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January 20, 2012, 6:37 PM CT

A fundamental malaria discovery

A fundamental malaria discovery

A team of scientists led by Kasturi Haldar and Souvik Bhattacharjee of the University of Notre Dame's Center for Rare and Neglected Diseases has made a fundamental discovery in understanding how malaria parasites cause deadly disease.

The scientists show how parasites target proteins to the surface of the red blood cell that enables sticking to and blocking blood vessels. Strategies that prevent this host-targeting process will block disease.

The research findings are reported in the Jan. 20 edition of the journal Cell, the leading journal in the life sciences. The study was supported by the National Institutes of Health.

Malaria is a blood disease that kills nearly 1 million people each year. It is caused by a parasite that infects red cells in the blood. Once inside the cell, the parasite exports proteins beyond its own plasma membrane border into the blood cell. These proteins function as adhesins that help the infected red blood cells stick to the walls of blood vessels in the brain and cause cerebral malaria, a deadly form of the disease that kills over half a million children each year.

In all cells, proteins are made in a specialized cell compartment called the endoplasmic reticulum (ER) from where they are delivered to other parts of the cell. Haldar and Bhattacharjee and collaborators Robert Stahelin at the Indiana University School of Medicine- South Bend (who also is an adjunct faculty member in Notre Dame's Department of Chemistry and Biochemistry), and David and Kaye Speicher at the University of Pennsylvania's Wistar Institute discovered that for host-targeted malaria proteins the very first step is binding to the lipid phosphatidylinositol 3-phosphate, PI(3)P, in the ER.........

Posted by: Mark      Read more         Source


December 28, 2011, 7:05 PM CT

New way to ensure effectiveness of TB treatment

New way to ensure effectiveness of TB treatment
Researchers included (from left) Drs. Shashikant Srivastava, Tawanda Gumbo and Jotam G. Pasipanodya."Tuberculosis is a common ailment, accounting for up to 3 percent of all deaths in many countries. Although effective therapy exists, there are still cases of treatment failure and drug resistance remains a threat," said Dr. Tawanda Gumbo, associate professor of internal medicine and senior author of the study.

The results seem to challenge the current approach endorsed by the World Health Organization. Under that method, directly observed
A UT Southwestern Medical Center study using a sophisticated "glass mouse" research model has observed that multidrug-resistant tuberculosis (TB) is more likely caused in patients by speedy drug metabolism rather than inconsistent doses, as is widely believed.

If the study published in The Journal of Infectious Diseases is borne out in future investigations, it may lead to better ways to treat one of the world's major infectious diseases. Health workers worldwide currently are mandatory to witness each administration of the combination of drugs during months of treatment.

"Tuberculosis is a common ailment, accounting for up to 3 percent of all deaths in a number of countries. Eventhough effective treatment exists, there are still cases of therapy failure and drug resistance remains a threat," said Dr. Tawanda Gumbo, associate professor of internal medicine and senior author of the study.

The results seem to challenge the current approach endorsed by the World Health Organization. Under that method, directly observed treatment-short-course strategy (DOTS), TB that responds to medicine is treated with a cocktail of drugs under the supervision of health care workers, who in a number of countries must travel to isolated villages - a costly and time-consuming process.........

Posted by: Mark      Read more         Source


May 19, 2011, 8:45 AM CT

African-Americans with SLE more responsive to flu vaccine

African-Americans with SLE more responsive to flu vaccine
New research shows that African Americans with systemic lupus erythematosus (SLE) had a higher antibody response to influenza vaccination than European American patients. Treatment with prednisone, a history of hemolytic anemia, and increased disease flares were also associated with low antibody response in SLE patients who received the flu vaccine as per the study now available in Arthritis & Rheumatism, a peer-evaluated journal published by Wiley-Blackwell on behalf of the American College of Rheumatology (ACR).

The ACR estimates that up to 322,000 adult Americans are burdened with SLE, a chronic autoimmune disease in which the immune system fails to recognize the difference between healthy cells and foreign substances (bacteria and viruses), producing autoantibodies that attack a person's own tissues and organs. Medical evidence shows that infectious diseases are a leading cause of morbidity and mortality for lupus patients, responsible for up to 23% of all hospitalization and 20% to 50% of all deaths. Current clinical practice advises vaccination against common infectious diseases, such as influenza, for patients with lupus to reduce their risk of infection.

"SLE patients are more susceptible to infection which is likely the result of immunosuppressive treatment and inherent deficiencies of the immune system," said lead researcher Dr. Judith James, Chair of the Arthritis and Clinical Immunology Program at the Oklahoma Medical Research Foundation and Professor of Medicine at the University of Oklahoma Health Sciences Center. "Our study explored multiple factors which influence response to influenza vaccination in SLE patients with active and inactive disease activity".........

Posted by: Mark      Read more         Source


April 3, 2011, 9:35 AM CT

Quadruple therapy shows 100 percent SVR for HCV patients

Quadruple therapy shows 100 percent SVR for HCV patients
Exciting new data presented today at the International Liver CongressTM 2011 show that quadruple treatment in chronic hepatitis C (HCV) patients suppressed the emergence of resistant variants and resulted in a 100% rate of sustained virological response - undetectable HCV RNA - 12 weeks after therapy (SVR12).1.

In the quadruple treatment study, HCV patients were given four drugs in combination; pegylated Interferon-alpha (PegIFN-alpha); ribavirin (RBV); and two different direct-acting antivirals (DAAs) BMS-650032 (an HCV NS3 protease inhibitor) and BMS-790052 (an HCV NS5A replication complex inhibitor).

The current standard of care (SoC) for HCV treatment is PegIFN-alpha plus RBV � a dual treatment. The addition of DAAs (currently in phase-III clinical trials) marks the next step in therapy evolution � a triple treatment. However, the new data presented today suggests that quadruple treatment could be the next generation of therapy for chronic HCV patients.

Professor Heiner Wedemeyer, EASL'S Secretary General, said: "Quadruple treatment is possibly the future of HCV therapy; this study goes a way to confirming that. While it's expected that the first DAAs and triple treatment will be approved for use later this year, quadruple treatment appears to have a more profound effect on virological response, with less of a resistance problem".........

Posted by: Mark      Read more         Source


April 1, 2011, 7:30 AM CT

Promising target for AIDS vaccine

Promising target for AIDS vaccine
A section of the AIDS virus's protein envelope once considered an improbable target for a vaccine now may be one of the most promising, new research by Dana-Farber Cancer Institute researchers indicates.

The section, a twisting strand of protein known as the V3 loop, is an attractive vaccine target because immune system antibodies aimed at the loop may offer protection against multiple genetic subtypes of HIV-1, the virus that causes AIDS. This is a key prerequisite of any AIDS vaccine because the viruses mutate rapidly and by now comprise millions of different strains that are grouped into different genetic subtypes, or "clades." The researchers' findings are published online in the Public Library of Science journal PLoS One. .

In the study, researchers injected a monoclonal antibody -- a preparation of millions of identical antibodies that fight viral infection -- into Asian monkeys known as macaques. The antibody came from a person infected with a specific clade of HIV-1. The macaques were then exposed to virus of a different clade. Investigators knew the antibody would latch onto a portion of the virus's V3 loop, potentially barring the virus from invading nearby cells, but they didn't know whether it would prevent infection from a separate subtype of the virus.........

Posted by: Mark      Read more         Source


March 31, 2011, 7:06 AM CT

Hepatitis C drug may revolutionize treatment

Hepatitis C drug may revolutionize treatment
The drug boceprevir helps cure hard-to-treat hepatitis C, says Saint Louis University investigator Bruce R. Bacon, M.D., author of the March 31 New England Journal (NEJM) article detailing the study's findings. The results, which were first reported at the 61st annual meeting of the American Association for the Study of Liver Disease's last November, offer a brighter outlook for patients who have not responded to standard therapy.

Bacon, who is professor of internal medicine at Saint Louis University School of Medicine and co-principal investigator of the HCV RESPOND-2 study, studied the protease inhibitor boceprevir and observed that it significantly increased the number of patients whose blood had undetectable levels of the virus.

"These findings are particularly significant for patients who don't respond to initial therapy," said Bacon. "When the hepatitis C virus is not eliminated, debilitating fatigue and more serious problems can follow".

Hepatitis C is caused by a virus that is transmitted by contact with blood. The infection may initially be asymptomatic, but for patients who develop chronic hepatitis C infection, inflammation of the liver may develop, leading to fibrosis and cirrhosis (scarring of the liver), as well as other complications including liver cancer and death.........

Posted by: Mark      Read more         Source


March 15, 2011, 10:52 PM CT

Better Images of Bacteria

Better Images of Bacteria
It's a cloak that surpasses all others: a microscopic carbon cloak made of graphene that could change the way bacteria and other cells are imaged.

Vikas Berry, assistant professor of chemical engineering at Kansas State University, and his research team are wrapping bacteria with graphene to address current challenges with imaging bacteria under electron microscopes. Berry's method creates a carbon cloak that protects the bacteria, allowing them to be imaged at their natural size and increasing the image's resolution.

Graphene is a form of carbon that is only one atom thick, giving it several important properties: it's impermeable, it's the strongest nanomaterial, it's optically transparent and it has high thermal conductance.

"Graphene is the next-generation material," Berry said. "Eventhough only an atom thick, graphene does not allow even the smallest of molecules to pass through. Furthermore, it's strong and highly flexible so it can conform to any shape".

Berry's team has been researching graphene for three years, and Berry recently saw a correlation between graphene and cell imaging research. Because graphene is impermeable, he decided to use the material to preserve the size of bacterial cells imaged under high-vacuum electron microscopes.........

Posted by: Mark      Read more         Source


March 15, 2011, 7:57 AM CT

Focus on Prion Diseases

Focus on Prion Diseases
New research by Chongsuk Ryou, researcher at the UK Sanders-Brown Center on Aging and professor of microbiology, immunology and molecular genetics in the UK College of Medicine, may shed light on possible therapys for prion diseases.

Prion diseases, which include Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy ("mad cow" disease) in cattle, are caused by prions - unconventional pathogens composed of infectious protein particles and resistant to conventional sterilization procedures. Presently there is no known agent or procedure that can halt or reverse damage caused by prion disease.

Ryou and his colleagues, however, have demonstrated through recent work that polymers of amino acid lysine (polylysines) are able to block propagation of prions by targeting plasminogen - a substance that stimulates the multiplication of prions. In test tubes and cultured cells, polylysines halted the spread of prions.

Furthermore, in an animal model of prion disease, mice treated with polylysines displayed symptoms later, survived longer and showed lower levels of prions in their brains than did untreated mice.

"Our study suggests that polylysine is a potential anti-prion agent and validates plasminogen as a therapeutic target to combat prion disease," said Ryou.........

Posted by: Mark      Read more         Source


March 10, 2011, 8:01 AM CT

Keeping an eye on H1N1

Keeping an eye on H1N1
An image of the H1N1 influenza virus taken in the CDC Influenza Laboratory.
Image courtesy of the Centers for Disease Control
In the fall of 1917, a new strain of influenza swirled around the globe. At first, it resembled a typical flu epidemic: Most deaths occurred among the elderly, while younger people recovered quickly. However, in the summer of 1918, a deadlier version of the same virus began spreading, with disastrous consequence. In total, the pandemic killed at least 50 million people - about 3 percent of the world's population at the time.

That two-wave pattern is typical of pandemic flu viruses, which is why a number of researchers worry that the 2009 H1N1 ("swine") flu virus might evolve into a deadlier form.

H1N1, first reported in March 2009 in Mexico, contains a mix of human, swine and avian flu genes, which prompted fears that it could prove deadlier than typical seasonal flu viruses. However, the death toll was much lower than initially feared, in large part because the virus turned out to be relatively inefficient at spreading from person to person.

In a newly released study from MIT, scientists have identified a single mutation in the H1N1 genetic makeup that would allow it to be much more easily transmitted between people. The finding, published in the March 2 edition of the journal Public Library of Science (PLoS) One, should give the World Health Organization, which tracks influenza evolution, something to watch out for, says Ram Sasisekharan, senior author of the paper.........

Posted by: Mark      Read more         Source


March 1, 2011, 9:28 PM CT

HIV vaccine impacts the genetic makeup of the virus

HIV vaccine impacts the genetic makeup of the virus
Dr. James I. Mullins, professor of microbiology at the University of Washington in Seattle, led a study of the selective pressure of an HIV-1 vaccine on the virus.

Credit: University of Washington

An AIDS vaccine tested in people, but found to be ineffective, influenced the genetic makeup of the virus that slipped past. The findings suggest new ideas for developing HIV vaccines.

The results were published Feb. 27 in Nature Medicine

This is the first evidence that vaccine-induced cellular immune responses against HIV-1 infection exert selective pressure on the virus. "Selective pressure" refers to environmental demands that favor certain genetic traits over others.

The senior author of the multi-institutional study is Dr. James I. Mullins, University of Washington (UW) professor of microbiology. The research team analyzed the genome sequences in HIV-1 isolated from 68 newly infected volunteers in the STEP HIV-1 vaccine trial. Mullins and the other principal scientists who carried out this study were not involved in the STEP trial.

The STEP trial was a double-blind, Phase 2B test-of-concept of a Merck HIV-1 subtype B vaccine. The vaccine, MRKAd5, was designed to make the body produce infection-fighting white blood cells, usually called killer T-cells, that could recognize and target specific parts of HIV-1 known as Gag, Pol and Nef.

The STEP trial was conducted at 34 North American, Caribbean, South American and Australian locations where the HIV-1 subtype B was the predominant virus in the local HIV-infected populations. The trial enrolled 3,000 participants.........

Posted by: Mark      Read more         Source


February 22, 2011, 7:32 AM CT

Vaccine made with synthetic gene

Vaccine made with synthetic gene
Scientists at Albert Einstein College of Medicine of Yeshiva University have developed an experimental vaccine that appears to protect against an increasingly common and especially deadly form of pneumococcal pneumonia. Details of the new vaccine, which was tested in an animal model, are reported in a paper published recently in the Journal of Infectious Diseases

Pneumococcal pneumonia can occur when the lungs are infected with the bacterial species Streptococcus pneumoniae (also known as pneumococcus). "Like a number of microbes that cause pneumonia, pneumococcus is spread from person to person through coughing or sneezing," said principal investigator Liise-anne Pirofski, M.D., professor of medicine and of microbiology & immunology and the Selma and Dr. Jacques Mitrani Chair in Biomedical Research. Symptoms include cough, fever, shortness of breath, and chest pain.

The National Foundation for Infectious Diseases estimates that 175,000 people are hospitalized with pneumococcal pneumonia in the United States each year. In addition to pneumonia, pneumococcus causes 34,500 bloodstream infections and 2,200 cases of meningitis annually. It is responsible for more deaths in the United States � 4,800 a year � than any other vaccine-preventable disease. It poses a particular problem in the developing world, where it is estimated to cause more than one million deaths in children each year, as per the World Health Organization.........

Posted by: Mark      Read more         Source


February 17, 2011, 7:16 AM CT

New pneumococcal vaccine approach

New pneumococcal vaccine approach
Pneumococcus (Streptococcus pneumoniae) accounts for as much as 11 percent of mortality in young children worldwide. While successful vaccines like Prevnar� exist, they are expensive and only work against specific pneumococcal strains, with the risk of becoming less effective as new strains emerge. Through a novel discovery approach, scientists at Children's Hospital Boston and Genocea Biosciences, Inc., in collaboration with the international nonprofit organization PATH, developed a new vaccine candidate that is potentially cheaper and able to protect against any pneumococcal strain.

Tested in mice, the protein-based vaccine successfully inhibited S. pneumoniae from establishing a foothold in the body, the scientists report in the February 17 issue of Cell Host & Microbe

The current multivalent conjugate pneumococcal vaccines work by inducing people to make antibodies against the sugars on the bacterium's outer capsule. The antibodies then help fight off development of disease after the bacteria have colonized the body. But these vaccines are complex to manufacture, requiring separate individual components for sugars produced by multiple pneumococcal strains. Since pneumococci can make more than 90 different types of sugars, the vaccines appears to become less effective over time.........

Posted by: Mark      Read more         Source


February 14, 2011, 6:59 AM CT

Gonorrhea acquires a piece of human DNA

Gonorrhea acquires a piece of human DNA
If a human cell and a bacterial cell met at a speed-dating event, they would never be expected to exchange phone numbers, much less genetic material. In more scientific terms, a direct transfer of DNA has never been recorded from humans to bacteria.

Until now. Northwestern Medicine scientists have discovered the first evidence of a human DNA fragment in a bacterial genome � in this case, Neisseria gonorrhoeae, the bacterium that causes gonorrhea. Further research showed the gene transfer may be a recent evolutionary event.

The discovery offers insight into evolution as well as gonorrhea's nimble ability to continually adapt and survive in its human hosts. Gonorrhea, which is transmitted through sexual contact, is one of the oldest recorded diseases and one of a few exclusive to humans.

"This has evolutionary significance because it shows you can take broad evolutionary steps when you're able to acquire these pieces of DNA," said study senior author Hank Seifert, professor of microbiology and immunology at Northwestern University Feinberg School of Medicine. "The bacterium is getting a genetic sequence from the very host it's infecting. That could have far reaching implications as far as how the bacteria can adapt to the host".

It's known that gene transfer occurs between different bacteria and even between bacteria and yeast cells. "But human DNA to a bacterium is a very large jump," said main author Mark Anderson, a postdoctoral fellow in microbiology. "This bacterium had to overcome several obstacles in order to acquire this DNA sequence".........

Posted by: Mark      Read more         Source


February 5, 2011, 7:21 AM CT

HPV Vaccine Works for Boys Too

HPV Vaccine Works for Boys Too
Joel Palefsky, MD
The vaccine for human papillomavirus (HPV) can prevent 90 percent of genital warts in men when offered before exposure to the four HPV strains covered by the vaccine, as per a new multi-center study led by H. Lee Moffitt Cancer Center and UCSF.

The four-year, international clinical trial, which also found a nearly 66 percent effectiveness in the general population of young men regardless of previous exposure to these strains, provides the first reported results of using the HPV vaccine as a prophylactic in men.

Initial data from this study informed the Food and Drug Administration's decision to approve the vaccine for boys in 2009 to prevent warts, while results from a substudy led the FDA to expand approval late last year to prevent anal cancer. Findings can be found in the Feb. 3 issue of the New England Journal (NEJM), or online at www.nejm.org.

While the HPV vaccine was approved in 2006 for girls to prevent cervical cancer, the vaccine's benefit for young men was not initially addressed. Yet infection and diseases caused by HPV are common in men, the scientists said, including genital warts, which are one of the leading sexually transmitted diseases (STD) for which therapy is sought nationwide. The Centers for Disease Control and Prevention estimate that half of all sexually active Americans will get HPV at some point in their lives.........

Posted by: Mark      Read more         Source


February 2, 2011, 7:47 AM CT

Teens with HIV at high risk for pregnancy

Teens with HIV at high risk for pregnancy
Teenage girls and young women infected with HIV get pregnant more often and suffer pregnancy complications more frequently than their HIV-negative peers, as per new research led by Johns Hopkins investigators.

A report on the multi-center study, based on an analysis of records from 181 patients with HIV, ages 13 to 24, treated at four hospitals over 12 years, would be reported in the Feb. 2 issue of the Journal of the American Medical Association

The findings are alarming for at least two reasons, the researchers say. First, teen pregnancies � planned or not � put these already vulnerable patients and their fetuses in grave danger for complications. Second, the findings signal that HIV-infected teens and young women continue to practice unsafe sexual behaviors and to have unprotected sex, the scientists say.

Pregnancy rates were particularly high in one subgroup of HIV-infected youth � teens who acquired the virus behaviorally rather than during birth. Behaviorally infected teens had five times the number of pregnancies in comparison to their HIV-negative counterparts and were more prone to premature births and spontaneous abortions than their HIV-negative peers.

Because of its retrospective nature, the study did not capture why the patients got pregnant. The answer to this question, the scientists say, would supply critical information for future pregnancy-counseling and risk-reduction efforts.........

Posted by: Mark      Read more         Source


January 28, 2011, 7:38 AM CT

Bacteria possible cause of preterm births

Bacteria possible cause of preterm births
The type of bacteria that colonize the placenta during pregnancy could be linked to preterm birth and other developmental problems in newborns as per research reported in the current issue of the online journal mBio�.

"The fetal inflammatory response appears to contribute to the onset of preterm labor, fetal injury and complications, underlying lifetime health challenges facing these children," say the scientists from Harvard Medical School, Brigham and Women's Hospital and Children's Hospital of Boston. "Our data suggest that placental colonization by specific groups of organisms can increase or decrease the risk of a systemic inflammatory condition".

Preterm birth occurs in nearly a half million pregnancies in the United States alone. Despite improved care, preterm and particularly extremely low-gestational-age newborns continue to be at a considerably higher risk of morbidity, mortality and developmental problems. Much of this risk is attributable to imbalanced inflammatory responses of the fetus and newborn.

The systemic fetal inflammatory response to intrauterine exposures, particularly intrauterine infections, is regarded as an important contributor to the onset and often lifelong consequences of preterm labor, fetal injury and early organ damage. Approximately half of all placentas delivered before the second trimester and 41% of those delivered by Caesarean section harbor microorganisms detectable by culture techniques.........

Posted by: Emily      Read more         Source



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Did you know?
Scientists at Baylor College of Medicine in Houston have found a genetic marker that may identify individuals at greater risk for life-threatening infection from the West Nile virus. Results of the study are reported in the Nov. 15 print edition of Journal of Infectious Diseases.

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