Medicare is a "Death Panel"

Medicare is a "death panel." Medicare rations care. Medicare can deny you care "...regardless as to medical necessity." Reform Medicare; do not expand it. If you support more Medicare, I suspect that you have not been deathly sick in way requiring individualized care, or you have not fought for someone else's life who needs the same. - Bradley Hennenfent, M.D., physician and economist

The fact that Medicare can deny care and that “This is true regardless as to medical necessity,” is a quote from MAXIMUS Federal Services MEDICARE Part D QIC Reconsideration Project.

Government rationing really does "pull the plug on Grandma."

www.BradMD.com

Repetitive prostatic massage therapy for chronic refractory prostatitis: the Philippine experience

Nickel JC, Downey J, Feliciano Jr. AE, Hennenfent BR:
Repetitive prostatic massage therapy for chronic refractory prostatitis: the Philippine experience. Tech Urol. 1999 Sep;5(3):146-51.

Patients frustrated with failure of traditional therapy for prostatitis have traveled to the
Philippines and elsewhere for repetitive prostatic massage combined with antibiotic therapy.
The aim of our study was to evaluate prospectively the response of patients who traveled to
Manila to undergo this treatment. Twenty-six patients consented and were registered by the
Prostatitis Foundation (B.H.) and subsequently evaluated (J.C.N., J.D.) prior to and following
treatment (A.E.F.). Evaluation at baseline and after treatment consisted of standardized
history and previously validated prostatitis-specific Symptom Frequency Questionnaire (SFQ)
and Symptom Severity Index (SSI), International Prostate Symptom Score (I-PSS) and Quality
of Life (QoL) questionnaire, the O'Leary Sexual Function Inventory (SFI), and a Subjective
Global Assessment (SGA). Treatment in Manila consisted of triweekly prostatic massage
combined with specific culture directed and/or empirical antimicrobial therapy for 6 to 12
weeks. Twenty-two patients completed at least one follow-up assessment and 12 patients
completed 2-year assessment (average follow-up of 17 months in 22 patients). There was a
significant decrease in average symptom severity (SSI) by 4 months that continued for 2
years, but less improvement in symptom frequency (SFQ) and quality of life (QoL), and no
significant improvement in voiding symptoms (I-PSS) or sexual function (SFI) at time of last
assessment. Forty-six percent of the 22 evaluable patients had >60% decrease (significant
improvement) in symptom severity (SSI), whereas 27% had similar significant improvement in
frequency of symptoms (SFQ) when last assessed. Thirty-three percent reported marked
subjective improvement (SGA) at last evaluation. Of the 12 patients who completed the 2-year
follow-up, 5 of the original 26 had a significant and sustainable improvement in objective and
subjective measurements of frequency and severity of symptoms. The combination of prostatic
massage and antibiotics for treating difficult refractory cases of prostatitis may be promising,
but its ultimate value needs to be confirmed. Studies in patients with less refractory and
shorter duration disease may allow us to predict who will respond to this therapeutic
approach.

nanobacteria levels and symptoms of nanobacteria-associated interstitial cystitis/painful bladder syndrome

Decreased nanobacteria levels and symptoms of nanobacteria-associated interstitial cystitis/painful bladder syndrome after tetracycline treatment

Urological Research Institute of PLA, Southwest Hospital, Third Military Medical University,

Chongqing, 400038, People's Republic of China.

This study was designed to detect whether nanobacteria (NB) reside in urine and bladder

tissue samples of patients with interstitial cystitis/painful bladder syndrome (IC/PBS) and

whether antibiotic therapy targeting these organisms is effective in reducing NB levels and

IC/PBS symptoms.

Twenty-seven IC/PBS patients underwent cystoscopy. Bladder biopsies and urine samples

were obtained and cultured for NB, which were identified by indirect immunofluorescent

staining and transmission electron microscopy.

Eleven bladder samples showed growth of microbes that were identified to be similar to NB.

Homologous study of the 16S ribosomal RNA gene suggested that the NB could be the

pathogen. For enrolled 11 patients, NB levels decreased dramatically after tetracycline

treatment, and they reported significant reduction in the severity of IC/PBS symptoms.

A high prevalence of NB was observed in female IC/PBS, and anti-NB treatment effectively

improved the symptoms, which suggest that NB may cause some cases of IC/PBS.

Written by:
Zhang QH, Shen XC, Zhou ZS, Chen ZW, Lu GS, Song B. Are you the author?

Reference:
Int Urogynecol J Pelvic Floor Dysfunct. 2009 Sep 17. Epub ahead of print.
doi:10.1007/s00192-009-0994-7

PubMed Abstract
PMID:19760079

CONSORTIUM OF RESEARCHERS DISCOVER RETROVIRAL LINK TO CHRONIC FATIGUE SYNDROME

From an NIH press release. A very important new finding that a virus may be linked to Chronic Fatigue Syndrome. - BRH

CONSORTIUM OF RESEARCHERS DISCOVER RETROVIRAL LINK TO CHRONIC FATIGUE SYNDROME

Scientists have discovered a potential retroviral link to chronic fatigue syndrome, known as CFS, a debilitating disease that affects millions of people in the United States. Researchers from the Whittemore Peterson Institute (WPI), located at the University of Nevada, Reno, the National Cancer Institute (NCI), part of the National Institutes of Health, and the Cleveland Clinic, report this finding online Oct. 8, 2009, issue of Science.

"We now have evidence that a retrovirus named XMRV is frequently present in the blood of patients with CFS. This discovery could be a major step in the discovery of vital treatment options for millions of patients," said Judy Mikovits, Ph.D., director of research for WPI and leader of the team that discovered this association. Researchers cautioned however, that this finding shows there is an association between XMRV and CFS but does not prove that XMRV causes CFS.

The scientists provide a new hypothesis for a retrovirus link with CFS. The virus, XMRV, was first identified by Robert H. Silverman, Ph.D., professor in the Department of Cancer Biology at the Cleveland Clinic Lerner Research Institute, in men who had a specific immune system defect that reduced their ability to fight viral infections.

"The discovery of XMRV in two major diseases, prostate cancer and now chronic fatigue syndrome, is very exciting. If cause-and-effect is established, there would be a new opportunity for prevention and treatment of these diseases," said Silverman, a co-author on the CFS paper.

Commonality of an immune system defect in patients with CFS and prostate cancer led researchers to look for the virus in their blood samples. In this study, WPI scientists identified XMRV in the blood of 68 of 101 (67 percent) CFS patients. In contrast, they found that eight of 218 healthy people (3.7 percent) contained XMRV DNA. The research team not only found that blood cells contained XMRV but also expressed XMRV proteins at high levels and produced infectious viral particles. A clinically validated test to detect XMRV antibodies in patients' plasma is currently under development.

These results were also supported by the observation of retrovirus particles in patient samples when examined using transmission electron microscopy. The data demonstrate the first direct isolation of infectious XMRV from humans.


"These compelling data allow the development of a hypothesis concerning a cause of this complex and misunderstood disease, since retroviruses are a known cause of neurodegenerative diseases and cancer in man," said Francis Ruscetti, Ph.D., Laboratory of Experimental Immunology, NCI.

Retroviruses like XMRV have also been shown to activate a number of other latent viruses. This could explain why so many different viruses, such as Epstein-Barr virus, which was causally linked to Burkitt's and other lymphomas in the 1970s, have been associated with CFS. It is important to note that retroviruses, like XMRV, are not airborne.

"The scientific evidence that a retrovirus is implicated in CFS opens a new world of possibilities for so many people," said Annette Whittemore, founder and president of WPI and mother of a CFS patient. "Scientists can now begin the important work of translating this discovery into medical care for individuals with XMRV related diseases."

Dan Peterson, M.D., medical director of WPI added, "Patients with CFS deal with a myriad of health issues as their quality of life declines. I'm excited about the possibility of providing patients, who are positive for XMRV, a definitive diagnosis, and hopefully very soon, a range of effective treatments options."

The Whittemore Peterson Institute for Neuro Immune Disease exists to bring discovery, knowledge, and effective treatments to patients with illnesses that are caused by acquired dysregulation of both the immune system and the nervous system, often resulting in lifelong disease and disability. www.wpinstitute.org.

The Lerner Research Institute is home to Cleveland Clinic's laboratory, translational and clinical research. Its mission: to promote human health by investigating in the laboratory and the clinic the causes of disease and discovering novel approaches to prevention and treatments; to train the next generation of biomedical researchers; and to foster productive collaborations with those providing clinical care. More than 1,200 people in 11 departments work in research programs focusing on cardiovascular, cancer, neurologic, musculoskeletal, allergic and immunologic, eye, metabolic, and infectious disease. The Institute also is an integral part of the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University.


The National Cancer Institute (NCI) leads the National Cancer Program and the NIH effort to dramatically reduce the burden of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at http://www.cancer.gov or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

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 .
-------------------------------
REFERENCE: Lombardi VC, Ruscetti FW, Gupta JD, Pfost MA, Hagen KS, Peterson DL, Ruscetti SK, Bagni RK, Petrow-Sadowski C, Gold B, Dean M, Silverman RH, and Mikovits JA. Detection of Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome. Online October 8, 2009. Science.
--------------------

U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH NIH News
National Cancer Institute (NCI)
Embargoed for Release: Thursday, October 8, 2009, 2 p.m. EDT

CONTACTS:
NCI Office of Media Relations, 301-496-6641,

Whittemore Peterson Institute, Frankie Vigil, 775-336-4555,

Cleveland Clinic Corp. Communications, Megan F. Pruce, 216-445-7452,

PROSTATE TUMORS CAN CHANGE THE FUNCTION OF IMMUNE CELLS IN MICE

From an NIH press release:

PROSTATE TUMORS CAN CHANGE THE FUNCTION OF IMMUNE CELLS IN MICE

Researchers have discovered that prostate tumors in mice can cause immune cells known as CD8+ T cells to change their function from cells that have antitumor activity to cells that suppress immune responses. This finding, by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, has important implications for the design of immune-based therapies for cancer. The new study, available online, appears in the Oct. 15, 2009, issue of the Journal of Immunology.

"The conversion of CD8+ T cells into suppressor cells may be one of the mechanisms by which tumors restrict the immune system's ability to control tumor growth," said Arthur A. Hurwitz, Ph.D., head of the Tumor Immunity and Tolerance Group at NCI's Center for Cancer Research. "Studying this process in mice may help explain why some cancer patients have an initial response from their immune-based therapy, but this response fails with time."

In mice and humans, when the immune system encounters a pathogen or other foreign invader, it responds by mounting an immune response. Part of this response involves the recruitment and activation of CD8+ T cells, which are also called cytotoxic T cells or killer T cells, to help destroy the invader. CD8+ T cells also play a role in immune responses against tumor cells. Other T cells, known as CD4+ T regulatory cells, work to suppress CD8+ T cell activity. Immune suppression by these regulatory T cells helps prevent the body from attacking its own cells. A high level of CD4+ T regulatory cells is also associated with poor prognosis of some cancers. Moreover, research in mice has shown that blocking the immune suppressive activity of these regulatory T cells enhances the body's immunity against tumors, causing tumor growth to slow and improving the antitumor immune responses elicited by cancer vaccines.

Recent evidence in mice has suggested that CD8+ T cells can develop suppressive activities similar to those of CD4+ T regulatory cells. In addition, CD8+ suppressor cells have been found in cancer patients. The presence of these suppressor cells could explain earlier findings by Hurwitz's team that prostate tumor-specific CD8+ T cells injected into prostate tumor-bearing mice migrate to the tumors but then become unresponsive, or tolerized, to the tumor cells. It remained unclear, however, whether the suppressive CD8+ T cells have suppressor activity before they reach the tumor or whether they are converted into suppressor cells by the tumor.

In the new research, Hurwitz's team found that CD8+ T cells acquire immune suppressive functions after they enter the mouse tumor microenvironment, which encompasses nearby noncancerous cells and immune cells in addition to tumor cells. The researchers found that tumor-specific CD8+ T cells isolated from the tumors were able to suppress the proliferative capacity of nonspecific T cells, whereas tumor-specific CD8+ T cells isolated from lymph nodes of the mice were unable to do so.

This anti-proliferative activity appeared to be caused, in part, by substances secreted by the CD8+ T cells after they had been converted to suppressor cells. One of these substances, TGF-beta, is a protein that controls cell proliferation and differentiation and plays a role in cancer and other diseases. TGF-beta is thought to be involved in the immune-suppressive activity of CD4+ T-regulatory cells.

Next, the team investigated whether the conversion of tumor-specific CD8+ T cells to suppressor cells could be prevented. To do this, they administered tumor-specific CD4+ and CD8+ T cells to prostate tumor-bearing mice. Some CD4+ T cells act as helper cells and enhance the activity of other immune cells, including CD8+ T cells. The researchers found that, under these conditions, CD8+ T cells isolated from the prostate tumors no longer suppressed the proliferation of other T cells. Moreover, these cells produced less TGF-beta than cells that were not exposed to CD4+ T cells.

The researchers propose that activated CD4+ T cells that enter tumors may secrete factors that support the CD8+ T cell antitumor functions, or may help other immune cells located in the tumor block the processes by which CD8+ T cells acquire their suppressive activity.

Future work by this team will focus on defining the mechanisms by which tumor-specific CD8+ T cells gain their suppressive functions upon entering the mouse tumor microenvironment. "It is important to understand how these cells become suppressive and how they mediate suppression to find approaches to block these processes," said Hurwitz. "This will enhance our ability to generate more effective antitumor T cell responses in mice, which then might be translated to human."

For more information on Dr. Hurwitz's research, please go to .

NCI leads the National Cancer Program and the NIH effort to dramatically reduce the burden of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

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 .

------------------------------------
REFERENCE:
Shafer-Weaver, KA, Anderson, MJ, Stagliano K, Malyguine, A, Greenberg, NM, and Hurwitz AA. Cutting Edge: Tumor-Specific CD8+ T Cells Infiltrating Prostatic Tumors Are Induced to Become Suppressor Cells. J Immunol. Oct. 15, 2009. Vol. 183, No. 8.


U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH NIH News
National Cancer Institute (NCI)
For Immediate Release: Wednesday, October 7, 2009

CONTACT: NCI Office of Media Relations, 301-496-6641,

H1N1 - Swine Flu Video

This is the best H1N1, swine flu, video that I have seen so far.

H1N1 Video

NIBIB SCIENTISTS COMBINE MICROSCOPY METHODS TO INCREASE IMAGING EFFICIENCY IN CELL STRUCTURE STUDIES

This is an excellent new advance in microscopy. - BRH

NIBIB SCIENTISTS COMBINE MICROSCOPY METHODS TO INCREASE IMAGING EFFICIENCY IN CELL STRUCTURE STUDIES

New Method Produces High-Resolution Images of Thicker Specimen Samples

Scientists in the National Institute of Biomedical Imaging and Bioengineering (NIBIB) Laboratory of Bioengineering and Physical Science have developed a new technique that allows researchers to visualize fine details of cell structure three-dimensionally in thick sections, thus providing greater insight into how cells are organized and how they function. The work is described in a report published online this week in Nature Methods.

The new electron tomography method, referred to as BF STEM tomography, lets researchers image samples that are more than three times the thickness of typical samples.

Electron tomography is carried out at the nanoscale on individual cells. Conventionally, high-resolution imaging of biological specimens has been accomplished by cutting cells into thin sections (300 nanometers or less) and imaging each section separately. Although reconstructing an entire structure from thin sections is laborious, thin sections are used because images of thicker sections typically are blurred. Serial BF STEM tomography accomplishes the same work using fewer yet thicker specimen sections, leading to faster reconstruction of intact organelles, intracellular pathogens, and even entire mammalian cells.

Drs. Alioscka Sousa, Martin Hohmann-Marriott, Richard Leapman and colleagues in NIBIB, in collaboration with Dr. Joshua Zimmerberg and colleagues in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), demonstrated feasibility and advantages of BF-STEM tomography in a study of red blood cells infected with Plasmodium falciparum, a parasite that causes malaria. High-resolution 3D reconstructions of entire cells were generated by serially imaging just a few thick sections. The intricate system of red blood cell and parasite membranes, as well as several organelles, can be seen in detail.

"We believe that the new technique, which was conceived by Dr. Sousa on the project team, will lead to improved 3D visualization of larger internal structures in mammalian cells at a nanoscale. And it will complement cryo electron tomography and super-resolution optical imaging approaches," according to Dr. Leapman.

Most high-performance electron microscopes can readily be equipped to utilize the BF STEM tomography approach. "This exciting new method, with its ability to provide nanoscale structural details over three dimensions, has the potential for broad application in cell biology," says NIBIB Director Roderic Pettigrew. "This should open new vistas in the understanding of the interplay between cellular structure and function, and is a great example of NIBIB-supported research that moves medical science forward through technological innovation."

This work was supported by the Intramural Research Programs of the NIBIB and the NICHD at the National Institutes of Health. In addition, Dr. Hohmann-Marriott received support through the Joint NIST/NIBIB Postdoctoral Associateship Program of the National Research Council, USA.

NIBIB, a component of NIH, is dedicated to improving health by bridging the physical and biological sciences to develop and apply new biomedical technologies. Additional information and publications are available at .

The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit the Institute's Web site at .

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 .
------------
REFERENCE: Nanoscale 3D cellular imaging by axial scanning transmission electron tomography. Martin F Hohmann-Marriott, Alioscka A Sousa, Afrouz A Azari, Svetlana Glushakova, Guofeng Zhang, Joshua Zimmerberg & Richard D Leapman. Published online: 30 August 2009 | doi:10.1038/nmeth.1367.

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This NIH News Release is available online at:
.


U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH NIH News
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
For Immediate Release: Thursday, September 3, 2009

CONTACT: Cheryl Fee, 301-451-6772,

MicroRNAS IN BLOOD MAY BE BIOMARKERS OF PANCREATIC CANCER

We desperately need this new test for pancreatic cancer and we need a cure ASAP. - BRH.

MicroRNAS IN BLOOD MAY BE BIOMARKERS OF PANCREATIC CANCER

Small molecules known as microRNAs, which can be detected in blood samples, have the potential to help identify patients with pancreatic cancer, a study finds. The study, by researchers at The University of Texas M.D. Anderson Cancer Center in Houston, was supported by the Early Detection Research Network (EDRN) of the National Cancer Institute (NCI), part of the National Institutes of Health. The paper appeared online Sept. 1, 2009, in Cancer Prevention Research.

Pancreatic cancer is a highly fatal disease that is difficult to detect at early stages. In most patients, symptoms do not appear until the cancer is locally advanced or has spread to other parts of the body. The absence of symptoms in early-stage disease and the current lack of effective, minimally invasive screening and diagnostic techniques limit the available treatment options. Both contribute to the high mortality rate observed for patients with pancreatic cancer.

"The development of a minimally invasive test for the early detection and diagnosis of pancreatic cancer is greatly needed," said Sudhir Srivastava, Ph.D., chief of the Cancer Biomarkers Research Group in NCI's Division of Cancer Prevention. "An important step is to identify biomarkers for pancreatic cancer, such as microRNAs, circulating in the bloodstream that can be used to distinguish individuals with pancreatic cancer from individuals without the disease."

MicroRNAs, or miRNAs, are short strands of RNA. The miRNAs regulate gene expression by controlling the translation of a specific type of RNA called messenger RNA which relays the genetic instructions for making proteins. Previous research has indicated that miRNAs play important roles in regulating normal cell proliferation and in cancer. Altered patterns of miRNA expression have been seen in pancreatic cancer as well as many other cancers. In addition, it has recently been reported that tumor-derived miRNAs can be detected in blood and that these molecules are stable in stored samples. Thus, miRNAs circulating in the blood may have the potential to serve as novel biomarkers for the detection and diagnosis of pancreatic cancer.

To evaluate the feasibility of using miRNAs in the blood as biomarkers for pancreatic cancer, the researchers selected a set of four miRNAs that have been associated with pancreatic cancer -- miR-21, miR-210, miR-155, and miR-196a. Among these, miR-155 has been identified as a candidate biomarker for early pancreatic cancer, and expression of miR196a has been shown to increase during disease progression. Levels of all four miRNAs were assessed in blood samples from 28 pancreatic cancer patients and 19 healthy volunteers. The study population consisted of patients with pathologically confirmed pancreatic cancer and healthy disease free individuals recruited at the M.D. Anderson Cancer Center between 2002 and 2008. The team found that sensitivity -- or ability to accurately detect pancreatic cancer -- using the panel of four miRNAs was 64 percent. The panel also showed an 89 percent specificity, which indicates the proportion of study participants who did not have pancreatic cancer and were correctly identified as being disease free.

"Our results demonstrate proof of principle in developing a blood test based on miRNA signatures for pancreatic cancer," said senior author Subrata Sen, Ph.D., of M.D. Anderson's Department of Molecular Pathology. "More work is needed to evaluate this strategy in different grades and stages of the disease. We are in the process of initiating such studies in collaboration with members of EDRN." For example, the researchers will test the ability of the miRNAs to detect pancreatic cancer in separate patient populations.

Pancreatic cancer, the fourth most common cause of cancer death in the United States, has a poor survival rate compared with that of other types of cancer. Less than five percent of the patients with pancreatic cancer survive five years past diagnosis.

For more information about the Department of Molecular Pathology at M.D. Anderson, please go to .

For more information on NCI's EDRN, please go to: .

NCI leads the National Cancer Program and the NIH effort to dramatically reduce the burden of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

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 .

##

This NIH News Release is available online at:
.

U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH NIH News
National Cancer Institute (NCI)
Embargoed for Release: Tuesday, September 1, 2009, 1 p.m., EDT

CONTACT: NCI Office of Media Relations, 301-496-6641, ncipressofficers@mail.nih.gov>

STUDIES IN ANIMALS SUGGEST 2009 H1N1 VIRUS MAY HAVE BIOLOGICAL ADVANTAGE OVER SEASONAL INFLUENZA VIRUSES

Another study that suggests that the swine flu may be a huge problem this winter. - BRH

STUDIES IN ANIMALS SUGGEST 2009 H1N1 VIRUS MAY HAVE BIOLOGICAL ADVANTAGE OVER SEASONAL INFLUENZA VIRUSES

U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH NIH News
National Institute of Allergy and Infectious Diseases (NIAID)
For Immediate Release: Monday, August 31, 2008

CONTACT: Anne A. Oplinger, 301-402-1663,

Preliminary findings in ferrets suggest that the novel 2009 H1N1 influenza virus may outcompete human seasonal influenza viruses, researchers say. Tests in animals showed that levels of the 2009 H1N1 virus rose more quickly than levels of the seasonal virus strains, and the new virus caused more severe disease. In line with previous findings by other research groups, the University of Maryland researchers also observed that the novel H1N1 virus was transmitted more easily from infected to uninfected ferrets than either of the two seasonal influenza viruses.

The researchers found no evidence that the 2009 H1N1 virus combined with either of two seasonal flu viruses to form new, so-called reassortant viruses. These findings suggest that while 2009 H1N1 virus probably will predominate in the coming flu season, there may not be biological pressure for the new virus to re-combine with other circulating viruses, the researchers say.

The work was done by Daniel Perez, Ph.D., and colleagues from the University of Maryland. The researchers were supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

"This elegant study, conducted in a useful animal model of human influenza, provides important information about how the 2009 H1N1 influenza virus interacts with other flu virus strains," says NIAID Director Anthony S. Fauci, M.D. "The results suggest that 2009 H1N1 influenza may outcompete seasonal flu virus strains and may be more communicable as well. These new data, while preliminary, underscore the need for vaccinating against both seasonal influenza and the 2009 H1N1 influenza this fall and winter."

When the investigators inoculated ferrets with 2009 H1N1 virus plus either seasonal H1N1 virus or seasonal H3N2 virus, the animals became co-infected with both viruses. However, only the 2009 H1N1 virus was then transmitted from co-infected ferrets to uninfected ferrets; there was no evidence that either of the seasonal flu viruses were transmitted between co-infected and uninfected animals. "The H1N1 pandemic virus has a clear biological advantage over the two main seasonal flu strains and all the makings of a virus fully adapted to humans," says Dr. Perez.

Next, the team conducted experiments to learn whether 2009 H1N1 virus would combine with seasonal flu viruses in co-infected animals to create new reassortant viruses. Some scientists have speculated that reassortant viruses may be more virulent or transmissible than either 2009 H1N1 or seasonal flu viruses alone. The researchers collected virus-containing material from the ferrets' nasal cavities, but found no evidence of reassortment between the 2009 H1N1 and seasonal influenza strains, either in ferrets that were directly infected with both viruses or in ferrets that came in contact with the co-infected animals.

The investigators' findings are posted on PLoS Currents: Influenza, a Web site for rapid communication of new scientific data on influenza. Submissions to PLoS Currents: Influenza are screened by a panel of leading influenza experts prior to posting but do not undergo formal peer review. The new research may be submitted later for peer review and eventual publication in scientific journals.

This research was supported in part through the NIAID Centers of Excellence for Influenza Research and Surveillance (CEIRS) program.

For more information on influenza, visit for one-stop access to U.S. government information on avian and pandemic influenza. Also, visit NIAID's Flu Portal,

NIAID conducts and supports research-at NIH, throughout the United States, and worldwide-to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.

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 .
---------------------------------
REFERENCE: Perez et al. Fitness of pandemic H1N1 and seasonal influenza A viruses during co-infection. PLoS Currents: Influenza. Posted Aug. 25, 2009. RRN1011. Available at:

Additional information about research in Dr. Perez's laboratory is at:


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This NIH News Release is available online at:
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NIH STUDY REVEALS NEW GENETIC CULPRIT IN DEADLY SKIN CANCER

New information may lead to a new treatment for deadly melanoma. This is why genetic testing is so important. - BRH

NIH STUDY REVEALS NEW GENETIC CULPRIT IN DEADLY SKIN CANCER
Sequencing Work Points to New Target for Melanoma Treatment

Drawing on the power of DNA sequencing, National Institutes of Health researchers have identified a new group of genetic mutations involved in the deadliest form of skin cancer, melanoma. This discovery is particularly encouraging because some of the mutations, which were found in nearly one-fifth of melanoma cases, reside in a gene already targeted by a drug approved for certain types of breast cancer.

In the United States and many other nations, melanoma is becoming increasingly more common. A major cause of melanoma is thought to be sun exposure; the ultraviolet radiation in sunlight can damage DNA and lead to cancer-causing genetic changes within skin cells.

In work published in the September issue of Nature Genetics, a team led by Yardena Samuels, Ph.D., of the National Human Genome Research Institute (NHGRI) sequenced the protein tyrosine kinase (PTK) gene family in tumor and blood samples from people with metastatic melanoma. The samples were collected by the study's coauthor Steven Rosenberg, M.D., Ph.D., a leading expert on melanoma and chief of surgery at the National Cancer Institute (NCI).

The PTK family includes many genes that, when mutated, promote various types of cancer. However, relatively little had been known about roles played by PTK genes in human melanoma. The NIH study was among the first to use large-scale DNA sequencing to systematically analyze all 86 members of the PTK gene family in melanoma samples.

The team's initial survey, which involved samples from 29 melanoma patients, identified mutations in functionally important regions of 19 PTK genes, only three of which had been previously implicated in melanoma. The researchers then conducted more detailed analyses of those 19 genes in samples from a total of 79 melanoma patients.

One of the newly implicated genes stood out from the rest. Researchers detected mutations in the ERBB4 gene (also known as HER4) in 19 percent of patients' tumors, making it by far the most frequently mutated PTK gene in melanoma. In addition, researchers found that many ERBB4 mutations were located in functionally important areas similar to those seen in other PTK oncogenes involved in lung cancer, brain cancer and gastric cancer.

Next, the researchers moved on to laboratory studies of melanoma cells with ERBB4 mutations. They found that these melanoma cells were dependent on the presence of mutant ERBB4 for their growth. What's more, the melanoma cells grew much more slowly when they were exposed to a chemotherapeutic drug known to inhibit ERBB4. The drug, called lapatinib (Tykerb), was approved by the Food and Drug Administration in 2007 for combination use in breast cancer patients already taking the drug capecitabine (Xeloda).

Encouraged by their study results, the researchers are planning a clinical trial using lapatinib in patients with metastatic melanoma harboring ERBB4 mutations. The clinical trial will be conducted under the direction of Dr. Rosenberg at the NIH Clinical Center. "This collaborative study represents an ideal example of how sophisticated genetic analyses can be translated to the benefit of cancer patients," said Dr. Rosenberg.

"We have found what appears to be an Achilles' heel of a sizable share of melanomas," said Dr. Samuels, who is an investigator in the Cancer Genetics Branch of the NHGRI's Division of Intramural Research. "Though additional work is needed to gain a more complete understanding of these genetic mutations and their roles in cancer biology, our findings open the door to pursuing specific therapies that may prove useful for the treatment of melanoma with ERBB4 mutations."

In addition to ERBB4, the researchers identified two additional PTK genes, FLT1 and PTK2B, with a relatively high rate of mutations in melanoma. Each of these genes was mutated in about 10 percent of the tumor samples studied.

NHGRI Scientific Director Eric D. Green, M.D., Ph.D., pointed out how such research is helping to lay the groundwork for the era of personalized medicine. "We envision a day when each cancer patient will have therapies tailored to the specific genetic profile of his or her tumor. Ultimately, this should lead to more effective and less toxic approaches to cancer care," said Dr. Green, who directs the NIH Intramural Sequencing Center, which generated the DNA sequence data for the melanoma study.

In addition to NIH scientists, the team included a researcher from the Johns Hopkins Kimmel Cancer Center in Baltimore.

In May 2009, Dr. Samuel's group reported in Nature Genetics another large-scale DNA sequencing study of a different group of genes involved in melanoma, the matrix metalloproteinase (MMP) gene family. This earlier study found that one gene, MMP-8, thought to spur cancerous growth actually served to inhibit it. Those findings are now helping to shape melanoma treatment strategies aimed at MMP genes.

For high resolution micrographs of metastatic melanoma, go to and .

NCI leads the National Cancer Program and the NIH effort to dramatically reduce the burden of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).



NHGRI is one of the 27 institutes and centers at the NIH, an agency of the Department of Health and Human Services. The NHGRI Division of Intramural Research develops and implements technology to understand, diagnose and treat genomic and genetic diseases. Additional information about NHGRI can be found at its Web site, .

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 .

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The NIH has a New Director

The NIH has sworn in a new director. Francis S. Collins, MD, PhD. He was a leader of the Human Genome Project. - BRH

FRANCIS S. COLLINS, M.D., PH.D., SWORN IN AS NIH DIRECTOR
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U.S. Department of Health and Human Services
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For Immediate Release: Monday, August 17, 2009

CONTACT: NIH Office of Communications, 301-496-5787,

FRANCIS S. COLLINS, M.D., PH.D., SWORN IN AS NIH DIRECTOR

Francis S. Collins, M.D., Ph.D., today became the 16th director of the National Institutes of Health. He was nominated to lead the NIH, the nation's premiere biomedical research agency, by President Barack Obama on July 8, and was unanimously confirmed by the U.S. Senate on August 7.

In his July 8 nomination announcement, President Obama stated: "The National Institutes of Health stands as a model when it comes to science and research. My administration is committed to promoting scientific integrity and pioneering scientific research and I am confident that Dr. Francis Collins will lead the NIH to achieve these goals. Dr. Collins is one of the top scientists in the world, and his groundbreaking work has changed the very ways we consider our health and examine disease."

"As a scientist, physician, and passionate visionary, Dr. Collins will further NIH's ultimate mission to improve human health," said U.S. Health and Human Services Secretary Kathleen Sebelius. "He is an ideal choice to lead the NIH and I look forward to working closely with him."

"I am truly honored and humbled to take the helm today of the world's leading organization supporting biomedical research," Dr. Collins said. "The scientific opportunities in both the basic and clinical realms are unprecedented, and the talent and dedication of the grantees and the staff guarantee that this will be a truly exciting era."

Dr. Collins, 59, a physician-geneticist noted for his landmark discoveries of disease genes and his leadership of the Human Genome Project, served as director of NIH's National Human Genome Research Institute (NHGRI) from 1993-2008. Under his direction, the Human Genome Project consistently met projected milestones ahead of schedule and under budget. This remarkable international project culminated in April 2003 with the completion of a finished sequence of the human DNA instruction book.

In addition to his achievements as the NHGRI director, Dr. Collins' own research laboratory discovered a number of important genes, including those responsible for cystic fibrosis, neurofibromatosis, Huntington's disease, a familial endocrine cancer syndrome, and most recently, genes for type 2 diabetes and the gene that causes Hutchinson-Gilford progeria syndrome. Dr. Collins has a longstanding interest in the interface between science and faith, and has written about this in The Language of God: A Scientist Presents Evidence for Belief (Free Press, 2006), which spent many weeks on The New York Times bestseller list. He is the author of a new book on personalized medicine, The Language of Life: DNA and the Revolution in Personalized Medicine (HarperCollins, to be published in early 2010).

Dr. Collins received a B.S. in chemistry from the University of Virginia, a Ph.D. in physical chemistry from Yale University, and an M.D. with honors from the University of North Carolina at Chapel Hill. Prior to coming to the NIH in 1993, he spent nine years on the faculty of the University of Michigan, where he was a Howard Hughes Medical Institute investigator. He is an elected member of the Institute of Medicine and the National Academy of Sciences. Dr. Collins was awarded the Presidential Medal of Freedom in November 2007.

Raynard S. Kington, M.D., Ph.D., who has served as acting NIH director since mid-October, will return to his role as NIH principal deputy director.

NIH has more than 19,000 employees and a fiscal year 2009 budget of $30.6 billion. It supports more than 325,000 research personnel at more than 3,100 institutions throughout the U.S., and around the world.

More information about Dr. Collins is available at , and a high-resolution photo is available for download at .

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 .

NEW DIAGNOSTIC IMAGING DEVICES AT THE NIH CLINICAL CENTER TO AUTOMATICALLY RECORD RADIATION EXPOSURE

It's about time we started keeping track of radiation exposure. I have seen the system fail to total up radiation exposures too many times and am fearful that there are going to be long term consequences for many people. Patients need total radiation exposure from X-rays, CT Scans, and dental X-rays tallied up each year. - BRH

NEW DIAGNOSTIC IMAGING DEVICES AT THE NIH CLINICAL CENTER TO AUTOMATICALLY RECORD RADIATION EXPOSURE

U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH NIH News
NIH Clinical Center (CC)
For Immediate Release: Monday, August 17, 2009

CONTACT: Bill Schmalfeldt, 301-496-2563,

NEW DIAGNOSTIC IMAGING DEVICES AT THE NIH CLINICAL CENTER TO AUTOMATICALLY RECORD RADIATION EXPOSURE

Radiology and Imaging Sciences at the National Institutes of Health Clinical Center has taken a significant step to further safeguard clinical research patients at the NIH Clinical Center who are exposed to radiation during certain imaging tests. Computed tomography (CT) and positron emission tomography (PET)/CT equipment purchased by the Clinical Center will now be required to routinely record radiation dose exposure in a patient's hospital-based electronic medical record.

"When a hospital or clinic patient receives a medication or a treatment, it is routinely recorded in the patient's medical record," said John I. Gallin, M.D., director of the Clinical Center, NIH's clinical research hospital in Bethesda, Md. "The Clinical Center's approach is an important first step in making it possible to more easily document and track information about a patient's exposure to radiation."

Today, electronic radiology information systems in hospitals generally do not collect or report radiation exposures. "CT and PET/ CT scanners do not currently forward data on radiation dose to our radiology information systems," said Dr. David A. Bluemke, M.D., Ph.D. Bluemke is director of Radiology and Imaging Sciences at the Clinical Center.

The risk of exposure to low doses of medical radiation from diagnostic medical-imaging tests isn't known, but very high radiation doses have the potential to cause cancer. The ability to keep track of an individual's exposure to radiation through routine imaging tests is needed so that researchers can begin to determine if these exposures pose a health risk.

"The National Council on Radiation Protection and Measurements reported recently that Americans received seven times more radiation exposure from medical tests in 2006 than was the case in the 1980s," said Ronald Neumann, M.D., chief of nuclear medicine and deputy associate director for imaging sciences at the Clinical Center. "CT and cardiac nuclear medicine studies accounted for much of this increased medical radiation exposure."

Ultimately, radiation dosage could become a standard element of a universal electronic medical record used to assess radiation risk from life-long medical testing, the Clinical Center radiologists said. "Recording radiation dose is technically possible and an ethical imperative," Neumann said.

"The NIH Clinical Center also will require that newly purchased equipment allows patients to record their radiation dose exposure in their own personal health record," Bluemke added. Online resources to help individuals organize their health information as a personal medical record are becoming more prevalent. Currently, patients can easily receive their diagnostic imaging studies records on CD-ROM, Bluemke said. The NIH Clinical Center's imaging program will work with vendors who supply Clinical Center imaging equipment to develop software tools to extract the examination type, date, and radiation dose exposure from the CD-ROM, for uploading to a personal health record. As both the American College of Radiology and the Radiological Society of North America have recommended, patients should keep a record of their X-ray history.

About 25,000 CT and 1,250 PET/CT scans are performed at the Clinical Center each year as part of NIH research protocols. The clinical research hospital currently houses five CT scanners, and two PET/CT scanners.

The NIH Clinical Center (CC) is the clinical research hospital for the National Institutes of Health. Through clinical research, physician-investigators translate laboratory discoveries into better treatments, therapies and interventions to improve the nation's health. For more information, visit .

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 .

Hereditary Spastic Paraplegias

A new study proposes a mechanism for the hereditary spastic paraplegias. The study suggests that a gene is defective and a substance called atlastin is defective in sufferers. Without these things a protein cannot be produced that supports the endoplasmic reticulum. - BRH

FROM NERVE ROOTS TO PLANT ROOTS - RESEARCHERS ARE GAINING UNEXPECTED INSIGHTS INTO HEREDITARY SPASTIC PARAPLEGIA

U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH NIH News
National Institute of Neurological Disorders and Stroke (NINDS)
Embargoed for Release: Thursday, August 6, 2009, Noon, EDT

CONTACT: Daniel Stimson, NINDS, 301-496-5751

FROM NERVE ROOTS TO PLANT ROOTS - RESEARCHERS ARE GAINING UNEXPECTED INSIGHTS INTO HEREDITARY SPASTIC PARAPLEGIA

Sprouting. Branching. Pruning. Neuroscientists have borrowed heavily from botanists to describe the way that neurons grow, but analogies between the growth of neurons and plants may be more than superficial. A new study from the National Institutes of Health and Harvard Medical School suggests that neurons and plant root cells may grow using a similar mechanism.

The research also sheds light on the hereditary spastic paraplegias (HSP), a group of inherited neurological disorders in which some of the longest neurons in the body fail to grow and function properly. The genes behind HSP and their roles inside neurons are poorly understood. However, the study suggests that several forms of HSP share an underlying defect with each other - and with abnormal root hair development in a plant widely used for agricultural research.

The strange implication is that the plant, Arabidopsis thaliana (mouse-ear cress), could prove useful for further research on HSP.

"This study provides us with valuable new insights that will stimulate research toward therapies for hereditary spastic paraplegias," says Craig Blackstone, M.D., Ph.D., an investigator at NIH's National Institute of Neurological Disorders and Stroke (NINDS) and an HSP expert. Dr. Blackstone performed the study in collaboration with William Prinz, Ph.D., an investigator at the NIH's National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and Tom Rapoport, Ph.D., a Howard Hughes Medical Institute investigator and a professor of cell biology at Harvard Medical School.

HSP primarily affects corticospinal neurons, which extend projections called axons from the brain's cerebral cortex to the spinal cord. The longest corticospinal axons extend nearly all the way down the spinal cord - a distance up to about three feet - in order to control movement in the legs. In HSP, these long axons develop abnormally or they degenerate later in life, causing muscle stiffness and weakness in the legs. HSP exists in many forms in different families, and more than 40 genes have been implicated in the disease.

In the new study, published in Cell, the researchers propose that defects in the shaping of a subcellular structure known as the endoplasmic reticulum (ER) are a common cause of HSP. The ER - named for its reticulated (or net-like) shape - is a cellular factory, where molecules such as proteins and lipids that are vital to cell growth are made and packaged for shipping to various cellular destinations. The researchers theorize that in several forms of HSP, the ER loses its complex shape and is unable to support the growth or maintenance of long corticospinal axons.

Several years ago, other researchers showed that similar ER defects in Arabidopsis impair the growth of the plant's root hairs. These are wispy, microscopic projections that grow from the plant's individual root cells.

The new study focuses on a gene called atlastin. This gene is defective in about 10 percent of HSP cases, and in previous research, Dr. Blackstone's group showed that it has a role in axon growth. The new study reveals that the atlastin protein is necessary for maintaining the shape of the ER in mammalian cells, and that an analogous protein called Sey1p performs the same function in baker's yeast.

The researchers demonstrate that ER shaping defects have general relevance for HSP, by showing a connection between atlastin and a group of proteins known as the DP1 family. Years ago, Drs. Prinz and Rapoport reported that a yeast analog of DP1 regulates the shape of the ER in yeast. Meanwhile, others researchers had independently reported that mutations in REEP1, a member of the DP1 family, cause 3 percent to 8 percent of HSP cases. The new study shows that atlastin interacts physically with DP1 in mammalian cells, and that Sey1p (the yeast atlastin) interacts with the DP1 analog in yeast.

Finally, Dr. Blackstone's study notes that Arabidopsis has an analog of atlastin, called Root Hair Defective 3 (RHD3). Mutations affecting RHD3 cause the plant to grow short, wavy root hairs.

If this connection between axon growth and root hair growth withstands further study, Arabidopsis could be a useful tool for investigating mechanisms of HSP. Arabidopsis is easy to raise in the lab, and the short root hairs of the RHD3 mutant are easy to observe, compared to the growth defects in atlastin-deficient neurons and yeast. Dr. Blackstone hopes to collaborate with other researchers to initiate a search for genes and compounds that correct root hair development in the RHD3 mutant, which might provide valuable therapeutic insights into HSP.

(HTML version includes photo):

The photo caption is: Top: Rat cortical neurons. Bottom: Arabidopsis roots. Left side shows normal neurons and root hairs. Right side shows the effects of atlastin/RHD3 deficiency, with shortening of both and waviness of root hairs. Neuron images courtesy of Dr. Craig Blackstone, NINDS. Arabidopsis images courtesy of Dr. John Schiefelbein, University of Michigan, Ann Arbor.

Reference: Hu J, Shibata Y, Zhu P-P, Voss C, Rismanchi N, Prinz W, Rapoport TA, and Blackstone C. "A Class of Dynamin-Like GTPases Involved in the Generation of the Tubular ER Network." Cell, Vol. 138, August 7, 2009.

NINDS is the nation's primary supporter of biomedical research on the brain and nervous system. NIDDK conducts and supports basic and clinical research and research training on some of the most common, severe and disabling conditions affecting Americans. The Institute's research interests include: diabetes and other endocrine and metabolic diseases; digestive diseases, nutrition, and obesity; and kidney, urologic and hematologic diseases.

Herpes Simplex II Increases Risk of HIV Regardless of Treatment

Infection with Herpes Simplex II increases the risk of contracting HIV even if the herpes lesions have healed over. This is because an increase in white blood cells remains at the site, even when it it is healed, and HIV uses these white blood cells (CD4+ T cells) to infect the human body. - BRH

SCIENTISTS LEARN WHY EVEN TREATED GENITAL HERPES SORES BOOST THE RISK OF HIV INFECTION

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SCIENTISTS LEARN WHY EVEN TREATED GENITAL HERPES SORES BOOST THE RISK OF HIV INFECTION

New research helps explain why infection with herpes simplex virus-2 (HSV-2), which causes genital herpes, increases the risk for HIV infection even after successful treatment heals the genital skin sores and breaks that often result from HSV-2.

Scientists have uncovered details of an immune-cell environment conducive to HIV infection that persists at the location of HSV-2 genital skin lesions long after they have been treated with oral doses of the drug acyclovir and have healed and the skin appears normal. These findings are published in the advance online edition of Nature Medicine on Aug. 2.

Led by Lawrence Corey, M.D., and Jia Zhu, Ph.D., of the Fred Hutchinson Cancer Research Center and Anna Wald, M.D., M.P.H., of the University of Washington, both in Seattle, the study was funded mainly by the National Institute of Allergy and Infectious Diseases (NIAID) with support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, both part of the National Institutes of Health.

"The findings of this study mark an important step toward understanding why HSV-2 infection increases the risk of acquiring HIV and why acyclovir treatment does not reduce that risk," says NIAID Director Anthony S. Fauci, M.D. "Understanding that even treated HSV-2 infections provide a cellular environment conducive to HIV infection suggests new directions for HIV prevention research, including more powerful anti-HSV therapies and ideally an HSV-2 vaccine."

One of the most common sexually transmitted infections worldwide, HSV-2 is associated with a two- to three-fold increased risk for HIV infection. Some HSV-2-infected people have recurring sores and breaks in genital skin, and it has been hypothesized that these lesions account for the higher risk of HIV acquisition. However, recent clinical trials, including an NIAID-funded study completed last year, demonstrated that successful treatment of such genital herpes lesions with the drug acyclovir does not reduce the risk of HIV infection posed by HSV-2 . The current study sought to understand why this is so and to test an alternative theory.

"We hypothesized that sores and breaks in the skin from HSV-2 are associated with a long-lasting immune response at those locations, and that the response consists of an influx of cells that are a perfect storm for HIV infection," says Dr. Corey, co-director of the Vaccine and Infectious Diseases Institute at The Hutchinson Center and head of the Virology Division in the Department of Laboratory Medicine at the University of Washington. "We believe HIV gains access to these cells mainly through microscopic breaks in the skin that occur during sex."

The research team took biopsies of genital skin tissue from eight HIV-negative men and women who were infected with HSV-2. These biopsies were taken at multiple time points: when the patients had genital herpes sores and breaks in the skin, when these lesions had healed, and at two, four and eight weeks after healing. The researchers also took biopsies from four of the patients when herpes lesions reappeared and the patients underwent treatment with oral acyclovir. The scientists continued to take biopsies at regular intervals for 20 weeks after the lesions had healed. For comparison, the investigators also took biopsies from genital tissue that did not have herpes lesions from the same patients.

Previous research has demonstrated that immune cells involved in the body's response to infection remain at the site of genital herpes lesions even after they have healed. The scientists conducting the current study made several important findings about the nature of these immune cells. First, they found that CD4+ T cells-the cells that HIV primarily infects-populate tissue at the sites of healed genital HSV-2 lesions at concentrations 2 to 37 times greater than in unaffected genital skin. Treatment with acyclovir did not reduce this long-lasting, high concentration of HSV-2-specific CD4+ T cells at the sites of healed herpes lesions.

Second, the scientists discovered that a significant proportion of these CD4+ T cells carried CCR5 or CXCR4, the cell-surface proteins that HIV uses (in addition to CD4+ T cells) to enter cells. The percentage of CD4+ T cells expressing CCR5 during acute HSV-2 infection and after healing of genital sores was twice as high in biopsies from the sites of these sores as from unaffected control skin. Moreover, the level of CCR5 expression in CD4+ T cells at the sites of healed genital herpes lesions was similar for patients who had been treated with acyclovir as for those who had not.

Third, the scientists found a significantly higher concentration of immune cells called dendritic cells with the surface protein called DC-SIGN at the sites of healed genital herpes lesions than in control tissue, whether or not the patient was treated with acyclovir. Dendritic cells with DC-SIGN ferry HIV particles to CD4+ T cells, which the virus infects. The DC-SIGN cells often were near CD4+ T cells at the sites of healed lesions-an ideal scenario for the rapid spread of HIV infection.

Finally, using biopsies from two study participants, the scientists found laboratory evidence that HIV replicates three to five times as quickly in cultured tissue from the sites of healed HSV-2 lesions than in cultured tissue from control sites.

All four of these findings help explain why people infected with HSV-2 are at greater risk of acquiring HIV than people who are not infected with HSV-2, even after successful acyclovir treatment of genital lesions.

"HSV-2 infection provides a wide surface area and long duration of time for allowing HIV access to more target cells, providing a greater chance for the initial 'spark' of infection," the authors write. This spark likely ignites once HIV penetrates tiny breaks in genital skin that commonly occur during sex. "Additionally," the authors continue, "the close proximity to DC-SIGN-expressing DCs [dendritic cells] is likely to fuel these embers and provide a mechanism for more efficient localized spread of initial infection." The investigators conclude that reducing the HSV-2-associated risk of HIV infection will require diminishing or eliminating the long-lived immune-cell environment created by HSV-2 infection in the genital tract, ideally through an HSV vaccine. Further, they hypothesize that other sexually transmitted infections (STIs) may create similar cellular environments conducive to HIV infection, explaining why STIs in general are a risk factor for acquiring HIV.

For more information about HIV/AIDS research, go to , and for more information about HSV-2 research, go to .

NIAID conducts and supports research-at NIH, throughout the United States, and worldwide-to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at .

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 .

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 .
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REFERENCES:

J Zhu et al. Persistence of HIV-1 receptor-positive cells after HSV-2 reactivation is a potential mechanism for increased HIV-1 acquisition. Nature Medicine DOI: 10.1038/nm2006 (2009).

C Celum et al. Effect of aciclovir on HIV-1 acquisition in herpes simplex virus 2 seropositive women and men who have sex with men: a randomised, double-blind, placebo-controlled trial. Lancet DOI: 10.1016/S0140-6736(08)60920-4 (2008).

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.National Institute of Health, National Institute of Allergy and Infectious Disease, Lawrence Corey, Infectious disease, HIV, Clinical trial, Fred Hutchinson Cancer Research Center, University of Washington

RISK OF PANCREATIC CANCER LINKED TO VARIATION IN GENE THAT DETERMINES BLOOD TYPE

A gene variation or gene defect has been found that increases the risk of pancreatic cancer, which is one of the deadliest of all cancers. - BRH

RISK OF PANCREATIC CANCER LINKED TO VARIATION IN GENE THAT DETERMINES BLOOD TYPE
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RISK OF PANCREATIC CANCER LINKED TO VARIATION IN GENE THAT DETERMINES BLOOD TYPE

Common variants of the gene that determines human blood type are associated with an increased risk of pancreatic cancer, according to a study by scientists at the National Cancer Institute (NCI), part of the National Institutes of Health, and colleagues from many universities and research institutions. The study, published online Aug. 2, 2009, in Nature Genetics, is consistent with an observation first made more than 50 years ago.

In the study, the researchers discovered that genetic variation in a region of chromosome 9 that contains the gene for ABO blood type was associated with pancreatic cancer risk. Individuals with the variant that results in blood types A, B, or AB were at an increased risk of pancreatic cancer, compared to those with the variant for blood type O. This finding is consistent with previous research, some of it dating back to the 1950s and 1960s, that had shown increased risks of gastric and pancreatic cancer among individuals of the A and B blood groups (i.e., blood types A, B, and AB). The latest results provide a genetic basis for those earlier observations.

A person's blood type depends on which form or forms of the ABO gene they inherit from their parents. The protein produced by the ABO gene determines the type of carbohydrates (complex sugars) that are present on the surface of red blood cells and other cells, including cells of the pancreas. The proteins encoded by the A and B forms of the gene transfer different carbohydrates onto the cell surfaces to make A and B blood types. The O form encodes a protein that is unable to transfer carbohydrates. Studies by other researchers have shown that ABO protein encoding in pancreatic tumor cells is different than in normal pancreatic cells.

To discover genetic variations that contribute to pancreatic cancer risk, the research team conducted a genome-wide association study (GWAS). In a GWAS, researchers analyze common variants, called single-nucleotide polymorphisms (SNPs), in the genomes of people with a disease and people without the disease. Initially, the research team studied the genomes of 1,896 patients with pancreatic cancer and 1,939 control subjects to identify SNPs with a strong association with pancreatic cancer. The team then verified its findings by studying the genomes of another 2,457 people with pancreatic cancer and 2,654 people without the disease. In the end, they identified several SNPs on the long arm of chromosome 9 that were associated with pancreatic cancer risk and mapped to the ABO gene.

"Only by working across disciplines and with more than a dozen research groups were we able to make this important discovery of the potential role of the ABO gene in pancreatic cancer risk," said co-author Patricia Hartge, Sc.D., of NCI's Division of Cancer Epidemiology and Genetics (DCEG). "Although it will take much more work, this finding may lead to improved diagnostic and therapeutic interventions that are so desperately needed."


Pancreatic cancer is the fourth leading cause of cancer death in the United States. It is difficult to detect, and in many people it is not diagnosed until after the disease has spread to other parts of the body. Less than five percent of Americans with pancreatic cancer survive five years past diagnosis. Risk factors include smoking, diabetes, race, and a family history of the disease.

"Pancreatic cancer is the newest beneficiary of so-called high-throughput genotyping that, over the past two years, has yielded scores of genetic hot-spots linked to risk for cancer and other diseases," said co-author Stephen J. Chanock, M.D., chief of NCI's Laboratory of Translational Genomics in DCEG. "As more variants are discovered and follow-up studies are conducted to examine the biological effects of these variants, a better understanding will emerge of the inherited risk factors and mechanisms that lead to the development of pancreatic cancer."

The study was part of PanScan, a GWAS of pancreatic cancer conducted by the Pancreatic Cancer Cohort Consortium, composed of 14 academic centers. The investigators are conducting whole-genome scans to identify common genetic variants that may be markers of susceptibility to pancreatic cancer.

Analyses and data from PanScan will be available through NCI's caBIG (Cancer Biomedical Informatics Grid). The summary results for similar data on breast and prostate cancer are already freely available to other researchers at this Web site.

For more information on Dr. Hartge's research, please go to .

For more information on Dr. Chanock's research, please go to .

For more information about PanScan, please go to .

NCI leads the National Cancer Program and the NIH effort to dramatically reduce the burden of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

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 .
----------------------
REFERENCE: Amundadottir L., et al. Genome-wide association study identifies ABO Blood Group Susceptibility Variants for Pancreatic Cancer. "Nature Genetics." Online August 2, 2009.

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Keywords: National Institute of Health, United States, National Cancer Institute, Genome-wide association study, United States Department of Health and Human Services, National Cancer Program, Single-nucleotide polymorphism

GENES KEY TO STAPH DISEASE SEVERITY, DRUG RESISTANCE FOUND HITCHHIKING TOGETHER

A new study finds that resistance and virulence can travel together. - BRH

GENES KEY TO STAPH DISEASE SEVERITY, DRUG RESISTANCE FOUND HITCHHIKING TOGETHER

U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH NIH News
National Institute of Allergy and Infectious Diseases (NIAID)
For Immediate Release: Friday, July 31, 2009

CONTACT: Ken Pekoc, 301-402-1663

GENES KEY TO STAPH DISEASE SEVERITY, DRUG RESISTANCE FOUND HITCHHIKING TOGETHER

Scientists studying Staphylococcus bacteria, including methicillin-resistant S. aureus (MRSA), have discovered a potent staph toxin responsible for disease severity. They also found the gene for the toxin traveling with a genetic component of Staphylococcus that controls resistance to antibiotics. The study, now online in PLoS Pathogens, shows for the first time that genetic factors that affect Staphylococcus virulence and drug resistance can be transferred from one strain to another in one exchange event.

One of the ways Staphylococcus bacteria become drug-resistant is through horizontal gene transfer, whereby resistance genes move from one bacterium to another. Staph bacteria also can exchange virulence genes using the same mechanism, but this was previously assumed to occur separately from the transfer of antibiotic resistance.

Scientists from the National Institute of Allergy and Infectious Diseases (NIAID), a component of the National Institutes of Health, led the study. They collaborated with researchers at the University of Tubingen in Germany and the University of Medicine and Dentistry of New Jersey.

"The discovery that bundled genes determine virulence and antimicrobial resistance suggests a new research focus for scientists trying to better prevent and treat serious staph infections," says Anthony S. Fauci, M.D., NIAID director.

The research involved more than 100 strains of S. aureus and S. epidermidis, both bacteria found on the skin of most people. In recent decades, these bacteria have become increasingly virulent, often causing severe disease that can be resistant to traditional antibiotics such as methicillin.

The studies were directed by NIAID senior investigator Michael Otto, Ph.D. In 2007, he and his colleagues found that staphylococci secrete toxins of the phenol-soluble modulin (PSM) family that are primarily responsible for attracting and killing human white blood cells called neutrophils. This process is critical for the ability of S. aureus-including community-acquired MRSA-to cause disease.

While screening S. aureus and S. epidermidis strains, Dr. Otto's group noticed that some strains produced one additional, previously unknown PSM toxin. The researchers hypothesized that the toxin was somehow connected to drug resistance. This idea surfaced because the toxin appeared in 10 percent of all MRSA strains and 68 percent of all methicillin-resistant S. epidermidis strains analyzed-whereas the researchers did not find it in strains of S. aureus or S. epidermidis that are sensitive to methicillin.

The research group confirmed its theory by identifying the specific location that encodes the toxin, which was in gene clusters that control drug resistance, known as SCCmec. The group named the new toxin PSM-mec.

"This work represents a previously unknown example of a toxin hitchhiking on staphylococcal mobile genetic elements that are primarily in charge of transferring antibiotic resistance," says Dr. Otto. He adds that the finding "should alert the research community that aggressive, drug-resistant staph can evolve more quickly than we assumed."

The research group is continuing its study of PSM-mec in S. epidermidis, where the toxin is more prevalent. Ultimately, being able to neutralize PSM-mec and other toxins that attack human defenses could lead to new treatments for S. aureus and S. epidermidis disease.

NIAID conducts and supports research-at NIH, throughout the United States, and worldwide-to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at .

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 .

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NIH STUDY FINDS LOW SHORT-TERM RISKS AFTER BARIATRIC SURGERY FOR EXTREME OBESITY

I have never been enamored of the way side effects can be trivialized when deaths actually occur. Do patients dying really support how safe an operation is? - BRH

NIH STUDY FINDS LOW SHORT-TERM RISKS AFTER BARIATRIC SURGERY FOR EXTREME OBESITY

U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH NIH News
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
For Immediate Release: Thursday, July 30, 2009

CONTACT: Leslie Curtis, Mary M. Harris,
301-496-3583

NIH STUDY FINDS LOW SHORT-TERM RISKS AFTER BARIATRIC SURGERY FOR EXTREME OBESITY

Short-term complications and death rates were low following bariatric surgery to limit the amount of food that can enter the stomach, decrease absorption of food or both, according to the Longitudinal Assessment of Bariatric Surgery (LABS-1). The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health. Results are reported in the July 30 issue of the New England Journal of Medicine.

Less than 1 percent (0.3 percent) of patients died within 30 days of surgery, further supporting the short-term safety of bariatric surgery as a treatment for patients with extreme obesity.

Bariatric surgery can have dramatic health benefits--such as improved blood sugar control or even reversal of type 2 diabetes. But it also carries serious risks, including death. The LABS-1 study aimed to evaluate the short-term safety of bariatric surgery to help doctors and patients understand the risks.

"Evaluating the 30-day safety outcomes of bariatric surgery in large populations is an essential step forward," according to co-author Myrlene Staten, M.D. senior advisor for diabetes translation research at NIDDK, part of NIH. "And LABS-1 data are from all patients who had their procedure performed by a surgeon participating in the study, not from just a select few patients."

Various types of bariatric surgery limit food intake, nutrient absorption or both. The major types of surgery undergone by participants in this study included laparoscopic adjustable gastric banding, laparoscopic Roux-en-Y gastric bypass and open Roux-en-Y gastric bypass. Gastric bands create a pouch around the top of the stomach to limit food intake at any one time. Gastric bypass also creates a pouch and redirects food around most of the stomach and part of the small intestine, limiting the absorption of food..

The LABS-1 consortium followed 4, 776 patients who had bariatric surgery for the first time, evaluating complications and death rates within the first 30 days after surgery. Patients were at least 18 years old and had an average body mass index (BMI) of 44, considered extremely obese. BMI measures weight in relation to height. As with most populations undergoing bariatric surgery, the majority of LABS-1 patients were white and female. The study took place over two years at 10 medical sites, with one additional center coordinating data collection and analyses.

Within 30 days of surgery, 4.1 percent of patients had at least one major adverse outcome, defined as death, development of blood clots in the deep veins of the legs or in the pulmonary artery of the lungs, repeat surgeries, or failure to be discharged from the hospital within 30 days of surgery.

Thirty day mortality was low, ranging from no deaths in the laparoscopic adjustable gastric band group, to six (0.2 percent) in the laparoscopic Roux-en-Y gastric bypass group, to nine (2.1 percent) in those undergoing open Roux-en-Y gastric bypass. The overall risk of complications also varied by procedure.

The investigators pointed out, however, that people undergoing some procedures, such as open Roux-en-Y gastric bypass, tended to be heavier and sicker than those undergoing laparoscopic adjustable gastric banding, and after adjusting for patient and center characteristics, there were no significant differences in complication risk that could be attributed to the type of procedure. There were some patient factors that increased the risk of complications, including a preoperative history of deep vein blood clots and sleep apnea. Patients with a very high BMI, a measure that relates weight to height, were also at increased risk--those with a BMI of 75 had a 61 percent higher risk of complications than those with a BMI of 53.

Currently, more than one third of U.S. adults are obese (BMI higher than 30) and an increasing number are extremely obese (BMI higher than 40), according to the U.S. Centers for Disease Control and Prevention. People who are extremely obese are potential candidates for bariatric surgery.

"There is a real need to determine safe and effective treatments for patients with extreme obesity and its associated medical conditions," said Susan Z. Yanovski, M.D., a co-author of the paper and co-director of NIDDK's Office of Obesity Research. "This study's results can help patients and physicians make informed decisions about potential risks and benefits of bariatric surgery."

LABS-1 is part of the Longitudinal Assessment of Bariatric Surgery consortium, an NIDDK-funded study launched in 2003 to examine the short- and long-term benefits and risks of bariatric surgery for adults with extreme obesity. LABS-2 will follow a subset of patients to gather longer-term information on patient characteristics, types of surgeries, medical and psychosocial outcomes and economic factors. The consortium brings together researchers with expertise in bariatric surgery, obesity research, internal medicine, endocrinology, behavioral science, outcomes research, epidemiology, and other relevant fields to collaboratively plan and conduct studies that will ultimately lead to better understanding of bariatric surgery and its impact on the health and well-being of patients with extreme obesity.

LABS-1 was conducted by researchers at the following centers:

-- Columbia University Medical Center, New York City
-- Cornell University Medical Center, New York City
-- East Carolina Medical Center, Greenville, N.C.
-- Neuropsychiatric Research Institute, Fargo, N.D.
-- Oregon Health & Science University, Portland
-- Legacy Good Samaritan Hospital, Portland, Ore.
-- Sacramento Bariatric Medical Associates, Sacramento, Calif.
-- University of Pittsburgh Medical Center
-- University of Washington, Seattle
-- Virginia Mason Medical Center, Seattle
-- University of Pittsburgh Graduate School of Public Health (Data Coordinating Center)

For more information about the LABS-1 study, search for NCT00433810 at . Information about the larger LABS study is at .

Learn more about weight control by visiting NIDDK's Weight-control Information Network at . "Bariatric Surgery for Severe Obesity" describes procedures, risks and potential benefits at .

More information about NIH's obesity research is available at .

The NIDDK, part of NIH, conducts and supports basic and clinical research and research training on some of the most common, severe and disabling conditions affecting Americans. The Institute's research interests include: diabetes and other endocrine and metabolic diseases; digestive diseases, nutrition, and obesity; and kidney, urologic and hematologic diseases. For more information, visit .


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 .

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