Research Roundup

$302,000 Award for Sumerian Dictionary Project

The University of Pennsylvania Museum’s Pennsylvania Sumerian Dictionary Project was awarded a two-year, $302,000 grant from the NEH.

"We are extremely grateful for the support that this grant provides," noted Dr. Jeremy A. Sabloff, the Williams Director of the Museum. "The Museum is committed to this unique and important project, a natural outcropping of more than one hundred years of UPM research and exploration."

Founded in 1976, the Pennsylvania Sumerian Dictionary Project set out on a mammoth mission: to produce the first comprehensive dictionary of the world’s oldest written language. The original goal, in an age before the internet and personal computers, was to produce an 18-volume work, a hard-back opus to incorporate all data then known, published and unpublished, from every possible source.

Now, according to Dr. Stephen Tinney, associate curator in the Museum’s Babylonian section and the Dictionary Project’s current director, the project will be implemented as a web-based work, also published on CD-ROM. The dictionary will be updated and augmented as new Sumerian writings are deciphered and scholarship at the Museum and around the world progresses.

"New technology, and new ways of communicating with our fellow scholars around the world, have given us an opportunity to re-conceive of the dictionary project, not as a static, finished end-product but as an evolving work-in-progress, " Dr. Tinney noted. "Unlike the Sumerian state, we don’t have a vast labor-pool which we can press into service for us. Instead, we have to work smarter, leave the heavy lifting to the computer, and exploit the power of the net."

The Museum has a long history of research and excavation work at ancient Mesopotamian sites. UPM sent the first U.S. expedition to the Near East-to Nippur, in Iraq-in 1887, and continues work in the region today. The Museum houses more than 30,000 cuneiform tablets, including the largest collection of Sumerian literary tablets in the world.

Studying Smallpox Without Smallpox

In this era of bioterrorism, researchers at Penn’s School of Medicine have discovered a way to study how smallpox overcomes the human immune system. Due to the nature of variola, the virus that causes smallpox, researchers cannot access the virus conventionally. Therefore, using previously published data on the DNA of smallpox, Penn researchers reverse-engineered a variola protein from vaccinia, a related virus used to vaccinate against smallpox. Their findings are presented in the May 28th edition of the Proceedings of the National Academy of Sciences and suggest new means to develop safer vaccines and potential therapies for smallpox.

The protein is called the smallpox inhibitor of complement enzymes, or SPICE for short. SPICE helps smallpox to elude complement, the collective name for a number of proteins that serve as the immune system’s first line of defense. SPICE does not cause smallpox itself and cannot spread the disease. SPICE is only one of several hundred proteins that contribute to the virus’ pathogenesis and host preference. To understand SPICE’s role, the researchers compared the activity of this protein to that of human complement regulatory proteins and the vaccinia virus complement control protein (VCP).

"We have devised a way to study variola without the risks associated with using the entire virus," said Dr. Ariella M. Rosengard, an immunobiology researcher in Penn’s department of pathology and laboratory medicine. "We need to study variola proteins if we are to make smallpox less virulent and make the smallpox vaccine safer. Achieving these goals would be the most effective way to disarm bioterrorists." Variola attacks only humans, and is fatal in 30 to 40 percent of cases. The only current defense against smallpox is containment, supportive measures, and vaccination.

Dr. Rosengard’s group molecularly engineered SPICE by an indirect method, which did not require the virus. The complement system defends against infectious microorganisms. It consists of bloodstream-based enzymes that, when activated, disable invading microorganisms directly or serve as beacons for other parts of the immune system, such as white blood cells. Viruses have evolved complement regulatory proteins such as SPICE and VCP to distract human complement in order to allow the virus to slip past. Humans also have complement regulatory molecules for a similar reason: to keep complement from attacking other human tissues. "Without our own complement regulators, we’d likely destroy our own cells," said Dr. Rosengard.

Other Penn researchers involved in this research include Yu Liu, Zhiping Nie, and Robert Jimenez. Funding for this research was supported in part by a grant from the NIH.

Urine Test Predicts Alzheimer’s Disease

A urine sample taken at the doctor’s office can be the step in determining your chances of developing Alzheimer’s disease (AD), according to researchers at Penn’s School of Medicine. They have determined that a urine test can reliably detect free radical damage associated with people with Mild Cognitive Impairment (MCI)–a recognized precursor to AD. The test detects isoprostanes, fatty acids that are formed as the result of free radical damage in the brain–damage that correlates with clinical diagnosis of AD.

"This is the first noninvasive test that can predict a clinical diagnosis of Alzheimer’s disease," said Dr. Domenico Praticò, assistant professor in the department of pharmacology. "Since there is no cure for Alzheimer’s disease, physicians could slow the course of the disease if it is caught early enough."

Within four years of initial diagnosis, up to 50% of people with MCI develop Alzheimer’s disease. As AD progresses, it attacks the brain and causes severe damage in the areas important for memory, judgement, and language. This destruction leads to other clinical complications and, eventually, death.

In the study, published in the June edition of Archives of Neurology, Dr. Praticò and his colleagues measured isoprostane in blood and urine samples obtained from 50 patients with a clinical diagnosis of AD, 33 patients with MCI, and 40 healthy volunteers The researchers found significantly higher levels of isoprostane in CSF, blood, and urine of MCI and AD subjects than in the volunteers. Remarkably, the samples taken from the MCI subjects and the volunteers differed only in respect to their isoprostane levels.

A urine sample taken in the doctor’s office may be a first point of decision in gauging the risk of developing AD. Further tests could then determine the severity of a patient’s condition and course of treatment.

While at the moment this test is not yet clinically available, the team is working on the development of a version of it that could be broadly and easily performed.

This research was supported by grants from the National Institutes of Health and the American Heart Association.

Implant May Stabilize Schizophrenia Patients’ Treatment for a Full Year

One of the greatest difficulties in treating schizophrenia has always been helping patients to stay on their medication. Now, that problem is closer to being solved.

Scientists at Penn’s School of Medicine have designed an implantable device capable of delivering anti-psychotic medication for a period of five months, and continuing work at Penn indicates that such devices may work for up to a full year. The device has been proven effective in initial laboratory studies, and more research is underway (in collaboration with the University of Pittsburgh School of Medicine) to lead to potential clinical trials.

Findings from the small-mammal study appear in the current issue of the scientific journal Neuropsychopharmacology. If the device can be demonstrated to work effectively in human subjects in future trials, it will offer a medical alternative that may relieve many patients of the threat of psychosis and chronic social instability.

"Patients who need anti-psychotic drugs often fail to comprehend the profound severity of their illness, and may stop taking their medication during temporary periods of impaired judgement. But when the majority of patients with psychiatric disorders take appropriate medicine, they do achieve periods of remission from psychotic symptoms," said Dr. Steven Siegel, division of neuropsychiatry in the deprtment of psychiatry. "The advantage of relying on an implantable anti-psychotic medicine is that patients are able to make decisions about the future course of their treatment during periods of relative health, but if a medical reason arises that necessitates curtailing treatment, the implant can be easily removed."

The delivery device consists of a surgically-implantable disc made of biodegradable polymers (a series of linked molecules) combined with medication. In the trials, a traditional anti-psychotic medicine, Haloperidol, was used. The discs have been modeled in a fashion that allows each type of polymer to disintegrate at a specific rate, so that exactly the prescribed volume of medication is released into the bloodstream each day for up to a year. About the size of a quarter, the device is held in place under the skin with a single surgical stitch. According to Dr. Siegel, the implantation procedure (and removal procedure) can be performed in about 15 minutes under local anesthetic.

Other Penn researchers who collaborated in the study are:  Dr. Karen I. Winey, department of materials science and engineering; Dr. Raquel Gur, and Dr. Robert H. Lenox, department of psychiatry; Dr. Warren B. Bilker,department of biostatistics and epidemiology, and Debbie Ikeda, Neel Gandhi, and Wen-Xiao Zhang, MS, also of psychiatry.