stanford medicine




Alzheimer’s or not

One of the most distressing aspects of memory loss for older adults is how hard it is to determine the cause. The question looms: Is it Alzheimer’s? But now Stanford researchers have developed a blood test that is a step toward answering that question two to six years before the onset of the disease.

Richard Downs
Alzheimerís or not pic

The test identifies changes in a handful of proteins in blood plasma that cells use to convey messages to one another. The research team discovered a connection between shifts in the cells’ conversations and the changes in the brain accompanying Alzheimer’s. They found that 90 percent of the time the blood test could indicate who had been diagnosed with Alzheimer’s and could predict 91 percent of the time the onset of Alzheimer’s two to six years before symptoms appeared.

“Just as a psychiatrist can conclude a lot of things by listening to the words of a patient, so by ‘listening’ to different proteins we are measuring whether something is going wrong in the cells,” says Tony Wyss-Coray, PhD, associate professor of neurology and neurological sciences and senior author of the study, which appeared in the Oct. 14, 2007, advance online edition of Nature Medicine. “It’s not that the cells are using new words when something goes wrong. It’s just that some words are much stronger and some are much weaker; the chatter has a different tone.”

No test yet

Currently, the clinical diagnosis for Alzheimer’s is one of exclusion — by testing for other causes of memory loss and cognitive declines, such as stroke, tumors and alcoholism. If those conditions are eliminated, what remains is Alzheimer’s, which is the most common cause of dementia. Even the clinical diagnosis is imperfect, and the only definitive diagnosis is by brain autopsy after a person has died.

The blood-test concept began when Wyss-Coray and his collaborators measured levels of 120 different proteins used by cells to communicate to see if any of them could be indicators for Alzheimer’s. After developing an analysis procedure to recognize any patterns, the researchers discovered that as few as 18 proteins were sufficient to identify an Alzheimer’s-specific pattern.

Among blood samples from 92 individuals whose symptoms ranged from none to full dementia, the protein analysis matched the clinical diagnosis 90 percent of the time. The researchers then asked if they could predict the development of Alzheimer’s among 47 people with mild cognitive impairment who had been followed from two to six years. The test — done on blood samples taken several years earlier — flagged 91 percent of the patients who developed Alzheimer’s by the end of the follow-up time, as diagnosed by conventional methods.

Satoris Inc., a company that Wyss-Coray co-founded, plans to develop a commercial Alzheimer’s blood test, initially for use in research labs. — Mitzi Baker

This study was funded by the John Douglas French Alzheimer’s Foundation, the Alzheimer’s Association, the U.S. National Institute of Aging and Satoris Inc.

Arthur Kornberg dies

Arthur Kornberg, MD, winner of the 1959 Nobel Prize for his work elucidating how DNA is built, died Oct. 26, 2007, at Stanford Hospital of respiratory failure. He was 89.

Jamie Kripke
Arthur Kornberg pic

“Dr. Kornberg was one of the most distinguished and remarkable scientists in American medicine,” says Dean Philip Pizzo, MD. “His towering contributions have continued virtually up until the time of his death. Without doubt, his legacy will certainly live on for many, many generations to come.”

Kornberg, professor emeritus of biochemistry, shared the Nobel Prize in Physiology or Medicine with Severo Ochoa, MD, who was then at New York University. Kornberg was honored for the test-tube synthesis of DNA, the blueprint of heredity, and Ochoa for the synthesis of RNA, the genetic message derived from DNA.

“The style in which he did his science was inspirational,” says Paul Berg, PhD, professor emeritus of biochemistry and winner of the 1980 Nobel Prize in Chemistry for his work with recombinant DNA.

Kornberg and Ochoa turned to enzymes to solve basic biology problems. Along the way, they discovered new enzymes that create the building blocks of DNA and RNA, as well as the enzyme, which Kornberg named DNA polymerase, that assembles those blocks. These basic studies paved the road to the creation of recombinant DNA and genetic engineering, as well as providing the basis for many drugs currently used to treat cancer and viral infections.

Kornberg was born in Brooklyn on March 3, 1918. He earned his bachelor’s degree in chemistry and biology from the City College of New York in 1937, and his MD from the University of Rochester in 1941.

In 1959, he came to Stanford as chair of the new department of biochemistry, at a time of great change for the school as it was moving from San Francisco to the Palo Alto campus. “He helped bring some important people to Stanford and during that first period when he was chairman we came to be known as probably the premier department in the country,” says Berg.

In 1988, Kornberg moved to emeritus status at Stanford, but he continued to run a lab until his death.

Although DNA replication held Kornberg’s attention for years, in 1991 he returned to an early interest: poly P, a long chain of phosphates. This polymer is found in every bacterial, plant and animal cell. Kornberg was convinced the molecule held a key to understanding how cells function.

In addition to research and teaching, Kornberg wrote several books. His last, Germ Stories, arrived in bookstores in the month after his death. It is a book of playful poems inspired by tales about bacteria he told his children when they were young. Those children, three sons, inherited his love of science. Roger Kornberg, PhD, professor of structural biology at Stanford, was awarded the 2006 Nobel Prize in Chemistry for his research on the enzyme that converts DNA into RNA. Thomas Kornberg, PhD, pro-fessor of biochemistry and biophysics at UC-San Francisco, discovered DNA polymerase II and III. Kenneth Kornberg, an architect, specializes in laboratory design.

Kornberg is survived by his sons, their families and his wife, Carolyn Frey Dixon Kornberg, whom he married in 1998. — Mitzi Baker

Minimizing multiples

An in vitro fertilization technique that can avoid multiple births appears to be effective not only for young women but also for those over 35, according to re-searchers at the medical school.

Richard Downs
Minimizing multiples pic

More than half the women in a retrospective study became pregnant after under-going the procedure, called a single blastocyst transfer, which transferred just one embryo into the womb.

Nearly 60 percent of IVF procedures in the United States are for women older than 35, and the study’s senior author, Amin Milki, MD, believes the findings are good news for those women who wish to become pregnant with just one child.

“Although these results represent a selected group of patients, we believe that they should serve as encourage-ment to patients and providers who are considering single blastocyst transfer in the older IVF population,” Milki and his co-authors note in the study, which was published online in May 2007 by Fertility and Sterility.

During the transfer procedure, an embryo is bathed in a culture of nutrients for five days until it reaches a developmental landmark known as the blastocyst stage. At that point, doctors are able to determine which embryos are most likely to thrive long term; they then transfer the best-quality ones into a woman’s uterus.

The American Society for Reproductive Medicine currently recommends that doctors transfer two or more embryos into women older than 35 to maximize their chance of becoming pregnant. “Many patients would prefer not to have two babies at once,” says Milki, professor of obstetrics and gynecology and director of Stanford’s IVF program. “But because the success rate is higher when multiple embryos are transferred, women are willing to take the gamble.”

In recent years, many reproductive specialists have embraced single embryo transfer as a way to prevent multiple gestations. And data now exist showing the procedure’s effectiveness among women of younger reproductive age.

But scant data existed on single blastocyst transfer in women over 35, so Milki and his colleagues reviewed the outcomes of older patients who underwent the procedure at Stanford. Milki says the procedure had been offered to those women with good-quality embryos, and the patients who elected to have only one embryo transferred did so to avoid twin pregnancy.

After reviewing the data from 45 patients, Milki and his colleagues found that 62.2 percent conceived, and 51.1 percent had pregnancies that went beyond the first trimester. Milki calls this an “excellent pregnancy rate,” adding that the findings demonstrate a clear role for the procedure in older IVF patients.

Milki did caution that for women with lower-quality embryos, transferring two or three embryos might be the better way to pursue a pregnancy. — Michelle L. Brandt

Drug free

People with organ transplants, resigned to a lifetime of drugs to stop their bodies from rejecting the organ, might now have reason to hope for a respite, say medical center researchers. By analyzing blood samples, scientists have identified a pattern of gene activity shared by a small group of patients who beat the odds and remained healthy for years without medication.

Richard Downs
Drug free pic

The findings suggest that transplant recipients who exhibit this same gene expression pattern might be able to reduce or eliminate their dependence on immunosuppressive drugs. The study could also help physicians determine how best to induce acceptance, or tolerance, of donor organs in all transplant patients, regardless of their gene expression profiles.

“Most transplant patients who stop taking their medications will reject their organ, but now we have the chance of telling someone committed to a lifetime of drugs that it may be possible to minimize their exposure to the drugs,” says pediatric nephrologist Minnie Sarwal, MD, PhD, senior author of the research published Aug. 20, 2007, in the advance online edition of the Proceedings of the National Academy of Sciences.

Although the anti-rejection medications tamp down the immune system enough to permit lifesaving organ transplants, they also quash the body’s natural response to dangerous invaders, such as bacteria and viruses, and to rogue cancer cells. Transplant physicians prescribing immunosuppressants to their patients walk a fine line between avoiding organ rejection and increasing the risk of infection and cancer.

Pattern revealed

The researchers used gene chip technology to compare gene activity in blood samples from 16 healthy volunteers with those from three groups of adult kidney transplant recipients from the United States, Canada and France: 22 people on anti-rejection medications who had healthy donor kidneys, 36 people who were taking their medications but who were still rejecting their organs and 17 “tolerant” people who had successfully stopped taking their medi-cations without rejecting their donated kidneys.

Sarwal and her collaborators found they could accurately pick out more than 90 percent of the tolerant patients based on the activity levels of just 33 particular genes. What’s more, one out of 12 stable, fully medicated patients and five out of 10 patients on a modified, low-dose immunosuppressant regimen had patterns of gene activity that were very similar to those of the tolerant patients.

“For the first time, we now have evidence that will help us say to the five out of 10 patients without this expression pattern, ‘Please, please don’t think about changing your medications,’” says Sarwal, an associate professor of pediatrics. “At the same time, we may be able to say to a different patient, ‘We’d like to try to cut back your drugs.’” — Krista Conger

The study was funded by the National Institutes of Health, the Clinical Center for Immunological Studies at Stanford, the Lucile Packard Foundation, the Foundation Progreffe, the Establishment Francais des Greffes, the Roche Organ Transplantation Research Foundation and the Juvenile Diabetes Research Foundation.

Fairchild farewell

After more than 30 years of use, Fairchild Auditorium has been demolished to make way for the school’s new Learning and Knowledge Center.

Steve Gladfelter/Visual Art Services
Fairchild farewell pic
Fairchild Auditorium was dismantled to make way for a new school building, scheduled for completion in 2010. It had been in use since 1976.

Beginning in late October and continuing through December, the auditorium and its bridges to nearby buildings were dismantled.

The new LKC will include classrooms, simulation-based learning centers, a conference center, student facilities and the dean’s suite of offices. Officials expect completion by March 2010.

Fairchild Auditorium was completed in 1976 as part of the Sherman Fairchild Center, which includes the adjacent Fairchild Science Building. Approved by former dean Clayton Rich during a time of rapid expansion at the medical school, the center was designed by the firm Stone, Marraccini and Patterson and was funded by the Sherman Fairchild Foundation for about $10 million.

The Fairchild Science Building housed the new departments of neurobiology and structural biology when it opened in October 1976. The auditorium, a one-story building of about 10,600 square feet, seated almost 400 and opened in November 1976.

Since its inception, the auditorium was an integral part of campus and community life. It was the site not only for lectures, courses, conferences and symposia, but also for receptions, poster sessions, town hall meetings, fairs and graduations. Each spring, graduating medical students gathered in the auditorium’s lobby area for the annual Match Day ceremony.

Artwork from the auditorium will go to Lane Library and the LKC, says project manager Maggie Saunders. The abstract Carla Lavatelli sculpture that was in the auditorium lobby is now part of the Cantor Arts Center collection. — Madolyn Bowman Rogers






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