The awe of similars
Samuel Hahnemann’s “law of similars" is one of the foundations of homeopathy and the notion that “like cures like.” That is, a substance that produces certain symptoms in a healthy person should be able to relieve those same symptoms in an unwell person.
For example, a person drinking a cup of strong coffee for the first time is likely to experience some or all of the effects of caffeine: racing thoughts, palpitations, increased urine production, shaky hands, excitability and restlessness (which is admittedly why many coffee drinkers consume the stuff in the first place).
According to Hahnemann’s law of similars, coffee should do just the opposite in a sick person already experiencing these symptoms. For example, a homeopath (someone who practices homeopathy) would treat a hyperactive child or an insomniac with a preparation of “coffee cruda,” or unroasted coffee beans. According to homeopathic hypothesis, the caffeine in the cruda would calm the kid and help the insomniac sleep.
Such notions are widely disputed, to say the least. There is very little empirical evidence, broadly accepted, that homeopathic remedies are effective treatments for any specific condition. Indeed, some homeopathic notions, such as medicinal concoctions in which the “active ingredient” has been diluted to the point of no longer actually existing in the concoction, fly in the face of scientific logic and reason.
But this blog post isn’t about celebrating the law of similars but rather the awe of the same. Many, many objects and phenomena in nature appear remarkably alike in appearance, but are, in fact, completely different or unrelated in function or purpose.
Take the two images above: The one on the left is a scanning electron micrograph of different human circulatory system cells: dimpled red blood cells, bumpy white blood cells, called lymphocytes, and disk-shaped platelets. The image on the right is a scanning electron micrograph of diverse pollen grains magnified many times.
The “Red Queen Effect” Writ Small
In what amounts to an evolutionary arms race at the molecular level, researchers at the University of California, San Diego School of Medicine describe how pathogens target or take advantage of key molecules on the surfaces of cells to evade detection or boost infection.
The findings are published in the March issue of The FASEB Journal.
All living cells are coated with chains of sugar molecules called glycans, with every organism sporting its own cloak of unique and characteristic glycan patterns, said first author Vered Padler-Karavani, PhD, a researcher at Tel Aviv University who originally worked with Ajit Varki, MD, co-director of UC San Diego’s Glycobiology Research and Training Center, and others on the study, including Takashi Angata, now at Academia Sinica in Taiwan.
In mammals, cell suface glycan chains are tipped with acidic sugars called sialic acids, which indicate to circulating immune system cells via receptors known as Siglecs that the cell is part of the host and not to be attacked as an invader.
However, certain pathogenic bacteria have evolved sialic acid containing glycans that mimic mammalian cells, using them to hide from and evade immune cells. Meanwhile, other pathogens, such as flu viruses, use sialic acids as binding targets to attack and infect host cells. In response to these dual pressures, mammalian sialic acids and Siglec receptors must be continuously tweaked to foil invasive microbes. But the faster evolving microbes adapt to the tweaks and the process repeats, over and over again.
The phenomenon is indicative of the so-called “Red Queen effect,” noted the researchers, a classic evolutionary concept inspired by Lewis Carroll’s novel Through the Looking-Glass. “Now, here, you see, it takes all the running you can do, to keep in the same place,” the queen says to Alice.
“Like Alice, who runs fast but finds herself still in the same spot, we find that certain sugar-receptors on our immune cells evolve rapidly in response to even more rapidly evolving pathogens, leading to a never-ending evolutionary arms race,” said Padler-Karavani.
The findings may have future implications for efforts to find new treatments and approaches to pathogens that try to take advantage of glycans, said Varki.
With MRI guidance, Chen can safely destroy tumors seated deep in the patient’s brain.
California’s First MRI-Guided Laser Treatment for Brain Cancer
Using a novel magnetic resonance imaging (MRI)-guided laser technology, neurosurgeons at UC San Diego Health System have successfully treated a malignant tumor deep inside a patient’s brain. This is the first time that this FDA-approved laser-based treatment has been performed in California.
“The patient’s brain tumor was located in the thalamus. Normally, to access a tumor in this region, the surgeon would have to remove considerable healthy brain tissue, thus subjecting the patient to significant neurologic injury,” said neurosurgeon Clark C. Chen, MD, PhD, vice chairman of research, UC San Diego Division of Neurosurgery. “This MRI-guided laser technology helps neurosurgeons preserve healthy brain tissues while allowing treatment of tumors that would otherwise be inoperable.”
Chen and his team used a technique called laser interstitial thermal therapy. The procedure is performed inside an MRI machine while the patient is under general anesthesia. A dime-size hole is created in the patient’s skull to access the tumor. A laser probe is then inserted into the tumor under real-time MRI monitoring and computer guidance. When the tumor is reached, the laser beam is activated, heating and destroying tumor cells.
“It is well-known that MRI can be used to generate detailed images of the brain. What is less known is that MRI can also be used to measure the internal temperature of the brain,” said Chen. “With this application, I can view the tumor in real time as it is being destroyed while customizing the effects of the laser to the tumor without injuries to the surrounding normal brain. This incredible visualization allows neurosurgeons to preserve billions of neuronal connections that are essential for normal brain function.”
A coronary aneurysm is an abnormal ballooning of a portion of the coronary artery and a potential consequence of Kawasaki disease. If untreated, it may result in irreversible heart damage and death. This angiography of an 18-year-old patient reveals a massive aneurysm in the right coronary artery compared to the normal left. Image courtesy of Tomio Kobayashi, Gunma University School of Medicine, Japan.
Study Evaluates Role of Infliximab in Treating Kawasaki Disease
Antibody treatment helps children with dangerous heart disorder
Kawasaki Disease (KD) is a severe childhood disease that many parents, even some doctors, mistake for an inconsequential viral infection. If not diagnosed or treated in time, it can lead to irreversible heart damage.
Signs of KD include prolonged fever associated with rash, red eyes, mouth, lips and tongue, and swollen hands and feet with peeling skin. The disease causes damage to the coronary arteries in a quarter of untreated children and may lead to serious heart problems in early adulthood. There is no diagnostic test for Kawasaki disease, and current treatment fails to prevent coronary artery damage in at least one in 10 to 20 children and death in one in 1,000 children.
Between 10 and 20 percent of patients with KD experience fever relapse following the standard therapy with a single infusion of intravenous immunoglobulin (IVIG) and aspirin. It is known that IVIG resistance increases the risk of heart damage, most commonly a ballooning of the coronary arteries called aneurysms. These children require additional therapy to interrupt the inflammatory process that can lead to damage of the coronary arteries.
A study led by physicians at the University of California, San Diego School of Medicine and Rady Children’s Hospital-San Diego looked at intensification of initial therapy for all children with KD in order to prevent IVIG-resistance and associated coronary artery abnormalities by assessing the addition of the medication infliximab to current standard therapy. The results of their study will be published in the February 24, 2014 online issue of the medical journal Lancet.
Improving Knee Replacements: UC San Diego Health System first in nation to use device that boosts surgical precision and accuracy
Each year, approximately 600,000 total knee replacement procedures are performed in the United States, a number that is expected to rise exponentially in the next decade as the population ages. Successful surgeries require precise alignment in the knee, a challenging task made even more daunting by the expected rise in procedures. To help meet this demand, UC San Diego Health System is the first in the nation to use iASSIST, a computer navigation system with Bluetooth-like technology that improves surgical precision and accuracy in total knee replacements, decreasing the need for revision surgery.
The FDA-approved iASSIST device, designed by Zimmer Holdings, Inc., allows the surgeon to verify each surgical step, such as bone cuts and overall alignment, in real time, reducing mechanical errors during total knee replacements. The device is made up of small electronic pods, which are essentially mini-computers with wireless technology similar to smartphones. These electronic pods snap onto conventional instruments used in knee replacement surgery. By simply moving the knee in different positions during surgery, the device registers the anatomic axis of the leg unique to that patient, which guides each bone cut and ultimately places the knee implant in a more accurate alignment.
“This innovative technology allows us to deliver a more personalized knee to the patient and provide extreme accuracy in implant placement. Studies have shown that total knee replacement surgery has a higher failure rate when the knee is mal-aligned. This device enables orthopedic surgeons to restore a patient’s normal alignment with precision in a reproducible fashion, decreasing revision surgery and providing a more natural feel of the implant for the patient,” said Francis Gonzales, MD, with the Department of Orthopedic Surgery.
Current robotic and computer-assisted systems are less efficient and rely upon additional equipment, such as a large computer monitor in the operating room. The new device, about two inches wide, is the only piece of equipment needed to guide surgeons during a knee replacement. There are other patient-specific instruments available, said Gonzales, but the patient must undergo additional procedures, such as computed tomography (CT) scans or magnetic resonance imaging (MRI) prior to surgery.
“The iASSIST system allows us to bypass additional imaging and still get a patient-specific knee. This technology is quite intuitive and adds accuracy and precision to our instruments, giving us the ability to restore mechanical alignment with all patients regardless of their deformity,” said Gonzales.
Spheres of influence
Specific language impairment (SLI) is something of a misnomer. It’s a condition in which a person, typically first identified as a child, has difficulty speaking or communicating normally, but without obvious cause. Their hearing and general health are fine. There are no environmental or rearing experiences to explain it. There are no other signs of developmental delay or neurological disorder.
SLI seems hardly specific at all. And it’s the most common of childhood language disorders, affecting 7 percent of children.
“The primary requirements for the diagnosis are the failure to master spoken and written language expression and comprehension despite normal nonverbal intelligence and no sensory or other physical or medical condition that could cause it,” said Tim Brown, PhD, a developmental cognitive neuroscientist in the UC San Diego School of Medicine’s Department of Neurosciences and the UC San Diego Center for Human Development.
“Because it’s largely a diagnosis of exclusions, SLI likely has more than one cause and might be made up of different subtypes. Different kids with SLI can have very different profiles of language strengths and weaknesses.”
Although there are standard clinical treatments for speech production disorders, said Brown, there is no universally accepted treatment for SLI, in part because the problem is believed to involve non-motor “high-level” aspects of language.
In a recent paper published in the journal Frontiers in Human Neuroscience, Brown, Julia L. Evans, PhD, of the Center for Research in Language at UC San Diego and the School of Behavioral and Brain Sciences at the University of Texas, Dallas, and colleagues, describe using a technology called anatomically constrained magnetoencephalography imaging to look for “higher-level” aspects of language in a young SLI patient without requiring him to make speech movements or process auditory input.
They discovered that the adolescent boy’s brain represented objects in the opposite side of the brain than most people. “When he thinks about common objects, like a mouse, house, door, leaf or whale, and processes them vividly (like imagining their size), he uses his right brain hemisphere whereas most people rely most strongly on their left, which is thought to be the language processing hemisphere,” said Brown.
“This was true whether he was reading printed words of the objects or viewing pictures of them. With aMEG, we were able to show the specific regions of his brain that were used, with timing accurate down to the millisecond, which has not been seen before in SLI.”
Brown said the combination of spatial and temporal resolution gained using aMEG make it a promising method for better understanding what’s happening inside the brains of individual SLI patients. He said such precision may improve diagnoses and treatment.
“For example, although all children with SLI have language impairment, it may turn out that only a subset with SLI relies heavily on their right hemisphere for the cognitive processing of objects. Because of this difference in their brain’s functional organization, we might expect different cognitive or behavioral therapies to be effective for right hemisphere object processors versus left hemisphere processors. So the information about the individual child may be useful for both a better understanding of their problem and for leading them to a more appropriate treatment.”
A hairy death
Apoptosis or programmed cell death is an essential part of life. For example, it’s critical to human development. Where would we be if every fetal cell survived? Some cells must die to form, say, our fingers and toes; others must perish to shape our functional brains.
Cells frequently commit suicide for the good of the whole. They may become apoptotic in response to viruses or gene mutations in order to prevent further damage. Menstruation relies upon programmed cell death.
Apoptosis may be necessary, but it’s not necessarily pretty. Above is a scanning electron micrograph of several cultured HeLa cancer cells. The cell at the center is undergoing apoptosis. During the process, the cell’s cytoskeleton breaks up, causing the outer membrane to bulge and decouple. The resulting wart-like structures are called blebs, which eventually break off and are consumed by phagocytic cells for recycling.
“Strawberry tongue” is a characteristic symptom of Kawasaki Disease, an autoimmune disorder that, if not correctly diagnosed and treated, can result in heart damage in children and possible death.
For KD, a model T (cell)
Kawasaki Disease is a severe childhood illness that can, without treatment, result in damage to coronary arteries and, possibly, premature death. There is currently no diagnostic test for KD and standard treatment – a single infusion of intravenous immunoglobulin (IVIG) – is not without its problems and concerns.
KD, though, is self-limiting. That is, the body produces a type of cell called regulatory T cells or Treg that act to mitigate the inflammatory effects of KD and related damage to coronary arteries.
In a paper published in the journal Autoimmunity, first author Alessandra Franco,MD, PhD, an associate professor in the Department of Pediatrics at UC San Diego School of Medicine, Division of Allergy Immunology and Rheumatology and Rady Children’s Hospital-San Diego, and colleagues elucidate the role of Treg in KD and the mechanism for IVIG treatment.
The researchers have identified the underlying mechanism that explains why IVIG stimulates production of a particular type of Treg that recognizes the heavy constant region of antibodies and reduces inflammation and pediatric vasculitis of coronary arteries.
More broadly, Franco and colleagues say “natural Treg,” which is derived from the thymus during fetal development, has beneficial effects beyond KD. It also helps prevent plaque formation in atherosclerosis, a major form of heart disease.
The findings have significant clinical implications. IVIG is an expensive treatment. It is not available in many parts of the world where KD patients are common. “With current recombinant peptide technology, it should be possible to develop a stable, peptide-based therapeutic for testing as an optimized treatment,” Franco said. “Beyond KD, such a therapeutic may have applications in other vasculopathies, including atherosclerosis.”
You can read Franco’s paper, with co-authors Ranim Touma, Yali Song, Chisato Shimizu, Adriana H. Tremoulet, John T. Kanegaye and Jane C. Burns, all at UC San Diego, here.