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Maternal floor infarction of theFrom: Terrence.Jones@ncal.kaiperm.orgThu Dec 31 18:10:54 1998
Luis, in the interest of time, which is lurking somewhere in the depths of the charts piled about me, will skip the ref's as You probably have 'em. My guess is MFI is related to MBP (major basic protein) binding to the chondroitin-SO4 moiety of thrombomodulin resulting in diminished enhancement of Thrombin binding. This then inhibits Protein C zymogen cleavage. The result being that Thrombin is now free to cleave fibrinogen and activate platelets. As the MBP is secondary to proliferation of placental X cells, the effect is most prononced at the trophoblast-decidual border. Had wanted to present this info at three recent M&M conferences, but got stuck in L&D each time, so have not had an opportunity to have this critically scrutinized. To take things further: as "polyanionic", heparin might serve a dual role - to promote AT-III fibrinolysis and VIII/TF suppression; along with electrostatic binding to (highly cationic) MBP? As cellular component of perivillous fibrin depostition is not accentuated, would wonder about the benefit of antiplatelet therapy in this setting (ie low dose ASA). Particularly since ASA works via cyclo- oxygenase inhibition, and has no impact on thrombin mediated platelet aggregation. Peter, whose grace has no bounds, as evidenced by his restraint after Thomas' unbridled ebullience over a 'sticky wicket'; was kind to mention my post from 1996. I think Luis was referring to a more recent thread which I had to let pass due to time constraints. This was from Richard Roberts (11/19/98) on AFLP, trifunctional protein deficiency and related fatty acid B-oxidation dysfunction, and their association with SIDS, myopathy,etc. Richard was fortunate to attend the March '98 Am Coll Med Genetics Mtng where Drs Ibdah (Wake Forest), Bennett (Dallas), and Rinaldo (Yale) had pooled their data on this topic (see also Pediatrics 1998, 132:913-14). Dr. Carpenter, in his f/u post 11/23/98 mentioned the work of Dr. Treem as well, in this field. Dr. Roberts further described the findings in OMIM on this topic: a good idea to review TFP (trifunctional protein deficiency) clinical features prior to taking the next step - searching for a connection to MFI (maternal floor infarct). Dr. Copel (of SVT fame) first mentioned the assoc of AFLP and LCAHD and was kind enuf to post Dr. Piero Rinaldo's e-mail address at Yale (see post from 1/12/96). In addition to testing Mom & Dad for specific defect(s), there is an option for prenatal diagnosis (Chalmers 8/97, J Ped 131:220-5) by testing fatty acid oxidation (Pourfarzam Clin Chem 12/94, 40:2267-75) in cultured amniocytes or (if anterior placenta) cultured chorionic villous cells. Careful, with CVS: if extended culture is required, and results suggest heterozygosity, confirm with molecular studies to r/o maternal contamination (Christidoulou 12/96, Am J Med Gen 66:21-4). You mentioned the hyperechogenic areas in the placenta, and have most likely seen the sono images from Terry Siddiqi and his crew in Cincinatti (O/G 5/94, 83:750-4). 'Member, only 2 of the 13 had the entire triad (Oligo, IUGR, Placental echogenicity) -- Any evidence of placental 'thickening' (see figure 3 on pg 752)? Might want to check with the folks in Cincinatti about any f/u experience with doppler in this setting, over the past 4-5 yrs. Step back for a minute, and reflect back on the evolution of our under- standing of MBP. The early studies from Mayo included such names as Coulam and Benirshke. Now Oxvig & Gleich have emerged, from contributors, to novel investigators. Do try and get their paper from J Biol Chem 6/95, 270:13645- 51. They constructed a mAB (monoclonal AB) against ProMBP (which is complexed in the X cell {AND the eosinophil} with PAPP-A (--> recognize Dr. Oxvig's work with this marker and first trimester aneuploidy detection?)). Using SDS-PAGE they isolated two additional complexes with ProMBP. These include angiotensin and complement C3dg. Turns out C3dg and EBV share the same target receptor in the B cell, CD21, which triggers activation. C3dg's been shown to have effects on platelet aggregation (Chen 2/94, J Immunol 152:1332-8), as well. CD21 has been assoc with an interesting liver lesion -- "Inflammatory Pseudotumor of the Liver" (Selves 6/96, Am J Surg Pathol 20:747-53). The spindle cells in this lesion are derived from FDRCs (follicular dendritic reticulum cells). So, maybe some complexed MBP happens upon a kupfer cell, triggers an inflam- matory response that pushes some poor vulnerable heterozygote hepatocyte over the edge, and the fatty acids start piling up in the cytoplasm. Next, albumen levels drop and fatty acids start heading into the circulation. Here they promote thrombosis (Hoak 5/97, Am J Clin Nut) which is inversely related to the (now decreasing) serum albumen concentration. Wonder re: complexed ProMBP & angiotensin? Who knows, I gotta' go get my Son; seems for every moment that passes, I get further behind! - now to find out there's another year before the next millenium?! Eberhard - You hang in there Buddy, We need Your perspective (tho some don't always express this!). The rest of Ya' - have a Happy (and safe) New Year! (No matter WHO has the ashes. Fair dinkum!) tj.
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