You’re More Like Your Mother Than You Know

May 22, 2015

By Medical Discovery News

Photo of mother and child

While the benefits of breast feeding have been well-documented, scientists were surprised to learn of another one: breast milk contains a mother’s stem cells that become a part of different organs of the baby’s body.

Breast feeding protects infants against infections early in life and reduces their risk of juvenile diabetes, heart disease, and cancer as children. It also helps mothers lose weight after giving birth and lowers their risk of osteoporosis and uterine and ovarian cancer.

In addition, seven years ago scientists discovered the presence of mammary stem cells in breast milk. The mammary gland is unique in its ability to go through different stages in anticipation of producing milk, then a period of milk secretion followed by a return to the non-lactating state. All of this can occur as many times as necessary. This massive restructuring of the breast suggested the presence of stem cells.

Human breast milk contains about 14,000 cells in each milliliter. Most of these are the epithelial cells that are abundant in the breast and cells of the immune system. Some of the cells in breast milk had a molecule called nestin on the surface, which in adults is a marker for multipotent stem cells that can develop into many different types of cells, like those in the brain, pancreas, liver, skin, and bone marrow. When scientists transplanted a single nestin-positive stem cells into the fat pad of a grown mouse, it reconstituted a functional mammary gland. Scientists wondered if such cells were serving the same function in humans.

However, further research revealed quite a surprise. First, they genetically modified mice to produce a protein that makes the cells glow red under fluorescent light. Mothers with this new feature were given normal pups to nurse. When they were examined as adult mice, they had cells that glowed red like the mice they had nursed from in their blood, brain, thymus, pancreas, spleen, and kidneys. These cells became functional cells within these organs, so the ones in the brain behaved like neurons and those in the liver made albumin. Based on this experiment, breast milk stem cells travel into the baby’s blood and become functional parts of various organs, at least in mice.

In the laboratory, these stem cells have also shown the ability to differentiate into breast cells that produce milk in a petri dish, as well as bone cells, joint cells, brain cells, heart cells, liver cells, and pancreatic cells that synthesize insulin. In addition, this study may have also discovered a non-invasive, ethical, and sustainable source of multipotent stems.

We don’t yet fully understand the role of these cells in offspring, whether they maintain a tolerance for the mother’s milk, play a role in normal growth and development, or both. Until then, know that your mother is more a part of you than you ever realized.

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The Bright Side of Black Death

April 17, 2015

By Medical Discovery News

Bright Side of Black Death

It’s easy to think that nothing good could come from a disease that killed millions of people. But Dr. Pat Shipman, an anthropologist at Pennsylvania State University, disputed that notion in his recent article in “American Scientist,” where he suggested the Black Death that ravaged Europe in the Middle Ages may have resulted in some positive effects on the human population. Considering that we are in the midst another significant plague (the Ebola virus in West Africa), we could certainly use more information about the role of pandemics on human populations.

The Black Death or Bubonic plague started in the mid-1300s and was caused by a bacterium called Yersinia pestis, which typically enters the body through the bite of a flea. Once inside, the bacterium concentrates in our lymph glands, which swell as the bacteria grow and overwhelm the immune system, and the swollen glands, called buboes, turn black. The bacteria can make their way to the lungs and are then expelled by coughing, which infects others who breathe in the bacteria. The rapid spread of the infection and high mortality rates wiped out whole villages, causing not only death from disease but starvation as crops were not planted or harvested. It killed somewhere between 100 million to 200 million people in Europe alone, which was one-third to one-half of the entire continent’s population at the time. The plague originated in the Far East and spread due to improved trade routes between these two parts of the world.

Today, global travel is easier than ever thanks to extensive international airline networks. Just like with the Black Death, our transportation systems could enhance the spread of a modern plague. Of course, modern healthcare is also more sophisticated and effective, but as the latest Ebola outbreak has reminded us, a pandemic is a realistic possibility.

Dr. Sharon DeWitte, a biological anthropologist at the University of South Carolina, recently made several discoveries from comparing the skeletal remains of those who died from the Black Death and those who died from other causes during the same era. First, she found that older people, who were therefore already frail, died at higher rates. Killing this group at a higher rate created a strong source of natural selection, removing the weakest part of the population.

After the plague years, she found that in general people lived longer. In medieval times, living to 50 was considered old age. But the children and grandchildren of plague survivors lived longer, probably because their predecessors lived long enough to pass on advantageous genes. Today, a genetic variant in European people called the CCR5-D32 allele, which was favored during the natural selection initiated by the plague, is associated with a higher resistance to HIV/AIDS.

Microbes have an intimate relationship with human populations and have shaped human evolution through the ages. We may see survivors of the Ebola virus passing on similarly advantageous genes through natural selection as well.

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The Berlin Patient

Feb. 27, 2015

By Medical Discovery News

Millions of people around the world are infected with HIV, the virus that causes AIDS, but only one has ever been cured. Known as the “Berlin Patient,” Timothy Ray Brown is a 48-year-old American living in Germany. Scientists and physicians have wondered how he was cured, and some recently published studies in monkeys have provided one clue.

Brown had been HIV positive since 1995. When HIV infects the body’s cells, it integrates its genetic information into cells, making the virus a permanent part of the host’s genetic information. Brown’s HIV was held at bay by antiretroviral drugs that have made this infection survivable.  However, in 2006 he was diagnosed with acute myeloid leukemia (AML), a cancer unrelated to HIV. AML affects a group of blood cells in bone marrow called the myeloid cells. Brown underwent grueling chemotherapy that failed. In the hope of saving his life, he received two bone marrow transplants. The year of his first transplant, he stopped taking the antiretrovirals, which would normally cause a patient’s HIV levels to skyrocket.

Yet, years later, there is no sign of the virus returning. Only traces of HIV’s genetic material have been found in his blood, and those pieces are unable to replicate. The big question now is: how was this accomplished?

His treatment for AML included three different factors that could have individually or collaboratively resulted in curing his HIV infection. First, in preparation for a bone marrow transplant, a patient is treated with a combination of chemotherapy and whole body radiation to eliminate the entire immune system in preparation for receiving a new one. Second, Brown received blood stem cell transplants from a person with a defective cell surface protein, CCR5, which is what HIV uses to enter cells. People with a CCR5 mutation are resistant to HIV infection. Third, his new immune system may have eliminated the virus and remnants of his old immune system that harbored it in something called a graft versus host reaction.

In an experiment to determine how Brown was cured of HIV, scientists isolated blood stem cells from three Rhesus Macaque monkeys and put them into cold storage. They then infected those monkeys as well as three control monkeys with an engineered version of HIV. Soon after infection, all six monkeys were treated with a cocktail of drugs, and just like in humans, the levels of the virus soon declined. A few months later, the first three monkeys underwent radiation treatments to eliminate their immune systems, and then their immune systems were restored using their own stem cells from storage. Months later, the antiretroviral drugs were withheld from all six monkeys, and the virus came roaring back in five of them. One of the monkeys who underwent the stem cell transplant did not have the virus return in its blood, but it was detected in some tissues.

This experiment established that the destruction of immune system prior to bone marrow transplant was not sufficient to eliminate the virus, so the selection of bone marrow cells resistant to HIV infection and/or the graft versus host reaction may be the reason Brown was cured of HIV. Further studies are needed before we will know exactly how HIV can be cured.

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Vaginal or C-section: Does it matter?

Feb. 20, 2015

An infant

In the climax of William Shakespeare’s “Macbeth,” the title character is sword fighting and believes himself invincible because he was given a prophesy that said “no man born of woman shall harm thee.” Yet, that is how he was tricked, for his rival, Macduff, was “from his mother’s womb untimely ripped.” This and other historical references show that cesarean sections have been used for centuries, but today the high success rate has made them more common than ever.

The origin of the term Cesarean is popularly and probably falsely attributed to the birth of Julius Caesar. This is unlikely, since C-sections at this time almost always resulted in the death of the mother, and historical records mention Caesar’s mother later in his life. However, the origin may still be linked to Caesar as a law enacted during Caesar’s reign stated that a dead or dying pregnant woman was to be cut open and the child removed from her womb to save the child. Widespread use of this procedure began after anesthetics and antimicrobial therapies became available in the 20th century.

In 1965, 4.5 percent of America’s babies were delivered via C-section. Today that figure has risen to almost one in three, and is on the rise worldwide as well. There are plenty of medical and nonmedical reasons for this shift from vaginal childbirth. Both come with side effects and consequences, some lasting longer than others. For example, C-sections have been linked to increased rates of diabetes and obesity, although we’re not sure why. In a recent study, birth by C-section lead to epigenetic changes in the child’s DNA.

Epigenetics are changes in our DNA that don’t result from changes in our genetic code. These changes can come from environmental factors, such as smoking, that alter the ability of a gene to be seen or expressed. What we didn’t understand until relatively recently is that epigenetic changes can be transmitted to offspring. So you are the product of your parents’ DNA and the environmental factors that affected your DNA in your lifetime and their lifetime before you were born. Then your DNA and epigenetic information is passed on to new generations. These changes accrue and could affect your children or grandchildren. So the descendants of a smoker may inherit more than their name, but epigenetic changes in DNA as well.

New research suggests certain epigenetic changes in a baby’s DNA called methylation are different depending on the type of birth. When DNA becomes methylated, it changes whether a gene is used to make a protein and this can then alter the properties of specific cells. In this study, researchers compared the DNA methylation patterns in stem cells of 25 vaginally delivered babies and 18 delivered by C-section. Distinct methylation changes were seen in more than 300 different regions of the genome between the two groups. Interestingly, many of these regions are associated with genes that control the immune system. We don’t know how these epigenetic changes affect the immune system and ability to fight disease, and don’t have sufficient information to link these differences to later health issues. But this remains an intriguing possibility and awaits more research.

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Organ Farming

March 14, 2014

By Medical Discovery News

Imagine that a patient needs an organ, like an airway to their lungs called a trachea. A scientist harvests some of the patient’s cells and attaches them to a scaffold the proper shape and size for the tube. The cells and scaffolds are placed into a tissue reactor and – ta da! – in a week or two there is an organ ready for the surgeon to transplant into the patient. While it sounds like a chapter from “Brave New World,” this science fiction scenario is a growing reality.

Bladders and ears have been grown in the laboratory, and hearts, eyes, and kidneys and other organs are in progress. These organs are close to the natural ones they’re copying – some even have their own immune system. In April 2013, surgeons at the Children’s Hospital of Illinois implanted a bioengineered trachea into a two-year-old child. This was the first surgery of its kind in the United States and one of only six worldwide.

The patient receiving the transplant was a girl named Hannah Warren who was born without a trachea, commonly called a windpipe. Since birth, she’s had a plastic pipe inserted in her mouth that went down into her lungs, allowing her to breathe. She could not eat normally or even speak. With few options available, this type of congenital defect has always meant an early death; only a few children live past the age of six.  

Bioengineered organs could change that. The key is stem cells – cells that are at an early stage of development and through the influence of their environment can produce the many specialized cells of organs and tissues. In this case, doctors harvested the girl’s immature stem cells from the marrow inside her bones. The stem cells were taken to the lab and allowed to adhere to a plastic fiber model precisely the size (about one-half inch in diameter) and structure of the trachea she needed. Once placed in an incubator called a tissue bioreactor, the stem cells colonized the plastic and started growing. While they were growing, cells communicated with neighboring cells and worked together to produce all the cells needed for a functioning trachea. 

At the end of this process, Dr. Paolo Macchiarini implanted the trachea with promising results. Since the cells in the bioengineered trachea were based on ones from her body, her immune system didn’t recognize it as foreign and reject it, a big worry for transplant recipients. Without a plastic pipe in her mouth, Hannah was able to smile for the first time.

Unfortunately, while her trachea functioned well after the surgery, her esophagus never recovered. She underwent a second surgery to fix her esophagus and died from complications. Macchiarini said that her death was not due to the implanted trachea but her own “very fragile” tissue. He called Hannah a “pioneer” in the field of regenerative medicine and plans to conduct similar operations.

The next step for bioengineered organs is clinical trials leading to Food and Drug Administration approval. This would give more scientists and physicians the opportunity to improve organ “farming” and extend this field into a therapy that could benefit many.

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The Virus in Your Mucus

Dec. 6, 2013

By Medical Discovery News

Though it has a reputation as slimy and gross, mucus is one of the most valuable lines of defense against the bacteria people are exposed to every day of their lives. It exists not only in a person’s nose, but their respiratory, digestive, urogenital, visual, and auditory systems. Now science shows it contains viruses called bacteriophage (phage for short) that attack and kill bacteria.

A virus is a tiny, infectious agent that is made of a protein coating and a core of genetic information. Although viruses can carry genetic information, undergo mutations, and reproduce, they cannot metabolize on their own and thus are not considered alive. Viruses are classified by the type of genetic information they contain and the shape of their protein capsule. There are viruses that infect every living thing on earth. There are even viruses that infect other viruses. Certain viruses that can infect bacteria have been found in mucus.

A healthy adult produces about one to one and one half liters of mucus per day. Mucus consists of water, salts, antibodies, enzymes, and a family of proteins called mucins. Different mucins are responsible for signaling between cells, forming a chemical barrier for protection, and working with the immune system.

Scientists know that wherever bacteria live, there are also phage viruses that infect them. Areas with mucus have 40 phage for every bacterium, while that ratio is only five to one in areas without mucus. To discover what these phage are doing in the mucus, scientists grew two types of lung tissue in the lab: one that produces mucus and one that cannot. When both lung cultures were exposed to the bacteria E. coli, about half the lung cells died. However, when phage that kill the bacteria were added, the lung cells in the presence of mucus survived. This suggests that the combination of phage and mucus can efficiently kill potentially harmful bacteria. 

The researchers also discovered that the outside of phage is studded with antibody-like proteins that attach the phage to the carbohydrates in the mucus. This would help keep the phage where the bacteria are likely to be. The host may use this system to select which phage are localized to the mucus layers and which can be washed away, explaining why beneficial bacteria are not harmed by phage. An important implication of this system is that it controls the microbial populations in the digestive tract, which play a role in obesity, diabetes, and inflammatory bowel disease.

It all started with investigating how phage actually work in the body, and uncovered the revelation that there are in fact beneficial viruses. In the future, this research could be the foundation for designing phage that reside in mucus and combat specific bacteria, or even change the body’s microbiome. 

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Sponges for Toxins

Sept. 6, 2013

By Medical Discovery News

People reach to sponges for soaking up messes, washing the dishes, and cleaning appliances. But sponges can also clean up toxins – inside the body, no less.

For years, scientists have worked to develop methods to remove toxins that destroy cells and tissues. This has been a challenge due the variety of infectious agents and poisons that produce toxins. Recently, a significant advance using nanosponges could lead to the removal of many life-threatening toxins from the bloodstream. 

Nanosponges, developed by bioengineers at the University of California-San Diego, work much like their name implies – they are designed to absorb specific substances. These nanoparticles can remove toxins produced by bacteria such as the common skin infection Staphylococcus aureus, even the antibiotic-resistant MRSA strain. These bacteria produce something called pore-forming toxins. These toxins attack cells by inserting themselves in the cell membranes, creating holes in the surface of the cell, and allowing cell contents to leak out or large amounts of external water to rush in.

In either case, this causes the cell to die. Significant or rapid loss of cells results in the damage seen during disease processes. Nanosponges work by absorbing dangerous toxins, thereby preventing them from destroying cells. To work at this level, nanosponges must be super small – 85 nanometers in diameter, about 90 times smaller than a red blood cell.  

A major issue with all drugs delivered by the bloodstream is how to prevent the immune system from removing them. Since the immune system’s job is to remove foreign agents, it is a challenge to thwart its attacks long enough for a drug to do its job. Nanosponges can overcome this with a clever technique called cloaking. Just like the enchanted invisibility cloak Harry Potter uses, nanosponges become “invisible” to the immune system by blending in with their surroundings. The nanosponge is coated with pieces of the membranes of red blood cells. This makes them look like smaller versions of red blood cells and not foreign invaders to the immune system. Cloaking is so effective that the nanosponges can still be detected in the blood 72 hours after injection, long enough to remove pore-forming toxins in the blood before the nanosponge is removed by the liver. And since they are much smaller than human cells, it’s safe to use a large dose where nanosponges outnumber red blood cells. 

The pore-forming toxins usually attack red blood cells, but when they attach to a nanosponge in disguise, they are trapped by the nanosponge’s core, which is made of a polymer called poly lactic co-glycolic acid. Each nanosponge can trap about 30 – 900 toxin molecules, depending on the type of toxin. A remarkable 90 percent of animals survived a lethal dose of MRSA toxin when they received nanosponge injections. 

MRSA is just the beginning. With this platform technology, scientists can jump into using nanosponges with other toxins as well, even bee venom. If the clinical trials in humans have similar results, nanosponges could revolutionize the way doctors treat these diseases. 

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Ticked Off Meateaters

August 2, 2013

By Medical Discovery News

Using bug spray is more important than ever – especially for those who particularly enjoy eating hamburgers. It might sound like those two things aren’t related, but a person bitten by a certain tick can develop a severe allergy to meat.

This type of food allergy only develops in people who have been bitten by the Lone Star Tick, which has previously been linked to a condition known as Southern Tick Associated Rash Illness (STARI). The tick bite that causes this illness results in a rash, fatigue, headache, fever, and muscle pains. It is often confused with Lyme disease, which is also spread by ticks.

After being bitten by the Lone Star Tick, a person develops antibodies, which are molecules of the immune system that normally target and destroy invaders like viruses and bacteria, against a complex sugar called galactose-alpha-1,3-galactose (alpha-gal). This sugar exists in all mammals except primates, including cows, pigs, and sheep. This specific allergy has a delayed response, so a person would experience symptoms like hives four to six hours after eating a meat such as bacon. Some people even suffer life-threatening anaphylactic shock.

It is unclear what in tick saliva triggers alpha-gal antibody production. When ticks latch on to people with their mouthparts they can remain attached for several days and introduce saliva into the skin at the bite site. Tick saliva contains molecules that keep the tick firmly attached to its host. It also keeps the blood at the site from clotting so the tick can continue its meal and can influence the immune response and angiogenesis, the development of new blood vessels. In addition, ticks can transmit a variety of viruses and bacteria through their saliva.

This allergy first came to light because some cancer patients were unusually sensitive to the cancer drug cetuximab, which includes the alpha-gal molecule. But only patients from the southeastern and eastern United States, where the Lone Star Tick lives, experienced this and they all had high levels of alpha-gal antibodies. Currently, more than 80 percent of the people with this meat allergy had tick bites before exhibiting symptoms.

But now that cases of this meat allergy have been reported outside the Lone Star Tick’s habitat, such as Hawaii, researchers are wondering whether this tick has spread further than they thought, or if other tick species can cause a similar reaction. The Lone Star Tick is very aggressive when it comes to biting people and animals, so to prevent tick bites use a bug spray with permethrin, avoid wooded areas, and frequently check for ticks when outside. Otherwise, a person may find themselves watching everyone else eat during a summer barbeque!

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Aging But Still Protected

June 14, 2013

By Medical Discovery News

The people who are at the highest risk of dying from common infections like pneumonia, influenza, and colds are 50 and older. Traditionally, scientists believed that as we age, our immune systems weaken, leaving us more vulnerable than ever to infections. But new research suggests that this isn’t completely true – certain parts of the immune system remain fully functional and robust longer.

It is true that older people make fewer antibodies, proteins that attach to viruses and cells infected with viruses to mark them for elimination by the immune system. This explains why some vaccines aren’t as effective in the elderly. The flu vaccine, for example, contains a “dead” virus that stimulates the body to make more protective antibodies against the flu.

However, other vaccines are well-received in older people, like the varicella zoster virus vaccine that prevents shingles. This vaccine does not involve antibodies, but T-cells, which kill infected cells, and memory T-cells, which recognize and respond to a reinfection.

White blood cells, formally called leukocytes, represent an army ready to defend the body from bacterial or viral attacks. T-cells are one type of soldier in this army, responsible for cellular immunity – killing infected cells to protect the body. The thymus, located between the breast bone and heart, produces T-cells. But as people age, the thymus does too.

The thymus shrinks by about 3 percent a year during middle age, and there is a corresponding fall in the production of T-cells. As humans age, their T-cells increasingly become memory cells. Therefore, it’s been assumed that the T-cell response to kill cells infected with a virus is impaired in older adults, making them more susceptible to viral infections.

To test that assumption, researchers at the McMaster Immunology Research Centre in Ontario isolated blood from people with one of three types of viral infections: West Nile Virus, Epstein-Barr Virus, and Cytomegalovirus. They divided the patients into three groups: those under 40, those middle-aged (41 – 59), and those over 60. They then measured the amount, type, and activity of the T-cells in each group. The older group did indeed have a shift toward the production of memory T-cells. But surprisingly, the amount of virus-specific T-cells did not decrease with age – the older group had roughly the same amount as the middle and younger groups.

These results suggest that the thymus continues to play an important role in producing T-cells that target viral infections as we age. It also indicates that vaccines designed to stimulate cellular immunity, instead of antibodies, would be more effective in older people. So the flu vaccine might prevent more flu cases in older people if the dead virus was replaced with a live but weakened virus, but currently that’s not approved in the U.S. for people over 50.

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