u015flang\u0131c\u0131n\u0131 hem de ge\u00e7 ilerlemesini \u00f6nler.&nbsp;<em>Proc Natl Acad Sci ABD.&nbsp;<\/em>2008;&nbsp;105&nbsp;: 15902\u20137.<\/li><\/ul>\n\n\n\n<ul><li>Varela I, Pereira S, Ugalde AP, Navarro CL, Su\u00e1rez MF, Cau P, vd.&nbsp;Statinler ve aminobisfosfonatlarla kombine tedavi, insan erken ya\u015flanmas\u0131n\u0131n fare modelinde uzun \u00f6m\u00fcrl\u00fcl\u00fc\u011f\u00fc sa\u011flar.&nbsp;<em>Nat Med.&nbsp;<\/em>2008;&nbsp;14&nbsp;: 767\u201372.&nbsp;<\/li><\/ul>\n\n\n\n<p><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4140030\/\">https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4140030\/<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>&#8220;Bana \u00fcz\u00fclmeniz i\u00e7in kendimi sizin \u00f6n\u00fcn\u00fcze koymad\u0131m. Benim i\u00e7in \u00fcz\u00fclmenize gerek yok. \u00c7\u00fcnk\u00fc beni tan\u0131man\u0131z\u0131 istiyorum. Bu benim hayat\u0131m.&#8220; &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;<\/p>\n","protected":false},"author":394,"featured_media":10911,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[1],"tags":[2147,64,115,2146,956,2142,110,1863],"acf":[],"views":1201,"_links":{"self":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/10910"}],"collection":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/users\/394"}],"replies":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/comments?post=10910"}],"version-history":[{"count":4,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/10910\/revisions"}],"predecessor-version":[{"id":11040,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/10910\/revisions\/11040"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/media\/10911"}],"wp:attachment":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/media?parent=10910"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/categories?post=10910"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/tags?post=10910"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}