There are a number of different artifacts that have come to be called 
nuclear bubbling. Denaturation in its mildest forms looks like bubbling 
(hypochromatic spots) and can be caused by heat or by unfixed tissue coming 
into contact with a non-aqueous solvent like xylene. In its extreme form 
denaturation looks like complete loss of cellular detail and cells tend to 
have hyperchromatic membranes with hypochromatic nucleo- and cytoplasm. 
This artifact is irreversible. There are at least two other types of 
bubbled or foamy nuclei. Both tend to be called "formalin artifact" by some 
pathologists (particularly pathologists attached to mercury fixatives). One 
does seem to be some sort of fixation inadequacy and can be ameliorated by 
post-fixing the cut slide. The second is actually inadequate 
deparaffinization or saturated xylene in the dewaxing runs. It tends to 
show up in skin and lymph node tissues first (or most noticeably). It is 
entirely reversible with clean xylene or more dewaxing time. Luna covered 
the denaturation artifacts in a number of his books (my handy reference is 
"an atlas of artifacts", Thompson and Luna).
The foamy nuclei issue (perhaps because it is so conveniently dismissed as 
a formalin fixation problem) is less well documented and the 
recommendations are from my experience in the lab.

Bert Dotson

-----Original Message-----
From:	Janice Mahoney [SMTP:jmahoney@alegent.org]
Sent:	Wednesday, June 14, 2000 1:19 PM
To:	histonet@pathology.swmed.edu
Subject:	nuclear bubbling

Hello,
Does anyone have any references regarding the causes of nuclear bubbling 
other than excess heat?  your help is greatly appreciated.
Jan Mahoney
Omaha