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Nisan 2010 TUS Sınavındaki Fibronektin Sorusuna Bir Bakış

Değerli arkadaşlar, Nisan 2010 TUS sınavını geride bıraktık. Öncellikle ilk dileğim şu, inşallah herkes hak ettiği ve kendisi hakkında en hayırlı sonucu alır. Bu sınav sonuçta bir sıralama sınavı olduğuna göre, bazı arkadaşlar istediği yeri kazanıp ihtisasa başlayacak, bazı arkadaşlar şansını bir kez daha denemek zorunda kalacak.

Ama bir gerçek var ki TUS’un arkasını kovalayan, bu işi azimle ve doğru bir şekilde sürdüren kişi, Allahın izni ile istediği yere gelecektir.

Bu sınavda biyokimya açısından birçok arkadaşın takıldığı ve cevabı yanlış açıklanmış bir soru vardı. A kitapçığı 31. soru olan fibronektin sorusu.

31. Fibronektin ile ilgili aşağıdaki ifadelerden hangisi yanlıştır?

A) Bir glikozaminoglikandır.
B) Ekstraselüler matrikste bulunur.
C) Fibroblastlar tarafından salgılanır.
D) Kollajene bağlanır.
E) Plazma proteinlerindendir.

Arkadaşlar, aşağıda çeşitli textbook ve yayınlardan derlediğim bazı bilgiler var. Hiçbir kaynakta fibronektinin glikozaminoglikan yani mukopolisakkarit olduğu yazmaz. Bütün kaynaklarda fibronektin’in glikoprotein olduğu açıkça ifade edilmektedir. Dolayısı ile bu soruda A şıkkı kesinlikle yanlıştır. Çünkü fibronektin bir glikozaminoglikan değil, glikoproteindir.

Gelelim ÖSYM’nin açıkladığı E şıkkına. Altta verdiğim örneklerde görüleceği üzere fibronektin hem hücre yüzeylerinde, hem ekstrasellüler matrikste hem de plazmada bulunmaktadır. Plazmadaki fibronektin konsantrasyonu yaklaşık 0,3 mg/ml yani 30 mg/dl ‘dir. (Kaynak; Alan H B WU, Tietz clinical guide to laboratory tests 4.baskı 2006 sayfa 404-405) Sonuçta fibronektinin hem doku kaynaklı, hem de suda çözünür formu olan plazma fibronektini şeklinde iki türü vardır.

Harper 26.baskı Sayfa 537-38

The same cells that secrete collagen also secrete fibronectin, a large glycoprotein present on cell surfaces, in the extracellular matrix, and in blood. Fibronectin binds to aggregating precollagen fibers and alters the kinetics of fiber formation in the pericellular matrix.

Cecil Textbook of Medicine, 21st ed., Copyright © 2000 W. B. Saunders Company

STRUCTURAL GLYCOPROTEINS.

The major non-collagenous glycoprotein present in the extracellular matrix is fibronectin. Fibronectins are dimeric cell adhesion glycoproteins composed of two disulfide-bonded subunits and found in rather large quantities in blood plasma (0.3 mg/mL).

Marks’ Basic Medical Biochemistry: A Clinical Approach, 2nd Edition

Adhesion proteins, such as fibronectin and laminin, are extracellular glycoproteins that contain separate distinct binding domains for proteoglycans, collagen, and fibrin.

Biochemistry of Atherosclerosis Edited by Sukhinder Kaur Cheema, PhD

Memorial University of Newfoundland, St. John’s NL, Canada © 2006 Springer

Human plasma contains soluble fibronectin, a 440-kDa glycoprotein consisting of two similar but nonidentical subunits. Fibronectin plays key roles in cell migration, cell adhesion, hemostasis, thrombosis, wound healing, and tissue remodeling. The fibronectin molecule has distinct domains for interactions with collagen, fibrin, heparin, and DNA. It was recently shown that L-35S-homocysteine targets both fibronectin in human plasma and purified human fibronectin. Sayfa 368

Molecular Biology of the Cell; Alberts

The extracellular matrix contains a number of noncollagen adhesive proteins that typically have multiple domains, each with specific binding sites for other matrix macromolecules and for receptors on the surface of cells. These proteins thus contribute to both organizing the matrix and helping cells attach to it. The first of them to be well characterized was fibronectin, a large glycoprotein found in all vertebrates.

Multiple Forms of Fibronectin Are Produced by Alternative RNA Splicing

There are multiple forms (isoforms) of fibronectin, including one called plasma fibronectin, which is soluble and circulates in the blood and other body fluids, where it is thought to enhance blood clotting, wound healing, and phagocytosis. Plasma fibronectin, for example, which is secreted mainly by liver cells, lacks two of the type III repeats that are found in cell- and matrix-associated forms of fibronectin.

Fibronectin is a larger protein that binds to many molecules, such as collagen, fibrin, proteoglycans, and cell-surface receptors. It consists of two glycoprotein chains, held together by disulfide bonds. Fibronectin mRNA has two splice forms, giving rise to tissue fibronectin and plasma fibronectin.

Plasma Fibronectin Synthesis in Normal and Injured Humans as Determined by Stable Isotope Incorporation

Claudia Thompson, Frank A. Blumenstock, Thomas M. Saba, Paul J. Feustel, John E. Kaplan, John B. Fortune, Lindsay Hough, and Vera Gray Departments of Biochemistry, Physiology, Surgery, and Pharmacology, Albany Medical College, Albany, New York 12208

Fibronectin is a high molecular mass dimeric glycoprotein (450 kD) that circulates in plasma at a concentration of 350-450 ,ug/ml (1-3). Plasma fibronectin mediates macrophage or reticuloendothelial phagocytic clearance of a variety of denatured or foreign particulate materials and Clq containing immune complexes, potentially in the blood after tissue injury, disseminated intravascular coagulation, or sepsis.

Cellular or tissue fibronectin is a less soluble form of fibronectin (4), localized in the extracellular matrix of many cells and in connective tissue matrices (5). Cellular fibronectin influences cell-to-substratum adherence as well as cell-to-cell interactions and accordingly plays a role in tissue integrity (2, 3). Plasma fibronectin is antigenically related to cellular fibronectin but differs especially with respect to subunit structure and solubility (4).

Plasma Fibronectin Levels In Preeclamptic Pregnancies

H. Doğan TÜRE, Sedat KARAOSMANOĞLU, Deniz KÖSE, Coşkun BAYSAL Zeynep Kamil Hastanesi, Kadın Hastalıkları ve Doğum Kliniği

Materials and Methods: This study was made prospectively on 40 preeclamptic and 28 normotensive gravid women between 31-41 gestational weeks. An arterial pressure of 140-90 mmHg or an elevation of 30 mmHg systolic, 15 mmHg diastolic pressure and ≥ 1 g/lt proteinuria on random urine or ≥ 2+ proteinuria on semiquantitative measurement were used as the diagnostic criteria of preeclampsia. Preclamptic cases were divided into two groups as mild preeclampsia (n: 20) and severe preeclampsia (n: 20). Normotenvive cases were used as a control group. Plasma fibronectin levels were measured on Behring plaques quantitatively by the immunodiffusion method.

Findings: Fibronectin concentrations were significantly higher in preeclamptic versus normotensive cases (p< 0.001) and in severe versus mild preeclamptic cases (p< 0.001). When the plasma fibronectin level of 400 mg/ml is acccepted as the cut-off values, sensitivity and the positive predictive values were found to be 72%-87% and 95%-65% respectively for determining preeclampsia and severe preeclamsia.

Results: Vascular endothelial dysfunction is one of the major subjects argued in the pathogenesis of preeclampsia. These findings suggest that plasma fibronectin levels, the determinant of endothelial cell damage, have a high predictive value in the determination of preeclampsia as well as it’s classification into the mild and severe form of the disease.

Diagnostic value of plasma fibronectin level in predicting the presence and severity of coronary arter disease

Authors: Ozcelik, Fatih1; Erdogan, Okan2; Aktoz, Meryem2; Ekuklu, Galip3; Tatli, Ersan2; Demir, Muzaffer4

Source: Annals of Hematology, Volume 88, Number 3, March 2009 , pp. 249-253(5)

The relation between fibronectin and coronary artery disease (CAD) according to previous study results is controversial. The aim of the present study is to investigate the predictive value of fibronectin in determining the presence and severity of CAD. Patients with stable angina (n = 62) who had angiographically documented CAD, and control patients (n = 31) who had normal coronary angiograms, were included in the study. Plasma fibronectin levels were determined in all patients. Plasma fibronectin level (milligrams per liter) in patients with CAD was higher than normal controls (364.2 ± 171 vs 265.1 ± 135.5, p = 0.006). The present study showed that plasma fibronectin level in CAD is significantly higher than normal control subjects.

Bazı arkadaşlar, plazma proteinleri konusu biyokimyada anlatılırken fibronektin orada geçmediği için plazma proteini değildir mantığı ile yaklaşıyor. Değerli arkadaşlar takdir edersiniz ki plazma veya serumda ölçülebilen binlerce protein var. Biz bu alt başlığı anlatırken rutinde en çok kullanılan 40 – 50 tane plazma proteininden bahsediyoruz.

Sonuçta yaklaşık 400 sayfalık bir notla elimizden geldiğince TUS’ta biyokimya da sorulması en muhtemel bilgileri yakalamaya çalışıyoruz. Yoksa biz her sınavda biyokimya ile ilgili her soruyu yaptırabiliriz veya yakalarız diye bir iddiamız yok. Ancak elimizden geldiğince TUS’u kazandıracak % 75-80 soruyu yakalamaya çalışıyoruz.

Takdir sizlerindir. Herkese başarılar dilerim, selamlar…

Dr. Ercan ÖZTÜRK

Bu yazı 8428 defa okundu.


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