Archive for November, 2009

By: Ed Susman

CHICAGO, IL – Mannequins have their place in medicine – helping to teach doctors-in-training how to do ultrasound-guided procedures.

Researchers at Henry Ford Hospital, Detroit, MI, said their study shows use of mannequins can be a valuable tool to improve medical residents’ knowledge, dexterity and confidence for performing some of the more common ultrasound-guided procedures, including breast biopsies, liver biopsies, thyroid biopsies and the removal of fluid in the body.

In a presentation here at the 95th scientific assembly and annual meeting of the Radiological Society of North America, John W. Bonnett, MD, a radiologist at Henry Ford Hospital, said, “The mannequins allow us to simulate actual ultrasound guided procedures, which offers residents a unique training opportunity prior to working on real patients, Ultimately, the residents in our study became more proficient and efficient in performing these procedures.”

For the study, researchers enrolled 29 radiology residents from all four levels of training. The residents were given written, video, and live interactive training from staff on the basics of ultrasound guided procedures.

Residents had six months to practice these skills at the 12,000-square-foot Center for Simulation, Education and Research at Henry Ford Hospital, the largest surgery simulation center in the Midwest. The facility houses two operating theatres, six clinical rooms, a minimally invasive procedure lab with more than 30 stations, and two classrooms. Fully-equipped, reconfigurable rooms simulate surgery, labor and delivery, intensive care, emergency and routine hospital scenarios.

As part of the study, residents used phantom mannequins that contained both hypo- and hyperechoic nodules to simulate the ultrasound procedure. Written and practical examinations were given before and after training to assess for changes in competency and proficiency.
Study results show a significant improvement between the residents’ pre- and post-test scores on both the written and practical exams. After training, residents also demonstrated improved dexterity in the technical aspects of ultrasound guided procedures.

On the survey questionnaire, residents said that the course improved their knowledge level and technical ability for ultrasound guided procedures. It also boosted their confidence for performing biopsies.

- MFP Wire Services
- 11-30-2009

ATHENS, GA – Bacteria don’t have easy lives. In addition to mammalian immune systems that besiege the bugs, they have natural enemies called bacteriophages, viruses that kill half the bacteria on Earth every two days.

Still, bacteria and another class of microorganisms called archaea (first discovered in extreme environments such as deep-sea volcanic vents) manage just fine, thank you, in part because they have a built-in defense system that helps protect them from many viruses and other invaders.

A team of scientists led by researchers at the University of Georgia has now discovered how this bacterial defense system works, and it could lead to new classes of targeted antibiotics, new tools to study gene function in microorganisms and more stable bacterial cultures used by food and biotechnology industries to make products such as yogurt and cheese.

The research was recently published in the journal Cell.

“Understanding how bacteria defend themselves gives us important information that can be used to weaken bacteria that are harmful and strengthen bacteria that are helpful,” said Michael Terns, a professor of biochemistry and molecular biology in University of Georgia – Athen’s Franklin College of Arts and Sciences. “We also hope to exploit this knowledge to develop new tools to speed research on microorganisms.”

Other authors on the Cell paper include Rebecca Terns, a senior research scientist in biochemistry and molecular biology at University of Georgia – Athen; Caryn Hale, a graduate student in the Terns lab at University of Georgia – Athen; Lance Wells, an assistant professor of biochemistry and molecular biology and Georgia Cancer Coalition Scholar at University of Georgia – Athen and his graduate student Peng Zhao; and research associate Sara Olson, assistant professor Michael Duff and associate professor Brenton Graveley of the University of Connecticut Health Center.

The system, whose mechanism of action was uncovered in the Terns lab (Michael and Rebecca Terns are a husband-wife team), involves a “dynamic duo” made up of a bacterial RNA that recognizes and physically attaches itself to a viral target molecule, and partner proteins that cut up the target, thereby “silencing” the would-be cell killer.

The invader surveillance component of the dynamic duo (an RNA with a viral recognition sequence) comes from sites in the genomes of bacteria and archaea, known technically as “clustered regularly interspaced short palindromic repeats” or more familiarly called CRISPRs. (A palindrome is a word or sentence that reads the same forward and backward.) CRISPR RNAs don’t work alone in fighting invaders, though.

Their partners in invader defense are Cas proteins that arise from a suite of genes called “CRISPR-associated” or Cas genes. Together, they form the “CRISPR-Cas system,” and the new paper describes this dynamic duo and how they protect bacteria from viruses.

“You can look at one as a police dog that tracks down and latches onto an invader, and the other as a police officer that follows along and `silences’ the offender,” said Rebecca Terns. “It functions like our own immune system, constantly watching for and neutralizing intruders. But the surveillance is done by tiny CRISPR RNAs rather than antibodies.”

What the team discovered was that a particular complex of CRISPR RNAs and a subset of the Cas proteins termed the RAMP module recognizes and destroys invader RNAs that it encounters.

“This work has uncovered intriguing parallels between the bacterial CRISPR-Cas system and the human immune system, suggesting a novel way to target disease-causing bacteria,” said Laurie Tompkins, Ph.D., who oversees genetic mechanisms grants at the National Institutes of Health’s National Institute of General Medical Sciences. “It may be possible to turn CRISPR-Cas into a suicide machine, killing pathogenic bacteria by an attack on their own molecules, similar to the self-destruction seen in human autoimmune diseases.”

Understanding how the system silences invaders opens up opportunities to exploit it. So far, CRISPRs have been found in about half of the bacterial genomes that have been mapped or sequenced and in nearly all sequenced archaeal genomes. Such pervasiveness indicates that an ability to manipulate the CRISPR-Cas system could yield a broad range of applications. For example, using the knowledge that they have obtained in this work, the Terns now envision being able to design new CRISPR RNAs that will take advantage of the system to selectively cleave target RNAs in bacterial cells.

“These could target viruses that wipe out cultures of bacteria used by industry to produce enzymes,” said Michael Terns, “or could target the gene products of the bacteria themselves. With this set of Cas proteins, we now know how to cut a target RNA at the site we choose.”

“Believe it or not, we have only recently recognized that these microorganisms have a heritable immune system [because it is so different from our own],” added Rebecca Terns.

Remarkably, scientists are already in a position to begin to capitalize on their rapidly growing knowledge of this bacterial immune system.

- MFP Wire Services
- 11-30-2009

PHILADELPHIA, PA – Researchers have found that hormones produced during pregnancy induce a protein that directly inhibits the growth of breast cancer. This protein, alpha-fetoprotein, may serve as a viable, well-tolerated agent for the treatment and prevention of breast cancer, according to findings published in Cancer Prevention Research, a journal of the American Association for Cancer Research.

“Hormones in pregnancy, such as estrogen, all induce alpha-fetoprotein, which directly inhibits the growth of breast cancer,” said lead researcher Herbert Jacobson, Ph.D., who is a basic breast cancer researcher in the Center for Immunology and Microbial Diseases and in the Department of Obstetrics, Gynecology and Reproductive Sciences at Albany Medical College, New York.

“The body has a natural defense system against breast cancer,” he added. “Alpha-fetoprotein needs to be safely harnessed and developed into a drug that can be used to protect women from breast cancer.”

Recent studies have shown that hormones released during pregnancy, such as estrogen, progesterone and human chorionic gonadotropin, reduce a women’s risk for breast cancer. Alpha-fetoprotein is a protein normally produced by the liver and yolk sac of a fetus. Jacobson and colleagues sought to determine whether administering pregnancy hormones to carcinogen-exposed rats led them to produce alpha-fetoprotein, which in turn produces the protective effect of pregnancy in the absence of pregnancy.

Results from this study showed that treatment with estrogen plus progesterone, estrogen alone or human chorionic gonadotropin reduced the incidence of mammary cancers in rats. Furthermore, the researchers noted that each of these treatments elevated the serum level of alpha-fetoprotein and that alpha-fetoprotein directly inhibited the growth of breast cancer cells growing in culture, suggesting that these hormones of pregnancy are preventing breast cancer through their induction of alpha-fetoprotein.

Cancer Prevention Research Editorial Board Member Powel Brown, M.D., Ph.D., said while these preclinical findings are important and suggest a role of alpha-fetoprotein in breast cancer prevention, they are not yet ready to be used in the clinic.

“The researchers have not directly demonstrated the cancer preventive activity of alpha-fetoprotein, instead they found an association of these hormones preventing mammary tumors. None of these treatments prevented mammary tumors in 100 percent of the rats, it appears to delay mammary tumor formation and prevent breast cancer development in approximately 30 to 50 percent of the rats,” said Brown, professor of medicine and cancer prevention and clinical cancer prevention department chairman at the University of Texas M. D. Anderson Cancer Center.

“This study is promising and suggests that additional animal studies need to be done before translation to humans,” he said. “We may want to further test alpha-fetoprotein for its cancer prevention activity.”

Jacobson and colleagues are currently conducting studies in which they have isolated a small piece of alpha-fetoprotein molecule and are working to convert it into a breast cancer preventative agent.

- MFP Wire Services
- 11-30-2009