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I am a little late posting Nov 98, but I wanted to prepare a change in format to
take greater advantage of the wonders of the net and the availability of JVS and
JCI e-articles on line. From now on, you can link directly to the paper cited:
#1. Curci JA, Petrinec D, Liao S. Golub LM, Thompson RW. Pharmacological
suppression of experimental AAA: A comparison of doxycycline and four
chemically modified tetracyclines.
Comment by MDT: Thompson and his asscociates continue their fine
laboratory investigations with study of substituted doxycycline derivatives, in
search of a non-antibiotic chemically-modified tetracycline that would be as
efficacious as doxycycline (DOX) in the prevention of AAA in the Anidjar/Dobrin
model. The rationale derives from the information that the molecular site
that confers antibiotic activity is different from the site with anti-MMP activity.
There were no significant differences between DOX and the others. These
observations also support the hypothesis that MMP's are important enzymes
in the matrix degradation of aorta that occurs in AAA.
2. Hamano K, Kuga T, Takahashi M, et al. The lack of type III collagen in a
patient with aneurysms and an aortic dissection.
Comment by mdt: The patient was a 55 y/o man with AAA and aortic dissection, who
was the only patient among 79 studied who was found to lack type III collagen. He did
not have clinical features of ED syndrome, although his skin did not have detectable
levels of type III. We also considered a possible abnormality of type III in a single
patient with AAA in 1988, as described in our paper on molecular heterogeneity in
AAA disease (Arch Surg 1988; 28: 385).
The first mutation in type III collagen that was proven to co-segregate with AAA disease in a family was reported by Kontusaari et al in 1990 (JCI; 86:1465). The following year I
speculated that the first and other patients with type III mutations might someday come
to be regarded as a subtype of ED IV, without the usual physical diagnostic features.
I believe that Kontusaari et al have sequenced the type III gene in quite a few patients,
and they have reported only one additional case. Thus ED IV is a small subset of the
overall problem of AAA.
It is interesting that total lack of expression of type III may be better tolerated than a
point mutation, probably because of the phenomenon referred to by Darwin Prockoff
as protein suicide.