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Behavioral Science, In the News, Patient Care, Research, Sleep, Stanford News

Watson, the narcoleptic Chihuahua, demonstrates symptoms on-air

Watson, the narcoleptic Chihuahua, demonstrates symptoms on-air

Watson - 560

What’s black and white (with just a few splotches of brown), understands French, and falls asleep at feeding times? A narcoleptic Chihuahua named Watson.

Watson’s becoming accustomed to the spotlight — he made his debut here at Scope, then went on to star in a KQED blog post. But today, Watson made it on air for The California Report. The segment begins – endearingly — with Emmanuel Mignot, MD, PhD, cooing to Watson in French. Mignot is Watson’s human and a sleep researcher known for the discovery of the gene that causes narcolepsy in dogs. (He also directs the Stanford Center for Sleep Sciences and Medicine).

Although Watson isn’t officially a Stanford dog — he’s Mignot’s pet — Mignot is hoping to use the slightly shy pup to help some of his patients, particularly children, who suffer from narcolepsy.

One of the symptoms of narcolepsy is cataplexy, a sudden loss of muscle control and Watson often suffers these attacks when he’s excited or spots tasty food.

“He looks at you with these eye half-closed and its almost like he’s just telling you, “Oh, I love you,” but in fact its because he’s having a sleep attack,” Mignot said.

Previously: Narcoleptic Chihuahua joins Stanford sleep researcher’s family, Stumbling upon circadian rhythms and Does influenza trigger narcolepsy?
Photo by Emmanuel Mignot

Microbiology, Research, Science, Stanford News

Tiny balloon-like vesicles carry cellular chatter with remarkable specificity, say Stanford researchers

Tiny balloon-like vesicles carry cellular chatter with remarkable specificity, say Stanford researchers

6292985963_bbc06df590_z“BRUSH YOUR TEETH,” I bellowed up the stairs last night at my (seemingly deaf and clueless) children for what seemed like the one-millionth time since their birth. “Surely there has to be a better way,” I pondered, as I trudged up the stairs to deliver my threatening message in person.

The cells in our bodies don’t have the option to, however reluctantly, leave their metaphorical couch and wag their fingers under the noses of their intended recipients. And yet, without a fail-safe method of communication among distant participants, the orderly workings of our bodies would screech to a halt.

Now biologists Masamitsu Kanada, PhD, and Christopher Contag, PhD, have published in the Proceedings of the National Academy of Sciences an interesting and revealing glimpse into one tool cells can use to do the job: tiny balloon-like vesicles capable of delivering a payload of protein or genetic information from one cell to another. As Contag and Kanada explained to me in an email:

Extracellular vesicles are nanosized little containers of information that are produced by most, if not all, cells in the bodies of plants, animals and humans. From many studies it is apparent that adding vesicles from one cell type to another can affect the behavior of the recipient cells, both in a culture dish and in the living body, even across species from plants to animals and presumably humans.

We wanted to assess, under controlled sets of conditions, which biomolecules within vesicles transfer the most information most efficiently. We learned that the process is complex, and that a biomolecule in one type of vesicle is transferred in a way that affects other cells, but the same molecule in another type of vesicle may not affect cell function.

In other words, Contag, who co-directs Stanford’s Molecular Imaging Program, and his colleagues found that not all these vesicles are created equal. Some, whose outer layer was derived from the cell’s external plasma membrane (these are known as micro-vesicles), handily delivered both protein and DNA to recipient cells. Others, with outer layers derived from internal membranes in the cell (known as exosomes), were less capable and didn’t deliver any functional DNA. Interestingly, neither kind was able to deliver RNA, which was instead swiftly degraded.

The distinction between vesicle type and function is important as researchers increasingly rely on them to eavesdrop on cellular conversations or even to deliver particular biomolecules to be used for therapy or imaging. Understanding more about how they work will allow researchers to both better pick the right type for the job at hand and to learn more about how cells talk with one another. As Contag and Kanada said:

How cells communicate across distances is relevant to mobilization of immune cells to attack pathogens, depression of immune responses by tumor cells, signaling of cancer cells to metastasize, modulation of physiological processes in intestinal cells in response to plant-derived diets and to many other biological process. Understanding this form of cell-to-cell communication will bring us closer to controlling how cells talk to one another inside the body.

Now if only I could find the right kind of vesicle to communicate with my recalcitrant children. Perhaps a helium-filled balloon with a pointed message inside could float up the stairs and pop next to their ears? On second thought, that might not be the best choice.

Previously: Researchers develop imaging technologies to detect cancer earlier, faster
Photo by Matthew Faltz

Medicine and Literature, Patient Care, Podcasts, Stanford News

Abraham Verghese: “A saintliness in so many of my patients”

Abraham Verghese: "A saintliness in so many of my patients"

Verghese lookingThere’s a quiet dignity that envelopes Abraham Verghese, MD. You can imagine other authors whose books have scaled to the top to be taken with themselves, hardly humble, but that’s not the case here. When you get to know him, you realize he’s a man of great depth, with a wonderful soul and a deeply felt sense of humanity. When he talks about treating patients it’s with reverence (“There’s a saintliness I saw in so many of my patients,” he told me) – as if each time he crosses the threshold into a patient’s room he’s entering hallowed ground.

Verghese has written two searing works of nonfiction: My Own Country, a paean to the young men he treated for HIV-AIDS when it was just emerging as a human scourge, and The Tennis Partner, a loving eulogy to a best buddy whose life went off the rails. Then the blockbuster novel Cutting for Stone: atop the New York Times best seller list for two years and selling more than one million copies. It’s a sweeping tale of how time transforms family – jolting the reader from the first page, where a Roman Catholic nun gives birth to twins boys and dies on the operating table. I read it during the height of the global economic chaos in 2009 and was transported each evening, thankfully, to another world outside of monetary meltdowns and fiscal maelstrom.

In this 1:2:1 podcast, Verghese and I talk about time’s impact on medicine, novels and life. (Time is the theme of the current issue of Stanford Medicine magazine.) About life, he tells me, “There’s a poignancy to living because we won’t live forever… As John Irving says in one of his books, ‘Life is a terminal condition. It’s about to run out on all of us…’ There’s no exception to that. And I think, in a way, that’s what makes life so beautiful.”

This podcast is accompanied by a Q&A with Verghese in the magazine.

Previously: Stanford Medicine magazine reports on time’s intersection with health, Abraham Verghese discusses stealing metaphors and the language of medicine at TEDMED, Stanford’s Abraham Verghese honored as both author and healer, Abraham Verghese’s Cutting for Stone: Two years as a New York Times best seller and Abraham Verghese at Work: A New York Times profile
Photo by Jason Henry

Chronic Disease, Immunology, Infectious Disease, Neuroscience, Research, Stanford News

ME/CFS/SEID: It goes by many aliases, but its blood-chemistry signature is a giveaway

ME/CFS/SEID: It goes by many aliases, but its blood-chemistry signature is a giveaway

signature

It’s the disease that dare not speak its name without tripping over one of its other names. Call it what you will – chronic fatigue syndrome (CFS), myalgic encephalomyelitis (ME) or its latest, Institute of Medicine-sanctioned designation, systemic exertion intolerance disease (SEID). It’s very real, affecting between 1 million and 4 million people in the United States alone, according to Stanford infectious-disease sleuth Jose Montoya, MD, who has closely followed more than 200 SEID patients for several years and done extensive testing on these patients in an effort to find out what’s causing their condition.

Different authorities have quoted different numbers regarding those with SEID. The name-calling and number-assigning squishiness stems from the fact that beyond its chief defining symptom – overwhelming, unremitting exhaustion lasting for six months or longer – it’s tough to pin down. Additional symptoms can range from joint and muscle pain, incapacitating headaches or food intolerance to sore throat, lymph-node enlargement, gastrointestinal problems, abnormal blood-pressure or hypersensitivity to light, noise or other sensations.

Research into the hows and whys of SEID has been plagued by the inability to establish any characteristic biochemical or neuroanatomical underpinnings of the disorder. Although many viral suspects have been interrogated, no accused microbial culprit has been indicted. To this day, there are no valid laboratory tests for diagnosing SEID.

But a burst of insight into SEID’s physiological substrate came only months ago when Stanford neuroradiologist Mike Zeineh, MD, PhD, working with patients from Montoya’s registry, found that they shared a pattern of white-matter loss in specific parts of the brain. The discovery drew a great deal of attention in the press as well as the CFS community. (See our news release about that study for details.)

Now a high-profile, multi-institution team including Montoya has published a study in Science Advances showing yet another physiological basis for a diagnosis of SEID: a characteristic pattern, or “signature,” consisting of elevated levels of various circulating immune-signaling substances in the blood.

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Bioengineering, Stanford News

Biodesign program welcomes last class from India

Biodesign program welcomes last class from India

Clark CenterIn January, three fellows from India arrived to Stanford to join the Biodesign program, which immerses clinicians, scientists, engineers and business people in the biodesign process for innovating successful medical devices.

What makes these three unique is that they’re the last class from the Stanford-India Biodesign program to visit home base, housed within the Clark Center and the interdisciplinary environment of Stanford Bio-X. The Indian program has been so successful that after this year they will become independent.

I’ll be following this final group of Indian fellows on their whirlwind tour of clinics, prototyping demos, brainstorming sessions, and courses on intellectual property and regulatory steps as they develop and prototype a medical device – and blogging about them along the way.

The three fellows I’ll be following – Debayan Saha, Shashi Ranjan, PhD, and Harsh Sheth, MD – all say they were drawn to the program in part because of its unique approach. Commonly, people develop medical devices and then look for a problem to apply it to. Or, they come up with a prototype that meets a real need, but don’t research the intellectual property or costs in advance and fail because of that oversight.

In the end, real needs are unmet.

In the Biodesign program, fellows first observe clinicians to learn what the needs are. Then they research the intellectual property, medical costs of the disease, and regulatory hurdles they would have to overcome before they ever start prototyping.

The end result has been 36 start-up companies and international programs in India, Singapore and Ireland all trying to replicate the process and meet their country’s own unique medical needs.

By June, Saha, Ranjan and Sheth will have developed a device prototype that solves a medical need in cardiovascular medicine, and that could potentially get to market. Sheth brings clinical expertise – he is a surgeon – while Ranjan and Saha both have engineering backgrounds.

So far, the group says their clinical visits have resulted in a list of more than 300 needs, which they say will grow before it shrinks down to the final one they decide to address. I’ll be documenting the process of whittling 300+ needs down to a single prototype, and interviewing leaders in Biodesign along the way.

For my next installment: The fellows visit a south Asian cardiovascular disease clinic run by Rajesh Dash, MD, PhD, and wonder if a device can change patient attitudes.

Previously: Biodesign fellows take on night terrors in children, Stanford Biodesign Program releases video series on the FDA system and A medical invention that brings tears to your eyes
Photo of the Clark Center by L.A. Cicero

Applied Biotechnology, Cancer, Evolution, Immunology, Research, Stanford News

Corrective braces adjust cell-surface molecules’ positions, fix defective activities within cells

Corrective braces adjust cell-surface molecules' positions, fix defective activities within cells

bracesStanford molecular and cellular physiologist and structural biologist Chris Garcia, PhD, and his fellow scientists have tweaked together a set of molecular tools that work like braces of varying lengths and torque to fix things several orders of magnitude too small to see with the naked eye.

Like faulty cell-surface receptors, for instance, whose aberrant signaling can cause all kinds of medical problems, including cancer.

Cell-surface receptors transmit naturally occurring signals from outside cells to the insides of cells. Molecular messengers circulating in the blood stumble on receptors for which they’re a good fit, bind to them, and accelerate or diminish particular internal activities of cells, allowing the body to adjust to the needs of the minute.

Things sometimes go wrong. One or another of the body’s various circulating molecular messengers (for example, regulatory proteins called cytokines) may be too abundant or scarce. Alternatively, a genetic mutation may render a particular receptor type overly sluggish, or too efficient. One such mutation causes receptors for erythropoietin – a cytokine that stimulates production of certain blood-cell types – to be in constant overdrive, resulting in myeloproliferative disorders. Existing drugs for this condition sometimes overshoot, bringing the generation of needed blood-cell types to a screeching halt.

Garcia’s team took advantage of the fact that many receptors – erythropoietin receptors, for example – don’t perform solo, but instead work in pairs. In a proof-of-principle study in Cell, Garcia and his colleagues made brace-like molecular tools composed of stitched-together antibody fragments (known in the trade as diabodies). They then showed that these “two-headed beasts” can selectively grab on to two members of a mutated receptor pair and force the amped-up erythropoietin receptors into positions just far enough apart from, and at just the right angles to, one another to slow down their hyperactive signaling and act like normal ones.

That’s a whole new kind of therapeutic approach. Call it “cellular orthopedics.”

Previously: Souped-up super-version of IL-2 offers promise in cancer treatment and Minuscule DNA ring tricks tumors into revealing their presence
Photo by Zoe

Neuroscience, Research, Sleep, Stanford News

Stumbling upon circadian rhythms

Stumbling upon circadian rhythms

PrintIn my job as a science writer, I get to hear lots of amazing stories of discovery. In some cases, researchers have worked diligently to solve one question for decades. Others I talk to describe exciting Eureka! moments where their data suddenly made sense. But some of my favorite stories are those where a scientist is studying one thing, only to make an off-the-cuff observation that leads them in a totally new direction.

In researching circadian rhythms for the latest issue of Stanford Medicine magazine, I heard lots of this last kind of story. There are many obvious ways that circadian rhythms influence biology: our sleep cycles, the way our stomachs start to grumble for lunch at the same time every day, and how many plants close their flowers each night. But scientists are also starting to reveal lots of hidden, unexpected ways that circadian rhythms – the natural cycles in living organisms – affect us. Over just the past few years, researchers in disparate fields have made chance observations that have made them think twice about the timing of their experiments; daily circadian cycles in our bodies can affect everything from how we metabolize drugs to how our immune system acts, they’ve found.

Craig Heller, PhD, who co-directs the Stanford Down Syndrome Research Center, told me about how he was testing a new drug to improve memory in mice with Down syndrome. During the course of his experiments, he noticed that mice who received the drug at night didn’t respond the same way as mice that received a dose in the morning. It led him to start investigating the link between learning, memory, and daily sleep cycles. What he discovered doesn’t just have implications for Down syndrome, but for learning and memory more broadly.

Then, sleep researcher Emmanuel Mignot, MD, PhD, of the Stanford Center for Narcolepsy, walked me through the story of how he and other scientists discovered a link between the immune system and narcolepsy. It all started, he explained, after an odd epidemiological observation: narcolepsy was more often diagnosed in the spring than in the fall.

Of course, lots of what we know about how circadian clocks tick along inside our bodies, keeping time with the world around us, comes from tireless, carefully planned out benchwork, and that can’t be discredited. But some of the most surprising new links I describe in my feature come from scientists taking leaps across fields to explain something they found curious. Check out my feature, “Hacking the Biological Clock,” to learn more about what Heller, Mignot, and other scientists have found on these journeys of discovery.

Sarah C.P. Williams is a freelance science writer based in Hawaii.

Previously: Stanford Medicine magazine reports on time’s intersection with health, Study shows altered circadian rhythms in the brains of depressed people and Narcolepsy = autoimmune disease
Illustration by Harry Campbell

Cancer, Evolution, Genetics, Infectious Disease, Microbiology, Research, Stanford News

Bubble, bubble, toil and trouble – yeast dynasties give up their secrets

Bubble, bubble, toil and trouble - yeast dynasties give up their secrets

yeasty brew

Apologies to Shakespeare for the misquote (I’ve just learned to my surprise that it’s actually “Double, double, toil and trouble“), but it’s a too-perfect lead-in to geneticist Gavin Sherlock’s recent study on yeast population dynamics for me to be bothered by facts.

Sherlock, PhD, and his colleagues devised a way to label and track the fate of individual yeast cells and their progeny in a population using heritable DNA “barcodes” inserted into their genomes. In this way, they could track the rise and fall of dynasties as the yeast battled for ever more scarce resources (in this case, the sugar glucose), much like what happens in the gentle bubbling of a sourdough starter or a new batch of beer.

Their research was published today in Nature.

From our release:

Dividing yeast naturally accumulate mutations as they repeatedly copy their DNA. Some of these mutations may allow cells to gobble up the sugar in the broth more quickly than others, or perhaps give them an extra push to squeeze in just one more cell division than their competitors.

Sherlock and his colleagues found that about one percent of all randomly acquired mutations conferred a fitness benefit that allowed the progeny of one cell to increase in numbers more rapidly than their peers. They also learned that the growth of the population is driven at first by many mutations of modest benefit. Later generations see the rise of the big guns – a few mutations that give carriers a substantial advantage.

This type of clonal evolution mirrors how a bacterium or virus spreads through the human body, or how a cancer cell develops mutations that allow it to evade treatment. It is also somewhat similar to a problem that kept some snooty 19th century English scientists up at night, worried that aristocratic surnames would die out because rich and socially successful families were having fewer children than the working poor. As a result, these scientists developed what’s known as the “science of branching theory.” They described the research in a paper in 1875 called “On the probability of extinction of families,” and Sherlock and his colleagues used some of the mathematical principles described in the paper to conduct their analysis.

Continue Reading »

Research, Science, Stanford News

Stanford researchers show how hijacking an enzyme could help reduce cancer risk

Stanford researchers show how hijacking an enzyme could help reduce cancer risk

Mochly-RosenFor the first time, Stanford researchers figured out a sneaky way to make an enzyme do something it wouldn’t normally do — imitate another enzyme and digest alcohol properly. Their work suggests a possible preventative mechanism for alcohol-related cancers in an at-risk population and is a promising new route for drug discovery.

Daria Mochly-Rosen, PhD, professor in chemical and systems biology, and Che-Hong Chen, PhD, senior research scientist, conducted the study, which was published online yesterday in Proceedings of the National Academy of Sciences.

Enzymes are notoriously choosy, selectively responding to certain molecules that bind precisely in their active site, but the researchers were able to change the selectivity of an enzyme’s active site by “hijacking” it with a small molecule.

Making an enzyme act like another enzyme isn’t just cool. It can have important health consequences for people who have broken enzymes because of genetic mutations.

I wrote about this enzyme deficiency in a press release on the study:

When most people and animals consume alcohol, the body digests it rapidly, within a few hours. One of the byproducts of alcohol metabolism is a chemical called acetylaldehyde. According to the World Health Organization, acetylaldehyde is a Group-1 carcinogen, which means there is a direct link between exposure and cancer.

For most people, acetylaldehyde is not a major health risk — though it can contribute to hangover symptoms — because an enzyme called ALDH2 quickly converts it to a harmless acid. But for some, acetylaldehyde is a big problem.

These people lack a working version of ALDH2 because of a genetic mutation. ALDH2 deficiency is the most common genetic mutation in humans, affecting about 40 percent of East Asians — some 560 million people, or nearly 8 percent of the world’s population. Without a working enzyme, the body cannot clear the toxic acetylaldehyde quickly.

Continue Reading »

Chronic Disease, Health Policy, Public Health, Public Safety, Stanford News

New uses for old polymers: Stanford Engineering team uses surgical glove material to make air filters

New uses for old polymers: Stanford Engineering team uses surgical glove material to make air filters

After visiting China and enduring the stifling air pollution, Stanford engineering professor Yi Cui, PhD, wanted to explore solutions to the problem. This week, his team published a paper in the scientific journal Nature Communications, detailing a new kind of highly effective air filter made out of polyacrylonitrile, a synthetic polymer that is used to make surgical gloves.

The researchers used a relatively new technique called electrospinning, or drawing out microscopically thin threads from a liquid to make a lightweight and fairly transparent filter out of PAN. The filter attracts particles from the air, especially those around 2.5 microns – or PM2.5 – which are among the most dangerous for the human respiratory tract.

The researchers make the case for the new PAN air filter pretty eloquently in a press release:

“It was mostly by luck, but we found that PAN had the characteristics we were looking for, and it is breathtakingly strong,” said Po-Chun Hsu, co-author on the study and a graduate student in Cui’s lab.

. . .

“The fiber just keeps accumulating particles, and can collect 10 times its own weight,” said Chong Liu, lead author on the paper and a graduate student in Cui’s lab. “The lifespan of its effectiveness depends on application, but in its current form, our tests suggest it collects particles for probably a week.”

The material collects 99 percent of air particles for up to a week, but is still 70 percent transparent, so it could be used as a window covering. “It might be the first time in years that people in Beijing can open their window and let in a fresh breeze,” Cui said in the statement.

Previously: The high cost of pollution on kids’ healthStudy shows air pollution may increase heart attack risk more than drug useContinuing pollution restrictions used during Beijing Olympics could reduce cancer rates and New insight into asthma-air pollution link
Video by Kurt Hickman

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