Author Interviews, Dermatology, Genetic Research / 28.05.2016
Genes That Activate Inflammation in Psoriasis Identified
MedicalResearch.com Interview with:
Ryuta Muromoto, Ph.D.
Department of Immunology,
Faculty of Pharmaceutical Sciences, Hokkaido University
Sapporo, Japan
MedicalResearch.com: What is the background for this study?
Dr. Muromoto: Psoriasis is an immune-mediated chronic inflammatory skin disorder that affects some 125 million people worldwide. It is characterized by itchy, scaly skin plaques. It has been known that a cytokine IL-17A, which is produced by immune cells, plays a central role in the development and maintenance of clinical features of psoriasis. IL-17A acts on keratinocytes and up-regulates anti-microbial peptides and a set of chemokines, that are important for immune cell infiltration. This immune cell feedback amplifies psoriatic inflammation. Also, other inflammatory cytokines such as TNF-alpha and interferon-gamma are up-regulated, and have been implicated in pathogenesis of psoriasis. So, the interplay between cytokines appears to be important for development of psoriasis through keratinocyte activation. In this study, we sought to clarify the actual role of IL-17A and its interplay with other cytokines in keratinocyte activation.
Dr. Michael Johnson[/caption]
Michael A. Johnson Ph.D
Associate Professor
Department of Chemistry
University of Kansas
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Johnson: We undertook these studies because chemotherapy induced cognitive dysfunction, also known as ‘chemobrain’, has become a major health issue in recent years. For example, up to a third of patients who have undergone chemotherapy treatment for breast cancer have reported symptoms of chemobrain. These symptoms may include loss of verbal and visual memory as well as decreased mental flexibility and difficulty focusing.
For this study, we wanted to understand how treatment with chemotherapeutic agents affects the ability of neurons to communicate. An impairment of neurotransmitter release would imply that communication is hindered. This inability to communicate normally could contribute to cognitive dysfunction.
We initially measured the release of dopamine in a region of the brain called the striatum. Our measurement of dopamine in this region was motivated by two key issues: its importance in cognitive function and our ability to measure it with high temporal resolution. From a cognitive standpoint, dopamine is important because the striatum helps translate signals, received from the cortex, into plans by forwarding wanted signals to other parts of the brain and suppressing unwanted signals. Fortunately, we can easily measure dopamine release using an electrochemical technique called fast-scan cyclic voltammetry. This method allows us to not only measure how much dopamine is released from a living brain slice, but also it affords us the capability to measure how quickly dopamine is taken back up. We also measured serotonin release using this method.
Our main finding was that the ability of neurons to release dopamine was impaired after carboplatin treatment. We also found that serotonin release was similarly impaired. These release impairments corresponded to a decrease in cognitive ability of the treated rats.
Maayan Yitshak Sade[/caption]
Maayan Yitshak Sade MPH
Chief Scientific Officer
Clinical Research Center,
Soroka University Medical Center, Israel and
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Dr. Victor Novack[/caption]
Victor Novack, MD, PhD
Soroka University Medical Center and Ben-Gurion University in Beer Sheva, Israel
MedicalResearch.com: What is the background for this study?
Response: Numerous studies found association between exposure the air pollution and increased risk of cardiovascular and respiratory diseases. In recent years links were found between air pollution and diabetes as well. The scientific evidence supports a causal association between air pollution and oxidative stress, possibly involving impaired metabolism of glucose and lipids. In a recent study performed by our group, we observed a significantly increased risk for ischemic stroke among young adults, associated with air pollution exposure. Following these findings, and as a part of the possible theory linking the association air pollution exposure and cardiovascular diseases, we sought to investigate if this association might be mediated through the well-established cardiovascular risk factors such as abnormal lipid and glucose metabolism.
Dr. Robert Ursano[/caption]
Robert J. Ursano, M.D.
Professor and Chair
Department of Psychiatry/ Director
Center for the Study of Traumatic Stress
Uniformed Services University of the Health Sciences
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Ursano: This study is part of STARRS-LS (Study to address risk and resilience in service members-longitudinal study). STARRS is a group of studies that address suicide risk in the US Army. Suicidal behavior includes suicide ideation, plans, attempts and completions. Understanding the transitions between these is an important goal.
One component of STARRS is the examination of data available on all soldiers who were in the Army 2004-2009. This study examines suicide attempts in soldiers serving 2004-2009 in order to understand the association with deployment and the timing of suicide attempts as well as their association with mental health problems. STARRS is directed to identifying the who, when and where of service member risk. Then interventions can better be developed for these soldiers.
Dr. Robert Levenson[/caption]
Robert W. Levenson, Ph.D.
Professor, Department of Psychology
Director, Institute of Personality
and Social Research (IPSR)
University of California
Berkeley, CA
MedicalResearch.com: What is the background for this study?
Dr. Levenson: This study comes from a 20-year longitudinal study of Bay Area married couples that we began in the late 1980s. The main purpose of the study was to understand the emotional qualities of successful marriages. Couples came to our laboratory every five years so that we could get a snapshot of the way they interacted with each. We also measured their psychological and physical health. This new paper connects the emotional behaviors we observed when couples discussed a problem in their marriage at the start of the study with the kinds of illnesses they developed over the ensuing decades.
Dr. Robert Wong[/caption]
Robert Wong, M.D., M.S.
Attending Physician, Gastroenterology & Hepatology
Director, GI Education & Research
Highland Hospital I A member of Alameda Health System
Oakland, CA
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Wong: Colorectal cancer is a leading cause of morbidity and mortality in the United States. Early diagnosis through implementation of effective screening and surveillance programs leads to earlier staged tumor at time of diagnosis, which increases the treatment opportunities and improves overall survival. However, disparities in access to effective screening and surveillance can impair timely diagnosis and lead to advanced disease, limited treatment options and poor outcomes. The current study evaluated race/ethnicity-specific disparities in colorectal cancer epidemiology at a large urban safety net hospital and observed African American patients had significantly more advanced cancer stage at the time of diagnosis. Our study observed that African Americans were over 5 times more likely to have advanced stage 3-4 colon cancer at time of diagnosis compared with non-Hispanic white patients with colon cancer. While these findings are likely multifactorial, it sheds important light on race/ethnicity-specific disparities in colorectal cancer epidemiology and helps target future education and research to improve outcomes.
Dr. Sibaji Sarkar[/caption]
Sibaji Sarkar Ph.D
Instructor of medicine
Boston University School of Medicine
Boston
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Sarkar: Although breast and ovarian cancers have different clinical presentations, there are certain molecular events that are conserved between the two types of cancers. For example, mutation in a few genes, such as BRCA1, BRCA2, is an indicator of possible development of both breast and ovarian cancers. ARHI, a pro-apoptotic imprinted gene is epigenetically silenced in both breast and ovarian cancers. A similar pattern was observed in microRNA as well. There are also several genes which are differentially expressed in these two types of cancers but few of these striking resemblances led us to investigate whether they have a common origin. In this paper, we compared genetic and epigenetic events in both breast and ovarian cancers and we hypothesize that they may have similar origin (mechanism of formation of cancer progenitor cells), which should be regulated by epigenetic mechanism.
Dr. Ingrid Elisabeth-Christophersen[/caption]
Ingrid Elisabeth Christophersen MD PhD
Postdoctoral research fellow
Cardiovascular Research Center (CVRC)
Massachusetts General Hospital
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Christophersen: Several recent studies have utilized the CHA2DS2-VASc risk score to predict risk of atrial fibrillation (AF). However, the CHA2DS2-VASc was developed for prediction of stroke risk in patients with AF and has not been validated for prediction of AF risk. We have evaluated how well the CHA2DS2-VASc performed at predicting risk of AF compared with the most validated clinical risk score for AF - the CHARGE-AF risk score - in the Framingham Heart Study. We showed that the CHARGE-AF risk score performed better at predicting risk of AF than the CHA2DS2-VASc.
Nana Keum[/caption]
NaNa Keum, ScD|
Harvard T. H. Chan
School of Public Health Department of Nutrition
Departments of Nutrition and Epidemiology,
Harvard T.H. Chan School of Public Health
Boston, MA 02115
MedicalResearch.com: What is the background for this study?
Response: While general health benefits of physical activity are well-known, evidence on its specific benefits on cancer endpoints is limited and physical activity guidelines for cancer prevention lack details in terms of the optimal dose, type and intensity of physical activity.
MedicalResearch.com: What are the main findings?
Response: We found that the optimal exercise regime to prevent overall digestive system cancers may be to accumulate 30 MET-hours/week of physical activity primarily through aerobic exercise and regardless of its intensity.
Dr. Jennifer Kuk[/caption]
Jennifer L. Kuk, PhD
Associate Professor
York University
School of Kinesiology and Health Science
Toronto, Ontario
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Kuk: Artificial sweeteners are used to help individuals manage their weight, however, individuals who consume aspartame (a type of artificial sweeteners) have worse glucose metabolism than individuals with the same body weight but do not consume aspartame. This observation was only true for adults with obesity. Further, saccharin and natural sugars were not associated with differences in health after considering differences in obesity.
Dr. Prateek Sharma[/caption]
Dr. Prateek Sharma MD
Professor, Gastroenterology, Hepatology and Motility
Kansas University Medical Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Sharma: Reflux symptoms are a risk factor for Barrett's esophagus and approximately 10-15% of patients with reflux are diagnosed with Barrett's esophagus. Barrett's esophagus is a risk factor for esophageal adenocarcinoma. We evaluated the trends in the prevalence of be in patients with reflux disease over years and found that the prevalence of be was decreasing.
Dr. Bo Qin[/caption]
Bo (Bonnie) Qin, Ph.D.
Postdoctoral Scholar
Rutgers Cancer Institute of New Jersey
New Brunswick, NJ 08903
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Qin: Preventing or delaying the age-related cognitive decline that typically precedes the onset of dementia is particularly important considering that no effective strategies for dementia treatment have been identified. Vascular conditions such as hypertension are thought to be risk factors for cognitive decline, but important gaps in the literature on this topic remain.
Randomized clinical trials of blood pressure-lowering treatments for reducing the risk of cognitive decline or dementia have largely failed to achieve beneficial effects. However, over the past 6 years, scientific evidence has accumulated that blood pressure variability over monthly or yearly visits may lead to greater risk of stroke and small and larger vessel cerebrovascular diseases. They could lead to subsequent changes related to cognitive dysfunction among older adults. We, therefore, hypothesized that blood pressure variability between visits is associated with a faster rate of cognitive function among older adults.
Dr. Alan Brown[/caption]
Alan S. Brown, M.D., M.P.H.
Professor of Psychiatry and Epidemiology
Columbia University Medical Center
Director, Program in Birth Cohort Studies, Division of Epidemiology
New York State Psychiatric Institute
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Brown: Smoking during pregnancy is a risk factor for several pregnancy-related outcomes including low birthweight and preterm birth. Evidence for a link with schizophrenia is scant. We analyzed a maternal biomarker of smoking called cotinine, a nicotine metabolite, in mothers of nearly 1,000 schizophrenia cases and 1,000 controls in a national birth cohort in Finland. We found that heavy smoking in pregnancy was related to a 38% increase in schizophrenia risk in offspring and that as cotinine levels increased even in the more moderate smokers risk of schizophrenia also increased.
Dr. Jiang He[/caption]
Jiang He, M.D., Ph.D.
Joseph S. Copes Chair and Professor
Department of Epidemiology
School of Public Health and Tropical Medicine
Tulane University, New Orleans
MedicalResearch: What is the background for this study?
Dr. Jiang He: Chronic kidney disease is associated with increased risk of end-stage renal disease, cardiovascular disease, and all-cause mortality. A positive association between sodium intake and blood pressure is well established in observational studies and clinical trials. However, the association between sodium intake and clinical cardiovascular disease remains less clear. Positive monotonic, J-shaped, and U-shaped associations have been reported. Methodologic limitations, including inconsistencies in dietary sodium measurement methods, could be contributing to these conflicting findings. Furthermore, no previous studies have examined the association between sodium intake and incident cardiovascular disease among patients with chronic kidney disease.
Dr. Brian Stansfield[/caption]
Dr. Brian Stansfield MD
Neonatologist
Children's Hospital of Georgia and the Medical College of Georgia
Augusta University
MedicalResearch.com: What is the background for this study?
Dr. Stansfield: Since the mid-20th century, we have experimental evidence in animal models and human data demonstrating the influence of maternal nutrition on the offspring - both in the short term and long term. Low birth weight has been connected with higher incidence of cardiometabolic diseases including insulin resistance, coronary artery disease, and hypertension. Interestingly, low birth weight infants grow up to be relatively thin adults compared to their normal or high birth weight counterparts. Conversely, high birth weight infants tend to become heavier adults and obesity is directly linked with the same adult outcomes. So the association of cardiac and metabolic diseases with low birth weight is not linked to adult obesity in general. Thus, speculation as to why extremes of birth weight lead to adult onset cardiometabolic disease suggests different mechanisms and modifying factors.
MedicalResearch.com: What are the main findings?
Dr. Stansfield: The findings of our study shed considerable light on the relationship between birth weight and risk factors for insulin resistance and visceral adiposity. Using magnetic resonance imaging (MRI) to achieve precise measurements of visceral adipose content and biomarkers for insulin resistance, we show that both low and high birth weight are associated with increased visceral adiposity and insulin resistance in a healthy population of adolescents aged 13-17 years. This association persists when we account for several recognized confounders including age, sex, race, activity level, and socioeconomic status. The most interesting finding of our study is that when you account for each adolescent’s current body mass index, a measure of obesity, the relationship between increased visceral fat and insulin resistance and low birth weight is strengthened suggesting that these adolescents had relatively high visceral adipose content despite obesity rates that were similar to their normal birth weight counterparts. On the other hand, correction for adolescent BMI (obesity) reduced the relationship between these metabolic markers and high birth weight infants. Thus, low birth weight infants may develop insulin resistance and increased visceral fat, both significant risk factors for cardiovascular disease and metabolic disease, despite having a relatively normal body shape in adolescents.
Dr. Sikarin Upala[/caption]
Sikarin Upala MD, MS, LLB
Internal Medicine, Bassett Medical Center and Columbia University College of Physicians and Surgeons, Cooperstown, New York
Preventive and Social Medicine
Mahidol University, Bangkok, Thailand
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Upala: Chronic hepatitis C virus infection is the most common cause of chronic liver disease and cirrhosis as well as the most common cause of liver transplantation in the United States. As caffeine has been found to be related to decreased liver enzymes, chronic liver disease,cirrhosis, and risk of hepatocellular carcinoma in several liver disease pathologies. There is inconclusive findings on the effect of caffeine on hepatitis C infected patients. Thus, we conducted a systematic review and meta-analysis to summarize the effect of caffeine consumption in patients with chronic hepatitis C.
We found that caffeine consumers have a 61% reduced risk of developing advanced hepatic fibrosis, which is one of the consequence of chronic hepatitis C. Our meta-analysis result is in the same way with other studies who found that coffee consumption could prevent the development of hepatic fibrosis in patients with liver disease. However, we cannot conclude about the effect of caffeine on HCV viral load as there is not enough information.
Dr. Deborah Cohen[/caption]
Deborah A. Cohen, MD, MPH
RAND Corporation
Santa Monica, CA 90407
MedicalResearch.com: What is the background for this study?
Dr. Cohen: An extensive infrastructure of neighborhood parks supports leisure time physical activity in most U.S. cities; yet, most Americans do not meet national guidelines for physical activity. Neighborhood parks have never been assessed nationally to identify their role in physical activity. We visited a representative sample of 174 parks in 25 cities across the United States and assessed their use as well as local park management policies.
MedicalResearch.com: What are the main findings?
Dr. Cohen: We found that nationwide, the average neighborhood park of 8.8 acres averaged 20 users/hour or an estimated 1,533 person hours of weekly use. Park use was higher in parks that were larger and had more facilities and that were in neighborhoods with a higher population density and lower percentage of households in poverty. Walking loops and gymnasia each generated 221 hours/week of moderate to vigorous physical activity. Seniors represented 4% of park users, but 20% of the general population. Programming and marketing were associated with 37% and 63% more hours of moderate to vigorous physical activity/week in parks, respectively.
The lower use of parks in low-income than in high-income neighborhoods was largely explained by fewer supervised activities and marketing/outreach efforts.
Dr. Annette Schürmann[/caption]
Prof-Dr. Annette Schürmann
Department of Experimental Diabetology
German Institute of Human Nutrition Potsdam-Rehbruecke
Nuthetal, Germany
MedicalResearch.com: What is the background for this study?
Dr. Schürmann: The aim of our study was to clarify why genetically identical mice respond very different to a high fat diet. Some of the mice react with an elevated body weight, others not. We analyzed the expression pattern
of liver at two time points, at the age of 6 weeks, (the earliest time
point to distinguish between those that respond to the diet (responder
mice) and those that did not (non-responders)), and at the age of 20
weeks. One transcript that was significantly reduced in the liver of
responder mice at both time points was Igfbp2. The reason for the
reduced expression was an elevated DNA-methylation at a position that is
conserved in the mouse and human sequence. The elevated DNA-methylation
of this specific site in human was recently described to associate with
elevated fat storage (hepatosteatosis) and NASH. However, as 6 weeks old
mice did not show differences in liver fat content between responder and
non-responder mice we conclude that the alteration of Igfbp2 expression
and DNA methylation occurs before the development of fatty liver.
Our data furthermore showed that the epigenetic inhibition of Igfbp2
expression was associated with elevated blood glucose and insulin
resistance but not with fatty liver.