Sniffing Out Leukemia?

3 doctorsOK Ladies – here’s a question for you.   If you suffer from seasonal allergic rhinitis who do you go and see?

(a)  An allergist

(b)  An oncologist

(c)  A hematologist

If you answered (a) you’re probably feeling pretty confident right now.  After all the more common term for seasonal allergic rhinitis is hayfever and that’s something best managed by an allergist.  Right?

Not so fast! Maybe (b) or (c) would have been better choices.  You see, a team of scientists looking into the interplay of the immune system and cancer have just found a link between a history of airborne allergies – in particular those to plants, grass and trees – with risk of blood cancers in women.

Notably, the study did not find the same association in men, which suggests a possible gender-specific role in chronic stimulation of the immune system that may lead to the development of hematologic cancers.

The findings were published online last week ahead of the December print issue of the American Journal of Hematology.

allergic rhinitisTo the best of our knowledge, ours is the first study to suggest important gender differences in the association between allergies and hematologic malignancies,” says Mazyar Shadman, MD, from the Fred Hutchinson Cancer Research Center.

According to Shadman, who led the research, the immune system’s potential role in the cause of cancer is a focus of intense scientific interest. “If your immune system is over-reactive, then you have problems; if it’s under-reactive, you’re going to have problems. Increasing evidence indicates that dysregulation of the immune system, such as you find in allergic and autoimmune disorders, can affect survival of cells in developing tumors.”

The study included a large sample of men and women aged 50-76 years old from western Washington from the VITamins And Lifestyle (VITAL) cohort study. Participants answered a 24-page questionnaire that focused on: (i) health history and cancer risk factors, (ii) medication and supplement use, and (iii) diet. Participants provided information on age, race/ethnicity, education, smoking, diet (fruit and vegetable intake), and other lifestyle characteristics, self-rated health, medical history, and family history of leukemia or lymphoma.

History of asthma and allergies was also taken, including allergies to plants, grasses or trees; mold or dust; cats, dogs or other animals; insect bites or stings; foods; and medications.  Of the 79,300 VITAL participants who filled out the questionnaires, more than 66,000 individuals were selected after eliminating those who had a prior history of malignancies other than non-melanoma skin cancers and missing information on baseline cancer history.

Participants were then followed for eight years until they either withdrew from the study, moved away, had a cancer diagnosis other than hematologic malignancy or non-melanoma skin cancer, or died.

seer_logoIncidence of hematologic malignancies and other cancers was identified via the Surveillance, Epidemiology and End Results (SEER) cancer registry of western Washington.

Of the participants, 681 developed a hematologic malignancy during the follow-up period. These participants were more likely to have two or more first-degree relatives with a family history of leukemia or lymphoma, to be less active and rank their health status as low.

A history of allergies to airborne antigens was associated with a higher risk of hematologic malignancies. The most statistically significant association was seen with allergies to plants, grass and trees.

cat allergyThere was also an increased risk of plasma-cell neoplasms for participants who reported a history of allergies to cats, dogs or other animals. Plasma-cell neoplasms are conditions, both cancerous and noncancerous, in which the body makes too many plasma cells.

When stratified by gender, the incidence of blood cancers in response to these allergens was increased in women but not in men. The reason for this is as yet unknown.

However, Shadman and colleagues warn, “Given the limited number of cases within each sub-type of hematologic cancer, the risk estimates need to be interpreted with caution … and the possibility of chance finding due to multiple testing should be recognized.”

Even so, if you’re a women with allergies, you may want to keep a close eye on your blood work.

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Immune to Stress?

mouse-frazzled-bit-stressedFollowing on from last Friday’s post on the beneficial effects of stress hormones, we bring you news of study that helps us to better understand the stress process at a cellular level and how stress can lead to mood disorders.

The new research from Ohio State University, published in The Journal of Neuroscience, shows that certain cells from the immune system are recruited to the brain during stress, causing symptoms of anxiety.

Researchers discovered the dynamic mind-body interaction – a two-way communication from the central nervous system to the rest of the body – and back to the central nervous system that ultimately influences behavior during prolonged stress.

Under prolonged stress, the brain sends signals out to the bone marrow, calling up monocytes. The cells travel to specific regions of the brain and generate inflammation that causes anxiety-like behavior.

In experiments conducted in mice, researchers showed that repeated stress exposure caused the highest concentration of monocytes migrating to the brain. The cells surrounded blood vessels and penetrated brain tissue in several areas linked to fear and anxiety, including the prefrontal cortex, amygdala and hippocampus, and their presence led to anxiety-like behavior in the mice.

“In the absence of tissue damage, we have cells migrating to the brain in response to the region of the brain that is activated by the stressor,” said John Sheridan, senior author of the study. “In this case, the cells are recruited to the brain by signals generated by the animal’s interpretation of social defeat as stressful.

mouse-in-fearThe mice in this study were subjected to stress that might resemble a person’s response to persistent life stressors. In this model male mice were given time to establish a hierarchy, and then an aggressive male was added to the group for two hours. This elicits a “fight or flight” response in the resident mice as they are repeatedly defeated. The experience of social defeat leads to submissive behaviors and the development of anxiety-like behavior.

MONOCYTEMice subjected to zero, one, three or six cycles of this social defeat were then tested for anxiety symptoms. The more cycles of social defeat, the higher the anxiety symptoms. For example, the mice took longer to enter an open space and opted for darkness rather than light when given the choice. Anxiety symptoms corresponded to higher levels of monocytes that had traveled to the animals’ brains from the blood. Additional experiments showed that these cells did not originate in the brain, but traveled there from the bone marrow.

Exactly what happens at this point in the brain remains unknown, but the research offers clues. The monocytes that travel to the brain don’t respond to natural anti-inflammatory steroids in the body and have characteristics signifying they are in a more inflammatory state.

These results indicate that inflammatory gene expression occurs in the brain in response to the stressor.

These findings do not apply to all forms of anxiety, the scientists noted, but they are a game-changer in research on stress-related mood disorders.

Our data alter the idea of the neurobiology of mood disorders,” said Eric Wohleb, a pre-doctoral fellow in Ohio State’s Neuroscience Graduate Studies Program. “We’re saying something outside the central nervous system – something from the immune system – is having a profound effect on behavior.”

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Springing Forward Safely

SRxA’s Word on Health reminds you to turns your clocks forward an hour before going to bed tomorrow night. But as your dream of that extra hour of daylight, remember all good things come with a price.  First, the switch to summer time means we all lose an hours’ sleep. More worryingly, the time change may be bad for your health.

According to experts at the University of Alabama in the days immediately following the time change your risk of having a heart attack goes up by about 10%.

Because the Sunday morning of the time change doesn’t require an abrupt schedule change for most people, the elevated risk doesn’t kick in until Monday when people rise earlier to go to work.

Interestingly, the opposite happens in the fall, when we turn the clocks back. Then, the risk of heart attacks drops by 10%.

Exactly why this happens is not known but there are several theories,” says Associate Professor Martin Young, Ph.D. from the University of Alabama’s Division of Cardiovascular Disease.  “Sleep deprivation, the body’s circadian clock and immune responses all can come into play when considering reasons that changing the time by an hour can be detrimental to someone’s health.”

Young offers several possible explanations:

Individuals who are sleep-deprived weigh more and are at an increased risk of developing diabetes or heart disease. Sleep deprivation also can alter other body processes, including inflammatory response, which can contribute to a heart attack. Apparently, your reaction to sleep deprivation and the time change also depends on whether you are a morning person or night owl. Night owls have a much more difficult time with springing forward.

Circadian clock – every cell in the body has its own clock that allows it to anticipate when something is going to happen and prepare for it. When there is a shift, such as springing forward, it takes a while for the cells to readjust. It’s comparable to knowing that you have a meeting at 2 p.m. and having time to prepare your presentation instead of being told at the last minute and not being able to prepare.

Immune function – immune cells have a clock, and the immune response depends greatly on the time of day. In animal studies, when a mouse is given a sub-lethal dose of an endotoxin that elicits a strong immune response, survival depends upon the time of day they were given this endotoxin. Mice that were put through a phased advance much like Daylight Savings Time, and then had a challenge to their immune system, died, whereas the control animals that were not subjected to a phased advance survive when given the same dose of the toxin.

Fortunately, the body’s clock eventually synchs to the new time on its own.  In the meantime we offer you some tips to help you ease your body into the adjustment.

  • Wake up 30 minutes earlier on Saturday and Sunday than you need to in preparation for the early start on Monday
  • Eat a decent-sized breakfast
  • Go outside in the sunlight in the early morning
  • Exercise in the mornings over the weekend

These tricks will help reset both the master, clock in the brain that reacts to changes in light/dark cycles, and the peripheral clocks — the ones everywhere else including the one in the heart — that react to food intake and physical activity, thereby reducing the chance of a heart attack on Monday.

Assuming we all survive the annual time change shock to our system, we look forward to seeing you back here after the weekend.

Kicking Up A (cytokine) Storm

The New Year brings with it many new possibilities, including, unfortunately a new flu season.

So far, the number of flu cases in 2012 is down, thanks largely to the unprecedented mild weather over most of the US. A sharp contrast to 2009 when H1N1 (or swine flu) killed more than 18,000 people worldwide or 1918 when the flu virus infected around a third of the world’s population and killed at least 50 million people.

New research shows that the reason so many people died in both of those years wasn’t the influenza virus itself, but the immune system’s reaction to it.  It turns out that the virus destroys its host by turning the body’s own defenses against itself.

While trying to destroy flu-infected cells, your immune system also destroys legions of perfectly healthy cells all over your body. This is why, even though the virus itself rarely ventures outside the lungs, the symptoms of the flu are so widespread” says , Michael Oldstone, a virologist at the Scripps Research Institute in La Jolla, Calif.

Most of the time this immune response isn’t too severe. As the virus runs its course, the response subsides. But in some cases, an infection can trigger a reaction so destructive it can be fatal. Scientists call this a cytokine storm, because of the violent way immune cells respond to a virus. Cytokines usually help fight off infections by telling the immune system which specific viral cells it should be attacking, but sometimes an overabundance of cytokines floods into a part of the body, and that’s when you get a storm.

Cytokine storms are rare, but they may be more common among younger people because they have stronger immune systems, and are more prone to overreactions. This may explain one of the more surprising outcomes of the 2009 swine flu: that it was deadlier among young people than it was among the elderly.

Cytokine storms can cause serious damage throughout the body, especially in the lungs, which is why most flu deaths are attributed to pneumonia.

After 5 years of research, Oldstone and his colleagues have identified a cell — they call S1P1 – that responds to cytokines. More importantly they’ve also figured out how to turn off that cell’s signals. This could pave the way for a new class of immune-reaction-blocking drugs that could provide protection against cytokine storms and be more effective than antiviral drugs.

Cytokine-blocking drugs could target the flu effects that cause the most damage to the body and would avoid the problems of virus mutation because they don’t affect the virus itself.

Still, it will probably be many years before those drugs reach your local pharmacy. Although preliminary experiments in mice have shown very promising results they still have to replicate these in ferrets, then primates and finally, humans.

Do you have any flu stories to share? SRxA’s Word on Health would love to hear from you.

Fighting Flu

Last night I participated in my annual healthcare lottery. Fortunately for my finances, this didn’t involve scratch cards, ticket stubs or wheel spinning of any kind, nor will it bring me great riches, a new car or a timeshare condo. Instead, if my gamble pays off, I might be spared the flu this winter season.

However, this may be one of the last years that I have to keep my fingers crossed that the vaccine might work.  In future years getting a flu shot may become a safe bet.

In a significant step against the disease that affects billions of people each year, scientists at Oxford University in the UK, just announced that they have successfully tested a universal flu vaccine that could work against all known strains of the illness.

This new vaccine targets a different part of the flu virus to traditional vaccines, meaning it does not need expensive reformulation and guess work  every year to try and match the most prevalent strains of the virus that are circulating the world.

The team, led by Dr Sarah Gilbert at the Jenner Institute, developed a vaccine that targets proteins inside the flu virus that are common across all strains, instead of those that sit on the virus’s external coat, which are liable to mutate.

If used widely, a universal flu vaccine could prevent pandemics, such as the swine flu outbreaks of recent years, and could even end the need for a seasonal flu jab.

A universal vaccine would save the time and money now needed to create vaccines to fight whatever particular virus has emerged in any given year.  The process of developing a seasonal vaccine takes at least four months and if the flu strain is highly pathogenic the delay means people get sick and die before the vaccine is ready.

If we were using the same vaccine year in, year out, it would be more like vaccinating against other diseases like tetanus,” said Gilbert. “It would become a routine vaccination that would be manufactured and used all the time at a steady level. We wouldn’t have these sudden demands or shortages – all that would stop.”

While traditional vaccines prompt the body to create antibodies, Gilbert’s vaccine boosts the number of the body’s T-cells, another key part of the immune system which can identify and destroy cells that have been infected by a virus.

In her trial, Gilbert vaccinated 11 healthy volunteers and then infected them, along with 11 non-vaccinated volunteers, with a strain of flu virus.  She then monitored the volunteers’ symptoms twice a day.  Her results showed that the vaccine worked as planned.

Fewer of the people who were vaccinated got flu than the people who weren’t vaccinated,” said Gilbert. “We did get an indication that the vaccine was protecting people, not only from the numbers of people who got flu but also from looking at their T-cells before we gave them flu. The people we vaccinated had T-cells that were more activated. The people we hadn’t vaccinated had T-cells as well but they were in a resting state so they would probably have taken longer to do anything. The volunteers we vaccinated had T-cells that were activated, primed and ready to kill. There were more T-cells in people we vaccinated and they were more activated.”

The trial proved two important things about the vaccine: First, it showed that it was safe; and second it proved that giving people flu virus in the presence of lots of T-cells induced by the vaccine was absolutely fine.

What we’ll probably do is take the existing flu vaccine and mix in the new virus-vector vaccine, so you get both good antibodies and good T-cells. As well as giving you the antibodies for this season’s strain of flu, we’ll give you some T-cells that will cover this season, next year, and thereafter. It may not be 100% effective against all strains, but at least if there were a pandemic coming around, it would cover you for any strain.”

It is also believed that the vaccine could provide better protection against flu for older people. Traditional flu vaccines are effective in about 70-80% of young people, but only 30-40% of older people, because the older people’s immune systems are less efficient at making new antibodies.

The next step for the new vaccine is a larger scale trial comparing several thousand people who are given and not given the vaccine.

Although that means a commercial product is still some years away, this study represents some potentially very exciting findings not only for flu but possibly for other infectious diseases.

SRxA’s Word on Health looks forward to bringing you this news as it happens.

Synchrotron scientists suggest solution to sneezing sans sleepiness

As allergy sufferers we know all too well that although many over-the-counter antihistamines relieve symptoms, we’re are often too groggy to enjoy the respite. Now, thanks to some sleuth work by a team of international scientists, the way has been paved for antihistamines with fewer side-effects.

An international team of scientists has successfully cracked the  code for the complex 3-D structure of the human histamine H1 receptor protein. Using an X-ray beam 100 billion times stronger than normal,  at Diamond Light Source, the UK’s national synchrotron facility, researchers were able to get a 3D picture of the shape of H1 receptors.

Published this week in Nature, this discovery opens the door for the development of ‘third-generation’ antihistamines.

The H1 receptor protein is found in the cell membranes of various human tissues including airways, vascular and intestinal muscles, and the brain. It binds to histamine and has an important function in the immune system. However, in susceptible individuals it can cause allergic reactions such as hay fever, food allergies and pet allergies. Antihistamine drugs work because they prevent histamine attaching to H1 receptors.

Dr. Simone Weyand, postdoctoral scientist at Imperial College London, who conducted much of the experimental work at Diamond, said: “First-generation antihistamines are effective, but not very selective, and because of penetration across the blood-brain barrier, they can cause side-effects including sedation, dry mouth and arrhythmias.”

The team comprised of leading experts from The Scripps Research Institute in California, Kyoto University, Imperial College London and Diamond worked for 16 months on the project.

Professor So Iwata, Director of the Membrane Protein Laboratory at Diamond, said: “It took a considerable team effort but we were finally able to elucidate the molecular structure of the histamine H1 receptor protein and also see how it interacts with antihistamines. This detailed structural information is a great starting point for exploring exactly how histamine triggers allergic reactions and how drugs act to prevent this reaction.”

Word on Health’s allergy prone bloggers will be eagerly awaiting developments and will bring you news as it happens…assuming of course we can stay awake to do so!