Technological leaps make multiple, kidney-swapping surgeries more common

Chronic kidney disease affects 26 million American adults, with millions of those affected unaware because there are no symptoms until the disease is severe. When a person’s kidneys fail, they can go on dialysis or try to get a kidney transplant, which provides a better quality of life. The latter options requires that a friend or family member be willing to donate one. Otherwise, they face many years on a waiting list. 

But what if you have a donor who is not a match, which means the donated organ will be rejected by your immune system?  

The answer in Birmingham is UAB’s paired exchange and incompatible transplant programs. Ann Marie Reynolds, Gwendolyn Goldsmith and Frank Peters each needed a kidney and had a donor lined up that turned out to be incompatible. The swapping enabling them to be entered into a database that made all participants more likely to get a kidney, and this powerful story by UAB’s Tyler Greer describes their recent three-way transplant surgery.   

Their multiple, living-donor transplant has made it possible for each patient to live free of the constraints of dialysis for what doctors hope will be at least a decade and maybe two. Each of those who donated the kidney did so even though they knew their organ would be going to someone other than their family member or loved one. By the end of 2013, UAB is expected to complete perhaps 30 kidney swap transplants as part of the program.

A team of UAB surgeons, physicians and researchers in UAB’s Kidney/Pancreas Transplant Center has assembled and developed the technologies needed to make the multiple surgeries successful. We thought to talk to one of the UAB surgeons who oversaw the three-way transplant that day, Dr. Jayme Locke, and to ask her about this emerging field and what it means for patients. 

Show notes for the podcast:

1:52  The kidneys filter the blood, divert waste into urine and return useful proteins to the bloodstream. but can be damaged by diabetes, high blood pressure and cancer. 

3:00 As diseases progress, the kidneys become less and less able to function until they fail, at which points patients either go on dialysis, a mechanical system that filters the blood, get a kidney transplant or die. 

3:51 The field has shifted over the years from implanting kidneys from a stranger who recently died to organs donated by living people known to the recipient. In the United States there are about 100,000 people waiting for a kidney, but only 10,000 and 15,000 transplants done a year. The need far outweighs the supply, and those who have a family member willing to donate a kidney instead of going on a waiting list (ten-year wait in Alabama for some) has a tremendous advantage.  

5:12 It is important to note that about 35 percent of people who come forward and volunteer to donate a kidney to loved one are found to be incompatible with their would-be recipient. They have a blood type that means the recipient's immune system will immediately attack the donated organ and prevent it from functioning. Another 11 percent of willing donors will be found to be tissue incompatible. So almost half of would be donors cannot donate to their intended recipient. 

6:10  Paired exchange and incompatible transplant programs were born to address this problem, and to make it possible for many to get kidneys that would not otherwise happen.

6:37:  Paired exchange programs started in single hospitals, and now national databases have begun.  At UAB, the list of would be donors and patients is so large that the database locally is effective at making swaps possible in Alabama.

7:37: Ann Marie Reynolds, one of three patients in the transplant swap described above, has had three kidney transplants over the last 25 years. Some patients need more than one transplant because of rejection (sometimes years later) or because a systemic disease comes back in the new organ. Getting a second transplant is more difficult than the first because patients become sensitized. 

8:44 We all have labels on our cells that say self (made of a protein called human leukocyte antigen or HLA). Our immune system looks for this tag and spares self-labelled cells from immune attack, whereas those with other tags like bacteria are targeted. Thus, the goal is to find a transplanted organ made up of cells with an HLA that matches pretty closely with the patient's own tags. In the last ten years, researchers have developed the technology that enables patients to overcome some degree of mismatch if their blood and tissue types are close enough.  

10:30 Dr. Locke discussed the work of UAB's Dr. Roz Mannon, whose specialty is keeping the immune system from attacking a transplanted organ over the long term. While the field has gotten very good at preventing transplant rejection in the first year, gradual damage can cause the organ to fail five years later.

11:10 One approach to preventing long-term rejection, says Dr. Locke, is to find people better blood and tissue matches in donated organs in the first place. By carefully testing the expanded pool of potential donors and recipients in a swapping system, the chances increase that each patient will not only get a kidney, but a better matched kidney.  

11:45 The transplant researcher community also continues to work urgently to improve immunosuppressive medications such that they stop immune attack on a transplanted organ without making patients overly vulnerable to infections. UAB is a national leader in this regard, participating in several, ongoing clinical trials. 

12:57 A unique team at UAB makes multiple swap transplant operations possible. In some cases, six operations are underway at the same time, which requires skilled support by teams of nurses, anesthesiologists, pharmacists, etc., both in preparation and follow up to surgery. This tremendous and coordinated effort by UAB Nursing is led by people like Katie Stegner who runs the operating rooms and Debbie Sparks, the nurse manager on the kidney floor. 

15:35 The living donors that make the swapping system possible are willing to sacrifice part of themselves for their loved ones, a choice that has Dr. Locke's respect. Beyond that are those that chose to donate an organ into the system in honor of a family member or friend, hoping the swap system can give an organ back to that loved one. 

17:28  Dr. Locke would like to see a truly national swapping system develop, one that was not for profit. The huge size of such a database would make a great difference for many more patients in need of transplant. 

 

Image post 10: stunning vertebra makes contest list

This image shows a lumbar vertebra from a mouse with its back to the upper-left and its belly to the lower-right. There are muscle fibers in the upper-left corner, cartilage in blue merging into bone in green at the ends of the vertebra, red blood cells in the middle and intestinal contents in orange in the bottom-right corner. The image, which won 13th place in the Nikon Small World Contest, was captured by Dr. Michael Paul Nelson in the Division of Neuropathology, part of the Department of Pathology within the UAB School of Medicine. Dr. Nelson says he created this image, not for a specific research goal, but instead to help him understand aspects of mammalian anatomy. The tissue sample in the image was prepared with a series of dyes and was revealed when Dr. Nelson switched his microscope to fluorescent mode.

When he took the image, Dr. Nelson was attending the Immunohistochemistry and Microscopy Short Course offered by the Histochemical Society at the Marine Biological Laboratory at Woods Hole, MA. Also credited for the Nikon content entry was Samantha Smith, the representative from Carl Zeiss Microscopy who helped Dr. Nelson with technical aspects of using a Zeiss microscope.

Damaged hearts may be healed by their own stem cells

Thanks to stem cells, each of us develops from a single-celled embryo into a fetus with hundreds of different cell types. Stem cells multiply and specialize until they become heart muscle, bone, nerves, etc. Tissues like skin keep pools of stem cells on hand into adulthood, activating them as needed to replace worn out cells in a constant turnover.

But not the heart. Cardiologists believed for a long time that you get one set of heart cells for life. If you lost a bunch in the wake of heart attack, you had to live with whatever was left. In recent years, however, researches have revised that view. There is cell turnover in the heart, albeit as a much slower pace than that seen in other tissues.

The existence of such replenishing mechanisms suggested that it may be possible to coax them into action to regenerate heart muscle damaged by disease. Results of early human trials have been positive, although there is still work to do before such treatments become part of clinical practice.

It may be no surprise then stem cell-based therapies were a focus of the recently held UAB Comprehensive Cardiovascular Center’s Annual Symposium. We sat down with Sumant Prabhu, M.D., director of the center and symposium organizer to talk about the promise of regenerative medicine.



1:32 Dr. Prabhu said he organized the symposium with this theme at this time because his team wanted to focus on the next wave of science and therapeutics in cardiology. He believes that stem cell-based, genetic and tissue regeneration therapies will dominate the field in the coming years, just as drugs and devices did in during eras past. The symposium was designed to foster new collaborations in these areas among leading researchers.

3:19 Several symposium presentations were dedicated to stem cells that are present in the heart, and on attempts to manipulate them such that the become needed replacement cells in damaged hearts. Over the last ten years, clinical trials have examined the value of stem cells taken from the bone marrow or blood to repair damaged hearts, but a more recent thrust is the use of stem cells in the heart itself.

4:37 Joshua Hare, M.D., from the University of Miami, described in his presentation the use of mesenchymal stem cells, which can become bone, cartilage or fat cells, and how they showed "incredible promise" in clinical trials.  The studies looked at whether they could repair heart tissue after heart attack, and heart failure, the loss of pumping efficiency, seen in the wake of heart attacks. While these studies are promising, the field still has a long way to go before stem cell treatments become part of standard medical practice.

5:35 Harvard's Piero Anversa, M.D., delivered the keynote lecture for the symposium on the topic of stem cells in the heart, their discovery, their use in animal studies to repair hearts damaged by heart attack. In particular he described strong, early results in the Phase I human Scipio trial. In this trial, researchers removed stem cells from the hearts of patients as they underwent coronary bypass surgery. The research team then reinfused each patient's stem cells into their hearts after the surgery, where they proved to be safe, to improve pumping function and to lessen the amount of dead tissue in the heart.

6:39 Stem cell therapies target tissue that forms scar when damaged by a heart attack. Scar tissue is made of structural cells instead of functional muscle cells, and scars interfere with the hearts ability to pump blood (heart failure). Dr. Prabhu said there are often pockets of live tissue within the scarred area.  The hope is that added stem cells will receive signals from the surviving areas that turn them into the kind of cells that either improve the remaining tissue or build new tissue.

9:04 It was actually the dawn the nuclear era that made possible the discovery of the slow stem-cell led turnover of heart muscle. Heart cells exposed to low level of radiation from power plants, for instance, could the be carbon dated to show cell turnover. There is not much turnover, but over a lifetime it makes hearts more durable. After a heart attack, the process of stem-cell based tissue replacement seems to kick up a notch, said Dr. Prabhu, but obviously not enough to counter the massive damage caused by a heart attack. What if researchers could temporarily pump up this natural response? Would more the presence of more stem cells mean more rebuilding of tissues in of damaged areas?

10:28 Whether injected stem cells themselves bring about cardiac repair or whether they trigger some chain reaction that brings about repair is a matter of debate. How much heart muscle for instance that grows back in damaged hearts after stem cells are infused has varied considerably from study to study. What has been shown in animal studies is that stem-cell driven regeneration can be manipulated to improve cardiac function. Human studies are seeking to confirm that now.

Nobel Prize focused on life-giving cellular cargo delivery system

A Nobel Prize was recently awarded to three researchers who discovered bubbles within bubbles that have tentacles. Award winners James Rothman, Randy Schekman and Thomas Südhof were pioneers in the study of vesicles, which are like bubbles inside human cells whose outer layers are made of the same stuff that separates cell insides from the outside world. Because the bubbles’ insides are kept separate from the rest of the cell’s interior, they can store, organize and deliver highly reactive biochemicals and proteins, releasing them only when and where they’re needed.

Electron microscope images of vesicles near Golgi complex in a cell.

Furthermore, the outer membranes of vesicles can fuse to outer cell membranes or to the membranes surrounding other cellular machines. This lets them take in contents from one compartment, move them to another walled-off area, and deposit them there. It also lets a cell start manufacturing a hormone or an antibody in one spot, truck it somewhere else for finishing, move it to the cell's surface, and secrete it to do a job elsewhere in the body.

To ensure that it dumps its contents into the right compartment, each vesicle has “tentacles,” squiggly proteins that “taste” the surface of other vesicles to make sure they have reached the right destination. Without vesicle formation and fusion, cells could neither live nor signal to each other as part of complex tissues. Vesicles are so central to cellular function that they are most likely involved in almost every disease when things go wrong, although we don’t yet know their role.

For his share of the prize, Dr. Rothman, a professor at Yale, discovered a protein complex that lets vesicles fuse with membranes to deliver their molecular cargo. He has a UAB connection in his former student, Dr. Elizabeth Sztul, Ph.D., professor in the UAB Department of Cell, Developmental and Integrative Biology and a vesicle expert in her own right. Dr. Sztul said she was “thrilled” to see vesicle research be recognized in the form of a Nobel Prize, and we thought to ask her why her field deserves notice.

Show notes from the podcast

1:56  A Nobel Prize win for vesicle research underscores just how vital basic scientific research is, along with the fundamental importance of vesicles in human life, said Dr. Sztul. Cells are made of compartments, and the prize went to the three-scientist team for discovering how proteins and genes work together to move key substances from one compartment to another.

3:02  Vesicular traffic has implication for all of life. Genetic mistakes that occur in genes that control this delivery system mean that an embryo does not often survive, and if so, with severe disabilities. The Nobel Prize winners designed tests that identified the cogs (proteins) that make possible the machinery behind vesicle formation and transport.

4:15 Specifically, Dr. Rothman, a biochemist, identified the proteins required for vesicle transport and then re-created vesicle trafficking in a test tube. Dr. Schekman identified some of the genes that control vesicle transport, and that have done so throughout evolution. He works one-celled organisms like yeast that share vesicle pathways with human cells. Dr Sudhof, a neurobiologist, showed how vesicles deliver proteins, not just to the right place, but also with perfect timing, to make cellular life possible. Together, the pioneers outlined how a vesicle "knows" where to go and when to fuse.

5:47  Genetic mutations, random changes in that occur in genes as they constantly get copied, are usually fatal within a few days when they occur within the central machinery proteins of vesicle trafficking in a human embryo. Dr. Stzul describes one key vesicle protein type as snares, which help a vesicle grab on to the outside of another compartment they want to fuse with. Genetic defects in snares are fatal, but people are born with genetic changes in less essential machinery related to vesicles and survive.

6:22 For instance, proteins on the sides of vesicles that are nicknamed tethers or tentacles, touch and "sample" the outer membranes of surrounding vesicles to determine which they should target for fusion.  A mutation in one these protein tentacles causes a very serious, rare disease called congenital disorder of glycosylation. Tethers and snares represent two ways that any vesicle chooses a specific vesicle that it will deliver its cargo into.

8:40 There are many types of payloads delivered by vesicle in human cells. The immune system uses them to swallow invading bacteria, and then to deliver chemicals to that vesicle that destroy the bacteria.  Nerve cells use them to deliver signaling molecules to the next cell in line as a nerve message runs along a nerve pathway. After you eat a meal, cells in your pancreas packs digestive enzymes into vesicles and ship them off to the gut.

10:38 Vesicle delivery of proteins by cells is tightly regulated and very precise, Dr. Sztul said. Even small genetic errors in the genes that make the vesicle proteins can cause disease, including one called craniofacial disorder. These patients have bones that don't form properly because the structural protein collagen, which makes the lion's share of skin and bones, is not delivered properly by vesicles.

12:37  Dr. Sztul's lab is trying to figure out all of the steps needed to move all important proteins in the cell from where they are made, through every required vesicle stop along the way and to a final destination.  Each stop in this journey involves a web of interacting proteins, and Dr. Sztul would like to map all of these interactions precisely in time and space. She believe that this map, once complete, will reveal links between mutations in vesicle trafficking genes and many diseases, both common and rare. These patterns will emerge, she said, as more and more patients routinely get their DNA sequenced as part of personalized medicine.

15:00 With the map in place, researchers will have a basis for the design of treatments that compensate for problems with specific vesicle proteins. At least theoretically, every protein that regulates trafficking will become targets for drug design. In cancer for instance, vesicles may be used by tumors to deliver proteins that cause cancer cells to spread or that encourage the growth of blood vessels that feed tumors. Drugs might be designed to keep vesicles from making these harmful deliveries.

18:15 The field is working to invent imaging technologies that can track the movement and action in a living cell, not just of a couple of interacting proteins at a time, but that can watch perhaps 60 vesicle trafficking proteins at work during one stage of trafficking. Also on the horizon, an in-depth understanding of the interaction between vesicle trafficking and outer key cellular actions. How do hormones effect vesicle trafficking in cells that secrete hormones? How vesicles in immune cells become filled with antibodies when the body senses that it has been infected with a bacterium or a virus, or in response to a vaccine?

Chimerism: not being yourself has medical implications

Science has demolished another idea that researchers once knew to be "true" about genes, the chains of molecules that encode the blueprint for the human body. The consensus a few years back was that every cell in each person's body has the same genetic signature, the same set of DNA unique to that person. It is a pretty important concept if you think about it.

Researchers determine things like paternity, genetic risk for disease and presence at crime scenes by examining just a few of the trillion cells in each a person.This practice is based on the assumption that the few cells taken accurately represent the genes in the rest of that individual.

But what if one person had different sets of genes, or genomes, in different cells? Some people, it turns out, have patches of cells with genetic changes in them not found in other parts of their bodies. Some have cells with genes that came from other people.

Such variety is called chimerism or mosaicism, depending on the details, both of which were the subject of a recent article by writer Carl Zimmer in the New York Times. We used the occasion of the article to ask Bruce Korf, M.D., Ph.D., chair of the UAB Department of Genetics, for his thoughts on the implications of these ideas for medicine. 

Show notes for the conference: 

0:35 To recap, the blueprint for the human body is encoded in genes, many of which hold the information necessary for the building of one or more proteins. Gene expression is the process by which information stored in genes is converted into proteins, the workhorse molecules that make up the body’s structures and carry its signals.

1:38 The dogma for decades in genetics was that all cells in one person, having all come from the same original cell (the embryo), had copies of the same genetic material throughout life. That belief was correct to a point, but did not tell the whole story, said Dr. Korf. Each person does indeed have a unique genome, a set of genetic material made up of about 3 billion bases, the “letters” that make up the DNA code, but changes in that code occur every time anyone our trillions of cells divides and multiplies. So mutations are underway constantly, with different changes building up in different groups of cells. Furthermore, several events, some of them more common that once thought, can inject other people's cells into our bodies.

6:35 Chimerism is the presence of two or more genetically different cells occurring in the same body. While we are taught the a fetus results when one sperm fertilizes one egg, more pregnanices than once thought may result from multiple fertilization events. More than one sperm fertilizes more than one egg in the womb get mixed to form one body. Beyond the number of twins born, researchers now suspect that many single baby pregnancies started as twins. One of the embryos then died early on, but not before sharing blood and cells with its twin. Thus you have one baby with the genomes of two babies mixed together. In other cases, two fertilized eggs may fuse together with no evidence they were once two individuals. Obviously, people who get an organ transplant are chimeras as well, as are most mothers, who absorbed their some of their babies' cells while pregnant.

8:15 Chimerism, which happens during conception, is different from the changes in genes that arise from constant small changes in genetic code underway in every human cell over a person's lifetime, a concept called mosaicism. Most of us have patches of cells in our body that have different genes than patches growing elsewhere. While the overall differences are small, mounting evidence suggests they may be meaningful. In the UAB Medical Genomics lab led by Dr. Korf,  the team studies many genetic orders that proceed from mosaicism. In many cases, a patient will have a genetic change that has caused cancer just in one patch of skin, instead of a change across the entire body.

11:06  When a person has two sets of different DNA in their cells, one set will greatly predominate with the other in relatively few cells. Until recently, DNA technologies often could not capture the less frequently occurring genome, losing it in the vast background of the majority. Next-generation sequencing technologies, however, can now identify rare cells that have a different genotype than most of the cells in a person, a capability which may explain why this topic has been more in the news lately. According to the Times article, recent cases have featured genetic test results that found a mother was not the mother of one of her children, and that a sexual assault suspect did not have the same genetic signature in his sperm as in his saliva. The fact both were chimeras threw the tests off.

12:56 While we don't yet know whether cells with different DNA have a big impact on say hearth disease risk, they are known to have a profound role in cancer. Whether the DNA is atypical from chimerism or mosaicism, it is possible the change may affect a cell's ability to divide and multiply, perhaps leading to abnormal growth. Cancer is a disease of mosaicism, said Dr. Korf, because a cell comes to include a small changes in its DNA that remove normal growth limits to create tumors.

16:45  We don't really know how many different genomes we have in the cells in our body. If you look at it one way, we have as many different sets of genetic material as we have cells, since small, unique and random changes slip in as each cell divides and multiplies into two more. Most of the changes have no impact on healthy function, but some do, and the trick is to pick out trillions the few that do.

17:22  Cells with slightly different DNA sequences obviously play a role in cancer, but the remaining question is whether or not small numbers of cells with differing genomes different play a role in other major diseases, like heart disease or Alzheimer's. Is it possible that chimerism or mosaicism in the heart can cause rhythm disorders or that such changes in the pancreas bring about diabetes?

Goal of next massive decades-long cancer study: reduce cancer to a nuisance

Before the first cancer prevention studies run by the American Cancer Society between 1952 to 1955, and again between 1959 and 1972, Americans had no idea that smoking causes cancer. Before the Cancer Prevention Study II, which started in 1982, physicians and patients didn't fully understand the link between nutrition, obesity and cancer.

The University of Alabama at Birmingham just became the largest enrolling center in the next study in this series, Cancer Prevention Study-3, or CPS-3, with a record 1,209 people signed up to participate at UAB. Nationally, the study will follow the health of 300,000 people for decades in hopes of making the next great leap in the understanding of what causes cancer.

Specifically, the study will track the lifestyle, environments, diet and genetics of people not previously diagnosed with cancer in hopes of understanding what causes or prevents cancer for each person in the coming decades. The ultimate goal is to turn cancer from a major killer into a manageable, chronic disease (a nuisance) or stop it before it starts.

We thought to ask Edward Partridge, M.D., director of the UAB Comprehensive Cancer Center, about the science behind massive, long-term studies like CPS-3, and about why they reveal clues about diseases that other studies miss. 

Show notes for the podcast:

1:06 Population-based studies like this are especially important because they enroll large numbers of people who are well at the beginning of study. Researchers can they see who gets sick over time, and go back to indetify which factors were associated most closely with disease. Sadly, a good many of the people in the study will develop cancer in the coming years, Dr. Patridge said. Was it a certain kind of food, or a certain certain of a gene that created risk? This is a different type of approach than studies that look at whether a drug will work in people who are already sick.

3:14 Massive, decades-long studies reveal patterns where other studies cannot because of the detailed tracking of so people and so many factors for so long. In addition, what the study designers decide to track in each patient is based on many studies in recent years that offered new clues about what to track. Participants take an original survey, which includes trying to recall what their lifestyle was like in their youth, and then repeat the survey every two years. The first of the CPS-3 study results might come out within a year, with more results will then continuing to come out for decades.

4:38 Importantly, this is the first large cancer prevention study that is taking a blood sample from every participant. That will enable researchers to study genetic factors, and their combination of withf other diseases, medications taken. diet, etc., over time.  The research team will also be able to look at epigenetics, the small chemical changes that turn genes on or off in reaction to the environment. In the future, this may enable the field to recognize future cancer risk from a blood sample taken from a perfectly healthy person and in time to intervene.

6:09  The CPS study before the current one, CPS II, led to a publication in 2001 that found obesity to be a major contributor to cancer. Today, some make the arugment that obesity has overtaken tabacco as the major cause of cancer.  In 1970, four percent of children between the ages of six and eleven were obese. Today, that number is 20 percent, a five-fold increase. Children who are obese are much more likely to become obese adults, and public health experts fear that a wave of obesity-related cancer is on its way. CPS-3 will include the largest percentage of obese people of any cancer prevention study so far, and the obesity-cancer link will be closely tracked. 

7:41 Other burning questions in cancer research that CPS-3 will help to answer are, for instance, what is the molecular basis of the increase in cancer risk related to obesity. Researchers will also be looking at what the drop in smoking has meant in terms of reduced risk. Researchers are also keen to study for the first time many of the pharmacuetical drugs taken now taken by so many Americans for large portions of their lives. For instance, what are the long-term effects of a drug like metformin, taken for Type 2 diabetes, on cancer risk?  It may actually reduce cancer risk and the study may explain why. 

9:23 Among the most exciting things about the study is the combination of taking blood samples and the fact that researchers have now mapped the human genome, the complete set of genetic material. That will enable researchers to see which deviations from normal genes are associated with cancer. Dr. Partridge said that he believes this study, and related efforts worldwide, will have eliminated cancer as a major public health threat half-way through the study, say by the year 2050.  By then, the field will detect and eliminate cancers before they become a health threat, or will be turning them into a chronic, manageable conditions, the way drug cocktials have enabled many AIDS patients to live normal lifespans. 

12:19  In a sign of the challenges involved in curing cancer, our society has not yet fully made use of the knowledge and data collected by cancer prevention studies that finished up decades ago, said Dr. Partridge. We all know that smoking causes cancer, and yet 22 percent of Americans still smoke, and even more Alabama. We know that colorectal cancer and mammography saves lives, and yet 40 percent of people with insurance don't opt for these tests. The new study will reveal many insights as well, but making the cultural changes needed to realize their value will be a larger task.

13:45 The fact that so many enrolled locally here in Birmingham says great things about the community, Dr. Partridge said.  He found it particularly gratifying that so many UAB employees enrolled. UAB is a major employer here, and to see nurses, staff, physicians and researchers, many of whom conduct research for a living, becoming participants in research.

14:54 Local enrollment in CPS-3 is closed, but folks can still visit the CPS-3 website to see what the 
nearest enrolling center is. The study will finish up enrolling nationally by December 2013.

Image post 9: infection blocks trash removal to cause ulcers, cancer

What's that ... a meteor blazing past a molten planet?  No, it's a self-destructing cell just shed from a gastric gland made up of the tightly packed blue cells running across the bottom.

Gastric glands that secrete digestive juices into the stomach, like all epithelial cells (skin, lining of blood vessels, etc.), constantly shed old cells from their outer layers and replace them with new ones. The turnover keeps tissues viable throughout adult life. When the shed cells sense they have outlived their usefulness, they initiate self-destruct mechanisms.

With some cells always in the process of self-destructing, other nearby cells are charged with swallowing up the dying cells and disposing of them. That explains the red cloud surrounding the yellow dot at the center of the image. An antigen-presenting cell (dyed red) has engulfed a self-destructing cell (yellow) to remove it.

The system works pretty well until a person's stomach gets infected with the bacteria Helicobacter pylori.

The infection causes cells to release TNF-alpha, a signaling chemical that triggers the waves of cell activation and chemical release meant to kill invading bacteria or viruses (inflammation). While the process protects us against infectious disease, it also plays a role in many disease processes when it goes too far.

A recent study by a team of UAB researchers found that, along with triggering inflammation, TNF-alpha also blocks the engulfment and removal of dying cells. Cellular debris builds up to drive further inflammation in a vicious cycle.

Why does this matter?  Inflammation caused by Helicobactor pylori is behind the development of nearly all ulcers. Furthermore, the same chronic inflammation damages DNA, creating risk for hard-to-treat gastric cancer.

The image was created by Diane Bimczok, DVM, Ph.D., an instructor in UAB's Division of Gastroenterology and Hepatology, using routine fluorescence microscopy and digital imaging. Phillip Smith, M.D., was senior author of the related study.