[Source ASU, Skip Derra] - Eight Arizona State University faculty members are among the 486 newly elected Fellows of the American Association for the Advancement of Science (AAAS), a prestigious international scientific society. AAAS is the world's largest general scientific society.
Brad Allenby, Richard Creath, James Elser, Patricia Gober, Nancy Grimm, Sudhir Kumar, Thomas Moore and John Spence will be recognized Feb. 14 at the Fellows forum, during the 2009 AAAS annual meeting in Chicago.
This year's election brings the total number of AAAS Fellows at Arizona State University to 54.
Becoming a Fellow is in recognition of efforts toward advancing science applications that are deemed scientifically or socially distinguished. Within that general framework, each awardee is honored for contributions to a specific field.
Braden Allenby is cited by the AAAS for "distinguished contributions to earth systems engineering and management, design for environment, industrial ecology and science and technology policy." He is a professor in ASU's Department of Civil and Environmental Engineering, as well as a professor of law and of engineering and ethics with the Joan and David Lincoln Center for Applied Ethics. Recognized as a pioneer of modern industrial ecology, Allenby is co-director of the Center for Sustainable Engineering and is helping establish a new Center of Earth Systems Engineering and Management. He recently was named as one of the U.S. Professors of the Year for 2008 by the Carnegie Foundation for the Advancement of Teaching and the Council for Advancement and Support of Higher Education.
Richard Creath is cited by AAAS for "achievements in archiving and interpreting key documents in the historical development of scientific philosophy and demonstrating their relevance to current problems." Creath, a professor in the School of Life Sciences, is a philosopher of science and epistemologist who uses historical methods to illuminate fundamental questions about the nature of scientific reasoning and knowledge. He is one of the world's foremost authorities on philosophers Rudolf Carnap and W.V.O. Quine. As general editor of the multi-volume Carnap Project, he leads an international team of two dozen leading researchers.
James Elser is cited by AAAS for "pioneering work in developing the theories of ecological and biological stoichiometry to integrate levels of biology from the genome to the biosphere and thereby improve our management of renewable resources." Elser, a professor in the School of Life Sciences, has built a career asking questions about evolutionary biology and energy and material flows in ecosystems, traveling from Antarctica to alpine lakes of Norway and Colorado to the Mongolian grasslands of China, to find answers. Understanding the balance of carbon, nitrogen and phosphorus in systems forms the backbone of Elser's worldview, known as "stoichiometric theory." He has taught more than 10,000 students and his pioneering studies have shaped young minds and jumpstarted new research approaches, as well as provided insights into nutrient limitation, trophic dynamics, and biogeochemical cycling, evolution and integrated levels of organization from molecules to cells to ecosystems.
Patricia Gober, a human geographer and demographer, is co-director of the National Science Foundation's Decision Center for a Desert City, part of ASU's Global Institute of Sustainability, and a professor in the School of Geographical Sciences. A former president of the Association of American Geographers, Gober's research focuses on the use of science and visualization for real-world decision-making, particularly in tackling the difficult water management decisions necessary in the face of growing climatic uncertainty in metropolitan Phoenix. Gober is cited by AAAS for her "outstanding record of scholarship and disciplinary leadership" and because she "clearly established herself as a leader within the discipline and has left a permanent mark within American geography."
Nancy Grimm is cited by AAAS for "pioneering studies of urban social-ecological systems that conceptually expand urban resource management, and for innovative contributions in stream ecology and biogeochemistry that have stimulated decades of research." Grimm, a professor in ASU's School of Life Sciences, has for the past 10 years led the Central Arizona-Phoenix Long-Term Ecological Research project. CAP-LTER is centered on the analysis of urban-semi-arid ecosystem relationships. Through her collaborative work, Grimm has established a conceptual basis for including human choice and action in theory of urban ecosystem dynamics. The work on biogeochemistry, species distribution and abundance, and designed aquatic ecosystems in cities has revealed that many ecological features are best explained by combinations of social and biophysical drivers.
Sudhir Kumar directs the Center for Evolutionary Functional Genomics in ASU's Biodesign Institute and is a professor of biology in the School of Life Sciences. He is cited by AAAS for "exemplary contributions in evolutionary bioinformatics, particularly in developing high-impact comparative analysis software for biologists and in illuminating the evolutionary dynamics of mutations and species through comparative genomics." Among his pioneering efforts was the software analysis of gene expression patterns from early gene expression patterns of fruit fly development, advanced work using protein molecular clocks to illuminate the Evolutionary Timescale of Life and the Molecular Evolutionary Genetics Analysis (MEGA) software package that makes useful methods of comparative sequence analysis easily accessible to the scientific community for research and education. Kumar also has received an Innovation Award in Functional Genomics from the Burroughs Wellcome Fund in 2000.
Thomas Moore, a biochemist, is cited by AAAS for "pioneering research in artificial photosynthesis including the design of artificial reaction centers, antenna and assembling an energy-converting artificial photosynthetic membrane." Moore is a professor in ASU's chemistry and biochemistry department and director of the Center for Bioenergy and Photosynthesis. Most recently, he served on the U.S. Department of Energy Basic Energy Sciences Grand Challenges Committee, which produced "Directing Matter and Energy: Five Challenges for Science and the Imagination," outlining research priorities for the foreseeable future. Moore and colleagues collaborate on research in artificial photosynthesis, which is aimed at providing a deeper understanding of natural photosynthesis and the design, synthesis and assembly of bio-inspired constructs capable of sustainable energy production and conversion for human use.
John C.H. Spence is a Regents Professor in ASU's Department of Physics. He was cited by the AAAS for "distinguished contributions to diffraction physics, especially atomic-resolution electron microscopy, electron diffraction studies of the chemical bond and diffractive (lens-less) x-ray imaging." Spence undertakes experiments in condensed matter physics based around the use of electron beams for imaging, spectroscopy and diffraction. The work requires Spence's group to build or modify advanced instruments in order to do their experiments. Spence is currently working with others to get femtosecond "snapshots" of individual proteins using the first hard x-ray laser facility in the U.S., which will begin operation next year.
Tuesday, December 23, 2008
UA losing major bioscience researcher
[Source: Aaron Mackey, ARizona Daily Star] - The leader of the UA's top research institute — whom colleagues hail as a key architect of the region's burgeoning bioscience industry — is leaving to head a San Francisco-based non-profit's scientific endeavors, the university announced Monday.
Vicki Chandler, director of the University of Arizona's Bio5 Institute, played a critical role in establishing the collaborative research center, which has brought tens of millions of grant dollars to the UA, including a $50 million award thought to be the largest grant in Arizona history.
The second high-profile professor with ties to Bio5 to leave the UA this year, Chandler will become chief program officer for the Gordon and Betty Moore Foundation's science efforts in February.
In July, Bio5 founder Thomas Baldwin left the UA to become dean of UC-Riverside's College of Natural and Agricultural Sciences. Baldwin founded the program, which at the time was known as the Institute for Biomedical Science and Biotechnology, in 2001.
Besides being one of the UA's premier scientists, Chandler has become a regional ambassador for bioscience research, lobbying for state money to build research facilities while striving to tell the public about the importance of the work.
"She had a vision for Bio5 that was about much more than just scientific research," said Leslie Tolbert, the UA's vice president for research. "She has an enthusiasm for outreach and the role a university can play in community development."
Taking over Bio5 in 2002, Chandler led several efforts that culminated in the UA's landing a $50 million grant in January to establish the iPlant Collaborative, a research program aimed at unlocking the secrets of plant biology. That alone accounted for roughly 10 percent of the UA's overall $500 million research budget.
The project, co-led by Chandler, was seeded by state support in research funding and new buildings — both of which Chandler lobbied for, Tolbert said.
Chandler "has been a strong spokesperson with the Legislature and with private donors as well," Tolbert said. "She gets them to see that it isn't just about the institute in the abstract, but the people doing the science and getting results."
The Bio5 Institute is the UA's most prominent interdisciplinary research center, blending researchers from five fields —agriculture, medicine, pharmacy, basic science and engineering — with industry leaders to find solutions to common problems, such as disease.
The institute has been a pipeline for grants and also has proved successful at creating a number of spin-off companies that use technologies developed in UA laboratories.
Managing the complex relationships between business leaders and researchers, Chandler was integral in convincing several bioscience companies to either expand in or move to Tucson, said Joe Snell, president and CEO of Tucson Regional Economic Opportunities Inc.
"Her leadership has been incredibly valuable in helping to position Tucson as the next bioscience hub," he said.
"I don't think we would be where we're at or where we're going without her efforts."
Chandler also has helped build interest in science among high school students and UA undergraduates. She holds summer programs that get high schoolers in laboratories with researchers and often touts how half the Bio5 researchers are undergrads.
She also has narrated the UA-produced PBS show "WaveLengths," which provides a 30-minute snapshot of some of the research produced on campus.
On top of that, Chandler maintains a full-time lab and conducts field research as a Regents Professor in both the plant science and molecular and cellular biology departments. She also holds the Weiler Endowed Chair for Excellence in Agriculture and Life Sciences.
Chandler, who has been at the UA since 1997, said she has mixed emotions about her new role.
"It's always exciting to take on a new challenge, but I poured my heart and soul into the University of Arizona and really care deeply for it," she said.
The move will take her back to her roots. She grew up in Northern California and studied at the University of California-Berkeley and UC-San Francisco while later working at Stanford after earning her Ph.D.
The foundation she is joining invests $300 million each year in projects, including science and environmental conservation research around San Francisco.
Even with her new job, Chandler will be in Tucson often. She plans to retain her endowed chair and conduct research as part of the iPlant Collaborative, a process she says will take up about 20 percent of her time.
"The university has been incredibly gracious to allow me to continue to research," she said. "By keeping my feet squarely planted in science, it will hopefully help me in my new position."
The UA will name an interim director of Bio5 early next year and plans to conduct a national search for a permanent replacement, Tolbert said.
Vicki Chandler, director of the University of Arizona's Bio5 Institute, played a critical role in establishing the collaborative research center, which has brought tens of millions of grant dollars to the UA, including a $50 million award thought to be the largest grant in Arizona history.
The second high-profile professor with ties to Bio5 to leave the UA this year, Chandler will become chief program officer for the Gordon and Betty Moore Foundation's science efforts in February.
In July, Bio5 founder Thomas Baldwin left the UA to become dean of UC-Riverside's College of Natural and Agricultural Sciences. Baldwin founded the program, which at the time was known as the Institute for Biomedical Science and Biotechnology, in 2001.
Besides being one of the UA's premier scientists, Chandler has become a regional ambassador for bioscience research, lobbying for state money to build research facilities while striving to tell the public about the importance of the work.
"She had a vision for Bio5 that was about much more than just scientific research," said Leslie Tolbert, the UA's vice president for research. "She has an enthusiasm for outreach and the role a university can play in community development."
Taking over Bio5 in 2002, Chandler led several efforts that culminated in the UA's landing a $50 million grant in January to establish the iPlant Collaborative, a research program aimed at unlocking the secrets of plant biology. That alone accounted for roughly 10 percent of the UA's overall $500 million research budget.
The project, co-led by Chandler, was seeded by state support in research funding and new buildings — both of which Chandler lobbied for, Tolbert said.
Chandler "has been a strong spokesperson with the Legislature and with private donors as well," Tolbert said. "She gets them to see that it isn't just about the institute in the abstract, but the people doing the science and getting results."
The Bio5 Institute is the UA's most prominent interdisciplinary research center, blending researchers from five fields —agriculture, medicine, pharmacy, basic science and engineering — with industry leaders to find solutions to common problems, such as disease.
The institute has been a pipeline for grants and also has proved successful at creating a number of spin-off companies that use technologies developed in UA laboratories.
Managing the complex relationships between business leaders and researchers, Chandler was integral in convincing several bioscience companies to either expand in or move to Tucson, said Joe Snell, president and CEO of Tucson Regional Economic Opportunities Inc.
"Her leadership has been incredibly valuable in helping to position Tucson as the next bioscience hub," he said.
"I don't think we would be where we're at or where we're going without her efforts."
Chandler also has helped build interest in science among high school students and UA undergraduates. She holds summer programs that get high schoolers in laboratories with researchers and often touts how half the Bio5 researchers are undergrads.
She also has narrated the UA-produced PBS show "WaveLengths," which provides a 30-minute snapshot of some of the research produced on campus.
On top of that, Chandler maintains a full-time lab and conducts field research as a Regents Professor in both the plant science and molecular and cellular biology departments. She also holds the Weiler Endowed Chair for Excellence in Agriculture and Life Sciences.
Chandler, who has been at the UA since 1997, said she has mixed emotions about her new role.
"It's always exciting to take on a new challenge, but I poured my heart and soul into the University of Arizona and really care deeply for it," she said.
The move will take her back to her roots. She grew up in Northern California and studied at the University of California-Berkeley and UC-San Francisco while later working at Stanford after earning her Ph.D.
The foundation she is joining invests $300 million each year in projects, including science and environmental conservation research around San Francisco.
Even with her new job, Chandler will be in Tucson often. She plans to retain her endowed chair and conduct research as part of the iPlant Collaborative, a process she says will take up about 20 percent of her time.
"The university has been incredibly gracious to allow me to continue to research," she said. "By keeping my feet squarely planted in science, it will hopefully help me in my new position."
The UA will name an interim director of Bio5 early next year and plans to conduct a national search for a permanent replacement, Tolbert said.
Monday, December 22, 2008
Economic downturn hurts ASU nursing school
[Source: Jahna Berry, The Arizona Republic] - Arizona State University's nursing school capped a historic and challenging year this week, honoring a record-breaking graduating class.
"It's been an unbelievable journey," graduate Gina Dioguardi, 24, said Wednesday as she helped fellow graduate Leticia Medina, 22, put on her cap and gown. The two were part of 276 graduates from ASU's College of Nursing and Healthcare Innovation who were recognized at the Phoenix Convention Center.
Like any new degree-holder, the nurses are worried about jobs.
"Because of the economy, there aren't a lot of places that are hiring," Medina said.
Even though the state has a nursing shortage, some employers have a limited number of slots for entry-level nurses because they cost more to train, Medina added.
The economic downturn is also taking a toll on the school.
As the nursing school celebrated its 50th year, the college was one of several ASU divisions hurt by university-wide budget cuts.
Officials say enrollment will be cut from 80 students to 40 at ASU's Polytechnic campus this spring and by the same amount at the West campus next fall.
Enrollment at the downtown Phoenix campus will remain the same. ASU plans to cut enrollment because it expects to lose some state funding.
The nursing school has 1,800 students. The college is based in downtown Phoenix, but students can take nursing classes on several ASU campuses.
The nursing cuts would come at a time when Arizona is struggling with a nursing shortage.
Last year, the state had 681 registered nurses per 100,000 people, below the national average of 825 registered nurses per 100,000, according to the U.S. Department of Health and Human Services.
"It's been an unbelievable journey," graduate Gina Dioguardi, 24, said Wednesday as she helped fellow graduate Leticia Medina, 22, put on her cap and gown. The two were part of 276 graduates from ASU's College of Nursing and Healthcare Innovation who were recognized at the Phoenix Convention Center.
Like any new degree-holder, the nurses are worried about jobs.
"Because of the economy, there aren't a lot of places that are hiring," Medina said.
Even though the state has a nursing shortage, some employers have a limited number of slots for entry-level nurses because they cost more to train, Medina added.
The economic downturn is also taking a toll on the school.
As the nursing school celebrated its 50th year, the college was one of several ASU divisions hurt by university-wide budget cuts.
Officials say enrollment will be cut from 80 students to 40 at ASU's Polytechnic campus this spring and by the same amount at the West campus next fall.
Enrollment at the downtown Phoenix campus will remain the same. ASU plans to cut enrollment because it expects to lose some state funding.
The nursing school has 1,800 students. The college is based in downtown Phoenix, but students can take nursing classes on several ASU campuses.
The nursing cuts would come at a time when Arizona is struggling with a nursing shortage.
Last year, the state had 681 registered nurses per 100,000 people, below the national average of 825 registered nurses per 100,000, according to the U.S. Department of Health and Human Services.
UA provost suggests pay cuts
[Source: AzCentral/AP] - When it comes to fixing budget shortfalls, some high earners at the University of Arizona should cut their pay.
That suggestion comes from one of the school's highest paid employees, University of Arizona Provost Meredith Hay, who earns more than $100,000 a year.
The number of employees making more than six figures at the UA has increased 45 percent since 2005 while costs of paying those workers jumped 53 percent, according to an Arizona Daily Star analysis.
Officials acknowledge there are more employees earning more than $100,000 in what they call the reality of the highly competitive academic market and a product of growth in programs such as the UA's medical school in Phoenix.
They add it's not as if those workers are getting raises at the expense of lower-paid staffers.
It costs the UA $76 million to pay 2,323 workers who earn less than $50,000 a year and account for nearly half of all state-paid employees.
It also costs about $71 million to pay the 568 employees making more than $100,000.
The idea to cut into UA employee earnings has gained steam as officials look at ways to offset what they expect to be a series of state cuts that could leave them $50 million in the red by next summer.
Cutting pay could pose potential long-term consequences that could affect the UA's ability to hire and retain employees.
"What does that do for our competitiveness? We're already below where we need to be," said Allison Vaillancourt, UA's vice president for human resources. "If we take another whack at employees, who will come to work for us? Will we be able to attract people in the future?"
Overall salary costs have increased by 18 percent since 2005, putting UA in line with other universities, she said.
Faculty members who get raises actually save the UA money in the long run because it's cheaper than advertising for an open position and training a new employee, university officials said.
"If they need lab equipment or special office space, we could be looking at several hundred thousand dollars," Vaillancourt said. "It doesn't make any sense for us to spend that money if we don't have to."
That suggestion comes from one of the school's highest paid employees, University of Arizona Provost Meredith Hay, who earns more than $100,000 a year.
The number of employees making more than six figures at the UA has increased 45 percent since 2005 while costs of paying those workers jumped 53 percent, according to an Arizona Daily Star analysis.
Officials acknowledge there are more employees earning more than $100,000 in what they call the reality of the highly competitive academic market and a product of growth in programs such as the UA's medical school in Phoenix.
They add it's not as if those workers are getting raises at the expense of lower-paid staffers.
It costs the UA $76 million to pay 2,323 workers who earn less than $50,000 a year and account for nearly half of all state-paid employees.
It also costs about $71 million to pay the 568 employees making more than $100,000.
The idea to cut into UA employee earnings has gained steam as officials look at ways to offset what they expect to be a series of state cuts that could leave them $50 million in the red by next summer.
Cutting pay could pose potential long-term consequences that could affect the UA's ability to hire and retain employees.
"What does that do for our competitiveness? We're already below where we need to be," said Allison Vaillancourt, UA's vice president for human resources. "If we take another whack at employees, who will come to work for us? Will we be able to attract people in the future?"
Overall salary costs have increased by 18 percent since 2005, putting UA in line with other universities, she said.
Faculty members who get raises actually save the UA money in the long run because it's cheaper than advertising for an open position and training a new employee, university officials said.
"If they need lab equipment or special office space, we could be looking at several hundred thousand dollars," Vaillancourt said. "It doesn't make any sense for us to spend that money if we don't have to."
Friday, December 19, 2008
Telemedicine protects Arizona, its many regional communities
[Source: Nogales International, Roger Conroy] - Centered in Phoenix and Tucson, a beneficial net covers Arizona communities from Ajo to Nogales to Yuma, the New Mexico communities of Bloomfield, Crownpoint, Gallup, Shiprock and Tohatchi and Utah’s Fort Duchesne and Salt Lake City.
The Arizona Telemedicine Network gives people in Santa Cruz County access to specialty care--that’s care beyond what is offered at Mariposa--applying the latest technology, said Mariposa Health Clinic CEO Jim Weldon. “Doctor (Ronald S.) Weinstein founded the program, and it’s very innovative--a national model.” Weinstein was the third guest speaker in the Mariposa Series on Thursday at Holiday Inn Express in Nogales.
The network gives local clinics access to information and specialties above the level normally available in Nogales, Mariposa chief of medicine Eladio Pereira said. Mariposa Clinic uses rheumatology, dermatology and gastroenterology services over the Telemedicine Network. “It’s incredible--speed, accuracy, consults right away. It’s very, very important.”
There are several cases each month that are aided by use of the network at Mariposa, Pereira said.
The network had it’s beginnings at Massachusetts General in 1968, Weinstein said. Telepathology, or remote diagnosis began in the 1980s. The concept is illustrated by the television shows “CSI,: and earlier, “Quincy, M.E.,” Weinstein said.
Arizona Sen. Robert Burns was instrumental in the establishment of the network, Weinstein said. “He’s now president of the Arizona state senate. He founded it. He came to us and asked us to do it.”
The network began at the Phoenix campus of the University of Arizona College of Medicine, where Weinstein is director of the program. It now includes 171 sites in 71 communities. “Doctor Pereira is the best director in those 71 communities,” Weinstein said. “He has been a supporter of Mariposa efforts in telemedicine since the beginning.”
24-hour access
The network gives 24/7 access to pathology (the study of disease) at the UA College of Medicine. “Telemedicine is a large program that provides services at a distance,” Weinstein said.
Nogales came on board through a grant from the Department of Agriculture. Originally, the program was designed for “end of the dirt road” clinics, Weinstein said. Mariposa was brought on to allow doctors in Phoenix and Tucson to travel to a remote site that was easily accessible to evaluate the network in the beginning.
The U of A created a unique network for Arizona. In 1996, there was a problem of broadband access in Arizona, and the U of A created the Telemedicine Network outside the Internet to meet its telecommunications needs, Weinstein said.
By 1998 there were 55 sites, including Nogales. Nogales was the first rural site, Weinstein said.
Communities served include remote Indian reservations and prisons in rural settings. The Department of Corrections facilities are placed in remote locations in Arizona. The Indian reservations saved $200,000 in costs over the last year. “The dollar savings in the Department of Corrections is enough to fund the entire program,” Weinstein said.
It is easier to use telemedicine for the prison system than to transport prisoners, and the prisoners like it better, Weinstein said.
Radiology is huge in the prison system, Weinstein said, but it is only one of the specialties that use the Telemedicine Network.
Real-time use
One example is doctors use real-time ultrasound to diagnose fetal problems. There are many applications, Weinstein said. They include tele-psychiatry, tele-dermatology, tele-cardiology, tele-ophthalmology, infectious disease diagnosis and family teleconferencing.
There are many times a patient is confined for long periods at a hospital and the family is in a remote community. The system allows families to continue interpersonal relations, which benefit the patient, Weinstein said.
Tele-pediatrics and tele-trauma, which began in Douglas, are also important, Weinstein said. “It provides a telepresence for trauma physicians. “It saves lives,” Weinstein said.
Broadband access promises more access for remote communities in the future, Weinstein said. “Many sites are now interoperable over the broadband network. Many of the communications issues are not minimized because of the availability of the Internet. That’s a real advance.”
Thus far, the network has handled more than 700,000 cases. More than 150 physicians from the college of medicine handle cases. “We have a long way to go,” Weinstein said. “The university still doesn’t have access to all the information to assist in all cases.”
That is due to the fragmented nature of the U.S. health-care system, Weinstein said. Some patient records may not be accessible through the network.
The latest advance is in digital mammography, Weinstein said. “The Navajo Nation wants to be first in telemedicine. They now have a 45-minute turn-around for digital mammography, where the follow up was only 50 percent, and entailed a long wait.”
Patients are often without communications on reservations, Weinstein explained. The network shortened a weeklong turnaround to allow patients to remain at the clinic to hear results.
Dramatic change
The change is dramatic. “It has altered the way physicians look at disease,” Weinstein said. It gives physicians the opportunity to communicate and to compare things.
Still, one of four to six visits should be in person, for most cases, Weinstein said. Some procedures can be completely remote, such as the digital mammography, with the on-site physician handling consultation.
The Mariposa Series of lectures is an opportunity to bring folks together for lunch and to hear about the latest developments in medical care from a well-respected speaker, Weldon said. The series began in 2007 and is held twice a year, said Norma Villasenor executive assistant to the CEO.
The Arizona Telemedicine Network gives people in Santa Cruz County access to specialty care--that’s care beyond what is offered at Mariposa--applying the latest technology, said Mariposa Health Clinic CEO Jim Weldon. “Doctor (Ronald S.) Weinstein founded the program, and it’s very innovative--a national model.” Weinstein was the third guest speaker in the Mariposa Series on Thursday at Holiday Inn Express in Nogales.
The network gives local clinics access to information and specialties above the level normally available in Nogales, Mariposa chief of medicine Eladio Pereira said. Mariposa Clinic uses rheumatology, dermatology and gastroenterology services over the Telemedicine Network. “It’s incredible--speed, accuracy, consults right away. It’s very, very important.”
There are several cases each month that are aided by use of the network at Mariposa, Pereira said.
The network had it’s beginnings at Massachusetts General in 1968, Weinstein said. Telepathology, or remote diagnosis began in the 1980s. The concept is illustrated by the television shows “CSI,: and earlier, “Quincy, M.E.,” Weinstein said.
Arizona Sen. Robert Burns was instrumental in the establishment of the network, Weinstein said. “He’s now president of the Arizona state senate. He founded it. He came to us and asked us to do it.”
The network began at the Phoenix campus of the University of Arizona College of Medicine, where Weinstein is director of the program. It now includes 171 sites in 71 communities. “Doctor Pereira is the best director in those 71 communities,” Weinstein said. “He has been a supporter of Mariposa efforts in telemedicine since the beginning.”
24-hour access
The network gives 24/7 access to pathology (the study of disease) at the UA College of Medicine. “Telemedicine is a large program that provides services at a distance,” Weinstein said.
Nogales came on board through a grant from the Department of Agriculture. Originally, the program was designed for “end of the dirt road” clinics, Weinstein said. Mariposa was brought on to allow doctors in Phoenix and Tucson to travel to a remote site that was easily accessible to evaluate the network in the beginning.
The U of A created a unique network for Arizona. In 1996, there was a problem of broadband access in Arizona, and the U of A created the Telemedicine Network outside the Internet to meet its telecommunications needs, Weinstein said.
By 1998 there were 55 sites, including Nogales. Nogales was the first rural site, Weinstein said.
Communities served include remote Indian reservations and prisons in rural settings. The Department of Corrections facilities are placed in remote locations in Arizona. The Indian reservations saved $200,000 in costs over the last year. “The dollar savings in the Department of Corrections is enough to fund the entire program,” Weinstein said.
It is easier to use telemedicine for the prison system than to transport prisoners, and the prisoners like it better, Weinstein said.
Radiology is huge in the prison system, Weinstein said, but it is only one of the specialties that use the Telemedicine Network.
Real-time use
One example is doctors use real-time ultrasound to diagnose fetal problems. There are many applications, Weinstein said. They include tele-psychiatry, tele-dermatology, tele-cardiology, tele-ophthalmology, infectious disease diagnosis and family teleconferencing.
There are many times a patient is confined for long periods at a hospital and the family is in a remote community. The system allows families to continue interpersonal relations, which benefit the patient, Weinstein said.
Tele-pediatrics and tele-trauma, which began in Douglas, are also important, Weinstein said. “It provides a telepresence for trauma physicians. “It saves lives,” Weinstein said.
Broadband access promises more access for remote communities in the future, Weinstein said. “Many sites are now interoperable over the broadband network. Many of the communications issues are not minimized because of the availability of the Internet. That’s a real advance.”
Thus far, the network has handled more than 700,000 cases. More than 150 physicians from the college of medicine handle cases. “We have a long way to go,” Weinstein said. “The university still doesn’t have access to all the information to assist in all cases.”
That is due to the fragmented nature of the U.S. health-care system, Weinstein said. Some patient records may not be accessible through the network.
The latest advance is in digital mammography, Weinstein said. “The Navajo Nation wants to be first in telemedicine. They now have a 45-minute turn-around for digital mammography, where the follow up was only 50 percent, and entailed a long wait.”
Patients are often without communications on reservations, Weinstein explained. The network shortened a weeklong turnaround to allow patients to remain at the clinic to hear results.
Dramatic change
The change is dramatic. “It has altered the way physicians look at disease,” Weinstein said. It gives physicians the opportunity to communicate and to compare things.
Still, one of four to six visits should be in person, for most cases, Weinstein said. Some procedures can be completely remote, such as the digital mammography, with the on-site physician handling consultation.
The Mariposa Series of lectures is an opportunity to bring folks together for lunch and to hear about the latest developments in medical care from a well-respected speaker, Weldon said. The series began in 2007 and is held twice a year, said Norma Villasenor executive assistant to the CEO.
Firms hope their compounds will be tomorrow’s medicines
[Source: Phoenix Business Journal, Angela Gonzales] - While only a handful of big pharmaceutical firms have a presence in Arizona, the Grand Canyon State is home to a plethora of smaller companies in the early stages of drug development.
The problem is, it’s getting more expensive and taking longer to get drugs to market, and most of the drugs being tested are failing long before they hit the shelves.
Only 16 new medicines were approved by the U.S. Food and Drug Administration in 2007 — one of the lowest totals in more than two decades, said Dr. Ray Woosley, president and CEO of the Tucson-based Critical Path Institute, which is working with big pharma and the FDA to get drugs to market quickly and safely.
As a result, the world’s pharmaceutical industry is turning its attention to biotech companies, hoping their compounds are tomorrow’s answer to today’s diseases.
Local biotech companies are positioning themselves to catch big pharma’s attention as they test their novel compounds in animal studies and early human trials. Many of them are counting on getting licensing agreements before their compounds reach the expensive phase three clinical trials.
For example, InNexus Biotechnology Inc. has a commitment from Ontario, Canada-based Royalty Pharma Inc. for $34.5 million in funding to help get its compounds through the early phases of human clinical trials. At that point, the goal is to hand the drugs off to the pharmaceutical industry, said Jeff Morhet, president and CEO of InNexus.
“Given this market, distinction is critical,” he said. “You’ve got to be able to show what you’ve been able to produce is going to provide value.”
John Carroll, editor of FierceBiotech, which tracks the industry nationwide, said it has been a seller’s market for quite some time, which has been good for biotech companies.
“I’ve seen some very sweet deals,” he said. “Pharma companies need these new therapies, and they haven’t done well coming up with new major drugs to replace the blockbusters that they’re losing off of patent.”
However, Carroll said the tide changed in October.
“It’s not a seller’s market anymore,” he said. “It’s more of a buyer’s market.”
Now, big pharma is in a position to swoop in and buy struggling biotech firms’ assets at a mark-down, he said.
“If you’re a little biotech company and got two years of operating capital, that’s OK,” he said. “It’s all a question of positioning right now.”
He’s seeing biotech companies laying off 25 percent to 40 percent of their work forces nationwide.
“Usually, if I had one biotech restructuring or laying off staff as a result of an FDA rejection or failure, that was not uncommon,” Carroll said. “Now, you’re just seeing a whole slate of different biotech companies laying off.”
2009 will be a ‘long, hard row’
Carroll said he doesn’t see any short-term prospects for a turnaround.
“We’re just getting into it,” he said. “2009 is going to be a long, hard row for a lot of people to hoe.”
Biotech companies that have two years of operating capital will be able to weather the storm, he said, but he doesn’t see many with that much capital.
Pharma doesn’t have to be so desperate anymore, according to Steven Burrill, president and CEO of San Francisco-based Burrill & Co., a financial firm that focuses on life sciences.
“They know biotechs will come and talk with them,” he said. “They can hang back and wait. They do have rapidly depleting pipelines, but they don’t have to be in as big a hurry and they may not have to pay as much.”
Michael Wilhelm, president and CEO of Scottsdale-based ImmuneRegen BioSciences Inc., said he hopes a large biotech or pharma will acquire or license his company’s drugs.
“Those conversations are happening more so than they were,” he said.
Spreading out the Risk
Large pharma companies have invested a lot of money in research and development, and they have not seen a commensurate increase in the number of drugs that have been approved, said Hal Siegel, chief scientific officer for ImmuneRegen.
“They’re looking to spread out the risk by partnering with small companies earlier in development so they can fund the research in a broad number of compounds that are still early-stage,” he said. “They’re hedging their bets, making larger investments in better compounds later on.”
Gail Thurston, vice president of corporate and business development for Apthera Inc. in Scottsdale, said the pharmaceutical companies have distribution networks set up to take new drugs to market — something Apthera and other small biotechs don’t have.
“We will provide the tools for a big pharma company to go out there and get the numbers that we projected for sale over the next decade or so,” she said. “Our patents are quite young. They won’t turn into generics any time soon anyway.”
She said she hopes Apthera’s compound will enter phase three clinical trials by the end of next year, with a global partner to co-develop its portfolio of cancer drugs.
“There are not a heck of a lot of companies like ours that have late-stage products that are available for licensing,” she said. “People are taking notice.”
Jeffrey Berk, president of Scottsdale-based MedPredict Market Research, said it’s crucial for biotech and pharmaceutical firms to trudge forward in their research efforts for new drugs and therapies.
He pointed to Novartis Pharma US’ 9-year-old drug, Gleevec, which treats chronic myeloid leukemia. Before the drug was invented, patients with that disease would live for about a year. With Gleevec, their life expectancy increases to eight to 10 years. About 4,500 Americans get the disease each year. Now, fewer than 400 die from it each year.
“You have to understand what pharma can deliver,” Berk said.
The problem is, it’s getting more expensive and taking longer to get drugs to market, and most of the drugs being tested are failing long before they hit the shelves.
Only 16 new medicines were approved by the U.S. Food and Drug Administration in 2007 — one of the lowest totals in more than two decades, said Dr. Ray Woosley, president and CEO of the Tucson-based Critical Path Institute, which is working with big pharma and the FDA to get drugs to market quickly and safely.
As a result, the world’s pharmaceutical industry is turning its attention to biotech companies, hoping their compounds are tomorrow’s answer to today’s diseases.
Local biotech companies are positioning themselves to catch big pharma’s attention as they test their novel compounds in animal studies and early human trials. Many of them are counting on getting licensing agreements before their compounds reach the expensive phase three clinical trials.
For example, InNexus Biotechnology Inc. has a commitment from Ontario, Canada-based Royalty Pharma Inc. for $34.5 million in funding to help get its compounds through the early phases of human clinical trials. At that point, the goal is to hand the drugs off to the pharmaceutical industry, said Jeff Morhet, president and CEO of InNexus.
“Given this market, distinction is critical,” he said. “You’ve got to be able to show what you’ve been able to produce is going to provide value.”
John Carroll, editor of FierceBiotech, which tracks the industry nationwide, said it has been a seller’s market for quite some time, which has been good for biotech companies.
“I’ve seen some very sweet deals,” he said. “Pharma companies need these new therapies, and they haven’t done well coming up with new major drugs to replace the blockbusters that they’re losing off of patent.”
However, Carroll said the tide changed in October.
“It’s not a seller’s market anymore,” he said. “It’s more of a buyer’s market.”
Now, big pharma is in a position to swoop in and buy struggling biotech firms’ assets at a mark-down, he said.
“If you’re a little biotech company and got two years of operating capital, that’s OK,” he said. “It’s all a question of positioning right now.”
He’s seeing biotech companies laying off 25 percent to 40 percent of their work forces nationwide.
“Usually, if I had one biotech restructuring or laying off staff as a result of an FDA rejection or failure, that was not uncommon,” Carroll said. “Now, you’re just seeing a whole slate of different biotech companies laying off.”
2009 will be a ‘long, hard row’
Carroll said he doesn’t see any short-term prospects for a turnaround.
“We’re just getting into it,” he said. “2009 is going to be a long, hard row for a lot of people to hoe.”
Biotech companies that have two years of operating capital will be able to weather the storm, he said, but he doesn’t see many with that much capital.
Pharma doesn’t have to be so desperate anymore, according to Steven Burrill, president and CEO of San Francisco-based Burrill & Co., a financial firm that focuses on life sciences.
“They know biotechs will come and talk with them,” he said. “They can hang back and wait. They do have rapidly depleting pipelines, but they don’t have to be in as big a hurry and they may not have to pay as much.”
Michael Wilhelm, president and CEO of Scottsdale-based ImmuneRegen BioSciences Inc., said he hopes a large biotech or pharma will acquire or license his company’s drugs.
“Those conversations are happening more so than they were,” he said.
Spreading out the Risk
Large pharma companies have invested a lot of money in research and development, and they have not seen a commensurate increase in the number of drugs that have been approved, said Hal Siegel, chief scientific officer for ImmuneRegen.
“They’re looking to spread out the risk by partnering with small companies earlier in development so they can fund the research in a broad number of compounds that are still early-stage,” he said. “They’re hedging their bets, making larger investments in better compounds later on.”
Gail Thurston, vice president of corporate and business development for Apthera Inc. in Scottsdale, said the pharmaceutical companies have distribution networks set up to take new drugs to market — something Apthera and other small biotechs don’t have.
“We will provide the tools for a big pharma company to go out there and get the numbers that we projected for sale over the next decade or so,” she said. “Our patents are quite young. They won’t turn into generics any time soon anyway.”
She said she hopes Apthera’s compound will enter phase three clinical trials by the end of next year, with a global partner to co-develop its portfolio of cancer drugs.
“There are not a heck of a lot of companies like ours that have late-stage products that are available for licensing,” she said. “People are taking notice.”
Jeffrey Berk, president of Scottsdale-based MedPredict Market Research, said it’s crucial for biotech and pharmaceutical firms to trudge forward in their research efforts for new drugs and therapies.
He pointed to Novartis Pharma US’ 9-year-old drug, Gleevec, which treats chronic myeloid leukemia. Before the drug was invented, patients with that disease would live for about a year. With Gleevec, their life expectancy increases to eight to 10 years. About 4,500 Americans get the disease each year. Now, fewer than 400 die from it each year.
“You have to understand what pharma can deliver,” Berk said.
When Medicine Meets Marketing
[Source: Newsweek, Mary Carmichael] - Dallas Hextell was just a baby when his parents bought him a walker—not because he was late reaching a milestone, but because they worried he might never toddle on his own. At 9 months he had been diagnosed with cerebral palsy, a form of brain injury caused by oxygen deprivation in utero or at birth. A neurologist had told Derak and Cynthia Hextell there was no cure, that it was best to wait and see if their son improved. But Cynthia, after months of research, enrolled Dallas in a highly experimental trial at Duke University, where a pediatric-transplant surgeon infused him with a sample of his own stem cells harvested from his umbilical-cord blood. A few days later, Derak and Cynthia went home with their son, who was 18 months old and still not crawling, much less walking or talking. They "stared at him" for a week, says Cynthia. "One day he just started saying, 'Mama, mama, mama.' And I started crying." The Hextells ended up donating the walker to another child. By 2, Dallas was not only walking unaided, he was chasing the family dogs.
If the Hextells' names sound familiar to some readers, it is because, in the wake of their son's remarkable recovery, they have become minor celebrities. Their story has appeared on the "Today" show and in advertisements in almost every pregnancy magazine in the country. The ads are not for the trial at Duke, which remains a small, academic endeavor. They are for a company called Cord Blood Registry, which charges parents $2,000-plus to freeze and store samples of their children's umbilical-cord blood, a fluid rich in stem cells. Cynthia Hextell paid the company to freeze Dallas's cord blood at his birth. That sample was the source of the stem cells used in the Duke trial—and as the ads remind parents, it was available only because the Hextells had paid for it to be.
The Hextells' story has become the centerpiece of CBR's marketing efforts. Recently the company invited about 30 obstetricians and midwives to the Westin La Paloma resort in Tucson, Ariz., for a weekend of sun, golf and medical briefings, including dinner in a ballroom with the Hextells as guest speakers. Since these doctors had collected cord blood for CBR clients in the past, the company hoped to turn them into evangelists. The next day, the group went for a tour of CBR's glittering 60,000-square-foot lab. The agenda also included more time at the La Paloma, home to a Jack Nicklaus golf course, a spa, five restaurants and a swim-up bar. CBR can easily afford to put on this kind of show. Ten years ago it was a fledgling business with 10,000 clients. Today it is the country's largest private cord-blood bank, with 250,000 samples in storage, 300 employees and $100 million in annual revenue.
In medicine, money often comes with controversy—and right now, CBR has plenty of both. The company says it is providing precious biological insurance, that to freeze a child's cord-blood stem cells is to provide him a medical option for the future, perhaps a lifesaving treatment for childhood cancer or brain injuries. But critics, including the American Academy of Pediatrics, accuse private cord-blood banks like CBR of making exaggerated medical promises and exploiting vulnerable new parents. Cord blood's uses are limited at best, they say. The blood does not provide enough cells to cure an adult of a disease or injury; it is not appropriate for treating genetic conditions; and thus far there have been few trials to determine how effectively the cells can repair damaged tissue. Even Joanne Kurtzberg, the Duke transplant specialist who treated Dallas Hextell, is skeptical. She says it's difficult to know if his improvement is related to the cells or would have occurred without them—he probably would have gotten better on his own; some cerebral-palsy patients do—and she points out that her trial is small and yet to be analyzed and published. But CBR has a response for this. It says more uses for cord-blood stem cells will surely be discovered in the future. It also knows the power of a good story. David Zitlow, the company's senior vice president of public affairs, says doctors "haven't made a big enough deal about anecdotes" like the Hextells'.
So what are other parents, faced with the choice of banking their children's cord blood or brushing off the idea as a luxury—the medical equivalent of an $800 stroller—supposed to make of Dallas Hextell's case? Is it a breakthrough, a harbinger? Or is it ultimately just an anecdote, a moving tale with a happy outcome that may or may not have anything to do with cord blood and stem cells?
Doctors have been wondering if cord blood is something of a miracle cure for the past 15 years. The blood—which is usually thrown away in delivery rooms—contains a distinct type of stem cell that may act as a biochemical foreman, helping to build healthy tissues and repair damaged ones. In the early 1990s— before embryonic stem cells took over the spotlight—researchers began to explore whether cord-blood cells might be of practical medical use. At Duke, Kurtzberg performed a few cord-blood transplants on patients with leukemia and rare types of bone-marrow failure, sending them into remission. Meanwhile, the National Institutes of Health started funding public banks of frozen, donated cord-blood samples, modeled on adult blood banks. A cord-blood stem-cell transplant at that point was a long shot, an experiment to see if stem cells could either become new tissue or trick the body into fixing itself. But the idea behind the public banks was to make the option available to all families who might want to try it as a last resort.
It was around this time, in 1992, that Tom Moore, a technology and pharmaceutical executive with passion for startups, hatched a plan to found a cord-blood bank of his own. Unlike the NIH banks, this one would operate for profit. Its clients would retain exclusive access to their own genetically identical samples, for a fee of $1,500 up front plus $125 for each year of storage. One problem: Moore "didn't really know anything about stem cells except the name," he admits. So he sought out David Harris, a University of Arizona immunologist and cord-blood researcher, to serve as CBR's scientific director; meanwhile, as the CEO, he took care of the business side. Now it takes care of him. CBR is the largest of 30-some private cord-blood banks in the United States, with a 45 percent share of the $250 million market. It's probably not done growing yet. Moore's "big, hairy, audacious goal" is a million clients, quadruple the company's current size.
A number of trends have likely contributed to CBR's growth, including the enormous boom in the baby-products market and the hype around stem cells in general. But one thing that has not been a factor is a rapid rise in medical uses for cord blood—because there hasn't been one yet. Just as it was in the '90s, a cord-blood stem-cell transplant is still an experimental procedure. This hasn't deterred CBR from publicizing the results of a few positive studies, including a small, preliminary trial in kids with type 1 diabetes from last year.
In Dallas Hextell, CBR has another case to promote. In ads, the Hextells call the cord-blood treatment "a miracle." But nobody really knows what has happened in Dallas's brain. The story sounds less clear-cut coming from Kurtzberg, the doctor who performed the transfusion and who examined Dallas again in November. "He has made progress, there's no question," she says. "But he still has a global developmental delay of about a year. He looks like where we would have expected him to be without cells." When she saw him at his follow-up visit, she adds, "I thought, wow, he doesn't look as good as I was expecting based on what's been in the press." (The Hextells find Kurtzberg's assessment frustrating and note that Dallas's therapists at home—who knew him before the transfusion—are impressed and surprised at his improvement.) Kurtzberg also has not completed the follow-up and analysis of the study or published the results from 50 other kids with cerebral palsy who have enrolled in her trial thus far.
Kurtzberg, it turns out, is not a big booster for private cord-blood banks; although she uses samples from CBR, she does not receive funding from the company, and also uses cells from public banks and other companies. In fact, she's one of the authors of a statement the American Academy of Pediatrics put out last year discouraging parents from using private banks on the grounds that the science isn't solid enough yet to justify a multi-thousand-dollar gamble. (The AAP does support public, nonprofit banks, which patients can use for free.) The American College of Obstetricians and Gynecologists released its own statement in February, noting that "there is no reliable estimate of a child's likelihood of actually using his or her own saved cord blood later." Then it made a guess anyway: 1 in 2,700, which Kurtzberg calls "generous."
Why is this number so small? There are reasons to think cord-blood treatment will never be a widespread medical procedure. The blood contains only enough stem cells to treat a small child; unlike embryonic stem cells, cord-blood cells cannot be multiplied into self-rejuvenating "lines" in a petri dish. The cells are limited in other ways, too. There's little point in treating a genetic condition with a patient's own cord-blood cells, which have the same DNA and thus the same deleterious mutations. Scientists could someday overcome these hurdles; they could develop new ways of cultivating and genetically tweaking cord-blood cells in the lab. But by then, the same scientists will probably know much more about all stem cells, especially once restrictions on embryonic research are lifted—and there may be better ways of getting safe, usable cells from other sources, ways that won't require a lot of technological wizardry.
These difficulties don't deter everyone, of course. The pediatrician Robert Sears, a talk-show regular and the coauthor of popular parenting books, supports private cord-blood banking; he froze his own kids' samples with CBR. It's also possible that 1 in 2,700 is too conservative. CBR's executives toss around much more dramatic odds. Harris, the scientific director, puts them at a breathtaking 1 in 3. His calculations, unlike the professional groups', include injuries to the brain. There is, he notes, "no genetic predisposition to falling out of a crib"—so as he sees it, every child, technically, is at risk.
Until widespread trials of cord-blood treatment take place, both sides will be able to use arbitrary calculations. Those trials, alas, are probably far off: rare conditions are difficult to study on a large scale, since by definition there aren't many patients to enroll. Three years ago, Congress tried to put cord-blood trials on a faster track by expanding funds for the NIH's public banks—more donations to the banks could mean more studies—but the law hasn't made much of an impact. Public banks have collected cord blood from just 105,000 babies, and fewer than 200 hospitals in the U.S. are able to draw and ship the blood to public centers. The private banks, of course, have larger stores. But they are not huge contributors to research either: only 100 of CBR's 250,000 clients have enrolled in trials thus far.
For now, parents are left to make the same speculative wager at the heart of CBR's business model: how much should you invest in science that's promising but not proven? Back in the ballroom in Tucson, the OBs and midwives on the CBR junket were considering that question too. They pressed Cynthia Hextell for more details. How were the other kids in the Kurtzberg trial doing? Cynthia said the few other families she had talked to had seen improvements like Dallas's. And what risks were they warned about? "The only risk was that it wouldn't work and we would be out the money," she said. "But we just knew in our hearts that it was going to work." Other parents will have to decide whether they have that kind of faith.
If the Hextells' names sound familiar to some readers, it is because, in the wake of their son's remarkable recovery, they have become minor celebrities. Their story has appeared on the "Today" show and in advertisements in almost every pregnancy magazine in the country. The ads are not for the trial at Duke, which remains a small, academic endeavor. They are for a company called Cord Blood Registry, which charges parents $2,000-plus to freeze and store samples of their children's umbilical-cord blood, a fluid rich in stem cells. Cynthia Hextell paid the company to freeze Dallas's cord blood at his birth. That sample was the source of the stem cells used in the Duke trial—and as the ads remind parents, it was available only because the Hextells had paid for it to be.
The Hextells' story has become the centerpiece of CBR's marketing efforts. Recently the company invited about 30 obstetricians and midwives to the Westin La Paloma resort in Tucson, Ariz., for a weekend of sun, golf and medical briefings, including dinner in a ballroom with the Hextells as guest speakers. Since these doctors had collected cord blood for CBR clients in the past, the company hoped to turn them into evangelists. The next day, the group went for a tour of CBR's glittering 60,000-square-foot lab. The agenda also included more time at the La Paloma, home to a Jack Nicklaus golf course, a spa, five restaurants and a swim-up bar. CBR can easily afford to put on this kind of show. Ten years ago it was a fledgling business with 10,000 clients. Today it is the country's largest private cord-blood bank, with 250,000 samples in storage, 300 employees and $100 million in annual revenue.
In medicine, money often comes with controversy—and right now, CBR has plenty of both. The company says it is providing precious biological insurance, that to freeze a child's cord-blood stem cells is to provide him a medical option for the future, perhaps a lifesaving treatment for childhood cancer or brain injuries. But critics, including the American Academy of Pediatrics, accuse private cord-blood banks like CBR of making exaggerated medical promises and exploiting vulnerable new parents. Cord blood's uses are limited at best, they say. The blood does not provide enough cells to cure an adult of a disease or injury; it is not appropriate for treating genetic conditions; and thus far there have been few trials to determine how effectively the cells can repair damaged tissue. Even Joanne Kurtzberg, the Duke transplant specialist who treated Dallas Hextell, is skeptical. She says it's difficult to know if his improvement is related to the cells or would have occurred without them—he probably would have gotten better on his own; some cerebral-palsy patients do—and she points out that her trial is small and yet to be analyzed and published. But CBR has a response for this. It says more uses for cord-blood stem cells will surely be discovered in the future. It also knows the power of a good story. David Zitlow, the company's senior vice president of public affairs, says doctors "haven't made a big enough deal about anecdotes" like the Hextells'.
So what are other parents, faced with the choice of banking their children's cord blood or brushing off the idea as a luxury—the medical equivalent of an $800 stroller—supposed to make of Dallas Hextell's case? Is it a breakthrough, a harbinger? Or is it ultimately just an anecdote, a moving tale with a happy outcome that may or may not have anything to do with cord blood and stem cells?
Doctors have been wondering if cord blood is something of a miracle cure for the past 15 years. The blood—which is usually thrown away in delivery rooms—contains a distinct type of stem cell that may act as a biochemical foreman, helping to build healthy tissues and repair damaged ones. In the early 1990s— before embryonic stem cells took over the spotlight—researchers began to explore whether cord-blood cells might be of practical medical use. At Duke, Kurtzberg performed a few cord-blood transplants on patients with leukemia and rare types of bone-marrow failure, sending them into remission. Meanwhile, the National Institutes of Health started funding public banks of frozen, donated cord-blood samples, modeled on adult blood banks. A cord-blood stem-cell transplant at that point was a long shot, an experiment to see if stem cells could either become new tissue or trick the body into fixing itself. But the idea behind the public banks was to make the option available to all families who might want to try it as a last resort.
It was around this time, in 1992, that Tom Moore, a technology and pharmaceutical executive with passion for startups, hatched a plan to found a cord-blood bank of his own. Unlike the NIH banks, this one would operate for profit. Its clients would retain exclusive access to their own genetically identical samples, for a fee of $1,500 up front plus $125 for each year of storage. One problem: Moore "didn't really know anything about stem cells except the name," he admits. So he sought out David Harris, a University of Arizona immunologist and cord-blood researcher, to serve as CBR's scientific director; meanwhile, as the CEO, he took care of the business side. Now it takes care of him. CBR is the largest of 30-some private cord-blood banks in the United States, with a 45 percent share of the $250 million market. It's probably not done growing yet. Moore's "big, hairy, audacious goal" is a million clients, quadruple the company's current size.
A number of trends have likely contributed to CBR's growth, including the enormous boom in the baby-products market and the hype around stem cells in general. But one thing that has not been a factor is a rapid rise in medical uses for cord blood—because there hasn't been one yet. Just as it was in the '90s, a cord-blood stem-cell transplant is still an experimental procedure. This hasn't deterred CBR from publicizing the results of a few positive studies, including a small, preliminary trial in kids with type 1 diabetes from last year.
In Dallas Hextell, CBR has another case to promote. In ads, the Hextells call the cord-blood treatment "a miracle." But nobody really knows what has happened in Dallas's brain. The story sounds less clear-cut coming from Kurtzberg, the doctor who performed the transfusion and who examined Dallas again in November. "He has made progress, there's no question," she says. "But he still has a global developmental delay of about a year. He looks like where we would have expected him to be without cells." When she saw him at his follow-up visit, she adds, "I thought, wow, he doesn't look as good as I was expecting based on what's been in the press." (The Hextells find Kurtzberg's assessment frustrating and note that Dallas's therapists at home—who knew him before the transfusion—are impressed and surprised at his improvement.) Kurtzberg also has not completed the follow-up and analysis of the study or published the results from 50 other kids with cerebral palsy who have enrolled in her trial thus far.
Kurtzberg, it turns out, is not a big booster for private cord-blood banks; although she uses samples from CBR, she does not receive funding from the company, and also uses cells from public banks and other companies. In fact, she's one of the authors of a statement the American Academy of Pediatrics put out last year discouraging parents from using private banks on the grounds that the science isn't solid enough yet to justify a multi-thousand-dollar gamble. (The AAP does support public, nonprofit banks, which patients can use for free.) The American College of Obstetricians and Gynecologists released its own statement in February, noting that "there is no reliable estimate of a child's likelihood of actually using his or her own saved cord blood later." Then it made a guess anyway: 1 in 2,700, which Kurtzberg calls "generous."
Why is this number so small? There are reasons to think cord-blood treatment will never be a widespread medical procedure. The blood contains only enough stem cells to treat a small child; unlike embryonic stem cells, cord-blood cells cannot be multiplied into self-rejuvenating "lines" in a petri dish. The cells are limited in other ways, too. There's little point in treating a genetic condition with a patient's own cord-blood cells, which have the same DNA and thus the same deleterious mutations. Scientists could someday overcome these hurdles; they could develop new ways of cultivating and genetically tweaking cord-blood cells in the lab. But by then, the same scientists will probably know much more about all stem cells, especially once restrictions on embryonic research are lifted—and there may be better ways of getting safe, usable cells from other sources, ways that won't require a lot of technological wizardry.
These difficulties don't deter everyone, of course. The pediatrician Robert Sears, a talk-show regular and the coauthor of popular parenting books, supports private cord-blood banking; he froze his own kids' samples with CBR. It's also possible that 1 in 2,700 is too conservative. CBR's executives toss around much more dramatic odds. Harris, the scientific director, puts them at a breathtaking 1 in 3. His calculations, unlike the professional groups', include injuries to the brain. There is, he notes, "no genetic predisposition to falling out of a crib"—so as he sees it, every child, technically, is at risk.
Until widespread trials of cord-blood treatment take place, both sides will be able to use arbitrary calculations. Those trials, alas, are probably far off: rare conditions are difficult to study on a large scale, since by definition there aren't many patients to enroll. Three years ago, Congress tried to put cord-blood trials on a faster track by expanding funds for the NIH's public banks—more donations to the banks could mean more studies—but the law hasn't made much of an impact. Public banks have collected cord blood from just 105,000 babies, and fewer than 200 hospitals in the U.S. are able to draw and ship the blood to public centers. The private banks, of course, have larger stores. But they are not huge contributors to research either: only 100 of CBR's 250,000 clients have enrolled in trials thus far.
For now, parents are left to make the same speculative wager at the heart of CBR's business model: how much should you invest in science that's promising but not proven? Back in the ballroom in Tucson, the OBs and midwives on the CBR junket were considering that question too. They pressed Cynthia Hextell for more details. How were the other kids in the Kurtzberg trial doing? Cynthia said the few other families she had talked to had seen improvements like Dallas's. And what risks were they warned about? "The only risk was that it wouldn't work and we would be out the money," she said. "But we just knew in our hearts that it was going to work." Other parents will have to decide whether they have that kind of faith.
TGen, Scottsdale Healthcare, Mayo Clinic study starts for new drug that could bolster the immune systems of cancer victims
[Source: TGen] - The Translational Genomics Research Institute (TGen), Scottsdale Healthcare and Mayo Clinic are testing a new drug that could help cancer patients by stimulating the immune system.
Clinical trials of the drug VTX-2337 are being conducted at TGen Clinical Research Services at Scottsdale Healthcare, a partnership of Phoenix-based TGen and Scottsdale-based Scottsdale Healthcare Corp., and at Mayo Clinic in Arizona.
Dr. Ramesh Ramanathan, Medical Director of TGen Clincal Research Services at Scottsdale Healthcare, said the new drug appears promising.
"VTX-2337 is a new, novel, small molecule aimed at stimulating the immune cells in the blood, lymph nodes, and in and around the tumor. It represents an exciting new class of agents for cancer therapy with good preclinical evidence of activity," Dr. Ramanathan said.
The Phase I trial, a yearlong first-in-humans test, will study the drug's safety. If successful, a Phase II trial will test the drug's effectiveness on tumors.
A weakened immune system is often the result of advanced cancer. The hope is that this new drug will actually help enable the immune system to slow down the growth of tumors, and perhaps even shrink them, Dr. Ramanathan said.
VTX-2337 is the first drug of its kind developed by San Diego-based VentiRx Pharmaceuticals Inc. The biopharmaceutical company is focused on the development of new Toll-Like Receptor 8 (TLR8) agonists, which are small molecules that prompt a response in the body's immune system. The drugs are intended to treat cancer, respiratory and autoimmune diseases.
"VentiRx is very excited to be working with TGen, Scottsdale Healthcare and Mayo Clinic on this important and novel program," said Michael Kamdar, Executive Vice President and Chief Business Officer at VentiRx. "Entering Phase I clinical trials represents a significant milestone for VentiRx and our TLR efforts in that we have rapidly advanced into a clinical development company with a novel molecule that may play an important role and have broad application in the treatment of cancer."
VTX-2337 is a small molecule TLR8 agonist that is expected to be used in combination with standard of care for the treatment of patients with cancer. Preclinical evaluation of VTX-2337 suggests that it may play a key role in augmenting the innate arm of the immune system.
There are two broad components of the immune system, the innate arm, and the adaptive arm. Both generally aim to eliminate viruses and bacteria.
-- The innate arm senses infectious agents as they infect the body by recognizing structures they have in common, such as lipids, proteins, sugars, and nucleic acids (DNA and RNA). This is an initial rapid response, which is not precise but potent.
-- The adaptive arm of the immune system is instructed by the innate arm to devise more specific responses to unique components of the invading pathogens. This is a more precise response and takes longer, especially when an infectious agent is encountered for the first time.
The first clinical trial at TCRS at Scottsdale Healthcare will investigate the safety and pharmacology of multiple doses of VTX-2337 in patients with late-stage cancer. For more information about this clinical trial, please call Joyce Ingold, R.N., research patient care coordinator for Scottsdale Healthcare, at 480-323-1339.
The clinical trial coordinator for Mayo Clinic is Dianna Boughter, who can be reached at 480-301-9875.
"VTX-2337 is the first selective TLR8 compound to reach the clinic, and we are hopeful that modulation of the innate immune response will provide a benefit to patients in a number of oncology indications," said Dr. Robert Hershberg, Executive Vice President and Chief Medical Officer at VentiRx.
Clinical trials of the drug VTX-2337 are being conducted at TGen Clinical Research Services at Scottsdale Healthcare, a partnership of Phoenix-based TGen and Scottsdale-based Scottsdale Healthcare Corp., and at Mayo Clinic in Arizona.
Dr. Ramesh Ramanathan, Medical Director of TGen Clincal Research Services at Scottsdale Healthcare, said the new drug appears promising.
"VTX-2337 is a new, novel, small molecule aimed at stimulating the immune cells in the blood, lymph nodes, and in and around the tumor. It represents an exciting new class of agents for cancer therapy with good preclinical evidence of activity," Dr. Ramanathan said.
The Phase I trial, a yearlong first-in-humans test, will study the drug's safety. If successful, a Phase II trial will test the drug's effectiveness on tumors.
A weakened immune system is often the result of advanced cancer. The hope is that this new drug will actually help enable the immune system to slow down the growth of tumors, and perhaps even shrink them, Dr. Ramanathan said.
VTX-2337 is the first drug of its kind developed by San Diego-based VentiRx Pharmaceuticals Inc. The biopharmaceutical company is focused on the development of new Toll-Like Receptor 8 (TLR8) agonists, which are small molecules that prompt a response in the body's immune system. The drugs are intended to treat cancer, respiratory and autoimmune diseases.
"VentiRx is very excited to be working with TGen, Scottsdale Healthcare and Mayo Clinic on this important and novel program," said Michael Kamdar, Executive Vice President and Chief Business Officer at VentiRx. "Entering Phase I clinical trials represents a significant milestone for VentiRx and our TLR efforts in that we have rapidly advanced into a clinical development company with a novel molecule that may play an important role and have broad application in the treatment of cancer."
VTX-2337 is a small molecule TLR8 agonist that is expected to be used in combination with standard of care for the treatment of patients with cancer. Preclinical evaluation of VTX-2337 suggests that it may play a key role in augmenting the innate arm of the immune system.
There are two broad components of the immune system, the innate arm, and the adaptive arm. Both generally aim to eliminate viruses and bacteria.
-- The innate arm senses infectious agents as they infect the body by recognizing structures they have in common, such as lipids, proteins, sugars, and nucleic acids (DNA and RNA). This is an initial rapid response, which is not precise but potent.
-- The adaptive arm of the immune system is instructed by the innate arm to devise more specific responses to unique components of the invading pathogens. This is a more precise response and takes longer, especially when an infectious agent is encountered for the first time.
The first clinical trial at TCRS at Scottsdale Healthcare will investigate the safety and pharmacology of multiple doses of VTX-2337 in patients with late-stage cancer. For more information about this clinical trial, please call Joyce Ingold, R.N., research patient care coordinator for Scottsdale Healthcare, at 480-323-1339.
The clinical trial coordinator for Mayo Clinic is Dianna Boughter, who can be reached at 480-301-9875.
"VTX-2337 is the first selective TLR8 compound to reach the clinic, and we are hopeful that modulation of the innate immune response will provide a benefit to patients in a number of oncology indications," said Dr. Robert Hershberg, Executive Vice President and Chief Medical Officer at VentiRx.
Thursday, December 18, 2008
Vit. E, selenium don't cut risk of prostate cancer, big study finds
[Source: Arizona Daily Star, Evan Pellegrino] - Two natural supplements that have been promoted as possibly helping prevent prostate cancer actually have no effect, according to a national study that included University of Arizona researchers at the Arizona Cancer Center.
According to the study, vitamin E and selenium supplements do not aid in preventing prostate cancer, the most common cancer in American men other than skin cancers.
The study examined the effects of both supplements in more than 35,000 men nationally, including several hundred in Tucson. It was the largest trial ever on prostate-cancer prevention, according to officials at the Arizona Cancer Center. The study included the Southern Arizona VA Health Care System.
Called SELECT (the Selenium and Vitamin E Cancer Prevention Trial), the study was funded by the National Cancer Institute and coordinated through the Southwest Oncology Group.
"A large trial like SELECT is the only way to determine for certain the real value of supplements," said Frederick Ahmann, professor of medicine and director of the Hematology/Oncology Fellowship Program at the Arizona Cancer Center, in a news release.
"Using science to study and determine whether there is value to taking a specific substance for health or disease prevention is vital, telling us what is helpful, what is harmful and what is not useful to take."
Millions of Americans take dietary supplements such as vitamins, minerals and herbs with the thought that they can help prevent or cure illnesses and ailments.
The Food and Drug Administration considers supplements foods, not drugs, so they don't need to be approved by the FDA before going on the market.
The SELECT study on vitamin E and the trace mineral selenium was based on previous research on other cancers that suggested the supplements might reduce the risk of prostate cancer.
In 1998, a study of 29,133 male smokers in Finland who took vitamin E to prevent lung cancer showed 32 percent fewer prostate cancers. In 1996, a study of 1,312 men and women with skin cancer who took selenium showed that men who took the supplement had 52 percent fewer prostate cancers than those who did not take it, according a National Cancer Institute news release.
Based on these and other earlier findings, men age 50 and older were recruited to participate in SELECT earlier this decade. The men were randomly chosen and grouped to take one of four combinations of supplements or placebos. One group took selenium and vitamin E; one took selenium and a vitamin E placebo; one took vitamin E and a selenium placebo; and the final group received placebos of both supplements.
It was a blinded study — neither the men nor their physicians knew who was taking supplements.
Now, five years after the trial phase of SELECT began, an initial, independent analysis of the study data determined that taking vitamin E and selenium together or alone didn't prevent prostate cancer.
The study actually showed very small increases in the number of cases of prostate cancer in men taking only vitamin E as well as diabetes in men taking only selenium, but researchers dismissed the increase as statistically insignificant.
Participants in the study are being told to stop taking their supplements; however, they will continue to have their health monitored.
Researchers intend to follow the participants for about three years to determine the long-term effects of having taken the supplements.
"As we continue to monitor the health of these 35,000 men, this information may help us understand why two nutrients that showed strong initial evidence to be able to prevent prostate cancer did not do so," said Eric Klein, a study co-chair for SELECT and a physician at the Cleveland Clinic, in the national news release.
The $114 million study was funded by the National Cancer Institute, with additional support from the National Center for Complementary and Alternative Medicine.
According to the study, vitamin E and selenium supplements do not aid in preventing prostate cancer, the most common cancer in American men other than skin cancers.
The study examined the effects of both supplements in more than 35,000 men nationally, including several hundred in Tucson. It was the largest trial ever on prostate-cancer prevention, according to officials at the Arizona Cancer Center. The study included the Southern Arizona VA Health Care System.
Called SELECT (the Selenium and Vitamin E Cancer Prevention Trial), the study was funded by the National Cancer Institute and coordinated through the Southwest Oncology Group.
"A large trial like SELECT is the only way to determine for certain the real value of supplements," said Frederick Ahmann, professor of medicine and director of the Hematology/Oncology Fellowship Program at the Arizona Cancer Center, in a news release.
"Using science to study and determine whether there is value to taking a specific substance for health or disease prevention is vital, telling us what is helpful, what is harmful and what is not useful to take."
Millions of Americans take dietary supplements such as vitamins, minerals and herbs with the thought that they can help prevent or cure illnesses and ailments.
The Food and Drug Administration considers supplements foods, not drugs, so they don't need to be approved by the FDA before going on the market.
The SELECT study on vitamin E and the trace mineral selenium was based on previous research on other cancers that suggested the supplements might reduce the risk of prostate cancer.
In 1998, a study of 29,133 male smokers in Finland who took vitamin E to prevent lung cancer showed 32 percent fewer prostate cancers. In 1996, a study of 1,312 men and women with skin cancer who took selenium showed that men who took the supplement had 52 percent fewer prostate cancers than those who did not take it, according a National Cancer Institute news release.
Based on these and other earlier findings, men age 50 and older were recruited to participate in SELECT earlier this decade. The men were randomly chosen and grouped to take one of four combinations of supplements or placebos. One group took selenium and vitamin E; one took selenium and a vitamin E placebo; one took vitamin E and a selenium placebo; and the final group received placebos of both supplements.
It was a blinded study — neither the men nor their physicians knew who was taking supplements.
Now, five years after the trial phase of SELECT began, an initial, independent analysis of the study data determined that taking vitamin E and selenium together or alone didn't prevent prostate cancer.
The study actually showed very small increases in the number of cases of prostate cancer in men taking only vitamin E as well as diabetes in men taking only selenium, but researchers dismissed the increase as statistically insignificant.
Participants in the study are being told to stop taking their supplements; however, they will continue to have their health monitored.
Researchers intend to follow the participants for about three years to determine the long-term effects of having taken the supplements.
"As we continue to monitor the health of these 35,000 men, this information may help us understand why two nutrients that showed strong initial evidence to be able to prevent prostate cancer did not do so," said Eric Klein, a study co-chair for SELECT and a physician at the Cleveland Clinic, in the national news release.
The $114 million study was funded by the National Cancer Institute, with additional support from the National Center for Complementary and Alternative Medicine.
UA Vice President Dr. William Crist to Lecture on Childhood Cancer
[Source: East Valley Living] - Conquering Childhood Cancer: A Paradigm for Translational Research; Lecture to be Held Wednesday January 14, 2009 at Virginia G. Piper Auditorium
PHOENIX - The advances in treatment of childhood cancer in the last generation have been nothing less than life-changing, says William M. Crist, MD, the new vice president for health affairs for The University of Arizona.
The University of Arizona College of Medicine-Phoenix in partnership with Arizona State University and the Flinn Foundation will host Dr. Crist, who will talk about his experience in a presentation titled, “Conquering Childhood Cancer: A Paradigm for Translational Research,” on Wednesday, Jan. 14, 2009, 5:30 p.m., in the Virginia G. Piper Auditorium, 550 E. Van Buren, in downtown Phoenix. The lecture is free and open to the public. Parking in the College of Medicine lot, with entrance on Seventh Street, also is free. (Dr. Crist also will speak in Tucson on Thursday, Jan. 15, 5 p.m., at DuVal Auditorium at University Medical Center, 1501 N. Campbell Ave.)
Dr. Crist is among the scientists credited with dramatically improving our understanding of childhood leukemias and their treatments. He spent much of his career from the 1970s through the 1990s in the field of pediatric hematology and oncology first at the University of Alabama, Birmingham, the University of Tennessee College of Medicine at Memphis, and St. Jude Children’s Hospital in Memphis before becoming chairman of pediatric and adolescent medicine at Mayo Medical Center in Rochester, Minn. Dr. Crist had been serving as dean of the School of Medicine at the University of Missouri before being named UA vice president for health affairs last summer. He began his new duties Oct. 31.
The Donald K. Buffmire Visiting Lectureship in Medicine, begun in 1997, continues the Flinn Foundation’s commitment to bringing to Arizona leading practitioners and thinkers in the medical field. The lectureship aims to offer to physicians, students and community members opportunities to hear from distinguished leaders in the field of medicine and medical education. In 2008, the annual lecture was expanded to a biannual basis and includes presentations in both Phoenix and Tucson.
The lectureship is named for late Donald K. Buffmire, MD, in recognition of his distinguished career as a medical practitioner in Arizona and his leadership role with the Flinn Foundation in supporting the College of Medicine. Dr. Buffmire, who died this year, served as a board director from 1965-99, including 15 years as president and chairman.
The Phoenix-based Flinn Foundation is a privately endowed organization that awards grants to nonprofit organizations in Arizona, primarily to improve the competitiveness of the state’s biomedical-research enterprise.
The UA College of Medicine is the only MD degree-granting college in Arizona. Beginning in 1967 with a class of 32 students on its Tucson campus, the college today encompasses full, four-year medical-education programs in Tucson and since 2007, in Phoenix.
PHOENIX - The advances in treatment of childhood cancer in the last generation have been nothing less than life-changing, says William M. Crist, MD, the new vice president for health affairs for The University of Arizona.
The University of Arizona College of Medicine-Phoenix in partnership with Arizona State University and the Flinn Foundation will host Dr. Crist, who will talk about his experience in a presentation titled, “Conquering Childhood Cancer: A Paradigm for Translational Research,” on Wednesday, Jan. 14, 2009, 5:30 p.m., in the Virginia G. Piper Auditorium, 550 E. Van Buren, in downtown Phoenix. The lecture is free and open to the public. Parking in the College of Medicine lot, with entrance on Seventh Street, also is free. (Dr. Crist also will speak in Tucson on Thursday, Jan. 15, 5 p.m., at DuVal Auditorium at University Medical Center, 1501 N. Campbell Ave.)
Dr. Crist is among the scientists credited with dramatically improving our understanding of childhood leukemias and their treatments. He spent much of his career from the 1970s through the 1990s in the field of pediatric hematology and oncology first at the University of Alabama, Birmingham, the University of Tennessee College of Medicine at Memphis, and St. Jude Children’s Hospital in Memphis before becoming chairman of pediatric and adolescent medicine at Mayo Medical Center in Rochester, Minn. Dr. Crist had been serving as dean of the School of Medicine at the University of Missouri before being named UA vice president for health affairs last summer. He began his new duties Oct. 31.
The Donald K. Buffmire Visiting Lectureship in Medicine, begun in 1997, continues the Flinn Foundation’s commitment to bringing to Arizona leading practitioners and thinkers in the medical field. The lectureship aims to offer to physicians, students and community members opportunities to hear from distinguished leaders in the field of medicine and medical education. In 2008, the annual lecture was expanded to a biannual basis and includes presentations in both Phoenix and Tucson.
The lectureship is named for late Donald K. Buffmire, MD, in recognition of his distinguished career as a medical practitioner in Arizona and his leadership role with the Flinn Foundation in supporting the College of Medicine. Dr. Buffmire, who died this year, served as a board director from 1965-99, including 15 years as president and chairman.
The Phoenix-based Flinn Foundation is a privately endowed organization that awards grants to nonprofit organizations in Arizona, primarily to improve the competitiveness of the state’s biomedical-research enterprise.
The UA College of Medicine is the only MD degree-granting college in Arizona. Beginning in 1967 with a class of 32 students on its Tucson campus, the college today encompasses full, four-year medical-education programs in Tucson and since 2007, in Phoenix.
Tissue samples collect, store and analyze
[Source: Luxemburger Wort (via Google Translate)] - (fh) - About 200 biobanks exist in Europe. The new Integrated biobank of Luxembourg (IBBL), which yesterday the press was presented, differs in two respects from other tissue banks: in addition to the collection and storage of biological samples (tissue, tumors, blood, urine, saliva ...) leads the IBBL also analyzes and stores this addition is a national project, which represents an independent unit. The samples or data of research made available. The IBBL is part of the biotechnology project in the field of molecular medicine, the 140 million euros over five years will cost and also the creation of a Center for Systems Biology and the implementation of a cancer research project covers. The goal of the biotech project is among other things, one day, drugs and therapies targeted to be able to treat patients more efficiently and reduce costs. Founded as the IBBL by CRPs Santé, Henri Tudor and Gabriel Lippmann and the University of Luxembourg. Has inspired a look at biobank model of the company "Translational Genomics Research Institute (TGen), by Dr. Jeffrey Trent, which, in Phoenix in the U.S. state of Arizona is located. The IBBL has the shape of a foundation. Your Board includes nine persons.Chairman of the Board is Dr. Jean-Claude Schmit, director of the CRP Santé. IBBL to include also a Board of Directors, an external ethics committee, a scientific project evaluation committee, a scientific council and a monitoring committee for the hospitals and the National Health Laboratory. Hospitals are important partners of the country and the wider region.
Strict conditions
The biobank itself has no research. It mainly manages data to interested researchers. If samples are made available, then only under very strict conditions. Each research project must be ethically tested and approved. The donations are voluntary, donors may withdraw their consent at any time.
If desired they can test for a special project available. The data of the donors are encrypted on several levels - the technology is called de-identification. It plays a so-called trusted third party, it still applies to define an important role. This alone can, if necessary, the data back together. This could for example be necessary if one for the health of the donor beneficial discovery is made.
In contact with the doctors
In Luxembourg, 200 people are annually diagnosed with lung cancer, but only a few surgery. These operations are carried out in two hospitals of the country. The IBBL is in contact with the concerned physicians, their patients about a possible use by the tissue biobank information. In addition, samples of healthy individuals to be collected. This is a call made via the press. Soon more information www.ibbl.lu available.
Strict conditions
The biobank itself has no research. It mainly manages data to interested researchers. If samples are made available, then only under very strict conditions. Each research project must be ethically tested and approved. The donations are voluntary, donors may withdraw their consent at any time.
If desired they can test for a special project available. The data of the donors are encrypted on several levels - the technology is called de-identification. It plays a so-called trusted third party, it still applies to define an important role. This alone can, if necessary, the data back together. This could for example be necessary if one for the health of the donor beneficial discovery is made.
In contact with the doctors
In Luxembourg, 200 people are annually diagnosed with lung cancer, but only a few surgery. These operations are carried out in two hospitals of the country. The IBBL is in contact with the concerned physicians, their patients about a possible use by the tissue biobank information. In addition, samples of healthy individuals to be collected. This is a call made via the press. Soon more information www.ibbl.lu available.
Arizona companies get $1.2 million cancer grant
[Source: Arizona Republic, Ken Alltucker] - Defense contractor Raytheon wants to parlay its knowledge of remote satellite systems into a new system capable of accurately and consistently detecting skin cancer.
Raytheon has teamed with the Arizona Cancer Center on a research project to build an automated imaging system that could create a standard way to detect cancerous skin lesions.
Researchers have spent about $1.3 million to develop the project over the past three years. Science Foundation Arizona has approved a $1.2 million grant to move the research forward.
Now, doing a whole-body scan for early detection of skin cancer is an inexact science. One method consists of doctors comparing multiple photographs of a patient's skin over time. So a diagnosis may vary, depending on a doctor's interpretation of the images. If a patient has dozens of moles, a harried doctor may miss a potentially dangerous skin lesion altogether.
"Being able to (diagnose) a lesion accurately, in a short period of time, is not an easy thing to do," said Dr. Clara Curiel, a dermatology professor at University of Arizona and a director at the Arizona Cancer Center.
Curiel and Karleen Seybold, a systems-engineering senior manager at Raytheon, have led a team of about 13 engineers and researchers who are working on a system that would automate the process.
Raytheon engineers are working to adapt remote-sensing algorithms that can lead to early skin-cancer detection. Researchers have a prototype of the imaging station that could be used with the Raytheon-developed algorithm to help doctors track skin cancer.
Researchers envision developing an imaging station similar to a metal cage with different bars that could hold cameras, which would snap images of a person's body and analyze the skin.
Raytheon has teamed with the Arizona Cancer Center on a research project to build an automated imaging system that could create a standard way to detect cancerous skin lesions.
Researchers have spent about $1.3 million to develop the project over the past three years. Science Foundation Arizona has approved a $1.2 million grant to move the research forward.
Now, doing a whole-body scan for early detection of skin cancer is an inexact science. One method consists of doctors comparing multiple photographs of a patient's skin over time. So a diagnosis may vary, depending on a doctor's interpretation of the images. If a patient has dozens of moles, a harried doctor may miss a potentially dangerous skin lesion altogether.
"Being able to (diagnose) a lesion accurately, in a short period of time, is not an easy thing to do," said Dr. Clara Curiel, a dermatology professor at University of Arizona and a director at the Arizona Cancer Center.
Curiel and Karleen Seybold, a systems-engineering senior manager at Raytheon, have led a team of about 13 engineers and researchers who are working on a system that would automate the process.
Raytheon engineers are working to adapt remote-sensing algorithms that can lead to early skin-cancer detection. Researchers have a prototype of the imaging station that could be used with the Raytheon-developed algorithm to help doctors track skin cancer.
Researchers envision developing an imaging station similar to a metal cage with different bars that could hold cameras, which would snap images of a person's body and analyze the skin.
Gut Instinct: Salmonella Bacteria's Molecular Tactics To Cause Illness
[Source: ScienceDaily] - Hundreds of trillions of bacteria make their home in the vertebrate gut. Though many of these microbes perform helpful duties for their host, others—the pathogens—are unwelcome visitors, causing disease.
Salmonella typhimurium is one such pathogenic bacterium. It has evolved sophisticated means of growth, replication, transport and survival within the forbidding environment of the body, where it is responsible for most cases of food-borne illness. Yixin Shi, a researcher at Arizona State University's Biodesign Institute, has taken a keen interest in the regulatory mechanisms that allow Salmonella bacteria to overcome their surroundings and continuously modify both their own and their host's responses in order to stay alive.
By cooperating with the Dr. Roy Curtiss' lab in the Biodesign Institute, Shi's research, which appears in the Proceedings of the National Academy of Sciences, (PNAS) unveils a key survival circuit, which activates a signaling cascade, switching on or off a suite of genes necessary to circumvent the body's multiple defense mechanisms.
A corrosive course
The bacteria are tenacious, surviving acidic pH conditions, digestive enzymes, bile salts, antimicrobial peptides, and other hazards as they pass through the stomach and intestine, and invade the mucosa of the small intestine. Once they make contact with the intestinal lumen, their goal is to secure a safe haven—within the cells of the intestinal epithelium.
To reach this sanctuary, Salmonella first invite themselves in by secreting specific protein factors derived from a region of DNA known as the Salmonella Pathogenicity Island 1 or SPI-1. These factors trick the body, inducing the reorganization of the host cell's cytoskeleton. Epithelial cells respond to the Salmonella secretions by surrounding the bacterial cell in a membrane-bound balloon—the Salmonella Containing Vacuole or SCV. Once the bacterium is taken up in the SCV by the epithelial cell, this secretion system is no longer needed and is switched off. At the same time, another system, SPI-2 is activated and will respond to the altered environment of the internalized Salmonella.
Starving the beast
As the Salmonella penetrates through the epithelial layer, it encounters a dense population of macrophages that normally act to engulf and digest pathogens and debris. Unlike other gut commensal microbes—E. coli for example—Salmonella is able to survive and replicate within SCV of these macrophages, which eventually transport it to organs including the liver and spleen. "The host cells isolate nutrients from bacteria," Shi explains. "They may deplete metal ions, nucleotides, and amino acids which are essential for bacterial life and growth. In this way, Salmonella are essentially starved to death."
But the Salmonella are prepared, and respond— first by sensing the new conditions, then synthesizing proteins allowing them to acquire nutrients from this new environment while switching on genes girding the bacteria against destructive host peptides.
A switch in time
As Shi explains, a regulatory system allowing Salmonella to monitor and respond to rapidly changing conditions is made up of two proteins: PhoP and PhoQ. The PhoP/PhoQ regulators act as a master control, switching off invasion proteins when they are no longer required while switching on a new set of protein factors necessary for intracellular survival. In a domino effect, part of this transition activates magnesium transporters, which act to reestablish metal ion levels in the depleted conditions of the vacuole.
But now a problem arises. Salmonella must maintain proper Mg2+ concentration in their cytoplasm, though PhoP, once turned on, acts to continually increase these levels. The single master switch PhoP/PhoQ is not sufficient to provide this level of control. Salmonella uses an RNA Mg2+ riboswitch to ensure downregulation of Mg2+ transporters without shutting down bacterial resistance to antimicrobial peptides. Likewise, instead of one regulatory switch, two are needed to properly mitigate conditions of resistance to the bacteriocidal peptides, and amino acid starvation. Enter SlyA.
Two to tango
SlyA is a regulatory protein which cleverly integrates itself into the PhoP/PhoQ regulatory system, allowing for multivariable control. Only when both the PhoP/PhoQ and SlyA regulatory systems are activated can the proper activation of genes for intracellular survival be switched on and delicately maintained.
The sequence of events appears as follows: after cellular invasion and formation of the vacuole, PhoP responds to antimicrobial peptides and/or low levels of Mg2+ within the vacuole by switching on, activating Mg2+ transporters and stimulating the production of SlyA. The PhoP/PhoQ system is sufficient to maintain proper Mg2+ levels, but it is SlyA's job to respond to nutrient starvation. Shi believes SlyA does this by sensing the presence of a particular chemical signal—ppGpp, (guanosine tetraphosphate), indicative of amino acid depletion. If SlyA detects this chemical, it will act in consort with the PhoP/PhoQ system. With both PhoP/PhoQ and SlyA switches thrown, all the necessary regulatory genes are brought into play, as conditions warrant.
Shi emphasizes that the cluster of genes responsible for this sequence of environmental adaptations to adversity in virulent bacteria like Salmonella are arranged in particular chromosomal regions, the so-called horizontally acquired loci, which are absent in helpful gut bacteria like E. coli.
Disabling either PhoP or SlyA renders Salmonella virtually impotent, its virulence severely attenuated. The bacteria lose their survivability within the macrophage environment, succumbing either to nutrient starvation or direct obliteration by host antimicrobial peptides.
Shi suggests that the specificity of SlyA's activity within Salmonella's regulatory universe may be good news for those hoping to target this system through vaccine development or other therapeutic intervention. Discovering competitive analogs of ppGpp, for instance, could provide an alternate approach, curtailing SlyA's function.
Shi is optimistic that a firmer grasp of such regulatory mechanisms of virulence as PhoP/PhoQ and SlyA will ultimately lead to life-saving applications. "I never think I'm doing basic science," Shi stresses. "I always think I'm working on the first steps of an application. "
Yixin Shi is an assistant professor of ASU's School of Life Sciences and researcher in the Biodesign Institute's Center for Infectious Diseases and Vaccinology.
Salmonella typhimurium is one such pathogenic bacterium. It has evolved sophisticated means of growth, replication, transport and survival within the forbidding environment of the body, where it is responsible for most cases of food-borne illness. Yixin Shi, a researcher at Arizona State University's Biodesign Institute, has taken a keen interest in the regulatory mechanisms that allow Salmonella bacteria to overcome their surroundings and continuously modify both their own and their host's responses in order to stay alive.
By cooperating with the Dr. Roy Curtiss' lab in the Biodesign Institute, Shi's research, which appears in the Proceedings of the National Academy of Sciences, (PNAS) unveils a key survival circuit, which activates a signaling cascade, switching on or off a suite of genes necessary to circumvent the body's multiple defense mechanisms.
A corrosive course
The bacteria are tenacious, surviving acidic pH conditions, digestive enzymes, bile salts, antimicrobial peptides, and other hazards as they pass through the stomach and intestine, and invade the mucosa of the small intestine. Once they make contact with the intestinal lumen, their goal is to secure a safe haven—within the cells of the intestinal epithelium.
To reach this sanctuary, Salmonella first invite themselves in by secreting specific protein factors derived from a region of DNA known as the Salmonella Pathogenicity Island 1 or SPI-1. These factors trick the body, inducing the reorganization of the host cell's cytoskeleton. Epithelial cells respond to the Salmonella secretions by surrounding the bacterial cell in a membrane-bound balloon—the Salmonella Containing Vacuole or SCV. Once the bacterium is taken up in the SCV by the epithelial cell, this secretion system is no longer needed and is switched off. At the same time, another system, SPI-2 is activated and will respond to the altered environment of the internalized Salmonella.
Starving the beast
As the Salmonella penetrates through the epithelial layer, it encounters a dense population of macrophages that normally act to engulf and digest pathogens and debris. Unlike other gut commensal microbes—E. coli for example—Salmonella is able to survive and replicate within SCV of these macrophages, which eventually transport it to organs including the liver and spleen. "The host cells isolate nutrients from bacteria," Shi explains. "They may deplete metal ions, nucleotides, and amino acids which are essential for bacterial life and growth. In this way, Salmonella are essentially starved to death."
But the Salmonella are prepared, and respond— first by sensing the new conditions, then synthesizing proteins allowing them to acquire nutrients from this new environment while switching on genes girding the bacteria against destructive host peptides.
A switch in time
As Shi explains, a regulatory system allowing Salmonella to monitor and respond to rapidly changing conditions is made up of two proteins: PhoP and PhoQ. The PhoP/PhoQ regulators act as a master control, switching off invasion proteins when they are no longer required while switching on a new set of protein factors necessary for intracellular survival. In a domino effect, part of this transition activates magnesium transporters, which act to reestablish metal ion levels in the depleted conditions of the vacuole.
But now a problem arises. Salmonella must maintain proper Mg2+ concentration in their cytoplasm, though PhoP, once turned on, acts to continually increase these levels. The single master switch PhoP/PhoQ is not sufficient to provide this level of control. Salmonella uses an RNA Mg2+ riboswitch to ensure downregulation of Mg2+ transporters without shutting down bacterial resistance to antimicrobial peptides. Likewise, instead of one regulatory switch, two are needed to properly mitigate conditions of resistance to the bacteriocidal peptides, and amino acid starvation. Enter SlyA.
Two to tango
SlyA is a regulatory protein which cleverly integrates itself into the PhoP/PhoQ regulatory system, allowing for multivariable control. Only when both the PhoP/PhoQ and SlyA regulatory systems are activated can the proper activation of genes for intracellular survival be switched on and delicately maintained.
The sequence of events appears as follows: after cellular invasion and formation of the vacuole, PhoP responds to antimicrobial peptides and/or low levels of Mg2+ within the vacuole by switching on, activating Mg2+ transporters and stimulating the production of SlyA. The PhoP/PhoQ system is sufficient to maintain proper Mg2+ levels, but it is SlyA's job to respond to nutrient starvation. Shi believes SlyA does this by sensing the presence of a particular chemical signal—ppGpp, (guanosine tetraphosphate), indicative of amino acid depletion. If SlyA detects this chemical, it will act in consort with the PhoP/PhoQ system. With both PhoP/PhoQ and SlyA switches thrown, all the necessary regulatory genes are brought into play, as conditions warrant.
Shi emphasizes that the cluster of genes responsible for this sequence of environmental adaptations to adversity in virulent bacteria like Salmonella are arranged in particular chromosomal regions, the so-called horizontally acquired loci, which are absent in helpful gut bacteria like E. coli.
Disabling either PhoP or SlyA renders Salmonella virtually impotent, its virulence severely attenuated. The bacteria lose their survivability within the macrophage environment, succumbing either to nutrient starvation or direct obliteration by host antimicrobial peptides.
Shi suggests that the specificity of SlyA's activity within Salmonella's regulatory universe may be good news for those hoping to target this system through vaccine development or other therapeutic intervention. Discovering competitive analogs of ppGpp, for instance, could provide an alternate approach, curtailing SlyA's function.
Shi is optimistic that a firmer grasp of such regulatory mechanisms of virulence as PhoP/PhoQ and SlyA will ultimately lead to life-saving applications. "I never think I'm doing basic science," Shi stresses. "I always think I'm working on the first steps of an application. "
Yixin Shi is an assistant professor of ASU's School of Life Sciences and researcher in the Biodesign Institute's Center for Infectious Diseases and Vaccinology.
Breast Cancer: Diet High In Vegetables, Fruit And Fiber May Cut Risk Of Cancer Recurrence In Women Without Hot Flashes
[Source: ScienceDaily ] - A secondary analysis of a large, multicenter clinical trial has shown that a diet loaded with fruits, vegetables and fiber and somewhat lower in fat compared to standard federal dietary recommendations cuts the risk of recurrence in a subgroup of early-stage breast cancer survivors – women who didn't have hot flashes – by approximately 31 percent. These patients typically have higher recurrence and lower survival rates than breast cancer patients who have hot flashes.
The study team, led by researchers at the Moores Cancer Center at the University of California, San Diego, along with six other sites, including the University of California, Davis, reported its results online December 15, 2008, in the Journal of Clinical Oncology.
The results come on the heels of a report last year on the findings of the original study, the Women's Healthy Eating and Living Trial (WHEL), which compared the effects of the two diets on cancer recurrence in more than 3,000 early-stage breast cancer survivors. That study showed no overall difference in recurrence among the two diet groups.
"Women with early stage breast cancer who have hot flashes have better survival and lower recurrence rates than women who don't have hot flashes," said Ellen B. Gold, Ph.D., professor and chair of the UC Davis Department of Public Health Sciences and first author of the study. "Our results suggest that a major change in diet may help overcome the difference in prognosis between women with and without hot flashes."
"Our interest in looking at this subgroup came because hot flashes are associated with lower circulating estrogen levels, while the absence of hot flashes is associated with higher estrogen levels. Reducing the effect of estrogen is a major treatment strategy in breast cancer," said the WHEL study principal investigator John P. Pierce, Ph.D., Sam M. Walton Professor for Cancer Prevention and director of Cancer Prevention and Control at the UC San Diego School of Medicine and the Moores UCSD Cancer Center. "It appears that a dietary pattern high in fruits, vegetables and fiber, which has been shown to reduce circulating estrogen levels, may only be important among women with circulating estrogen levels above a certain threshold."
About 30 percent of the original group of 3,088 breast cancer survivors did not report hot flashes at study entry. The women had been randomly assigned to one of the two diets between 1995 and 2000 and were followed until 2006. About one-half (447) of the "no hot flashes" group were randomized to the special, "intervention" high-vegetable fruit diet while the other half (453) was given the generally recommended diet of five servings of fruits and vegetables a day. The team found that those on the intervention diet had a significantly lower rate of a second breast cancer event (16.1 percent) compared to those eating the government-recommended five-a-day dietary pattern (23.6 percent).
The dietary effect was even larger (a 47 percent lower risk) in women who had been through menopause.
According to Pierce, another possible mechanism has been proposed recently for why this diet may have affected only 30 percent of the WHEL study population. Women with estrogen receptor-positive cancers usually receive hormone therapy (tamoxifen or aromatase inhibitors) aimed at combating the effect of circulating estrogen. However, more than 30 percent of these women appear to have a gene-drug interaction that prevents them from getting an effective dose of this therapy.
"This hypothesis says that if the endocrine therapy is working, no further reduction in estrogen levels would be needed," said Pierce. "If your genes are preventing you from getting a therapeutic dose, then following this rigorous dietary pattern may reduce estrogen levels enough to reduce risk." Because this is speculation, he said, the research team will be using biological samples collected throughout the study to further investigate the mechanisms behind the study diet's protective effects.
Other co-authors include: Cheryl Rock, Ph.D., Barbara Parker, M.D., Lisa Madlensky, Ph.D., Loki Natarajan, Ph.D., Linda Wasserman, M.D., Vicky Jones, M.D., Gail Laughlin, Ph.D., Nazmus Saquib M.D., Ph.D., Sheila Kealey MPH, Shirley Flatt, Jennifer Emond and Minya Pu, UCSD; Joanne Mortimer, M.D., City of Hope; Marcia Stefanek, Ph.D., Stanford University; Bette Caan, Dr.P.H, Kaiser Permanente, Oakland, Cynthia Thomson, Ph.D., University of Arizona, Njeri Karanja, Ph.D., Kaiser Permanente, Portland, OR; Richard Hajek, Ph.D., M.D. Anderson Cancer Center.
The study team, led by researchers at the Moores Cancer Center at the University of California, San Diego, along with six other sites, including the University of California, Davis, reported its results online December 15, 2008, in the Journal of Clinical Oncology.
The results come on the heels of a report last year on the findings of the original study, the Women's Healthy Eating and Living Trial (WHEL), which compared the effects of the two diets on cancer recurrence in more than 3,000 early-stage breast cancer survivors. That study showed no overall difference in recurrence among the two diet groups.
"Women with early stage breast cancer who have hot flashes have better survival and lower recurrence rates than women who don't have hot flashes," said Ellen B. Gold, Ph.D., professor and chair of the UC Davis Department of Public Health Sciences and first author of the study. "Our results suggest that a major change in diet may help overcome the difference in prognosis between women with and without hot flashes."
"Our interest in looking at this subgroup came because hot flashes are associated with lower circulating estrogen levels, while the absence of hot flashes is associated with higher estrogen levels. Reducing the effect of estrogen is a major treatment strategy in breast cancer," said the WHEL study principal investigator John P. Pierce, Ph.D., Sam M. Walton Professor for Cancer Prevention and director of Cancer Prevention and Control at the UC San Diego School of Medicine and the Moores UCSD Cancer Center. "It appears that a dietary pattern high in fruits, vegetables and fiber, which has been shown to reduce circulating estrogen levels, may only be important among women with circulating estrogen levels above a certain threshold."
About 30 percent of the original group of 3,088 breast cancer survivors did not report hot flashes at study entry. The women had been randomly assigned to one of the two diets between 1995 and 2000 and were followed until 2006. About one-half (447) of the "no hot flashes" group were randomized to the special, "intervention" high-vegetable fruit diet while the other half (453) was given the generally recommended diet of five servings of fruits and vegetables a day. The team found that those on the intervention diet had a significantly lower rate of a second breast cancer event (16.1 percent) compared to those eating the government-recommended five-a-day dietary pattern (23.6 percent).
The dietary effect was even larger (a 47 percent lower risk) in women who had been through menopause.
According to Pierce, another possible mechanism has been proposed recently for why this diet may have affected only 30 percent of the WHEL study population. Women with estrogen receptor-positive cancers usually receive hormone therapy (tamoxifen or aromatase inhibitors) aimed at combating the effect of circulating estrogen. However, more than 30 percent of these women appear to have a gene-drug interaction that prevents them from getting an effective dose of this therapy.
"This hypothesis says that if the endocrine therapy is working, no further reduction in estrogen levels would be needed," said Pierce. "If your genes are preventing you from getting a therapeutic dose, then following this rigorous dietary pattern may reduce estrogen levels enough to reduce risk." Because this is speculation, he said, the research team will be using biological samples collected throughout the study to further investigate the mechanisms behind the study diet's protective effects.
Other co-authors include: Cheryl Rock, Ph.D., Barbara Parker, M.D., Lisa Madlensky, Ph.D., Loki Natarajan, Ph.D., Linda Wasserman, M.D., Vicky Jones, M.D., Gail Laughlin, Ph.D., Nazmus Saquib M.D., Ph.D., Sheila Kealey MPH, Shirley Flatt, Jennifer Emond and Minya Pu, UCSD; Joanne Mortimer, M.D., City of Hope; Marcia Stefanek, Ph.D., Stanford University; Bette Caan, Dr.P.H, Kaiser Permanente, Oakland, Cynthia Thomson, Ph.D., University of Arizona, Njeri Karanja, Ph.D., Kaiser Permanente, Portland, OR; Richard Hajek, Ph.D., M.D. Anderson Cancer Center.
Just A Little Squeeze Lets Proteins Assess DNA
[Source: ScienceDaily] - To find its target, all a protein needs to do is give quick squeezes as it moves along the DNA strand, suggests new research from The University of Arizona in Tucson.
Scientists had thought DNA-binding proteins primarily used full-body hugs for accurate readings of the information coded in the DNA's sequence.
Even a protein known to use the hug method, called direct readout, can effectively pinpoint sites on DNA using indirect readout, found researcher Nancy C. Horton and her colleagues.
"It was a total surprise," said Horton, a UA associate professor of biochemistry and molecular biophysics. "No one had ever seen it before."
Doing the quick squeezes that scientists call indirect readout probably works faster than requiring full-body contact with all the DNA, the researchers suggest. Quick and accurate identification of key sites on DNA is important for the health of all kinds of cells, from bacteria to humans.
To detect the protein-DNA connection in such detail, Horton and her co-authors Elizabeth J. Little and Andrea C. Babic studied a DNA-binding protein that bacteria use to protect themselves from viral infections.
The finding has implications for the development of designer drugs.
"People have and are developing DNA-binding proteins to turn genes on and off," Horton said. Such designer proteins can be used to cut out the bad copy of a gene and help replace it with good copy.
"We found that indirect readout is important for finding the right sequence, and we now think indirect readout is also important for finding it quickly," she said.
The team published their paper, "Early Interrogation and Recognition of DNA Sequence by Indirect Readout," in the December issue of the journal Structure. First author Little and co-author Babic were postdoctoral research associates in Horton's laboratory when they did the research. The two are now senior scientists at Ventana Medical Systems, Inc. in Tucson, Ariz.
The National Institutes of Health funded the research.
Horton studies proteins that bind to DNA.
Seven years ago, she figured out the structure of a protein called HincII that snips up DNA. The protein is a type of enzyme called a restriction endonuclease and comes from Haemophilus influenzae bacteria.
Since that time, Horton has been trying to learn how HincII interrogates the DNA to find the right place to cut.
The protein protects bacteria by cutting up DNA from invading viruses. Without the protective protein, viral DNA would commandeer the bacterium's cellular machinery to produce viruses and ultimately kill the bacterial cell.
The HincII protein distinguishes between bacterial DNA and viral DNA by recognizing certain sequences on DNA. Such a defense requires speed to prevent the marauding virus from killing the cell and also accuracy so the protein doesn't accidentally hack up the bacterium's own DNA.
Horton knew from her previous work that the HincII protein used the direct readout method to find the particular sequence of DNA that corresponded to enemy DNA. The protein seemed to distort the DNA to read it.
Removing the direct readout contact between the protein and the DNA might show whether the DNA distortion or the contact itself was important, Horton said.
Therefore Little and Babic created a mutant protein that couldn't hug DNA closely and therefore couldn't use the direct readout method. Little described the mutant protein as missing the fingers the normal protein used to probe the DNA.
"If the finger was doing all the recognition, then the mutant should cut any DNA sequence," Horton said.
To see how the mutant interacted with DNA, the researchers crystallized the mutant protein-DNA complex in action.
Initially, Horton thought the assay had gone wrong and almost threw the results in the trash, she wrote in an e-mail.
The mutant protein had chosen the proper site on the DNA with 100 percent specificity, which was opposite from what she expected. In addition, the DNA was distorted, even though the mutant couldn't make the strong contact a normal protein would.
"I did a double-take. I was just taking a picture to have a record that it was non-specific," she said.
Understanding how endonucleases and other DNA binding-proteins recognize a particular DNA sequence provides insight into key cellular processes including the replication, transcription and repair of DNA.
Little said, "In every single one of your cells are proteins looking for the proper sequences in DNA in order to make the proteins you need to stay alive."
Horton added, "Understanding how these processes work helps in the understanding of diseases so that we could potentially cure the disease."
Scientists had thought DNA-binding proteins primarily used full-body hugs for accurate readings of the information coded in the DNA's sequence.
Even a protein known to use the hug method, called direct readout, can effectively pinpoint sites on DNA using indirect readout, found researcher Nancy C. Horton and her colleagues.
"It was a total surprise," said Horton, a UA associate professor of biochemistry and molecular biophysics. "No one had ever seen it before."
Doing the quick squeezes that scientists call indirect readout probably works faster than requiring full-body contact with all the DNA, the researchers suggest. Quick and accurate identification of key sites on DNA is important for the health of all kinds of cells, from bacteria to humans.
To detect the protein-DNA connection in such detail, Horton and her co-authors Elizabeth J. Little and Andrea C. Babic studied a DNA-binding protein that bacteria use to protect themselves from viral infections.
The finding has implications for the development of designer drugs.
"People have and are developing DNA-binding proteins to turn genes on and off," Horton said. Such designer proteins can be used to cut out the bad copy of a gene and help replace it with good copy.
"We found that indirect readout is important for finding the right sequence, and we now think indirect readout is also important for finding it quickly," she said.
The team published their paper, "Early Interrogation and Recognition of DNA Sequence by Indirect Readout," in the December issue of the journal Structure. First author Little and co-author Babic were postdoctoral research associates in Horton's laboratory when they did the research. The two are now senior scientists at Ventana Medical Systems, Inc. in Tucson, Ariz.
The National Institutes of Health funded the research.
Horton studies proteins that bind to DNA.
Seven years ago, she figured out the structure of a protein called HincII that snips up DNA. The protein is a type of enzyme called a restriction endonuclease and comes from Haemophilus influenzae bacteria.
Since that time, Horton has been trying to learn how HincII interrogates the DNA to find the right place to cut.
The protein protects bacteria by cutting up DNA from invading viruses. Without the protective protein, viral DNA would commandeer the bacterium's cellular machinery to produce viruses and ultimately kill the bacterial cell.
The HincII protein distinguishes between bacterial DNA and viral DNA by recognizing certain sequences on DNA. Such a defense requires speed to prevent the marauding virus from killing the cell and also accuracy so the protein doesn't accidentally hack up the bacterium's own DNA.
Horton knew from her previous work that the HincII protein used the direct readout method to find the particular sequence of DNA that corresponded to enemy DNA. The protein seemed to distort the DNA to read it.
Removing the direct readout contact between the protein and the DNA might show whether the DNA distortion or the contact itself was important, Horton said.
Therefore Little and Babic created a mutant protein that couldn't hug DNA closely and therefore couldn't use the direct readout method. Little described the mutant protein as missing the fingers the normal protein used to probe the DNA.
"If the finger was doing all the recognition, then the mutant should cut any DNA sequence," Horton said.
To see how the mutant interacted with DNA, the researchers crystallized the mutant protein-DNA complex in action.
Initially, Horton thought the assay had gone wrong and almost threw the results in the trash, she wrote in an e-mail.
The mutant protein had chosen the proper site on the DNA with 100 percent specificity, which was opposite from what she expected. In addition, the DNA was distorted, even though the mutant couldn't make the strong contact a normal protein would.
"I did a double-take. I was just taking a picture to have a record that it was non-specific," she said.
Understanding how endonucleases and other DNA binding-proteins recognize a particular DNA sequence provides insight into key cellular processes including the replication, transcription and repair of DNA.
Little said, "In every single one of your cells are proteins looking for the proper sequences in DNA in order to make the proteins you need to stay alive."
Horton added, "Understanding how these processes work helps in the understanding of diseases so that we could potentially cure the disease."
Male Circumcision May Decrease Risk Of HPV Infection And Cervical Cancer
[Source: ScienceDaily] - Two new studies suggest that male circumcision may assist in the prevention of human papillomavirus (HPV) infection, particularly infection with the high-risk subtypes associated with cervical, penile, and other cancers.
Both studies are published in the January 1 issue of The Journal of Infectious Diseases, now available online.
High-risk subtypes of HPV have been estimated to be present in 99.7 percent of cervical cancers worldwide. Evidence has shown that women with circumcised partners have a reduced risk for genital cancer. Two new studies sought to discover if HPV infection is more likely to occur in uncircumcised compared with circumcised men.
Bertran Auvert MD, PhD, and his team of researchers in France and colleagues from South Africa studied data from a trial conducted in Orange Farm, South Africa. Uncircumcised men aged 18-24 years were randomized into either an intervention group, to be circumcised, or a control group, to remain uncircumcised. During this study, urethral swab samples were collected and analyzed for presence of HPV among men followed up for 21 months. Information about sexual behavior was also collected.
Dr. Auvert and colleagues found that the percentage of high-risk HPV genotypes was lower in the circumcised group than in the control group. The most important implication, according to researchers, was that “reducing the frequency of HPV infection among men will reduce the risk of exposure in their female sexual partners.”
A second study by Carrie Nielson PhD, at the Oregon Health & Science University and colleagues at the University of Arizona, H. Lee Moffitt Cancer Center and Research Institute, and the Centers for Disease Control and Prevention tested more than four hundred men aged 18-40 years in two U.S. cities during 2002-2005. Sixteen percent of participants were uncircumcised. Researchers tested for HPV in skin swabs of the anogenital area and semen samples in participants with no HPV symptoms (such as warts or lesions).
Investigators found that circumcised men were about half as likely to have HPV as uncircumcised men, after adjustment for other differences in the two groups. These results demonstrated that lack of circumcision is associated with cervical cancer because of the increased risk of HPV infection. Nielson suggested that it may be useful to consider circumcising newborn boys in order to decrease the risk of HPV infection for them and their future partners. “Parents are not currently advised of this risk,” she said. “These studies contribute to the evidence that might help to inform that decision.”
In an accompanying editorial, Ronald H. Gray, MD, of Johns Hopkins University, said that the evidence was persuasive but not entirely consistent and that it may be premature to promote circumcision as a way to prevent HPV infection in men and to protect female sex partners from infection. He advised that policy decisions should await results from two ongoing trials of male circumcision. Alternatively, Gray noted that consistent evidence has suggested that male circumcision reduces the frequency of HIV infection in men.He also pointed out that because of the lack of conclusive data relating circumcision and prevention of HPV, Medicaid does not cover circumcision costs, which may account for a decline in neonatal circumcisions in the United States.
According to Dr. Nielson, the findings they reported present compelling arguments to promote male circumcision in developing countries where circumcision is not widely used and the HIV epidemic is severe. Additionally, she said, it is “the first clear demonstration of the indirect but substantial beneficial effect of male circumcision for women.” The authors of both studies and the editorialist agreed that more studies will be needed to confirm the efficacy of male circumcision in HPV prevention.
Both studies are published in the January 1 issue of The Journal of Infectious Diseases, now available online.
High-risk subtypes of HPV have been estimated to be present in 99.7 percent of cervical cancers worldwide. Evidence has shown that women with circumcised partners have a reduced risk for genital cancer. Two new studies sought to discover if HPV infection is more likely to occur in uncircumcised compared with circumcised men.
Bertran Auvert MD, PhD, and his team of researchers in France and colleagues from South Africa studied data from a trial conducted in Orange Farm, South Africa. Uncircumcised men aged 18-24 years were randomized into either an intervention group, to be circumcised, or a control group, to remain uncircumcised. During this study, urethral swab samples were collected and analyzed for presence of HPV among men followed up for 21 months. Information about sexual behavior was also collected.
Dr. Auvert and colleagues found that the percentage of high-risk HPV genotypes was lower in the circumcised group than in the control group. The most important implication, according to researchers, was that “reducing the frequency of HPV infection among men will reduce the risk of exposure in their female sexual partners.”
A second study by Carrie Nielson PhD, at the Oregon Health & Science University and colleagues at the University of Arizona, H. Lee Moffitt Cancer Center and Research Institute, and the Centers for Disease Control and Prevention tested more than four hundred men aged 18-40 years in two U.S. cities during 2002-2005. Sixteen percent of participants were uncircumcised. Researchers tested for HPV in skin swabs of the anogenital area and semen samples in participants with no HPV symptoms (such as warts or lesions).
Investigators found that circumcised men were about half as likely to have HPV as uncircumcised men, after adjustment for other differences in the two groups. These results demonstrated that lack of circumcision is associated with cervical cancer because of the increased risk of HPV infection. Nielson suggested that it may be useful to consider circumcising newborn boys in order to decrease the risk of HPV infection for them and their future partners. “Parents are not currently advised of this risk,” she said. “These studies contribute to the evidence that might help to inform that decision.”
In an accompanying editorial, Ronald H. Gray, MD, of Johns Hopkins University, said that the evidence was persuasive but not entirely consistent and that it may be premature to promote circumcision as a way to prevent HPV infection in men and to protect female sex partners from infection. He advised that policy decisions should await results from two ongoing trials of male circumcision. Alternatively, Gray noted that consistent evidence has suggested that male circumcision reduces the frequency of HIV infection in men.He also pointed out that because of the lack of conclusive data relating circumcision and prevention of HPV, Medicaid does not cover circumcision costs, which may account for a decline in neonatal circumcisions in the United States.
According to Dr. Nielson, the findings they reported present compelling arguments to promote male circumcision in developing countries where circumcision is not widely used and the HIV epidemic is severe. Additionally, she said, it is “the first clear demonstration of the indirect but substantial beneficial effect of male circumcision for women.” The authors of both studies and the editorialist agreed that more studies will be needed to confirm the efficacy of male circumcision in HPV prevention.
Tuesday, December 16, 2008
Medipacs named best of show at Invest Southwest
[Source: Phoenix Business Journal,Patrick O'Grady ] - Medipacs, a maker of infusion pumps for the medical industry, was named the top presenter at the annual Invest Southwest conference Thursday in Scottsdale.
The Tucson company received a $200,000 prize from SCF Arizona for the presentation and idea judged to be the best of the year’s crop — just a drop in the bucket toward Medipacs’ quest to land $8 million to $10 million.
The conference brought together a dozen companies from throughout the Western U.S. — and for the first time, a company from Mexico. Unima Bioseguridad Integra presented its method for using natural methods to prevent food-borne illnesses. The company already has another technology, Custovac, being distributed by German pharmaceutical company Boehringer Ingelheim for use in animal vaccinations.
The conference had more attendees this year than last, a feat praised by organizers given the economic climate. Still, it may be a few weeks or months before this year’s attendees find out whether they will garner funding.
Other presenters at the event:
• AmpliMed Corp of Tucson brought in its phased cancer drug approach. The company has gone through three funding rounds and is working on its fourth as it moves to a trial for the drug.
• CaptiveMotion LLC of Tempe brought its computer face modeling technology. The startup by former video-game developer Adam Kraver allows game and film companies an easier way to convert images of the human face for digital uses.
• CellTrust Corp. displayed its technology to encrypt and store secure text and voice messages. The Scottsdale-based company sees a large market for the technology, particularly in medical fields where new federal laws require patient data be kept confidential.
• Consolidated Energy Systems LLC of Salt Lake City brought its technology for taking petroleum-based fuels that ordinarily could not be used and converting them to run large diesel electrical generating plants. To keep the project carbon-neutral, the plan would be to use the carbon dioxide in underground oil recovery.
• Eco Pool Technologies Inc. of Phoenix has begun production of a solar pool cleaner on a limited basis. The company also is developing a new version that would be able to work 24 hours a day, and other products that could lower electric costs for pool owners.
• Grip Audio LLC of Glendale presented a way to use computer software and local-area networks to replicate the cabling necessary for live music and studio productions. The company is looking at the professional audio market and has begun testing with several businesses and groups.
• Targeting the home video market, iMemories LLC of Scottsdale has developed a way to transfer VHS tapes to digital format and gives users the option of storing them online.
• MedTrust Online LLC, a spinoff of the Translational Genomics Research Institute, is an online resource for oncologists looking for up-to-date information in the fight against cancer. The database will provide physicians with data to help them better and more accurately treat their patients.
• NanoMR of Albuquerque, N.M., offered a patented medical diagnostic tool that could examine blood cultures in minutes, targeting detection of blood-borne bacteria.
• Protein Genomics Inc. of Sedona made its pitch for Tropoelastin, a device that can help in healing and preventing scarring.
The Tucson company received a $200,000 prize from SCF Arizona for the presentation and idea judged to be the best of the year’s crop — just a drop in the bucket toward Medipacs’ quest to land $8 million to $10 million.
The conference brought together a dozen companies from throughout the Western U.S. — and for the first time, a company from Mexico. Unima Bioseguridad Integra presented its method for using natural methods to prevent food-borne illnesses. The company already has another technology, Custovac, being distributed by German pharmaceutical company Boehringer Ingelheim for use in animal vaccinations.
The conference had more attendees this year than last, a feat praised by organizers given the economic climate. Still, it may be a few weeks or months before this year’s attendees find out whether they will garner funding.
Other presenters at the event:
• AmpliMed Corp of Tucson brought in its phased cancer drug approach. The company has gone through three funding rounds and is working on its fourth as it moves to a trial for the drug.
• CaptiveMotion LLC of Tempe brought its computer face modeling technology. The startup by former video-game developer Adam Kraver allows game and film companies an easier way to convert images of the human face for digital uses.
• CellTrust Corp. displayed its technology to encrypt and store secure text and voice messages. The Scottsdale-based company sees a large market for the technology, particularly in medical fields where new federal laws require patient data be kept confidential.
• Consolidated Energy Systems LLC of Salt Lake City brought its technology for taking petroleum-based fuels that ordinarily could not be used and converting them to run large diesel electrical generating plants. To keep the project carbon-neutral, the plan would be to use the carbon dioxide in underground oil recovery.
• Eco Pool Technologies Inc. of Phoenix has begun production of a solar pool cleaner on a limited basis. The company also is developing a new version that would be able to work 24 hours a day, and other products that could lower electric costs for pool owners.
• Grip Audio LLC of Glendale presented a way to use computer software and local-area networks to replicate the cabling necessary for live music and studio productions. The company is looking at the professional audio market and has begun testing with several businesses and groups.
• Targeting the home video market, iMemories LLC of Scottsdale has developed a way to transfer VHS tapes to digital format and gives users the option of storing them online.
• MedTrust Online LLC, a spinoff of the Translational Genomics Research Institute, is an online resource for oncologists looking for up-to-date information in the fight against cancer. The database will provide physicians with data to help them better and more accurately treat their patients.
• NanoMR of Albuquerque, N.M., offered a patented medical diagnostic tool that could examine blood cultures in minutes, targeting detection of blood-borne bacteria.
• Protein Genomics Inc. of Sedona made its pitch for Tropoelastin, a device that can help in healing and preventing scarring.
Monday, December 15, 2008
NHLBI Opens Resource for Genetic and Clinical Asthma Data
[Source: GenomeWeb News, a GenomeWeb staff reporter] — The National Heart, Lung, and Blood Institute has expanded its genetic and clinical data collection to include information collected from three asthma research networks, the National Institutes of Health said today.
The new project is part of the NHLBI’s SNP Health Association Resource (SHARe), a web-based dataset that provides researchers with free access to data from multiple, large population-based studies such as the Framingham Heart Study.
The new asthma component, called the SHARe-Asthma Resource Project (SHARP), includes data on 2,332 people with asthma and 805 families whose DNA was tested for 1 million genetic variations. SHARP also includes clinical data about lung function, allergy status, and respiratory symptoms.
The clinical data used in SHARP is being provided by the Childhood Asthma Management Program, the Childhood Asthma Research and Education Network, and the Asthma Clinical Research Network, all of which are funded by NHLBI.
The project will enable scientists to link participants’ genetic variations to their lab test results, making it possible to find out more about genetic influence on asthma and other airway diseases.
“Expanding the SHARe program to include asthma through the SHARP initiative will greatly expand our understanding of lung disease biology using genetic and genomic technologies,” NHLBI Director Elizabeth Nabel said in a statement.
SHARP data is available through the database of Genotypes and Phenotypes, or dbGaP, hosted by the National Center for Biotechnology Information.
Affymetrix developed SNP genotyping data for the asthma program under a contract with NHLBI.
More information about the new asthma program is available at the NIH’s website.
The new project is part of the NHLBI’s SNP Health Association Resource (SHARe), a web-based dataset that provides researchers with free access to data from multiple, large population-based studies such as the Framingham Heart Study.
The new asthma component, called the SHARe-Asthma Resource Project (SHARP), includes data on 2,332 people with asthma and 805 families whose DNA was tested for 1 million genetic variations. SHARP also includes clinical data about lung function, allergy status, and respiratory symptoms.
The clinical data used in SHARP is being provided by the Childhood Asthma Management Program, the Childhood Asthma Research and Education Network, and the Asthma Clinical Research Network, all of which are funded by NHLBI.
The project will enable scientists to link participants’ genetic variations to their lab test results, making it possible to find out more about genetic influence on asthma and other airway diseases.
“Expanding the SHARe program to include asthma through the SHARP initiative will greatly expand our understanding of lung disease biology using genetic and genomic technologies,” NHLBI Director Elizabeth Nabel said in a statement.
SHARP data is available through the database of Genotypes and Phenotypes, or dbGaP, hosted by the National Center for Biotechnology Information.
Affymetrix developed SNP genotyping data for the asthma program under a contract with NHLBI.
More information about the new asthma program is available at the NIH’s website.
DFMO May Affect Barrett's Esophagus
[Source: ScienceDaily] - "While there was a suggestion that DFMO may influence the extent of Barrett's dysplasia, this finding is very preliminary and further study of this agent in a larger number of patients is needed," said Frank A. Sinicrope, M.D., professor of medicine and oncology at the Mayo Clinic, Rochester, MN.
Sinicrope presented his findings at the American Association for Cancer Research's Seventh Annual International Conference on Frontiers in Cancer Prevention Research.
The single-arm study included 10 patients with Barrett's esophagus and low-grade dysplasia. The patients received 0.5 g/m2/d of DFMO for six months. Using an endoscope, the researchers examined esophageal biopsies at enrollment and at three, six and 12 months (where available). A gastrointestinal pathologist who was blinded to the clinical/biomarker data graded the dysplasia.
Sinicrope conducted this study while at The University of Texas M. D. Anderson Cancer Center. He collaborated with colleagues at the National Cancer Institute, and the Arizona Cancer Center, Tucson.
After six months of DFMO treatment, one patient's dysplasia regressed, one patient's progressed, and eight patients had stable disease. At six months, two patients in the stable group who started with extensive low-grade abnormal cells had only limited or focal dysplasia based on four or more biopsies. These improvements remained at 12 months.
DFMO lowered the level of the polyamine putrescine, a target of the drug and a possible cancer risk marker. The agent works by inhibiting an enzyme in polyamine synthesis called ornithine decarboxylase (ODC). "ODC activity in Barrett's mucosa has been shown to be significantly higher in Barrett's than in normal adjacent mucosa from the same patients," Sinicrope said.
"Since DFMO inhibits polyamine synthesis, the fact that putrescine levels were decreased at six months and later returned to baseline after being off the drug for six months suggests that the drug is affecting its target."
Interestingly, DFMO also reduced expression of Kruppel-like factor 5 (KLF5) gene, an important marker of abnormal cell proliferation in the esophagus that may represent a novel drug target.
"The results are encouraging because they identify KLF5 as a potential target of DFMO, which suggests a potential mechanism contributing to the chemopreventive effects of DFMO," Sinicrope said. "KLF5 has been shown to regulate proliferation, apoptosis and invasion in esophageal cancer cells."
Generally, DFMO was well tolerated. One patient had hearing loss and balance-related problems related to treatment.
"DFMO warrants further evaluation as a chemopreventive agent in patients with Barrett's esophagus and mucosal dysplasia," Sinicrope said. Currently, the Mayo Clinic researcher and his colleagues are planning a placebo-controlled chemoprevention trial in this patient population.
Sinicrope presented his findings at the American Association for Cancer Research's Seventh Annual International Conference on Frontiers in Cancer Prevention Research.
The single-arm study included 10 patients with Barrett's esophagus and low-grade dysplasia. The patients received 0.5 g/m2/d of DFMO for six months. Using an endoscope, the researchers examined esophageal biopsies at enrollment and at three, six and 12 months (where available). A gastrointestinal pathologist who was blinded to the clinical/biomarker data graded the dysplasia.
Sinicrope conducted this study while at The University of Texas M. D. Anderson Cancer Center. He collaborated with colleagues at the National Cancer Institute, and the Arizona Cancer Center, Tucson.
After six months of DFMO treatment, one patient's dysplasia regressed, one patient's progressed, and eight patients had stable disease. At six months, two patients in the stable group who started with extensive low-grade abnormal cells had only limited or focal dysplasia based on four or more biopsies. These improvements remained at 12 months.
DFMO lowered the level of the polyamine putrescine, a target of the drug and a possible cancer risk marker. The agent works by inhibiting an enzyme in polyamine synthesis called ornithine decarboxylase (ODC). "ODC activity in Barrett's mucosa has been shown to be significantly higher in Barrett's than in normal adjacent mucosa from the same patients," Sinicrope said.
"Since DFMO inhibits polyamine synthesis, the fact that putrescine levels were decreased at six months and later returned to baseline after being off the drug for six months suggests that the drug is affecting its target."
Interestingly, DFMO also reduced expression of Kruppel-like factor 5 (KLF5) gene, an important marker of abnormal cell proliferation in the esophagus that may represent a novel drug target.
"The results are encouraging because they identify KLF5 as a potential target of DFMO, which suggests a potential mechanism contributing to the chemopreventive effects of DFMO," Sinicrope said. "KLF5 has been shown to regulate proliferation, apoptosis and invasion in esophageal cancer cells."
Generally, DFMO was well tolerated. One patient had hearing loss and balance-related problems related to treatment.
"DFMO warrants further evaluation as a chemopreventive agent in patients with Barrett's esophagus and mucosal dysplasia," Sinicrope said. Currently, the Mayo Clinic researcher and his colleagues are planning a placebo-controlled chemoprevention trial in this patient population.
Friday, December 12, 2008
The Medium Is The Message: Manipulating Salmonella In Spaceflight Curtails Infectiousness
[Source: ScienceDaily] - Infectious pathogens like Salmonella typhimurium employ a startling array of techniques to skillfully outwit the body's defense mechanisms and produce illness. Through their expression of genes—the fundamental building blocks of cellular physiology—such microbes ingeniously adapt to varied environments, modifying their disease-causing potential or virulence.
Although the study of a broad range of microbial virulence factors is now well advanced, many pieces of the puzzle are still missing. Cheryl Nickerson, a researcher at Arizona State University's Biodesign Institute, has explored the novel environment of space to investigate the cellular and molecular machinery of virulence. There, the space shuttle crew grow the bacteria in triple-enclosed containers under conditions of minimized gravity (or microgravity). Nickerson's spaceflight experiments have shown that Salmonella gene expression and virulence are profoundly altered by microgravity, with the pathogenic cells undergoing a significant increase in their infectious disease potential.
Nickerson's latest findings, published in the journal PLoS ONE, are derived from experiments aboard NASA space shuttle mission STS-123, launched in March, 2008. This research validated results and broadened the scope of spaceflight experiments from STS-115, conducted two years earlier.
In addition to confirming the effects of microgravity observed in the STS-115 experiments (known as MICROBE), the new study homed in on the importance of the microbial growth medium to gene expression and virulence during spaceflight. "Pathogenic cells are smart," Nickerson stresses, pointing to their remarkable ability to fine-tune virulence factors in response to subtle environmental cues.
S. typhimurium, Nickerson's pathogen of choice, is a rod-shaped, motile bacterium and occasional unwelcome visitor to the human gastrointestinal tract, where it is a leading cause of food poisoning and related illnesses.
In both spaceflights, bacteria cultured in a nutrient-rich medium known as Lennox Broth (LB) consistently displayed a heightened virulence and exhibited differential expression of 167 distinct genes. These results were largely consistent with previous earthbound experiments in the laboratory, in which microgravitational conditions were simulated using a rotating wall vessel bioreactor—a device designed by NASA engineers to replicate elements of spaceflight.
Nickerson was able to examine the activity of genes in fine-grained detail through a technique known as microarray analysis, which allowed for a complete profile of gene expression across the entire 4.8 million DNA base pairs that make up the circular Salmonella chromosome. The 167 changes in gene levels produce a tremendous diversity of protein products, pointing to a global transformation in response to microgravity.
Interestingly, many of the 167 differentially expressed genes observed in the space-traveling microbes coded for an assortment of ionic response pathways. To Nickerson, these compelling results now suggested a possible means of limiting or eliminating the enhanced virulence imparted by spaceflight, through manipulation of the ionic content of the bacterium's surrounding environment.
In both the STS-115 and STS-123 missions, Nickerson compared the spaceflight response of Salmonella grown in Lennox Broth to the same bacteria grown in a minimal medium—one requiring the cells to synthesize most of their metabolic needs from scratch. This alternate growth medium, dubbed M9, contained high concentrations of five critical ions. The effects of this medium were dramatic, with the M9 cultures exhibiting a decrease in virulence in response to microgravity, despite exhibiting altered expression of many of the same genes and gene families that were observed in the LB cultures, where virulence under microgravity was intensified.
To test the hypothesis that ionic concentrations present in the M9 medium played a role in virulence reduction, a hybridized culture media known as LB-M9 was prepared for the March 2008 mission, consisting of the LB formula supplemented with five ions occurring in the M9 medium, but which were found to be at lower concentrations in LB. Bacteria cultured with LB-M9 again displayed a decreased virulence in response to microgravity. Subsequent bioreactor studies conducted by Nickerson's team on earth have hinted that phosphate ions may be a principle component of the observed virulence reduction.
One of Nickerson's most intriguing findings involves a specific RNA-binding protein known as Hfq, which appears to regulate central aspects of S. typhimurium's response to the spaceflight environment, acting as a "global molecular master switch." Hfq is known to regulate one third of the 167 differentially expressed genes in the spaceflight LB cultures. Interestingly, a large number of Hfq-regulated genes were also found to be differentially expressed in the M9 flight samples. In addition to Hfq's known properties as a virulence factor, the protein also acts to regulate ion response pathways,and has been associated with phosphate regulation. Moreover, Hfq appears to be an evolutionarily conserved regulatory factor, and may serve to globally modify bacterial responses to microgravity, regardless of the phenotypic outcome—a decrease in virulence for M9 cultures grown in microgravity environments and an increase for bacteria steeped in the LB medium.
But what was causing Salmonella to undergo such a dramatic transformation under conditions of microgravity? At least part of the answer, Nickerson believes, is related to the mechanical forces exerted upon the bacterial cell's membrane by the growth conditions—a property known as fluid shear. Specifically, the microgravity conditions aboard the space shuttle produce a condition of reduced fluid shear, an effect that appears to trigger an intensification of virulence in Salmonella grown in LB medium. As Nickerson points out, "No one had thought to look at a mechanical force like fluid shear on the disease-causing properties of a microorganism."
If a rolling stone gathers no moss, a bacterium like S. typhimurium appears to gather virulence when its movement is slowed down and fluid shear across its surface is minimized. Nickerson speculates that Salmonella encounters just such conditions not only during spaceflight but also in vivo in an infected individual when the bacterium makes contact with an intestinal host cell and becomes ensnared in the fingerlike projections known as microvilli.
Thus, space travel may trick the microbes into behaving as though they were in an environment hospitable to cell infection, thereby switching on an increased virulence response, given appropriate environmental preconditions. "They're responding to an environmental signal that they're used to seeing right here on earth, during the natural course of the infectious disease process," Nickerson states, emphasizing that this response is masked in traditional microbial studies performed using lab cell cultures, which fail to replicate the low fluid shear conditions found in vivo, particularly in the gastrointestinal tract—Salmonella's favored site of infection.
One result of spaceflight not replicated in the earthly bioreactor simulations was the formation of what appear to be biofilms—conglomerations of bacterial cells associated with infectious virulence. Nickerson emphasizes the potential importance, should such findings be confirmed. Up to 70 percent of bacterial infections in humans may be associated with the formation of such biofilms, which seem to arm bacterial pathogens with formidable resistance to the host's immune system as well as to antibiotics.
How do the disparate variables—extracellular phosphate concentration, mechanical forces like fluid shear and genetic regulation of pathogenic virulence—combine and interact during the infection process? While the current research provides tantalizing hints, a full understanding of the complex interplay of forces and the in vivo mechanisms of Salmonella pathogenesis await further research.
Fortunately, new opportunities for study are opening up, which may illuminate these issues. NASA is one of the primary partners in the construction and operation of the International Space Station (ISS), a semi-permanent research platform allowing for further investigations into microbial responses to low fluid shear environments. Because cells cultured in microgravity exhibit biomedically relevant phenotypes that can not be observed using traditional experimental approaches, Nickerson believes the therapeutic benefits of such research will extend beyond infectious pathogens like S. typhimurium, eventually inspiring new clinical approaches to cancer, aging, bone and muscle wasting diseases, among other earthly afflictions.
"We can use the innovative research platform of the ISS to contribute to these new translational advances for the development of new strategies to globally advance human health."
Although the study of a broad range of microbial virulence factors is now well advanced, many pieces of the puzzle are still missing. Cheryl Nickerson, a researcher at Arizona State University's Biodesign Institute, has explored the novel environment of space to investigate the cellular and molecular machinery of virulence. There, the space shuttle crew grow the bacteria in triple-enclosed containers under conditions of minimized gravity (or microgravity). Nickerson's spaceflight experiments have shown that Salmonella gene expression and virulence are profoundly altered by microgravity, with the pathogenic cells undergoing a significant increase in their infectious disease potential.
Nickerson's latest findings, published in the journal PLoS ONE, are derived from experiments aboard NASA space shuttle mission STS-123, launched in March, 2008. This research validated results and broadened the scope of spaceflight experiments from STS-115, conducted two years earlier.
In addition to confirming the effects of microgravity observed in the STS-115 experiments (known as MICROBE), the new study homed in on the importance of the microbial growth medium to gene expression and virulence during spaceflight. "Pathogenic cells are smart," Nickerson stresses, pointing to their remarkable ability to fine-tune virulence factors in response to subtle environmental cues.
S. typhimurium, Nickerson's pathogen of choice, is a rod-shaped, motile bacterium and occasional unwelcome visitor to the human gastrointestinal tract, where it is a leading cause of food poisoning and related illnesses.
In both spaceflights, bacteria cultured in a nutrient-rich medium known as Lennox Broth (LB) consistently displayed a heightened virulence and exhibited differential expression of 167 distinct genes. These results were largely consistent with previous earthbound experiments in the laboratory, in which microgravitational conditions were simulated using a rotating wall vessel bioreactor—a device designed by NASA engineers to replicate elements of spaceflight.
Nickerson was able to examine the activity of genes in fine-grained detail through a technique known as microarray analysis, which allowed for a complete profile of gene expression across the entire 4.8 million DNA base pairs that make up the circular Salmonella chromosome. The 167 changes in gene levels produce a tremendous diversity of protein products, pointing to a global transformation in response to microgravity.
Interestingly, many of the 167 differentially expressed genes observed in the space-traveling microbes coded for an assortment of ionic response pathways. To Nickerson, these compelling results now suggested a possible means of limiting or eliminating the enhanced virulence imparted by spaceflight, through manipulation of the ionic content of the bacterium's surrounding environment.
In both the STS-115 and STS-123 missions, Nickerson compared the spaceflight response of Salmonella grown in Lennox Broth to the same bacteria grown in a minimal medium—one requiring the cells to synthesize most of their metabolic needs from scratch. This alternate growth medium, dubbed M9, contained high concentrations of five critical ions. The effects of this medium were dramatic, with the M9 cultures exhibiting a decrease in virulence in response to microgravity, despite exhibiting altered expression of many of the same genes and gene families that were observed in the LB cultures, where virulence under microgravity was intensified.
To test the hypothesis that ionic concentrations present in the M9 medium played a role in virulence reduction, a hybridized culture media known as LB-M9 was prepared for the March 2008 mission, consisting of the LB formula supplemented with five ions occurring in the M9 medium, but which were found to be at lower concentrations in LB. Bacteria cultured with LB-M9 again displayed a decreased virulence in response to microgravity. Subsequent bioreactor studies conducted by Nickerson's team on earth have hinted that phosphate ions may be a principle component of the observed virulence reduction.
One of Nickerson's most intriguing findings involves a specific RNA-binding protein known as Hfq, which appears to regulate central aspects of S. typhimurium's response to the spaceflight environment, acting as a "global molecular master switch." Hfq is known to regulate one third of the 167 differentially expressed genes in the spaceflight LB cultures. Interestingly, a large number of Hfq-regulated genes were also found to be differentially expressed in the M9 flight samples. In addition to Hfq's known properties as a virulence factor, the protein also acts to regulate ion response pathways,and has been associated with phosphate regulation. Moreover, Hfq appears to be an evolutionarily conserved regulatory factor, and may serve to globally modify bacterial responses to microgravity, regardless of the phenotypic outcome—a decrease in virulence for M9 cultures grown in microgravity environments and an increase for bacteria steeped in the LB medium.
But what was causing Salmonella to undergo such a dramatic transformation under conditions of microgravity? At least part of the answer, Nickerson believes, is related to the mechanical forces exerted upon the bacterial cell's membrane by the growth conditions—a property known as fluid shear. Specifically, the microgravity conditions aboard the space shuttle produce a condition of reduced fluid shear, an effect that appears to trigger an intensification of virulence in Salmonella grown in LB medium. As Nickerson points out, "No one had thought to look at a mechanical force like fluid shear on the disease-causing properties of a microorganism."
If a rolling stone gathers no moss, a bacterium like S. typhimurium appears to gather virulence when its movement is slowed down and fluid shear across its surface is minimized. Nickerson speculates that Salmonella encounters just such conditions not only during spaceflight but also in vivo in an infected individual when the bacterium makes contact with an intestinal host cell and becomes ensnared in the fingerlike projections known as microvilli.
Thus, space travel may trick the microbes into behaving as though they were in an environment hospitable to cell infection, thereby switching on an increased virulence response, given appropriate environmental preconditions. "They're responding to an environmental signal that they're used to seeing right here on earth, during the natural course of the infectious disease process," Nickerson states, emphasizing that this response is masked in traditional microbial studies performed using lab cell cultures, which fail to replicate the low fluid shear conditions found in vivo, particularly in the gastrointestinal tract—Salmonella's favored site of infection.
One result of spaceflight not replicated in the earthly bioreactor simulations was the formation of what appear to be biofilms—conglomerations of bacterial cells associated with infectious virulence. Nickerson emphasizes the potential importance, should such findings be confirmed. Up to 70 percent of bacterial infections in humans may be associated with the formation of such biofilms, which seem to arm bacterial pathogens with formidable resistance to the host's immune system as well as to antibiotics.
How do the disparate variables—extracellular phosphate concentration, mechanical forces like fluid shear and genetic regulation of pathogenic virulence—combine and interact during the infection process? While the current research provides tantalizing hints, a full understanding of the complex interplay of forces and the in vivo mechanisms of Salmonella pathogenesis await further research.
Fortunately, new opportunities for study are opening up, which may illuminate these issues. NASA is one of the primary partners in the construction and operation of the International Space Station (ISS), a semi-permanent research platform allowing for further investigations into microbial responses to low fluid shear environments. Because cells cultured in microgravity exhibit biomedically relevant phenotypes that can not be observed using traditional experimental approaches, Nickerson believes the therapeutic benefits of such research will extend beyond infectious pathogens like S. typhimurium, eventually inspiring new clinical approaches to cancer, aging, bone and muscle wasting diseases, among other earthly afflictions.
"We can use the innovative research platform of the ISS to contribute to these new translational advances for the development of new strategies to globally advance human health."
Thursday, December 11, 2008
ASU study aims to fight symptoms of Parkinson's
[Source: Scott Huscher, ASUWebDevil] - Although many wouldn’t think ski poles could fight the symptoms of Parkinson’s disease (PD), a new Arizona State University study is trying to prove just that.
“Exercise training in Parkinson’s disease: Neural and functional benefits” aims to see if exercise is a key component in decreasing the symptoms of PD. The study will utilize “polestriding,” which is walking with the aid of ski-like poles. Also known as Nordic walking, the poles will help with balance, which many people with PD have trouble with.
“PD is a progressive disease in which the cells in an area of the brain called the substantia nigra that produce the neurotransmitter called dopamine keep dying,” said Narayanan Krishnamurthi, principal investigator for the study and assistant professor of research at ASU’s Center for Adaptive Neural Systems in the Ira A. Fulton School of Engineering. “So if exercise can protect neurons or it can create new neurons it’s a good possibility that the progression of the disease can be stopped or reversed.”
Krishnamurthi said that he was motivated to do the study based on previous reports that animals with PD-like symptoms benefited from exercise.
“The animals that participated in the exercise program had less severe symptoms and didn’t lose as many neurons as the animals that didn’t participate in the exercise.” Krishnamurthi said.
Krishnamurthi said that other studies have shown that people with higher cardiac and aerobic fitness have better brain health than those who do not regularly exercise.
“This study investigates the functional benefits with respect to motor and non-motor symptoms before and after the exercise training for 12 weeks,” Krishnamurthi said.
This study, which was recently funded by the National Institutes of Health, is a collaborative effort between the Center for Adaptive Neural Systems at ASU, the Muhammad Ali Parkinson Center at the Barrow Neurological Institute, the PET Imaging Center at the Banner Alzheimer’s Institute, and the Christopher Center for Parkinson’s Research at Sun Health Research Institute.
It will involve sixteen participants with PD between the ages of 50-70, because PD usually has its onset after the age of 50.
Each participant will be involved in a 36-week period in which half of the participants will receive PET scans before and after the exercise period to see if there are any positive changes in their brain glucose consumption. The PET scans will be conducted at the Banner Alzheimer’s Institute.
“We’ll see if the exercise training produces changes in the brain metabolic activity patterns from abnormal patterns specific to PD towards the patterns of healthy people,” Krishnamurthi said. “That will give us an indication whether exercise is capable of improving brain health in PD.”
The functional outcome measurements will be completed at the Sun Health Research Institute in Sun City. The exercise sessions will be conducted by Darolyn O’Donnell, recreation therapy coordinator at the Muhammad Ali Parkinson Center at the Barrow Neurological Institute.
“What we aim to do is establish and provide exercise therapy people can do on their own,” O’Donnell said.
The initial idea to use poles came from a personal experience. James Abbas, a co-investigator on the study and co-director of the Center for Adaptive Neural Systems at ASU, learned about how the use of poles can increase the intensity of walking exercise and observed how they helped his mother feel more secure while walking. Since previous research results suggested an important role for exercise and clinical experience pointed to the need for some assistance during walking, the team decided to go forward with the study.
O’Donnell also said that the polestriding was chosen because it provides balance, helps work the upper body and targets core muscle. It’s also more aerobic than normal walking.
The exercise will last 45 minutes to an hour, three times per week.
Right now, the study is still in its initial phases, setting up software and hardware and recruiting participants for the study. Krishnamurthi said they should begin data collection with the first group of participants either this February or March.
“If it is really beneficial, it will be very helpful to alleviate the symptoms since current treatments do not provide cure and are generally ineffective during advanced stages of the disease,” Krishnamurthi said.
If the exercise helps fight against symptoms of PD, he said it will help those with PD everywhere.
“Since exercise can be done in any part of the world, people in underdeveloped countries where medical treatment for diseases like PD is not easily affordable can also benefit significantly.”
“Exercise training in Parkinson’s disease: Neural and functional benefits” aims to see if exercise is a key component in decreasing the symptoms of PD. The study will utilize “polestriding,” which is walking with the aid of ski-like poles. Also known as Nordic walking, the poles will help with balance, which many people with PD have trouble with.
“PD is a progressive disease in which the cells in an area of the brain called the substantia nigra that produce the neurotransmitter called dopamine keep dying,” said Narayanan Krishnamurthi, principal investigator for the study and assistant professor of research at ASU’s Center for Adaptive Neural Systems in the Ira A. Fulton School of Engineering. “So if exercise can protect neurons or it can create new neurons it’s a good possibility that the progression of the disease can be stopped or reversed.”
Krishnamurthi said that he was motivated to do the study based on previous reports that animals with PD-like symptoms benefited from exercise.
“The animals that participated in the exercise program had less severe symptoms and didn’t lose as many neurons as the animals that didn’t participate in the exercise.” Krishnamurthi said.
Krishnamurthi said that other studies have shown that people with higher cardiac and aerobic fitness have better brain health than those who do not regularly exercise.
“This study investigates the functional benefits with respect to motor and non-motor symptoms before and after the exercise training for 12 weeks,” Krishnamurthi said.
This study, which was recently funded by the National Institutes of Health, is a collaborative effort between the Center for Adaptive Neural Systems at ASU, the Muhammad Ali Parkinson Center at the Barrow Neurological Institute, the PET Imaging Center at the Banner Alzheimer’s Institute, and the Christopher Center for Parkinson’s Research at Sun Health Research Institute.
It will involve sixteen participants with PD between the ages of 50-70, because PD usually has its onset after the age of 50.
Each participant will be involved in a 36-week period in which half of the participants will receive PET scans before and after the exercise period to see if there are any positive changes in their brain glucose consumption. The PET scans will be conducted at the Banner Alzheimer’s Institute.
“We’ll see if the exercise training produces changes in the brain metabolic activity patterns from abnormal patterns specific to PD towards the patterns of healthy people,” Krishnamurthi said. “That will give us an indication whether exercise is capable of improving brain health in PD.”
The functional outcome measurements will be completed at the Sun Health Research Institute in Sun City. The exercise sessions will be conducted by Darolyn O’Donnell, recreation therapy coordinator at the Muhammad Ali Parkinson Center at the Barrow Neurological Institute.
“What we aim to do is establish and provide exercise therapy people can do on their own,” O’Donnell said.
The initial idea to use poles came from a personal experience. James Abbas, a co-investigator on the study and co-director of the Center for Adaptive Neural Systems at ASU, learned about how the use of poles can increase the intensity of walking exercise and observed how they helped his mother feel more secure while walking. Since previous research results suggested an important role for exercise and clinical experience pointed to the need for some assistance during walking, the team decided to go forward with the study.
O’Donnell also said that the polestriding was chosen because it provides balance, helps work the upper body and targets core muscle. It’s also more aerobic than normal walking.
The exercise will last 45 minutes to an hour, three times per week.
Right now, the study is still in its initial phases, setting up software and hardware and recruiting participants for the study. Krishnamurthi said they should begin data collection with the first group of participants either this February or March.
“If it is really beneficial, it will be very helpful to alleviate the symptoms since current treatments do not provide cure and are generally ineffective during advanced stages of the disease,” Krishnamurthi said.
If the exercise helps fight against symptoms of PD, he said it will help those with PD everywhere.
“Since exercise can be done in any part of the world, people in underdeveloped countries where medical treatment for diseases like PD is not easily affordable can also benefit significantly.”
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