�Molecular perceptivity into one form of the hemorrhage disorder von Willebrand disease
Individuals with von Willebrand disease (vWD) are at increased risk of bleeding compared with intelligent individuals, for example, they tend to bruise more than easily and suffer more nosebleeds and bleeding gums. There ar four types of transmitted vWD, and type 2B vWD is caused by genetic mutations that resolution in the generation of mutant forms of the protein vWF that differ from normal vWF in a area of the protein known as the A1 arena. A team of researchers at Georgia Institute of Technology, Atlanta, and Oklahoma Medical Research Foundation, Oklahoma City, has now characterized in great molecular contingent how the function of mutant forms of vWF found in individuals with type 2B vWD and normal vWF differ, providing insight into why these mutant proteins cause an increased risk of bleeding. In an accompanying comment, Michael Berndt, at the University College Cork, Ireland, and Robert Andrews, at Monash University, Australia, discuss the importance of these results.
TITLE: Platelet glycoprotein Ib-alpha forms catch bonds with human WT vWF just not with type 2B von Villebrand disease vWF
AUTHOR CONTACT:
Cheng Zhu
Georgia Institute of Technology, Atlanta, Georgia, USA.
Roger P. McEver
Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
View the PDF of this article at: https://www.the-jci.org/article.php?id=35754
ACCOMPANYING COMMENTARY
TITLE: Platelet adhesion: a game of catch and release
AUTHOR CONTACT:
Michael C. Berndt
University College Cork, Cork, Republic of Ireland.
View the PDF of this article at: https://www.the-jci.org/article.php?id=36883
Insight into the physiological role of the blood protein Factor XII last revealed
The organization of a blood clabber is the culmination of a series of events that involve a telephone number of proteins in the bloodstream, including Factor XI, which is one of the proteins activated early on in this cascade of events. Surprisingly, Factor XI is activated in different shipway in the body and in a glass screen tube. In a glass test tube, Factor XI is activated by a protein known as Factor XII, which is itself activated when it comes into contact with the glass. However, Factor XII plays no role in Factor XI activation in the torso and its physiologic function and mechanism of activation have non been determined.
New data, generated by Martijn Gebbink and colleagues, at the University Medical Center Utrecht, The Netherlands, ingest identified the aggregates of misfolded proteins present in the rip of individuals with systemic amyloidosis (a disease in which misfolded blood proteins are abnormally deposited in organs and/or tissues, causing disease) as activators of Factor XII. Interestingly, activation of Factor XII by isolated misfolded proteins and misfolded proteins in the blood of individuals with systemic amyloidosis did not trigger the cascade of events that lead to blood curdle formation. Rather, it triggered another series of events known as the kallikrein-kinin system, which influences the inflammatory reaction. In an accompanying comment, Alvin Schmaier, at Case Western Reserve University, Cleveland, discusses these results in the circumstance of previously published data.
TITLE: Misfolded proteins activate Factor XII in humans, leading to kallikrein formation without initiating coagulation
AUTHOR CONTACT:
Martijn F.B.G. Gebbink
University Medical Center Utrecht, Utrecht, The Netherlands
.
View the PDF of this article at: https://www.the-jci.org/article.php?id=35424
ACCOMPANYING COMMENTARY
TITLE: The elusive physiologic role of Factor XII
AUTHOR CONTACT:
Alvin H. Schmaier
Case Western Reserve University, Cleveland, Ohio, USA.
View the PDF of this article at: https://www.the-jci.org/article.php?id=36617
Source: Karen Honey
Journal of Clinical Investigation
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