Health,Stem Cells, and Technology

Wednesday, August 31, 2011

Large RNA Switch for Stem Cells

RNA molecules have long been known for their role in translating DNA to proteins inside a cell, but more recently, scientists have found large numbers of RNA molecules that don't code for proteins but seem to have other cellular roles. Most research in mammals has focused on tiny RNA molecules called microRNAs, but a new study, published in Nature, describes a new function of much larger and relatively unstudied RNA molecules called lincRNAs (short for large intergenic noncoding RNAs). The study identifies lincRNAs that play a role in the function of embryonic stem cells, and suggests that the use of lincRNAs can help to manipulate the ESCs to spawn other cell types.
Researchers at MIT focused on understanding lincRNAs' role in embryonic stem cells. Using a technique called RNA interference, they systematically ceased the function of each of more than 200 lincRNAs previously identified as playing a role in embryonic stem cells. They then profiled the genes expressed in the cells and studied their functions. The scientists found that most lincRNAs have widespread effects on cells, and that they help control the fate of stem cells. The team identified about two dozen lincRNAs that help maintain the cell's pluripotency, which is ESC's ability to transform into all other kinds of cells, and a similar number of lincRNAs that repress genes involved in differentiating into other cell types. In this manner scientists hope to be able to transform ESCs into many other types of cells, such as heart cells, kidney cells, islet cells, and many other cells types needed for regenerative medicine procedures.

Nudging stem cells to differentiate has proved challenging so far, and most stem cells show a predisposition to transform into neurons, and scientists have been looking for better methodologies to predictively induce transformation. One hope is that inhibiting lincRNAs in specific combinations may make it possible to direct stem cells to transform in specific ways. 

Avastin Injections Are Reported to Cause Blindness

The following article appeared in the NY Times. Physicians using Avastin as an off-label treatment for macular degeneration, instead of using the prescription drug Lucentis, have apparently induced infections of the eye in a few cases because of adulterated Avastin. The adulteration of the Avastin is apparently caused by poor handling of the Avastin as the drug is repackaged for injection into the eye. Blame may be placed either on the pharmacy that has repackaged the drug, or on the physician who repeatedly uses one package of Avastin to perform many injections, thus increasing the chances of introducing infectious agents into the bottle of Avastin. Off label use of Avastin is common because of a significantly lower price than Lucentis. The Times article follows:

At least 16 people in two states have gotten severe eye infections, and some have been blinded, from injections of the drug Avastin, according to health authorities and to lawyers representing the patients.
Genentech, via Associated Press
The cancer drug Avastin has been used by some doctors to treat macular degeneration, an off-label application.
The incidents, in Florida and Tennessee, demonstrate the risks associated with the money-saving practice of injecting Avastin into the eye to treat the wet form of age-related macular degeneration, a common cause of severe vision loss in the elderly.
Avastin, sold by Genentech, is approved to treat cancer, not eye disease. But many retina specialists use Avastin off label because it costs only about $50 an injection, compared with $2,000 for Lucentis, another Genentech drug that has the same mode of action and is approved as an eye treatment.
The off-label use of Avastin has saved Medicare and patients hundreds of millions of dollars a year. But dividing a vial of Avastin into numerous tiny doses for injection into the eye introduces the risk of bacterial contamination. That is apparently what has happened in the cases in Florida and Tennessee.
The Food and Drug Administration issued an alert late Tuesday saying that at least 12 patients in Miami, treated at three clinics, had suffered eye inflammations. While all had impaired eyesight to begin with, some lost all remaining vision in the treated eye, the agency said.
The F.D.A. said all the infections involved a single lot of Avastin and had been traced to a single pharmacy in Hollywood, Fla., that had repackaged the drug for use in the eye.
In Tennessee, four patients received shots contaminated by bacteria, according to a statement provided to The Tennessean newspaper by the Tennessee Valley Healthcare System, part of the United States Department of Veterans Affairs. The Avastin doses were prepared in the pharmacy of the V.A. hospital in Nashville.
One of the patients, Lloyd Mason Sylvis, 77, suffered an eye infection of Streptococcus viridans that spread to his brain, according to a claim for $4 million in damages that his family has filed with the V.A. Mr. Sylvis received the injection on March 29, but his family went public with its complaint only recently.
“He’s permanently blinded, permanently brain damaged,” said his son, Lloyd Mason Sylvis Jr. “He came in walking and talking, and he remains in a vegetative state as we speak.”
The Florida patients received their injections in early July and were apparently infected with Streptococcus oralis.
Last week, the F.D.A. announced a recall of syringes containing Avastin from Chroniscript, a part of Walgreens pharmacy in Miami.
Jim Cohn, a spokesman for Walgreens, said the syringes had been supplied to “a limited number of physician offices in Miami-Dade and Broward counties.”
Antonio Salgado, 79, of Miami got an injection of Avastin into his right eye on July 8. While there were no problems with the seven previous injections of the drug, this one caused tremendous pain and caused a white film to grow over his eye, according to his lawyer, Philip A. Gold.
“There was a point in time where his eye was completely white, without coloration, no pupil, no nothing,” Mr. Gold said.
Mr. Salgado has filed a lawsuit in state court in Miami-Dade County. Among those sued was Infupharma, a compounding pharmacy that was said to have divided the Avastin into tiny doses. It is not clear what the relationship was between Infupharma and Chroniscript.
Another lawyer, Gary Alan Friedman, said he represented six patients, four of whom have already filed suit.
“They all have either significantly lost vision or have been blinded completely by the contamination,” Mr. Friedman said.
Infupharma said it would not discuss details because of the continuing investigation and litigation.
Genentech said it would not comment on the litigation, but said that it had always cautioned against use of Avastin in the eye.
“Avastin is not manufactured or approved and to date has not been proven safe for use in the eye,” a spokesman for the company said Tuesday.
While the company is being sued, it could benefit overall if the incidents discourage use of Avastin in favor of the far more lucrative Lucentis.
Ophthalmologists who use Avastin have played down concerns about the risk of bacterial contamination.
Dr. Philip Rosenfeld, a retina specialist at the University of Miami who pioneered the use of Avastin for macular degeneration, said the recent incidents apparently stemmed from careless procedures by pharmacies and should not discourage the use of the drug.
“It took six years for something like this to happen,” he said, noting that there have been more than two million injections of Avastin into eyes in the United States alone since the practice began in 2005.
A clinical trial sponsored by the National Eye Institute found that Avastin and Lucentis were equivalent in preserving or improving vision after one year.

Sunday, August 21, 2011

UC Riverside: Medical School Opens First New Building

Congrats to UC Riverside:

On March 18th, the UCR Medical School opened its first building. This is an historic event in the establishment of the UCR Medical School, which will be the first new Medical School in California in over 40 years. The event was attended by over 200 people including dignitaries from the U.S Department of Health and Human Services, medical profession, and Riverside County. The School of Medicine Research Building has state of the art research space and offices for new faculty. The building is also designed to meet the LEED Silver sustainability standards of the U.S. Green Building Council.

The Medical School is currently recruiting new faculty to occupy the building and is on track to admit its first class in 2012

Saturday, August 20, 2011

IBM's New Cognitive Computing Chip

IBM has unveiled a new "cognitive computing" semiconductor chip that, according to the company, emulates the architecture and function of the brain. The chip is the latest development in an ongoing program by the Defense Advanced Research Projects Agency (DARPA), based in Arlington, Va., to develop systems that can analyze complex information.

At the component level the chip unveiled this week uses the same technology as other chips known as complementary metal-oxide semiconductors (CMOSs). Each core contains 256 clusters of transistors and thousands of random access memory (RAM) elements. Compared to other electronics, the standard computing power is small.
The brain, which at the component level uses relatively slow and noisey elements, the brain's power is derived from the way in which it is wired. Likewise, in the IBM chip, the difference is the way the transistors and memory are wired together. In a conventional computer, the computational elements are mostly in the central processing unit, while the RAM sits off to one side. In the cognitive chips, the computational elements and RAM are wired together.
The theory of the new chip’s wiring is that the computational components act as "neurons," while the RAM units act as the "synapses," which connect the neurons together. In the brain, neurons receive electrical pulses from synapses until a sufficient voltage builds up across their membrane. The neuron then discharges, sending signals to other neurons mostly through the synapses.
In the cognitive chip, a pattern of signals from the RAM can cause a computational element to carry out a simple operation. The result goes to another RAM synapse that send signals to other computational neurons. In this way, the chip reflects the brain's architecture.
The main benefit is decreasing power consumption. Because the memory and computation are intermingled, less energy is wasted shuffling electrons back and forth. The new chips have the potential to be orders of magnitude more efficient than a conventional computer In terms of speed, it's believed that the chips will be particularly good at crunching certain kinds of problems, such as pattern recognition, but they may not be as good as a regular computer at processing traditional numerical tasks.
The success of these first chips has led DARPA to award $21 million for further development. Meanwhile, IBM researchers are constructing algorithms that are adept at speech recognition and problem solving. Their Watson supercomputer, for example, which was victorious over human competitors, currently requires a room full of power-hungry processors. IBM hopes that low-power, space-saving cognitive chips will perform just as well.

Friday, August 19, 2011

FDA’s Strategic Plan for Regulatory Science: Prevention and Personalized Medicine

FDA has developed a strategic plan for regulatory science, the science of developing new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of FDA-regulated products. This plan identifies eight priority areas of regulatory science where new or enhanced engagement is essential to the continued success of FDA’s public health and regulatory mission.  The priority areas are:
  1. Modernize Toxicology to Enhance Product Safety
  2. Stimulate Innovation in Clinical Evaluations and Personalized Medicine to Improve Product Development and Patient Outcomes
  3. Support New Approaches to Improve Product Manufacturing and Quality
  4. Ensure FDA Readiness to Evaluate Innovative Emerging Technologies
  5. Harness Diverse Data through Information Sciences to Improve Health Outcomes
  6. Implement a New Prevention-Focused Food Safety System to Protect Public Health
  7. Facilitate Development of Medical Countermeasures to Protect Against Threats to U.S. and Global Health and Security
  8. Strengthen Social and Behavioral Science to Help Consumers and Professionals Make Informed Decisions about Regulated Products 
FDA will apply available resources to implement the Strategic Plan for Regulatory Science through management of scientific programs within FDA and engagement of collaborators and partners in industry, academia, and government.  FDA’s Strategic Plan for Regulatory Science is designed to allow the FDA both to meet today’s public and animal health needs and to be fully prepared for the challenges and opportunities of tomorrow to help harness revolutions in science that can be translated into products that help make and keep our nation both safe and healthy.
New emphasis appear to be placed on: 1. Personalized medicine, and 2. Prevention-focused foods, both of which are rapidly growing markets in the USA and the world.

Thursday, August 18, 2011

Multipotency Of Stem Cells Retained Using Nanoscale Surfaces

Stem cells that are cultured in the laboratory differentiate in response to the topography and mechanical properties of the substrate on which the cells are grown.  Now Professors Nikolaj Gadegaard and  Matthew J. Dalby at the University of Glasgow in Scotland have shown that mesenchymal stem cell multipotency is prolonged when the cells are cultured on a surface patterned with an ordered arrangement of nanoscale pits.

There is currently an unmet need for the supply of autologous, patient-specific stem cells for regenerative therapies in the clinic. Mesenchymal stem cell differentiation can be driven by the material/cell interface suggesting a unique strategy to manipulate stem cells in the absence of complex soluble chemistries or cellular reprogramming. However, so far the derivation and identification of surfaces that allow retention of multipotency of this key regenerative cell type have remained elusive. Adult stem cells spontaneously differentiate in culture, resulting in a rapid diminution of the multipotent cell population and their regenerative capacity. The study identifies a nanostructured surface that retains stem-cell phenotype and maintains stem-cell growth over eight weeks. Furthermore, the study implicates a role for small RNAs in repressing key cell signalling and metabolomic pathways, demonstrating the potential of surfaces as non-invasive tools with which to control the stem cell niche.

Tuesday, August 16, 2011

The Allosphere: Big Data's Game-Changing Machine

The Allosphere is a tool for new means for visualizing enormous amounts of data. The Allosphere is egg-shaped, three stories tall, and located on the campus of the University of California, Santa Barbara. Scientists stand on a catwalk that runs through the middle of the machine, and wearing 3D glasses look at enormous representations of such things as human brains, molecular bonds, economic data, and quantum physical events. The visuals stretch around vision’s periphery to simulate immersion in an object, and sound from banks of speakers provide other pathways to information. The idea is to present enormous data sets in such a manner that the human brain, the world’s most powerful computer, can process the data in a meaningful way. Visualization is a primary means for the human brain’s enormous analytical capabilities, and so the Allosphere presents data in a way that is visually meaningful.
Recent modeling projects at the Allosphere have included that of a giant human brain constructed from 256 MRI images. Standing in the Allosphere one can move over folds and through color-coded lobes, the density of blood flow  reflected in the pitch of a background thrum, with higher pitches for higher densities.
Other explorations have included examining the bonds of 2000 zinc, hydrogen and oxygen atoms, an experimental lattice created to explore new solar cells that had taken five supercomputers six months to create. In the background  the orchestra played the emission spectrum of electrons jumping to different orbits from the hydrogen.
 Professsor JoAnn Kuchera-Morin, the Allosphere’s creator, has said that information technology systems, and the association of visualization with meaning, make the computer into a kind of instrument. The Allosphere will allow us to work with complex information in close to real time, and in a manner easily visualized and understood by the human brain.

Monday, August 15, 2011

Mechanism Of How Fatty Diets Cause Diabetes

Newly diagnosed type 2 diabetics tend to be obese. Exactly how diet and obesity trigger diabetes has long been the subject of intense scientific research. A new study led by Dr. Jamey D. Marth, Ph.D., director of the Center for Nanomedicine, University of California, Santa Barbara, has revealed a pathway that links high-fat diets to a sequence of molecular events responsible for the onset and severity of diabetes. These findings were published online August 14 in Nature Medicine. 

In healthy people, pancreatic beta cells monitor the bloodstream for glucose using glucose transporters anchored in the cellular membranes of the beta cells. When blood glucose is high, such as after a meal, beta cells take in this additional glucose and respond by secreting insulin in a timed and measured response. In turn, insulin stimulates other cells in the body to take up glucose, a nutrient they need to produce energy. 

In this newly discovered pathway, Professor Marth shows that high levels of fat were found to interfere with two key transcription factors - proteins that switch genes on and off. These transcription factors, FOXA2 and HNF1A, are normally required for the production of an enzyme called GnT-4a glycosyltransferase that modifies proteins with a particular glycan (polysaccharide or sugar) structure. Proper retention of glucose transporters in the cell membrane depends on this modification, but when FOXA2 and HNF1A aren't functioning properly, GnT-4a's ability to act as a transferase is greatly diminished. Therefore when the researchers fed otherwise normal mice a high-fat diet, they found that the animals' beta cells could not sense and respond to blood glucose. Preservation of GnT-4a function was able to block the onset of diabetes, even in obese animals. Diminished glucose sensing by beta cells was shown to be an important determinant of disease onset and severity. 

Friday, August 12, 2011

RNAi Systems Center Opened By La Jolla Institute for Allergy & Immunology in San Diego

A new center for studying the gene-blocking technology called RNA interference (RNAi) has been opened by La Jolla Institute for Allergy & Immunology. The center was funded through a $12.6 million NIH grant under the American Recovery and Reinvestment Act of 2009 (Recovery Act), popularly known as the federal stimulus.
As its name implies RNAi interferes with the activity of certain types of RNA, used to make proteins. The technology resembles antisense and overlaps with it. Using RNAi, genes can be selectively switched off to help determine that gene's function. The RNAi process has been compared to taking out pieces of a vehicle's electrical system and noting what happens, and although imperfect, an important means for helping to deduce the role of each component. The RNAi center will vastly scale up this process from looking at single genes to examining biological systems and processes, such as cancers and other disease states.

Sunday, August 7, 2011

Stem Cells Grow New Cells In Irradiated Brain

Dr. Charles Limoli, professor at the University of California, Irvine has just published results of a study that could offer hope for brain cancer patients, who often suffer debilitating cognitive problems as a result of radiation treatment. Radiation treatment for brain cancer can be lifesaving, but the radiation process that kills cancer cells also kills brain cells, destroying memories, impairing intelligence, and causing confusion.

Professor Limoli and colleagues have shown that stem cells could help reverse some of this damage. Published in the journal Cancer Research, Limoli’s study shows that new brain cells grow by injecting human neural stem cells into the brains of mice whose cognitive abilities had been damaged by radiation. The mice also regained lost function after the stem-cell treatment.

Stem cells have long been used to repair the damage caused by cancer treatment. Bone-marrow transplants for leukemia rely on stem cells to replenish blood cells, for instance. If the findings continue to be as positive as what's published in this paper, I expect great effort to try to move the technique into the clinic as quickly as possible.
Limoli's team irradiated three groups of mice, later treating two of them with human neural stem cells. The third, a control group, received a sham surgery, but no cells were implanted. One month after the damage, 23 percent of implanted stem cells were active in the brains of the first group of mice. After four months, 12 percent were still active in the second group. Using cellular labeling, the study also showed that tens of thousands of new neurons and astrocyte cells had grown in the brains of the treated mice. The treated mice performed better than the untreated ones on cognitive tests, and recovered their preradiation abilities. Further, protein activity in the treated mice suggests that the implanted stem cells are integrating into the brain. 
The treatment regimen may also be effective against  damaged brains in chemotherapy and other insults to neural tissue.

Friday, August 5, 2011

Eviscerating The Technological Future Of The USA: Debt Deal Threatens R&D Spending

Congress agreed to spending limits this week as part of a deal to raise the debt ceiling that could hurt U.S. spending on R&D and infrastructure. Such spending is essential for the country to remain competitive globally, and at a time when the economy is contracting and jobs are being lost, this is the wrong time to focus on spending cuts. Indeed, unlike the Tea Party's idiotic approach of extreme cutting, economists are arguing for more stimulus using "low interest money" that is currently available to build for the future though increased spending on infrastructure and R&D. Because of House Republicans and their Tea Party mentality, the US is doing the exact opposite of what is needed to prepare for our future.
The budget deal sets spending caps that will reduce spending by $1 trillion over the next decade, and sets up a committee that will attempt to find an additional $1.5 trillion in reductions. The spending limit for the 2012 fiscal year, which starts in October 2011, would reduce discretionary spending by $7 billion compared to last year, and by $73 billion compared to what President Obama asked for in his budget.
The deal does not specify how funding under that cap will be distributed among agencies and programs. Those decisions will be settled in appropriations bills. In theory, Congress could increase funding for R&D and infrastructure by making cuts elsewhere. However that scenario is a long shot. As described by Professor Robert Reich, I believe the debt deal is going to have a bad impact. I don't see Congress having the sophistication, insight, or political will to separate out, in a serious way, funding for infrastructure and research. Instead political hackery and uninformed decisions by the House will likely prevail. 
Reductions to R&D spending have already been seen in spending bills passed by the House earlier this year. President Obama made boosting clean energy development a centerpiece of his policy agenda this year, and as part of that, he called for a more than $1 billion increase in funding for energy efficiency and renewable energy R&D at the U.S. Department of Energy. But the House passed an appropriations bill that instead cut funding for that R&D by $60 million. Obama also asked for $620 million for the Advanced Research Projects Agency for Energy, but the House only approved $173 million.
Even keeping R&D level with recent years would not address a decades-long slump in the growth of R&D spending that has seen the U.S. lose ground against other countries, Atkinson says. In a recent study by ITIF of 36 countries around the world, the growth in R&D averaged 16 percent over the last decade. In the U.S., federal R&D funding decreased by 1 percent, he says. "By any measure, it's clear that we're underinvesting," he says.
The prospects for investment in infrastructure improvements, which have been chronically underfunded, also look bad. Atkinson estimates that it would take $180 billion a year to keep up with the needs of transportation infrastructure, but only $60 billion is being spent. Even the temporary boost from the Recovery Act of 2009 only made up one-third of the shortfall.
Although President Obama proposed significant increases in transportation infrastructure funding this year, Senate Democrats decided to maintain current levels, while the House recommended cuts of one-third, says Donna Cooper, a senior fellow at the Center for American Progress. She also notes that federal loan programs for large-scale infrastructure projects under the U.S. Department of Transportation, the DOE, and the EPA are all at risk in budget negotiations. "People who are concerned about infrastructure have a whole lot to be worried about," Cooper says.
Chad Evans, senior vice president at the Council on Competitiveness, says that the council's members, which include CEOs at major companies, recognize the need to address the debt. Yet the council also emphasizes the need for R&D and infrastructure, and is disappointed that recent progress on increasing funding is now at risk. The council's business leaders are putting together recommendations for what funding should be prioritized as Congress makes decisions on specific programs. Balancing cuts and investments is a "nuanced position," he says. "The recent rush and panic mutes nuance. We have to return to a place of reasoned discussion."
As I have published elsewhere, a strong government with support of the "Triad" is essential to the future of the US economy. Funding, and a close working relationship of government, academia, and business, the so-called "Triad" will build for our future just as the "Triad" has done in the past leading to birth of whole new industries such as biotech, semiconductors, communications, computers, the internet, aerospace, and many others. We should be spending to build our future now, not foolishly cutting those things that build a great economy and provide jobs.