Earnest Starling Lecture 2018 #ExpBio

On Sunday David Mattson presented the Starling Distinguished Lecture of the American Physiological Society Water and Electrolyte Homeostasis Section. His talk addressed the role of inflammation in salt-sensitive hypertension, using the Dahl salt-sensitive rat and some supporting human data.

About half of human adults have hypertension, and about half of those patients are salt-sensitive like this rat. Feeding this rodent a high salt diet leads to rising blood pressure and albuminuria, with enlarged glomeruli, tubular damage, and inflammation. Other types of rats given the same level of sodium intake do not develop these findings. Studies from people with hypertension also show increased lymphocytes in their kidneys, suggesting that there are parallels with human disease.

In a series of experiments, Dr. Mattson showed that there were increased B and T cells in these rat kidneys and that the immune cells were activated and producing a number of cytokines. Inhibiting the presence and activity of these immune cells attenuated both the hypertensive and renal damages induced by salt loading. They then took genes identified in human association studies of hypertension and mutated the analogous genes in rats. They transplanted bone marrow from these mutant animals into Dahl rats without the mutation, so only hematopoietic cells carried the mutation in question. When salt loaded, these rats showed less hypertension than intact Dahl rats, suggesting that the immune response provided major input for hypertension.

What about the role of hypertension beating up on these kidneys? Dahl rats have poor autoregulation, so systemic hypertension gets transmitted to the kidneys. They placed an aortic cuff just above the left renal artery in rats and used it to maintain a normal blood pressure into that kidney. The right kidney saw and felt the higher pressure. This maneuver alleviated the inflammatory response in the cuffed kidney.

In the Dahl model of salt-sensitive hypertension, both inflammation and barotrauma appear to contribute to kidney damage. The story does not end here; the Mattson lab is presenting more fascinating work on this topic at this year’s meeting.

Smells and Tastes #ExpBio

This year the Renal Section Young Investigator Award goes to a favorite of mine, and not just because her work has let me create a great image of the kidney. Jennifer Pluznick, now an Associate Professor at Johns Hopkins, began her journey in physiology as a doctoral student at University of Nebraska while I was there. While a post-doctoral fellow at Yale, she began exploring G-protein-coupled-receptors (GCPRs) in the kidney, especially those previously involved with smell, and her lab now explores their role in kidney function. Her lab logo is pretty cool; I’ll wait while you take a look.

 

Olfactory receptors constitute the largest gene family with 350 members in humans and approximately 1000 members in rodents. So far, 18 of these olfactory receptors have been located in the kidney with an additional 11 taste-associated GCPRs and 76 without known ligands. She first studied olfactory receptor 78 (Olfr78), an interesting chemosensor that localizes to the afferent arteriole, a major site of control for blood pressure and kidney function. It’s ligands (activators) include short-chain fatty acids such as acetate and proprionate, molecules derived primarily from our gut microbiota. Proprionate has been shown to cause the release of renin via its interactions with Olfr78.

Changes in gut microbiota have been associated with changes in blood pressure, so her lab wanted to explore changes in the metabolites that might occur with hypertension. They implanted micro pumps into conventional mice and into germ-free mice (mice in a plastic bubble) and infused them with angiotensin II, an established model of hypertension. Germ-free mice showed no changes (no microbiome, no metabolites), but of more than 800 substances studied, 13 were unregulated with angiotensin II infusion. Some are uremic toxins and many are known to lower blood pressure; perhaps our microbiome is trying to help us out when our kidneys fail or our blood pressures otherwise get elevated. After all, our death would not be particularly helpful for the bacteria residing in our gut. Also interesting were some sex-specific changes identified. The meaning of these differences should provide fertile ground for further study.

As expected, Dr. Pluznick delivered an excellent presentation of her impressive work. If you aren’t here, you missed a great talk. You can still catch her on the TED stage:

A Gathering Crowd #ExpBio

Saturday of Experimental Biology can be a bit slow. Some folks are still traveling, while others are already exhausted by committee work. My flights yesterday proved uneventful, and I even got moved from 24F (coach window seat) to 3F (first class window) on the longer segment from Houston to San Diego (after I was settling into my narrow chair in the mid plane). Thanks to free red wine, I took cab to my hotel, unpacked, and hit the feather bed early.

Morning View

This morning a gentle sunrise woke me to a lovely view of distant mountains and the bridge to Coronado. Eventually I collected my meeting materials and attended two sessions.

The first one dealt with considering sex and age as biological variables in applications to the National Institutes of Health. Popular perception suggests that this is a mandate to look for sex differences, but really you just have to consider them.

  • Sometimes it’s inappropriate since a condition is sex-limited: prostate cancer, pregnancy, etc.
  • Sometimes a lack of sex differences have already been demonstrated
  • Sometimes you need to do a pilot experiment to show sex differences are not in play and then justify a single-sex study

Now the NIH will be adding consideration of age as a variable in the same manner. I see this as a bigger problem, because while there are two sexes, there could be infinite divisions of age!

I then moved on to a session on Social Media for Science, presented by the American Physiological Society Communications Committee. It provided basic introductions to Facebook, Twitter, and blogging, with brief shout-outs to LinkedIn, Instagram, and Research Gate.

#ISpyMarty

I am posting this blog before the Opening Receptions start. One fun activity this year is #ISpyMarty. The long-standing Executive Director of APS, Marty Frank, is retiring. To mark the occasion, Flat Marty is making the rounds for selfies that can be tagged with #ISpyMarty on Instagram, Facebook, and Twitter. Be on the lookout for everyone’s favorite cardboard cutout!

Now, let the science (and shenanigans) begin!

It’s #ExpBio Time Again!

It’s that time of year when all sorts of scientists head to Experimental Biology, this year in San Diego. I will once again be blogging the meeting, so cool cutting-edge kidney science will decorate these pages over the next week.

I’ve been planning my packing for a few days, including my electronic gizmos, cool shoes (of course), and background material for some of the studies. Friends will be there, and you can hear more details about scientists behaving badly in my twitter feed (@PHLane).

Yesterday I got a pre-meeting manicure. Don’t think of it as primping; its sharpening my claws for the wild world of science, even if the color does have the name Pinky Swear.

Go Kidneys!

No Mystery Here

As long as I can remember, I loved science. My copy of All About Dinosaurs suffered frequent readings. I went through a rock and mineral phase that I’m sure dismayed my parents. Finally I found biology, and eventually I picked medicine as a career option.

I also loved to read. For my elementary school years, publication of a new Nancy Drew book was cause for major celebration. When I ran out of her adventures, I tackled my brother’s Hardy Boys. Eventually, I graduated to Agatha Christy and other classic mysteries. I read a wide variety of things, but of the more than 400 books in my Kindle library, well over half involve solving crime.

Medicine, science, and mysteries involve many of the same processes. In all three, there is a problem to be solved. In medicine, we want to know what’s wrong with the patient. In science, we need to understand a phenomenon. In a mystery, we want to know whodunit. In all these fields, we collect information to help us first: a history and physical, a literature review, and looking for clues. In each area, we then formulate a hypothesis. In medicine, it’s a differential diagnosis. In science, it’s actually called a hypothesis. In a mystery, suspects are assembled and assessed for means, motive, and opportunity. Finally, any hypothesis has to be tested. In medicine, we run tests or try a treatment. In science, experiments get performed. In the world of crime, evidence gets accumulated until there is proof that someone did it and/or they confess. The results can thenI be examined to see if we accept our diagnosis/hypothesis/result or if we have to rethink everything again.

I’ve written a lot of biomedical papers and a handbook for academic medical faculty. I began blogging to communicate about science and found I loved writing in this less formal way. Now I’m exploring the world of fiction, especially trying to put together mysteries. I’ve perhaps come full circle.

Treading Water

Blogging used to be a habit, something I did.

Needless to say, I am out of the habit.

Lately I have been writing but not blogging. I signed up for a wonderful course, a do-it-yourself MFA. Oh sure, a lot of it could be learned by reading the book of the same title. But paying for the course gives me

  • motivation to get my money’s worth out of it
  • writing peers
  • an interactive experience

I find this relaxing (I have a day job, so no financial pressure to get that draft done), and the process has taught me a lot. No one will give me a bad grade for not keeping up with the class, either.

As I write, I realize that this site will change. What has been primarily a source of information about kidneys with a pediatric focus will now include other stuff. I may start pitching that children’s book about my cat with kidney disease again. I may post bits and pieces of other works here.

I hope you go along with me for the ride. It should be fun. And I hope I get around to putting a few more words on the internet!

Best Practices May Not Be

Another writing prompt today asked about so-called best practices for writing that have failed epically when I have tried them.

My biggest failure was the year I tried to do NaNoWriMo. In November each year a whole bunch of people sign up for National Novel Writing Month, pledging to write 50,000 words (the length of a short novel) during that month. I knew this was not a good time for me. I travel to two national meetings in November (although that airport time should be a bonus), and there are these holidays at the end of the month. Nevertheless, I gave it a shot. I was going well until about 5,000 words into it. It was time to write something about the antagonist, and I knew immediately it was bad. The earlier bits about the protagonist and her world, based on things I knew well, came easily. I needed to learn more about the villain(s) before I could write about them.

The idea of grinding out a first draft of crap is fine. I’ve done that a lot with scientific writing. In this case, the need for further research became crystal clear, and I started in on that. I’ve also started a different project where the antagonist is in a more familiar world. I’m hoping I can get my feet wet with this one and go back to my NaNoWriMo project when I understand my villains better (although that may take some time).

I’ve since met people who have written and published novels drafted in a November frenzy. It just didn’t work out for me this time.

Reality Demands It Be Honored

I signed up for a bookclub with writing prompts recently to get back in the habit of writing for myself. The newest prompt really hits the target:

Prompt: Tell a story about a time when you had to honor your reality.

Sometimes life gets in the way of writing, which pretty much describes the past two years. In January 2016, my husband started acting weird enough that work colleagues noticed. I had seen some subtler issues for a couple of months, but of course, he would not go to the doctor. When the department chair said he needed medical attention, he got medical attention.

We found a grapefruit sized brain tumor.

For the past two years, my posts have been few and irregular. Some have been updates about my spouse, and occasionally I have pulled off a real post. I have been scribbling in a journal on a more regular basis, but that is really digital screaming, not writing I would share without a great deal of editing.

Treatment has not worked well with this cancer, and Jim had to enter a nursing home last September. As I faced the inevitable conclusion to his journey, I realized that I wanted to write for me again.

And here we are.

Sometimes your reality means you miss a scheduled post. Sometimes it means you dwindle for a couple of years. Either way, reality demands it be honored.

Thank you to DIYMFA for providing so many resources to get me back on track.

Past, Present, and Future

I always loved to write. I remember creating “newspapers” in my room after I got a typewriter, and I spent a lot of time working on the yearbook and newspaper for my high school. My love of writing kept me going in research, even when the experiments did not turn out as planned. Over time, I have found joy in non-scientific writing. I got to help create a magazine and write a handbook.

One could see my biomedical career as a response to my childhood reading habits. I explored books about science and biographies of famous people in science and medicine. My other love was mysteries. What is a hypothesis or a diagnosis but a mystery? In every case, the reader wants, no, needs, to figure out what happened and why. I dabbled in other genres, but I always returned to mysteries, even after I outgrew Nancy Drew.

Now I want to write fiction. and I really want to create my own mysteries. I am exploring possible characters and scenarios. I need to post these from time to time to get feedback and have the fun of others reading my words.

I will still write about kidney science and nephrology. I hope you enjoy the ride as I explore my creative side.