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EXTRA CREDIT
MEDICINE

Count Down
By Mubarak S. Dahir

THOUGH MOST PEOPLE WHO ARE HIV-POSITIVE WILL EVENTUALLY DEVELOP AIDS, THE EXACT REASONS AND TIMING HAVE REMAINED UNKNOWN. YET THE LATEST DISCOVERY BY RESEARCHERS AT PITT AND AT OTHER SITES ACROSS THE COUNTRY MAY ENABLE PHYSICIANS AND PATIENTS TO PREDICT THE ONSET OF FULL-BLOWN AIDS.
For the past 12 years, men have filed through Pitt clinics, offered blood samples, had cells counted, and answered the most personal questions about their health and sexual practices. Yet, unlike most research projects where participants volunteer in exchange for experimental treatments, these men have come back year after year as true altruists, with little in return for the data collected except the hope that someday the information may be used to fit together the mostly missing pieces of the AIDS puzzle. Thanks to more than 5,000 volunteers at four sites around the country-including those involved with the Pitt Men's Study, one of the oldest ongoing AIDS research projects- researchers believe they have found another small but significant fragment to the understanding of HIV infection and AIDS. "The critical loss of T cells appears to be an important marker in signaling the onset of AIDS," says Charles Rinaldo, pathology professor and head of the Pitt Men's Study.

In the body, there are several kinds of CD3 T cells, immune cells that act as the major line of defense against viral disease. Two of the most important of the CD3 T cells--and thus most studied and most counted--are CD4 T cells and CD8 T cells. If the immune system is thought of as an army that fights off disease, then CD4 cells are the generals and CD8 cells are the foot soldiers. When an infection occurs, CD4 cells respond by directing CD8 cells to the front lines. There, the armed CD8 cells attack and fight off the foreign invaders.

In a healthy person, the number of T cells in the body is held constant by an internal mechanism known as homeostatic control. In ways not yet understood, the body is able to measure the number of T cells present in the blood. When the quantity is low, the homeostatic control mechanism works much like a home thermostat, telling the body to churn out T cells. When enough have been produced, it signals the body to stop manufacturing them. The CD3 T cell count of a healthy person typically ranges from 1,200 to 2,000/ mm3.

When a person is infected with HIV, the body ceases to produce enough T cells and cannot fight off infections and disease. Researchers now believe it is the breakdown of homeostasis, called the inflection point, that causes a patient to move from being HIV- positive to developing full-blown AIDS when the CD4 T cell count often drops below 200/mm3. Furthermore, they believe they can predict when it will happen, and thus when a patient may expect the onset of AIDS.

"Our research strongly suggests that breakdown of homeostasis is mechanically linked to AIDS," says Albert Donnenberg, associate professor of hematology and one of the study's principal investigators. "It could be the event that causes the body to become vulnerable to infections that characterize AIDS."

The researchers found that a swift, profound fall in T cells often preceded the development of full-blown AIDS by one-and-a-half years. Before homeostasis broke down in men who were HIV-positive, they experienced a slight decrease in their T cells, losing about 0.5 percent every six months. But when homeostasis failed, T cells dropped at a rate of 11 percent every six months.

"It's very dramatic to see this drop," says Rinaldo. Until now, researchers have held that the immune system gradually failed until the onset of AIDS. However, according to this new finding, the immune system may undergo a major, abrupt decline much, much sooner.

Unfortunately, scientists still do not know what triggers homeostatic failure, though there are several theories. Some suspect that enough HIV in the blood may permanently disable CD4 and CD8 cells from reproducing. Pitt investigators suggest that homeostasis may fail when the number of mature CD4 cells falls so low that they are unable to "teach" new CD4 and CD8 cells to mature. Until the actual cause is pinned down, says Rinaldo, studying how the virus changes from before to after homeostatic failure will provide at least some clues to eventually stopping it.

While his study's finding offers little in terms of solutions, Rinaldo says it certainly should not be viewed as a gloom and doom discovery. Determining how HIV works is key to finding better ways to intervene in the virus' life cycle. For such a large and complex puzzle, the pieces that make up AIDS seem incomparably small. Yet each discovery brings researchers and patients one step closer to understanding--each in their own ways. Step by step. Piece by piece.



LITERATURE
Can You Say
Neighbor?

By Laura Shefler
MISTER ROGERS' NEIGHBORHOOD, A COLLECTION OF ESSAYS EDITED BY SIS PROFESSOR MARGARET MARY KIMMEL AND PITT MAGAZINE'S OWN MARK COLLINS, OFFERS NEW PERSPECTIVES ON AMERICA'S MOST FAMOUS NEIGHBOR.


Most people learn cynicism in the first grade. That's when the easy-going years of preschool and kindergarten end, and suddenly you're in "real" school. You start taking tests and bringing home report cards. As you discover how much the world expects of you, you develop a first-grade version of machismo. You figure out how to tie your shoes because kids who can't tie their shoes are babies. And you stop watching Mister Rogers (or at least stop admitting that you watch it) because everybody knows that Mister Rogers is a baby show.

Adults, too, may harbor a certain cynicism toward Mister Rogers, an impatience with the gentle way he talks. For grown-ups who do complicated things like analyze the stock market, recombine DNA, or compete for parking, there is something unsettling about a grown man who can sit at a table and earnestly demonstrate how to slip a triangle-shaped block into a triangle-shaped hole.

Still, the qualities that may unnerve us about this television legend --his soft-spokenness, his unhip cardigan, his insistence on warm-and-fuzzy messages like "You are special"--have also made him a remarkable figure, a powerful force for good. Rogers has courageously dared to be uncool. He has addressed childhood anxieties that some adults would laugh away. (Take, for instance, his bathtub song, "You'll Never Go Down the Drain.") He has dared to be gentle and open-hearted in a society that encourages slickness and toughness, and he has stood up for such unglamorous values as honesty, decency, and civility.

Now, a new collection of essays, Mister Rogers' Neighborhood: Children, Television, and Fred Rogers, published by the University of Pittsburgh Press, explores the impact and meaning of Rogers' work. In the essay "With an Open Hand," for instance, psychologist and puppeteer Susan Linn probes the personalities of King Friday, X the Owl, Lady Elaine, and Daniel Striped Tiger, four puppets who inhabit Rogers' Neighborhood of Make-Believe. These puppets lead emotionally rich and complex lives. Daniel Striped Tiger, for instance, frets about Santa Claus: "He sees you when you're sleeping, he knows when you've been bad or good. Oh dear." Lady Elaine, nettled by curiosity, demands to see what's in a package delivered to her neighbor Cornflake S. Pecially. She exits in a huff when Corny insists on his privacy. These characters, writes Linn, "tap into the vein of fear, anger, awkwardness, and unadulterated self-centeredness that lies beneath the sunny surface of childhood." Linn suggests that viewing the expressive outbursts of these puppets may help kids better understand and cope with their own feelings.

In "The Reality of Make-Believe," Nancy Curry, Pitt professor emerita of child development and child care, argues that Rogers' television blend of reality and fantasy grows out of a thorough understanding of the needs of small children. Curry notes, "His final song is always the same, with the reassurance that he'll be back next time." She explains its importance: "Young children like and need ritual, to know what to expect, and in a sense to be 'in the know.'"

The book pulls together an impressively broad variety of perspectives. Cellist Yo-Yo Ma marvels at the program's innovative use of music. Mary Rawson, a writer-producer for WQED Pittsburgh, discusses Rogers' popularity among adults over 60. Paula Lawrence Wehmiller, a teacher and civil rights activist, lauds his contributions to the fight against racism.

On a more personal note, writer Jeanne Marie Laskas (Arts and Sciences '85) takes us on a visit to Fred and Joanne Rogers' Cape Cod summer home, cluttered with thrift-store furniture. In conversations with Laskas, Rogers shares stories about the loneliness of his childhood, which was brightened in part by the care of a nurturing grandfather.

Finally, in an impassioned afterword, Marian Wright Edelman, president of the Children's Defense Fund, emphasizes the national importance of Fred Rogers' efforts to support children's social and emotional growth. Such efforts, she writes, are indispensable at a time when one-fifth of American children live in poverty, when the threat of violence overshadows many young lives, when economic pressure makes it hard for many parents to give their children the time and attention they need. Ultimately, Mister Rogers' Neighborhood is a book that encourages us to put aside our cynicism, to take emotional concerns seriously, to open our hearts not just to our television neighbor, Mister Rogers, but also to the neighbors that we find all around us.


SOCIOLOGY
Hidden
Treasure

By Alan Friedman
AS HAITI MAKES ITS HALTING WAY BACK TO DEMOCRACY, A PREMIER ARCHIVAL COLLECTION ON HAITI AND SLAVERY, SCATTERED AND CONCEALED FOR 30 YEARS IN BASEMENTS OF BUILDINGS THROUGHOUT PORT-AU-PRINCE, COMES OUT OF HIDING.

BEFORE TAKING REFUGE himself 26 years ago when he fled the Duvalier regime in Haiti, Father Antoine Adrien delayed his departure to tend to the politically endangered of another nature. At a time when so many cultural institutions and historical records were being destroyed, Adrien vowed to save the Spiritan seminary library. As if he were sending Moses down the Nile, he bundled the seminary's collection--10,000 books and 70 boxes of archives--and stashed it in sympathetic homes throughout Port-au-Prince.

Now, with democracy being restored, Adrien returned to recover his precious boxes, brushing off almost three decades of dust from one of the western hemisphere's most extensive collections on the histories of Haiti, the Caribbean, and slavery. The library offers an amazing range of archival documents: records of a 1791 slave revolt, slave ship journals, transcripts from debates over the wording of the Haitian constitution, and French-, Spanish-, and Creole-language newspapers. A sepia-toned photograph of a slave breaking her back in the fields, another of the liberator Toussaint L'Ouverture have been returned to their hooks. From a painting, the Virgin Mary once again watches over this assembly of nearly lost souls.

Unfortunately much of the material hasn't aged gracefully. Though faring better than the Haitian people--the bloodiest years in Haiti's history left thousands dead and hundreds of thousands exiled--the library's singular collection has fallen victim to mold and water marks. Books and journals printed on highly acidic nineteenth-century paper have embrittled to the point of disintegration. Insects have nested in newspapers dating from 1800.

As experts in preservation and rare books, respectively, School of Information Sciences profs Sally Buchanan and Father Stephen Almagno traveled to Haiti expecting to prescribe a plan for preserving and cataloguing only a modest collection. Instead, they found themselves in awe of the depth and rarity of the materials. To Buchanan, that the collection survived the Duvalier and subsequent military regimes seems nothing short of miraculous. "Books represent, if not the truth," she reflects, "at least another version of the truth. It's what they represent that makes it necessary for them to be destroyed. Information provides people with the tools they need to decide right from wrong, which is a great threat to authoritarians. Libraries help to maintain our democratic state. Duvalier couldn't allow information to be made available to the poor, the repressed."

"Duvalier was concerned about archives, records," Almagno adds. "If we destroy you and destroy your family, then it's very important that we also destroy the records about you. If I'm expropriating your property, it's important to say that that property never existed." Of course, the library's manuscripts of twentieth-century Haitian writers and rare sixteenth-century maps of Port-au-Prince possess great intrinsic value. But for this country's impoverished majority, whose political voice has yet to be heard, what means the most are things like the nineteenth-century guide to Port-au-Prince, which names every family, street by street; the room full of newspapers chronicling the day-to-day affairs of the people. For those from whom so much has been taken, these records of more peaceful, if not more prosperous, days offer a source of pride in their state and a more hopeful vision for their future.

Buchanan and Almagno faced a formidable challenge in trying to save the library. They prescribed ways to safely clean and repair the paper and bindings, underscored the value of publicizing the material on an international bibliographic network, and recommended microfilming to ensure survival. Almagno points out that the loss of the library would be tragic. "It preserves all Haitian culture," he says. "This is really the cultural patrimony of the nation."

"To move on," former Haitian president Aristide has said, "you have to be willing to tolerate certain aspects of the past." As a window into Haiti's history, the library may provide some guidance to help heal the nation. In fact, with the addition of new books, the library is setting an example of recovery and growth. Although a new section focuses on the plight of Haitian refugees, every page that spent years in hiding is a study in exiles finding their way home.


HEALTH
To E
or Not to E

By Christine McCammon
VITAMIN K IS ESSENTIAL FOR BLOOD TO CLOT. VITAMIN E, ON THE OTHER HAND, CAN SLOW THE PROCESS DOWN. BUT EXACTLY HOW MUCH OF EACH VITAMIN IS ENOUGH TO KEEP BLOOD CLOTTING IN BALANCE--AND PREVENT BOTH STROKE AND HEMORRHAGE? CHEMISTRY PROFESSOR PAUL DOWD IS IN HOT PURSUIT.

IT'S A DELICATE BALANCING act, keeping the blood that courses through our veins "thin" enough so as not to choke our arteries with heart- and brain-damaging clots, but not so diluted that the slip of a knife or nail could turn an otherwise minor cut into an uncontrollable and life-threatening hemorrhage.

Cheap and plentiful vitamin E, which already enjoys headlines and celebrity associated with its ability to search out and destroy the body's highly reactive and damaging free radicals, may be of aid in maintaining this delicate blood-balancing act, says chemistry professor Paul Dowd.

Dowd and graduate student Barbara Zheng have discovered that as the body metabolizes vitamin E, it produces a substance called vitamin E quinone. Vitamin E quinone appears to function as a mild anticoagulant, inhibiting the function of carboxylase, an enzyme made by the body that causes blood to clot.

The action of carboxylase requires vitamin K. The generosity with which nature supplies vitamin K is a blessing. "Without it, one would simply hemorrhage," Dowd says.

Too much vitamin K, however, could present a problem for someone who has had a heart attack or stroke. Enter Coumadin, the drug most frequently prescribed for these patients. In a healthy person, blood will clot in approximately 12 seconds. Coumadin interrupts the body's metabolic cycling of vitamin K and thus "thins" the blood. (Doctors aim at an 18-second clotting rate for heart and stroke patients.)

But a diet rich in vitamin K can offset the Coumadin, possibly increasing the risk of another heart attack or stroke. Dowd recounts the story of one patient for whom doctors had an especially difficult time getting the Coumadin to function effectively until they realized that the patient had a voracious appetite for broccoli--a vegetable loaded with vitamin K.

This is where Dowd hypothesizes that vitamin E quinone might offer a more effective therapy. While Coumadin blocks one of the later steps in the cycle, effectively reducing the amount of vitamin K in the bloodstream, vitamin E quinone seems to block the key initial step that activates the proteins for clotting. (Vitamin E supplements sold over the counter are called alpha-tocopherol. Pure vitamin E itself has little or no anti-clotting properties until it is transformed in the body into vitamin E quinone.)

The level of vitamin E quinone that is manufactured by an individual is dependent on the amount of vitamin taken and on his or her unique metabolism. Dowd suspects that vitamin E quinone taken at a proper--and probably physician-prescribed--dosage will be able to "thin" the blood to a level that is therapeutic, but not to the point that it could endanger a patient in the event of a skin injury. "Which form of vitamin E is the anti-clotting form, and how does the anti-clotting form work chemically and biochemically?" asks Dowd. "We're trying to understand it better."


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