‘Reverse-Ecology’ Tool Demonstrated By Analysis Of Bread Mold Genomes

In a demonstration of “reverse-ecology,” biologists at the University of California, Berkeley, have shown that one can determine an organism’s adaptive traits by looking first at its genome and checking for variations across a population.

The study, to be published the week of Jan. 31 in the journal Proceedings of the National Academy of Sciences, offers a powerful new tool in evolutionary genetics research, one that could be used to help monitor the effects of climate change and habitat destruction.

The researchers scanned the genes of 48 different strains of Neurospora crassa, a type of red bread mold commonly used in genetics research. It is considered a model microbe because different strains can be mated and grown very quickly, and its growth occurs in a light-sensitive daily cycle that has been useful for studying circadian rhythms.

Yet for all its popularity in the lab, little was known about this fungus in its natural habitat, so the researchers specifically chose wild samples of the microbe from the Caribbean basin, South America and Africa. From this population-wide analysis, they found a striking pattern of variation in two regions of the genome that indicated the action of natural selection.

Within one of these regions, they found a gene that is known to be important to survival at cold temperatures, and posited that genes in the other region might play the same role. They then showed that members of the population that contained unique variants of their candidate cold-tolerant genes lived in regions with lower minimum temperatures – up to 9 degrees Celsius – on average and were able to grow better at cold temperatures than were strains found in more tropical climates.

The researchers also grew wild strains of Neurospora crassa in the lab alongside strains where the candidate cold-tolerant genes had been deleted from the genome, keeping all things the same except for the temperature. They confirmed that the strains with the genes for cold tolerance disabled fared more poorly in chillier temperatures.

“This is the first time that population genomics has been used to find genes important for adaptation without any idea of the environmental parameters, phenotype, candidate genes or even the population boundaries,” said the study’s principal investigator, John Taylor, UC Berkeley professor of plant and microbial biology.

Taylor pointed out that the normal route for adaptation studies is to first look at obvious differences – such as hair or skin color – between two closely related organisms. Scientists next observe the environment in which the organism lives to see if it might explain those differences, and then examine the genes to see if there is evidence of natural selection.

For example, the researchers referred to a 2003 study noting that rock pocket mice with tan-colored fur are often found among light-colored rocks, while those with black fur were found on dark lava flows. They identified the genetic basis of this adaptive trait by targeting genes for further study that were known to be involved in pigmentation and showed that different gene variants were associated with the different habitats.

“For our study, we turned this around, beginning with genes that showed evidence of selection, and then looking at the environmental factors that might influence those genes,” said Taylor.

This “reverse-adaptation” approach is especially useful when studying microbes, the researchers argued.

“Microbes are inconspicuous by nature and, unlike mice which can have different colored coats, different strains and species look pretty much the same,” said study lead author Christopher Ellison, a UC Berkeley graduate student in plant and microbial biology.

As if to demonstrate this point, the researchers discovered that what had been considered a single group of interrelated strains was instead two distinct populations.

The relative ease of studying a microbe such as Neurospora crassa in the lab may make it an appealing tool to monitor the impact of environmental stress, the researchers said.

“If temperature is a key adaptive factor in populations of fungi and microbes in general, this could have important implications in the study of climate change,” said Ellison. “Adaptation is a crucial part of evolution, so microbes could be used to monitor global temperature change.”

Notes:

Other UC Berkeley co-authors of the study are Rachel Brem, professor of molecular and cell biology; N. Louise Glass, professor of plant and microbial biology; and members of the Glass Lab – Charles Hall, post-doctoral researcher, and staff researchers David Kowbel and Juliet Welch.

The National Institute of General Medical Sciences helped support this research.

Source:
Sarah Yang
University of California – Berkeley Continue reading

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Alzheimer’s Enzyme Acts As A Tumor Suppressor

Researchers at Burnham Institute for Medical Research (“Burnham”) have provided the first evidence that gamma-secretase, an enzyme key to the progression of Alzheimer’s, acts as a tumor suppressor by altering the pathway of epidermal growth factor receptor (EGFR), a potential treatment target for cancer. Expedited to publication online by Proceedings of the National Academy of Sciences, these findings reveal a limitation of targeting gamma-secretase for treatment of Alzheimer’s and potentially other diseases.

Amyloid precursor protein (APP) is found inside all cells. Though its function is unknown, it is associated with Alzheimer’s in the following way. APP can be cleaved by the enzymes beta-secretase and gamma-secretase, sequentially. Upon gamma-secretase cleavage, amyloid-beta (AB) peptides are dispelled into the extracellular matrix region and eventually aggregate into senile plaques, characteristic of Alzheimer’s.

Residing inside cells, gamma-secretase is a complex of four proteins, including a family of proteins known as the presenilins (PS). Mutations in PS are found in approximately 5% of individuals suffering Alzheimer’s, resulting in early onset of the disease.

At the center of the activities governing AB production is gamma-secretase, the subject of intensive interest as a potential therapy target for Alzheimer’s. Mice deficient in PS/gamma-secretase activity tend to develop skin cancer. EGFR is known to be upregulated in a variety of tumors, including various skin cancers. Elevated EGFR levels in tumors are linked with poor clinical prognosis and tumor resistance to chemotherapy. EGFR is therefore the subject of intensive investigation by pharmaceutical companies as a potential treatment target for cancer.

The Xu laboratory set out to determine whether there might be a correlation between PS/gamma-secretase activity and EGFR. They examined mice with reduced PS gene dosage and found that there is an inverse relationship between the level of EGFR and PS. They discovered that APP intracellular domain (AICD), another cleavage product of PS/gamma-secretase, negatively regulates transcription of the EGFR gene by binding the gene’s promoter region. They also demonstrated that deficient levels of APP correlate with increased levels of EGFR.

“Alzheimer’s disease and cancer are two of the most important medical research areas today”, said Huaxi Xu, associate professor and program director at Burnham. “We believe that our studies, which reveal a key role of Alzheimer’s PS/gamma-secretase-generated APP metabolite AICD in gene transcription and in EGFR-mediated tumorigenesis, should have a significant impact on both fields of research.”

This research was supported in part by grants from the Alzheimer’s Association, the American Health Assistance Foundation, and grants from the National Natural Science Foundation in China, and the National Institutes of Health.

Burnham Institute for Medical Research conducts world-class collaborative research dedicated to finding cures for human disease, improving quality of life, and thus creating a legacy for its employees, partners, donors, and community. The La Jolla, California campus was established as a nonprofit, public benefit corporation in 1976 and is now home to three major centers: a National Cancer Institute-designated Cancer Center, the Del E. Webb Center for Neurosciences and Aging, and the Infectious and Inflammatory Disease Center. Burnham today employs more than 750 people and ranks consistently among the world’s top 20 organizations for the impact of its research publications. In 2006, Burnham established a center for vascular mapping and bionanotechnology in Santa Barbara, California. Burnham is also establishing a campus at Lake Nona in Orlando, Florida that will focus on diabetes and obesity research and will expand the Institute’s drug discovery capabilities, employing over 300 people. For additional information about Burnham and to learn about ways to support its research, visit burnham/.

Contact: Nancy Beddingfield

Burnham Institute Continue reading

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Antibiotic-resistance, Avian Flu And Other Viral Epidemics At ECCMID In Nice

16th European Congress of Clinical Microbiology and Infectious Diseases

Nice, France – Globalisation is a phenomenon involving ever wider spheres: economic, social, cultural, and religious. But these are not the only areas to be affected. Fading national boundaries caused by intensification of commercial trading and increased migration, as well as the tendency for more “exotic” tourism, has caused a globalisation of infectious diseases that is involving all European countries.

This is the background to the importance of a European organisation such as ESCMID (European Society of Clinical Microbiology and Infectious Diseases), which pursues as its major goal the improvement of the diagnosis, prevention and clinical management of infections, including those with a high public health impact.

Indeed, there is currently a paradoxical situation: despite the enormous progress made in medical science, there are new diseases emerging, either as adaptations of existing diseases which lose their responsiveness to traditional treatments, or as new diseases based on previously unknown pathogens for which a mode of transmission and control still have to be established and treatment regiments still to be developed.

The ECCMID (European Congress of Clinical Microbiology and Infectious Diseases), organized by ESCMID in Nice from 1 – 4 April 2006, is the most important annual event of its kind in Europe. Now in its 16th edition, the Congress unites a large number of European and other international experts and over 6000 delegates with the aim of increasing knowledge and discussing future research, treatment and public health strategies needed to tackle infectious diseases.

Resistance to antibiotics

The first problem, the loss of efficacy in treating some common infectious diseases, is predominantly due to antibiotic resistance. The alarm raised by infection experts is serious: the dramatic increase of bacteria resistant to antibiotics paralleled by a lack of new antibiotics has already led to infections being no longer curable.

In fact, it has been seen that some pathogens, particularly those occurring in hospitals (e.g. Staphylococcus aureus and Pseudomonas aeruginosa), are now extensively resistant to widely used antibiotics. Furthermore, recent studies have demonstrated that genes conveying antibiotic resistance can spread between different strains even across species barriers. Combined, all of the above leads to an ever increasing number of difficult-to-treat bacterial infections. In the case of Pseudomonas, but now even in the case of common and “easy-to-treat” bacteria such as Escherichia coli, the most recent and dangerous mechanisms of resistance are the so-called “carbapenemase” enzymes, which attack and destroy the most frequently used antibiotics and make bacteria, which produce these enzymes, resistant to all drugs.

The problem of antibiotic-resistance is further worsened by the disinvestment of several pharmaceutical companies in the field of antibiotic research and development and the resulting shortage of new drugs.

The experts at ECCMID therefore consider measures to contain antibiotic resistance by optimally using the currently available drugs absolutely essential.

“The key to controlling the development of antibiotic resistance”, explains Prof. Hermann Goossens of the Department of Medical Microbiology at Antwerp University Hospital, Edegem, Belgium, “is the ability to choose antibiotics selectively.” Making a precise diagnosis and understanding the probable aetiology should enable the correct treatment of the main community-acquired infections. “However, in order to do this,” continues Goossens, “it is very important that fast, new diagnostic tools are developed for the identification of diseases of bacterial origin. This would permit the prescription of antibiotics only in the case of real need.”

Although the main cause of antibiotic resistance in community-acquired infections is inappropriate prescribing of antibiotics, another important factor is patients’ non-compliance.

It has, in fact, been demonstrated that the therapeutic efficacy of antibiotics also depends heavily on patients respecting the prescriptions and instructions received from their doctors about the correct dose, the dosing interval and the duration of treatment.

Prevention is another aspect that should not be forgotten when discussing antibiotic resistance. It was found that the introduction of the pneumococcal conjugate vaccine in Europe often coincided with a decrease in the resistance to macrolides and to penicillin. Streptococcus pneumoniae, also called pneumococcus, is one of the most important pathogens of the respiratory tract, with a high frequency of resistance to commonly used antibiotics.

Another important factor for treating infectious diseases and surveillance of resistance is the definition of “susceptible” or “resistant” pathogens; paradoxically, these definitions are not the same in all European countries.

In this regard, ESCMID has convened a strategically important committee, called EUCAST (European Committee on Antimicrobial Susceptibility Testing), with the goal to produce uniform guidelines for susceptibility testing of antibacterial drugs and to define “breakpoints” (that is, the values differentiating susceptible form resistant bacteria) in Europe.

The importance of tackling resistance through co-ordinated action of all European countries is further confirmed by the support that ESCMID gave to the creation of GRACE (Genomics to combat Resistance against Antibiotics in Community-acquired LRTI in Europe), a network of excellence financed by the European Union which brings together major European experts to increase knowledge, guarantee the practical application of research, develop new diagnostic tests and improve the prescribing habits and training of health care workers.

Avian flu

Another issue discussed in particular detail by the experts at ECCMID was avian flu. “Also in this case,” said Albert Osterhaus, Head of the Department of Virology and Director of the National Influenza Centre, Erasmus Medical Centre, Rotterdam, “a better co-ordination is needed in Europe among all the stakeholders, researchers, public health care workers and veterinarians in order to prevent a possible pandemic. This can be achieved by creating a European task force to share knowledge and to tackle the possible risks.”

Osterhaus continued, “So far, the crisis in Europe has predominantly affected the avicultural sector. Community regulations to safeguard this production chain and those working in the sector are needed. The most important message to convey to the population is that of not confusing the problems related to the avicultural sector with the possibility of a pandemic developing.”

Scientific societies, such as ESCMID, which have access to a network of experts throughout the continent, can contribute to this co-operation by acting as interlocutor with academia, health authorities of individual states, the European Commission and the EDCD (European Centre for Disease Prevention and Control).

Ragnar Norrby, Director of the Swedish Institute for Infectious Diseases Control in Stockholm and current President of the ESCMID, re-addressed the “basic” information to be conveyed to the population, confirming that “avian flu is a disease of birds and that the risk of humans catching the infection, although theoretically possible, is very low and limited to those people who have direct contact with infected birds. However, as of today, there is no convincing evidence of man-to-man transmission.”

Turkey, the only large reservoir so far observed in Europe, is a paradigmatic example: the cases of transmission of the virus to humans was limited mainly to the rural areas, where direct contact with animals is frequent, and did particularly involve children who have deliberately touched dead or sick birds. Also in these cases, the danger can be limited by applying ordinary rules of hygiene such as frequent hand-washing, not eating meat that is of suspicious provenance or poorly cooked and prohibiting hunting within a 10 km radius of where an animal infected by H5N1 has been found.

Although the H5N1 virus (responsible for avian flu) can cross the barriers between species and infect other animals, such as cats, so far the virus has not spread from cats to different species.

Concerning the possibility of a pandemic to occur, Norrby emphasized that “the worldwide spread of influenza among humans occurs when a new influenza virus develops, usually as a result of recombination of genetic material from a human influenza virus with genetic material from an animal influenza virus. A pandemic virus can, therefore, arise anywhere in the world, but the probability is higher in countries with a high population density and many domestic birds and pigs such as in Asia or Africa.”

“So far,” continued Norrby, “pandemics have developed at irregular intervals (Spanish ‘flu in 1918, the Asiatic pandemic of 1957 and the one arising in Hong Kong in 1968). Therefore, although it can be presumed that another will occur, no-one is able to predict when and with what variant of the influenza virus”.

Norrby concluded, “it is important to emphasize two aspects: although the high density of H5N1 virus in birds from all over the world (and particularly in Asian and African countries) facilitates the development of a pandemic infection caused by the virus, the fact that millions of Asians have probably been in contact with infected, dead birds since 1997 (the year in which the first severe spread of avian flu occurred in Hong Kong) without the virus having mutated into a pandemic variant, speaks against a variant of H5N1 virus becoming a pandemic virus.”

As far as regards the availability of a human vaccine against avian flu, it was repeated during the ECCMID Congress that large-scale production of such a vaccine requires from four to six months. Considering that avian influenza has had a seasonal trend so far, affecting the population during the winter in countries with a temperate climate, it is probable that if a vaccine is needed it will be scarce during the first wave of infections, but fully available for the second season.

The most important antiviral drug on the market is oseltamivir (Tamiflu), since it has few side effects and is easy to administer. It is important to highlight that oseltamivir can be used for prophylaxis, but considering that the influenza season lasts four to six months it is not feasible to store the supplies necessary to administer the drug to a large number of people. Although studies have not been carried out in patients infected by H5N1, it has been documented that in order to reduce the duration and the severity of symptoms, oseltamivir-based treatment must be administered within 48 hours of the onset of the symptoms. It is also important to remember that treatment with antiviral agents can lead to the development of resistance.

Finally, it should be appreciated that – even in the absence of a vaccine against avian influenza – primary prevention, in particular vaccination against “common” influenza and pneumococcal respiratory infections, plays an essential role in the defence against a possible pandemic.

In fact, immunization could increase resistance to strains never previously encountered, such as a potentially pandemic virus. For example, in the case of the H5N1 strain, it is known that N1 (neuroaminidase 1) is contained in other viruses and vaccines. It is, therefore, possible that a previous infection or vaccination with virus containing N1 can provoke a certain response that then remains in the immunological “memory” of the individual.

Antipneumococcal vaccination should also play a strategic role in prevention, since it has been demonstrated that a considerable proportion of the pulmonary complications in previous pandemics was linked to superimposed bacterial infections, including those caused by pneumococci.

Chikungunya

During the ECCMID another epidemic was discussed: chikungunya, a rare viral disease transmitted by mosquitoes (Aedes albopictus). This epidemic appeared one year ago in La RŠ¹union, where 186,000 cases, including 93 deaths, have been registered so far. The infection has spread to Mayotte (924 cases), to the Seychelles (4650 suspected cases), to Mauritius (2553 cases notified, of which 1173 confirmed) and to Madagascar (sporadic cases). In Europe “imported” cases have been reported in France (n=160), Switzerland (n=12) and Germany (n=4).

The current level of risk of chikungunya (a fever that causes violent joint pains) being introduced into Europe is low, given the unfavourable climatic conditions in this period of the year, although the risk cannot be excluded completely. There is lack of consensus on whether there will be a real risk of autoctonous spread of the virus in the warmer season, when the number of mosquitoes increases.

What is certain, as concluded by the experts meeting at the ECCMID, is the need to activate close monitoring of the epidemic at a European level and to identify efficient diagnostic tools.

escmid

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Emerging Drug Class May Enhance Red Blood Cell Production In Anemic Patients

FINDINGS: By determining how corticosteroids act to increase production of red blood cell progenitors, Whitehead Institute researchers have identified a class of drugs that may be beneficial in treating some erythropoietin-resistant anemias. One such anemia is Diamond-Blackfan anemia (DBA), which is frequently treated with corticosteroids, despite their severe side-effects. The identified class of drugs may be able to treat other anemias, including those resulting from trauma, sepsis, malaria, kidney dialysis, and chemotherapy.

RELEVANCE: Some common anemias can be treated with the hormone erythropoietin (EPO), which stimulates red blood-cell production. However, certain anemias, including DBA, do not respond to EPO, creating a large unmet medical need.

By determining how corticosteroids act to promote red blood cell progenitor formation, Whitehead Institute researchers have identified a class of drugs that may be beneficial in anemias, including those resulting from trauma, sepsis, malaria, kidney dialysis, and chemotherapy.

Anemia occurs due to a breakdown in erythropoiesis, the multi-step process that creates red blood cells. Some common anemias can be treated with a recombinant form of the hormone erythropoietin (EPO), which normally stimulates red blood-cell production at a fairly early stage of erythropoiesis.

However, certain anemias fail to respond to EPO, creating a large unmet medical need. In the case of Diamond Blackfan anemia (DBA), patients lack a sufficient number of EPO-responsive cells. Instead, corticosteroids such as prednisone or prednisolone are used to treat DBA, although it has been unclear exactly how these agents affect erythropoiesis.

To see how corticosteroids are able to increase red blood cell counts, Johan Flygare, a postdoctoral researcher in the lab of Whitehead Institute Founding Member Harvey Lodish, purified two progenitors of red blood cells, called burst forming unit-erythroids (BFU-Es) and colony forming unit-erythroids (CFU-Es), from mouse fetal liver cells. During erythropoiesis, BFU-Es produce CFU-Es, which are then stimulated by EPO to generate the pro-erythroblasts that eventually become red blood cells. By dividing numerous times before maturing, both BFU-Es and CFU-Es have a limited ability to self-renew. When Flygare exposed BFU-Es and CFU-Es in vitro to a corticosteroid, only the BFU-Es responded–dividing 13 times instead of the usual 9 times before maturing into CFU-Es. These additional cell divisions ultimately led to a 13-fold increase in red blood-cell production.

Flygare identified 83 genes in BFU-Es that are stimulated by the corticosteroid, and he examined the promoters that facilitate those genes’ transcription. The promoters appeared to have binding sites for a transcription factor, called hypoxia-induced factor 1-alpha (HIF1-alpha), that is activated when an organism is deprived of oxygen. To prolong the 83 genes’ promotion by HIF1-alpha, Flygare used a class of drugs known as prolyl hydroxylase inhibitors (PHIs), which extends HIF1-alpha’s effectiveness. PHIs have also been used in early-stage clinical trials to increase EPO production.

When Flygare added both a corticosteroid and a PHI to BFU-Es in culture, the cells produced 300 times more red blood cells than did cells without exposure to the drugs. Flygare repeated the experiment with adult human BFU-Es, and found that a corticosteroid plus a PHI generated 10 times more red blood cells than BFU-Es exposed to a corticosteroid alone.

Flygare hopes this research eventually leads to improved treatment for DBA patients who currently suffer from a host of corticosteroid-induced side effects, including decreased bone density, immunosuppression, stunted growth, and cataracts.

“If you could lower the dose of steroids so DBA patients would get just a little bit, and then add on this kind of drug, like a PHI, that would boost the effect, maybe you could get around the steroids’ side effects,” says Flygare. “That would be good.”

This new approach to increasing erythropoiesis by extending the self-renewal of BFU-Es – resulting in creation of more EPO-responsive cells – could lead to novel therapies for other anemias.

“There are a number of anemias that are much more prevalent than DBA and that cannot be treated with EPO, either, such as anemias from trauma, sepsis, malaria, and anemia in kidney dialysis patients,” says Lodish, who is also a professor of biology and bioengineering at MIT. “Whether these treatments will work in those conditions remains to be seen.”

Notes:

This research was supported by the Diamond Blackfan Anemia Foundation, the Swedish Research Council, Maja och Hjalmar Leanders Stiftelse, The Sweden-America Foundation, and the National Institutes of Health (NIH).

Nicole Giese

Harvey Lodish’s primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also a professor of biology and a professor of bioengineering at Massachusetts Institute of Technology.

Full Citations:

“HIF-1 Alpha synergizes with glucocorticoids to promote BFU-E progenitor self-renewal”

Blood, published online the week of December 22, 2010

Johan Flygare (1), Violeta Rayon Estrada (1), Chanseok Shin (1, 2), Sumeet Gupta (1), and Harvey F. Lodish (1, 3, 4).

1. Whitehead Institute for Biomedical Research, Cambridge, MA 02142
2. Department of Agricultural Biotechnology, Seoul National University, Seoul, 151-921, Republic of Korea
3. Departments of Biology and Bioengineering, Massachusetts Institute of Technology, Cambridge, MA

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Nicole Giese
Whitehead Institute for Biomedical Research Continue reading

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American Medical Systems Announces FDA Clearance For MiniArc(R) Precise Single Incision Sling

American Medical Systems® (AMS) (Nasdaq: AMMD), a leading provider of world-class devices and therapies for both male and female pelvic health, announced the Food and Drug Administration (FDA) has cleared the MiniArc® Precise Single-Incision Sling System, a product for the treatment of female stress urinary incontinence (SUI). MiniArc Precise is the next generation sling in the MiniArc family sling system, the number one selling single-incision sling in the United States.

“We are excited to receive clearance on this important product. It further demonstrates our commitment to product innovation and is a good example of using physician feedback to improve a surgical procedure and support improved outcomes,” says John Nealon, senior vice president and general manager of women’s health at American Medical Systems.

Over 33 million women worldwide are affected by SUI, a condition in which activities such as coughing, sneezing, or heavy lifting put pressure on the bladder resulting in unintentional loss of urine. SUI is more common in women than men and is caused by weakening of pelvic floor muscles often tied to tissue and nerve damage resulting from pregnancy, childbirth, radiation, hormone changes or a prior surgery.

To treat SUI with the MiniArc Precise system, the physician surgically places a narrow strip of mesh material called a sling under the urethra to give it a point of support. This procedure is minimally invasive with only one small incision. MiniArc Precise is built upon the success of the original MiniArc single-incision sling which since its launch in late 2007, has been implanted in more than 75,000 patients and incorporates proven mesh that has been used in more than 750,000 procedures.

“MiniArc Precise builds upon the existing MiniArc Sling. With the new design and fixed needle to sling connection, MiniArc Precise further simplifies the ease of use while maintaining the integrity of the existing MiniArc clinical evidence,” says John Nealon. “Its slim needle profile minimizes the potential for tissue trauma and allows for precise placement of the sling under the urethra for support. A limited launch is underway with a full commercial launch later in 2010.”

MiniArc Precise’s design incorporates low profile self-fixating tips that provide immediate fixation of the mesh. As an outpatient procedure, the MiniArc Precise generally allows patients to return to normal activities within a few days. The single-incision approach minimizes the potential for tissue trauma, which may provide for enhanced patient recovery.

About American Medical Systems:

American Medical Systems, headquartered in Minnetonka, Minnesota, is a diversified supplier of medical devices and procedures to cure incontinence, erectile dysfunction, benign prostate hyperplasia (BPH), pelvic floor repair and other pelvic disorders in men and women. These disorders can significantly diminish one’s quality of life and profoundly affect social relationships. In recent years, the number of people seeking treatment has increased markedly as a result of longer lives, higher-quality-of-life expectations and greater awareness of new treatment alternatives. American Medical Systems’ products reduce or eliminate the incapacitating effects of these diseases, often through minimally invasive therapies. The Company’s products were used to treat more than 335,000 patients in 2009.

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“Food Insecure” Appalachians More Likely To Be Obese, Diabetic, Study Finds

Members of rural Appalachian households who lack access to food or experience hunger are more likely to be obese and have diabetes, according to an Ohio University study.

Researcher David Holben found that subjects from households with greater levels of what medical, nutrition and dietetic professionals call “food insecurity” had a greater body mass index (BMI) than those with smaller levels of food insecurity (an average BMI of 30.3 vs. average BMI of 29). Those from food insecure households also were more likely to have diabetes (37.9 percent) and to be overweight (48.1 percent) than subjects from food secure households (25.8 percent and 35.1 percent, respectively). The study was published in the July 2006 issue of Preventing Chronic Disease, a publication of the Centers for Disease Control.

A total of 2,580 people participated in the Ohio University project, with 72.8 percent from food secure households and 27.2 percent from food insecure households that may or may not be experiencing hunger. That’s higher than the national average: In 1999, the year the Ohio University study was conducted, 10.1 percent of U.S. households were food insecure.

Food insecurity is associated health problems such as stress, obesity, diabetes and heart disease, as well as with poor management of chronic disease, said Holben, who recently wrote a major position paper about the problem for the American Dietetic Association.

The survey included residents of Athens, Hocking, Meigs, Perry, Pike and Vinton counties in Ohio. Researchers asked participants about food access of their households, as well as health care access and use. Those who agreed to an additional health exam were checked for weight, blood pressure, hemoglobin levels, total cholesterol and blood glucose control, said Holben, associate professor of human and consumer sciences and the director of the Didactic Program in Dietetics in Ohio University’s College of Health and Human Services.

Volunteers were recruited from community sites, such as fairs and festivals, food distribution programs, churches, senior centers, community centers, grocery stores and shopping malls. While the sample is not representative of the region in which it was collected, the study provides an impression of the problems faced by residents of rural Appalachia.

“This does have implications for policy, and it has implications for patient care,” Holben said about the study findings. “Physicians, nurses – not just dietitians – need to be aware that people may not have money to buy medicine, and that they have a harder time managing a chronic disease if they’re food insecure.”

While it might be surprising that someone can be overweight while experiencing hunger, Holben explained that low-cost foods such as fast food “are lower in cost, usually are high fat and high sugar and taste good,” which makes it easier for families to rely on these foods. He also pointed to preliminary studies conducted elsewhere that show that malnourishment at a young age can result in adults whose metabolism works more slowly, predisposing them for quick weight gain.

An irregular food supply, caused by monthly food allotments that may run out by the end of the month, also can set up periods of bingeing and fasting, which in turn prompt the body to store as much energy as possible for those times when food is in short supply, Holben said.

To address the food insecurity problem, Holben suggests educational programs on better managing food supply, nutrition education (such as recipe ideas for some of the foods provided by the food assistance programs) and proper interpretation of sell-by dates on food labels.

“(Those dates) don’t mean that magically on that date the food rots, but if we have people throwing away foods, and yet they don’t have resources to buy foods, that could be a problem,” said Holben, who is continuing to study issues of food security, obesity and diabetes in a national sample.

###

Co-author on the Preventing Chronic Disease paper is Alfred Pheley, a former Ohio University College of Osteopathic Medicine professor who is now on the faculty of the Virginia College of Osteopathic Medicine in Blacksburg, Va. The study was funded by a grant from the Ohio University College of Osteopathic Medicine.

Christina Dierkes.
Contact: David Holben, holbenohio.edu

Contact: Andrea Gibson
Ohio University Continue reading

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Mice Protected From Avian Flu By Human Antibodies

An international team of scientists, including researchers from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, report using antibodies derived from immune cells from recent human survivors of H5N1 avian influenza to successfully treat H5N1-infected mice as well as protect them from an otherwise lethal dose of the virus.

“The possibility of an influenza pandemic, whether sparked by H5N1 or another influenza virus to which humans have no natural immunity, is of serious concern to the global health community,” says NIAID Director Anthony S. Fauci, M.D. “If the success of this initial study is confirmed through further laboratory and clinical trials, human monoclonal antibodies could prove to be valuable therapeutic and prophylactic public health interventions for pandemic influenza.”

The research published in PLoS Medicine, represents a three-way collaboration among Kanta Subbarao, M.D., and her coworkers at NIAID; Antonio Lanzavecchia, M.D., and colleagues from the Institute for Research in Biomedicine, Bellinzona, Switzerland; and Cameron Simmons, Ph.D., from the Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.

Four Vietnamese adults diagnosed with H5N1 influenza infection between January 2004 and February 2005 agreed to donate blood soon after they had recovered from their illness. In Switzerland, Dr. Lanzavecchia extracted antibody-producing white blood cells, called memory B cells, from the Vietnamese samples and treated them with a process he developed so that they rapidly and continuously produced large amounts of antibody. Next, researchers in Dr. Subbarao’s lab screened 11,000 antibody-containing samples provided by the Swiss team and found a handful able to neutralize H5N1 influenza virus. Based on these results, Dr. Lanzavecchia purified the B cells and ultimately created four monoclonal antibodies (mAbs) that secrete H5N1-specific neutralizing antibodies.

Dr. Subbarao and her coworkers first tested whether the human H5N1 mAbs could protect mice from severe H5N1 infection. Groups of five mice received either of two human H5N1 mAbs at one of three dosages or human mAbs against diphtheria or anthrax. One day later, the mice were exposed through their noses to lethal doses of H5N1 influenza virus.

All the control mice – those receiving non-H5N1 mAbs – rapidly developed severe illness and died within a week. In contrast, all the mice that received the first H5N1 mAb tested – regardless of dose – survived, while 80 percent of mice receiving the highest dose of the second H5N1 mAb survived. Additional tests showed that mice receiving either of the two protective H5N1 mAbs had levels of virus in the lungs that were 10 to 100 times lower than those in control mice, and little or no virus moved beyond the lungs.

The investigators also tested the therapeutic potential of the human H5N1 mAbs. Using blood products from influenza survivors is an old idea, the researchers note. During the flu pandemic of 1918-19, for example, physicians took serum from recovered flu patients and gave it to new victims; recent historical research indicates that those blood transfusions, when given early in the illness, sometimes saved recipients’ lives.

In their study, Dr. Subbarao and her colleagues infected groups of mice with a lethal dose of an H5N1 virus that had circulated in Vietnam in 2004. A total of 60 mice were given one of the four H5N1 mAbs at 24, 48 or 72 hours after infection while a control group received non-influenza mAbs. All the mice in the control group died within 10 days of infection, while 58 of the 60 treated mice survived. All four H5N1 mAbs conferred robust protection. Most surprisingly, says Dr. Subbarao, the survival rate was excellent even when treatment was delayed for three days.

Spurred by these results, the NIAID investigators next tested whether the H5N1 mAbs might be used to treat mice infected with a related but distinct H5N1 virus. Although the four mAbs used in the experiment originated after infection with the 2004 H5N1 virus, three of them nevertheless prevented the mice from dying when given 24 hours after they were infected with a 2005 H5N1 virus. This suggests, the researchers say, that human mAbs may provide broad protection against variant H5N1 viruses – a desirable quality in any therapeutic aimed at the constantly evolving flu virus.

Taken together, the findings from this international collaboration are encouraging, says Dr. Subbarao. They show that fully human mAbs with potent H5N1 influenza virus neutralizing ability can be rapidly generated from the blood of convalescent patients and that these mAbs work well to both treat H5N1 infection and prevent death from such infection in a mouse model. The authors plan to take the research forward by scaling up the production of H5N1 mAbs and, if the technique proves safe and effective in additional animal tests, to evaluate these human mAbs in clinical trials in humans.

For more information on influenza see www3.niaid.nih/news/focuson/flu.

Also visit pandemicflu/ for one-stop access to U.S. Government information on avian and pandemic flu.

NIAID is a component of the National Institutes of Health. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on basic immunology, transplantation and immune-related disorders, including autoimmune diseases, asthma and allergies.

The National Institutes of Health (NIH) – The Nation’s Medical Research Agency – includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments and cures for both common and rare diseases. For more information about NIH and its programs, visit nih/.

Reference: CP Simmons et al. Prophylactic and therapeutic efficacy of human monoclonal antibodies against H5N1 influenza. PLoS Medicine (2007) DOI:10.1371/journal.pmed.0040178

Contact: Anne A. Oplinger

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