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Comparative medicine

The lifecycle of epithelial cells, and a most wonderful coincidence (#30/31)

(This is a reworking of a post I originally wrote in 2007.)

So here's a wonderful example of modeling physiological processes across species: Schutte [1] details the reproductive cycle of the dog, Durrant adapts that information and applies it to the panda, and then Durrant's group and ours uses that panda information to study other species of bear--specifically, sun bears.

Anyway, this is a presentation slide that I adapted (animated, colored) from Schutte's 1967 original drawing [2,3,4] for a talk on using informatics to aid in the reproduction of endangered species at the 2004 American Veterinary Medical Association conference:
 



What you are seeing, as you read left to right, is the change over time in the shape and color of the vaginal epithelial cells, collected by swabbing the animal (like taking a Pap smear).

Shape changes (from more round to more irregular and from a high nucleus-to-cell size ratio to a much lower one, approaching or reaching zero in some cases), and color changes between pink/red (acidophilic) and blue (basophilic) can be seen as the cycle progresses. Although the hormone level peaks and the white and red blood cells (leukocytes and erythrocytes) are shown as well, we'll ignore those for the moment to concentrate on the changes in the colored cells in the middle of the diagram.

With a break in between, the cycle resumes at the left, and the whole process is repeated over and over again through the animal's reproductive life.

The important take-away points from this slide are the irregular borders and small nuclei of the aging cell, and the colors blue and pink (depicted above), and golden (which is also significant in pandas, but which Schutte did not address in dogs in his work).

So keeping those factors in mind, you can see why I was practically dumbstruck when I walked into a glass art studio in Fremont (a Seattle neighborhood) and noticed the piece by James Curtis titled "Little Bang":
 



I mean, it's all there! Large, irregular cell borders, tiny nuclei, and pink (cranberry), blue (teal), and golden color. Even the rack on which it is mounted looks like a graph over time of a cycle.

I swear, if I had commissioned the artist to render mature vaginal epithelial cells in glass, he could not have carried it out more faithfully.

A huge shout-out to James and his assistant Tara for patiently working with me while I arranged financing and donation of the work to our sun bear reproductive project for auction at a later date. If you're looking for glass art, I would recommend The Edge of Glass in Seattle unconditionally for their quality, their vision, and their customer service. On several subsequent occasions, they have donated pieces to support my research, and I am deeply grateful.

James told me he probably will not use the teal again, or if he does, it won't be very often--it is simply so hard to work with that it's not practical. So the bears and I did indeed get very lucky to get in there before someone else bought the piece, and we would never had known about it.

I also thank my husband, Iain, for deciding to surprise me with a drop-in visit there; it worked out so much more beautifully than I could ever have imagined.

References

  1. Durrant B, Czekala N, Olson M, Anderson A, Amodeo D, Campos-Morales R, Gual-Sill F, Ramos-Garza J. Papanicolaou staining of exfoliated vaginal epithelial cells facilitates the prediction of ovulation in the giant panda. Theriogenology. 2002 Apr 15;57(7):1855-64.
  2. Schutte AP. Canine vaginal cytology. I. Technique and cytological morphology. J Small Anim Pract. 1967 Jun;8(6):301-6.
  3. Schutte AP. Canine vaginal cytology. II. Cyclic changes. J Small Anim Pract. 1967 Jun;8(6):307-11.
  4. Schutte AP. Canine vaginal cytology. III. Compilation and evaluation of cellular indices. J Small Anim Pract. 1967 Jun;8(6):313-7.

 

Littoral interpretation (#18/31)

Water, water, every where,

And all the boards did shrink;

Water, water, every where,

Nor any drop to drink.

--Wikipedia, "The Rime of the Ancient Mariner", Samuel Taylor Coleridge, 1798 accessed 18 August 2012

 


The poem on the surface explores violation of nature and its resulting psychological effects on the Mariner, who interprets the fates of his crew to be a direct result of his having shot down an albatross.----Wikipedia, "The Rime of the Ancient Mariner: Interpretations", Samuel Taylor Coleridge, 1798 accessed 18 August 2012

 

Spoiler alert! (although there's a decent chance you already had to read this poem in elementary school, so in that case, you already know what happens to the Ancient Mariner and his crew).

The Ancient Mariner is a sailor who commits an unnecessary act of cruelty, even a crime in Coleridge's estimation--with his bow and arrow, he shoots the albatross (a water bird, like a seagull) who had led his lost ship out of dangerous waters.

With his cruel bow he laid full low
The harmless Albatross.

 

After the killing of the bird, more bad things continue to happen to the ship and crew. All the other crew members are eventually killed, but his punishment is to remain alive, tormented, and to wander the earth telling his story as a warning to others.

He partially redeems himself when--seeing the sea creatures that he had earlier despised, he recognizes how beautiful they really are. He wanders the earth eternally, trying to reach others with his lesson before it's too late for them to learn from it.

There is a metric boatload of things we could discuss about this poem, anywhere from conservation biology, history, psychology, and literature aspects, just to scratch the surface--but I want to talk about my trip to Padilla Bay estuary today, and what living in a littoral environment means for kidney function in animals--and Coleridge's observation about water is the perfect jumping-off point for that discussion.

 

 

 

 


An estuary is a body of water where fresh water from rivers and oceanic saltwater come together and mingle. So it's a complex transition zone, and organism functions that work one way in fresh water and another way in saltwater have to be covered in both cases there.

The littoral zone is the area of a body of water closest to the shoreline. So in an estuary, the littoral zone is where the fresh water and the saltwater mix--it's saltier than the fresh water is, but it's also less salty than the ocean water.

You probably know that, if you're ever lost on a boat on the ocean, you shouldn't drink seawater--not even a little bit, not even if you're very, very thirsty.

The reason is that your body tries to maintain a balance between the concentration of solutions (like dissolved salt) inside your cells and outside of them. Globetrooper has some good diagrams of what the process looks like, both when it's going right and when it's not.

Globetrooper's diagram shows what it looks like when things are balanced inside the cell and outside of it: a situation called "isotonic": the "same pressure" by water on the cell membrane from both sides.

Source: http://globetrooper.com/notes/wp-content/uploads/isotonic-state.png accessed 18 August 2012

 

The large gray circles represent salt ions (to be more specific, sodium ions and chloride ions), and the small blue circles represent water. The proportion of salt dissolved in the water--the concentration--inside the cell is about the same as the proportion of salt dissolved in the water outside the cells. The inside and the outside of the cell are in equilibrium (isotonic), and there is no pressure from the water either to leave or to enter the cell.

Globetrooper's next illustration shows a situation that is no longer isotonic. Salt ions (the gray circles) are dissolved in the water (the blue circles) inside the cell, but outside the cell, there are no salt ions--the water outside the cell is pure water, with no salt in it. This situation is called a hypotonic solution.

Source: http://globetrooper.com/notes/wp-content/uploads/too-much-fresh-water.png accessed 18 August 2012

 

Since the inside and the outside of the cell are no longer in balance, a process called osmosis occurs--the movement of fluid (in this case, water) across a semipermeable membrane (a membrane that substances can move through) from an area of lower concentration (in this case, of salt) to a area of higher concentration.

The effect is to bring the concentrations more into balance (isotonic).

The green arrow in this figure shows the movement of water (its osmotic pressure) from the area of low salt concentration outside of the cell to the area of higher salt concentration inside the cell. That movement of water into the cell dilutes the salt concentration, making it lower inside the cell.

This is what happens when we drink fresh water.

The opposite situation occurs when the water outside the cell is more salty (has a higher salt concentration: lots of gray circles, very few little blue circles) than the water inside the cell. This situation is called a hypertonic solution.

Source: http://globetrooper.com/notes/wp-content/uploads/too-much-salt-water.png accessed 18 August 2012

 

In a hypertonic solution, water flows out of the cells--the osmotic pressure of the water is toward the higher concentration of salt.

So you see what would happen? If you drank even a little salt water, it would draw water out of your cells. Instead of quenching your thirst, salt water would leave you more dehydrated than you were when you started.

At the cellular level, this is what it would look like:

Source: http://upload.wikimedia.org/wikipedia/commons/7/76/Osmotic_pressure_on_blood_cells_diagram.svg accessed 18 August 2012

 

In the hypertonic solution, the osmotic pressure comes from the water leaving the cells, leaving behind shriveled, badly dehydrated, cells (left side of image).

In the isotonic solution, the osmotic pressure balances out to zero, as equal amounts of water enter and leave the cells. The red blood cells in an isotonic state look normal and healthy with the indentation in the center that is typical of them.

In the hypotonic solution, the osmotic pressure pushes water into the cells, stuffing and waterlogging them--the normal indentation starts to disappear as the cell is too full of water.

These microphotographs of real red blood cells show how they really look, as they react to the different solutions we just described.

Source: http://upload.wikimedia.org/wikipedia/commons/6/62/Human_Erythrocytes_OsmoticPressure_PhaseContrast_Plain.svg accessed 18 August 2012

 

So now that we've discussed how cells behave in different kinds of solutions (hypertonic, isotonic, and hypotonic), does Coleridge's verse

And all the boards did shrink;

 

make even more sense now?

Why is that?

What is he describing, and why did the boards shrink as a result?

 

 


Osmoregulation (the control of osmotic pressure in body fluids, such as blood) is controlled in humans and other vertebrates by the kidneys--that's an important function they have in addition to production and excretion of urine.

Hormones produced by the pituitary gland and the adrenal glands, among others, signal to the kidneys what state the solutions in the blood are--hypertonic, isotonic, or hypotonic--and the kidney responds accordingly by reserving water or by releasing it to restore the balance.

As we are land animals, our kidneys have to respond to fluids we drink or take in in other ways (like an IV solution in the hospital, for example), but that's basically it. Fish, on the other hand, are surrounded by fluid, and their kidneys have to respond to that fluid and balance the water that their cells take in.

Too much water, and the cells swell up and get waterlogged--the hypotonic solution in the previous pictures.

Too little water, and the cells shrink and dehydrate and rupture--the hypertonic solution in the previous pictures.

The fish kidneys have to get the solution just right, and in a situation where the fish is surrounded by fluid of a different concentration.

Freshwater fish adapt to this situation by not drinking very much, and by urinating a lot; ocean fish (except sharks, which are a whole different story for another time) adapt by drinking a lot and not urinating very much.

So freshwater fish and ocean fish have adapted to this problem in pretty much opposite ways--that would seem to make a lot of sense.

But salmon live part of their lives in fresh water, and part of the time in salt water--so how can they have adapted to both, when the adaptations are the opposite of each other?

Salmon have adapted to both lifestyles--they can barely drink and urinate a lot when they live in fresh water, and then change to drinking a lot and barely urinating when they're out in the ocean.

Specialized cells in their body can work in opposite ways, depending on what they need at which stage they are in their lives.

But they can't turn it on a dime--they need days or weeks to make the transition between fresh water and ocean water.

And that's where the importance of the estuarine environment, like Padilla Bay, comes in--as an intermediate zone between the two other environments, it provides a place where salmon can make the transition.

In a region where the salmon can move around in the littoral zone to find the right amount of salt concentration they need, estuaries ensure the survival of those salmon leaving the fresh water where they were born, to go out and spend a large part of their lives in the ocean.

And they also ensure a place where--when it's time to go back up the freshwater river and breed--salmon have a place to adjust back from the ocean to the river environment, so that they can give birth to the next generation, and continue the cycle.

So often, in massage school, we don't have time to teach anatomy this deeply, and that's a real shame. If you just have time to memorize the fact that the kidneys control osmoregulation, so that you can recognize it when the MBLEX or the NCBTMB/NCBTM asks you about it, then that doesn't give you any particular preparation for clinical practice.

But if, at a deeper level, you understand what is going on, and you can draw a line from how the kidneys are involved in salt balance to what happens when that balance gets out of control one way or another, then you can understand what is going on with people living with renal failure or other kidney disease, and you are better equipped to know whether or not it's safe for you to provide massage under the circumstances.

It happens to the best of us--we all make mistakes

Kelli Wise has issued an August Blog Challenge, and this post is part of the my response to the challenge.

Can I write 31 blog posts in 31 days?

 

We'll see. I'm getting a late start, coming in on the 5th of August, but I think that's not going to be a problem. As she said, there are no blog police enforcing this goal.

 

Can I keep those blog posts to less than 350 words?

 

No, I can't--asked and answered. What I will aim for is to stay on point, and provide valuable information, rather than just indulging my long-windedness.

You'll be the ones to let me know how well--or not--I have succeeded at that task.

 

 


The Renaissance artist Leonardo da Vinci is famous for, among other things, his sketches in which his eye for detail and his technical proficiency are immediately evident.

The veterinary medicine program at Colorado State University offers tons of information for free about comparative anatomy, physiology, and pathology in different species of animals, enough information to lose yourself in hours of reading, learning, and imagination.

In the reproductive biology e-Book, Richard Bowen has a post called "Leonardo's Error", demonstrating how even an artist as meticulous as Leonardo da Vinci can make a mistake--in his case, one that continues to this day, since he's no longer in any position to correct it.

No blame, no shame: we all make errors, and if we are fortunate, then we get an opportunity to correct those errors. The most important thing is to learn from the errors we make, and use them to do better in the future.

To understand Leonardo's error in his embryological drawings, we'll first talk a little bit about the placenta, and then go back to see how and why he got that confused.

In mammals, including humans, the placenta is an organ shared by a pregnant female and the developing fetuses.

The shared blood supply between the mother and the fetuses permits food, other nutrients, and oxygen to be delivered from the mother, and it also takes waste products away from the fetuses to be disposed of. 

Source: http://upload.wikimedia.org/wikipedia/commons/f/f1/Placenta.svg accessed 6 August 2012

 

That's where the comparative anatomy and physiology comes it--what we just said about the placenta is true for mammals in general.

But when we look more closely at how the placenta does that job in specific mammals, then we see very real differences in how it goes about doing it.

Bowen describes the different structures in this way, with a couple of explanatory notes added in brackets:

Classification Based on Placental Shape and Contact Points

Examination of placentae from different species reveals striking differences in their shape and the area of contact between fetal and maternal tissue:

  • Diffuse: Almost the entire surface of the allantochorion [the membranes between the mother and fetuses] is involved in formation of the placenta. Seen in horses and pigs.
  • Cotyledonary: Multiple, discrete areas of attachment called cotyledons are formed by interaction of patches of allantochorion with endometrium. The fetal portions of this type of placenta are called cotyledons, the maternal contact sites (caruncles), and the cotyledon-caruncle complex a placentome. This type of placentation is observed in ruminants.
  • Zonary: The placenta takes the form of a complete or incomplete band of tissue surrounding the fetus. Seen in carnivores like dogs and cats, seals, bears, and elephants.
  • Discoid: A single placenta is formed and is discoid in shape. Seen in primates and rodents.

Source: http://www.vivo.colostate.edu/hbooks/pathphys/reprod/placenta/plac_types.jpg accessed 6 August 2012

 

The discoid placenta--the kind we humans have--is one discrete organ, and looks kind of like a single disk, which is where the name comes from. You can see it in the previous drawing of the mother and child--it's drawn in a uniform red color.

By contrast, a cotyledonary placenta, like sheep and other similar animals have, looks like this:

Source: http://www.ansci.wisc.edu/jjp1/ansci_repro/lab/lab12_03/images/cotelydonary_lec.jpg accessed 6 August 2012

 

And now, you can see Leonardo's error. He drew the human fetus like this:

 

 

 

Clearly, he envisioned it having a cotyledonary placenta. He confused it with the kind of placenta cows, sheep, and other similar animals have--probably because he had access to dissections of those animals, but opportunities to observe autopsies of pregnant women were relatively rare or non-existent for him.

There are, I think, 2 lessons for us here. The first is:

Consult the final authority, the human body itself.

--Stephen W. Carmichael

 

Even more than that, though, don't be afraid to make mistakes.

Errors happen to the best of us, even to famous artists like Leonardo da Vinci.

We can't hope to never make a mistake--they're unavoidable, simply by nature of our being human.

What we can do is to approach learning with a certain amount of humility in the face of that fact, and to hope that, when we inevitably do make errors, that we get an opportunity to correct them and to continue learning.

 

 

 

 

 

Quick anatomy question for a Saturday morning

I don't have time for a long post, as I'm about to rush out the door to the airport, but there's just enough time before leaving for a quick anatomy question.

What anatomical feature in humans does both of the following:

  1. gives us the ability to speak, and
  2. subjects us to a risk that many non-speaking animals don't have to worry about at all?

 

Also, what is that particular risk I'm referring to here?

As aspiring healthcare practitioners--what should we do to address that risk?

Source: http://upload.wikimedia.org/wikipedia/commons/4/44/Anatomical_Male_Figure_Showing_Heart%2C_Lungs%2C_and_Main_Arteries.jpg accessed 23 June 2012

 

 

Miscellaneous red blood cell morphology topics

Notice anything unusual about the red blood cells (RBCs) in this microphotograph?

Source: http://www.spcollege.edu/hec/vt/vtde/avianhemo/avian1/21.jpg accessed 2 May 2012

 

On the topic of blood, National Geographic has an interesting article on the oldest red blood cells found, in the body of Ötzi the Iceman.

The 5300-year-old homicide victim, discovered in the Alps in 1991, did not have any visible blood left after the trauma that killed him. But a microscope that can "see" down to the atomic level was able to find traces of blood that remained intact in frozen temperatures for almost 5-1/2 millenia.

What you're looking at here is an image of one of Ötzi's red blood cells, created by atomic force microscopy (AFM).

The Wiki article on AFM is kind of tough going, technically, but the important points from it are that it can scan at a scale about 1000 times finer than optical (light) microscopes can, and that it opens the door to visualizing atoms and other things at the nanoscale level--as tiny as one-billionth of a meter, or about one-billionth the size of a yardstick.

Source: http://images.nationalgeographic.com/wpf/media-live/photos/000/524/cache/otzi-iceman-red-blood-cells-found-cell_52466_200x150.jpg accessed 2 May 2012

 

What do you notice about the shape of Otzi's red blood cell?

 

 

Why POEM's developing an e-Book on evolutionary biology for MTs

One of POEM's main raisons d'être (reasons for being/existing) is to provide solid and validated support for learning and exploration in massage.

Because all of us are curious and engaged, and because we care about the world around us, we naturally try to explore further, and sometimes we take a leap into the unknown to try to figure it out.

There's absolutely nothing wrong with that--it's one of the core things that makes us human. I want to continue to encourage that exploration, because out of it will come new knowledge that will eventually benefit our clients/patients, and make us better MTs through improving our understanding.

It's easier to give updated information to someone who's already exploring than it is to try to spark curiosity in someone who, for whatever reason, doesn't demonstrate it spontaneously.

So when I see someone making a leap into the unknown, but--through no fault of their own--going down the wrong path because they're missing a crucial piece of information, that tells me that there's a need for that information, and that it therefore falls within POEM's mission to provide that information on a universal level.

If you've been shamed and shut down before by others for not knowing something, then having misinformation corrected by someone else, even by a caring teacher, may feel similar to that previous situation.

That's understandable, but that's not the intent here. A better analogy is that you're exploring a trail through an unfamiliar forest, and you come to a fork in the trail. Not knowing which branch will lead to your goal, you guess which one to take. Then, on your journey, you meet someone who has traveled that path before, and--while not knowing your exact destination--at least knows the area you are traveling toward.

For that person to tell you "that trail over there goes where you want to go; this one doesn't" isn't a criticism--it's encouragement to keep going to where you want to be, in a way that makes it more likely for you to get there.

Source: http://matadornetwork.com/wp-content/uploads/2011/05/20090923-wanderlust.jpg accessed 5 April 2012

 

In keeping with that mission, when the emphasis is on correcting what appears to be a genuine misunderstanding on someone's part, I don't plan to single them out by name. Doing that can make it feel more personal and more critical than it is intended to be.

Instead, I'll quote them anonymously here, in order to focus on the ideas, and to involve us all in the search for the right path.

 


As a teacher of, and a research scientist in, anatomy, it absolutely warms my heart when I see people using anatomical reasoning to try to figure out how the body works, why something might not be working as we would expect or want it to, and what we might be able to do to help support it returning to optimal function.

When I see someone applying anatomical reasoning to assess a client's situation and make a recommendation to improve care, as Kim LeMoon does here:

In reviewing Louisa's case, the possibility of lumbar radiculopathy was reconsidered. A previously overlooked sign was that the injury had occurred during a twisting motion. The lumbar intervertebral discs are thought to be more vulnerable to herniation in rotation. Between the clinical pattern recognition and Louisa's report of hearing a "loud pop" during a twisting motion, the new hypothesis was that Louisa may have herniated a lumbar disc and that lumbar radiculopathy could be the source of her referred pain symptoms. I described the hypothesis to Louisa and advised her to seek the advice of an orthopedic surgeon.

During this time, for reasons unknown, Louisa had started working with a different chiropractor. She was asked to describe the hypothesis to the new chiropractor to solicit his opinion.

Results

The chiropractor considered the new hypothesis plausible and referred Louisa to an orthopedic surgeon who specializes in treating low back pain. As a result of a magnetic resonance imaging investigation ordered by the surgeon, an L5-S1 herniation was found.

 

I do a little happydance, often literally or sometimes, if I'm in a public place, figuratively.

I'm also very pleased to see the openness to evolutionary biological explanations among members of the MT community. Based on my experience (and, of course, as we know, the plural of "anecdote" is NOT "data"), I'm under the impression that there is very little actual evolution denial in the MT community, when compared to the larger American public.

The following graph shows where the US rates in knowledge of evolution, as measured by their acceptance of the statement of a non-controversial statement based on foundational biological knowledge.

http://upload.wikimedia.org/wikipedia/commons/5/5c/Views_on_Evolution.svg accessed 5 April 2012

 

Only 40% of Americans got the correct answer, "true", compared with about 75-80% in countries such as the Scandinavian nations, and France, Japan, and Germany.

While the American public at large's knowledge and acceptance of evolutionary biology comes in almost last among developed countries (ahead only of Turkey), I don't see that in the MTs I come into contact with. They seem open to anatomical explanations and reasoning grounded in rigorous biological science.

The only wrinkle is, if you're going to use evolutionary explanations, you need to be sure you're getting the science right. Otherwise, rather than actually explaining or understanding, you're only passing along yet another "just-so story".

When this anatomy teacher sees MTs making statements such as:

If, besides sensing temperature, skin was truly as vital as scientists claim it is, wouldn't the body protect it better?

 

then I would say to the MT, "It is very good that you are grappling with your questions in this way. There are a couple of pieces of information you need, in order to make sure you stay on track with what you want to figure out.".

First, of course, a review of the skin's barrier function is in order.

But, significantly, this MT is clearly open to evolutionary explanations, in the linkage between the survival value of the skin's function and the body's "investment" in it.

The problem is that, as we humans often do, this practitioner has fallen into a pattern of teleological, or goal-directed (from Ancient Greek τέλος/telos, purpose) + λόγος/logos, word, speech, discourse), thought, and then applies that teleological thinking in an arena where it doesn't apply--that is, evolution.

Evolution is a blind, unguided process--the body doesn't "decide" to "protect" the skin. It's the other way around--those organisms that happened to develop protective barriers happened to survive longer, because of the survival value those barriers provided, than those that didn't have them.

So in that longer time, they had more offspring, who then were able to out-reproduce the offspring of organisms without those barriers, and this cycle continued for thousands of generations.

There's no "why" for the body to make a decision about. There's just what anatomy came about blindly back in the deep past, and what physiological and pathological consequences resulted from that chance development.

With that bit of foundational knowledge from evolutionary biology, this MT is much more likely to find the answer they are seeking than by continuing down the path of teleological thinking about anatomy.

Another example of a question from an MT wanting to know about the brain puts them right on the verge of an important discovery:

Earlier you said the brain had an old bossy part and some younger naive parts that don't get along with each other. I'd consider that mismatch to be a systemic flaw. With all those faults why would MTs even want to work with the brain?

 

Yes! You're almost there! You're so close!

Yes, there are old bossy parts of the brain that don't get along with the younger naive parts (h/t Diane Jacobs for the terminology!).

Yes, that is a systemic flaw.

And that's one of the threads in the multiple lines of evidence for evolutionary biology, and that reinforces it as a basis for anatomical reasoning--if the body were specially created by a designer, you'd expect it to work better than having parts of the brain that don't play well together, or Kim LeMoon's client having the inherent weakness in the lumbar discs that come from starting to walk on 2 legs at some point in our history as modern humans, or hundreds of other examples that a brief glance at any A&P/pathology book will provide.

So it's not that the neuroscientist is mistaken, as the MT thought by finding that flaw--scientists know that already.

If you understand that parts of our anatomy are systemically flawed--and that that's ok by evolution, because evolution doesn't teleologically "seek" a perfect solution; it blindly makes do with a "good-enough" workaround--then you are that much further to being able to apply real and solid anatomical reasoning and gain understanding that puts you in a position to help clients better.

We work with the systemically flawed human brain (and some of us with the brains of other animals as well), because that's what we have before us. We meet the clients where they really and truly are right now, not where we might want them to be in a different universe that operated by different rules, and provided them with perfectly-optimized brains.

That's the demonstrated need for evolutionary biological information to support clinical reasoning that I'm planning to meet with POEM's introductory evolutionary biology for MTs e-Book. At the moment, I project it will be available in 2.5-3 years (roughly, between November 2014 and May 2015), after the research literacy book and several others that are more directly connected to the material tested on MT certification exams.

 

 

http://upload.wikimedia.org/wikipedia/commons/d/dd/Horseevolution.png accessed 5 April 2012

"A very sad dinosaur"


Cancer is different from other diseases, because cancers are not natural to the Universe. The man-made chemicals that cause cancers are foreign to the Universe. Man created the cancer; Man must treat the cancer, by killing or excising the cancer. Because Man created the cancer: Man must kill it.
 
--variations on this idea have been seen around the net on different MT forums
 
 

This article is an older one, but since we're talking about brains this month, it is still timely. It contains interesting information both about cancer, and about the scientific method--how scientists know about things that happened millions of years before any of us were ever born.
 
 
On October 23, [2003,] a team of paleontologists and pathologists announced that they had discovered a massive, possibly lethal brain tumor in the fossilized skull of a Gorgosaurus,
 

Source: http://upload.wikimedia.org/wikipedia/commons/8/80/Gorgosaurus_BW.jpg accessed 7 December 2011
 
 
a 25-foot-long relative of Tyrannosaurus rex
 
 
 
 
 
 
 
that lived 72 million years ago.
 
You can read this as a clock that starts just past noon at 4.6 billion years ago (4.6 Ga). Continuing clockwise, the formation of the earth takes place 4550 million years ago (= 4550 Ma). At 3 billion years ago (3 Ga), 2 Ga, and 1 Ga, things are happening, but life on Earth doesn't really explode into prominence until about 530 Ma with the Cambrian explosion.
 
The dinosaurs lived alongside early mammals from about 230 Ma to 65 Ma, and humans arrived just before midnight on this clock: around 2 Ma.
 
The Cretaceous period, where this case report happened, follows the Jurassic period of Hollywood fame, and both are part of the green band representing the Mesozoic ("middle-life" or "middle-animal") era. Gorgosaurus roamed what would eventually become North America about 75 Ma or so.
 
 
 
 
 
 
Fossils of dinosaur bones are no surprise, but soft tissue doesn't fossilize the same way bones do, which is why we have so little information on dinosaur viscera. How, then, do we have a fossil sample of brain tumor?
 
A matrix of bone within this dinosaur's brain tumor allowed it to fossilize along with the rest of the animal's skeleton.
 
 
 
 
 
The tumor, possibly an unusual type of bone-forming cancer called an extraskeletal osteosarcoma, filled nearly the entire area formerly occupied by the cerebellum and brainstem and probably impaired the cerebrum, the part of the brain that controls thought and memory.
 
How do we know that dinosaur brains work like ours do--that the cerebellum and brainstem control movement and autonomic functions, and that the cerebrum controls thought and memory?
 
Like us, dinosaurs are vertebrates, and moreover--just like us--they are tetrapods.
 
Understandably, this vocabulary might be confusing: τετρά/tetra is Greek for 4, and quadr- is Latin for 4. πόδ/pod is Greek for foot, and ped is Latin for foot. And we know that quadrupeds are animals who walk on all fours, like dogs, cats, and horses, right?
 
So since tetrapod means the same thing in Greek as quadruped means in Latin, and since we're not quadrupeds (we're bipeds), how can we possibly be tetrapods?
 
It's because--although the meanings of the word roots are the same in their respective languages--they've come to mean different things in biology. Tetrapod refers roughly to structure, while quadruped refers roughly to function. So all animals that descended from the paired-limbed fish who evolved into land vertebrates are tetrapods, either because we all have two pairs of limbs (our arms and our legs), or because we used to have them before they changed a great deal (birds' and bats' wings are modified arms), or because we used to have them before they diminished greatly in size (whales, dolphins) or disappeared altogether (snakes).
 
Quadruped, on the other hand, refers to the action of walking on all fours, whether flat-footed like a bear, or on the toes like dogs and cats, or on the toenail, like horses. All of the animals listed in this paragraph are quadrupeds and tetrapods, because they walk on their pairs of limbs. The animals in the previous paragraph, on the other hand, do not walk on all fours--so although they are tetrapods, they are not quadrupeds.
 
So as different as we look on the outside, you see that there is a deep structural similarity we share.
 
And that structural similarity about vertebrate brains is the basis for how we reason about what effects the tumor must have had on this dinosaur when it began compressing structures in her brain.
 
We know how such a tumor affects other vertebrates, and we reason from that similarity about how it must have affected her vertebrate brain.
“As the tumor grew, the dinosaur—a female perhaps three years old— would have forgotten where she left her last kill, and then she would have forgotten to go to the bathroom,” says paleontologist Peter Larson of the Black Hills Institute in Hill City, South Dakota.
 
Sadly, you can see the same progression in loss of function in people living with the effects of brain tumors or other brain conditions. First, it can affect higher-order cerebral functions like thought and memory, but it can progress to a point where the autonomic functions directed by the cerebellum and the brainstem--the ones we don't consciously think about, like breathing or urinating--can be compromised.
The tumor would also have put pressure on the dinosaur’s cerebellum and brain stem, which regulate motor function and other autonomic functions such as heart rate. “The tumor would have impaired mobility and affected the animal’s balance. She would have fallen down a lot,” says veterinary pathologist Rachel Reams of Eli Lilly & Company, who studied the fossil.
 
Usually, as MTs, we don't see clients in this condition, because they are so compromised that other health issues are of much higher priority at that point.
 
Unfortunately for what the poor dinosaur went through, there is physical evidence to back up Reams' inferences about what happened to her.
Larson and his colleagues found ample evidence confirming that conclusion. Throughout the Gorgosaurus’s skeleton, the researchers saw signs of debilitating injuries: a smashed shoulder blade, a bad infection in the lower jaw, broken ribs, and a torn tendon in the left leg. “The leg eventually healed and became useful again, but for a while she would have been dragging that leg around,” Larson says. The creature never recovered from a badly broken right fibula, the small bone of the lower leg. The fracture had healed for barely two weeks at the time of the animal’s death. That was probably the last injury the she suffered, although scientists do not know exactly what killed her. “She was a very sad dinosaur,” says Larson.
 

 


Nobody likes to think of an animal in distress, even as long ago as this happened, and even as scary a predatory beast as she was. The poor sad dinosaur lived and died alone with her disease, experiencing all the problems it created for her quality of life.

The only possible silver lining to suffering is if we can learn something from it that we can, in turn, use to prevent further suffering.

From what the poor Gorgosaurus has taught us through her brief life and awful death in the Cretaceous, how could you change the quotation at the very top so that MTs could share correct information about cancer with other MTs in public forums?

What do we now know about cancer from this 75-million-year-old "case report"?

 


cheers, to Bab Hambilus!

Notes on Guzzetta et al's article, "Massage Accelerates Brain Development and the Maturation of Visual Function", Introduction

These notes are intended to serve as a guide to reading the article by Guzzetta et al. There is a great deal of scientific jargon in the article, and the style is telegraphic--factors which make the article less accessible to people who might otherwise like to read the research for themselves.

This post is intended to accompany a reading of that article, to demystify the jargon for a non-specialist reading audience, to expand the telegraphic style, and to make explicit the implicit knowledge contained within.

The article under study is:

Guzzetta A, Baldini S, Bancale A, Baroncelli L, Ciucci F, Ghirri P, Putignano E, Sale A, Viegi A, Berardi N, Boldrini A, Cioni G, Maffei L. Massage accelerates brain development and the maturation of visual function. Journal of Neuroscience. 2009 May 6;29(18):6042-51. PMID: 19420271 Free fulltext PDF of article available here.
 
Abstract: Environmental enrichment (EE) was shown recently to accelerate brain development in rodents. Increased levels of maternal care, and particularly tactile stimulation through licking and grooming, may represent a key component in the early phases of EE. We hypothesized that enriching the environment in terms of body massage may thus accelerate brain development in infants. We explored the effects of body massage in preterm infants and found that massage accelerates the maturation of electroencephalographic activity and of visual function, in particular visual acuity. In massaged infants, we found higher levels of blood IGF-1. Massage accelerated the maturation of visual function also in rat pups and increased the level of IGF-1 in the cortex. Antagonizing IGF-1 action by means of systemic injections of the IGF-1 antagonist JB1 blocked the effects of massage in rat pups. These results demonstrate that massage has an influence on brain development and in particular on visual development and suggest that its effects are mediated by specific endogenous factors such as IGF-1.
 
 

The first paragraph is pretty straightforward and relatively easily readable, although there are a few points worth remarking upon.

When you read their sentence "EE has remarkable effects on adult brain function in several species", this is a good opportunity to remember that we used to think the adult brain was far less plastic than it turns out to be in reality.

Here, I am using the word "plastic" as in "plastic surgery", meaning that it lends itself to being molded or shaped or formed. The fact that the adult brain is somewhat plastic means that negative experiences in the past that influenced the brain have at least a hope of being recovered from.

Let's review how the visual system works, to ensure that we're all on the same page.

  • Action item (AI) 1/Raven: review of the visual system: I'll post it in this discussion, and in the human systems e-Book, when it is finished--most likely, by end of day (EOD) Monday.

 

"Appreciable" means empirically detectable, measurable.

  • AI 2/Raven: put definition of "appreciable" in the wiki.
 
 
For many of us--not all, since massage education in the United States is so variable--one of the first things we learned in anatomy and physiology class was the various levels of analysis that we could look at in an anatomical structure and its physiological function. Even so, those we learned did not represent all possible levels, but just the ones most useful at the beginning, such as the gross anatomical level or the systems level.
 
  • Question 1: Can you give an example of a structure and its function at the behavioral level, at the electrophysiological level, and at the molecular level?
 


There is a lot of technical language in the 2nd paragraph, but it really refers to only a few foundational concepts. Once you know how, for example, a BDNF receptor works, you will understand how an NMDA receptor works when you come across it, because it's the same general idea--the specific molecule involved is the only change.

So don't let a skim of this paragraph discourage you--it's not nearly as hard as it looks at first glance.

  • Question 2: What seems to be the cause-and-effect connection between EE and improved function and behavior in pups?
  • Question 3: Can you think of an analogy in human behavior? Remember, we are not claiming that we know that this is true, but that it could possibly serve as a testable hypothesis for further study.
 
 
"[L]icking and grooming provided by the mother has been shown to influence [here, positive influence is implied]: 

 

Although there remains a lot that we don't know about what the hippocampus does, it is fairly well-established that it plays a major role both in memory and in spatial coding (mental representations of the spatial relations between objects). [1]

 


Guzzetta also states that the level of licking and grooming provided by the mother affects molecules crucial for plasticity, meaning the brain's ability to be shaped or formed in new ways and to form new connections, rather than being frozen and relatively unable to change.

In this context of the brain, this refers to proteins and other molecules that promote the growth and development of brain cells (a process called neurogenesis), since the dynamics governing that growth and development is where plasticity comes from.

BDNF, short for Brain-Derived Neurotrophic Factor, is:

  • is a protein expressed by the BDNF gene;
  • is a growth factor;
  • is involved in neurogenesis;
  • is suppressed in cases of depression;
  • increased by the neurotransmitter glutamate, exercise, caloric restriction, intellectual stimulation
  • active and present in high concentrations in brain areas vital to learning, memory, and higher thinking, such as the hippocampus and cortex. [2]
 
 

NMDA, short for N-Methyl-D-aspartic acid, is a molecule that mimics the action of the neurotransmitter glutamate, so it can stand in for glutamate when investigating the neurotransmitter's action under certain circumstances.

 
 
 
 

 
  • novelty reaction
  • exploratory behavior
 
Exploration is the act of making the unknown known and is a fundamental adaptive behavior across many species. A related adaptive behavior is novelty seeking, defined as a proclivity to approach unfamiliar situations. Abnormal exploratory behavior and novelty seeking are characteristic of many neuropsychiatric conditions, including excessive activity observed in bipolar mania, increased novelty seeking in substance use disorders, and prominent inactivity and withdrawal as observed in schizophrenia. For several decades, numerous animal paradigms of neuropsychiatric illness have assessed the multiple dimensions of exploratory behavior and novelty seeking. These models have been useful in elucidating underlying neurobiological mechanisms and testing novel psychotropic treatments. [3]
 
 
 

  • spatial learning and memory
  • level of glucocorticosteroid receptors in the hippocampus
Glucocorticoids are steroid hormones that play a role in reducing inflammation and in normal brain development. [4]
 
  • feedback control on hypothalamus-pituitary-adrenal axis
The hypothalamic–pituitary–adrenal (HPA) axis is a major system of hormonal control over many functions in the body. Much like a thermostat uses surrounding heat to tell if it needs to continue heating or to turn off the heat, the HPA axis checks blood levels of circulating hormones to determine whether to stimulate or stop stimulating hormone production in the glands in the system.
 
  • spine density and synaptic plasticity in hippocampus
This refers to the structure and plasticity of neurons in the hippocampus.
 
 

negative effects produced by maternal separation/deprivation or prenatal stress on:
  • pup growth
  • growth hormone (GH) secretion

Growth hormone, secreted by the anterior pituitary gland, plays a major role in structure growth and regulation of other hormonal systems in the body, such as the production of IGF-1.

 

 
 
 
 
 
  • HPA axis
  • BDNF expression
  • synaptophysin expression

Synaptophysin is a protein expressed by the SYP gene. The exact function of the protein is unknown...Recent research has shown, however, that elimination of synaptophysin in mice creates behavioral changes such as increased exploratory behavior, impaired object novelty recognition, and reduced spatial learning. [5]

 

 
"rescued": here it means "mitigated", or "alleviated"
 
"Working in preterm infants, Schanberg and Field (1987) found evidence that massage promoted a faster weight gain and a lower level of cortisol in massaged infants."
 
  • Question 4: What's wrong with this sentence?
 
 

Paragraph 3 is relatively straightforward and easy to understand.
 
 

Paragraph 4
 
Visual evoked potentials (VEPs) are measurements of electrical activity in the nervous system after some source of visual stimulation has occurred. For example, an investigator might use VEPs to trace the activity in the brain to see what happens when the subject is watching a flashing light.
 
Visual acuity is the sharpness or clearness of someone's vision--how clearly they can see.
 
Source: http://upload.wikimedia.org/wikipedia/commons/9/9f/Snellen_chart.svg accessed 4 December 2011
 
 
 
Electroencephalography (EEG) is the measurement of the brain's electrical activity
 
 
 
by means of electrodes placed along the scalp.
 
 
 
 
 
 
 

In paragraph 5, Guzzetta states that "IGF-1 mediates EE effects on visual cortical development". To "mediate" means to be in the middle of other things. Let's say the independent variable (roughly, the "cause") in the following figure is EE, and the dependent variable (roughly, the "effect") is visual cortical development.

Path C shows a connection where EE directly causes visual cortical effects. But here, Guzzetta is saying that that is not the case--instead, EE has an effect on IGF-1 (path A), and IGF-1 then has an effect on visual cortical effects (path B). IGF-1, then, mediates (is a mediator variable between) EE effects and visual cortical development.

 
 
 
 
So now that we've established the role that Guzzetta's team proposes it plays in mediating the effects of EE into visual cortex development, let's talk about what IGF-1 is.
 
IGF-1:
  • is a protein molecule, encoded by the IGF1 gene, that functions as a hormone;
  • is named Insulin-like Growth Factor 1:
    • "Insulin-like" because of its structural similarity to insulin;
    • "Growth Factor" because of its lifelong anabolic role;
    • "1" because it is a member of a family of structurally-related proteins, such as IGF-2;
  • is produced mostly by the liver;
  • is a primary mediator of Growth Hormone (GH);
  • appears to play a major role in biological aging and cancer, as well as in normal growth. [6]
 
 
 
How it works:
  1. the anterior pituitary in the brain produces GH, and releases it into the blood;
  2. GH goes to the liver, and stimulates it to produce IGF-1, and release it into the blood;
  3. IGF-1 causes growth in many different kinds of cells in the body, including the ones we're interested in here: the visual cortical cells in the occipital lobe.
     
Guzzetta also states that EE increases the number of IGF-1-positive neurons in the visual cortex; this is an example of neurogenesis.
 
They describe how increasing IGF-1 in the visual cortex of non-EE rats by means of osmotic minipumps mimics EE effects, accelerating visual acuity development.
 
An osmotic minipump is a tiny implantable device that delivers IGF-1, which the rat's cells then take up by osmosis.
  • AI 3/Raven: finish demonstration of diffusion, use that to lead into osmosis
 
 
The visual cortex is the part of the brain that processes information delivered from the eyes. This is the brain of a person whose hair, skin, and skull have been digitally removed from the image.
 
The person is facing away from you, so you are looking at the back of their head: the occipital lobe.
 
A funny thing is that--although the eyes are in the front of the head, the information they deliver has to travel all the way to the back to be processed, and then is projected all the way back up front to the eyes again, which gives the perception that vision is in our eyes.
 
 
The name "visual cortex" tells us that it's in the cortex, or outer layer of the cerebrum--the darker purple in this picture of a slice of brain tissue; the gray matter of the brain, as opposed to the inner layer of white matter.
 
 
 
 
 
Guzzetta observes that blocking IGF-1 action in the visual cortex of EE rats by means of the IGF-1 receptor antagonist JB1 blocks EE action on visual acuity development. JB-I blocks IGF-I signaling; in the following discussion of antagonists, we'll discuss in more detail how it does so.
 
They also observe that massage led to increased levels of blood IGF-1 and IGF1BP3 in human infants. IGFBP-3 is a carrier or a binding protein for IGF-1, preventing the kidney from quickly clearing it from the blood, as it normally would. [6]
 
Guzzetta states that massage led to increased number of IGF-1 positive neurons in the cortex in rat pups.
  • Question 5: Why didn't they test this in human infants?
 
 
Guzzetta also observes that antagonizing IGF-1 action blocked the effects of massage in rat pups. You can think of an antagonist at a molecular level as being both similar to and different from an antagonist at the muscular level.
 
Like a muscular antagonist, a molecular antagonist works against, or opposes, another molecule. But the way in which it opposes that other molecule is not like how an antagonist muscle works.
 
A molecular antagonist is similar enough to the other molecule that it can slip into the "lock-and-key" receptor, and block it off, so that when the other molecule arrives, it cannot find a receptor to take it up.
 
So Guzzetta is saying that they hypothesize that the effects of massage are mediated by IGF-1, and the fact that an IGF-1 antagonist blocked the effects of massage reinforces the hypothesis that massage affects the visual cortical neurons in a way that is mediated by IGF-1.
  • Question 6: Why didn't they test this in human infants?
 
  • Question 7: What is the purpose of Guzzetta's study?
Imagine you're explaining it to someone you just met at a party, or on the bus, not in the lab or clinic--use that level of language, rather than Guzzetta's jargon.
 
  • Question 8: What did they say about their results in this paragraph?
 
 
 

References

[1] Wikipedia: Hippocampus accessed 4 December 2011

[2] Wikipedia: BDNF accessed 4 December 2011

[3] Minassian A, Henry BL, Young JW, Masten V, Geyer MA, Perry W. Repeated assessment of exploration and novelty seeking in the human behavioral pattern monitor in bipolar disorder patients and healthy individuals. PLoS One. 2011;6(8):e24185. PMID: 21912623

[4] Wikipedia: Glucocorticoid accessed 4 December 2011

[5] Wikipedia: Synaptophysin accessed 4 December 2011

[6] Wikipedia: IGF-1 accessed 4 December 2011

 

Canine PTSD and the case for interdisciplinary learning

Reading this story in the New York Times this morning, I was struck by not only the content of the story--which is important, and which I'll bring up over at Journal Club, where we're discussing massage for female veterans with PTSD--but also by the very topic.

After Duty, Dogs Suffer Like Soldiers 

By JAMES DAO
Published: December 1, 2011

SAN ANTONIO — The call came into the behavior specialists here from a doctor in Afghanistan. His patient had just been through a firefight and now was cowering under a cot, refusing to come out.

Post-traumatic stress disorder, thought Dr. Walter F. Burghardt Jr., chief of behavioral medicine at the Daniel E. Holland Military Working Dog Hospital at Lackland Air Force Base. Specifically, canine PTSD.

If anyone needed evidence of the frontline role played by dogs in war these days, here is the latest: the four-legged, wet-nosed troops used to sniff out mines, track down enemy fighters and clear buildings are struggling with the mental strains of combat nearly as much as their human counterparts. [1]

 
 

Among many people in my family, as well as some I grew up with, the concept of a psychological condition like canine PTSD is laughable--or it would be, if they did not find it so offensive and disrespectful. 

They are firmly committed to the idea of human exceptionalism: the idea that humans are categorically special and different from other animals by virtue of human cognition, emotions, and other features of our brains and minds.

There is nothing wrong at all with wanting to feel special--without that impetus, the entire corpus of unique human self-expression, such as paintings, sculptures, and poetry, would not exist. Nor, probably, would large parts of the motivation behind exploring universals in knowledge.

At some level, everyone wants to feel special, and there is no mistake in that, as long as that feeling is not used as a filter for evaluating evidence.

The problem lies in accepting or rejecting evidence based on whether it reinforces our feeling of specialness rather than on whether the evidence itself is valid or trustworthy.

If you choose to think that only humans are capable of tool use, or self-awareness, or emotions, or of moral value judgments, or of cultural learned behavior, or of problem-solving, then you have to ignore a great deal of accumulated evidence that contradicts those views.

 

 

These traits may appear rudimentary or different in other animals, compared to how humans express them, but that does not necessarily mean that the underlying neural mechanisms are qualitatively or essentially different.

To accept the evidence of those cognitive, emotional, and psychological processes in other animals that we had once thought only humans were capable of is not to diminish or insult humans as a result. It is perfectly reasonable to say both that humans in distress are worthy of caring for, and that animals in distress are also worthy of caring for--it is not a zero-sum game, where one detracts from the other.

In my opinion, a passing acquaintance with foundational knowledge in the following disciplines would be very useful for a better understanding among MTs about our natural world, and--through that understanding--about how we can better provide help, support, and service to our clients:

  • evolutionary biology: the structural and functional similarities and differences among animals (including ourselves) over time, and what we know about the genetics/genomics involved in those similarities and differences;
  • comparative neuroscience: what we know about the brains and minds of other species, and what insight that knowledge provides about our own;
  • comparative psychology: what we know about the minds and behavior of other species, and what insight that knowledge provides about our own;
  • comparative history of ideas: what we have thought about the world around us at certain parts of our history in light of what we knew at the time, and the effect those ideas have had upon us and upon our environment.

 

That's why POEM is committed to providing high-quality, validated, universally accessible, and user-friendly information resources in all these areas, and more.

 

Source: http://graphics8.nytimes.com/images/2011/12/02/us/02canine/02canine-articleLarge-v2.jpg accessed 2 December 2011

 


References

[1] New York Times: More Military Dogs Show Signs of Combat Stress accessed 2 December 2011 

 

 

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