Reaction To The Judgement In The Skanda Vale Court Case, UK

The British Veterinary Association welcomes the judgement made in relation to the Skanda Vale Community bullock, Shambo.

While we appreciate the religious sensitivities surrounding this case and have absolutely no wish to be in any way inflammatory, Shambo has tested positive to bovine tuberculosis, a devastating disease with serious animal and public health implications. According to standard procedures used world-wide, including in Hindu countries, the animal should be humanely destroyed and we are relieved that the courts agree.

The implications of any other judgement for the UK, and indeed much of the world’s, disease control would have been immense and undermined the vital importance of ensuring that public and animal health concerns remain at the heart of responsible disease control policies.

British Veterinary Association

Many Companies Sent Warning Letters About Marketing Alternative HRT Still Selling Products, FTC Official Says

Many of the Web sites targeted by the Federal Trade Commission in 2005 for illegally claiming their alternative hormone replacement therapies were safer than prescription HRT still are selling the products, Eileen Harrington, deputy director of FTC’s Bureau of Consumer Protection, said at a Senate Special Committee on Aging hearing on Thursday, CQ HealthBeat reports (Reichard, CQ HealthBeat, 4/19). FDA in November 2005 sent warning letters to 16 companies that market alternatives to approved HRT. FTC that same month also sent warning letters to 34 Web site operators marketing similar therapies, saying the sites make claims that “may be false or unsubstantiated and therefore may violate the law.” The Web sites were identified during an FTC search of sites asserting that alternative HRT products — including progesterone creams, sprays or dietary supplements — could cure or prevent diseases. Some of the companies that received letters claim their products prevent cancer, osteoporosis-related bone deterioration or arthritis. Such claims would cause the products to fall under the auspices of FDA’s Food, Drugs and Cosmetic Act. The companies were given 15 days to respond to FDA after receiving the letters (Kaiser Daily Women’s Health Policy Report, 11/14/05).

Hearing
According to an unnamed FTC official, 19 of the 34 companies that received letters from the FTC are still selling the alternative HRT products, the AP/USA Today reports. Harrington said that many of the Web sites have modified or removed the unsupported claims that the treatments could cure or prevent diseases. Harrington added that the agency is following up the companies that have not made changes. Sen. Gordon Smith (R-Ore.), the committee’s ranking Republican, said to reporters that FDA and FTC need to “step … up” enforcement on the issue. Harrington said, “We could have moved faster here, and we should have” (Bridges, AP/USA Today, 4/19). The customized HRT alternatives are sold without warnings about the risks associated with the drugs, witnesses at the hearing said. According to CQ HealthBeat, Smith said that he plans to introduce legislation to strengthen regulation and that he hopes publicity about the issue will encourage FTC and FDA to better monitor sales of HRT alternatives. In addition, Smith at the hearing said he has requested a study by the Congressional Research Service to determine how well each state is regulating pharmacy compounding. Harrington said FTC would take further action against the companies but did not say when, CQ HealthBeat reports (CQ HealthBeat, 4/19).

“Reprinted with permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

Growing Old Together: Yeast, Worms, And People May Age By Similar Mechanisms

A study published online in Genome Research provides new insight into the evolutionary conservation of the genes and pathways associated with aging. This report describes the identification of conserved aging-related genes in simple model organisms that may lead to the characterization of similar genes playing a role in human aging and age-associated diseases.

While nearly all organisms experience aging, the underlying mechanisms have eluded geneticists and evolutionary biologists. Many different theories have been suggested, yet experimental evidence strongly suggests that aging is modulated, at least in part, by genetic factors. Previous studies have implicated a number of conserved genes in model organisms as regulators of aging, such as the Sirtuins and insulin/IGF1 receptors. However, no investigations to date have quantified the degree to which aging-related genes are conserved across the genome among distantly related species.

In the study published today, a group of researchers led by Drs. Matt Kaeberlein and Brian Kennedy of the University of Washington conducted a genome-wide analysis of the yeast Saccharomyces cerevisiae and the nematode worm Caenorhabditis elegans, to identify genes that may regulate aging in humans. “Nematodes and humans are more similar to each other on an evolutionary scale than nematodes and yeast,” explains Dr. Erica Smith, primary author of the study. “We reasoned that if a particular gene modulates aging in both yeast and nematodes, there is a good chance that gene plays a similar role in people.”

The researchers compiled a set of 276 C. elegans genes that were known to modulate aging, and scanned the yeast genome for genes with highly similar sequences. The highly similar yeast genes were then individually analyzed for a potential role in longevity by measuring the life span of yeast cells lacking each gene. “Our study identified 25 genes that regulate aging in both yeast and nematodes, 22 of which were not previously known to be conserved modulators of aging,” says Kaeberlein. As 15 of the 25 yeast genes are highly similar to known human genes, Kaeberlein adds that this work is readily applicable to human aging research. “It is reasonable to speculate that many of the genes identified in our study also regulate longevity in humans.”

In addition to identifying related pairs of aging-associated genes in yeast and nematodes, the group also investigated whether these genes are involved in common functional pathways. “We find that there is significant overlap between nematode and yeast aging genes, particularly those in nutrient-response pathways,” describes Kennedy. Signaling pathways involved in the response to nutrients have previously been implicated in the regulation of aging. “This finding indicates that two very different species age through overlapping mechanisms and suggests that these mechanisms are likely to also contribute to human aging.”

The genes identified in this study now provide a foundation for extending this research to a higher model organism, and ultimately for understanding human aging. “It will be important to determine how each of these genes modulate aging at the molecular level, and to test whether they also modulate aging in a mammalian model, such as mice,” says Kaeberlein. “In principle, any of these genes could be a useful therapeutic target for treating age-associated diseases.”

Scientists from the University of Washington (Seattle, WA) and the University of Georgia (Athens, GA) contributed to this study.

This work was supported by grants from the Ellison Medical Foundation and the National Institutes of Health.

“Quantitative evidence for conserved longevity pathways between divergent eukaryotic species.”
Smith, E.D., Tsuchiya, M., Fox, L.A., Dang, N., Hu, D., Kerr, E.O., Johnston, E.D., Tchao, B.N., Pak, D.N., Welton, K.L., Promislow., D.E.L., Thomas, J.H., Kaeberlein, M., and Kennedy, B.K.

Genome Res. doi:10.1101/gr.074724.107.

About Genome Research

Genome Research is an international, continuously published, peer-reviewed journal published by Cold Spring Harbor Laboratory Press. Launched in 1995, it is one of the five most highly cited primary research journals in genetics and genomics. Genome Research

About Cold Spring Harbor Laboratory Press

Cold Spring Harbor Laboratory Press is an internationally renowned publisher of books, journals, and electronic media, located on Long Island, New York. It is a division of Cold Spring Harbor Laboratory, an innovator in life science research and the education of scientists, students, and the public.

Cold Spring Harbor Laboratory Press

Gene Mutations Responsible For 10 Percent Of Schizophrenia Pinpointed By Researchers

Scans of the genome of patients with schizophrenia have revealed rare spontaneous copy number mutations that account for at least 10 percent of the non-familial cases of the disease. Researchers describe specific genetic mutations present in individuals who have schizophrenia, but not present in their biological parents who do not have the disease. These individuals were eight times more likely to have these mutations than unaffected individuals. This new data, reported in the May 30 on-line issue of Nature Genetics, will help researchers account for the persistence of schizophrenia in the population despite low birth rates among people with the disease.

Researchers at Columbia University Medical Center scanned the genome of 1,077 people which included 152 individuals with schizophrenia, 159 individuals without schizophrenia, and both of their biological parents for copy number mutations. They found mutations, either a gain or loss of genes, in 15 individuals diagnosed with schizophrenia that were not present in the chromosomes of either biological unaffected parent. Only two of such mutations were found in those without schizophrenia. Study subjects were from the European-origin Afrikaner population in South Africa, a genetically homogenous population that is ideal for genetic evaluation.

“We now know the cause of around 10 percent of the cases of sporadic schizophrenia,” said Maria Karayiorgou, M.D., professor of psychiatry, Columbia University Medical Center, the senior author on the study. “Schizophrenia is not as much of a ‘big black box’ as it used to be. The identification of these genes lets us know what brain development pathways are involved in disease onset, so that in the future we can look at better ways of treating this devastating disease.”

Schizophrenia affects approximately 1 percent of the population worldwide. About 40 percent of the disease is thought to be inherited, with the other 60 percent sporadically showing up in people whose family history does not include the disease.

One of the new or de novo mutations researchers found in more than one affected individual in this study was a deletion of a region of chromosome 22. Dr. Karayiorgou had previously provided evidence that loss of genes in this region, 22q11.2, was responsible for introducing “new” or sporadic cases of schizophrenia in the population. This confirms 22q11.2 as the only known recurrent such mutation linked to schizophrenia.

“We have already demonstrated 22q11.2 to be involved in sporadic schizophrenia and we have made considerable progress in understanding the underlying biological mechanisms,” said Dr. Gogos. “Now, we have a new set of mutations that we can investigate. The more information we have about the biological basis for this disease, the more information we can provide to those who suffer from it and their families.”

“Such abnormal deletions or duplications of genetic material are increasingly being implicated in schizophrenia and autism,” explains National Institute of Mental Health Director Thomas R. Insel, M.D. “Now we have a dramatic demonstration that genetic vulnerabilities for these illnesses may stem from both hereditary and non-hereditary processes. This line of research holds promise for improved treatments – and perhaps someday even prevention – of developmental brain disorders.”

Karayiorgou and co-senior author Joseph A. Gogos, M.D., Ph.D., associate professor of physiology and neuroscience at Columbia University Medical Center, agree that the goal is for psychiatrists to be able to inform patients that they have a mutation that is causing their disease and ultimately to be able to tailor treatments to individual patients based on their specific mutation. This tailored treatment is a ways off, according to Dr. Karayiorgou, but she says patients and their families are relieved to know that there is a biological cause of their illness.

The researchers plan to extend their screen for additional de novo mutations by using increased resolution scans to study additional families. They also plan to scrutinize further genes affected by the identified mutations through human genetics and animal model approaches.

###

The first author of this study, Bin Xu, is also from CUMC. Co-authors include J. Louw Roos from the Department of Psychiatry and Elizabeth J. van Rensburg from the Department of Genetics at the University of Pretoria in Pretoria in South Africa, and Shawn Levy from the Microarray Shared Resource at Vanderbilt University in Nashville, Tenn.

This study was supported by the National Institutes of Health’s (NIH) National Institute of Mental Health (NIMH) and the Lieber Center for Schizophrenia Research at Columbia University Medical Center.

Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, in medical and health sciences education, and in patient care. The medical center trains future health care leaders at the College of Physicians & Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Established in 1767, Columbia’s College of Physicians & Surgeons was the first in the country to grant the M.D. degree. CUMC is home to the largest medical research enterprise in New York state and one of the largest in the United States. Visit cumclumbia.edu/.

Columbia Psychiatry is ranked among the best departments and psychiatric research facilities in the nation and has contributed greatly to the understanding of and current treatment for psychiatric disorders including depression, suicide, schizophrenia, bipolar and anxiety disorders, and childhood psychiatric disorders. Located at the New York State Psychiatric Institute on the NewYork-Presbyterian Hospital/Columbia University Medical Center campus in the Washington Heights community of Upper Manhattan, the department enjoys a collaborative relationship with physicians in various disciplines at Columbia University’s College of Physician and Surgeons. Visit columbiapsychiatry/.

Source: Susan Craig

Columbia University Medical Center

A World First: Dutch Invention Makes Unsuccessful Punctures A Thing Of The Past

On October 6, the VascuLuminator was introduced in the Netherlands. Dutch professor Ruud Verdaasdonk developed the device at University Medical Center (UMC) Utrecht. When the device is used, the chance of unsuccessful punctures drops from 13% to 2%.

Getting it right the first time

Many children and adults are frightened of having their blood drawn or having an intravenous line inserted. The procedure sometimes does indeed go wrong, and then another puncture is necessary. This is distressing, and what’s more, it increases the risk of bruises and complications. Dutch professor Ruud Verdaasdonk developed a device that makes it much easier for doctors to get it right the first time. He hit upon the idea because punctures were often unsuccessful in his young son, who has dark skin.

Veins can be hard to find

Some people have blood vessels that are harder to see, which makes it more difficult to insert a needle into a blood vessel for drawing blood or placing an intravenous line. For example, there is a greater risk of missing the blood vessel in babies because of their baby fat. Obese people’s veins are also deeper down, which means they are more difficult to find. In addition, the VascuLuminator is particularly suited for use in people with dark skin. Children with chronic diseases can also benefit, because they regularly undergo such procedures and the punctures are often unsuccessful. As a result, they are more likely to be frightened.

Giraffe

Children quickly dubbed the long, narrow device the “Giraffe.” The official name of the “VascuLuminator” refers to what it does. “Vascu” comes from the word “vascular” (vein), and “Luminator” stands for “illumination”: So, it is a device that illuminates veins. The VascuLuminator uses an infrared LED light that shines thorough a patient’s limb and makes it possible to see the blood vessels on a screen at the very same moment. This means the anesthesiologist or laboratory technician is able to have a normal view of the skin and puncture site, unlike other devices that project an image onto the hand. It works like a GPS: The device is used to navigate around the vascular system, so that the doctor or technician knows exactly where to insert the needle. What is also “handy” is that the VascuLuminator can be operated with only one hand.

Research

At UMC Utrecht, Natascha Cuper is studying how the VascuLuminator works, and, based on her work, will receive her PhD in early 2011: “This research has shown that by using the VascuLuminator, the percentage of unsuccessful punctures has dropped from 13% to 2%.” It is also more efficient, because the doctor needs less time to insert the needle right the first time in a child who is likely to be afraid.

Innovations in health care

The VascuLuminator was invented at UMC Utrecht. It was developed by Pontes Medical, a new cooperative venture involving three Dutch university medical centers (Academic Medical Center (AMC) in Amsterdam, UMC Utrecht, and VU University Medical Center (VUmc), also in Amsterdam) in the field of practical innovations in health care.

Source :

University Medical Center Utrecht (UMC Utrecht)

Pontes Medical

Grandparents, Older Adults Encouraged To Seek Help For A Sleep Disorder

September 9 is National Grandparents Day, a day to honor grandparents across America as important members of our families and communities. Grandparents play important roles in life, including that of guardian, comforter, and mentor. As they get older, however, several aspects of their lives change, including their sleep patterns. While older adults need about seven to eight hours of sleep each night, many often get less sleep, which may make them more susceptible to health problems.

“As we get older, our sleep is more easily disturbed,” says James P. Krainson, MD, of the South Florida Sleep Diagnostic Center in Miami and a spokesperson for the American Academy of Sleep Medicine (AASM). “Underlying health issues are often the cause of these disturbances. Arthritis and pain can cause frequent awakenings and interfere with falling asleep. Cardiovascular, neurologic, urologic and psychologic disturbances can likewise play havoc with our sleep. In fact, most all medical problems can disturb our sleep, and the older adults’ sleep is most vulnerable.”

Many older adults often have more trouble falling asleep than persons in other age groups. A study of adults over the age of 65 found that 13 percent of men and 36 percent of women take more than 30 minutes to fall asleep.

There are many other possible explanations for changes in older adults’ sleep patterns, says Dr. Krainson. Older adults may produce and secrete less melatonin, the hormone that promotes sleep. They may also be more sensitive to changes in their environment, such as noise, and this may cause them to awaken. Further, older adults may also have other medical and psychiatric problems that can affect their sleep, says Dr. Krainson, adding that researchers have noted that people without major medical or psychiatric illnesses report better sleep.

Several studies that outline the negative consequences of bad sleep among older adults were presented at SLEEP 2007, the 21st Annual Meeting of the Associated Professional Sleep Societies, this past June:

пЃ® Cognitive behavioral therapy successfully improves both immediate and long-term self-reported sleep and pain in older osteoarthritis patients. This demonstrates that improving sleep can be “analgesic” in older osteoarthritis patients, and that techniques to improve sleep should be considered for addition to treatment programs for pain management in osteoarthritis and possibly other pain-states.

– Regular aerobic exercise, combined with sleep hygiene education, improves sleep and quality of life in older adults with chronic insomnia.

– Untreated sleep complaints may pose a risk for falls.

– Older adults who reported engaging in shorter and less frequent naps during the day also reported spending more time asleep at night. Such older individuals also experienced more sleep time and slept more efficiently at night.

– A sleep-related breathing disorder may be associated with impairments in cognitive function in older men.

– Objectively determined estimates of short sleep were strongly related to obesity in older men and women.

Dr. Krainson notes that several studies published in recent issues of the journal SLEEP have some interesting findings about older persons and sleep:

– The effects of insomnia are different in older and younger people. While associations between insomnia and separated, divorced or widowed marital status were strongest in younger age groups, longer bouts with insomnia were more common in the older population, who are also more likely to be taking types of sedatives that have particular problems with addiction and side effects.

– As sleep quality and quantity typically decrease with age, objectively measured differences in the amount of sleep a healthy older man gets can affect his level of testosterone in the morning.

– A brief behavioral treatment for insomnia appears to be a promising intervention for older adults who suffer from insomnia.

According to Dr. Krainson, some of the more common sleep disorders in older adults include:

– Insomnia affects almost half of adults 60 and older.

– Obstructive sleep apnea (OSA) can elevate the risk for high blood pressure, stroke, heart disease, and cognitive problems. Snoring, a symptom of OSA, is a very common condition affecting nearly 40 percent of adults, and is more common among older people.

– Restless legs syndrome, where one experiences uncomfortable feelings in the legs, affects more than 20 percent of people 80 years and older.

– Periodic limb movement disorder, a condition that causes people to jerk and kick their legs every 20-40 seconds during sleep, is evident in almost 40 percent of older adults.

Not sleeping well can lead to a number of problems. Older adults who have poor nighttime sleep are more likely to have a depressed mood, attention and memory problems, excessive daytime sleepiness, more nighttime falls and use more over-the-counter or prescription sleep aids. In addition, recent studies associate lack of sleep with serious health problems such as an increased risk of obesity, cardiovascular disease and diabetes.

Despite obstacles many older adults have to overcome in order to get a good night’s sleep, Dr. Krainson says that it does not mean they are doomed to chronic sleep deprivation. While most people require seven to eight hours of sleep a night to perform optimally the next day, older adults might find this harder to obtain, says Dr. Krainson, adding that they must be more aware of their sleep and maintain good sleep hygiene by following these tips:

– Establishing a routine sleep schedule.

– Avoiding utilizing bed for activities other than sleep or intimacy.

– Avoiding substances that disturb your sleep, like alcohol or caffeine.

– Not napping during the day. If you must snooze, limit the time to less than one hour and no later than 3 p.m.

– Stick to rituals that help you relax each night before bed. This can include such things as a warm bath, a light snack or a few minutes of reading.

– Don’t take your worries to bed. Bedtime is a time to relax, not to hash out the stresses of the day.

– If you can’t fall asleep, leave your bedroom and engage in a quiet activity. Return to bed only when you are tired.

– Keep your bedroom dark, quiet and a little cool.

Dr. Krainson says that, although sleep patterns change as people age, disturbed sleep and waking up tired every day are not part of normal aging. Those who have trouble sleeping are advised to see a sleep specialist at a facility accredited by the AASM.

“Be prepared to tell the doctor how you spend your day and night, including your medicines, fluid intake and activities so that they will have all the information needed to decide how best to help you,” says Krainson.

For a listing of AASM-accredited facilities in your area, visit SleepCenters.

AASM is a professional membership organization dedicated to the advancement of sleep medicine and sleep-related research.

aasmnet

Smoking Indicator Of Alcohol Misuse

Where there is cigarette smoking there is probably misuse of alcohol too, according to a study by Yale School of Medicine researchers in the Archives of Internal Medicine.

“This means cigarette smoking status can be used as a clinical indicator for alcohol misuse, which presents an opportunity for intervention,” said the principal investigator, Sherry McKee, assistant professor of psychiatry.

She said that although brief screening and brief intervention provided in primary care settings are effective, clinicians do not frequently screen for alcohol misuse. This is a matter of concern because 26 percent of the U.S. population is drinking at hazardous levels, which puts them at increased risk for alcohol-related consequences such as injuries from motor vehicle crashes, hypertension, depression, and certain cancers.

“Only an estimated 30 percent of individuals who had a primary care visit reported being screened for an alcohol or drug use problem,” McKee said. “Physicians are much more likely to ask patients whether and how often they smoke.”

She and her collaborators arrived at their conclusions after analyzing data obtained from 42,374 adults in a national epidemiological survey on alcohol misuse and other related conditions. Following guidelines that physicians use to assess tobacco and alcohol use, they found that non-daily smokers are five times more likely to have a problem with alcohol compared to people who have never smoked. Daily smokers are three times more likely to have an alcohol problem.

“This is the first study to document that individuals who are smokers, but don’t smoke every day, have the highest rates of problem drinking,” McKee said. “Using smoking status as a ‘red flag’ for more aggressive assessment of alcohol use is a highly feasible and clinically sensible approach to screening.”

The findings, she said, highlight the importance of physicians adopting standard alcohol screening questions into their practice.

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) defines hazardous drinking as exceeding either daily or weekly drinking limits. Men should consume no more than four drinks in a day, and no more than 14 drinks in a week. Women should consume no more than three drinks in a day, and no more than seven drinks in a week. Additional information about NIAAA guidelines concerning problem drinking can be found here .

The NIAAA and the Robert Wood Johnson Foundation supported the study.

Archives of Internal Medicine 167: 716-721 (April 9, 2007)

yale.edu

Salt’s Effect On Blood Pressure Decreased By Physical Activity

The more physically active you are, the less your blood pressure rises in response to a high-salt diet, researchers reported at the American Heart Association’s Nutrition, Physical Activity and Metabolism/Cardiovascular Disease Epidemiology and Prevention 2011 Scientific Sessions.

“Patients should be advised to increase their physical activity and eat less sodium,” said Casey M. Rebholz, M.P.H., lead author of the study and a medical student at the Tulane School of Medicine and doctoral student at the Tulane University School of Public Health & Tropical Medicine in New Orleans. “Restricting sodium is particularly important in lowering blood pressure among more sedentary people.”

Investigators compared study participants’ blood pressure on two one-week diets, one low in sodium (3,000 mg/day) and the other high in sodium (18,000 mg/day).

The American Heart Association recommends consuming less than 1,500 mg/day of sodium.

If a person’s average systolic blood pressure (the top number in the reading, measured when the heart is contracting) increased 5 percent or more from the low-sodium to the high-sodium regimen, the researchers labeled them as high salt-sensitive.

Based on physical activity questionnaires, researchers divided participants into four groups ranging from very active to quite sedentary.

The average increases in systolic blood pressure after switching from low to high sodium, adjusted for age and gender, were:
5.27 mm Hg in the least active group
5.07 mm Hg in the next-to-lowest activity group
4.93 mm Hg in the next to highest activity group
3.88 mm Hg in the most active group

Compared with the sedentary group, the odds of being salt-sensitive, adjusted for age and gender, fell:
10 percent in the next-to-lowest activity group
17 percent in the next-to-highest activity group
38 percent in the most active group

“In all the analyses we found a dose-response relationship with the more activity, the better,” Rebholz said.

The participants were 1,906 Han Chinese adults (average age 38) in the Genetic Epidemiology Network of Salt Sensitivity (GenSalt), a large project to identify genetic and environmental factors contributing to salt sensitivity. Siblings and their parents were invited to become involved in GenSalt if at least one sibling had pre-hypertension (blood pressure between 120/80 and 139/89 mm Hg) or stage-1 hypertension (between 140/90 and 159/99 mm Hg). No one was on blood pressure medication during the study.

The GenSalt project is located in rural China because the homogeneous population makes it more likely that genes influential to blood pressure control will be identified.

“The study needs to be repeated, but I suspect that the relationship between physical activity and salt-sensitivity will apply to other populations,” Rebholz said.

Notes:

Co-authors are: Dongfeng Gu, Ph.D.; Jing Chen, M.D., M.S.; Jian-feng Huang, M.D.; Jie Cao, M.D., M.S.; Ji-chun Chen, M.D., M.S.; Jianxin Li, M.D.; Fanghong Lu, M.D.; Jianjun Mu, M.D.; Jixiang Ma, M.D.; Dongsheng Hu, M.D., M.S.; Xu Ji, M.D.; Lydia A. Bazzano, M.D., Ph.D.; Depei Liu, M.D., Ph.D.; and Jiang He, M.D., Ph.D.

Author disclosures and sources of funding are on the abstract.

Source:
American Heart Association

U Of MN Adult Stem Cell Research Shows Promise For Transplant Therapies

University of Minnesota stem cell researchers, together with collaborators at Stanford University, have successfully used adult stem cells to replace the immune system and bone marrow of mice, offering the promise of new therapies for people in the future. With this advance and other recent discoveries, the researchers are winning over previous skeptics.

For decades, researchers have tried in the lab to expand hematopoietic stem cells (cells that give rise to the blood system). Success in this venture would mean increasing the supply of cells available for bone marrow transplant patients. The researchers used multipotent adult progenitor cells (MAPCs), which can be isolated from bone marrow and have the ability in the laboratory to differentiate into different specific types of cells such as liver, bone and neural cells.

Catherine Verfaillie, M.D., director of the University’s Stem Cell Institute, first identified MAPCs in 2001. Since then, many in the scientific community have been skeptical of their existence and their functioning as Verfaillie has described. This skepticism mostly arose due to difficulty in reliably growing these cells, which made reproduction in other labs problematic. Since their identification, the methods to isolate and grow MAPCs have been improved (see publication in Experimental Hematology, October 2006). This latest research will be available online from the Journal of Experimental Medicine on January 15; it will appear in the Jan. 22, 2007; print edition of the journal.

Verfaillie and her team isolated MAPCs from mice and expanded them for at least 80 doublings in the lab. They then transplanted the cells into mice that received radiation and thus had no immune system.

“The cells not only survived when transplanted but they completely repopulated the blood system of the mice,” Verfaillie said. The MAPCs did not differentiate into other cell types, such as liver or brain cells, nor did they form tumors in any animals.

Irving Weissman, M.D., Stanford University professor of pathology and developmental biology and co-author on the manuscript, was admittedly skeptical at first about the ability of MAPCs to contribute to blood formation. This skepticism made him an ideal collaborator, as he insisted on rigorous evaluation of the data. “These experiments point to potential precursors of blood forming stem cells in an unexpected population of cultured cells,” said Weissman, who directs Stanford’s Institute for Stem Cell Biology and Regenerative Medicine.

“Scientists must now understand that mouse MAPCs can make normal blood, and we need to explore how they do it,” Weissman said. “It is very important to note that MAPCs were not themselves radioprotective, thus they alone could not be used in patients in whom the bone marrow is totally eliminated due to radiation or chemotherapy, but it is still remarkable that they can give rise to blood cells.”

Bruce Blazar, M.D., professor of Pediatrics at the University of Minnesota, who is co-author of the paper, has continued with experiments conducted in his laboratory after the completion of this study. “Our results independently confirmed in an additional series of animals the finding that MAPCs can make blood cells,” Blazar said. While more research will need to be done and studies need to be replicated with human MAPCs before human treatments are available, this research suggests that MAPCs could be used to help reduce rejection of tissue transplants. In the future, physicians may be able to introduce MAPCs in the blood system of the recipient to trick the immune system into accepting the MAPC-generated transplanted tissue. In addition to this paper, in the last few months further evidence of MAPCs existence and function was published in scientific peer-reviewed journals based on research done at the University and other research institutions across the world. “I am pleased to see this science replicated at other research universities,” Verfaillie said. “Now there is further confirmation that the MAPCs could be a valid source of new therapies.” Verfaillie added this research shows the importance of continuing to pursue all types of stem cell research, adult and embryonic, because scientists do not yet know which cell type will prove most promising for treating a particular disease.

MAPCs found in pigs

Verfaillie and colleagues had previously isolated MAPCs from bone marrow of humans, mice and rats. But in order to study potential treatments for people, the research needs to be tested in animal models that are more physiologically similar to humans. In the November 2006 issue of the journal Stem Cells, Verfaillie described how MAPCs can be isolated from pig bone marrow. Pigs are routinely used as a model for humans, especially in cardiovascular research. The researchers were able to isolate and grow the pig MAPCs with some modifications much like they identify human, mouse and rat MAPCs. After isolating the MAPCs, the scientists were able to differentiate the cells into different types of cells that give rise to bone, smooth muscle, fat, cartilage, endothelium (cells that line blood vessels), and cells that are similar to liver and brain cells.

MAPCs and endothelial cells

A team of researchers from the University of Navarra in Pamplona, Spain, the Catholic University of Leuven, Belgium, and the University of Minnesota published in the journal Blood (November 2006) on the ability of MAPCs to differentiate into two types of endothelial cells, which line the inner walls of blood vessels. By adding various growth factors, the researchers, led by Felipe Prosper, M.D., of Spain, were able to make the human MAPCs differentiate into both arterial endothelial and venous endothelial cells in both a laboratory environment and in mice. Like the studies showing that MAPCs can make blood when transplanted, this is a second example demonstrating that MAPCs can contribute to a tissue when grafted in vivo. “This work provides the first evidence that human MAPCs can be induced to differentiate into the different types of cells needed to form arteries,” Prosper said. “This may suggest future clinical applications for MAPCs in diseases and conditions such as stroke and heart attack.” In addition, this discovery provides researchers a model to study how human arteries and veins develop.

MAPCs create smooth muscle

Verfaillie and colleagues published in the December 2006 issue of the Journal of Clinical Investigation that MAPCs can generate smooth muscle cells in the laboratory. Smooth muscle cells contract, often without conscious control, regulating body functions such as blood pressure and movement of food through the digestive system.

“While previous research has demonstrated that various types of stem cells can turn into cells that express the proteins consistent with smooth muscle, this is the first study that shows that the cells we generated have the same functional properties as smooth muscle, as well as express the same proteins,” said Jeffrey Ross, Ph.D., research associate at the Stem Cell Institute. These observations suggests that in the future, researchers may be able to make functional tissue in the lab from MAPCs, such as engineering a new blood vessel for use in bypass surgery. As smooth muscle cells are involved in many diseases like hypertension or asthma, the ability to generate smooth muscle cells with all functional attributes of this cell type also opens the possibility that they can be used to screen new drugs in the lab to determine how the cells react to potential new therapies.

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Contact: Sara E. Buss

University of Minnesota

House Approves Stem Cell Research Enhancement Act; Bush Threatens Veto

The House on Thursday voted 247-176 to pass a bill (S 5) that would allow federal funding for research using stem cells derived from human embryos originally created for fertility treatments and willingly donated by patients, the New York Times reports (Zeleny/Wade, New York Times, 6/8).

Federal funding for human embryonic stem cell research is allowed only for research using embryonic stem cell lines created on or before Aug. 9, 2001, under a policy announced by President Bush on that date. The Senate in April voted 63-34 to pass the bill, called the Stem Cell Research Enhancement Act of 2007. The measure differs from a House-approved bill (HR 3) of the same name because it includes language that would require NIH to research and fund methods of creating embryonic stem cell lines without destroying embryos (Kaiser Daily Women’s Health Policy Report, 6/1).

Bush — who is attending the Group of Eight industrialized nations 2007 summit in Heiligendamm, Germany — said he plans to veto the measure after he returns June 11 (George, CQ Today, 6/7). House Speaker Nancy Pelosi (D-Calif.), Senate Majority Leader Harry Reid (D-Nev.) and other Democratic lawmakers on Thursday at a ceremony marking the bill’s passage called on Bush to not veto the legislation, CongressDaily reports (Edney, CongressDaily, 6/7).

Vote Details
According to the Times, 210 Democrats and 37 Republicans in the House voted for the measure, which is 35 votes short of what would be needed to override a presidential veto. Sixteen Democrats and 160 Republicans voted against the legislation, the Times reports. If Bush vetoes the measure, the Senate would attempt to override the veto first; however, even counting the three Democratic senators that were absent for the original vote, the chamber is one vote short of the two-thirds majority needed to override a veto, the Times reports (New York Times, 6/8).

Comments
Bush in a statement said, “I am disappointed the leadership of Congress recycled an old bill that would simply overturn our country’s carefully balanced policy on embryonic stem cell research.” He added that under the bill, “American taxpayers would for the first time in our history be compelled to support deliberate destruction of human embryos. Crossing that line would be a grave mistake. For that reason, I will veto the bill.”

Rep. Diana DeGette (D-Colo.) — noting a Gallup poll that indicates that 64% of U.S. residents support embryonic stem cell research — said, “The Senate gets it. The public gets it. The House gets it. Why doesn’t the president of the United States get it?” DeGette added that “stem cell research is the most promising source of potential treatments and cures,” but “[u]nfortunately, because of the stubbornness of [Bush], these people continue to suffer and wait” (Weiss, Washington Post, 6/7).

According to the Times, several Republicans who voted against the measure cited new research reported on Wednesday (New York Times, 6/8). Three independent teams of scientists said they have developed experimental approaches using the skin cells of mice to create embryonic stem cells without creating or destroying embryos (Kaiser Daily Women’s Health Policy Report, 6/7). Bush said, “Recent scientific developments have reinforced my conviction that stem cell science can progress in ethical ways.” DeGette said that “this new scientific research should not be used as an excuse to say that it is a substitute for embryonic stem cell research” (New York Times, 6/8).

Sen. Dianne Feinstein (D-Calif.), a sponsor of the bill, said, “We will continue to [pass the legislation] again, and again, and again until this bill becomes law” (Epstein, San Francisco Chronicle, 6/8). House Minority Leader John Boehner (R-Ohio) said, “This is politics. This is not about expanding research.” He added, “They understand clearly that the president has vetoed this bill in the past and will veto it again” (New York Times, 6/8).

Broadcast Coverage
Several broadcast programs on Thursday reported on the House vote and studies released on Wednesday about embryonic stem cells.
CBS’ “Evening News”: The segment includes comments from Bruce Stillman of Cold Spring Harbor Laboratory; David Stevens, CEO of the Christian Medical Association; Evan Snyder of the Burnham Institute for Medical Research; and Reid (LaPook, “Evening News,” CBS, 6/7). Video of the segment is available online.

C-SPAN’s “Washington Journal”: The segment includes a discussion with Reps. James Lagevin (D-R.I.) and Dave Weldon (D-Fla.) (“Washington Journal,” C-SPAN, 6/7). Video of the segment is available online.

MSNBC: The segment includes comments from Pelosi; Reps. Ed Perlmutter (D-Colo.), Mike Pence (R-Ind.) and Randy Neugebauer (R-Texas); Kathrin Plath of the University of California-Los Angeles; and Karl Robb, an advocate for embryonic stem cell research (Potts, MSNBC Web site, 6/7). Video of the segment is available online.

NPR’s “Day to Day”: The segment includes a discussion with NPR science correspondent Joe Palca (Brand, “Day to Day,” NPR, 6/7). Audio of the segment is available online.

PBS’ “NewsHour with Jim Lehrer”: The segment includes a discussion with Kenneth Miller, a stem cell biologist at Brown University, and Rick Weiss, a science reporter for the Washington Post (Brown, “NewsHour with Jim Lehrer,” PBS, 6/7). Audio and a transcript of the segment are available online. Video will be available Friday afternoon.

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