BreakThrough Digest Medical News |
| Control gene for ‘conveyor belt’ cells could help improve oral vaccines, treat intestinal disease Posted: 16 Jun 2012 09:00 PM PDT Scientists have found a master regulator gene needed for the development of M cells, a mysterious type of intestinal cell involved in initiating immune responses. M cells act like “conveyor belts,” ingesting bacteria and transporting substances from the gut into Peyer’s patches, specialized tissues resembling lymph nodes in the intestines. Better knowledge of M cells’ properties could aid research on oral vaccines and inflammatory bowel diseases.
A team of researchers at Emory University School of Medicine and RIKEN Research Center for Allergy and Immunology in Japan has identified the gene Spi-B as responsible for the differentiation of M cells. The results are published Sunday, June 17 in the journal Nature Immunology. “This discovery could really unlock a lot of information about the sequence of events needed for M cells to develop and what makes them distinctive,” says co-author Ifor Williams, MD, PhD, associate professor of pathology and laboratory medicine at Emory University School of Medicine. “M cells have been difficult to study because they are relatively rare, they are only found within the Peyer’s patches and can’t be grown in isolation.” Scientists at RIKEN, led by senior author Hiroshi Ohno, MD, PhD, teamed up with Williams’ laboratory, taking advantage of a discovery by Williams that a protein called RANKL, which is produced by cells in Peyer’s patches, can induce M cell differentiation. Research scientist Takashi Kanaya is first author of the paper. Kanaya and colleagues found that the gene Spi-B is turned on strongly at early stages of M cell differentiation induced by RANKL. Their suspicion of Spi-B’s critical role was confirmed when they discovered that mice lacking Spi-B do not have functional M cells, and the cells in the intestines lack several other markers usually found on M cells. “It was somewhat surprising to find Spi-B expressed in intestinal epithelial cells,” Williams says. “Because Spi-B is known to be important for the development of some types of immune cells, it was thought to be expressed only in bone marrow-derived cells.” In fact, the M cells in Spi-B deficient mice can’t be restored by a transplant of normal bone marrow, the researchers found. That means Spi-B has to be active in intestinal epithelial cells (not immune cells) for M cells to develop. Williams says information about M cells ? in particular, what molecules they have on their surfaces ? could be useful for targeting oral vaccines. Most vaccines in use today are administered by injection. But immunologists believe that in some cases, it may be better to deliver vaccines through the mouth or nose, thus strengthening the body’s defenses where an infection starts. Because M cells are involved in the uptake of bacteria, the study of M cells could also guide development of treatments for inflammatory bowel diseases, in which immune responses to intestinal bacteria appear to become dysregulated. ### The research at RIKEN was supported by the Ministry of Education, Culture, Sports, Science and Technology of Japan, the Japan Society for the Promotion of Science, the Japan Science and Technology Agency, the Japan Science Society, the Takeda Science Foundation, the Mitsubishi Foundation and the Uehara Memorial Foundation. The research in Williams’ lab is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (5R01DK064730-07) and the Bill & Melinda Gates Foundation. Reference:
T. Kanaya et al. The Ets Transcription Factor Spi-B Is Essential for the Differentiation of Intestinal Microfold (M) Cells. Nat. Immunol. (2012) doi:10.1038/ni.2352 The Robert W. Woodruff Health Sciences Center (http://www.whsc.emory.edu/home/about) of Emory University is an academic health science and service center focusing on teaching, research, health care and public service. Contact: Quinn Eastman |
| Freud’s theory of unconscious conflict linked to anxiety symptoms in new U-M brain research Posted: 15 Jun 2012 09:00 PM PDT
An experiment that Sigmund Freud could never have imagined 100 years ago may help lend scientific support for one of his key theories, and help connect it with current neuroscience. Today at the 101st Annual Meeting of the American Psychoanalytic Association, a University of Michigan professor who has spent decades applying scientific methods to the study of psychoanalysis will present new data supporting a causal link between the psychoanalytic concept known as unconscious conflict, and the conscious symptoms experienced by people with anxiety disorders such as phobias.
Howard Shevrin, Ph.D., emeritus professor of psychology in the U-M Medical School’s Department of Psychiatry, will present data from experiments performed in U-M’s Ormond and Hazel Hunt Laboratory. The research involved 11 people with anxiety disorders who each received a series of psychoanalytically oriented diagnostic sessions conducted by a psychoanalyst. From these interviews the psychoanalysts inferred what underlying unconscious conflict might be causing the person’s anxiety disorder. Words capturing the nature of the unconscious conflict were then selected from the interviews and used as stimuli in the laboratory. They also selected words related to each patient’s experience of anxiety disorder symptoms. Although these words differed from patient to patient, results showed that they functioned in the same way. These verbal stimuli were presented subliminally at one thousandth of a second, and supraliminally at 30 milliseconds. A control category of stimuli was added that had no relationship to the unconscious conflict or anxiety symptom. While the stimuli were presented to the patients, scalp electrodes record the brain responses to them. In a previous experiment Shevrin had demonstrated that time-frequency features, a type of brain activity, showed that patients grouped the unconscious conflict stimuli together only when they were presented subliminally. But the conscious symptom-related stimuli showed the reverse pattern ? brain activity was better grouped together when patients viewed those words supraliminally. “Only when the unconscious conflict words were presented unconsciously could the brain see them as connected,” Shevrin notes. “What the analysts put together from the interview session made sense to the brain only unconsciously.” However, the experimental design in this first experiment did not allow for directly comparing the effect of the unconscious conflict stimuli on the conscious symptom stimuli. To obtain evidence for that next level, the unconscious conflict stimuli were presented immediately prior to the conscious symptom stimuli and a new measurement was made, of the brain’s own alpha wave frequency, at 8-13 cycles per second, that had been shown to inhibit various cognitive functions. Highly significant correlations, suggesting an inhibitory effect, were obtained when the amount of alpha generated by the unconscious conflict stimuli were correlated with the amount of alpha associated with the conscious symptom alpha — but only when the unconscious conflict stimuli were presented subliminally. No results were obtained when control stimuli replaced the symptom words. The fact that these findings are a function of inhibition suggests that from a psychoanalytic standpoint that repression might be involved. “These results create a compelling case that unconscious conflicts cause or contribute to the anxiety symptoms the patient is experiencing,” says Shevrin, who also holds an emeritus position in the Department of Psychology in U-M’s College of Literature, Science and the Arts. “These findings and the interdisciplinary methods used ? which draw on psychoanalysis, cognitive psychology, and neuroscience — demonstrate that it is possible to develop an interdisciplinary science drawing upon psychoanalytic theory.” He notes that a prominent critic of psychoanalysis and Freudian theory, Adolf Grunbaum, Ph.D., professor of the philosophy of science at the University of Pittsburgh, has expressed satisfaction that the new results, when added to previous evidence, show that fundamental psychoanalytic concepts can indeed be tested in empirical ways. For more than 40 years, Shevrin has led a team that has pushed at the boundaries between the disciplines of neuroscience, cognitive psychology, and psychoanalysis, looking for evidence that Freudian concepts such as the unconscious and repression could be documented through physical measures of brain activity. His work has explored the territory where neurobiology, thoughts, emotions and behavior meet. In 1968 he published the first report of brain responses to unconscious visual stimuli in Science, thus providing strong objective evidence for the existence of the unconscious at a time when most scientists were skeptical of Freud’s ideas. In that same study, he showed that unconscious perceptions are processed in different ways from conscious perceptions, a finding consistent with Freud’s views on how the unconscious works. In recent years, exchanges between Grunbaum and Shevrin explored the nature of the evidence for the existence and impact of unconscious conflicts. In a 1992 publication, the first study referred to, Grunbaum agreed that Shevrin had obtained objective brain based evidence for the existence of unconscious conflict, but Grunbaum noted that he had not shown that these conflicts caused psychiatric symptoms. His response to being informed of the new findings was an email stating: “I am satisfied”. Contact: Kara Gavin |
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