Sickle Cell Disease


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The flu vaccine works, in part, by creating memory T cells that have experienced the flu's antigen. When these memory T cells encounter the same antigen from an actual flu virus, they react much more quickly, having been "primed" by the vaccine. Within hours, the T cells ramp up the production of cytokines, which increase the immune response to prevent infection.

How are memory T cells able to respond so quickly? Part of the reason appears to be that the cells are already prepared for increasing cytokine production before they ever encounter an antigen, according to a new report by Dr. Jeremy Luban, associate professor of microbiology and the Richard J Stock Associate Professor of Medicine; Dr. John Colgan, associate research scientist in microbiology; and Dr. Mohammed Asmal, a graduate of the M.D./Ph.D. program. The research was published in the October issue of Immunity.

To find out what makes the memory T cells react so quickly, the researchers used Affymetrix chips to compare gene expression in memory T cells before and after encountering antigen.

The biggest difference between the two states, not surprisingly, is an increase in the expression of cytokine genes. To produce those cytokines quickly, the cells turn on a set of genes involved in the creation of ribosomes, the molecular machines that build the cytokines. The genes process the RNA destined for the ribosomes, which are part RNA and part protein.

But the researchers didn't see any change in the expression of genes (or more precisely, the genes' messenger RNA, or mRNA, levels) that produce the protein part of the ribosomes. Since T cells can't produce cytokines with only half a ribosome, Drs. Luban, Colgan, and Asmal looked into the cells for more details. They found that the T cells seemed to have made the protein's mRNAs earlier, in preparation for cytokine production. After the cells encounter antigen, the cells start translating the mRNAs into protein.

Together, both processes rapidly accelerate ribosome production to turn the memory T cells into cytokine factories.

The research was supported by the NIH and the Sandler Program for Asthma Research.

—Susan Conova

In recent years, living donor liver transplantation (LDLT) – in which a part of a liver is removed from a healthy person and transplanted into someone with end-stage liver disease – has gained wider acceptance. But as questions about the feasibility of this procedure were answered, new ones about the cost and cost-effectiveness of LDLT have sprung up.

Now, a team of researchers from P&S and the University of North Carolina has published a study comparing the costs and benefits of LDLT vs. deceased donor transplantation.

The researchers, including Dr. Robert S. Brown, associate professor of medicine and pediatrics at P&S, identified substantial cost benefits associated with LDLT, such as shorter waiting times, reduced hospitalizations for the recipient because of pre-transplant complications (such as those related to hepatitis C and cirrhosis of the liver), and less severe recipient illness at the time of transplantation. However, the researchers caution these benefits are frequently offset by the expense of evaluating donors and providing donor postoperative care, as well as costs related to higher complication rates after surgery in LDLT.

The few other cost studies of liver transplantation do not point to a substantial cost difference between the two types of procedures. Dr. Brown says, though, that most of these other studies were flawed because they did not include the cost of the long periods of time a patient usually has to wait to receive a liver from a deceased donor – time that often requires costly pre-transplant care.

"We maintain that with improved LDLT outcomes and refinements in the procedure, LDLT will be a more cost-effective approach than deceased donor liver transplantation in the management of end-stage liver disease," Dr. Brown says. The study was published in the October issue of Liver Transplantation.

Factors Affecting Cost of Liver Transplants

  • Severity of patient illness
  • Intensive care unit stay
  • Presence of renal failure
  • Presence of cytomegalovirus infection
  • Presence of bacterial or fungal infection
  • Length of total hospital stay

The research was funded in part by the NIH.

—Leslie Boen

Why is it so difficult to keep weight off? In a recent study, P&S researchers showed that after losing weight people burn about 300 to 400 fewer calories per day than expected and that this decline in daily energy expenditure seems to be largely due to an increase in efficiency of skeletal muscle. Initial findings from this study, which is ongoing, were published in the July issue of the American Journal of Physiology.

"You might predict that someone who has lost 10 percent of his or her weight would burn about 10 percent fewer calories walking a mile," says Dr. Michael Rosenbaum, associate professor of clinical medicine and pediatrics and the study's lead author. "In actuality, they will burn about 20 percent fewer calories walking that mile. This points out the long-term commitment necessary to keep weight off. If you want to maintain weight loss you will need to exercise that much more – or eat that much less per day – than someone whose usual weight is exactly the same as yours. You also will probably need to maintain this lifestyle change for the rest of your life."

Dr. Rosenbaum adds that this type of study demonstrates that, in most cases, the origins of obesity are primarily biological rather than psychological.

—Leslie Boen