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A Door Opens in the World of Kidney Transplants
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| The transplant surgeon: Robert Montgomery; the patient: Alan Goody. |
Alan Goody had all but given up. For seven years he'd hoped for a kidney
transplant, his name on three separate lists. And yet, because he himself
is a nephrologist, he understood all too well why his chances of receiving
a new kidney were next to nil. Two transplants he'd undergone years before
almost certainly would make his body reject another organ the minute it
was implanted.
Goody's first donated kidney served him for 13 years. But when it failed
in 1995, his second organ, which came from his mother, lasted less than
a week. During the transplant, his immune system became highly sensitized
to proteins on his mother's kidney, and his antibodies immediately set
out to destroy the donated organ. Within a week, the kidney had to be
removed. Now, at age 30, with no working kidney, he was looking at a lifetime
on dialysis.
But Goody was lucky. A protocol developed at Hopkins under the leadership
of transplant surgeon Robert A. Montgomery has just made it possible for
patients who are highly sensitized to donor tissue to have a kidney transplant.
The technique, in fact, works so well it even allows patients to receive
an organ from a donor whose blood type is incompatible with their own.
The key is to cleanse the recipient's blood of all the antibodies (blood
proteins) that cause rejection.
Plasmapheresis is what does the job. The procedure relies on a spinning
device, known as a cell separator, to remove the antibody-containing plasma
from the blood cells of the person to receive the kidney. The blood cells
then are returned to the patient, while the plasma is replaced with other
fluids.
Patients typically go through three or four plasmapheresis treatments
starting about 10 days before the transplant and three more after the
surgery. An intravenous drip of medication prevents them from developing
new antibodies.
Because Goody's antibody levels were so high, he required no fewer than
13 plasmapheresis treatments before surgery. But they did the job. On
July 27, he received a new kidney from his father. Today, the organ is
working away in his body.
"This new technique opened a lot of doors for me," Goody says.
— Gary Logan
The Yeast-infection Detectives
Has anyone not seen those TV pharmaceutical commercials with attractive
30-something women discussing their yeast infections? The culprits of
these hushed conversations-and of 10 percent of hospital infections-are
Candida yeasts.
Molecular biologist Brendan Cormack is trying to unravel the mechanisms
through which Candida yeast causes infections. To be precise, he's
trying to pinpoint the few genes that allow Candida to trigger
disease, while all over the world people happily ingest one of Candida's
close cousins, baker's yeast (Saccharomyces cerevisae),
in their staffs of life, bread and wine.
To gather their information, the Cormack group is studying one specific
species of Candida, called Candida glabrata. In fact, they've
created 20,000 different versions of Candida glabrata. Their plan
is to identify the few mutants among these that are not infectious and
thereby gain insight into how the infection process works.
The lab group already has identified one gene, the EPA1 gene (for epithelial
adhesion 1), as an important player. The protein produced by the EPA1
gene, it seems, helps the yeast bind to human cells, a step crucial for
infection. By searching through all the genes in Candida glabrata,
the Cormack group has discovered that the EPA1 gene is surrounded by other
genes closely related to it that also may be involved in the critical
binding step of infection.
What's more, Cormack has found that EPA1 and its neighbors are physically
located in a region generally reserved for those genes that allow the
cell to survive in different environments (like the human host). Eventually,
what the group has learned about adherence could prove critical in designing
drugs that target the proteins involved in this early step in the infection
process. One thing seems certain: if the lab succeeds in exposing the
workings of Candida glabrata, pharmaceutical companies will
be beating a path to their door.
— Raj Mukhopadhyay
