The last week has been quite hot and humid over here at D'Adamo World Headquarters. We've finally put in a ‘deer-proof' fence around a bit of the property, so for the first time since we've moved here (perhaps a decade or so) I can plunk in a few plants and not be forced to view a scene of desolation and carnage the next morning. Apparently from a low of 27 in 1939, the number of deer in Connecticut has now risen to somewhere between one and two million, which is not surprising considering that their natural predator, the wolf, is long gone and the state is full of yummy suburban yards full of tasty treats.

We've put in a variety of things, which I hope to add to over the season. One plant I always try to use is Baptisia tinctoralis (Wild Indigo) which grows well, if slowly in these parts. Baptisia has always interested me in a medical manner, having many immuno-stimulatory polysaccharides, and a few fascinating alkaloids as well. It is one of the few natural products that are known to stimulate the anti-T (Thomsen-Freidenreich) antibody, which may help explain its long use in traditional medicine for the treatment of cancer.

Interestingly, Georg Springer's anti-T vaccine was partly composed of the typhoid vaccine; he felt that it amplified the effect of the other components. Baptisia has a long history of use by many cultures for treating typhoid fever.

The British Naturopathic Association had an editorial on the Blood Type Diet Theory. You can read it here, including an afterpiece by Tom Greenfield. The article is pretty flaccid and tries to be humorous, but I wonder about the appropriateness of editorializing about ‘things' in a medical journal. Typically, medical journals editorialize about the results of research included in that issue, and often only to speculate on what further conclusions may be drawn from it. The major gripe the author seems to have is that Red Clover, another plant I'm going to plunk in my garden, is an ‘avoid' for everyone. But that is only to keep it out of the hands of people who don't know how to use it. Hey guys! Knock! Knock!

However, I do think that the British naturopaths (by-and-large) ‘get it' when it comes to the essence of what all this ‘polymorphism stuff' means to the practitioner. A lot of the US naturopaths are still incredulous that one of their number could possibly come up with a discovery --the significance of which, if correct-- would have wide and far-reaching implications. Others think everyone should just be vegan and that would solve everything.

Typically when it arrives, like all medical folk, they then trip over themselves so as to not be ‘the last.'

As I wrote on the Forums, a lot of ND's have the opposite of the ‘not invented here syndrome,' which is the ‘I can't believe it was invented here syndrome.'

In both cases, considering the enormous amount of woo-hoo, mumbo-jumbo fantasy that masquerades for ‘cutting edge' alternative treatments and devices (if my office mail slot is to be believed) it certainly can't be the lack of science that is holding them back. If ideas, as Schopenhauer observed, do go through three phases (ridicule, rejection, acceptance) then we've still got some time. Unfortunately, often by the time you get to the ‘acceptance' stage, all the fun has been sucked out of things.

Research-wise, this has been a busy week.

Traded emails with Dr. Linda Kim, whose with the Southwest College Research Department over the last two weeks. The microbial adhesion study and the clinical trial of blood type and endothelial dysfunction are on schedule and within budget. Enrollment will be completed for the clinical trial by 7/31 and experiments completed for the adhesion study by 9/30.

Had a wonderful meeting with Dr. Carlo Calabrese and Dr. Heather Zwickey over at the Helfgott Research Institute, which is associated with the National College of Naturopathic Medicine. We're hoping to develop a series of studies that can test the BTD across a variety of conditions and parameters. What is great about working with Carlo --whom I've know for decades-- is that he attracts the very best thinkers, and so much of the work with blood groups (which are really genes when you think of it) is high level math and statistics, and area in which I am not all that muscular.

Someone wrote me that the BTD was discussed in a book called "The Chemistry of Joy�. I've not heard of it, but it's got a heck of a title.

Unless you happen to be named Joy.

Been reading about a new class of cancer chemotherapy drug, called the epothilones, which seem to offer the promise of greater efficacy, with perhaps a special relevance for blood group A cancer patients. The epothilones are much like the taxol class of chemotherapy drugs in that they inhibit mitotic spindle degradation in the malignant cell (mitotic spindles are the delicate network of tubes that act as a scaffold for the migration of the split chromosomes as the become two new ‘daughter cells.' In essence, promoting tubulin polymerziation prevents the mitotic spindle from being broken down by stabilizing the microtubule bundles, so the cell cannot replicate.

Taxol class chemotherapy drugs represent one of the most effective classes of anticancer therapeutics; however many human cancers either do not respond or become resistant to taxol-based therapy. Since 1995 Epothilone B, a new drug class sharing the same mechanism as taxol, has been in development. But, unlike taxol type drugs, epothilones have cytotoxic activity on cells overexpressing P-glycoprotein. P glycoprotein is rewsponsible in part, for drug resistance associated with many anti-cancer treatments.

This may be important for type A individuals, who appear to have increased level of p-glycoprotein in their malignancies, which may explain why in my clinical observances, they tend to be under-represented in the long term survivor groups. A drug that does not appear to be inhibited by p-glycoprotein may be just what the patient ordered.

In contrast to taxol class drugs, epothilones demonstrate a 2.5-fold greater potency than taxol, cause virtually complete cell-cycle arrest and are active in a large panel of cell lines and multi drug-resistant cancer types.

Obviously, I'm not a big fan of chemotherapy. But, as of right now, it is a part of the cancer treatment landscape and if it can be made to work better in certain individuals, so much the better.

Got this note in my comments file:

"Peter, you may be interested in some recent articles in the April, 2004 issue of the Journal of Allergy and Clinical Immunology re: lectin binding pathway of complement activation and fucosylated proteins that function as selectin ligands. [J Allergy Clin Immunol, Volume 113, Number 4] Regards, Ann Robb, MD�

Thought it would make a good teaching point.

Warning! Technical stuff follows!

Selectins are multifunctional adhesion molecules that mediate the initial interactions between circulating white blood cells and cells lining the blood vessels, usually with the intent of allowing the white blood cells passage through the vessels walls and on into the tissues. They play a role in arteriosclerosis, inflammatory diseases, and metastatic spreading of some cancers. The best understood selectins, E-selectin and P-selectin, show some variation according to ABO type, with higher levels of E-selectin shown to occur in individuals who are type A. The sugar fucose appears to be critical the proper function of selectins. Interestingly, most likely through the interaction of the selectin molecule with variations of the Lewis A (non-secretor) and Lewis X antigens, which are in themselves fucosylated.

In a 1999 study published in the Journal Blood, leukocyte adhesion deficiency type II (LAD II), a rare inherited disorder of fucose metabolism that leads to severe mental retardation and immunodeficiency (caused by the absence of carbohydrate-based selectin ligands on the surface of the white blood cells) was reversed by oral supplementation of fucose, which induced the expression of fucosylated selectin ligands on the patient's white blood cells. During 9 months of treatment, infections and fever disappeared, elevated white blood cell counts returned to normal, and psychomotor capabilities improved.

In short, fucose is important for proper selectin function, proper selectin function is critical for efficient regulation of inflammation --and a host of other metabolic and immune functions.

The Complement System is a part of the immune response that occurs when an antibody comes into contact with the antigen to which it was manufactured. In some instances, such as when a transfusion is mismatched, the antibody-antigen interaction is so lethal that the foreign object is destroyed immediately. More commonly, the antibody-antigen interaction stimulates an ‘effector mechanism' that actually does the dirty work.

There are three pathways to complement activation, though as a student twenty-five years ago, I was taught that there were only two. The two I was taught were referred to as the ‘classic' and ‘alternative' pathways.

The Classic Pathway is the standard way that an antibody-antigen complex stimulates complement, usually by activating a chain reaction resulting in the conversion of a preexisting circulating inactive molecule into a new molecule that coats the membrane of the invader and then itself is converted into another molecule that attacks the membrane of the invader by boring holes in it.

The Alternative Pathway to activating complement is really much like the Classic, except that instead of antigen-antibodies triggering the complement cascade, many bacteria and foreign objects trigger it directly.

Recently, it was discovered that lectins form a unique, third way to activate complement, most notably through the example of a lectin that is found in our blood serum called Manna Binding Protein (MP. Non-secretors appear to have lower levels of complement than secretors.

Put another way, antibodies ‘finger' the target, complement destroys it.

Someone asked about whether celiac disease and blood types have any link. There is a published study that claims a strong link between non-secretor status and celiac disease, and other authors have seen a link between the variations in intestinal alkaline phosphatase seen with the ABO types and celiac.