Tuesday, September 10, 2013

Clinical genetic questions in Hepatitis

As we discuss deeper about the NOTCH and its activity, one of the disease syndrome that comes to mind is the pathobiology of conditions such as Hepatitis. we know the NOTCH is involved in both cellular membrane events as well epigenetic phenomena in the cell.  By epigenetic phenomena, we would consider cytokines/growth factors production as a result of gene activity in this are of the cell.  The NOTCH delve into these activities heavily. Cell to cell contacts and adhesion, loss of tissue boundaries and eventual transformation in recalcitrant Neoplasms are all potential activities of the NOTCH at liver lesion.
In Hepatitis, "liver injury is thought to be mediated by a strong cytotoxic T cell mediated reaction against infected hepatocytes that express viral Antigens at their surface". (Wedemer et al).  Well T cell differentiation is ensured by The NOTCH.
Viral entrance in the cell occurs at the menbrane, the cell membrane where the NOTCH is ultimately located, the cell membrane where all receptors, Metalloproteases and ADAMS12 have been discussed to be active.  The NOTCH is very much present.
Other aspects of interest in this disease are the chronicity of certain viral hepatitis and their leading to Cirrhosis which include an unfortunate commitment to disorderly nodular regeneration as if pushed by the NOTCH.  The fact that it does not occur in Hepatitis A is an exciting observation.  Is there links to the single RNA nature of the Virus instead of a larger Double stranded gene material of the Hepatitis B.  Is this linked to certain the silencing of certain Histocompatibility Antigens.  We know that Fulminant disease expression might be linked to HLA expression as well as patterns of gene silencing by epigenetic events.   Attack of cytokines of self tolerance mechanisms of defense have been insufficiently studied, basically until we re-examine this disease at molecular level, progress in this are will be profoundly limited.  We tend to stop our interest as soon as a vaccine has been developed (such as in in Hepatitis A ).
NOTCH activity in this disease is a legitimate target of studies...At CRBCM, we keep this in mind while fighting BAYLOR University Tissue bank which until now is trying to stop our research progress, using CPRIT funds (Texans'money).   In life never dismiss the weak!
A coalition will fight until the end for its cause...let it be known!

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