A pair of Princeton scientists have found that it has a lot to do with the brain circuits that control eye movements. Neuroscientists Tirin Moore and Katherine Armstrong showed that these brain circuits serve a double function: In addition to programming eye movements, they also trigger amplification or suppression of signals that pour in from the locations where the eyes could move.

The finding, published in the Jan. 23 issue of Nature, is the first to pinpoint a neural mechanism behind one of the most fundamental aspects of mental activity — the ability to direct attention to one thing as opposed to another.

“Without regulating your attention, you would orient to everything that appears and moves. An organism that couldn’t filter anything just wouldn’t work. It would be in a state of constant distraction,” said Moore. “This work shows that, whether we are moving our eyes or not, the networks that control eye movements may be a source of that filtering.”

Working with monkeys, the researchers picked a site in the brain area that controls eye movements and established exactly where neurons at that site made the eyes move. They then located a single neuron, in another part of the brain, that was responsible for processing visual stimuli from precisely the same location targeted by neurons at the eye movement site.

With the monkeys trained to fixate on the center of their visual field, the researchers displayed an image in the location associated with the two brain areas. They then electrically stimulated the eye movement neurons, but not strongly enough to actually make the eyes move. When this microstimulation was applied, the visual processing neuron showed a much greater response to the displayed image than when the electrical stimulation was not applied. On the other hand, when no image was being displayed, microstimulation of eye movement neurons had no effect on the visual neuron.

The researchers concluded that the very act of preparing an eye movement to a particular location caused an amplification of signals from that area. These eye movement neurons acted like a volume control on an amplifier, controlling the strength of the signal from one particular spot in space, but not altering the quality of that signal. By stimulating neurons in the eye movement area, the researchers in effect forced the animal to shift its attention from one location to another even though it did not move its eyes.

The study hinges on a long-known fact in visual attention — that humans and primates can attend to something without moving their eyes to that object. This ability is useful for many animals that encounter social situations in which there is a potential danger in looking directly at another animal. But scientists were unsure how closely eye movements were tied to the phenomenon of attention.

Moore and Armstrong’s finding builds on an earlier study in which Moore observed behavioral effects of electrically stimulating eye movement neurons. In that study, monkeys were better able to detect subtle changes in a visual target when their eye movement neurons had been stimulated. The new study, which measured electrical output of visual neurons rather than measuring a behavioral effect, draws a much more powerful conclusion about how the brain is wired.

Calling the study a “landmark,” neuroscientist William Newsome of Stanford University compared the work to discovering how the ignition system of a car is wired. “You know, from looking at the car behaviorally, that if you put the key in the ignition and turn the crank it leads to the car starting,” said Newsome. “But if you really want to understand what’s going on inside that car — if you want to go in there and fix things when they go wrong — you need to know how that behavior comes to pass. Where does the signal go? And then where does it go from there?”

There are many human diseases and disorders that involve defects in information processing and attention — most famously attention deficit disorder — for which scientists would like a firm idea of what neural circuits are involved, said Newsome.

“It takes the whole attention field and steps it up a notch, because now people can start asking questions about mechanisms,” said Michael Shadlen, an expert in visual perception at the University of Washington.

Apart from the particular finding about spatial attention, the study reveals an important technique that could be used to trace many other types of neural circuits, the researchers said. “Short-term memory, decision-making, planning motor acts all involve flow of information from one area to another and until now we have had no real way to monitor that information flow or reproduce it in the laboratory,” said Newsome.

A next step, said Moore, will be to further analyze the eye movement neurons and find out whether they act alone in regulating spatial attention. Another experiment would be to see whether manipulating these neurons and ostensibly making an animal attend to one place or another can determine what information the animal remembers. “If you don’t attend to something, you don’t see it,” Moore said. “There are many things that hit our retinas, but we don’t experience them and don’t remember them unless we pay attention to them.”

A new study used the Sleeping Beauty transposon system to profile the repertoire of genes that can drive colorectal cancer, identifying many more than previously thought. Around one third of these genes are mutated in human cancer, which provides strong evidence that they are driver mutations in human tumours.

The collaborative project, funded principally by Cancer Research UK and the Wellcome Trust, was led by Dr David Adams from the Wellcome Trust Sanger Institute, and Dr Douglas Winton, of the Cancer Research-UK Cambridge Research Institute.

"These findings, when combined with mutation data from human colon cancers, will drive forward our understanding of the processes that lead to colorectal cancer," says Dr Adams, senior author from the Sanger Institute. "They demonstrate how many genes can contribute to this cancer and how these genes work together in the development of this disease."

The Sleeping Beauty transposon system induces genetic mutations at random, identifying and tagging candidate cancer genes, the drivers that cause colorectal cancer. This system has become critical in uncovering the genetic pathways that cause cancer, and, in this study, the team identify more than 200 genes that can be disrupted in human colorectal cancers.

Colorectal (bowel) cancer is the third most common cancer in the UK, and the second most common cause of cancer deaths after lung cancer; just under 40,000 people were diagnosed with bowel cancer in the UK in 2008 — around 110 people every day — a figure which has shown little improvement over the last decade.

"Our research provides a rich source of candidate genes that represent potential diagnostic,prognostic and therapeutic targets, and defines the breadth of genes that can contribute to cancer of the intestine," says Dr Winton, senior author from the Cancer Research UK Cambridge Research Institute. "It is becoming increasingly clear that cancers are driven by mutations in disparate collections of genes and it is essential that we tease apart the important changes."

Current thinking is that perhaps around 5-20 major drivers are mutated in any one cancer cell, but the number and identity of all of the cancer drivers, and how many drivers are found in each type of cancer, is largely unknown. By performing screens for cancer genes in the mouse and by then comparing them to data from human tumours the team identified a rich catalogue of new candidate genes helping to refine the genes that genetic pathways that drive bowel cancer development.

The research complements studies by The Cancer Genome Atlas and the International Cancer Genome Consortium, which are cataloguing the mutations responsible for cancer development using next generation DNA sequencing.

"At its heart, cancer is a disease driven by faulty genes," says Dr Lesley Walker, director of cancer information at Cancer Research UK. "Research suggests that each cancer cell has a number of ‘driver’ faults that make them grow out of control, as well as ‘passenger’ faults that they pick up as the disease develops. This technique is helping us to tease out the key drivers of bowel cancer, laying the foundations for more effective, targeted treatments for the disease in the future."

The researchers call for a randomized clinical trial to confirm their analysis. Meanwhile, they advise cardiologists to begin treatment with sufficient doses of nitroglycerin to relive pain before resorting to morphine.

In their analysis of the clinical data and outcomes of more than 57,000 high-risk heart attack patients — 29.8 percent of whom received morphine within the first 24 hours of hospitalization — the researchers found that those who received morphine had a 6.8 percent death rate, compared to 3.8 percent for those receiving nitroglycerin. The increase in mortality persisted even after adjustment for the patients’ baseline clinical risk.

"The results of this analysis raise serious concerns about the safety of the routine use of morphine in this group of heart patients," said Duke cardiologist Trip Meine, M.D., who presented the results of the Duke analysis Nov. 10, 2004, at the American Heart Association’s (AHA) annual scientific sessions in New Orleans.

"Since randomized clinical trials evaluating the safety or effectiveness of morphine for these patients have not been conducted, official guidelines for its use are based solely on expert conjecture," Meine continued. "Given the adverse outcomes associated with morphine use found in our analysis, a randomized clinical trial is in order."

Morphine was first used to relieve the chest pain associated with heart attacks in 1912 and has been used regularly ever since. Nitroglycerin has been used for more than 130 years for the relief of chest pain, also known as unstable angina. It works by relaxing blood vessels and allowing blood flow to increase.

"Nitroglycerin has a physiological effect that may, at least temporarily, influence the underlying ischemia," Meine said. "Morphine, on the other hand, doesn’t do anything about what is actually causing the pain. It just masks it, and may, in fact, make the underlying disease worse.

"Morphine has the well-known and potentially harmful side effects of depressing respiration, reducing blood pressure and slowing heart rate," he continued. "These side effects could explain the worse outcomes in patients whose heart function has already been compromised by disease."

For their analysis, the researchers consulted the nationwide quality improvement initiative named CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology and AHA Guidelines) The registry continually collects data from more than 400 hospitals on outcomes and on the use of proven drugs and procedures used to restore blood flow to the heart.

From this registry, the researchers identified 57,039 high-risk patients with non-ST-segment elevation myocardial infarction (non-STEMI), a categorization of heart attack based on electrocardiogram (ECG) readings. These patients typically arrive at emergency rooms with chest pain, but often will not have telltale signs of a heart attack on the initial ECG. They might be diagnosed with a heart attack only when the results of the blood tests are reported a few hours later.

The researchers found that patients who were given morphine had 48 percent higher risk of dying and 34 percent higher risk of suffering another heart attack while in the hospital.

"This increase in mortality was present in every subgroup of patients we studied," Meine said. "What we found interesting was that patients given morphine were more likely to receive evidence-based medicine, were more likely to be treated by a cardiologist and were more likely to receive an invasive cardiac procedure."

Meine recommends that physicians with hospitalized heart attack patients should begin with nitroglycerin therapy to control pain. Our recommendation is that patients should receive the full dose of nitroglycerin. Based on our analysis, morphine should be the last resort after else has been tried."

While patients with acute STEMI are at higher risk of dying within 30 days of their hospital stay, patients with non-STEMI actually have a higher risk of dying six months and one year after initial hospital presentation. It is estimated that about 1.3 million Americans are hospitalized each year with non-STEMI.

CRUSADE continuously gathers data from participating U.S. hospitals on treatments for patients with non-STEMI and provides quarterly feedback to hospitals with the ultimate goal of improving adherence to the ACC/AHA treatment guidelines and patient outcomes.

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The CRUSADE registry is funded by Millennium Pharmaceuticals, Cambridge, Mass., and Schering Corp, Kenilworth, N.J. Bristol-Meyers Squibb/Sanofi Pharmaceuticals Partnership, NY, provided an unrestricted grant in support of CRUSADE.

“It’s not surprising that no one has really heard about them; archaea have still not even penetrated mainstream biology textbooks,” said David Relman, MD, associate professor of medicine (infectious diseases) and of microbiology and immunology. There are, however, at least as many of them as there are bacteria, he said.

Archaea look a lot like bacteria, but appearances can be deceiving. Genetically and biochemically they are as different from bacteria as bacteria are from humans. The microbes live in many extreme environments – from hot springs to salt lakes to submarine volcanoes – but also within animals, including the human colon, vagina and mouth.

“To me it is one of those fundamental puzzles: they are everywhere and, given that we must be exposed to them somewhat frequently, if not all the time, why is it that we can’t name one disease-causing member of this enormous domain?” Relman wondered. He and his group at the Veterans Affairs Palo Alto Health Care System have shown a never-before-known connection between the abundance of archaea and the severity of a human gum disease called periodontitis.

Chronic periodontitis, which affects about one-third of Americans, may result in tooth loss and is thought to play a role in a range of conditions including atherosclerosis, stroke and early delivery of low birth-weight infants. While there is a general consensus that bacteria play a role in gum disease, no single microbe has been implicated as the culprit.

Relman and members of his lab embarked on a comprehensive, controlled study of the archaea found in the subgingival crevice – the deep gap between the gums and teeth – where periodontitis begins. They rigorously analyzed samples from 58 patients’ mouths taken by their collaborator, Gary Armitage, DDS, at the UC-San Francisco School of Dentistry, and found that more than one-third of the periodontitis patients had archaea in their diseased subgingival spaces, but nowhere else in their mouths. In addition, the relative abundance of archaea correlated with disease severity. Their findings are published in this week’s issue of the Proceedings of the National Academy of Sciences.

“Of course we’d ultimately like to say archaea caused disease, but it’s a horse-and-cart problem right now because we haven’t shown that the archaea come before the disease,” Relman said. In the future, he noted, they will collect specimens repeatedly from the same spot in the subgingival pocket in hopes of being able to pinpoint the moment when the archaea start to increase in number and then determine whether that predicts the later development of the disease.

The paper’s first author, Paul Lepp, PhD, research associate in microbiology and immunology, explained that while a third of the periodontitis sufferers harbored archaea, many of the others had high levels of bacteria that – like archaea – consume hydrogen. Hydrogen consumption creates a more hospitable environment for bacteria long known to play a role in gum disease.

The group speculates that archaea may not directly cause periodontal disease. Rather, the microbes may indirectly contribute to it by helping other organisms – in this case, gum-damaging bacteria – grow more productively. Lepp said they are now looking for other hydrogen consumers to test their theory.

“In my mind, it’s increasingly clear that the disease may be the result of a community disturbance rather than the presence or absence of a particular organism,” Relman said.

Relman also sees a potentially broader side to this research. “Maybe we should look a little harder for evidence of archaea as promoting or causing other diseases. We certainly have them in our bodies and we are exposed to them, so the archaea have the opportunity to cause disease if they are capable of doing so. We haven’t been looking for them so we wouldn’t know.”

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Other Stanford researchers involved in this study include graduate student Mary Brinig and postdoctoral scholar Cleber Ouverney, PhD, in microbiology and immunology, and research assistant Katherine Palm, in the division of infectious diseases and geographic medicine. This study was funded by a grant from the National Institute of Dental and Craniofacial Research, one of the National Institutes of Health, along with grants from the Ellison Medical Foundation and the University Exploratory Research Program of Procter & Gamble.

Stanford University Medical Center integrates research, medical education and patient care at its three institutions – Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children’s Hospital at Stanford. For more information, please visit the Web site of the medical center’s Office of Communication & Public Affairs at mednews.stanford.

“This is the first evidence that leptin may be an independent risk factor for the development of coronary heart disease,” says Sattar, senior lecturer in endocrinology and metabolism and an honorary consultant in clinical biochemistry at Glasgow Royal Infirmary in Scotland. “Leptin appears to be as strong a predictor as some well-recognized risk factors such as high systolic blood pressure or low levels of high-density lipoprotein (HDL) cholesterol.”

He cautions that these results must be confirmed by other studies before recommending routine leptin testing.

“Leptin is such a brilliant blood marker for body fat for people at any weight and it is not difficult to measure,” he says.

Sattar’s study used frozen blood samples from the 1989 landmark West of Scotland Coronary Prevention Study (WOSCOPS), a prospective trial that showed that pravastatin, a cholesterol-lowering statin drug, could prevent coronary disease in people with no previous history of it. The current research compared 377 men from the original study who had heart attacks or procedures to open clogged arteries during five years of follow-up and 783 controls who remained free of heart disease events. The controls were matched to cases on the basis of age and smoking history.

The researchers found that leptin levels in the men with heart disease were 16 percent higher than in controls. When they looked at risk of cardiovascular events, Sattar’s team found a 25 percent increased risk for every 30 percent rise in leptin levels, an amount identified in the article as one standard deviation.

The researchers report that leptin remained a risk factor independent of body mass index (BMI), a commonly used way to determine if someone is overweight (BMI of 25 or higher) or obese (BMI of 30 or greater). In addition, leptin levels increased along with levels of C-reactive protein (CRP) – a marker for inflammation in the body that is strongly associated with the development of heart disease. However, when the two proteins were studied together, leptin was still a significant marker for heart disease.

Regarding the BMI findings, he explains that leptin is a better indication of fat mass, since people can have the same body mass index but have different amounts of fat in their bodies. The finding that leptin, a fat protein, is linked to heart disease risk independently from CRP, an inflammation marker, strongly suggests that fat may be important in heart disease risk, says Sattar.

“Leptin may give important information about the development of heart and blood vessel disease,” he says. “Perhaps because it is a good indicator of the amount of body fat a person has or an independent correlate of insulin resistance, since both leptin and CRP levels increase along with that condition.” Insulin resistance is a condition in which the body makes adequate amounts of insulin but the cells are resistant to using it efficiently.

“Our findings could also point toward some new way in which fat tissue promotes cardiovascular disease,” he says. Sattar notes that regular exercise can have immediate effects on leptin levels because it reduces the body’s fat content, even in the absence of weight loss.

Co-authors include: A. Michael Wallace, Ph.D.; Alex D. McMahon, Ph.D.; Chris J. Packard, D.Sc.; Anne Kelly, MIBiol; James Shepherd, Ph.D.; and Allan Gaw, M.D.

Researchers found that the TB bacterium has a molecule on its outer surface called lipomannan that can stop production of an important protein in the body’s immune cells that helps contain TB infection and maintain it in a latent state. This protein is called tumor necrosis factor (TNF). When TNF is not produced in sufficient quantities, the TB bacterium can grow unchecked and cause an uncontrolled active infection inside and outside of the lungs.

"There are several unique components on the Mycobacterium tuberculosis outer cell wall that help it sneak into the lung relatively unnoticed," said Larry Schlesinger, professor and chair of the Department of Microbial Infection and Immunity at Ohio State University and senior author of the study. "The more we can learn about how these cell wall structures influence the human immune response, the closer we can get to developing a more effective strategy to treat or even prevent an active tuberculosis infection."

Lipomannan resembles a tree branch sprinkled with smaller sugar molecules protruding from the outer cell wall of the bacterium. The findings show that lipomannan can block TNF production at the microRNA level. MicroRNAs are small segments of RNA that regulate — or fine-tune — a gene’s protein-building function.

To date, microRNAs have been implicated most frequently in the development of cancer. Schlesinger said this research is among the first studies to show that pathogenic bacteria can influence microRNA activation in immune cells and is the first to explore how microRNAs regulate the macrophage inflammatory response to Mycobacterium tuberculosis.

Macrophages are first-responder cells in the immune response. They eat TB bacteria at the point of infection in the lung and then normally activate molecules that make pieces of the bacteria visible to infection-fighting warriors, triggering an eventual T-cell response to come to the macrophages’ aid.

The research is published this week in the online early edition of the Proceedings of the National Academy of Sciences.

About 2 billion people worldwide are thought to be infected with TB bacteria. People who are infected can harbor the bacterium without symptoms for decades, but an estimated one in 10 will develop active disease characterized by a chronic cough and chest pain. Both active and latent infections are treated with a combination of antibiotics that patients take for at least six months, and such treatment is becoming less effective with more drug-resistant bacterial strains.

Schlesinger and colleagues conducted the study comparing lipomannans from two types of bacteria — a virulent strain of Mycobacterium tuberculosis and a harmless strain called Mycobacterium smegmatis, which is often used as a control bacterium in TB research.

Many of these same researchers, led by Schlesinger, had previously isolated the lipomannans from each type of bacterial cell’s surface and used powerful biochemical analyses to characterize the significance of the lipomannans’ structural differences. In a study published recently in the Journal of Biological Chemistry, the group reported on how the surface structures on virulent TB bacteria lowered the response of a specific T-cell that typically gets recruited to fight tuberculosis.

In this newer study, the scientists compared how the structures affected the production of TNF in primary human macrophage culture experiments.

They first established that human macrophages respond differently to the two different types of bacteria lipomannans after 24 hours of exposure. Lipomannan from the virulent TB bacterium produced significantly less TNF than lipomannan from the M. smegmatis bacterium.

Though the study showed that the harmless cells increase production of TNF through a well-known receptor pathway as expected, the virulent TB bacteria did not make use of that receptor pathway. This supported the concept that the pathogenic TB bacterium has figured out another way to block the TNF protein in its quest to keep the immune system guessing, said Schlesinger, also the director of Ohio State’s Center for Microbial Interface Biology.

A single microRNA can affect the production of hundreds of proteins, and the process of identifying those relationships is ongoing. However, two microRNAs in this study were known to be relevant for their connections to genes and proteins already established as players in the immune response to TB infection: miR-125b and miR-155.

Biochemical and genetic experiments showed that macrophages stimulated with lipomannan from TB bacteria had enhanced expression of miR-125b, effectively inhibiting the production of TNF. In contrast, the lipomannan from the harmless bacteria had enhanced expression of miR-155, which regulates other compounds in a way that stimulates TNF production.

Researchers’ experimental manipulation to lower the expression of miR-125b in macrophages increased production of TNF in response to the TB bacteria lipomannan, further confirming that this regulation of TNF occurred at the microRNA level, Schlesinger said.

"This really speaks to the power of the tuberculosis bacterium to adapt to the human host," he said. "It has had centuries to develop a sophisticated way to deal with its encounter with the human. Fortunately, genomic technology is allowing us to identify microRNAs more and more rapidly, which might allow us to catch up with the TB bacterium and figure out a way to outsmart it."

This work was supported by grants from the National Institutes of Health.

Now, in research to be published March 15 online by Nature, scientists at The Rockefeller University have laid out a new approach. They have identified a diverse team of antibodies in "slow-progressing" HIV patients whose coordinated pack hunting knocks down the virus just as well as their super-antibody cousins fighting solo.

By showcasing the dynamic, natural immune response in these exceptional patients, the research, led by Michel C. Nussenzweig, Sherman Fairchild Professor and head of the Laboratory of Molecular Immunology, suggests that an effective HIV vaccine may come from a shotgun approach using of a wide range of natural antibodies rather than an engineered magic bullet.

"We wanted to try something different, so we tried to reproduce what’s in the patient. And what’s in the patient is many different antibodies that individually have limited neutralizing abilities but together are quite powerful," says Nussenzweig, who also is a Howard Hughes Medical Institute investigator. "This should make people think about what an effective vaccine should look like."

HIV strains mutate rapidly, making them especially wily adversaries of the immune system. But one element is shared almost universally among the diverging strains — a protein on the envelope of the virus called gp140 that HIV needs to infect immune cells. Prior research has shown that four randomly engineered antibodies that block the activity of that protein prevent the virus from infecting immune cells in culture, but all attempts to coax the human body into producing those four have failed.

So Johannes Scheid, a visiting student in Nussenzweig’s lab who is now a doctoral candidate, turned his attention to the antibodies produced by six people infected with HIV whose immune systems put up an exceptionally strong fight. The patients represent the roughly 10 to 20 percent of HIV patients who are able to control the virus and are very slow to progress to disease. Their immune systems’ memory B cells produce high levels of antivirus antibodies, but until now, researchers have known little about the antibodies or how effective they are.

With help from Rockefeller’s Center for Clinical and Translational Science and Rockefeller scientists David D. Ho and Jeffrey V. Ravetch, Scheid and colleagues isolated 433 antibodies from these individuals’ blood serum that specifically targeted the envelope protein — the chink in HIV’s protean armor. He cloned the antibodies and produced them in bulk, mapped which part of the envelope protein each targeted, and gauged how effective each was in neutralizing the virus. In the process, he identified a new structure within the envelope protein — called the gp120 core — that had never been recognized as a potential target for antibodies. "It’s the first time that anyone has defined what is really happening in the B cell response in these patients," says Scheid.

Scheid’s work shows that it’s common for these antibodies to have neutralizing activity, says Nussenzweig. But each antibody alone has limited ability to fight the virus. "Individually, they’re not as strong as the Famous Four," says Nussenzweig, referring to the high-profile super antibodies on which several vaccine attempts have been based. But in high concentrations, a combination of the sets of antibodies cloned from the individual patients seemed to act as teams to knock down the virus in cell culture as well as any single antibody studied to date. These natural antibodies were also able to recognize a range of HIV strains, indicating that their diversity may be an advantage over a single super antibody that focuses on only one part of the virus, which can mutate. The findings suggest that research into vaccines that mimic this natural antibody response could pay off.

Although many investigators have reported the prevalence of erosive esophagitis, the prevalence of non-erosive reflux disease (NERD) has not been investigated in China.

A research article published in the World Journal of Gastroenterology addresses this question. The research team led by Dr. You-Ming Li analyzed a spectrum of GERD subjects based on presenting symptoms and endoscopic findings.

One conclusion reported by the investigators is that of the 2231 recruited participants, 31.4% were diagnosed as having GERD, 10.6% were NERD patients, while 20.80% had objective findings of reflux esophagitis, including 19.5% patients with grade A or B reflux esophagitis, 0.90% with grade C and 0.40% with grade D.

Another conclusion is that old age, being male, having a moderate working burden, being divorced/widowed and heavy tea consumption remained significant independent risk factors for erosive esophagitis. Routine consumption of greasy food and constipation were considered significant independent risk factors for NERD.

GERD is one of the common GI diseases with a high occurrence rate in China, and its main associated factors include sex, anthropometrical variables and social-psychological characteristics.

Journal reference: Juan Du, Jiang Liu, Hong Zhang, Chao-Hui Yu, You-Ming Li. Risk factors for gastroesophageal reflux disease, reflux esophagitis and non-erosive reflux disease among Chinese patients undergoing upper gastrointestinal endoscopic examination. World J Gastroenterol 2007; 13(45): 6009-6015.

The T-rapa cell is a type of white blood cell that is cultured with rapamycin, co-stimulation and interleukin-4. These cells express a balanced Th2/Th1 effector phenotype — a T-cell profile that is thought to protect against transplant rejection and improve the outcome of patients by reducing graft versus host disease and improving graft versus tumor effect.

Patients were assigned to one of two study arms: those receiving T-rapa cell therapy (day 14) after transplantation with a pre-transplantation regimen of either induction chemotherapy (Arm A) or after outpatient, low-preparative chemotherapy (on day 0) (Arm B). Of 65 patients between the two groups, high-risk non-Hodgkin’s lymphoma (NHL) was the most frequent diagnosis (25 patients), followed by non-high-risk NHL (11), acute myelogenous leukemia/myelodysplastic syndrome (8), myeloma (7), chronic lymphocytic leukemia (6), Hodgkin’s disease (5), and chronic myelogenous leukemia (3).

Arm A had the best results, with 37.5% (15/40) of recipients in sustained complete remission following the study and a median survival probability of 63.6% at 24 months post-transplantation. The authors conclude that pre-emptive infusion with T-rapa cells (ex-vivo manufactured T-rapa donor derived cells) that express a balanced Th2/Th1 effector phenotype represents a novel approach to safely accelerate transplant engraftment and harness graft-versus-tumor effects after low-intensity conditioning.

This research was presented at the annual meeting of the American Society of Hematology (ASH) taking place December 4-7, 2010 in Orlando, Florida.

"Various techniques available until now for evaluating the small bowel have been either inadequate or have various disadvantages and limitations," said Birinder Nagi, MD, lead author of the study. "Radiologic evaluation of the small bowel is usually done by barium examination which cannot evaluate the bowel wall and surrounding structures. With CT enteroclysis, another method, mucosal details cannot be well seen. Both of these techniques are associated with increased exposure to radiation. PET-CT enteroclysis is a new promising technique, but also requires ionizing radiation. MR enteroclysis is not widely available and there is concern about patients vomiting in the gantry while they are undergoing the examination.

The study consisted of 50 patients with suspected small bowel disorder who underwent sonoenteroclysis followed by barium enteroclysis. The findings of the two were compared. The researchers noted small bowel thickness, luminal diameter, peristalsis and extra intestinal lesions. Of the 50 patients, 10 showed normal small bowel on both sonoenteroclysis and barium enteroclysis. The study also showed that 25 of the remaining 40 patients showed abnormality in the form of: strictures, dilated loops, thickened folds, mass lesions, etc. on both techniques as well. Additional findings on sonoenteroclysis were thickened bowel wall with loss of stratification, ascites, and lymphadenopathy. These were later diagnosed as cases of tuberculosis.

"The results of sonoenteroclysis were comparable to barium enteroclysis and also provided additional information regarding bowel wall and surrounding structures," said Dr. Nagi. "This examination is simple, non-invasive, without radiation, cheap and can be used as an initial investigation in patients with suspected small bowel diseases," he said.

The full results of this study will be presented on Thursday, April 17, 2008 during the American Roentgen Ray Society’s annual meeting in Washington, DC.