Biology 446    Unsolved Problems Fall 2011


(An excellent quote from the third LoTR movie)

"The day may come when the courage of men fails;
When we forsake our friends and break all bonds of fellowship.
But it is not this day."


Regarding the disease discussed in class on Wednesday, October 26, 2011


Because I have only the most amateurish understanding of this disease, & don't want any web searches about it leading to this course web site, let us call it JQG. (from the letters alphabetically adjacent).

The following fact-like statements have been gathered from web sites. The Wikipedia site is excellent!

This disease kills half of its victims by only three years after first symptoms! It kills about 20 people per hundred thousand. In England, over 5,000 people per year die of it, which is said to be slightly more than die of leukemia or ovarian cancer. (!?)

Despite being defined by its cause not being known (and no good ideas for treatment, either!), it turns out not to be just a grab-bag of different diseases, but has very consistent and well-defined symptoms.

My more-than-tentative conclusions are:

#1) That JQG has a specific cause, which is either over-secretion of type I collagen, or excess traction forces exerted on collagen by the mesenchymal cells in between the alveoli of the lungs.

#2) That some positive feed-back occurs, in which tighter packing of collagen either stimulates more secretion of collagen and/or stimulates stronger traction (maybe more actin, more myosin, phosphorylation of myosin chains, among other possibilities). Ironically, "traction bronchiectasis" is a radiological synonym for "honeycombing", which is the most characteristic geometric abnormality of JQG.

(I don't understand in what sense the word "traction" is meant, here. The force of crawling cells?)

#3) JQG is very different from emphysema - opposite to it in several key ways. [Less fiber matrix.]

In emphysema, there is a collapse of elasticity of extracellular matrix (which is collagen, plus elastin).

"-air sacs unable to hold their functional shape upon exhalation." QUOTE from the Wikipedia article.

That seems to me to be opposite to excess rigidity of extracellular fibrous support of alveoli: JQG.

The Wikipedia article on emphysema mentions "destruction of structures feeding the alveoli, in some cases owing to the action of alpha 1-antitrypsin deficiency." That is what it says. I guess "feeding" is a mistake?

Either a "typo", or a misunderstanding of relations between alveoli and collagen fibers surrounding them?

My guess is that normal blood serum contains a trypsin and also proteins that block the action of trypsin;

And that some people have a genetic deficiency of one of these enzyme-blocking proteolytic enzymes, predisposing those people to enzyme digestion of the collagen network supporting their alveoli.

Incidentally, much research has been done on protein-digesting enzymes in body fluids.

We can't do without them. An important example is plasmin, and its self-blocked precursor "plasminogen".

It digests blood clots; without it, clots accumulate (bruises, etc.); excess "plasminogen activator" is produced by some (many?) cancer cells, and may be a cause of invasiveness and metastasis.

Not beyond hope are possibilities for inventing and testing treatments that break the positive feed-back cycle, weaken the traction of lung mesenchymal cells, activate protein-digesting enzymes (e.g. trypsin?), stimulate macrophages to consume some of the extra collagen, or break bonds between collagens.

A treatment as simple as stimulation of secretion of more plasminogen might be a cure for "JQG" but nothing remotely analogous to such a treatment is considered on any of the web sites about the disease.


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