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Type 1 diabetes patients have lower blood levels of four proteins that protect against immune attack

Patients with type 1 diabetes have significantly lower blood levels of four proteins that help protect their tissue from attack by their immune system, scientists report.

Conversely, their first-degree relatives, who share some of the high-risk genes but do not have the disease, have high levels of these proteins circulating in their blood, said Dr. Jin-Xiong She, director of the Center for Biotechnology and Genomic Medicine at the Medical College of Georgia at Georgia Regents University.

Healthy individuals without the risky genes also have higher levels of the four proteins, IL8, IL-1Ra, MCP-1 and MIP-1β, according to the study in the Journal of Clinical Endocrinology & Metabolism.

The findings point toward a sort of protein cocktail that could help at-risk children avoid disease development as well as new biomarkers in the blood that could aid disease diagnosis, prognosis and management, said She, Georgia Research Alliance Eminent Scholar in Genomic Medicine and the study’s corresponding author.

The scientists looked at a total of 13 cytokines and chemokines, which are cell signaling molecules involved in regulating the immune response. They first looked at blood samples from 697 children with type 1 diabetes and from 681 individuals without antibodies to insulin-producing cells, a hallmark of this autoimmune disease. They then analyzed the blood of a second and larger set of individuals, which included 1,553 children with type 1 diabetes and 1,493 individuals without any sign of antibodies.

In this largest study of its kind, they consistently found a higher percentage of type 1 diabetes patients had significantly lower levels of the same four proteins.

“Their pancreatic cells are not secreting enough of these proteins,” said Dr. Sharad Purohit, MCG biochemist and the study’s first author. “Normally you are secreting enough of these cytokines so you prevent attack by the immune system.”

Individuals who have three of the known high-risk genes for type 1 diabetes but high serum levels of these four proteins are less likely to have disease, suggesting that these proteins may provide dominant levels of protection against type 1 diabetes even in a genetically high-risk group, Purohit said.

“If the individuals with high-risk genes weren’t making more of the proteins, they likely would have diabetes, said Dr. Ashok Sharma, an MCG bioinformatics expert and study co-first author.

One of the proteins found at low levels in patients, MIP-1β, has been shown in animal models to protect against type 1 diabetes development. A recombinant version of IL-1Ra, already used to combat rheumatoid arthritis, is also under study for both type 1 and 2 diabetes. And, human studies have shown that newly diagnosed patients with type 1 diabetes who go into remission have higher levels of IL-1Ra than those who don’t.

Cytokines and chemokines can promote or inhibit inflammation – cytokines such as MIP-1β can do both – and the proper mix helps keep inflammation in check. As an example, IL-1Ra, a cytokine secreted by several cell types, including immune cells, is a natural antagonist of the inflammation promoting cytokine IL-1β.

“We are providing evidence that clinical trials with any of these four molecules may work, and if we use them in combination, they may work even better,” She said. “One of the major research foci in our group is to identify biomarkers for various diseases, diabetes, cancer and others. We also want to identify new therapeutic strategies or targets through the discovery of biomarkers.”

Type 1 diabetes is an autoimmune disease, which primarily surfaces in childhood, where the immune system attacks the insulin-producing cells of the pancreas, leaving children facing a lifetime of daily insulin therapy to try to keep blood sugar levels under control.

Some of the 13 cytokines and chemokines originally screened for the study were known factors in type 1 diabetes, and the scientists were curious about the role of others.

Research funding was provided by the National Institutes of Health and the Juvenile Diabetes Research Foundation. Endocrine clinics based in Atlanta, including Atlanta Diabetes Associates, Pediatric Endocrine Associates and Southeastern Endocrine and Diabetes, contributed to the study.

Rawson selected to design, lead new Commission on Patient Experience for American College of Radiology

Dr. James V. Rawson, chairman of the Department of Radiology and Imaging at the Medical College of Georgia at Georgia Regents University, will design and lead a new Commission on the Patient Experience for the American College of Radiology.

Rawson, who also holds the P.L., J. Luther, Ada Warren Chair of Radiology at MCG, was recently elected to a three-year term on the 33-member Board of Chancellors of the American College of Radiology.

He has lectured and consulted nationally on bringing the patient centered focus to radiology. Leading this new commission, he will help his big machinery, high-tech specialty shift its focus even more toward patients.

“We have to put the patient in the center of health care,” said Rawson, an advocate for doing just that during his 15-year tenure as MCG’s Radiology chairman. “Everything has to be about the patient,” from how appointments are scheduled to parking to care delivery to timely receipt of study results, he said.

Rawson had sick family members throughout his medical school years at Tufts University in Boston and while completing a diagnostic radiology residency at New York Medical College, and a Body Magnetic Resonance Imaging Fellowship at Mallinckrodt Institute of Radiology at Washington University. He believes those experiences made him a better doctor and encouraged him early on to build care around the patient.

“I never was very far from the experiences patients and families were having in health systems because I was always on both sides of the table,” said Rawson. He serves on the Patient Experience Operations Committee of Georgia Regents Medical Center and works closely with the GRHealth Center for Patient and Family Centered Care to ensure patient advisors are involved in every facility and service decision made in radiology, from the patient-friendly Breast Health Center to extensive changes still underway in the Children’s Hospital of Georgia.

“The challenge was and is to think about how you can improve a child’s experience coming to a strange place that is potentially scary,” Rawson said of changes being made at the children’s hospital that will include color, lighting, and child-friendly technology. Even large imaging machines, such as MRIs, for adults already have lighted overhead boxes with soothing scenes for patients to focus on as they prepare for their exam. Adult waiting rooms also now have the look and feel of a coffee shop. Review of patient satisfaction surveys are part of regular radiology faculty meetings.

Mounting evidence indicates that a patient and family focus also yields shorter hospital stays and better outcomes; in fact, hospital reimbursement from federal health insurance programs are now tied to patient satisfaction. “Patient satisfaction surveys are part of the culture of medicine now,” said Rawson, who is excited and honored to help further incorporate this approach into his chosen specialty. He plans to populate the new American College of Radiology commission with a strong cross section of radiologists, related administrators, as well as patients with experience and/or interest in enhancing the philosophy and practice.

Rawson’s other leadership roles with the American College of Radiology include serving as Chair of the Committee on Governmental and Regulatory Issues in Academic Radiology, and the Committee on Economic Issues in Academic Radiology. He is on the editorial board of the Journal of the American College of Radiology and just completed an 11-year term as Chair of Hospital Outpatient Prospective Payment System/Ambulatory Payment Categories for the college.

High blood levels of growth factor correlate with smaller brain areas in patients with schizophrenia

High blood levels of a growth factor known to enable new blood vessel development and brain cell protection correlate with a smaller size of brain areas key to complex thought, emotion and behavior in patients with schizophrenia, researchers report in the journal Molecular Psychiatry.

Higher blood levels of vascular endothelial growth factor, or VEGF, also correlate with high blood levels of interleukin 6, a cytokine that can cross the protective blood-brain barrier and typically promotes inflammation, said Dr. Anilkumar Pillai, neuroscientist in the Department of Psychiatry and Health Behavior at the Medical College of Georgia at Georgia Regents University. As with many disease types, inflammation is increasingly associated with schizophrenia, and high blood levels of IL-6 already have been found in these patients.

The new findings appear to point toward a blood test as an easier way to confirm the diagnosis of schizophrenia, rather than complicated and expensive imaging studies of the brain, and, ultimately, better disease understanding and treatment, said Pillai, the study’s corresponding author. “We are talking about a molecule where you can just draw blood and look at the lab profile,” he said.

A smaller prefrontal cortex is one of the brain abnormalities identified through brain scans of living patients as well as autopsies. Pillai’s lab had earlier shown low brain levels of VEGF, which could help explain lower blood flow and brain volumes in these patients. “Decreased blood flow leads to decreased brain tissue volume,” he said. Inflammation also can reduce brain size.

While findings of higher blood levels may sound counterintuitive to low VEGF levels in the brain, they likely indicate a “feedback inhibition” with the brain recognizing high circulating levels and deciding to produce less VEGF itself, Pillai said. In fact, high blood levels of VEGF may contribute to the disease process, the researchers write.

More patients need to be studied to see if the correlations hold up, Pillai said, and work also is needed to determine which comes first: high blood levels or low brain levels of VEGF.

The study, in collaboration with scientists at the School of Psychiatry at the University of New South Wales in Australia, looked at 96 people with schizophrenia as well as 83 healthy individuals. Brain scans were available on 59 of the patients and 65 healthy controls. Patients were recruited to Neuroscience Research Australia, a not-for-profit research institution based in Sydney that focuses on the brain and nervous system, as well as Lyell McEwin Hospital, a teaching hospital in South Australia affiliated with the University of Adelaide and the University of South Australia.

While likely best known for its role in making new blood vessels, VEGF also is key to the brain’s ability to adapt to change, such as respond to an injury, and protect against brain cell loss.

Kidney, bladder stones do not increase postmenopausal women’s risk of osteoporosis

Postmenopausal women with kidney or bladder stones are not at increased risk for osteoporosis, but they do have about a 15 percent increased risk of another painful stone, physician-scientists report.

Researchers looked at data on approximately 150,000 postmenopausal women and found, despite the two conditions being clearly associated in men, the same did not hold true for women, said Dr. Laura D. Carbone, chief of the Section of Rheumatology at the Medical College of Georgia at Georgia Regents University.

“We know in men that if you have a kidney stone, you are more likely to have osteoporosis,” said Carbone, corresponding author of the study in the Journal of Bone and Mineral Research. “We were trying to find out if that is also the case for women. We found that, unlike what has been reported in men, a woman having a kidney stone is not a risk factor for osteoporosis. However, having one urinary tract stone does put women at increased risk for a second stone.”

“We wanted women and their physicians to have this information,” said Dr. Monique Bethel, a research resident in the MCG Department of Medicine and study co-author. “If the two relate, and a patient who has not been screened for osteoporosis comes to the office with a kidney stone, her physician might have been concerned she also has a higher risk for osteoporosis. Our studies indicate she likely does not.”

However, women with a stone likely should work with their physician to reduce their increased risk of a subsequent stone, the physicians said, noting that low water/fluid intake and a high-salt, high-calorie diet are common stone risks. Having a stone also was known to put people at risk for subsequent stones, but the new study helps clarify the risk, Carbone said.

Their data came from participants in the National Institutes of Health Women’s Health Initiative, a major study to address common health problems, such as osteoporosis and cancer, in postmenopausal women. Out of more than 150,000 women followed in the WHI, 9,856 women reported urinary tract stones at the start of or over the course of the study. They were followed about eight years, on average. MCG researchers believe theirs is the largest, most comprehensive study of the association of the two conditions in postmenopausal women. They looked at the data several different ways, adjusting for factors that could also influence outcome, such as physical inactivity, a known risk factor for both osteoporosis and kidney stones. They only looked at whether urinary tract stones increased the risk of osteoporosis, not the reverse.

The incidence of urinary tract stones is on the rise generally, particularly in women, with a 70 percent increase in the last 15 years. Osteoporosis already affects about 1 in 3 postmenopausal women and 1 in 5 older men, although the incidence of hip fractures is trending downward, Bethel said.

The Osteoporotic Fractures in Men, or MrOS, study, which looked at nearly 6,000 men with a mean age of 73.7 to determine risk factors for osteoporosis, identified urinary tract stones are a risk factor.

One link between the seemingly disparate conditions of stones and weak bones is an excess of calcium in the urine, which tends to be more common in men, Carbone said. Sodium and calcium share a common transport mechanism at the kidney, and sodium affects reabsorption of calcium by that organ. When sodium levels are high, from eating too much processed or fast food, for example, more calcium is eliminated in the urine. Also, overactivity of the parathyroid glands, which regulate levels of calcium in the blood, is associated with both urinary tract stones and fractures of the vertebra in the spine, a sign of the typically silent osteoporosis.

Interestingly some treatments for osteoporosis, including calcium supplements, can increase the risk of stones. Conversely, individuals who’ve already experienced a urinary tract stone might avoid calcium to help avoid a subsequent stone and inadvertently increase their osteoporosis risk, the researchers write.

Khan named administrative director for MCG Admissions

Dr. Iqbal Khan, founding dean of the Medical College of Georgia Southwest Campus in Albany, has been named administrative director of the Office of Admissions at the Medical College of Georgia at Georgia Regents University.

Khan, who was assistant dean of the Southwest Campus from 2005-10, also serves as assistant dean of the University of Georgia College of Pharmacy’s Southwest Campus, also in Albany, where he oversaw the design and build-out of the new campus and spearheaded its accreditation process.

In his new role, he will help organize and manage the medical school admissions process, which, each year, includes the processing of more than 3,000 applications, more than 8,000 reference letters and transcripts and more than 1,000 applicant interview reports. Khan will also help with recruitment, advising, enrollment and retention. He will also chair the GRU Medical Scholars Admissions Committee and serve on the MCG Scholarship Committee. He has been a member of the MCG Admissions Committee since 1999.

As assistant dean of the MCG Southwest Campus, Khan established relationships with community physicians and hospitals across a 1,600 square-mile area and negotiated affiliation agreements with 14 hospitals and health care facilities in the region. He recruited 148 new faculty and worked to recruit students from rural communities to the campus, more than doubling the number from five to 14.

Prior to his appointment at the Southwest Campus, Khan, a reproductive physiologist, served as director of undergraduate medical education in the MCG Department of Obstetrics and Gynecology from 1998-2005 and as director of the department’s IVF and Andrology laboratories from 1990-2002.

He serves on the board of directors for the Health Care Ethics Consortium of Georgia and is a member of the National and International Team of Inspectors for the College of American Pathologists for Reproductive Laboratories.

Khan received his bachelor’s and master’s degrees in physiology from the University of Karachi in Pakistan and his doctoral degree in reproductive physiology from the University of Gothenberg in Sweden.

Higher vitamin D doses may be needed to restore healthy levels in overweight blacks

The current recommended minimum daily dose of vitamin D is not sufficient to restore healthy vitamin D levels in overweight or obese blacks, researchers report.

Rather, daily intake of more than three times the recommended minimum is needed to restore what is generally considered a healthy blood level of vitamin D, said Dr. Yanbin Dong, geneticist and cardiologist at the Georgia Prevention Institute at the Medical College of Georgia at Georgia Regents University.

Overweight blacks are at increased risk for vitamin D deficiency because darker skin absorbs less sunlight – the skin makes vitamin D in response to sun exposure – and fat tends to sequester vitamin D for no apparent purpose.

The study, published in the journal BioMed Central Obesity, looked at the effects of three levels of vitamin D supplementation in 70 overweight-to-obese blacks under age 50 living in the Southeastern United States who appeared healthy, although their circulating level of vitamin D was considered low.

The Institute of Medicine recommends a daily intake of 600 international units of vitamin D for most children and adults; 800 IUs for those age 70 and older. For adolescents and adults, they recommend 4,000 IUs as the upper daily limit; 2,000 was the previous upper limit.

In what appears to be the first randomized controlled study in this cohort, researchers found that 600 IUs did not restore what many experts consider the optimal blood level of vitamin D within 16 weeks.

However, both 2,000 and 4,000 IUs restored the desirable levels of 30 nanograms per milliliter to individuals with previous levels of less than 20 ng/mL, levels which put them at high risk for bone-weakening rickets and potentially other maladies.

The 4,000 upper-limit dose restored the healthy blood level quicker – by eight weeks – and was also better at suppressing parathyroid hormone, which works against vitamin D’s efforts to improve bone health by absorbing calcium, said Dong, the study’s corresponding author.

“We hope these studies will give physicians better guidelines for some of their patients,” said Dong.  “As with many therapies in medicine today, evidence is emerging that a more personalized approach is likely the best approach when determining how much vitamin D is optimal for an individual. Dose definitely matters.”

As an example, participants in the group he studied who had high parathyroid hormone levels likely should take 4,000 IUs daily while the remainder appear to achieve desired results with 2,000 IUs.

Although long known as a way to build strong bones and teeth, there is increasing evidence of vitamin D’s role in the cardiovascular and immune systems, kidneys, mental health, and more. It’s likely, as with high parathyroid hormone levels, patients at high risk for cardiovascular disease might benefit from higher doses, said Dong, noting that much work is needed to identify optimal dosing for specific conditions.

Although wide ranges of daily doses already have been studied and there are no known serious side effects, there is no point in people taking more than they should, even if it’s only to save money, Dong said. Also, correlations are emerging –  but no hard science yet – that at too-high doses, for example, vitamin D can go from being a cancer preventer to a cause, he said.

For the study, researchers gave all doses of vitamin D monthly rather than daily to help ensure that all participants were getting the correct doses. Giving this once-monthly version of even the maximum recommended daily dose was equivalent to spending an afternoon at the beach in a bathing suit, Dong said.

Dr. Jigar Bhagatwala, a research resident in the MCG Department of Medicine, is the study’s first author.  The research was funded by the National Institutes of Health and the American Heart Association.

Rawson elected to American College of Radiology leadership

Dr. James V. Rawson, Chairman of the Department of Radiology and Imaging at the Medical College of Georgia at Georgia Regents University, has been elected to a three-year term on the 33-member Board of Chancellors of the American College of Radiology.

Rawson, who holds the P.L., J. Luther, Ada Warren Endowed Chair of Radiology at MCG, also was recently named President of the Georgia Radiological Society, the Georgia chapter of the national group.

His leadership roles with the American College of Radiology include serving as Chair of the Committee on Governmental and Regulatory Issues in Academic Radiology, the Committee on Economic Issues in Academic Radiology, and the Committee on Hospital Outpatient Prospective Payment System and Ambulatory Patient Classification.

He is on the editorial board of the Journal of the American College of Radiology and just completed an 11-year term as Chair of Hospital Outpatient Prospective Payment System/Ambulatory Payment Categories for the college.

Rawson has served on the Georgia Radiological Society’s Executive Committee since 1999.  His other national leadership roles in radiology include serving on the Association of University Radiologists Board of Directors, as a Councilor for the Board of the Society of Chairs of Academic Radiology Departments, and a one-year term on the Society of Health Systems Content and Connections Committee.

Lokeshwar named Chairwoman of MCG Department of Biochemistry and Molecular Biology

VinataLokeshwarwebDr. Vinata B. Lokeshwar, Professor and Co-Director of Urology Research in the Departments of Urology and Cell Biology at the University of Miami-Miller School of Medicine, is the new Chairwoman of the Department of Biochemistry and Molecular Biology at the Medical College of Georgia at Georgia Regents University.

Lokeshwar also is one of two Directors of the Pilot and Collaborative Translational and Clinical Studies component of the Miami Clinical And Translational Science Institute, one of 61 translational centers in the nation funded by the National Institutes of Health’s National Center for Advancing Translational Sciences.

The cancer researcher, who studies the metastasis of prostate, bladder, and kidney cancer with the goal of better diagnosis and treatment, assumes her new duties at MCG in September.

“We are very pleased that Dr. Lokeshwar, an accomplished scientist, educator, and leader, will be joining the MCG team,” said Dr. Peter F. Buckley, Dean of the state’s public medical school; Interim Executive Vice President for Health Affairs, Georgia Regents University; and Interim CEO, Georgia Regents Medical Center & Medical Associates.

“One of her many great strengths is that she is strongly committed to the tenet that great science, great education, really any great accomplishments require a great team and hard work and that the best leaders are ones who nurture and practice both. Her scientific expertise also is a terrific addition to our collaborative efforts to grow cancer research in our state where the cancer incidence exceeds the national rate and to our already strong urology program. Those attributes and many more make her a great fit for our medical school,” Buckley said.

The Dean thanked Dr. Shuang Huang for his service as interim Chair and Drs. Clinton Webb and Nita Maihle for co-chairing the national search.

Lokeshwar’s research has had continuous external funding for 18 years. She is currently Principal Investigator on three National Institutes of Health grants as well as two additional grants from the Women’s Cancer Association of the University of Miami to help develop a urine test for bladder cancer and pursue early diagnosis and new treatment for kidney cancer.

She is a past President of the Society for Basic Urologic Research; an ad hoc member of the Research Advocacy and NIH Relations workgroup of the American Urological Association Office of Research; and recently chaired the Bladder Cancer – Basic Research Session at the American Urological Association Annual Meeting two years in a row.

She is Senior Editor of the textbook, “Bladder Tumors: Molecular Aspects and Clinical Management,” Associate Editor of the journal Bladder, Consulting Editor of the journal Urologic Oncology, and a member of the editorial board of World Journal of Urology and Bladder Cancer.

She has mentored more than 30 graduate students, residents, fellows, and junior faculty. Recent educational honors include the 2015 Sylvester Comprehensive Cancer Center Outstanding Mentor of the Year for Trainees. Urology residents at the Miller School of Medicine honored her with the 2011 Urology Teacher of the Year Award, and the American Urological Association honored her as a Female Leader in Urology that same year.

Lokeshwar earned a PhD from St. Louis University in Missouri and completed postdoctoral studies in the Department of Cell Biology and Anatomy at the University of Miami Miller School of Medicine. During her postdoctoral work, she completed American Heart Association and National Cancer Institute fellowships. She joined the university’s faculty in 1994.