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TODAY news for Thursday, October 29, 2007

Loma Linda University Medical Center news

Tenth annual research symposium highlights interdisciplinary cooperation

Second-year medical student Samantha Stout displays the poster board for a study she conducted with five other researchers at Loma Linda University.
Second-year medical student Samantha Stout displays the poster board for a study she conducted with five other researchers at Loma Linda University. Although her team’s contribution did not receive a prize in the student poster contest, the value of studies such as the one represented by Ms. Stout cannot be underestimated. Winners of the poster competition were announced during the 10th annual research symposium of the Loma Linda University School of Medicine on Monday, September 10, 2007, in Wong Kerlee International Conference Center.
Recent developments in basic science and clinical medical research towards finding effective new treatment modalities for nervous system disorders attracted more than 260 participants to the 10th annual research symposium of the Loma Linda University School of Medicine on Monday, September 10, 2007, in Wong Kerlee International Conference Center.

The first speaker of the morning was Ronald L. Carter, PhD. In his capacity as vice chancellor for academic affairs at Loma Linda University, Dr. Carter first welcomed participants and attendees, then affirmed his belief that the hallmark of any institution of higher education is the ability to “create new knowledge” through research. He further stated that new scientific knowledge is only useful when published and shared among peers, and stated that “today’s symposium is of particular import” since “basic inquiry in the foundational research sciences is where new knowledge ultimately begins.” He finished by thanking everyone involved in research at Loma Linda for “making us a uni-versity in the purest sense.”

In his introductory comments, Kerby C. Oberg, MD, PhD, noted that “the melding of clinical and basic science work is critical to making progress in the lives of our patients. It is also an essential part of the University’s mission ‘to make man whole.’”

Dr. Oberg said the focus of the symposium would be on research contributions to the field of translational medicine, which he defined as the process of “converting basic science questions into clinical applications to benefit the public health.” Dr. Oberg expanded the idea by specifically narrowing the focus to “understanding the molecular, genetic, and genomic biochemical basis for Alzheimer’s disease.” Dr. Oberg, who served as chairman of the organizing committee for the symposium, is an assistant professor of pathology and human anatomy at the LLU Scho
Melanie Mediavilla-Varela discusses the findings of her research into �Characterization of Caspase-Independent Cell Death Induced by Docetaxel� to attendees at the 10th Annual Research Symposium of the Loma Linda University School of Medicine.
Melanie Mediavilla-Varela discusses the findings of her research into “Characterization of Caspase-Independent Cell Death Induced by Docetaxel” to attendees at the 10th Annual Research Symposium of the Loma Linda University School of Medicine. Ms. Mediavilla-Varela, a PhD student in microbiology at the University, won one of two first prizes awarded in the student poster contest. The other first-prize winner, Claudius Mueller, is not pictured.
ol of Medicine.

After Dr. Oberg finished his remarks, John Buchholz, PhD, professor of physiology and pharmacology at the School of Medicine, introduced a mini-symposium on “The Pathogenesis of Nervous System Disease.” The presenters were introduced as Jiping Tang, MD, PhD; Stephen Ashwal, MD; and Wolff Kirsch, MD.

As first presenter of the mini-symposium, Dr. Tang discussed the methodology and results of a series of studies which she and several colleagues (K. Yata, G. Matchett, T. Tsubokawa, J. Kanamura, J. Calinisan, R. Martin, I. Solaroglu, J. Cahill, and J.H. Zhang) conducted into “The Neuroprotective Effect of G-CSF.”  Specific areas of inquiry included G-CSF’s role in reversing the progress of brain injury resulting from cerebral and focal ischemia, global ischemia, and neonatal-hypoxia ischemia.

In a spirited, half-hour presentation liberally illustrated with slides, Dr. Tang discussed the role of G-CSF (granulocyte colony-stimulating factor) in stimulating the production of granulocytes and stem cells within the bone marrow. 

Dr. Tang, who serves as associate professor of physiology and pharmacology at the LLU School of Medicine, concluded her presentation by noting that G-CSF therapy increased the survival of neuronal cells, significantly reduced the infarct volume, prevented brain tissue loss, and improved neurological function in a rat model of cerebral focal ischemia and neonatal-hypoxia ischemia. She also noted that G-CSF therapy produced a transient improvement in hippocampal function in a rat model of cerebral global ischemia. The neuroprotective effects of G-CSF are associated with the inhibition of apoptosis, the suicidal death of certain cells within an organism.

The second presenter of the mini-symposium was Stephen Ashwal, MD, chief of the division of pediatric neurology in the department of pediatrics at Loma Linda University School of Medicine. At the beginning of his articulate presentation on “Neonatal Brain Ischemia: Neuroimaging as a Basis for Rational Stem Cell Therapy,” Dr. Ashwal noted that magnetic resonance imaging (MRI) allows scientists to see how common arterial ischemic injury is in newborn infants. He pointed out that until the imaging breakthroughs of the last 10 years, it has been hard to study the extent of ischemic injury in neonates. In addition, advanced imaging techniques can also be used to study these problems in small animal models.

Dr. Ashwal observed that neural stem cells have the potential to offer physicians a powerful post-injury treatment modality by helping brain tissue repair itself in both infants and adults. While he noted that stem cell therapy can repair damage in adult stroke victims, he cautioned that the severity of the individual injury is an important consideration in the selection of candidates for treatment. He also stated that much research is still needed to make sure such treatments are safe as well as effective.

In the current climate of agitated discussion on stem cell research, it is important to differentiate between embryonic and neural stem cells. While embryonic stem cell research has drawn fire from many quarters for its use of cells taken from living human organisms, the use of neural stem cells is not controversial as they are frequently obtained from animal sources. 

“With neural stem cells there’s no ethical controversy,” Dr. Ashwal noted. “Our proposal has been reviewed by the ethics committee here at Loma Linda and they were very supportive as they realize the importance of doing careful scientific studies to best help children.”

The final presenter of the mini-symposium was Wolff Kirsch, MD, professor of neurosurgery and biochemistry at the School of Medicine and director of the Neurosurgery Center for Research, Training and Education.

Dr. Kirsch peppered his presentation on “A Progressive Increase in Brain Microhemorrhages Correlates with Sporadic Late-Onset Dementia Development” with touches of humor. Pointing to a slide of himself with colleague Harry Vinters, MD, taken beside the geyser fields of Reykjavik, Iceland—where the two scientists recently participated in a conference on dementia—Dr. Kirsch noted that the image should be titled “Geezers at the Geysers.” He then went on to explain that in Iceland, they pronounce the word “geysers” identically to the way we say “geezers.”

“The other presenters have called attention to research that benefits neonates,” he observed. “My report concerns the loss of dignity and cognitive power at the other end of life.” He went on to a discussion of dementia from early stages of mild cognitive impairment through very advanced cases of fully developed Alzheimer’s.

To demonstrate the effects of Alzheimer’s disease, Dr. Kirsch showed two video segments of the same retired academic administrator answering questions on two separate occasions. During the first video clip, the gentleman was able to handle routine questions about recent events in his life with relative ease.

But in the second clip, filmed only 18 months later, he could not recall the names of family members and friends he had known for decades. Dr. Kirsch then depicted images of human brains with varying degrees of microhemorrhaging that correlated to the development of the symptoms the subject had displayed in the progressive stages of Alzheimer’s shown in the video clips.

Dr. Kirsch concluded by noting that uncontrolled inflammation may be a key factor in the development of Alzheimer’s disease and that new imaging and biomarker technology show great promise of offering significant new insights into how this insidious disease develops, and, perhaps, into how it can be combated in the future.

At the conclusion of the mini-symposium, Dr. Kirsch introduced his friend and colleague Harry V. Vinters, MD. Dr. Kirsch discussed Dr. Vinters’ seminal contributions to both basic science and clinical research in the fields of pediatric epilepsy, cerebral amyloid angiopathy (CAA) and Alzheimer’s disease. He mentioned that Dr. Vinters is the professor of pathology and laboratory medicine and chief of the neuropathology section at UCLA as well as the Daljit S. and Elaine Sarkaria, MD, chair of diagnostic medicine at the David Geffen School of Medicine at UCLA.

He described Dr. Vinter’s prolific literary contributions as the author of more than 300 peer-reviewed publications and recent past presidency of the American Association of Neuropathologists.

After more of good-natured jocularity regarding their mutual friendship, Dr. Kirsch announced that Dr. Vinters was here to deliver the keynote scientific presentation of the symposium, the Mortensen Lecture, and that the title of his presentation was “The Pathogenesis of Dementia: How Clinical and Basic Scientists Interact to Tackle a Public Health Problem.”

Dr. Vinters took a moment to acknowledge Dr. Kirsch as “a remarkable scientist.” He noted that Dr. Kirsch stopped doing surgery in 2002 after receiving a large National Institutes of Health grant for Alzheimer’s research and that since then, he’s been doing groundbreaking work at a very high level at a time in his career when most people would be content to rest on their laurels.

Dr. Vinters began his presentation with an ironic twist on an old observation: Although he has been conducting basic science research at UCLA for the past 22 years, he does not consider himself a basic researcher. “I’ve always been a translational researcher,” he said.

“There are an estimated three and-a-half to four million people with Alzheimer’s and pre-Alzheimer’s disease in the United States. And 20 to 40 percent of the populace more than 80 years of age has Alzheimer’s disease. This is a major public health issue.”

In a wide-ranging discussion, Dr. Vinters described the history of dementia research beginning with immunohistochemical studies on the empirical use of antibodies in the treatment of Alzheimer’s disease during the 1970s. He then described the explosion of dementia investigations that occurred from the 1980s onward.

“In 1984, Drs. G.G. Glenner and C.W. Wong released a biochemical and biophysical research communications paper that was absolutely groundbreaking in scope. Had Dr. Glenner lived, he probably would have won the Nobel Prize,” Dr. Vinters speculated. “Ironically, he died of amyloidosis, a condition associated with Alzheimer’s.” Dr. Vinters stated that overwhelming hemorrhaging results from severe amyloid angiopathy and pointed out that the tau protein is often “the guilty party in neurofibrillary tangles.” Next, he mentioned that beta-amyloid precursor protein (BAPP) is also on the short list of contributory factors. He continued to lay the groundwork for an unexpected pun by pointing out that researchers are divided as to whether tau or BAPP plays the larger role in the development of Alzheimer’s.

At that point, the trap was set and Dr. Vinters casually displayed the next slide on the screen. The headline wryly hinted at a major theological division among Alzheimer’s researchers: “BAPP’tists vs. Tau’ists” it proclaimed, “in the formation of Alzheimer’s disease.”

Dr. Vinters next shared his thoughts on such divergent topics as the future of brain biopsy in Alzheimer’s research—“it will only be performed rarely and mostly in cases of young people who contract the disease and die from it”—and the role of molecular enzymatic abnormalities in smooth muscle cells. He also talked about UCLA’s role in providing optimized quality brain tissue samples for scientists at other facilities. Then he offered an observation about the limitations implicit in the design of Alzheimer’s studies from previous generations.

The problem with earlier studies involving rats and mice was that “they followed relatively simple memory tasks,” he noted. “But dementia is a very complex process that involves thousands of macrogenetic invaders attacking the brain. Recent studies tend to be more sophisticated and far-reaching in their approach.”

In his conclusion, Dr. Vinters referenced his long-standing friendship with Loma Linda University and expressed appreciation for the opportunities afforded him to take part in the education of our graduate students and work together to improve the lives of the millions of individuals with Alzheimer’s disease.

As the previous speakers had done, Dr. Vinters answered questions from the audience at the conclusion of his presentation.

When Dr. Vinters finished, Dr. Oberg briefly outlined the afternoon’s schedule and then dismissed participants for lunch.

The afternoon action shifted from the Slate conference room to the Jesse-Peterson conference room where participants examined this year’s crop of student research posters, and perused the booths of vendors supporting the symposium with an interesting array of products and services. Many participants took advantage of the opportunity to question students regarding the focus and findings of their research.

During the senior graduate student presentations at 5:00 p.m., Hansel Fletcher, PhD, professor of biochemistry and microbiology, presided over the short, 12-minute reports and brief question/answer period that followed.

First of the student presenters was Frankis Almaguel, a senior physiology PhD candidate working in the laboratory of Marino De Leon, PhD, director of the Center for Health Disparities and Molecular Medicine at the School of Medicine. Mr. Almaguel spoke on the topic of “Fatty Acid-Induced Lipotoxicity and Neuronal Cell Death.”

Mr. Almaguel was followed by Kurt Meyers, an MD/PhD microbiology candidate working with Lubo Zhang, PhD, professor of physiology and pharmacology in the Center for Perinatal Biology at the School of Medicine. Mr. Meyer’s presentation was titled “Fetal Cocaine Exposure and Cardiac Ischemia Preconditioning.”

The third student presenter was Sandy Tungteakkhun, a microbiology PhD candidate working in the lab of Penny Duerksen-Hughes, PhD, professor of biochemistry in the School of Medicine. Ms. Tungteakkhun’s report was titled “A Novel E6 Binding Domain Mediates the Interaction Between HPV16 E6 and FADD.”

The final student presentation came from Vladimir Vargas, a physiology PhD candidate working with Charles Ducsay, PhD, professor of physiology in the Center for Perinatal Biology at the School of Medicine. Mr. Vargas discussed his research into “Long Term Hypoxia Enhances ACTH-Induced Corticol Secretion in the Near Term Ovine Fetal Adrenal In Vitro.” 

At the conclusion of the student presentations, H. Roger Hadley, MD, dean of the School of Medicine, welcomed participants to the symposium.

In his remarks, Dr. Hadley noted that “the remarkable advances in patient care are only occurring because of diligent, thoughtful, and innovative work that the research scientists do every day. On the behalf of the clinicians, and especially on behalf of all the patients who have benefited dramatically from your scientific accomplishments, I would like to say a big ‘thank you!’”

At the student poster awards session, Dr. Oberg presented a special LLU hospitality gift to Dr. Vinters along with an honorarium of appreciation for his willingness to contribute to the intellectual life of the symposium as keynote speaker.

At that point, Dr. Oberg noted that the steering committee had awarded the six poster awards to the following student presenters: two third-place awards—one to Grant McAuley for “Brain Iron Quantification Using Magnetization Phase,” and the other to Teka-Ann Lawrence for “Regulation of Ceramide Levels in Apoptosis;” two second-place awards—one to Jason L. Herring for “GRX5 Regulates Osteoblast Cell Functions by Protecting Against Oxidative Stress,” and the other to Gabriel R. Linares for “Monitoring DNA Methylation Flux Using Stable Isotope Tracers and GC/MS;” and two first-place awards—one to Melanie Mediavilla-Varela for “Characterization of  the Caspase-Independent Cell Death Induced by Docetaxel in PCA Cells,” and the other to Claudius Mueller for “Identification of Candidate Biomarkers for Alzheimer’s Disease.”

The final event of the 2007 symposium was the closing remarks by Lawrence C. Sowers, PhD, associate dean for basic science faculty at the School of Medicine. Dr. Sowers awarded the Outstanding Oral Presentation Award to Sandy Tungteakkhun for her talk during the senior graduate student presentations. He then commended the high academic quality of both the research presented and the questions asked by participants.

After that, Dr. Sowers closed the meeting by thanking participants and organizers of the event for such an excellent symposium and invited them to stay for the reception, which began immediately.

At the end of the day, Wolff Kirsch was justifiably proud of “our” graduate students, as he called them. And while he was speaking specifically of Grant McAuley and Claudius Mueller, the neurosurgery students who took third and first place respectively in the poster competition, all student participants deserve commendation for the exceptional quality of their research projects and posters. Several guests commented on the high level of work represented at the student exhibit.

Dr. Oberg summarized his feeling that the symposium was everything it should have been. “From my perspective, I felt like it was successful and accomplished the goals and objectives we set,” he noted. “It gathered both clinical and research scientists together, acquainted our new students with colleagues and some of the research activities going on at the University, and provided a forum for a vendor show to introduce new technological discoveries that can enhance research productivity.”

By James Ponder

TODAY news for Thursday, October 29, 2007