Mathematical biologists study how to best prevent bullet deaths

Main Category: Public Health
Article Date: 30 Jul 2013 - 1:00 PDT Current ratings for:
Mathematical biologists study how to best prevent bullet deaths

Aiming to quell heated national debate about gun control with factual answers, two UC Irvine mathematicians have designed parameters to measure how to best prevent both one-on-one killings and mass shootings in the United States. Their paper appears in the journal PLOS ONE.

"It's time to bring a scientific framework to this problem," said lead author Dominik Wodarz, a mathematical biologist who works on disease and evolutionary dynamics. His co-author and wife, Natalia Komarova, a mathematician who studies biomedical and social trends, added: "Can we design a rational way to argue about guns?"

Both were appalled not just by the December shooting deaths of 20 youngsters and eight adults in Newtown, Conn., but also by the bitterly emotional dispute over weapons that erupted anew. They decided to put their professional expertise to work.

"This debate cannot be settled satisfactorily by verbal arguments alone, since these are often driven by opinion and lack a solid scientific backing," the authors write. "What is under debate is essentially an epidemiological problem: How do different gun control strategies affect the rate at which people become killed by attackers, and how can this rate be minimized?"

The duo reviewed available data stretching as far back as World War I, then drew up equations to compute whether policies ranging from a total firearm ban to "arm everyone" increase or decrease homicides. After running the numbers, they found that in more common domestic and one-on-one crimes, reduced legal gun availability - if properly enforced - is likelier to lower deaths. But in rare mass shootings, armed citizens might save lives if sufficiently trained to avoid accidentally shooting fleeing bystanders.

They note that data is missing that could strengthen their results. For instance, homeowners who used a weapon to stop a robbery might not make a report to police. "Stand your ground" laws being widely discussed in the wake of Trayvon Martin's killing could influence the parameters too. "Whether such laws better protect the public or increase deaths needs to be determined statistically," Wodarz said. "Do you have a greater chance of dying if you run or if you face your attacker with a weapon?"

The authors say key parts of their equations should be studied more closely: the fraction of offenders who illegally possess a gun, the statistical degree of protection provided by legal gun ownership, and the number of people who are legally carrying a gun when attacked. Comprehensive data in those areas, they say, could further aid the development and implementation of effective policies.

Federal funding for gun control research was essentially nonexistent for nearly two decades, but President Barack Obama in January labeled firearm deaths a public health crisis and ended the longstanding freeze. About 11,000 Americans die each year from gunshot homicides.

A large number of peer reviews - 11 in total - were solicited by journal editors; two or three are the norm. A wide array of opinions were expressed, ranging from enthusiastically positive and constructive to a critic who stated that scientific methods would never be useful in this area.

The authors were warned to be prepared for heated responses to their paper but believe it's critical to bring the best tools of research to the issue.

"If the current discussion could be steered toward science, rather than having a heated debate without much of a logical foundation, a big step forward toward saving lives would be achieved," they said.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our public health section for the latest news on this subject. Please use one of the following formats to cite this article in your essay, paper or report:

MLA

University of California - Irvine. "Mathematical biologists study how to best prevent bullet deaths." Medical News Today. MediLexicon, Intl., 30 Jul. 2013. Web.
30 Jul. 2013. APA

Please note: If no author information is provided, the source is cited instead.

'Mathematical biologists study how to best prevent bullet deaths'

Please note that we publish your name, but we do not publish your email address. It is only used to let you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.

If you write about specific medications or operations, please do not name health care professionals by name.

All opinions are moderated before being included (to stop spam). We reserve the right to amend opinions where we deem necessary.

Contact Our News Editors

For any corrections of factual information, or to contact the editors please use our feedback form.

Please send any medical news or health news press releases to:

Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.

View the original article here

New stem cell gene therapy gives hope to prevent Sanfilippo - an inherited neurological disease

Main Category: Neurology / Neuroscience
Also Included In: Stem Cell Research;  Genetics
Article Date: 25 Jul 2013 - 1:00 PDT Current ratings for:
New stem cell gene therapy gives hope to prevent Sanfilippo - an inherited neurological disease

Scientists from The University of Manchester have used stem cell gene therapy to treat a fatal genetic brain disease in mice for the first time.

The method was used to treat Sanfilippo - a fatal inherited condition which causes progressive dementia in children - but could also benefit several neurological, genetic diseases.

Researchers behind the study, published in the journal Molecular Therapy this month, are now hoping to bring a treatment to trial in patients within two years.

Sanfilippo, a currently untreatable mucopolysaccharide (MPS) disease, affects one in 89,000 children in the United Kingdom, with sufferers usually dying in their mid-twenties. It is caused by the lack of SGSH enzyme in the body which helps to breakdown and recycle long chain sugars, such as heparan sulphate (HS). Children with the condition build up and store excess HS throughout their body from birth which affects their brain and results in progressive dementia and hyperactivity, followed by losing the ability to walk and swallow.

Dr Brian Bigger, from the University of Manchester's Institute of Human Development who led the research, said bone marrow transplants had been used to correct similar HS storage diseases, such as Hurler syndrome, by transplanting normal cells with the missing enzyme but the technique did not work with Sanfilippo disease. This is because monocytes, a type of white blood cell, from the bone marrow, did not produce enough enzyme to correct the levels in the brain.

Dr Bigger said: "To increase SGSH enzyme from bone marrow transplants, and to target it to the cells that traffic into the brain, we have developed a stem cell gene therapy which overproduces the SGSH enzyme specifically in bone marrow white blood cells.

"We have shown that mice treated by this method produce five times the normal SGSH enzyme levels in the bone marrow and 11 per cent more compared to normal levels in the brain.

"The enzyme is taken up by affected brain cells and is enough to correct brain HS storage and neuro inflammation to near normal levels and completely corrects the hyperactive behaviour in mice with Sanfilippo.

"This is extremely exciting and could have huge implications for treatments. We now hope to work to a clinical trial in Manchester in 2015."

The University of Manchester team is now manufacturing a vector - a tool commonly used by molecular biologists to deliver genetic material into cells - for use in humans and hope to use this in a clinical trial with patients at Central Manchester University Hospital NHS Foundation Trust by 2015.

The stem cell gene therapy approach was recently shown by Italian scientists to improve conditions in patients with a similar genetic disease affecting the brain called metachromatic leukodystrophy, with results published in the journal Science earlier this month.

Manchester scientists refined the vector used by the Italian scientists. "This approach has the potential to treat several neurological genetic diseases," Dr Bigger added.

The research was funded by the UK MPS Society and the Sanfilippo Children's Research Foundation based in Canada.

Christine Lavery MBE, Chief Executive of the UK MPS Society, said: "Since 1970 over 130 children and young adults have lost their lives to Sanfilippo disease (MPS III) in the UK alone.

"Whilst new therapies for other MPS diseases are changing children's lives, parents of children with Sanfilippo disease can do no more than give the best possible care and live in hope that a treatment is around the corner. The positive results of Dr Brian Bigger's gene therapy programme in mice provides optimism for future generations of Sanfilippo children."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our neurology / neuroscience section for the latest news on this subject.

The research is published in the journal Molecular Therapy this month.

The University of Manchester

Please use one of the following formats to cite this article in your essay, paper or report:

MLA

The University of Manchester. "New stem cell gene therapy gives hope to prevent Sanfilippo - an inherited neurological disease." Medical News Today. MediLexicon, Intl., 25 Jul. 2013. Web.
25 Jul. 2013. APA

Please note: If no author information is provided, the source is cited instead.

'New stem cell gene therapy gives hope to prevent Sanfilippo - an inherited neurological disease'

Please note that we publish your name, but we do not publish your email address. It is only used to let you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.

If you write about specific medications or operations, please do not name health care professionals by name.

All opinions are moderated before being included (to stop spam). We reserve the right to amend opinions where we deem necessary.

Contact Our News Editors

For any corrections of factual information, or to contact the editors please use our feedback form.

Please send any medical news or health news press releases to:

Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.

View the original article here

Discovery of gene function may help prevent kidney stones

Main Category: Genetics
Also Included In: Urology / Nephrology
Article Date: 26 Jul 2013 - 2:00 PDT Current ratings for:
Discovery of gene function may help prevent kidney stones

The discovery of a gene's function in E. coli and other bacteria might lead to a probiotic to prevent the most common type of kidney stone, according to a Purdue University study.

Human cells can't metabolize oxalate, an acidic chemical found in nearly all plants we eat, so any oxalate we absorb from food must be excreted from the body. Calcium-oxalate urinary stones can form when oxalate reaches a high concentration in the kidneys. About 80 percent of kidney stones are composed of insoluble calcium oxalate.

T. Joseph Kappock, assistant professor of biochemistry, and his research team made the discovery during a study of genes in Acetobacter aceti, a harmless bacterium that is typically used to convert wine to vinegar. Acetobacter aceti, which normally lives on plant tissue, thrives in acidic conditions that easily kill most other bacteria, Kappock said.

The researchers were searching for other acids in addition to acetic acid, the acid present in vinegar, that the bacterium can metabolize.

"We were very excited when we realized E. coli has the same genetic setup as Acetobacter aceti," said Kappock, whose findings were published in the journal PLOS ONE.

Kappock and doctoral students Elwood A. Mullins and Kelly L. Sullivan found that Acetobacter aceti and E. coli each contain an enzyme with a previously unknown function, called YfdE in E. coli.

DNA sequencing had identified related genes in each bacterium, but provided little insight about its function.

"When we look at a bacterial genome by DNA sequencing, we can't tell what many of the proteins in the organism do," Kappock said. "I compare it to knowing that a vehicle has an internal combustion engine. You don't know if it's in an Indy car or a diesel truck. DNA sequencing tells us we have an internal combustion engine in this organism, but we don't know what it's for or what it can do."

Many other bacteria have the same genes but don't seem to be capable of using them.

"A few bacteria in the gastrointestinal tract eat oxalate, and we think we know how those work," Kappock said. "But we don't know why so many others are killed by oxalate, even though they have genes that would seem to be able to protect them. Oxalate is a very hard nut to crack. It's a very stable molecule that is difficult to decompose. The enzymes that process it are pretty specialized and don't seem to connect to normal bacterial metabolic pathways in an obvious way."

The researchers determined which chemicals are processed by the YfdE enzyme, following a hunch that it would use oxalate. Their results connected oxalate degradation to the core of bacterial metabolism.

Assigning a function to YfdE may help identify beneficial bacteria that could serve as probiotic agents in the human gastrointestinal tract to reduce the risk of kidney stone formation. Kidney stones, which affect more than 5 percent of the U.S. population, can cause painful blockages of the urinary tract.

"If we understand what bacteria need to degrade oxalate, then we might have a better idea how to identify strains that can do that, and thereby suppress the uptake of dietary oxalate" he said. "There are probably bacteria out there that have engineered themselves to do this for us."

Genome-sequencing information will increase the speed of the search, Kappock said.

"Because we've figured out what the gene product does, we will be able to find it in any organism and can zero in on those that might be beneficial," he said.

The researchers used X-ray crystallography to pinpoint the most important regions of the YfdE enzyme.

Kappock said the information has other applications, as well. Scientists and engineers who are interested in mapping and reprogramming microbial metabolism now know what one more gene product does.

"Our one piece of the puzzle will help others understand other metabolic networks," he said.

Agricultural Research at Purdue, the National Science Foundation and the U.S. Department of Energy funded the research.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our genetics section for the latest news on this subject.

Abstract:

Acetyl-CoA:Oxalate CoA-transferase 1 Function and X-ray Crystal Structure of Escherichia coli YfdE

Elwood A. Mullins 1, 2; Kelly L. Sullivan 1; T. Joseph Kappock 1;

1 Dept. of Biochemistry, Purdue University, West Lafayette, Indiana, USA

2 Dept. of Chemistry, Washington University, St. Louis, Missouri, USA

Many food plants accumulate oxalate, which humans absorb but do not metabolize, leading to the formation of urinary stones. The commensal bacterium Oxalobacter formigenes consumes oxalate by converting it to oxalyl-CoA, which is decarboxylated by oxalyl-CoA decarboxylase (OXC). OXC and the class III CoA-transferase formyl-CoA:oxalate CoA-transferase (FCOCT) are widespread among bacteria, including many that have no apparent ability to degrade or to resist external oxalate. The EvgA acid response regulator activates transcription of the Escherichia coli yfdXWUVE operon encoding YfdW (FCOCT), YfdU (OXC), and YfdE, a class III CoA-transferase that is ~30% identical to YfdW. YfdW and YfdU are necessary and sufficient for oxalate-induced protection against a subsequent acid challenge; neither of the other genes has a known function. We report the purification, in vitro characterization, 2.1- A crystal structure, and functional assignment of YfdE. YfdE and UctC, an orthologue from the obligate aerobe Acetobacter aceti, perform the reversible conversion of acetyl-CoA and oxalate to oxalyl-CoA and acetate. The annotation of YfdE as acetyl-CoA:oxalate CoA-transferase (ACOCT) expands the scope of metabolic pathways linked to oxalate catabolism and the oxalate-induced acid tolerance response. FCOCT and ACOCT active sites contain distinctive, conserved active site loops (the glycine-rich loop and the GNxH loop, respectively) that appear to encode substrate specificity.

Purdue University

Please use one of the following formats to cite this article in your essay, paper or report:

MLA

University, Purdue. "Discovery of gene function may help prevent kidney stones." Medical News Today. MediLexicon, Intl., 26 Jul. 2013. Web.
27 Jul. 2013. APA

Please note: If no author information is provided, the source is cited instead.

'Discovery of gene function may help prevent kidney stones'

Please note that we publish your name, but we do not publish your email address. It is only used to let you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.

If you write about specific medications or operations, please do not name health care professionals by name.

All opinions are moderated before being included (to stop spam). We reserve the right to amend opinions where we deem necessary.

Contact Our News Editors

For any corrections of factual information, or to contact the editors please use our feedback form.

Please send any medical news or health news press releases to:

Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.

View the original article here

Inovio Pharmaceuticals' potent hTERT DNA cancer vaccine shows potential to reduce tumors and prevent tumor recurrence

Main Category: Cancer / Oncology
Also Included In: Immune System / Vaccines
Article Date: 24 Jul 2013 - 4:00 PDT Current ratings for:
Inovio Pharmaceuticals' potent hTERT DNA cancer vaccine shows potential to reduce tumors and prevent tumor recurrence

Inovio Pharmaceuticals, Inc. (NYSE MKT: INO) announced today that in a preclinical study with two animal models, Inovio's hTERT (human telomerase reverse transcriptase) DNA cancer vaccine administered with Inovio's CELLECTRA® adaptive electroporation delivery technology generated robust and broad immune responses, broke the immune system's tolerance to its self-antigens, induced T-cells with a tumor-killing function, and increased the rate of survival. Because high levels of hTERT expression are found in 85% of human cancers, regardless of type, Inovio's cancer candidate holds the potential to perform as a "universal" cancer therapeutic based on these early but unprecedented results. Following this strong preclinical data, Inovio plans to advance its synthetic hTERT cancer vaccine, INO-1400, into clinical trials in 2014.

These results appear in the American Association for Cancer Research journal, Cancer Immunology Research, in a paper entitled: "Highly optimized DNA vaccine targeting human telomerase reverse transcriptase stimulates potent antitumor immunity," authored by Inovio researchers and collaborators.

Dr. J. Joseph Kim, Inovio's president and CEO, said: "Inovio has demonstrated in multiple published human studies that our synthetically optimized DNA vaccines delivered with our CELLECTRA delivery system generate best-in-class T-cell immune responses. Here we show that in monkeys our hTERT DNA cancer vaccine generated T-cell immune responses more than 18-fold higher than the previous best results of a peer's hTERT therapeutic vaccine, which was also a DNA vaccine delivered with electroporation. We are particularly enthusiastic about our vaccine's potential use as a "universal" cancer therapeutic, given that hTERT is present in the vast majority of cancer types yet rare in normal cells. We plan to develop INO-1400 to treat breast and lung cancers and then expand to other cancer types. This hTERT therapy adds to a growing Inovio oncology franchise spearheaded by our phase II candidate, VGX-3100 for treating HPV-related pre-cancers and cancers, as well as our near clinical INO-5150 to treat prostate cancer."

Data from both murine and human systems over the past 10 years have demonstrated that TERT-specific cytotoxic T-lymphocytes (CTLs) can recognize and kill TERT-expressing tumor cells in multiple types of cancers. In fact, previous research has shown that breast cancer patients who mounted an hTERT-specific CTL response exhibited significantly longer rates of survival. However, the immune system's tolerance of cancer cells and their associated antigens produced in the body, which exists to prevent autoimmune diseases, often restricts the immune system's antitumor response. A major challenge for cancer vaccine development has been to develop approaches to break this tolerance in tumor-bearing hosts. Recent advances in our understanding of antigen presentation and tolerance have led Inovio to create this synthetic DNA vaccine targeting the hTERT antigen.

Inovio constructed a highly optimized synthetic DNA vaccine with multiple proprietary features. Using its novel consensus design approach, two differentiating mutations were incorporated in the vaccine sequence to assist T-cells to more readily recognize self-made hTERT antigens and kill the cancer cells to which these antigens are attached (i.e. break tolerance). In addition, Inovio's use of a full length antigen DNA sequence encompasses multiple epitopes (parts of an antigen that are recognized by the immune system), potentially helping the immune system by providing multiple opportunities to overcome a tumor's ability to evade recognition by T-cells.

In the study, Inovio researchers confirmed that vaccination with Inovio's DNA vaccine delivered by adaptive electroporation induced hTERT-specific cellular immune responses with significantly greater T-cell magnitude compared to prior non-Inovio studies. Over four vaccinations there was a significant dose response, showing the value of multiple vaccinations to increase the immune response and highlighting the limitation of alternative technologies that are not amenable to multiple vaccinations such as viral vectors. Vaccination elicited multiple epitopes not only in mice, but also in monkeys, indicating a broad vaccine-induced immune response.

Study results showed that mice vaccinated with Inovio's DNA cancer vaccine and then challenged with a cancerous tumor experienced delayed tumor growth and longer overall survival compared with non-vaccinated mice. Mice first challenged with a tumor and then treated with the hTERT DNA vaccine displayed killing activity of the targeted cancer cells expressing the hTERT antigen, with no killing of normal cells that did not express the hTERT antigen. The treated mice experienced significantly smaller tumors and also longer overall survival. Vaccinated animal results were compared to a control group of animals that did not receive Inovio's DNA cancer vaccine.

In monkeys, whose TERT is 96% similar to human TERT and therefore a highly relevant model for immunotherapeutic vaccine development, the hTERT DNA vaccine elicited strong and broad TERT-specific immune responses and demonstrated the potential to eliminate tumor cells.

Overall, in these studies researchers observed that administration of a synthetic highly optimized hTERT DNA vaccine delivered with electroporation was capable of breaking immune tolerance, and eliciting robust and diverse antigen-specific CTLs, which are responsible for clearing cancerous cells, as well as a potent antitumor response. A favorable safety profile emerged from this study, showing that the vaccine-induced CTLs appeared not to be associated with any major toxicities or organ damage.

The expression of hTERT is thought to correlate with tumor survival and hTERT is associated with 85% of human tumors. Furthermore, there is growing recognition that it may be necessary to target stem cells that produce cancerous cells and recent studies have suggested that cancer stem or stem-like cells also express hTERT. These factors highlight the importance of an effective hTERT-targeting vaccine/immunotherapy and point to the potential benefit of Inovio's novel cancer vaccine.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our cancer / oncology section for the latest news on this subject. Please use one of the following formats to cite this article in your essay, paper or report:

MLA

Pharmaceutical, Inovio. "Inovio Pharmaceuticals' potent hTERT DNA cancer vaccine shows potential to reduce tumors and prevent tumor recurrence." Medical News Today. MediLexicon, Intl., 24 Jul. 2013. Web.
24 Jul. 2013. APA

Please note: If no author information is provided, the source is cited instead.

'Inovio Pharmaceuticals' potent hTERT DNA cancer vaccine shows potential to reduce tumors and prevent tumor recurrence'

Please note that we publish your name, but we do not publish your email address. It is only used to let you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.

If you write about specific medications or operations, please do not name health care professionals by name.

All opinions are moderated before being included (to stop spam). We reserve the right to amend opinions where we deem necessary.

Contact Our News Editors

For any corrections of factual information, or to contact the editors please use our feedback form.

Please send any medical news or health news press releases to:

Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.

View the original article here

Innovative technique seeks to prevent lymphedema in breast cancer patients

Main Category: Breast Cancer
Also Included In: Clinical Trials / Drug Trials;  Lymphology/Lymphedema
Article Date: 24 Jul 2013 - 2:00 PDT
Current ratings for:
Innovative technique seeks to prevent lymphedema in breast cancer patients

A team of surgeons and members of the breast cancer program of the Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian Hospital/Columbia University Medical Center is conducting a two-year pilot study of an innovative microsurgery technique coupled with imaging technology to not only prevent lymphedema but also potentially detect and treat it early.

Lymphedema, the accumulation of lymph fluid in the arm and painful swelling due to blocked lymph drainage, occurs in up to 13 percent of breast cancer patients after sentinel node biopsy and external-beam radiation, increasing to 40 percent following complete axillary lymph node dissection (ALND) and radiation.

Lymphedema can also affect other cancer patients. Surgery and radiation after lymph node removal can cause scarring that blocks the lymph ducts, not only in the underarm but also in the legs, groin, pelvis, or neck after treatment for uterine, prostate, ovarian, or prostate cancer, as well as lymphoma and melanoma.

It can be difficult to treat lymphedema, which often requires lifelong therapy with compression garments to prevent lymphangitis (inflammation) and cellulitis in the affected limb. The condition can greatly affect quality of life for breast cancer patients and, some studies suggest, is associated with a two-to-three-fold increase in mortality in the six years following a cancer diagnosis.

The current study of the lymphatic microsurgical preventive healing approach (LYMPHA) is the first to be conducted outside of the University of Genoa in Italy, where it was developed. Dr. Sheldon M. Feldman, the principal investigator, was invited by the developers, Drs. Francesco Boccardo and Corradino Campisi, to observe their team in 2012.

The LYMPHA technique creates a bypass to restore lymphatic flow by connecting lymph vessels to a branch of the axillary vein, a pathway normally severed by node removal or blocked by tissue fibrosis resulting from radiation, says Dr. Feldman, chief of the Division of Breast Surgery and the Vivian L. Milstein Associate Professor of Clinical Surgery at NewYork-Presbyterian/Columbia University Medical Center.

Previous techniques for preserving lymphatic flow were lengthy and complex, and surgeons could not predict which patients would develop lymphedema or benefit from intervention. The LYMPHA bypass adds only 20-30 minutes to breast cancer surgery and ALND. "In addition to removing all potentially cancerous lymph nodes, we can now restore lymphatic flow and reduce the patient's risk of developing lymphedema," says Dr. Feldman.

Prior to ALND, a blue dye normally used to identify sentinel nodes is injected into the upper arm to map the lymphatic circulation from the arm. During the node dissection, the surgeon preserves a branch of the axillary vein and keeps a suitable length for reaching the lymphatic vessels.

The vein connection, or anastomosis, is then performed by a microvascular surgeon, using a sleeve technique in which the lymphatic vessels are inserted into the cut end of the vein to restore normal lymph flow. A mastectomy is performed at the same time as the node removal and LYMPHA procedure.

Before their surgery, study patients undergo an imaging technique known as lymphoscintigraphy, using a radiotracer such as technetium, and bioimpedance spectroscopy with a device called the L-Dex, to establish baseline lymphatic volume in the arms.

In addition to the regular follow-up visits normally scheduled after an ALND, postoperative monitoring includes physical exams for lymphedema, lymphoscintigraphy, and L-Dex bioimpedance spectroscopy to confirm that the LYMPHA bypass is open and functioning.

"We actually use the L-Dex routinely before breast cancer surgery. Then if patients need lymph node dissection, we carefully monitor them with the L-Dex. If they begin to develop increasing lymph volume in their arm, even if there's been no external change, we know they are on their way to developing lymphedema," says Dr. Feldman. "By using a support sleeve and seeing a physical therapist (for range-of-motion exercises), they may never experience lymphedema."

This study is part of a comprehensive lymphedema management in the breast cancer program at NewYork-Presbyterian/Columbia encompassing education, lymphedema prevention, and, in the future, potential treatment of patients with lymphedema who have not responded to decongestive therapy, which involves wrapping of the limb and specialized massage for drainage.

The LYMPHA pilot study seeks to enroll 10 patients with confirmed nodal metastases whose veins are suitable for the bypass.

The next step would be a multicenter trial throughout the U.S. to confirm the efficacy of the LYMPHA procedure. Eventually it could become the standard of care for cancer patients needing ALND. The lymphatic-venous bypass could also potentially be used to treat patients with lymphedema that is not well controlled with decongestive therapy. The earlier treatment begins, the more likely the condition is to be reversible.

Says Dr. Feldman, "We can now help patients maintain a normal quality of life by most effectively preventing and treating lymphedema without compromising their cancer treatment. We never want to let quality of life trump the cancer treatment. We want both - we don't want people to experience lymphedema."

To be considered for the study, breast cancer patients needing lymph node dissection should contact Amiya Vaz at 212-305-1317 or by email at: av2454@columbia.edu.

Article adapted by Medical News Today from original press release. Source: NewYork-Presbyterian Hospital
Visit our breast cancer section for the latest news on this subject. Please use one of the following formats to cite this article in your essay, paper or report:

MLA

Hospital, NewYork-Presbyterian. "Innovative technique seeks to prevent lymphedema in breast cancer patients." Medical News Today. MediLexicon, Intl., 24 Jul. 2013. Web.
24 Jul. 2013. APA

Please note: If no author information is provided, the source is cited instead.

'Innovative technique seeks to prevent lymphedema in breast cancer patients'

Please note that we publish your name, but we do not publish your email address. It is only used to let you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.

If you write about specific medications or operations, please do not name health care professionals by name.

All opinions are moderated before being included (to stop spam). We reserve the right to amend opinions where we deem necessary.

Contact Our News Editors

For any corrections of factual information, or to contact the editors please use our feedback form.

Please send any medical news or health news press releases to:

Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.

View the original article here

Quickly clearing away damaged proteins may help prevent neurodegenerative disorders

Main Category: Huntingtons Disease
Also Included In: Neurology / Neuroscience
Article Date: 24 Jul 2013 - 0:00 PDT Current ratings for:
Quickly clearing away damaged proteins may help prevent neurodegenerative disorders

Recycling is not only good for the environment, it's good for the brain. A study using rat cells indicates that quickly clearing out defective proteins in the brain may prevent loss of brain cells.

Results of a study in Nature Chemical Biology suggest that the speed at which damaged proteins are cleared from neurons may affect cell survival and may explain why some cells are targeted for death in neurodegenerative disorders. The research was supported by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.

One of the mysteries surrounding neurodegenerative diseases is why some nerve cells are marked for destruction whereas their neighbors are spared. It is especially puzzling because the protein thought to be responsible for cell death is found throughout the brain in many of these diseases, yet only certain brain areas or cell types are affected.

In Huntington's disease and many other neurodegenerative disorders, proteins that are misfolded (have abnormal shapes), accumulate inside and around neurons and are thought to damage and kill nearby brain cells. Normally, cells sense the presence of malformed proteins and clear them away before they do any damage. This is regulated by a process called proteostasis, which the cell uses to control protein levels and quality.

In the study, Andrey S. Tsvetkov and his colleagues from the University of California, San Francisco (UCSF) and Duke University, Durham, N.C., showed that differences in the rate of proteostasis may be the clue to understanding why certain nerve cells die in Huntington's, a genetic brain disorder that leads to uncontrolled movements and death.

To measure how quickly proteins are cleared away from cells, the researchers developed a new technique called optical pulse-labeling, allowing them to follow specific proteins in individual living cells. To test the technique, they grew brain cells in a dish and turned on Dendra2, a photoswitchable protein that glows from green to red after being hit by a specific type of light. Both the red and green glow can be followed until the protein is cleared from the cell. In this way, the researchers could track the lifetime of newly produced Dendra2 (which glows green) and older, photoswitched Dendra2 (which glows red) until the protein was cleared away from the cell.

"Before this new technique, there was no way to look at individual neurons and their capacity to handle proteins. This method provides a real-time readout of how fast proteins are turned over in neurons and gives us a look at some of the mechanisms involved," said Margaret Sutherland, Ph.D., program director at NINDS.

The researchers followed Dendra2 in a set of striatal neurons, which they obtained from rats. The striatum (where striatal neurons are located) is a brain region involved in a number of brain functions including planning movements and is most heavily affected in Huntington's disease. They discovered that the mean lifetime of the protein (how long it remained in the cell) varied three- to fourfold, suggesting that rates of proteostasis were different among individual neurons. In other words, some cells may process an identical protein much slower than others.

Then, the researchers investigated how cells deal with different forms of huntingtin, the protein involved in Huntington's. They fused Dendra2 on the end of a normal or mutant version of huntingtin to track how long the protein remained in cells. The mutant version of huntingtin is longer, and contains three building blocks of the protein repeated an abnormal number of times. These repeats in huntingtin are what cause it to misfold, eventually leading to neuron death and the symptoms of the disease. As predicted, in their experiments, the mutant form of huntingtin caused more rat cells to die than did the normal form of the protein.

The researchers found that the amount of time the mutant protein remained in the cell predicted neuronal survival: shorter mean lifetimes of mutant huntingtin were associated with longer neuronal survival. A shorter mean lifetime indicates that a protein does not remain in the cell for a long time, and that proteostasis is working effectively to clear it away. This suggests that improving proteostasis in Huntington's brains may improve neuronal survival.

To test this idea, the researchers activated Nrf2, a protein known to regulate protein processing. When Nrf2 was turned on, the mean lifetime of huntingtin was shortened, and the neuron lived longer.

"Nrf2 seems like a potentially exciting therapeutic target. It is profoundly neuroprotective in our Huntington's model and it accelerates the clearance of mutant huntingtin," said Dr. Steven Finkbeiner, senior author of the paper.

Although both striatal and cortical neurons are affected by mutant huntingtin, striatal neurons are more susceptible to cell death. The investigators found that striatal neurons were not as effective as cortical neurons in recognizing and clearing away the mutant protein.

"One surprising finding from these experiments was the significance of single cells' ability to clear mutant huntingtin. It turned out that this ability largely predicted their susceptibility, whether that neuron came from the most vulnerable region of the brain - the striatum, or the cortex, which is less vulnerable," said Dr. Finkbeiner. The findings indicate that the toxicity of the damaged proteins may cause neurodegeneration by interfering with the proteostasis system, affecting how quickly they are cleared from neurons.

"The results should remind us that focusing on the disease-causing proteins is only one side of the coin. To understand why some cells die and others are spared, we may need to recognize that there are major, largely unrecognized cell-specific differences in the ways that various types of neurons recognize and dispose of disease-causing proteins," continued Dr. Finkbeiner.

The researchers explored potential mechanisms behind differences in proteostasis. One way that cells normally get rid of proteins is through autophagy - a process in which proteins are packed up into spheres and then broken down. Results in this paper suggested that neurons increased the rate of autophagy when they sensed that the mutant form of huntingtin was accumulating, indicating the autophagy system may be a drug target.

"These findings provide evidence that our brains have powerful coping mechanisms to deal with disease-causing proteins. The fact that some of these diseases don't cause symptoms we can detect until the fourth or fifth decade of life, even when the gene has been present since birth, suggests that those mechanisms are pretty good," said Dr. Finkbeiner.

Future research is needed to determine why coping mechanisms fail as brain cells age and how neurons in the healthy brain keep the proteostasis system functioning.

"New research methods that help us understand how individual neurons function will increase our understanding of central nervous system disorders and help identify new treatments. It is critical to continue working on the methods such as those described in this paper," said Dr. Sutherland.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our huntingtons disease section for the latest news on this subject.

This study was supported by grants from NINDS (R01 3NS039746, 2R01NS045191) and the National Institute on Aging (P01 2AG022074). Additional funding was provided by the Taube/Koret Center, the National Science Foundation (DMS-0914906), the Huntington's Disease Society of America, the Milton Wexler Award, and the Hillblom Foundation.

Reference: Andrey S. Tsvetkov et al. "Proteostasis of Polyglutamine Varies among Neurons and Predicts Neurodegeneration," Nature Chemical Biology, July 21, 2013

NIH/National Institute of Neurological Disorders and Stroke

Please use one of the following formats to cite this article in your essay, paper or report:

MLA

NIH/National Institute of Neurological Disorders a. "Quickly clearing away damaged proteins may help prevent neurodegenerative disorders." Medical News Today. MediLexicon, Intl., 24 Jul. 2013. Web.
24 Jul. 2013. APA

Please note: If no author information is provided, the source is cited instead.

'Quickly clearing away damaged proteins may help prevent neurodegenerative disorders'

Please note that we publish your name, but we do not publish your email address. It is only used to let you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.

If you write about specific medications or operations, please do not name health care professionals by name.

All opinions are moderated before being included (to stop spam). We reserve the right to amend opinions where we deem necessary.

Contact Our News Editors

For any corrections of factual information, or to contact the editors please use our feedback form.

Please send any medical news or health news press releases to:

Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.

View the original article here

Study suggests that turning on a gene may prevent diabetes

Main Category: Diabetes
Also Included In: Genetics
Article Date: 24 Jul 2013 - 1:00 PDT Current ratings for:
Study suggests that turning on a gene may prevent diabetes

Type 2 diabetes accounts for 90 % of cases of diabetes around the world, afflicting 2.5 million Canadians and costing over 15 billion dollars a year in Canada. It is a severe health condition which makes body cells incapable of taking up and using sugar. Dr. Alexey Pshezhetsky of the Sainte-Justine University Hospital Research Center, affiliated with the University of Montreal, has discovered that the resistance to insulin seen in type 2 diabetics is caused partly by the lack of a protein that has not previously been associated with diabetes. This breakthrough could potentially help to prevent diabetes.

"We discovered that Neu1, a protein nicknamed after "neuraminidase 1", turns the absorption of sugar "on" or "off" in body cells, by regulating the amount of sialic acid on the surface of cells", Dr. Pshezhetsky explains.

"We are now trying to find a way to restore Neu1 levels and function in diabetes. If we can remove sialic acid residues from the cell surface, this will force the insulin receptor do its job of absorbing blood sugar properly. This could give doctors an opportunity to reduce the use of insulin therapy, and might help to reduce the diabetes epidemic, says Dr. Pshezhetsky.

The results of his study done on cells and mice were published this month in the journal Diabetes. Dr Pshezhetsky and his team are now testing their results in diabetic patients.

Although type 2 diabetes is initially treated with diet, exercise and tobacco avoidance, doctors try to restore normal levels of insulin by prescribing it when this fails. The number of cases diagnosed around the world continues to grow incredibly quickly: according to the United States Center Disease Control, cases in that country grew on average by 82% between 1995 and 2010. In Oklahoma, the number increased by 226%. The disease accounts for 90% of diabetes cases around the world, and its prevalence has increased in parallel with the obesity epidemic. Obesity is in fact thought to cause this disease which can in turn lead to heart disease, strokes and even limb amputation due to poor circulation.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our diabetes section for the latest news on this subject.

About this study: Dr Alexey Pshezhetsky and his colleagues published "Positive Regulation of Insulin Signaling by Neuraminidase 1" in the July, 2013 edition of Diabetes. The study was partially supported by research grants from Canadian Diabetes Association and the Canadian Institutes for Health Research.

University of Montreal

Please use one of the following formats to cite this article in your essay, paper or report:

MLA

University of Montreal. "Study suggests that turning on a gene may prevent diabetes." Medical News Today. MediLexicon, Intl., 24 Jul. 2013. Web.
24 Jul. 2013. APA

Please note: If no author information is provided, the source is cited instead.

'Study suggests that turning on a gene may prevent diabetes'

Please note that we publish your name, but we do not publish your email address. It is only used to let you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.

If you write about specific medications or operations, please do not name health care professionals by name.

All opinions are moderated before being included (to stop spam). We reserve the right to amend opinions where we deem necessary.

Contact Our News Editors

For any corrections of factual information, or to contact the editors please use our feedback form.

Please send any medical news or health news press releases to:

Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.

View the original article here