RE: Re: DiMauro on fresh vs. frozen

[Guest guest]

You're welcome, Dawn. Just wanted to add my sympathy and prayers for your

domestic situation.

Hugs,

Barbara

_____

From: dawnanich

Sent: Thursday, December 30, 2004 9:48 AM

To:

Subject: Re: DiMauro on fresh vs. frozen

---Thank you so much for posting this valuable information!

Dawn A

In , " Barbara Seaman "

wrote:

> Some of you might be interested in this info from DiMauro on the

MDA site:

>

> QUESTION: Can you tell if a mitochondrial myopathy is or is not

maternally

> inherited by a frozen muscle biopsy alone? What information does a

fresh

> biopsy give as opposed to a frozen biopsy?

>

> REPLY from MDA: Salvatore DiMauro, M.D., Prof. of Neurology, New

York

>

> A frozen muscle biopsy can provide clues suggesting a

mitochondrial DNA

> (mtDNA) mutation and, therefore, maternal inheritance of the

related

> disorder. The clues are of two types: (i) if the biopsy is

adequate for

> histochemistry, evidence of scattered cytochrome c oxidase-

deficient

> (COX-negative) fibers, having a " mosaic " distribution among COX-

positive

> (normal) fibers, is a good indication of a mtDNA mutation, probably

> affecting mtDNA genes involved in protein synthesis (such as tRNA

genes);

> (ii) biochemical analysis of respiratory chain enzymes may reveal

decreased

> activities of those complexes that contain mtDNA-encoded subunits,

i.e.

> complexes I, III, and IV (complex V is not assayed routinely in

frozen

> tissue). This is additional circumstantial evidence of a mtDNA

mutation

> affecting mitochondrial protein synthesis.

>

> A fresh muscle biopsy allows careful isolation of a mitochondrial

fraction;

> the isolated mitochondria can be used to assess respiration and

> phosphorylation using different substrates and an oxygen electrode

> ( " polarographic analyses " ), or to study ATP synthesis from ADP and

> radio-labeled inorganic phosphate (Pi). These studies can provide

> information on the site of a metabolic block in the electron

transport chain

> (complexes I to IV) and on the function of ATP synthetase (complex

V).

>

> ------------

> There is also an interesting 2003 abstract on the subject:

> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

cmd=Retrieve&db=PubMed&list_ui

> ds=12542905&dopt=Abstract

>

> As I understand it, this says something similar to DiMauro but may

be a

> little easier to understand. They both say that complexes I-IV can

be

> assayed in frozen tissue, but to look at overall OXPHOS capacity

one needs

> fresh tissue. According to this abstract of a study in the

Netherlands,

> about 25% of their mito cases do not manifest as specific

deficiencies in

> one of the complexes, but only show up as reduced overall OXPHOS

> capacity--which can only be measured in fresh tissue. If correct,

this would

> mean that 25% of mito patients could only get a diagnosis from

fresh muscle

> tissue. I don't know if all experts agree with these authors (or

their

> percentages) that a person can have normal activity in complexes I-

V and

> still have reduced overall OXPHOS capacity that causes disease.

But this

> distinction may explain why Dr. Korson and others feel some of

their

> patients with typical mito symptoms do have mito in spite of

normal complex

> I-V activity in muscle.

>

> B

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