Research into the evolution of protein design by a University of Houston professor will be featured among nearly 20 presentations at the 2005 Nano Summit Research Conference July 28.
Kurt L. Krause, an associate professor of biology and biochemistry at UH, will give a presentation at 11 a.m. on the "Role of Protein Design in Bionanotechnology."
Sponsored by the Nanotechnology Foundation of Texas, the 2005 Nano Summit is a daylong forum for Texas natural science, engineering and medical researchers to meet and exchange information on their respective areas of expertise. With a focus on major nanoscience research activities across Texas, the conference also is of benefit to corporate research and development executives, as well as students in related disciplines. UH is a co-host of the event.
Held from 8:30 a.m. to 6:30 p.m. at the Edwin Hornberger Conference Center in the Texas Medical Center in Houston, the Nano Summit will provide presentations, a poster session and networking opportunities that cover leading nanotechnology research and practical applications in life science, materials science, energy, electronics and semiconductors. Both presenters and attendees will be able to explore the specific research needs and opportunities associated with the multidisciplinary field that is nanotechnology.
Krause's work deals with the significant effort in bionanotechnology today being devoted to the use of naturally occurring proteins in the diagnosis and treatment of disease and as reagents in bioengineering applications. The proteins used in these experiments are almost always naturally occurring and derived from living organisms. However, these proteins are not optimized to carry out anything other than their natural role. Krause proposes that if the widespread use of proteins in nanotechnology is to be achieved, then much more will need to be done in the area of protein design.
He will discuss current advances in the use of selection and randomization to intelligently evolve protein function, as well as the role of these advances in the application of nanotechnology. For instance, in Krause's laboratory, what starts off as a mere molecule may soon become a potential drug to treat HIV, one of the diseases he actively targets with his research.
uh/newsroom
понедельник, 6 июня 2011 г.
Researchers Identify The Gene Responsible For A Rare Form Of Congenital Anemia
The latest electronic edition of the journal Nature Genetics reports the discovery of a new gene responsible for congenital sideroblastic anemia, a rare disease, mainly characterized by the presence of ringed sideroblasts in the patients' bone marrow. This Genome Canada project, co-directed by Dr. Mark Samuels, an investigator with the Sainte-Justine University Hospital Research Center and a professor at the UniversitГ© de MontrГ©al Department of Medicine, is being conducted under the Atlantic Medical Genetics and Genomics Initiative (AMGGI).
The clinical research team identified three families from Canada's Maritime provinces, each with a child suffering from this disease. Even though these families were not related officially, it seemed very likely that it was possible to establish a genealogical link uniting them generations ago and that they exhibited what is called a founder effect.
Thanks to the new technologies developed by the Human Genome Project, the AMGGI's molecular analysis team succeeded in delimiting a genomic region likely to contain the gene responsible for congenital sideroblastic anemia in these families.
The direct resequencing of this gene made it possible to identify a causal mutation in a gene to which no physiological role could have been attributed. Subsequently, in collaboration with researchers in the United States, the team identified 10 additional causal mutations of this gene in other unexplained cases of congenital sideroblastic anemia. In collaboration with the laboratory of Dr. Louis Saint-Amant of the UniversitГ© de MontrГ©al's Department of Pathology, the research team showed a direct role of the gene in hemoglobin synthesis in zebra fish.
The gene identified is part of a gene family involved in the transport of nutrients to and from the mitochondria, the power plant of the cells. Some mutations of other members of this gene family cause distinct genetic diseases in humans, but this is the first disease of this type associated with the SLC25A38 gene.
The identification of the causal gene can now offer patients and their family members direct molecular confirmation of their condition, allowing them to know whether they are sufferers or asymptomatic carriers of the disease. More generally, this discovery shows that even well-known scientific processes, such as hemoglobin biosynthesis, still have surprises in store.
Source:
MГ©lanie Dallaire
University of Montreal
The clinical research team identified three families from Canada's Maritime provinces, each with a child suffering from this disease. Even though these families were not related officially, it seemed very likely that it was possible to establish a genealogical link uniting them generations ago and that they exhibited what is called a founder effect.
Thanks to the new technologies developed by the Human Genome Project, the AMGGI's molecular analysis team succeeded in delimiting a genomic region likely to contain the gene responsible for congenital sideroblastic anemia in these families.
The direct resequencing of this gene made it possible to identify a causal mutation in a gene to which no physiological role could have been attributed. Subsequently, in collaboration with researchers in the United States, the team identified 10 additional causal mutations of this gene in other unexplained cases of congenital sideroblastic anemia. In collaboration with the laboratory of Dr. Louis Saint-Amant of the UniversitГ© de MontrГ©al's Department of Pathology, the research team showed a direct role of the gene in hemoglobin synthesis in zebra fish.
The gene identified is part of a gene family involved in the transport of nutrients to and from the mitochondria, the power plant of the cells. Some mutations of other members of this gene family cause distinct genetic diseases in humans, but this is the first disease of this type associated with the SLC25A38 gene.
The identification of the causal gene can now offer patients and their family members direct molecular confirmation of their condition, allowing them to know whether they are sufferers or asymptomatic carriers of the disease. More generally, this discovery shows that even well-known scientific processes, such as hemoglobin biosynthesis, still have surprises in store.
Source:
MГ©lanie Dallaire
University of Montreal
Blood-Brain Barrier Used As Therapy Delivery System By University Of Iowa Scientists
The blood brain barrier is generally considered an obstacle to delivering therapies from the bloodstream to the brain. However, University of Iowa researchers have discovered a way to turn the blood vessels surrounding brain cells into a production and delivery system for getting therapeutic molecules directly into brain cells.
Working with animal models of a group of fatal neurological disorders called lysosomal storage diseases, the UI team found that these diseases cause unique and disease-specific alterations to the blood vessels of the blood brain barrier. The scientists used these distinct alterations to target the brain with gene therapy, which reversed the neurological damage caused by the diseases.
The findings, which were published in Nature Medicine's Advance Online Publication (AOP), could lead to a new non-invasive approach for treating neurological damage caused by lysosomal storage diseases.
"This is the first time an enzyme delivered through the bloodstream has corrected deficiencies in the brain," said lead investigator Beverly Davidson, Ph.D., UI professor of internal medicine, neurology, and molecular physiology and biophysics. "This provides a real opportunity to deliver enzyme therapy without surgically entering the brain to treat lysosomal storage diseases.
"In addition, we have discovered that these neurological diseases affect not just the brain cells that we often focus on, but also the blood vessels throughout the brain. We have taken advantage of that finding to delivery gene therapy, but we also can use this knowledge to better understand how the diseases impact other cell types such as neurons," she added.
Lysosomal storage diseases are individually quite rare, but as a group they affect approximately 1 in 8,000 live births. The diseases are caused by deficiencies in enzymes that break down larger molecules. Without these enzymes, the large molecules accumulate inside cells and cause cell damage and destruction.
Enzyme replacement therapy has been successful in treating one form of lysosomal storage disease called Gaucher disease. However, storage diseases that affect the central nervous system remain untreatable because it has not been possible, to this point, to get the missing enzymes past the blood-brain-barrier and into the brain.
"Our discovery allowed us to test the idea that the brain cells might be able to make use of the reintroduced enzyme to stop or reverse the damage caused by the accumulated materials," said Davidson, who also is the Roy J. Carver Professor in Internal Medicine. "In the treated mice, the affected brain cells go back to looking normal, the brain inflammation goes away and the impaired behaviors that these mice have is corrected."
To develop their gene therapy targeting system, Davidson and colleagues used a technique called phage panning to identify peptides that hone in on the blood vessels surrounding the brain. Surprisingly, they found that peptides that targeted the brain blood vessels in mice with lysosomal storage diseases were distinct from the peptides that targeted brain blood vessels in healthy mice. Moreover, the peptides that targeted blood vessels in different diseases were distinct from each other, suggesting that each disease causes specific alterations to the blood vessels.
The team modified a deactivated virus used for gene therapy so that the virus expressed copies of the unique brain-targeting peptide on its outer coat, and also carried the genetic blueprint for the missing enzyme.
The study showed that the modified virus targeted the blood vessels in the brain and caused the blood vessel cells to produce the enzyme. Most importantly, the researchers found that the enzyme was secreted into the brain tissue in sufficient quantities to correct the disease symptoms and problems.
The team was able to use this approach to treat two types of lysosomal storage disease in mice, suggesting that the approach could be used for other types of lysosomal storage disease and possibly other neurological disorders.
In addition to Davidson, the research team included UI postdoctoral researcher Yong Hong Chen, Ph.D., and Michael Chang, M.D., Ph.D., who was a student in the UI Medical Scientist Training Program when the study was conducted.
The study was funded by grants from the National Institutes of Health and from the Batten Disease Support and Research Association.
Source:
Jennifer Brown
University of Iowa
Working with animal models of a group of fatal neurological disorders called lysosomal storage diseases, the UI team found that these diseases cause unique and disease-specific alterations to the blood vessels of the blood brain barrier. The scientists used these distinct alterations to target the brain with gene therapy, which reversed the neurological damage caused by the diseases.
The findings, which were published in Nature Medicine's Advance Online Publication (AOP), could lead to a new non-invasive approach for treating neurological damage caused by lysosomal storage diseases.
"This is the first time an enzyme delivered through the bloodstream has corrected deficiencies in the brain," said lead investigator Beverly Davidson, Ph.D., UI professor of internal medicine, neurology, and molecular physiology and biophysics. "This provides a real opportunity to deliver enzyme therapy without surgically entering the brain to treat lysosomal storage diseases.
"In addition, we have discovered that these neurological diseases affect not just the brain cells that we often focus on, but also the blood vessels throughout the brain. We have taken advantage of that finding to delivery gene therapy, but we also can use this knowledge to better understand how the diseases impact other cell types such as neurons," she added.
Lysosomal storage diseases are individually quite rare, but as a group they affect approximately 1 in 8,000 live births. The diseases are caused by deficiencies in enzymes that break down larger molecules. Without these enzymes, the large molecules accumulate inside cells and cause cell damage and destruction.
Enzyme replacement therapy has been successful in treating one form of lysosomal storage disease called Gaucher disease. However, storage diseases that affect the central nervous system remain untreatable because it has not been possible, to this point, to get the missing enzymes past the blood-brain-barrier and into the brain.
"Our discovery allowed us to test the idea that the brain cells might be able to make use of the reintroduced enzyme to stop or reverse the damage caused by the accumulated materials," said Davidson, who also is the Roy J. Carver Professor in Internal Medicine. "In the treated mice, the affected brain cells go back to looking normal, the brain inflammation goes away and the impaired behaviors that these mice have is corrected."
To develop their gene therapy targeting system, Davidson and colleagues used a technique called phage panning to identify peptides that hone in on the blood vessels surrounding the brain. Surprisingly, they found that peptides that targeted the brain blood vessels in mice with lysosomal storage diseases were distinct from the peptides that targeted brain blood vessels in healthy mice. Moreover, the peptides that targeted blood vessels in different diseases were distinct from each other, suggesting that each disease causes specific alterations to the blood vessels.
The team modified a deactivated virus used for gene therapy so that the virus expressed copies of the unique brain-targeting peptide on its outer coat, and also carried the genetic blueprint for the missing enzyme.
The study showed that the modified virus targeted the blood vessels in the brain and caused the blood vessel cells to produce the enzyme. Most importantly, the researchers found that the enzyme was secreted into the brain tissue in sufficient quantities to correct the disease symptoms and problems.
The team was able to use this approach to treat two types of lysosomal storage disease in mice, suggesting that the approach could be used for other types of lysosomal storage disease and possibly other neurological disorders.
In addition to Davidson, the research team included UI postdoctoral researcher Yong Hong Chen, Ph.D., and Michael Chang, M.D., Ph.D., who was a student in the UI Medical Scientist Training Program when the study was conducted.
The study was funded by grants from the National Institutes of Health and from the Batten Disease Support and Research Association.
Source:
Jennifer Brown
University of Iowa
Misfolded Proteins: The Fundamental Problem Is Aging
Proteins are essential for all biological activities and the health of the cell. Misfolded and damaged proteins spell trouble and are common to all human neurodegenerative diseases and many other age-associated diseases. But when during a lifespan do proteins start to misbehave?
A new Northwestern University study reports that protein damage can be detected much earlier than we had thought, long before individuals exhibit symptoms. But the study also suggests if we intervene early enough, the damage could be delayed.
In studying seven different proteins of the worm C. elegans, the researchers discovered that each protein misfolds at the same point: during early adulthood and long before the animal shows any behavioral, or physiological, change. (Each protein had a minor mutation that affects folding.)
The misfolding coincided with the loss of a critical protective cellular mechanism: the ability to activate the heat shock response, an ancient genetic switch that senses damaged proteins and protects cells by preventing protein misfolding.
The results will be published online during the week of Aug. 24 by the Proceedings of the National Academy of Sciences (PNAS).
"I didn't expect the results to be so dramatic, for these different proteins that vary in concentration and are expressed in diverse tissues to collapse at the same time," said lead researcher Richard I. Morimoto. "This suggests the animal's protective cellular stress response becomes deficient during aging."
Could the damaging events of protein misfolding be prevented or at least delayed?
To find out, the researchers gave the animals the equivalent of a vitamin, boosting the heat shock response early in the animal's development, prior to protein damage. Now, instead of misfolding around day four, the equivalent of early adulthood in the worm, the proteins didn't start misfolding until day 12. (Behavioral changes didn't appear for at least three days after misfolding. The average lifespan of the worm is 21 days.)
"Our data suggest that, in terms of therapeutics, you have to start early to prevent damage and keep cells healthy," said Morimoto, Bill and Gayle Cook Professor of Biochemistry, Molecular Biology and Cell Biology in Northwestern's Weinberg College of Arts and Sciences. "When you see a loss of function, it's too late."
Genes that regulate lifespan were first discovered in C. elegans. The transparent roundworm is a favorite organism of biologists because its biochemical environment and fundamental mechanisms are similar to that of human beings and its genome, or complete genetic sequence, is known.
The title of the PNAS paper is "Collapse of Proteostasis Represents an Early Molecular Event in C. elegans Aging." In addition to Morimoto, other authors of the paper are Anat Ben-Zvi and Elizabeth A. Miller, both from Northwestern.
Source:
Megan Fellman
Northwestern University
A new Northwestern University study reports that protein damage can be detected much earlier than we had thought, long before individuals exhibit symptoms. But the study also suggests if we intervene early enough, the damage could be delayed.
In studying seven different proteins of the worm C. elegans, the researchers discovered that each protein misfolds at the same point: during early adulthood and long before the animal shows any behavioral, or physiological, change. (Each protein had a minor mutation that affects folding.)
The misfolding coincided with the loss of a critical protective cellular mechanism: the ability to activate the heat shock response, an ancient genetic switch that senses damaged proteins and protects cells by preventing protein misfolding.
The results will be published online during the week of Aug. 24 by the Proceedings of the National Academy of Sciences (PNAS).
"I didn't expect the results to be so dramatic, for these different proteins that vary in concentration and are expressed in diverse tissues to collapse at the same time," said lead researcher Richard I. Morimoto. "This suggests the animal's protective cellular stress response becomes deficient during aging."
Could the damaging events of protein misfolding be prevented or at least delayed?
To find out, the researchers gave the animals the equivalent of a vitamin, boosting the heat shock response early in the animal's development, prior to protein damage. Now, instead of misfolding around day four, the equivalent of early adulthood in the worm, the proteins didn't start misfolding until day 12. (Behavioral changes didn't appear for at least three days after misfolding. The average lifespan of the worm is 21 days.)
"Our data suggest that, in terms of therapeutics, you have to start early to prevent damage and keep cells healthy," said Morimoto, Bill and Gayle Cook Professor of Biochemistry, Molecular Biology and Cell Biology in Northwestern's Weinberg College of Arts and Sciences. "When you see a loss of function, it's too late."
Genes that regulate lifespan were first discovered in C. elegans. The transparent roundworm is a favorite organism of biologists because its biochemical environment and fundamental mechanisms are similar to that of human beings and its genome, or complete genetic sequence, is known.
The title of the PNAS paper is "Collapse of Proteostasis Represents an Early Molecular Event in C. elegans Aging." In addition to Morimoto, other authors of the paper are Anat Ben-Zvi and Elizabeth A. Miller, both from Northwestern.
Source:
Megan Fellman
Northwestern University
Prevention Of Dangerous Corn Toxin Hinges On Defining Gene's Role
Discovery that a specific gene is integral to both fungal invasion of corn and development of a potentially deadly toxin in the kernels may lead to ways to control the pathogen and the poison.
Purdue University researchers evaluated the fungal gene ZFR1 and found that it is vital to the process of the fungus growing on corn kernels. Production of the toxin decreased when the scientists disabled the gene.
At certain levels, the toxin can cause illness in humans and most domestic livestock. Horses and pigs are at particular risk and can develop fatal diseases by ingesting feed containing one of a group of toxins called fumonisins (few-mahn-ah-sins). About $40 million of the U.S. corn crop is lost annually due to presence of these toxins, according to experts.
"Our main research question has been what triggers toxin production when the fungus attacks the corn kernel; it appears that kernel starch plays an important role," said Charles Woloshuk, a Purdue plant pathologist. "When ZFR1 is deleted, the resulting mutant fungus has a problem transporting sugars that are produced from the degradation of kernel starch."
The resulting sugars must be transported to cells as fuel for other biochemical processes.
"The pathogen - the fungus Fusarium verticillioides - has a number of putative sugar transporter genes that are expressed during its growth on kernels and toxin production," Woloshuk said. "Disruption of ZFR1 also affects expression of the sugar transporter genes."
Woloshuk and his colleague, Bert Bluhm, now at the University of Arkansas, report in the current issue of Molecular Plant Pathology that when the gene ZFR1 is turned off, it reduces manifestation of genes involved in production of the most prevalent and dangerous fumonisin, FB1.
The researchers studied ZFR1 regulation of fungal growth and toxin production in the starch-rich areas of corn kernels and the conversion of starch to glucose, glucose recognition and the expression of sugar transporter genes. From this information, Woloshuk and his team identified a specific sugar transporter, FST1 (fusarium sugar transporter1), that is necessary for FB1 production.
Although FST1 is required for FB1 production, it is not involved with the fungus infecting corn kernels. This led the scientists to hypothesize that FST1 acts as a molecular sensor necessary for toxin production.
Kernels with lower starch content, most notably immature kernels, don't support toxin production, Woloshuk said. This is evidence that the kernel makeup dictates how this pathogen controls toxin production.
Corn and fungal growth were unaffected when the sugar transporter gene was disrupted, but toxin production on the kernels was cut by about 82 percent, Woloshuk said.
When fusarium invades corn in the field, it causes an ear rot disease. Even knowing that ear rot is present doesn't help identify corn containing toxin because obvious signs of the fungus don't correlate with presence of toxins. The only way to confirm toxin is present is to test for it. Testing is so expensive, however, that it usually isn't done unless the disease is highly evident.
Weather and insect damage impact development of a variety of fungi and toxins and also influence the level of poisons that are present. Toxins are more likely to develop in corn when hot, dry weather is followed by highly humid or wet weather.
The group of toxins associated with varieties of fusarium species are known as mycotoxins. Some clinical evidence links these toxins with certain human cancers.
Grains grown for cereal and feeds are susceptible to one or more of the fusarium fungi species. Wheat and barley attacked by one of the species closely related to Fusarium verticillioides can develop head blight and accumulate mycotoxins, causing billions of dollars in crop losses worldwide.
Further study is needed because the researchers still don't know what triggers the biochemical process that regulates ZFR1 and consequently leads to toxin production, Woloshuk said. The scientists also are investigating the sugar transporter genes to discover if they have other roles in the fungus and what molecular interactions between the fungus and the plant allow infection and toxin production.
"We're closer to finding some of the triggers in corn that assist the fungus in toxin production," Woloshuk said.
The other researchers involved in this study were Department of Botany and Plant Pathology doctoral student Hun Kim and Robert Butchko of the USDA National Center for Agricultural Utilization Research Service in Peoria, Ill. Bluhm is a former graduate student in Woloshuk's laboratory who recently joined the University of Arkansas faculty as an assistant professor.
A USDA-National Research Initiative grant provided support for this work.
Writer: Susan A. Steeves
Related Web sites:
Purdue Department of Botany and Plant Pathology
USDA-Agricultural Research Service, Crop Production & Pest Control Research Unit
National Center for Agricultural Utilization Research Service
Molecular Plant Pathology
Click here for abstract on the research in this release.
Source: Susan A. Steeves
Purdue University
Purdue University researchers evaluated the fungal gene ZFR1 and found that it is vital to the process of the fungus growing on corn kernels. Production of the toxin decreased when the scientists disabled the gene.
At certain levels, the toxin can cause illness in humans and most domestic livestock. Horses and pigs are at particular risk and can develop fatal diseases by ingesting feed containing one of a group of toxins called fumonisins (few-mahn-ah-sins). About $40 million of the U.S. corn crop is lost annually due to presence of these toxins, according to experts.
"Our main research question has been what triggers toxin production when the fungus attacks the corn kernel; it appears that kernel starch plays an important role," said Charles Woloshuk, a Purdue plant pathologist. "When ZFR1 is deleted, the resulting mutant fungus has a problem transporting sugars that are produced from the degradation of kernel starch."
The resulting sugars must be transported to cells as fuel for other biochemical processes.
"The pathogen - the fungus Fusarium verticillioides - has a number of putative sugar transporter genes that are expressed during its growth on kernels and toxin production," Woloshuk said. "Disruption of ZFR1 also affects expression of the sugar transporter genes."
Woloshuk and his colleague, Bert Bluhm, now at the University of Arkansas, report in the current issue of Molecular Plant Pathology that when the gene ZFR1 is turned off, it reduces manifestation of genes involved in production of the most prevalent and dangerous fumonisin, FB1.
The researchers studied ZFR1 regulation of fungal growth and toxin production in the starch-rich areas of corn kernels and the conversion of starch to glucose, glucose recognition and the expression of sugar transporter genes. From this information, Woloshuk and his team identified a specific sugar transporter, FST1 (fusarium sugar transporter1), that is necessary for FB1 production.
Although FST1 is required for FB1 production, it is not involved with the fungus infecting corn kernels. This led the scientists to hypothesize that FST1 acts as a molecular sensor necessary for toxin production.
Kernels with lower starch content, most notably immature kernels, don't support toxin production, Woloshuk said. This is evidence that the kernel makeup dictates how this pathogen controls toxin production.
Corn and fungal growth were unaffected when the sugar transporter gene was disrupted, but toxin production on the kernels was cut by about 82 percent, Woloshuk said.
When fusarium invades corn in the field, it causes an ear rot disease. Even knowing that ear rot is present doesn't help identify corn containing toxin because obvious signs of the fungus don't correlate with presence of toxins. The only way to confirm toxin is present is to test for it. Testing is so expensive, however, that it usually isn't done unless the disease is highly evident.
Weather and insect damage impact development of a variety of fungi and toxins and also influence the level of poisons that are present. Toxins are more likely to develop in corn when hot, dry weather is followed by highly humid or wet weather.
The group of toxins associated with varieties of fusarium species are known as mycotoxins. Some clinical evidence links these toxins with certain human cancers.
Grains grown for cereal and feeds are susceptible to one or more of the fusarium fungi species. Wheat and barley attacked by one of the species closely related to Fusarium verticillioides can develop head blight and accumulate mycotoxins, causing billions of dollars in crop losses worldwide.
Further study is needed because the researchers still don't know what triggers the biochemical process that regulates ZFR1 and consequently leads to toxin production, Woloshuk said. The scientists also are investigating the sugar transporter genes to discover if they have other roles in the fungus and what molecular interactions between the fungus and the plant allow infection and toxin production.
"We're closer to finding some of the triggers in corn that assist the fungus in toxin production," Woloshuk said.
The other researchers involved in this study were Department of Botany and Plant Pathology doctoral student Hun Kim and Robert Butchko of the USDA National Center for Agricultural Utilization Research Service in Peoria, Ill. Bluhm is a former graduate student in Woloshuk's laboratory who recently joined the University of Arkansas faculty as an assistant professor.
A USDA-National Research Initiative grant provided support for this work.
Writer: Susan A. Steeves
Related Web sites:
Purdue Department of Botany and Plant Pathology
USDA-Agricultural Research Service, Crop Production & Pest Control Research Unit
National Center for Agricultural Utilization Research Service
Molecular Plant Pathology
Click here for abstract on the research in this release.
Source: Susan A. Steeves
Purdue University
Renal Transplant Recipients' Genetic Makeup Does Not Negatively Impact Fluvastatin Use
Scientists report that when people with a transplanted kidney take fluvastatin, a drug against cardiovascular disease, their response to the drug is not influenced by their genetic composition.
People who receive a transplanted kidney are at risk of developing potentially fatal premature cardiovascular disease. One way to prevent this from happening is by taking fluvastatin, a drug that significantly reduces myocardial infarction and cardiac death. But patients' genetic makeup has been reported to prevent similar cholesterol-lowering drugs, such as pravastatin, from working properly.
To examine potential effects of a genetic makeup on the efficacy of fluvastatin after patients receive a kidney transplant, Hallvard Holdaas and colleagues examined 42 genetic variations previously reported to affect fluvastatin metabolism, cholesterol regulation, cardiovascular disease, and the functioning of a transplanted kidney.
The scientists compared the effects of these genetic variations in 707 renal transplant patients who received fluvastatin and 697 patients who received a placebo and showed that the variations do not increase risks of developing a cardiovascular disease or a kidney disease. Consequently, statin therapy continues to be recommended to patients who received a transplanted kidney, regardless of their genetic makeup, the researchers concluded.
Article: "Genetic analysis of fluvastatin response and dyslipidemia in renal transplant recipients," by Jonathan B. Singer, Hallvard Holdaas, Alan G. Jardine, Bengt Fellstrom, Ingrid Os, Georgina Bermann, and Joanne M. Meyer, on behalf of the Assessment of Lescol in Renal Transplantation (ALERT) Study Investigators
The American Society for Biochemistry and Molecular Biology is a nonprofit scientific and educational organization with over 11,900 members in the United States and internationally. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, nonprofit research institutions and industry. The Society's student members attend undergraduate or graduate institutions.
Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for Experimental Biology. The Society's purpose is to advance the science of biochemistry and molecular biology through publication of the Journal of Biological Chemistry, the Journal of Lipid Research, and Molecular and Cellular Proteomics, organization of scientific meetings, advocacy for funding of basic research and education, support of science education at all levels, and promoting the diversity of individuals entering the scientific work force.
For more information about ASBMB, see the Society's Web site at asbmb.
View drug information on Lescol.
People who receive a transplanted kidney are at risk of developing potentially fatal premature cardiovascular disease. One way to prevent this from happening is by taking fluvastatin, a drug that significantly reduces myocardial infarction and cardiac death. But patients' genetic makeup has been reported to prevent similar cholesterol-lowering drugs, such as pravastatin, from working properly.
To examine potential effects of a genetic makeup on the efficacy of fluvastatin after patients receive a kidney transplant, Hallvard Holdaas and colleagues examined 42 genetic variations previously reported to affect fluvastatin metabolism, cholesterol regulation, cardiovascular disease, and the functioning of a transplanted kidney.
The scientists compared the effects of these genetic variations in 707 renal transplant patients who received fluvastatin and 697 patients who received a placebo and showed that the variations do not increase risks of developing a cardiovascular disease or a kidney disease. Consequently, statin therapy continues to be recommended to patients who received a transplanted kidney, regardless of their genetic makeup, the researchers concluded.
Article: "Genetic analysis of fluvastatin response and dyslipidemia in renal transplant recipients," by Jonathan B. Singer, Hallvard Holdaas, Alan G. Jardine, Bengt Fellstrom, Ingrid Os, Georgina Bermann, and Joanne M. Meyer, on behalf of the Assessment of Lescol in Renal Transplantation (ALERT) Study Investigators
The American Society for Biochemistry and Molecular Biology is a nonprofit scientific and educational organization with over 11,900 members in the United States and internationally. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, nonprofit research institutions and industry. The Society's student members attend undergraduate or graduate institutions.
Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for Experimental Biology. The Society's purpose is to advance the science of biochemistry and molecular biology through publication of the Journal of Biological Chemistry, the Journal of Lipid Research, and Molecular and Cellular Proteomics, organization of scientific meetings, advocacy for funding of basic research and education, support of science education at all levels, and promoting the diversity of individuals entering the scientific work force.
For more information about ASBMB, see the Society's Web site at asbmb.
View drug information on Lescol.
Avian Influenza Survivors' Antibodies Effective At Neutralising H5N1 Strain
Adults who have recovered from the potentially deadly H5N1 strain of avian influenza may hold the key to future treatments for the virus, according to an international team of researchers. In a study published in the open access journal PLoS Medicine, the researchers have shown how specific antibodies taken from avian flu survivors in Vietnam can be reproduced in the laboratory and prove effective at neutralising the virus in culture vitro and in mice.
The H5N1 influenza virus has caused disease and death in millions of poultry across the globe and occasionally has been transmitted to humans, often fatally. By mid-May 2007, according to the World Health Organization, there had been 306 known cases in humans, 185 of them fatal.
Now, doctors based at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam, the Institute for Research in Biomedicine in Bellinzona, Switzerland and the National Institute of Allergy and Infectious Diseases in Bethesda, US, have shown that monoclonal antibodies generated from blood of human survivors of the H5N1 virus are effective at both preventing infection in mice and neutralising the virus in those already infected. The research had been fast-tracked for funding by the UK's Wellcome Trust and is also supported by grants from the National Institutes of Health in the US and the Swiss National Science Foundation.
The researchers found that the antibodies provided significant immunity to mice that were subsequently infected with the Vietnam strain of H5N1. This reduced significantly the amount of virus found in the lungs and almost completely prevented the virus reaching the brain or spleen. In those people in Vietnam who died from the H5N1 strain, the virus was found to have spread from the lungs; this was not the case in those who survived.
"We have shown that this technique can work to prevent and neutralise infection by the H5N1 'bird flu' virus in mice," says Dr Cameron Simmons, a Wellcome Trust researcher at the Oxford University Clinical Research Unit, Vietnam. "We are optimistic that these antibodies, if delivered at the right time and at the right amount, could also provide a clinical benefit to humans with H5N1 infections."
"In particular, we found that it was possible to administer the treatment up to 72 hours after infection. This is particularly important as people who have become infected with the virus do not tend to report to their local healthcare facilities until several days after the onset of illness."
The antibodies were discovered in the laboratory of Professor Antonio Lanzavecchia at the Institute for Research in Biomedicine in Switzerland. The researchers used a new technique that allows them to rapidly reproduce human monoclonal antibodies starting from a small sample of blood.
"We can't say for certain that a pandemic influenza virus will resemble the H5N1 strain that we have been studying or that the monoclonal antibodies generated using our technique will be able to tackle such a virus," says Professor Lanzavecchia. "Nevertheless, we are encouraged by the broad neutralizing activity of these antibodies in the lab and the moderate doses required."
Using administered antibodies has a historical precedent. During the 1918 Spanish H1N1 influenza pandemic, there were multiple reports of physicians administering blood taken from survivors to patients infected with the disease. A recent review suggested that this treatment was associated with a halving in mortality. However, directly administering blood carries a risk of infection with other blood diseases, such as Hepatitis C and HIV.
Contact: Craig Brierley
Wellcome Trust
The H5N1 influenza virus has caused disease and death in millions of poultry across the globe and occasionally has been transmitted to humans, often fatally. By mid-May 2007, according to the World Health Organization, there had been 306 known cases in humans, 185 of them fatal.
Now, doctors based at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam, the Institute for Research in Biomedicine in Bellinzona, Switzerland and the National Institute of Allergy and Infectious Diseases in Bethesda, US, have shown that monoclonal antibodies generated from blood of human survivors of the H5N1 virus are effective at both preventing infection in mice and neutralising the virus in those already infected. The research had been fast-tracked for funding by the UK's Wellcome Trust and is also supported by grants from the National Institutes of Health in the US and the Swiss National Science Foundation.
The researchers found that the antibodies provided significant immunity to mice that were subsequently infected with the Vietnam strain of H5N1. This reduced significantly the amount of virus found in the lungs and almost completely prevented the virus reaching the brain or spleen. In those people in Vietnam who died from the H5N1 strain, the virus was found to have spread from the lungs; this was not the case in those who survived.
"We have shown that this technique can work to prevent and neutralise infection by the H5N1 'bird flu' virus in mice," says Dr Cameron Simmons, a Wellcome Trust researcher at the Oxford University Clinical Research Unit, Vietnam. "We are optimistic that these antibodies, if delivered at the right time and at the right amount, could also provide a clinical benefit to humans with H5N1 infections."
"In particular, we found that it was possible to administer the treatment up to 72 hours after infection. This is particularly important as people who have become infected with the virus do not tend to report to their local healthcare facilities until several days after the onset of illness."
The antibodies were discovered in the laboratory of Professor Antonio Lanzavecchia at the Institute for Research in Biomedicine in Switzerland. The researchers used a new technique that allows them to rapidly reproduce human monoclonal antibodies starting from a small sample of blood.
"We can't say for certain that a pandemic influenza virus will resemble the H5N1 strain that we have been studying or that the monoclonal antibodies generated using our technique will be able to tackle such a virus," says Professor Lanzavecchia. "Nevertheless, we are encouraged by the broad neutralizing activity of these antibodies in the lab and the moderate doses required."
Using administered antibodies has a historical precedent. During the 1918 Spanish H1N1 influenza pandemic, there were multiple reports of physicians administering blood taken from survivors to patients infected with the disease. A recent review suggested that this treatment was associated with a halving in mortality. However, directly administering blood carries a risk of infection with other blood diseases, such as Hepatitis C and HIV.
Contact: Craig Brierley
Wellcome Trust
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