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Parkinson’s as Autophagy Failure

Posted: May 18, 2010 at 8:17 am

Autophagy is important in determining life span, probably because of its role in clearing out damaged mitochondria (a process known as mitophagy) before they can cause other forms of harm. Here is evidence for that view in the form of a link between Parkinson’s disease and autophagy: “Mutations that cause Parkinson’s disease prevent cells from destroying defective mitochondria … Defects in the ubiquitin ligase Parkin are linked to early-onset cases of this neurodegenerative disorder. The wild-type protein promotes the removal of impaired mitochondria by a specialized version of the autophagy pathway called mitophagy, delivering mitochondria to the lysosomes for degradation. Mitochondria are often dysfunctional in Parkinson’s disease … cells expressing mutant forms of Parkin failed to clear their mitochondria after the organelles were damaged. Different mutations blocked mitophagy at distinct steps: mitochondria accumulated in the perinuclear region of cells expressing Parkin lacking its ubiquitin ligase activity, for example. The researchers found that ubiquitination of defective mitochondria by Parkin normally recruits the autophagy proteins HDAC6 and p62 to clear these mitochondrial aggregates. … The clearance of defective mitochondria is therefore similar to the removal of damaged proteins, another autophagic process that goes wrong in Parkinson’s disease resulting in the accumulation of toxic protein aggregates. Both pathways rely on microtubules, HDAC6, and p62, [providing] a common link between the two main features of the neurodegenerative disorder.”

View the Article Under Discussion: http://www.eurekalert.org/pub_releases/2010-05/rup-mtc050610.php

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

Recommendation and review posted by Fredricko

Parkinson's as Autophagy Failure

Posted: May 18, 2010 at 8:17 am

Autophagy is important in determining life span, probably because of its role in clearing out damaged mitochondria (a process known as mitophagy) before they can cause other forms of harm. Here is evidence for that view in the form of a link between Parkinson’s disease and autophagy: “Mutations that cause Parkinson’s disease prevent cells from destroying defective mitochondria … Defects in the ubiquitin ligase Parkin are linked to early-onset cases of this neurodegenerative disorder. The wild-type protein promotes the removal of impaired mitochondria by a specialized version of the autophagy pathway called mitophagy, delivering mitochondria to the lysosomes for degradation. Mitochondria are often dysfunctional in Parkinson’s disease … cells expressing mutant forms of Parkin failed to clear their mitochondria after the organelles were damaged. Different mutations blocked mitophagy at distinct steps: mitochondria accumulated in the perinuclear region of cells expressing Parkin lacking its ubiquitin ligase activity, for example. The researchers found that ubiquitination of defective mitochondria by Parkin normally recruits the autophagy proteins HDAC6 and p62 to clear these mitochondrial aggregates. … The clearance of defective mitochondria is therefore similar to the removal of damaged proteins, another autophagic process that goes wrong in Parkinson’s disease resulting in the accumulation of toxic protein aggregates. Both pathways rely on microtubules, HDAC6, and p62, [providing] a common link between the two main features of the neurodegenerative disorder.”

View the Article Under Discussion: http://www.eurekalert.org/pub_releases/2010-05/rup-mtc050610.php

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

Recommendation and review posted by Fredricko

US Patent: Isolation and use of solid tumor stem cells

Posted: May 18, 2010 at 8:17 am

Isolation and use of solid tumor stem cells, United States Patent 7,713,710. [FreePatentsOnline][PatentStorm].
Publication Date: May 11, 2010.
Inventors: Clarke; Michael F. (Ann Arbor, MI), Morrison; Sean J. (Ann Arbor, MI), Wicha; Max S. (Ann Arbor, MI), Al-Hajj; Muhammad (Ann Arbor, MI).
Assignee: The Regents of the University of Michigan (Ann Arbor, MI) .
Appl. No.: 11/753,191
Filed: May 24, 2007
Abstract:

A small percentage of cells within an established tumor have the properties of stem cells. These solid tumor stem cells give rise both to more tumor stem cells and to the majority of cells in the tumor that have lost the capacity for extensive proliferation and the ability to give rise to new tumors. The solid tumor heterogeneity reflects the presence of tumor cell progeny arising from a solid tumor stem cell. This discovery is the basis for solid tumor stem cell compositions, methods for distinguishing functionally different populations of tumor cells, methods for using these tumor cell populations for studying the effects of therapeutic agents on tumor growth, and methods for identifying and testing novel anti-cancer therapies directed to solid tumor stem cells.

Parent Case Text:

CLAIM OF PRIORITY
This application is a Continuation of U.S. patent application Ser. No. 11/150,073, filed Jun. 10, 2005, which is a Continuation of U.S. patent application Ser. No. 09/920,517, filed Aug. 1, 2001, now U.S. Pat. No. 6,984,522, which claims priority to U.S. provisional applications Ser. No. 60/222,794, filed Aug. 3, 2000, and Ser. No. 60/240,317, filed Oct. 13, 2000, all of which are herein incorporated by reference in their entireties.

Google patents entry for Application Number 11/753,191 (The application that led to patent 7,713,710. The filing date was 24 May 2007).

Google patents entry for Application Number 11/150,073 (See Parent Case Text above: the filing date was 10 June 2005).

Google patents entry for Patent Number 6,984.522 (See Parent Case Text above: the filing date was 1 August, 2001 and the issue date was 10 Jan 2006). [FreePatentsOnline][PatentStorm].

Comment:

Not mentioned in the Parent Case Text above is United States Patent 7,115,360. [FreePatentsOnline][PatentStorm]. This patent was issued October 3, 2006 and filed on August 2, 2001.

The Parent Case Text for patent 7,115,360:

CLAIM OF PRIORITY
This patent is the United States national stage of PCT patent application PCT/US01/24243, published Feb. 14, 2002 as WO 02/12447, which is a continuation of U.S. Ser. No. 09/920,517, filed Aug. 1, 2001, now U.S. Pat. No. 6,984,522. This patent also claims priority to provisional patent applications U.S. Ser. Nos. 60/222,794, filed Aug. 3, 2000, and 60/240,317, Oct. 13, 2000.

Information about this patent was found via a Google search for “Isolation and use of solid tumor stem cells”.

Recommendation and review posted by Fredricko

Hospitalist evolution? "Extensivist" = hospitalist who prevents readmissions by seeing patients after discharge

Posted: May 18, 2010 at 8:15 am

“On a typical morning, Sandip Patel, MD, a hospitalist employed by a health plan in Southern California, rounds on patients at the hospital, then meets with case managers and a medical director to review care plans and decide which patients will stay or go.

In the afternoon, Dr. Patel may see recently discharged patients—those coded “red” or “yellow,” based on medical complexity—at an integrated-care center, which is also owned and run by the health plan. Then he might head to a nursing home to check on patients discharged a week ago.

Dr. Patel considers himself an “extensivist” with a goal to reduce readmissions. “Lowering readmission rates is within the purview of the hospitalists.”

References:
Health-plan hospitalists cut readmissions—by sometimes leaving the hospital. Today’s Hospitalist, 2010.

Image source: sxc.hu

Posted at Clinical Cases and Images. Stay updated and subscribe, follow us on Twitter and connect on Facebook.


Recommendation and review posted by G. Smith

Potential of genomic medicine, LOST

Posted: May 18, 2010 at 8:14 am

I was reading and often read Mark Henderson of the Times



The piece basically comes down to one conclusion.

We have no proof that most of this stuff is useful in any form.

This is something that I have been shouting from the roof tops ever since some self deluded socialite from Mountain View decided to say “Genetic testing is for fun”

Seriously DTCG. You knew this day was coming. You tried to play yourself off as hip, cool, sexy/ Yet at the same time to avoid regulation you played, not serious, not clinical, and in essence, not valuable.

I was deeply concerned about precisely this issue. By putting yourselves out there as an invalid in the clinical world, you cheapened the field and some of the tests that you offered.

Because of this conglomeration of useless with useful, the field of medicine and healthcare as a whole needs to create systems to sift between marketing and PR spin/hype from truth and medical utility.

Luckily in the US we have such a system EGAPP. We also have things such as the CPMC ICOB. But in England, they have no such official system.

What is even more troublesome is the lack of clinical utility of such tests and lack of funding to evaluate the utility. The problem with this rush to market the next GWAS is emblematic of this over hype cycle that exists in medical science.

Why?

Medical scientific discovery can or cannot be useful in medicine.

That is all.

Saying something promotes “Health” rather than treats,cures, prevents or diagnoses disease to avoid regulation confuses the public and unsophisticated venture capital. Which really makes me wonder if that is what you had intended in the first place……..

What should have been said is “These tests have not been proven to prevent/diagnose/treat disease nor have they been proven to aid in healthcare

But that probably wouldn’t have sold many kits……Thus the problem with medicine, you can’t just “fake it” with Time Magazine…….

What your “faking it” has done is created a hornets nest on both sides of the pond with governments scrambling to decide what matters.

Caroline Wright, head of science at the PHG Foundation, said: “The heart of the problem is that we do not have enough data on whether these tests actually help patient care. We desperately need the equivalent of clinical trials for diagnostics.”

Further, the UK doesn’t have a team equivalent to EGAPP over here. Which BTW, K.O. if you are listening, I would love to be a part of…”I’m just saying……”

We need to ask ourselves as Andrew Yates points out, what results can we expect when the average death percentage over time in this country or any others is 100%

Will a flashy test keep you alive longer? Not if it has no clinical data proving that it does.

No amount of blimps and SoHo parties will prevent death or disease. Sorry.

The Sherpa Says: The Quake paper was their best shot of integrating this into clinical care and they are arguing about whether or not to put him on a prophylactic statin? Which BTW has no evidence behind it……..Personally I think that shot was misfired……

Recommendation and review posted by G. Smith

TED video: CIO of Cleveland Clinic talks about electronic medical records (EMR)

Posted: May 18, 2010 at 3:37 am

Video – TEDxCLE – Dr. C. Martin Harris, CIO of Cleveland Clinic talks about EMR. The Cleveland Clinic uses Epic Systems EMR and, although the system costs millions of dollars to purchase and maintain, it has been perceived as very useful by both physicians and patients.

Disclaimer: I was a Clinical Assistant Professor of Medicine at the Cleveland Clinic until 2008.

Posted at Clinical Cases and Images. Stay updated and subscribe, follow us on Twitter and connect on Facebook.


Recommendation and review posted by G. Smith


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