UC San Diego Health Sciences News

Study Identifies Protein Essential for Normal Heart Function

Mon, 17 Jun 2013 09:24:49 -0700

Study Identifies Protein Essential for Normal Heart Function: Protein being studied to fight cancer;...

A micrograph by Thomas Deerinck of the National Center for...

Fri, 14 Jun 2013 11:49:50 -0700

A micrograph by Thomas Deerinck of the National Center for Microscopy and Imaging Research at UC San Diego reveals the organization of stained glial cells (cyan), neurofilaments (green) and DNA (yellow) in a section of rat hippocampus.

Remembering why we’re so alike

In 1859, not long before Charles Darwin would publish his seminal On the Origin of Species, the renowned British comparative anatomist and paleontologist Sir Richard Owen published a controversial work of his own – an essay contending that humans should be reclassified as distinct and separate from other primates.

Owen was among the scientific greats of his day, a hugely influential figure who was, among other feats, the first to recognize that the fossilized remains being discovered around the world represented a distinct group of prehistoric animals he dubbed “Dinosauria.”

In other words, they weren’t just old, dead reptiles.

But Owen proved to be wrong-headed about other things, most notably his stubborn opposition to Darwin’s theories about evolution and human origins. In his 1859 paper, Owen argued that modern humans represented a singular species based, in part, upon three ostensibly unique neuroanatomical differences in brain structure with nonhuman primates.

In a paper published online this week in PNAS, Larry R. Squire, PhD, professor in the departments of neurosciences, psychiatry and psychology at the UC San Diego School of Medicine and Veteran Affairs San Diego Healthcare System, and Robert E. Clark, PhD, associate professor of psychiatry, recount Owen’s misthinking and go on to explain how memory systems involving the hippocampus are quite similar in form and function in rodents, monkeys and humans.

I won’t go into great detail here about Squire’s and Clark’s observations. They tell a great story, including a brief recounting of patient H.M., who suffered from profound amnesia. Their basic point: There are multiple memory systems among animals, but their differences also highlight their similarities. Rodents, monkeys and other non-humans think a lot like us.

As for Sir Richard, he met up with Thomas Henry Huxley, one of Darwin’s most ardent advocates, a few years later in a famed debate about evolution in general and his notions of brain structure in particular. This debate is not to be confused with Huxley’s 1860 rhetorical romp with the redoubtable Bishop Wilberforce on the merits of evolutionary theory. But like that debate, Huxley easily rebutted all of Owen’s assertions, noting that his three criteria for human uniqueness (one being the existence of a brain region called the hippocampus minor) were found in all primate species. Indeed, in some species the size of the hippocampus minor was larger than in humans.

After Owen’s death in 1892, Huxley reviewed his work, perhaps ungraciously concluding that “hardly any of these speculations and determinations have stood the test of investigation, or, indeed, that any of them were ever widely accepted.”

To be fair, Owen did leave a distinguished scientific legacy, not least of which was the founding of the magnificent British Museum of Natural History. It’s just that in terms of brain anatomy and memory, his ruminations are perhaps better forgotten.

Metastasized human breast cancer cells (magnified 400 times,...

Fri, 14 Jun 2013 08:50:21 -0700

Metastasized human breast cancer cells (magnified 400 times, stained brown) in lymph nodes. Image courtesy of National Cancer Institute.

Developmental Protein Plays Role in Spread of Cancer

A protein used by embryo cells during early development, and recently found in many different types of cancer, apparently serves as a switch regulating the spread of cancer, known as metastasis, report researchers at the University of California, San Diego School of Medicine and UC San Diego Moores Cancer Center in the June 15, 2013 issue of the journal Cancer Research.

Metastasis is responsible for 90 percent of cancer-related deaths. More than 575,000 Americans die of cancer each year, the second leading cause of death in the United States after cardiovascular disease.

The scientists, led by principal investigator Thomas Kipps, MD, PhD, Evelyn and Edwin Tasch Chair in Cancer Research at UC San Diego, discovered an association between the protein, called Receptor-tyrosine-kinase-like Orphan Receptor 1 or ROR1, and the epithelial-mesenchymal transition (EMT), a process that occurs during embryogenesis when cells migrate and then grow into new organs during early development.

In research published in 2012, Kipps and colleagues reported for the first time that ROR1 is expressed during embryogenesis and by many different types of cancers, but not by normal post-partum tissues. They also discovered that silencing the protein impaired the growth and survival of human breast cancer cells.

More here

Pilot Program Using Telemedicine to Decrease Emergency Room Wait Times

Tue, 11 Jun 2013 09:51:35 -0700

Pilot Program Using Telemedicine to Decrease Emergency Room Wait Times: Emergency department (ED)...

Not your dad’s Folger’s crystalsGranted when the above-imaged...

Tue, 11 Jun 2013 08:26:07 -0700

Not your dad’s Folger’s crystals

Granted when the above-imaged substance is described as “a bitter, crystalline xanthine alkaloid,” it’s not likely to generate much consumer buzz, but then most Americans have something of a love-hate affair with caffeine.

Depending on what day it is, it seems like there is a new scientific study either extolling the under-appreciated health benefits of caffeine or reporting a new heightened health risk from over-consumption. Sometimes things seem to change between cups.

Here’s just a taste:

On the plus side, varying degrees of caffeine consumption have been associated with a lower risk of cardiovascular disease, some kinds of cancer and diabetes; slower cognitive decline related to aging; lower risk of Alzheimer’s disease and improved abilities (perhaps temporary) to pay attention, concentrate, learn and remember.

On the negative side, caffeine can increase blood pressure, a risk factor for strokes and cerebral vascular disease, which in turn increase the risk of multi-infarct dementia. Caffeine may reduce fine motor control movements while conversely increasing the need to urinate. That’s not necessarily a neat combination. High doses are linked to anxiety, accelerated bone loss and “auditory hallucinations.” That voice telling you to have a 20th cup may not be your favorite barista.

So, if you haven’t already concluded, there are lots of pros and cons to caffeine, and lots of myths to, according to sources like WebMD.

Its bottom line: There’s nothing wrong with moderate consumption if you’re a healthy adult. Moderation in this case being something less than a triple venti café latte with multiple add-shots of espresso and syrups.

There is no pretty picture for that.

Image source: Wellcome Images

Do New Dads Get Blue, Too? Three questions for our expert Much...

Mon, 10 Jun 2013 08:40:47 -0700

Do New Dads Get Blue, Too? Three questions for our expert

Much is known about the sympathy symptoms men experience when their partners are pregnant –everything from weight gain to nausea. It’s called Couvade syndrome and has been used as fodder for plots in many a romantic comedy or television sitcom. But what about after the baby is born?

Both the “baby blues” and postpartum depression and anxiety (PPD/A) are characterized with irritability, restlessness and anxiety in women who’ve recently given birth. PPD/A is a more serious condition with lasting symptoms that can range from hopelessness to confusion to fear of harming the newborn.

If dads-to-be can experience nausea, fatigue and weight gain concurrent with moms-to-be, can new dads also experience PPD/A?

We’ve asked Katie Hirst, MD, director of UC San Diego Health System’s Maternal Mental Health Clinic, three questions about the baby blues, postpartum depression and new dads.

Question: First things first, what should women be aware of in order to discern between the “baby blues” and PPD/A?

Answer: “Baby blues” is related to the combination of a few major events that occur around childbirth: 1) you have a baby! (a pretty big emotional impact); 2) there is a massive drop in hormones immediately after the placenta is delivered, which can make chemicals in the brain go haywire for a little while; and 3) sleep deprivation from the third trimester and labor/delivery. The majority of women find that, within a few days of delivery, these three factors lead to tearfulness (often for no clear reason), irritability, mild insomnia and/or anxiety.

The important differences between “baby blues” and PPD/A are severity and duration: “baby blues” does not impact your ability to take care of your newborn or yourself, and does not last for more than 2 weeks postpartum. In contrast, PPD/A typically starts anytime in the first 6 weeks postpartum and (if untreated) can last for months or even a year. Women with PPD/A may be too depressed or anxious to take care of their newborn like they would normally be able to do, and almost always feel very overwhelmed and/or irritable.

Q: A 2010 study in the Journal of the American Medical Association (JAMA) reported that up to 10 percent of new dads may experience PPD/A. Are the symptoms in men similar to those in women or are there specific factors that new parents should be on the look-out for? Does it differ from feeling overwhelmed by new responsibilities of fatherhood?

A: Just as with women, men with PPD/A report feeling overwhelmed and are typically irritable or “snappy” as a result. While most people expect a depressed mother or father to feel sad, both men and women with PPD/A often deny feeling sad but do report less enjoyment in their everyday life. I commonly hear statements such as, “I just feel ‘blah,’” “nothing excites me anymore,” and “I’m just going through the motions.”

While most new fathers feel tired and overwhelmed, and couples can certainly get a bit snappy with each other from the stress of caring for a newborn, a father with PPD/A feels all of this much stronger than expected. Guilt over not being the “perfect dad” in his mind, feeling trapped and losing the ability to concentrate are also common. The most notable (and frustrating) symptom is often difficulty sleeping—either trouble falling asleep or waking up even though the baby is sleeping. New dads are tired, for sure, but this is even worse with insomnia.

Q: Men are notorious for not seeking medical care and especially mental health care. If PPD/A is suspected in a new dad, what can friends or family do to help?

A: Talking with a new dad about how he is feeling, and letting him know that fathers are almost as likely as mothers to have PPD/A are the most important first steps. Just as women think “it won’t happen to me,” men often think “it can’t happen to me because I’m a man.” Awareness is the first step, then acceptance—letting him know that it’s a common occurrence and that getting better will help him be the best father possible. Giving him the articles and website listed below may show him that he is not the only man to go through this.

Understanding Male Post-Partum Depression
Slouching Toward Fatherhood
postpartummen.com

Image source: Sports Law blogspot

A transmission electron micrograph (four views) of a herpes...

Thu, 06 Jun 2013 10:39:15 -0700

A transmission electron micrograph (four views) of a herpes simplex virus. Courtesy David Gregory and Debbie Marshall, Wellcome Images.

Herpes Virus Exploits Immune Response to Bolster Infection

Researchers at the University of California, San Diego School of Medicine and colleagues report that the herpes simplex virus type-1 (HSV-1), which affects an estimated 50 to 80 percent of all American adults, exploits an immune system receptor to boost its infectivity and ability to cause disease.

The findings are published in the June 6, 2013 issue of Nature Communications.

HSV-1 is a persistent and problematic pathogen. Typically, it infects victims through oral secretions (kissing, sharing a contaminated toothbrush) or through openings in the skin. In healthy people, the result may be cold sores or fever blisters. In people with compromised immune systems, HSV-1 can pose more serious and chronic health problems. It can spread, for example, to organs like the brain, lungs and liver, where the infection may become life-threatening. Some patients, such as those with atopic dermatitis – a common form of eczema that accounts for roughly 20 percent of all dermatologic referrals, are especially vulnerable to serious complications stemming from an HSV-1 infection.

Led by principal investigator Richard L. Gallo, MD, PhD, professor of medicine and chief of UC San Diego’s Division of Dermatology, the scientists found that HSV-1 launches an infection by binding to receptors on the surface of skin cells. Ordinarily, if a cell recognizes the virus as an invader, an immune response is immediately triggered, which includes a group of proteins called scavenger receptors that help identify and remove harmful viruses.

But sometimes the process goes awry. While studying HSV-1 and scavenger receptors in cultured human skin cells, Gallo and colleagues in the Atopic Dermatitis Research Network, funded by the National Institute of Allergy and Infectious Diseases, discovered that the virus strongly interacts with a particular receptor called a macrophage receptor with collagenous structure or MARCO, which it uses to gain entry into cells.

More here

A team from National Geographic was in our Neonatal Intensive...

Tue, 04 Jun 2013 15:13:27 -0700

A team from National Geographic was in our Neonatal Intensive Care Unit (NICU) today to do a photo-shoot for the January 2014 issue of the magazine. The article will focus on the study of the use of tattoo electronics to monitor newborns and how this innovation will improve neonatal health overall.

The study was led by Todd Coleman, a bioengineering professor at the UC San Diego Jacobs School of Engineering – read more about here: Hugs From Mom and Dad, Without the Wires

A case of unilateral dermatoheliosis. Image courtesy of the New...

Tue, 04 Jun 2013 09:10:38 -0700

A case of unilateral dermatoheliosis. Image courtesy of the New England Journal of Medicine

Use an ocean of lotion

By now, you should be well-versed in the health benefits of applying sunscreen (and other forms of protection) to prevent skin cancer.

If not, then you’ve probably been living in a cave, which, if you think about it, is also a pretty good way to way to avoid excessive ultraviolet radiation.

But for those who aren’t familiar with the Food and Drug Administration’s guidelines on the subject, here’s a little added impetus: A new study out of Australia (where they know a thing or two about sun exposure) has found that using a sunscreen lotion regularly can slow signs of aging skin well into middle age.

Scientists at the Queensland Institute of Medical Research with colleagues split 903 Aussies aged 55 and younger into two groups: One group used a sunscreen with an SPF of at least 15 at their own discretion on their faces, necks, arms and hands; the other group used sunscreen much more regularly: every morning, after swimming, heavy sweating or spending several hours in the sun.

Four-and-a-half years later, the skin of the latter group was found to be 24 percent less likely to show signs of increased aging. The benefit did not appear to be influenced by pre-existing skin damage from the sun, but rather by how liberally participants slathered the lotion on.

As for the image above, courtesy of the New England Journal of Medicine, it’s more compelling visual evidence of what happens from a relative lifetime of unabated, unprotected sun exposure.

The face belongs to a 69-year-old man who drove a delivery truck for 28 years. Ultraviolet A rays streaming through his vehicle’s windows consistently struck the left side of his face, slowly and gradually thickening and wrinkling the skin while simultaneously destroying its elasticity. The condition is called dermatoheliosis. The patient’s doctor prescribed the use of sun protection, topical retinoids and periodic monitoring for skin cancer.

Altered Neural Circuitry May Lead to Anorexia and Bulimia

Tue, 04 Jun 2013 08:43:12 -0700

Altered Neural Circuitry May Lead to Anorexia and Bulimia : Anorexia nervosa and bulimia nervosa...

Human breast cancer cell. Image courtesy of the National Cancer...

Mon, 03 Jun 2013 16:30:57 -0700

Human breast cancer cell. Image courtesy of the National Cancer Institute.

Enhancer RNAs Alter Gene Expression
New class of molecules may be key emerging “enhancer therapy”

In a pair of distinct but complementary papers, researchers at the University of California, San Diego School of Medicine and colleagues illuminate the functional importance of a relatively new class of RNA molecules. The work, published online this week in the journal Nature, suggests modulation of “enhancer-directed RNAs” or “eRNAs” could provide a new way to alter gene expression in living cells, perhaps affecting the development or pathology of many diseases.

Enhancers are sequences in the genome that act to boost or “enhance” the activity or expression of nearby genes. They “often behave in a cell-specific manner and play an important role in establishing a cell’s identity and functional potential,” said Christopher Glass, MD, PhD, a professor in the department of Medicine and Cellular and Molecular Medicine at UC San Diego and principal investigator of one of the papers.

Although enhancers have been recognized for more than 25 years, scientists have labored to fully flesh out the breadth and complexity of what enhancers do and how they do it. In 2010, it was discovered that enhancers directed expression of RNA on a broad scale in neurons and macrophages, a type of immune system cell. Dubbed eRNAs, they were different from other classes of nuclear non-coding RNAs, and raised new questions about their potential roles in the functions of enhancers. The two Nature papers attempt to answer some of these questions.

In the first, principal investigator Glass and colleagues investigated a pair of related transcriptional repressors called Rev-Erb-alpha and Rev-Erb-beta (proteins with important roles in regulating the circadian rhythm in many cell types) in mouse macrophages. Using genome-wide approaches, they found that the Rev-Erb proteins repressed gene expression in macrophages primarily by binding to enhancers. Collaboration with researchers at the Salk Institute for Biological Studies revealed that the repressive function of Rev-Erbs was highly correlated with their ability to repress the production of eRNAs.

In the second paper, principal investigator Michael G. Rosenfeld, MD, a professor in the UC San Diego Department of Medicine and Howard Hughes Medical Institute investigator, and colleagues looked at estrogen receptor binding in human breast cancer cells – and its impact on enhancer transcription. In contrast to the repressive functions of Rev-Erbs, estrogen receptors (ERs) activate gene expression; but, like Rev-Erbs, they primarily function by also binding to enhancers. ER binding was shown to be associated with increases in enhancer-directed eRNAs in the vicinity of estrogen-induced genes, and to exert roles on activation of coding target genes.

Both papers offer new evidence that eRNAs significantly contribute to enhancer activity, and therefore to expression of nearby genes. “Because many broadly expressed genes that play key roles in essential cellular functions are under the control of cell-specific enhancers, the ability to affect enhancer function by knocking down eRNAs could potentially provide a new strategy for altering gene expression in vivo in a cell-specific manner,” said Glass, noting that in his research, anti-sense oligonucleotides were developed in conjunction with Isis Pharmaceuticals, which suppressed enhancer activity and reduced expression in nearby genes.

A scanning electron micrograph of ovarian cancer cells forming a...

Mon, 03 Jun 2013 12:25:35 -0700

A scanning electron micrograph of ovarian cancer cells forming a small tumor. Image courtesy of the University of Gothenburg.

Potential New Way to Suppress Tumor Growth Discovered

Researchers at the University of California, San Diego School of Medicine, with colleagues at the University of Rochester Medical Center, have identified a new mechanism that appears to suppress tumor growth, opening the possibility of developing a new class of anti-cancer drugs.

Writing in this week’s online Early Edition of the Proceedings of the National Academy of Sciences (PNAS), Willis X. Li, PhD, a professor in the Department of Medicine at UC San Diego, reports that a particular form of a signaling protein called STAT5A stabilizes the formation of heterochromatin (a form of chromosomal DNA), which in turn suppresses the ability of cancer cells to issue instructions to multiply and grow.

Specifically, Li and colleagues found that the unphosphorylated form of STAT promotes and stabilizes heterochromatin, which keeps DNA tightly packaged and inaccessible to transcription factors. “Therefore, genes ‘buried’ in heterochromatin are not expressed,” explained Li.

Phosphorylation is a fundamental cellular function in which a phosphate group is added to a protein or molecule, causing it to turn it on or off or to alter its function. An unphosphorylated STAT lacks this phosphate group.

More here

Oncogene Mutation Hijacks Splicing Process to Promote Growth and...

Fri, 31 May 2013 10:37:43 -0700

Oncogene Mutation Hijacks Splicing Process to Promote Growth and Survival

An international team of researchers – led by principal investigator Paul S. Mischel, MD, a member of the Ludwig Institute for Cancer Research and professor in the Department of Pathology at the University of California, San Diego School of Medicine – has found that a singular gene mutation helps brain cancer cells to not just survive, but grow tumors rapidly by altering the splicing of genes that control cellular metabolism.

The findings are published online in the journal Cell Metabolism.

Mischel, who heads the Ludwig Institute’s molecular pathology laboratory based at UC San Diego, and colleagues focused upon a process called alternative splicing, in which a single gene encodes for multiple proteins by including or excluding different, specific regions of DNA.

Alternative splicing is a tightly regulated and normal activity in healthy cells. For Mischel and colleagues in Los Angeles, Ohio and Japan, the question was whether mutations of a gene called EGFRvIII caused differential alternative splicing in glioblastoma multiformes (GBMs), the most common and aggressive type of malignant brain tumor. Median survival after GBM diagnosis is just 15 months with standard-of care radiation and chemotherapy. Without treatment, it is less than five months.

The scientists were particularly interested in whether the EGFRvIII mutation induced alternative splicing events that resulted in deregulation of normal cellular metabolism. “We focused on the ‘Warburg Effect,’ a common metabolic derangement in cancer that enables tumor cells to metabolize glucose in a way that provides both a sufficient supply of energy and a source of building blocks that can be used for growth,” Mischel said.

More here

Disorganized blood vessels shown in AIBP knockdown zebrafish....

Wed, 29 May 2013 11:00:19 -0700

Disorganized blood vessels shown in AIBP knockdown zebrafish. Green, endothelial cells; red, fluorescent dextran injected to visualize the blood vessel lumen.

Cholesterol Sets Off Chaotic Blood Vessel Growth

A study at the University of California, San Diego School of Medicine identified a protein that is responsible for regulating blood vessel growth by mediating the efficient removal of cholesterol from the cells. Unregulated development of blood vessels can feed the growth of tumors.

The work, led by Yury Miller, MD, PhD, associate professor of medicine at UC San Diego, will be published in the advance online edition of the journal Nature on May 29.

Cholesterol is a structural component of the cell and is indispensable for normal cellular function, although its excess often leads to abnormal proliferation, migration, inflammatory responses or cell death. The researchers studied how the removal of cholesterol from endothelial cells (cells that line the blood vessels) impacts the development of new blood vessels, the process called angiogenesis.

According to Miller, removal of excess cholesterol from endothelial cells is essential for restraining excessive growth of blood vessels.

“Too much cholesterol increases the abundance of lipid rafts, areas in the plasma membrane where surface receptors initiate signaling events leading to angiogenesis,” Miller said. VEGFR2 is such a receptor, playing a central role in the development of blood vessels. Research into the process of angiogenesis suggests that VEGF-induced signaling within endothelial cells is important to tumor growth.

In this study, the scientists show that apoA-I binding protein (AIBP) is secreted by surrounding tissues and facilitates cholesterol removal from endothelial cells. This process interferes with the VEGFR2 receptor function, in turn inhibiting angiogenesis.

“Studying the process in zebrafish, we found that the timing and the pattern of AIBP expression is such that it helps guide segmental arteries to grow strictly in the dorsal direction, instead of an aberrant sideways direction,” said first author Longhou Fang, who added that future studies will explore if AIBP or its derivatives can be used to inhibit pathologic angiogenesis in tumors. Alternatively, blocking AIBP activity in the heart may, in principle, stimulate re-growth of blood vessels after a heart attack.

Cultured fungus in the genus Trichphyton, the culprit behind...

Tue, 28 May 2013 11:00:00 -0700

Cultured fungus in the genus Trichphyton, the culprit behind athlete’s foot.

Close to you

It has been well-reported that there is much more to us – and much less.

To wit: It has been estimated that the total number of cells associated with our bodies outnumbers the total number of cells comprising our bodies by a ratio of 10 to 1. It’s estimated 500 to 1,000 species of bacteria live in our guts alone. Your personal mass of microbes works out to roughly 1 to 3 percent of your total mass. If you could effectively rid yourself of them, you could immediately drop a few pounds, though you’d also likely kill yourself since many of these microbes calling you home perform vital life-preserving functions, like aiding digestion.

In recent years, researchers participating in the Human Microbiome Project, have assiduously worked to produce the first full census of our little cootie cousins. Most of the work thus far has focused upon bacteria and, to a lesser degree, viruses. Not so much for the fungus among us.

That has changed with a new study out of the National Human Genome Research Institute (NHGRI), which looked specifically at the fungal species that inhabit different parts of our bodies, inside and out. The work is published in the journal Nature.

“We did an exploration where we looked at all the different little crevices of your body,” Julie Segre, a senior investigator with the NHGRI, told NPR.

Not surprisingly, Segre and colleagues discovered scores of fungi types, more than suspected in more places than previously suspected. Most of the fungi belonged to the genus Mallassezia. The place with the most fungi were – again, no surprise – the feet, where researchers found at least 80 varieties on the heel, 60 or so between the toes and more than 40 on toenails.

No one’s sure why our feet provide such a, uh, great foothold for fungi. One suggestion is the wide variety of temperatures found there, which offer a greater choice of housing options. Segre proffered a simpler explanation to NPR: “Even those of us who wear shoes a lot still walk around barefoot, either in our homes or in locker rooms. And there’s just great exposure to fungi.”

Aside from the yuck factor, some free-booting fungi pose health hazards, minor to deadly serious. The fungal family of Trichphyton causes skin to scale, crack and itch – otherwise known as athlete’s foot. The condition is typically treated with topical ointments, but severe cases can require oral antibiotics.

More alarming are fungal infections like Valley Fever, an ailment caused by inhaled soil-dwelling Coccidioides fungi that can, in severe cases, result in chronic, significant damage to many of the body’s major organs, including the brain.

Like bacteria and other microbes, we need and rely upon at least some forms of fungus to help us get by. But, as John Upton notes in this Slate article about the rise of killer fungi, the microorganisms thrive on environmental chaos and pose a real threat to man, beast and other life forms. It behooves us to get know them better.

Hold your friends close and your enemies closer, just not too close.

A three-dimensional, reconstructed magnetic resonance image...

Tue, 28 May 2013 08:43:19 -0700

A three-dimensional, reconstructed magnetic resonance image (upper) shows a cavity caused by a spinal injury nearly filled with grafted neural stem cells, colored green. The lower image depicts neuronal outgrowth from transplanted human neurons (green) and development of putative contacts (yellow dots) with host neurons (blue).

Stem Cell Injections Improve Spinal Injuries in Rats

An international team led by researchers at the University of California, San Diego School of Medicine reports that a single injection of human neural stem cells produced neuronal regeneration and improvement of function and mobility in rats impaired by an acute spinal cord injury (SCI).

The findings are published in the May 28, 2013 online issue of Stem Cell Research & Therapy.

Martin Marsala, MD, professor in the Department of Anesthesiology, with colleagues at UC San Diego and in Slovakia, the Czech Republic and The Netherlands, said grafting neural stem cells derived from a human fetal spinal cord to the rats’ spinal injury site produced an array of therapeutic benefits – from less muscle spasticity to new connections between the injected stem cells and surviving host neurons.

“The primary benefits were improvement in the positioning and control of paws during walking tests and suppression of muscle spasticity,” said Marsala, a specialist in spinal cord trauma and spinal injury-related disorders. Spasticity – exaggerated muscle tone or uncontrolled spasms – is a serious and common complication of traumatic injury to the spinal cord.

The human stem cells, said the scientists, appeared to vigorously take root at the injury site.

“In all cell-grafted animals, there was robust engraftment, and neuronal maturation of grafted human neurons was noted,” Marsala said. “Importantly, cysts or cavities that can form in or around spinal injuries were not present in any cell-treated animal. The injury-caused cavity was completely filled by grafted cells.”

The rats received the pure stem cell grafts three days after injury (no other supporting materials were used) and were given drugs to suppress an immune response to the foreign stem cells. Marsala said grafting at any time after the injury appears likely to work in terms of blocking the formation of spinal injury cavities, but that more work would be required to determine how timing affects functional neurological benefit.

More here

Degenerative Scoliosis: a Q & A with neurosurgeon William...

Wed, 22 May 2013 13:58:32 -0700

Degenerative Scoliosis: a Q & A with neurosurgeon William Taylor

More than half of all adults over the age of 70 have degenerative scoliosis – a curving of the spine that may cause pain, numbness and postural changes that result in decreased height and the appearance of shrinking.

When conservative approaches like physical therapy, steroid injections or bracing do not produce satisfying results, surgery becomes a primary option. A new minimally invasive alternative called lateral lumbar interbody fusion permits certain patients to avoid the current, typical open surgery, and return to everyday activities more quickly.

We asked William Taylor, MD, a neurosurgeon at UC San Diego Health System, to explain the nature of degenerative scoliosis and how some patients can stand a taller, faster.

Q: What causes curvature of the spine as we age?

A: Curvature of the spine may be caused by a number of factors, including fractures, congenital defects and even prior back surgery. In adults, scoliosis is usually related to degenerative disc disease, living longer and conditions such as osteoporosis and osteoarthritis. Everyone’s spine has a slight natural “S” curve, but with degenerative scoliosis, the spine is tilted more than 10 degrees in one direction. Sometimes patients may be teased about getting shorter in older age, but in reality this is a serious health condition that can cause pain and distressing neurological symptoms, such as numbness or tingling in the legs or difficulty taking deep breaths.

Q: How does the new surgical option differ from the current standard of care?

A: This new approach, which emerged about one year ago as part of a broader, on-going progression toward minimally invasive surgery, allows correction of up to 30 degrees per spinal segment in a minimally invasive procedure under general anesthesia. I’m able to make a 3-inch incision on a person’s side near their rib cage. I can then pass instruments through the incision to rebuild the defective portion of the spine with a small permanent implant. I like this approach because I can avoid all of the major organs and structures, such as muscles and ligaments.

In contrast, the other option is a major surgery in which the spine is rebuilt with long incisions in both the front and the back of the patient’s body. With this approach, there is a greater likelihood of trauma, blood loss and complications.

Eligibility for either surgery depends on the severity of the scoliosis. Both are appropriate for different types of patients.

Q: Are there age constraints to these techniques?

A: Because lateral lumbar interbody fusion is designed to be less invasive, it is appropriate for patients of all ages. I have treated patients from the ages of 25 to 80. When the quality of the patient’s life has decreased or if curvature of the spine is so severe that it displaces the internal organs, causing cardiovascular or pulmonary dysfunction, it’s time to consider treatment.

Also in older adults, if the spine is curved so much that the person’s balance is unsettled, there may be an increased risk of falls and fractures. That presents other health risks. By using a less invasive approach, patients may experience decreased pain, a shorter hospital stay, and most important, a quicker return to what was once their normal way of life. Of course there are always risks involved with any surgery. These should be discussed at length with one’s doctor.

UC San Diego Receives Grand Challenges Explorations Grant For...

Tue, 21 May 2013 13:13:27 -0700

UC San Diego Receives Grand Challenges Explorations Grant For Groundbreaking Research in Global Health and Development

The University of California, San Diego School of Medicine announced today that it is a Grand Challenges Explorations winner, an initiative funded by the Bill & Melinda Gates Foundation. Greg G. Goldgof, a graduate student in UC San Diego’s Biomedical Sciences Graduate Program and the Medical Science Training Program will pursue an innovative global health and development research project, titled “Outsmarting Malaria: Developing next generation anti-malarials that prevent the evolution of drug resistance.”

Grand Challenges Explorations (GCE) funds individuals worldwide to explore ideas that can break the mold in how we solve persistent global health and development challenges. Goldgof’s project is one of over 50 Grand Challenges Explorations Round 10 grants announced today by the Bill & Melinda Gates Foundation.

To receive funding, Goldgof and other Grand Challenges Explorations Round 10 winners demonstrated in a two-page online application a bold idea in one of four critical global heath and development topic areas that included agriculture development, neglected tropical diseases and communications.

“I am very appreciative that the Bill & Melinda Gates Foundation has funded my proposal to develop a new technology for drug development to treat malaria,” said Goldgof. “This information will be used to prioritize drug candidates for clinical trials and to identify new malaria drug targets for future therapies.”

More here

Escherichia coli bacteria, magnified 10,000 times Summer...

Tue, 21 May 2013 08:35:48 -0700

Escherichia coli bacteria, magnified 10,000 times

Summer bummer

With hot days ahead, thoughts naturally turn to the cool blue of swimming pools. Alas, not everything floating in those crystalline waters these days turns out to be an inflatable toy. A new report from the Centers for Disease Control surveyed 161 heavily used pools in metro-Atlanta in 2012. They ranged from public pools to pools at private clubs and water parks.

The CDC researchers sampled the pools’ filters, looking at what they contained. Of the 161 tested pools, more than half – 93 or 58 percent – contained Escherichia coli, a bacterium that lives abundantly in the gut of humans and other warm-blooded animals.

For the most part, E. coli is harmless, but some strains are pathogenic and are culprits behind many contaminated food events and recalls. In this case, however, the presence of E. coli is particularly icky since the bacterium is a strong indicator that someone (plural?) didn’t quite make it out of the pool to the restroom.

Actually, the CDC puts an even ickier spin on it, as only science can: “Each person has an average of 0.14 grams of fecal material on their perianal surface that could rinse into the water,” the authors observed (metaphorically).

Public pools had the highest incidence at 70 percent, followed by water parks at 66 percent and private clubs at 49 percent.

On the plus side, the researchers didn’t find any evidence in the pool filters of O157:H7, the E. coli strain most associated with food contamination and illness.

While distinguished in its disgustingness, E. coli wasn’t the most abundant of the microbes found doing the backstroke next to swimmers. That claim fell appropriately to Pseudomonas aeruginosa, a bacterium that causes swimmer’s ear. It was found in 95 of the 161 filter samples, a 59 percent incidence.

The CDC scientists were quick to note their Atlanta survey can’t be generalized to pools everywhere, but they did say the rates of pool-related illnesses nationally have been rising. Part of the problem is pool maintenance, to be sure, but swimmers have to take some of the blame.

“Swimmers have the power and responsibility to decrease the risk for recreational water illnesses by practicing good hygiene,” they wrote, suggesting that people shower thoroughly before entering a pool, take regular restroom breaks followed by another quick shower rinse before re-entering a pool and if you’re suffering from a diarrheal ailment, best stick to lounging in the sun.

Just remember to use sunscreen.

Angelina Jolie and the oncogene It’s not surprising that...

Tue, 14 May 2013 11:12:00 -0700

Angelina Jolie and the oncogene

It’s not surprising that Angelina Jolie’s announcement that she had preventive double mastectomy is big news. You can read about it here, here, here and here – among myriad places.

The fact remains, though, that Jolie’s dilemma and decision is far from novel. It’s one faced by many women, almost all without the glare or notice of media.

With that in mind, we reprise a pair of Q&As posed to breast cancer experts at UC San Diego: Teresa Helsten, MD, assistant clinical professor in the School of Medicine’s Division of Hematology-Oncology at Moores Cancer Center and Sarah Blair, MD, associate professor of Surgery at Moores Cancer Center.

Question: Angelina Jolie opted for her surgery based on the fact she carried the BRCA1 oncogene, which reportedly boosted her risk of breast cancer to 87 percent. How can a woman know if she should be tested for this genetic mutation?

Helsten: Above all, any woman (or man, in the case of breast cancer) who is concerned about the possibility of carrying a genetic mutation for breast/ovarian cancer should consult with her physician. Physicians may provide counseling or refer patients to trained genetic counselors for evaluation.

Things that might make a woman think about her risks include the following:

A family history of breast and other cancers: Think about both sides of the family (mother’s and father’s sides) and think about family members up to and including two generations away (up to and including grandparents or grandchildren). Any family that has two or more members with breast cancer or breast and ovarian cancer on the same side of the family, particularly if anyone has had breast cancer when younger than 50 years old, or has had two separate breast cancers. Any men with breast cancer. Breast cancer and one of the following cancers on the same side of the family: thyroid cancer, sarcoma, adrenal cancer, uterine (endometrial cancer), stomach (gastric) cancer, and leukemia/lymphoma.
Being from a population at risk: People of Ashkenazi Jewish descent have a higher risk of carrying a BRCA1/2 mutation. Women who are Ashkenazi Jewish may not need to have as strong a family history of breast and other cancers to be considered for testing. However, women of Ashkenazi Jewish descent with no personal or family history of breast cancer are probably not at risk.

Q: Once tested and the gene is present, what are a woman’s options?

Helsten: If a woman is found to carry a genetic mutation that increases her risks of breast and ovarian cancer, there are several things to think about:

What about screening for other family members? A trained genetic counselor or physician can counsel as to who should consider testing and how. When in doubt, other family members can discuss with their own physicians.

Does she want to do anything to reduce her risks of developing breast and ovarian cancer? If so, she will need to discuss carefully with her physician to help make the right decision for her as every case is unique. Options include increased surveillance (which doesn’t lower the risk of cancer, but increases chances of detection); taking risk-reducing medications (e.g., tamoxifen); and surgical removal of breasts and/or ovaries. For example, removal of both breasts by mastectomy reduces the risk of breast cancer by approximately 90-95 percent. These decisions can be very personal and very difficult, but the good news is that they almost never need to be made in a rush. It is worth taking the time to get informed in order to make a decision that is fits the individual.

Q: Does having the genetic mutation for breast cancer mean breast cancer is inevitable?

Helsten: No, cancer is not inevitable, but the risks are usually quite high. Depending on the specific mutations discovered, the lifetime risks of breast cancer for BRCA1/2 carriers are estimated to be 56-84 percent. For ovarian cancer, the lifetime risks are a bit lower. They are estimated to be 36-46 percent for BRCA1 and 10-27 percent for BRCA2 mutation carriers.

Q: Last year, comedian and actress Wanda Sykes underwent a double mastectomy for “stage zero breast cancer.” People are fairly familiar with stages I through IV, which denote the progressive size and spread of a tumor and its likely prognosis. What is stage 0 breast cancer?

Blair: When I counsel my patients, I show them a picture to demonstrate the difference. Basically these tumors start in the duct, which is a tube that drains milk when you breast feed. Tumors that are stage 0 are confined inside the duct and cannot spread outside to other parts of the body. However, if the tumor is left alone they can eventually break through the duct and become invasive. Early treatment prevents spread of the tumor.

Q: Was Sykes’ decision to have a radical mastectomy based on her family history of breast cancer typical for a stage 0 patient?

Blair: Most women are good candidates for breast conservation, which is removal of that area of the breast or lumpectomy plus radiation. I would also recommend the drug Tamoxifen for women with estrogen sensitive tumors. This drug treats the tumor itself and helps prevent future tumors. However, some women do not want to take Tamoxifen because of its side effects. For the average woman with stage 0 their lifetime risk of developing a second cancer in either breast is 20 percent. Some women with a strong family history of breast cancer, i.e. multiple relatives with breast cancer, may have a higher risk of a second cancer, particularly if they are diagnosed at a young age. These women may consider more aggressive surgical treatment to prevent future cancers. Typically, most women do not have radical surgery but those that do have much better cosmetic outcomes than in the past.

Q: Does a diagnosis of stage 0 mean that the cancer is 100 percent curable?

Blair: Unfortunately, nothing is 100 percent in medicine but there is a high likelihood of being cured. The chance of being cured depends on the size of the tumor and its appearance under the microscope or grade. In general the chance of being cured is greater than 90 percent.

Photo courtesy of AP