Re: Here's and intersting article ...

[Guest guest]

Hi ,

This article is intersting. I am sorry to always ask this but could you put this in lamens terms for me. Sounds like the herpes virus effects the bile ducts thru inflamation contributing to PSC?? My dad with PSC has always had herpes virus 1 (coldsores/fever blisters on the mouth). Thanks in advance.

Lori A.

"Aggressively Pursuing Solutions To Your Real Estate Needs!"

First Weber Group

Cell:

1507 E. Sunset Drive

Waukesha, WI 53189

LoriUSA@...

www.Lori.FirstWeber.com

To: Sent: Thursday, January 29, 2009 11:13:55 PMSubject: Here's and intersting article ...

Here's an interesting article that links a PSC-like disease to a virus infection (murid herpesvirus- 4) in a mouse model, where the mice are defective for the gamma interferon receptor:____________ _________ ____Hepatology Research Volume 39 Issue 2, Pages 187 - 194 (2009)Murid herpesvirus- 4 induces chronic inflammation of intrahepatic bile ducts in mice deficient in gamma-interferon signalling.Babunilayam Gangadharan, 1 * Bernadette M Dutia, 1 M Rhind 2 and A Nash 1 1 Centre for Infectious Diseases, University of Edinburgh, Edinburgh, and 2 Division of Veterinary Clinical Sciences, Royal (Dick) School of Veterinary Studies, Midlothian, UK Correspondence to Professor A. Nash, Centre for Infectious Diseases, University of Edinburgh, Royal (Dick) School of Veterinary Studies, Summerhall, Edinburgh, EH9 1QH, UK. Email: Tony.Nash (AT) ed (DOT) ac.uk * Present address: Neuropathogenesis Division, The Roslin Institute, Edinburgh. KEYWORDSarginase • cholangitis • gamma interferon • gamma herpes virusABSTRACTAim: Infection of gamma interferon receptor defective mice with murid herpesvirus- 4 also known as murine gammaherpesvirus- 68 results in multi-organ fibrosis. In this paper we characterise the pathological changes occurring in the liver in this model.Methods: Standard immunohistochemistr y and in situ hybridisation techniques were used to identify the cellular changes and the presence of virus at different times post infection.Results: In liver sections from infected gamma interferon receptor defective mice sampled on day 16 to at least day 120, 79% showed proliferating intrahepatic bile ducts associated with a chronic

mononuclear cell inflammation. Only 8% of wild type mice showed similar lesions. Coincident with the inflammatory response bile duct epithelial cells were positive for arginase 1. Around day 50 post infection onwards focal fibrotic lesions appeared in approximately 30% of gamma interferon receptor defective mice resulting in destruction of intrahepatic bile ducts. In contrast to the chronic persisting inflammatory response the presence of virus infected cells were only observed between day 12–20 post-infection.Conclusion: Infection of gamma interferon receptor defective mice with a murine gammaherpesvirus initiates a chronic persisting inflammatory response with a pathological profile similar to the human fibrotic liver disorder Primary Sclerosing Cholangitis.____________ _________ ______Dave (father of (23); PSC 07/03; UC

08/03)

[Guest guest]

Hi ,

This article is intersting. I am sorry to always ask this but could you put this in lamens terms for me. Sounds like the herpes virus effects the bile ducts thru inflamation contributing to PSC?? My dad with PSC has always had herpes virus 1 (coldsores/fever blisters on the mouth). Thanks in advance.

Lori A.

"Aggressively Pursuing Solutions To Your Real Estate Needs!"

First Weber Group

Cell:

1507 E. Sunset Drive

Waukesha, WI 53189

LoriUSA@...

www.Lori.FirstWeber.com

To: Sent: Thursday, January 29, 2009 11:13:55 PMSubject: Here's and intersting article ...

Here's an interesting article that links a PSC-like disease to a virus infection (murid herpesvirus- 4) in a mouse model, where the mice are defective for the gamma interferon receptor:____________ _________ ____Hepatology Research Volume 39 Issue 2, Pages 187 - 194 (2009)Murid herpesvirus- 4 induces chronic inflammation of intrahepatic bile ducts in mice deficient in gamma-interferon signalling.Babunilayam Gangadharan, 1 * Bernadette M Dutia, 1 M Rhind 2 and A Nash 1 1 Centre for Infectious Diseases, University of Edinburgh, Edinburgh, and 2 Division of Veterinary Clinical Sciences, Royal (Dick) School of Veterinary Studies, Midlothian, UK Correspondence to Professor A. Nash, Centre for Infectious Diseases, University of Edinburgh, Royal (Dick) School of Veterinary Studies, Summerhall, Edinburgh, EH9 1QH, UK. Email: Tony.Nash (AT) ed (DOT) ac.uk * Present address: Neuropathogenesis Division, The Roslin Institute, Edinburgh. KEYWORDSarginase • cholangitis • gamma interferon • gamma herpes virusABSTRACTAim: Infection of gamma interferon receptor defective mice with murid herpesvirus- 4 also known as murine gammaherpesvirus- 68 results in multi-organ fibrosis. In this paper we characterise the pathological changes occurring in the liver in this model.Methods: Standard immunohistochemistr y and in situ hybridisation techniques were used to identify the cellular changes and the presence of virus at different times post infection.Results: In liver sections from infected gamma interferon receptor defective mice sampled on day 16 to at least day 120, 79% showed proliferating intrahepatic bile ducts associated with a chronic

mononuclear cell inflammation. Only 8% of wild type mice showed similar lesions. Coincident with the inflammatory response bile duct epithelial cells were positive for arginase 1. Around day 50 post infection onwards focal fibrotic lesions appeared in approximately 30% of gamma interferon receptor defective mice resulting in destruction of intrahepatic bile ducts. In contrast to the chronic persisting inflammatory response the presence of virus infected cells were only observed between day 12–20 post-infection.Conclusion: Infection of gamma interferon receptor defective mice with a murine gammaherpesvirus initiates a chronic persisting inflammatory response with a pathological profile similar to the human fibrotic liver disorder Primary Sclerosing Cholangitis.____________ _________ ______Dave (father of (23); PSC 07/03; UC

08/03)

[Guest guest]

Hi Lori;

Sorry for my typo in the title .. I meant to say " Here's AN

interesting article ... " I'll try my best to explain why I found it

interesting.

I need to start by saying that some other " autoimmune diseases "

appear to be triggered by infectious agents, such as viruses. The

best known example of this is multiple sclerosis. When a patient has

a certain genetic background (particularly a certain variant of the

human leukocyte antigen (HLA) gene, HLA-DRB1) and is then infected

with the virus causing infectious mononucleosis (the Epstein-Barr

virus), they are at a greatly increased risk of developing multiple

sclerosis in comparison to non-infected persons with the same HLA-

DRB1 variant, or in comparison to infected persons without the

particular HLA-DRB1 variant.

In other words, there is a strong genotype x environment interaction

in triggering multiple sclerosis. In this case the genotype is a

particular variant of HLA-DRB1, and the environment is the virus.

We know that PSC risk is also associated with a particular variant of

HLA-DRB1. But we do not know the environmental factor that triggers

it. Could it be a virus, as in the case of multiple sclerosis?

I was interested in the article that I posted yesterday because it

dealt with a virus infection in an animal model (mice with a

particular genetic defect), that caused a PSC-like disease. The virus

they were studying was the " Murid herpesvirus-4. " As Barb has already

mentioned the herpes viruses are related to Epstein-Barr virus.

It seems to me (and I'm pretty sure that Barb feels the same way;

correct me if I am wrong Barb!) that we shouldn't rule out an

infectious agent, such as a virus, as a potential trigger for PSC ...

but only in individuals with a particular genetic background (such as

a certain variant of HLA-DRB1).

You are correct that in the mouse model the herpes virus infection

(in the genetically susceptible mice) caused bile duct inflammation

resembling PSC in humans. But whether your Dad's herpes virus

infection could be the cause of his PSC ... I'm sorry I cannot answer

this question with any certainty because there are no equivalent

human studies to go on.

Best regards,

Dave

(father of (23); PSC 07/03; UC 08/03)

>

> Hi ,

> This article is intersting.  I am sorry to always ask this but

could you put this in lamens terms for me.  Sounds like the herpes

virus effects the bile ducts thru inflamation contributing to PSC?? 

My dad with PSC has always had herpes virus 1 (coldsores/fever

blisters on the mouth). Thanks in advance.

>  

> Lori A.

[Guest guest]

Hi

I certainly think that the virus-PSC model is one that is worth

investigating. In the 6-9 months prior to my diagnosis of UC, I had

a variety of GI infections that were treated with antibiotics.

However, when the same symptoms returned, I thought it was a

recurrence of the previous GI infections. Then I was scoped [oh joy]

and I was informed I had UC. Two years later, when my liver function

tests kept skyrocketing, an ERCP confirmed my PSC.

Now of course it's entirely possible that I already had the PSC

longer than that since I recall many years earlier having pain that

radiated from my liver area and upwards to my sternum as well as

towards my right shoulder. [Of course these episodes were so

infrequent that I ignored them ... .] However, it never seemed to

develop into anything further--until the above events that started

in 2002. As it's impossible to turn back the hands of time and see

if I'd still develop everything without the GI infections, I suppose

it would be worth seeing if genetically, I have the genes you

mentioned.

[Guest guest]

Hi

I certainly think that the virus-PSC model is one that is worth

investigating. In the 6-9 months prior to my diagnosis of UC, I had

a variety of GI infections that were treated with antibiotics.

However, when the same symptoms returned, I thought it was a

recurrence of the previous GI infections. Then I was scoped [oh joy]

and I was informed I had UC. Two years later, when my liver function

tests kept skyrocketing, an ERCP confirmed my PSC.

Now of course it's entirely possible that I already had the PSC

longer than that since I recall many years earlier having pain that

radiated from my liver area and upwards to my sternum as well as

towards my right shoulder. [Of course these episodes were so

infrequent that I ignored them ... .] However, it never seemed to

develop into anything further--until the above events that started

in 2002. As it's impossible to turn back the hands of time and see

if I'd still develop everything without the GI infections, I suppose

it would be worth seeing if genetically, I have the genes you

mentioned.