Ιστοσελίδες μαθημάτων

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Ιστοσελίδες μαθημάτων http://kyttariki.biol.uoa.gr , http://multimedia.biol.uoa.gr ΕΙΔΙΚΑ ΚΕΦΑΛΑΙΑ ΚΥΤΤΑΡΙΚΗΣ ΒΙΟΛΟΓΙΑΣ ΕΙΔΙΚΑ ΚΕΦΑΛΑΙΑ ΚΥΤΤΑΡΙΚΗΣ ΒΙΟΛΟΓΙΑΣ Διάλεξη: ΚΛΗΡΟΝΟΜΙΚΕΣ ΔΙΑΤΑΡΑΧΕΣ ΤΗΣ ΕΡΥΘΡΟΚΥΤΤΑΡΙΚΗΣ ΜΕΜΒΡΑΝΗΣ Διάλεξη: ΚΛΗΡΟΝΟΜΙΚΕΣ ΔΙΑΤΑΡΑΧΕΣ ΤΗΣ ΕΡΥΘΡΟΚΥΤΤΑΡΙΚΗΣ ΜΕΜΒΡΑΝΗΣ 11 11 -0 -0 3 3 - - 11 11 Ι. Παπασιδέρη Ι. Παπασιδέρη
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ΕΙΔΙΚΑ ΚΕΦΑΛΑΙΑ ΚΥΤΤΑΡΙΚΗΣ ΒΙΟΛΟΓΙΑΣ Διάλεξη: ΚΛΗΡΟΝΟΜΙΚΕΣ ΔΙΑΤΑΡΑΧΕΣ ΤΗΣ ΕΡΥΘΡΟΚΥΤΤΑΡΙΚΗΣ ΜΕΜΒΡΑΝΗΣ 11 -0 3 - 11 … Ι. Παπασιδέρη. Ιστοσελίδες μαθημάτων. http://kyttariki.biol.uoa.gr , http://multimedia.biol.uoa.gr. ΚΛΗΡΟΝΟΜΙΚΕΣ ΜΕΜΒΡΑΝΟΠΑΘΕΙΕΣ. Αλλαγή της κυτταρικής γεωμετρίας. - PowerPoint PPT Presentation

Transcript of Ιστοσελίδες μαθημάτων

  • http://kyttariki.biol.uoa.gr, http://multimedia.biol.uoa.gr

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    11-03-11

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  • 1:3.000 (. ) (75%) (Sp, 4.2, / .) ()

  • : ()

  • OFT MCHC ( )

    (10% )

    rEpo ()

  • HS MSk (n & Mohandas, Br.J.Haematol., 141(3):367, 2008) ()

  • band 3 SLC4A1RhAG RH, RHAGankyrin ANK1protein 4.2 EPB42spectrin SPTB, SPTA1(n & Mohandas, Br.J.Haematol., 141(3):367, 2008) (3, RhAG) (ank, 4.2) HS ()

  • Loss of membrane surface area (severity of anemia)Discocytes stomatocytes spherocytesUnable to traverse the spleen ()

  • (Gallagher PG; Hematology Am Soc Hematol Educ Program, 2005;13-18) Loss of membrane-surface area ()

  • Human 4.2(-)HS CD47 (80%-) Mouse ank(-)HS (-) Rh, (-)RhAG ()

  • HS, de novo ( ) ( )Mild to severe clinical severitySDS-PAGE: ank/Sp/4.2 ( ), . ()

  • SPT1(-)HS HS, / ( ) ()

  • RBCs/ - E HS M (cyt/TM)SDS-PAGE: 20-40% -3 ( 4.2, CD47)3 (viable)3 Coimbra-Western: 3, / (-) 4.2, G3PD, Sp, ank1 M ( ) ()

  • SLC4A1(-)HS -3 ()

  • 3 ()(1) Red cell-specific disease: HS, SAO, Hst(2) Kidney-specific disease: Distal Renal Tubular Acidosis (dRTA)Defective acid secretion to urine by the -intercalated cellsMetabolic acidosis, hypokalaemia, metabolic bone disease () (dRTA) - , ,

  • (Williamson & Toye, BCMD, 2008)1st homozygous individual(Ribeiro et al., Blood, 2000)Near lethal, Anemic, HS*/dRTA, traces B3, Most dRTA mutations of B3 do not cause RBC phenotype due to the presence of GpA

  • ( )SDS-PAGE: , (ovalocytes, stomatocytes, RBCs, ), OFT 7 NH2- ( 3)4.2 ippon (GCTACT, Ala42Thr) () ( HS)/ 4.2(-) (3-complex) CD47 (Rh-complex) ( (-)) ()

  • RhAGMild to moderate hemolytic anemiaBetween stomatocytes and spherocytes Rh-complex (association with ankyrin, 4.2): Rh null syndrome = HS(Nicolas et al., Transf Clin Biol 13:23, 2006) ()

  • DD2(-)HS -adducin, JC (Sp/actin) : , - ()

  • 10% HS ()

  • 0,25m0,35m(Reinhardt et al., 2001; BCMD 27:399)E HS ()

  • : (b4.2) 90%actin (b5) 40%G3PD (b6) 40%band 8 65%hemoglobin (Hb)* >85%IgGs 80%(Margetis P, Antonelou M, Karababa F, Loutradi A, Margaritis LH, Papassideri I, 2007; BCMD 38:210)25% HS = sorcin37% HS = cyt peroxiredoxin-2(Rocha et al., BCMD, 2008) ()

  • (Margetis P, Antonelou M, Karababa F, Loutradi A, Margaritis LH, Papassideri I, 2007; BCMD 38:210) ()

  • MCHC(Margetis P, Antonelou M, Karababa F, Loutradi A, Margaritis LH, Papassideri I, 2007; BCMD 38:210) ()

  • / Ca++ LR HS( )(Margetis P, Antonelou M, Karababa F, Loutradi A, Margaritis LH, Papassideri I, 2007; BCMD 38:210) ()

  • : 1/5.000-1/10.0002% malaria regions (west Africa) de novo ()

  • (asymptomatic to hydrops fetalis)10% patients: moderate to severe anemia Heterozygous: asymptomatic HEHomozygous or compound heterozygous: mild to severe HE (HPP hereditary pyropoikilocytosis) ()

  • RBCs % .(n & Mohandas, Br.J.Haematol., 141(3):367, 2008)Poikilocytes, fragmented RBCselliptocytesSevere anemia ()

  • SpT The severity of the disease is directly related to the extent of the decrease in membrane mechanical stability (S) ()

  • (n & Mohandas, Br.J.Haematol., 141(3):367, 2008) ()

  • Sp (95% of all H cases) ( ) ( )SpT SpD, - (Pro, Gly) Sp (HS), ()

  • O (1-8, 15-17) ( )20 aHE , - ()

  • Sp ()

  • SPTA1-65% of HE casesSDS-PAGE: (-)Sp , , 2 -Sp, SPT, COOH -Sp, LELY -30% of HE cases: (.hydrops fetalis)SDS-PAGE: (-)Sp , truncated variants - ()

  • 4.1RE, / ( ) (100%) 10 ( , (-)) Sp/Actin (-)Sp/actinM COOH-: 70Kb 5% of HE cases 4.1R ()

  • 4.1R 4.1R, GpC p55 (70%) ()

  • GpC(-)HE ( Leach)A 4.1R p55 ( 4.1/GpC/p55 ) (GpC/GpD) - : Gerbich, Yus, Webb ( ). cyt ()

  • - (moderately severe severe) , , Stomatocytes: major feature ofRBC morphology on blood smears( ) ( ), ( MCV) MCHC ( HS)

    1/100.000, dominant inheritance (

  • M ??????????Spleen sequestration of stomatocytesMechanistic basis of OHS: Stomatocytes: +, (

  • (7.2b, LR), 72 ( 24 ) OHS: : , , (

  • Red cell membrane transport defect, cation homeostasis, cell water content : Hereditary xerocytosis cell water content cell volume net cation content cell water content cell volume : 1/50.000 (10-20x HS) ()

  • 16q23-qter ( ) (- K+ RT) Well-compensated anemia, borderline macrocytosis, mild to moderate enlarged spleenBlood smears: usually less than 10% stomatocytosisRBC dehydration, increase in MCHC, decreased osmotic resistance ()

  • (L. Bruce, BCMD 2006, 36:331)T 3 ereditary Stomatocytosis and Band 3 HSt

  • Ko (5-25%) (, ., )Protection against all forms of malariaNo (Southeast Asian Ovalocytosis, SAO) (O)

  • Infected RBCs (O)

  • - RBCs ( .)elliptocytes ovalocytes (O)

  • - ( , )(Homozygosity may lead to embryonic or fetal lethality) (O)

  • 27nt SLC4A1, 9 (400-408) cyt TM1 , , 3, Tyr SAO : , / (O)

  • -3 ??? 3 Sp (O)

  • /