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DISCUSSION 
CHAIRMAN KussEROW: Thank you, Dr. 
Thomas, I think after hearing Dr. Thomas, we 
will start worrying the moment that we swal- 
low the next glass of milk, if things start as 
early as he says. 
Keith McCullagh, Cleveland Clinic : I won- 
der, Dr. Thomas, whether you can speculate as 
to the cause of the increase in protein synthesis, 
oxygen uptake, and everything else. Is the lipo- 
protein, which is infiltrating the wall, di- 
rectly stimulating these events, or is it an indi- 
rect effect of cell death where the necrotic cell is 
releasing an activating factor? 
Dr. Thomas : Well, that is certainly an inter- 
esting question that goes right to the heart of 
the matter. One way of looking at it is that we 
are simply dealing with injury. In some un- 
known way, the cholesterol diet is damaging 
vessels, then all we see is repair, more damage, 
and more repair, and so on down the line. 
That's a hypothesis. I liked it better myself be- 
fore we found the increase in the number of 
cells that were dividing so very, very early. I 
would like to have seen more injury followed by 
the increase than we saw, but we haven't found 
it that way so far. We know, however, that with 
any type of injury, repair starts almost immedi- 
ately. So that doesn't rule it out. 
You asked for speculation, so I'll speculate on 
another thing. There are some interesting "sub- 
stances" that have been described as regulating 
the rate of multiplication of cell growth in skin 
and a number of other tissues which are some- 
times referred to as chalones. They haven't been 
identified well enough really to glorify them 
with a name. But whatever it is, there is a prop- 
erty of tissue extract (skin for example) that 
will decrease the rate that cells divide or syn- 
thesize DNA in some animals. This is one spec- 
ulation that we've made in our own laboratory. 
There may be a substance normally present that 
is involved in the control of the division rate of 
arterial smooth muscle cells. Then somehow or 
other, the cholesterol changes in the blood inter- 
fere with this action and allows the cell to di- 
vide faster. We've been looking for this sub- 
stance, and we think we have found it. That 
doesn't prove the theory; it is a speculation. 
Dr. Blackshear : Did you look at the oxygen 
saturation curve with and without high choles- 
terol to see what the P450 shift was in the two 
cases ? 
Dr. Thomas: The oxygen uptake studies, 
studies of isolated mitochondria and so on, were 
done in my laboratory by other people. I'm 
afraid I can't answer that. Mitochrondrial func- 
tion was one thing we thought might be wrong. 
Others have suggested that there was an uncou- 
pling or a partial uncoupling of the mitochon- 
dria which might lead to some of these events, 
but we have not been able to see that. The mito- 
chrondria in vitro appear to be as well-coupled 
as they are in the controls. 
