Margulis does it again

We all know of once-respected scientists who ended up going off the deep end, adhering to an unproven idea despite massive evidence to the contrary. Linus Pauling and his advocacy of megadoses of Vitamin C, or Peter Duesberg’s descent into HIV denial. It’s all the more disappointing when the one taking a dive is a woman, since there are, compared to men, relatively fewer female “big names” in the sciences. So when one goes from views that were, perhaps, outside of the mainstream (but later proven largely correct) to complete science denialism, it makes it all the more depressing. Even worse, mainstream popular science magazines like Scientific American (with this article by Peter Duesberg) and Discover (Duesberg again) give these ideas reputable press. And now Discover has done it again by giving “maverick” biologist Lynn Margulis a profile in their latest issue. More after the jump.
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New site–“History of Vaccines”

This is great. The College of Physicians of Philadelphia has launched a site on The History of Vaccines. I’ve been poking around, and there’s an incredible amount of stuff to check out. They have a nice FAQ, Top 20 questions about vaccination, as well as some great activities (herd immunity! learn about Koch’s postulates! understand the relative risk of vaccination versus other events!) and a metric fuckton of articles and images. Looks to be a fantastic resource for students, and for anyone interested in understanding vaccination.

Worms: Are they good or bad for us?

Student guest post by Shylo Wardyn

“Of all the parasites I’ve had over the years, these worms are among the… hell, they are the best”.

Was Fry from the animated show ‘Futurama’ right in his assessment of worms being good for him? Did he know something about parasitic worm infections that I was unaware of? Well, in the show, his parasites were doing remarkable things for his body, but does this translate to real life at all? Some people think so. Altman reviews the idea that over evolutionary time, our ancestors were infected with all sorts of parasites and this led to an interaction between the worm gene products and the immune system. These interactions led to modulation of dendritic cells and establishment of T-cell networks. It has been hypothesized that in an environment without these interactions, as is the case for most people living in “Westernized” countries, there is a loss of the ‘fine tuning’ of the adaptive immune system.

In another review, Jackson et al. discuss how this mechanism could have co-evolved. It is generally believed that the T helper cell type 2 (Th2) evolved to counter infections with parasitic worms. These cells are activated in response to parasitic worm infection, which leads to a large regulatory T cell response. Our response to worms seems to involve an immune response that is less inflammatory than our response to microbes, and it also takes much longer to reach the peak of effectiveness. This is due in large part to an initial systemic suppression of innate and adaptive immunity in the host. This is likely caused by regulatory CD4+ and CD25+ T cells producing suppressive cytokines or other suppressor T cell subsets. Anti-inflammatory responses are also caused by alternatively activated macrophages. These macrophages secrete anti-inflammatory cytokines and express genes whose functions relate to wound healing and repair. Therefore, being infected with parasitic worms leads to a down-regulation of proinflammatory responses, while allowing mechanisms for wound repair and a controlled development of the Th2 response. This Th2 and T regulatory response is beneficial for both the worm and the host. For us, the regulated Th2 response is less costly than the generation of a strong immune response, which often can be detrimental to our own cells. For the parasites, they are able to survive the initial immune response and therefore reproduce, while later parasites would not be able to survive the developed immune response.

The overall thought is that since parasitic worm infections are ubiquitous in mammals and have been since mammals first evolved, there would be a positive selective pressure for those individuals whose immune systems respond well to worm infections. Our immune systems may have been selected to anticipate a chronic exposure to Th2 and T regulator inducing pathogens. Since our ancestors were chronically infected by worms, their immune systems would have developed to work well in this context, while not necessarily working as well in the absence of worms. This scenario may explain why in some cases the immune system goes haywire in populations that are free from parasitic worms.

So is there any strong evidence linking parasites with populations free from allergies and autoimmune diseases? There have been many ecological studies which show an inverse correlation between the parasite load and allergy level for a particular region. Does this prove anything? Not really, the data is simply correlative. There have been other studies showing that treatment of worm infections is accompanied by an increase in skin test reactivity to allergens and IgE antibody levels. It appears that in the absence of worms, the immune system overreacts to allergens to which it normally wouldn’t mount a response in the presence of worms. This gives us a better idea about the link between parasitic worms and immune responses. While the evidence is still shaky, it is biologically plausible that the lack of worms in our environment has led to the massive increase in the amount of immune related diseases, such as asthma, multiple sclerosis, type 1 diabetes, and general allergies. However, the immune system is incredibly complex, as are those diseases, and I’ve barely scratched the surface of it for this topic. So while it seems being infected with worms may prevent immune system diseases, I doubt anyone would trade their asthma for a tapeworm. It does make for an interesting hypothesis (and Futurama episode) though and should be researched more thoroughly.


Altmann D. M. (2008). Review series on helminths, immune modulation and the hygiene hypothesis: Nematode coevolution with adaptive immunity, regulatory networks and the growth of inflammatory diseases. Immunology, 126(1); 1-2.

Jackson J. J., Friberg I.M., Little S. and Bradley J. E. (2008). Review series on helminths, immune modulation and the hygienehypothesis: Immunity against helminths and immunological phenomena in modern human populations: coevolutionary legacies? Immunology, 126(1); 18-27.

Weiss S.T. (2000). Parasites and asthma/allergy: What is the relationship? Journal of Allergy and Clinical Immunology, 105(2); 205-210.

Potential for common bacteria to cause colorectal cancer

Student guest post by Desiré Christensen

Colorectal cancer (aka colon cancer) includes cancers of the colon, rectum, and appendix. Colorectal cancer is more common in developed countries (e.g. United States and Japan) compared to developing countries in Africa and Asia. Each year in the United States, there are around 150,000 cases of colorectal cancer diagnosed and about 50,000 people die from this cancer. Risk factors for colorectal cancer include lifestyle factors (e.g. habitual alcohol use; high-fat, low-fiber diet; obesity; sedentary lifestyle; smoking), family history of intestinal polyps or colorectal cancer, and medical conditions (e.g. diabetes, familial polyposis syndromes, hereditary non-polyposis colon cancer syndrome, inflammatory bowel disease, intestinal polyps). [1]

Lifestyle factors are considered important risk factors for colorectal cancer, and they are modifiable unlike family history. Among the most important determinants of colorectal cancer are dietary habits. High-fat, low-fiber diets are associated with an increased risk for colorectal cancer. Diets with a protective effect include those high in vegetables, fruits, fiber, folate, and calcium. [2]

In addition to the risk factors listed above, an infectious cause of colorectal cancer has been suggested. Many bacterial species inhabit the human colon. Some may be friends, and others foes. Friendly colonic bacteria help with digestion, and in return, the colon provides the bacteria a place to live. The presence of friendly bacteria generally goes unnoticed by the host. Other bacteria in the colon may be harmful and are being investigated as potential causes for irritable bowel disease [3] and colorectal cancer. Enteroccocus faecalis (or E. faecalis) is one such bacterium under study for its role in colorectal cancer.

E. faecalis is common and present in most colons. It lives in disease-free individuals as well as people with colorectal cancer. For most, E. faecalis appears to be harmless. But recent studies have shown evidence that E. faecalis is not an innocent bystander in susceptible hosts.[4] The question arises: How could E. faecalis cause cancer in some and be harmless in others?

A characteristic feature of colorectal cancer is genomic instability. Genomic instability refers to chromosomal rearrangement, duplications, and other types of DNA damage. Theories have developed to explain how E. faecalis could contribute to genomic instability. One theory is that E. faecalis produces free radicals such as extracellular superoxide and hydrogen peroxide. Free radicals are highly reactive with other molecules. The free radicals could directly cause mutations in colonic DNA; it is also possible for free radicals to form carcinogens indirectly from dietary procarcinogens (a substance that becomes a carcinogen after being altered). [4]

Results from a study by Huycke et al [3] supports this theory. The investigators found that E. faecalis produces extracellular superoxide and reactive oxygen species capable of causing genomic instability. Free radical production by E. faecalis has the potential to damage DNA in the colon. If production of these free radicals becomes chronic, DNA damage would be ongoing leading to increased genomic instability and mutations. [4]

Dietary risk factors could be combined with the theory about DNA damage induced by E. faecalis to explain some cases of colorectal cancer. An interaction between diet and E. faecalis could also explain why some people develop cancer and others remain disease free. High-risk diets include diets rich in meat and iron. High concentrations of iron in the colon could accelerate formation of free radicals and mutagenic products. Low-risk diets such as those rich in fruits, vegetables and fiber, contain antioxidants that can “round-up” free radicals and reactive oxygen species to limit the potential for DNA damage. Dietary intake could influence the amount and types of carcinogens E. faecalis and other bacteria produce in the colon. Studies are needed to investigate the interaction between infectious causes such as E. faecalis and dietary intake. [5]

The link between colorectal cancer and an infectious agent has been investigated for other bacteria. Streptococcus bovis (S. bovis) has also been linked to colorectal cancer. A case-control study was done to determine the presence of S. bovis in 16 patients with colonic cancer and 16 age matched controls. The presence of E. faecalis was determined by looking for antibodies against E. faecalis. More antibodies often indicate a larger response by the host to bacteria in the body. An increase in antibodies against S. bovis was detected in patients with colonic cancer, but an increase in antibodies against E. faecalis was also seen. In fact, there was a greater increase in antibodies against E. faecalis compared to S. bovis. [5]

There are few epidemiological studies on E. faecalis in colorectal cancer. One study collected stools from patients undergoing colonoscopy who had no prior history of colonoscopy or colorectal cancer. Enterococci were later isolated from the stool samples. Free radical producing enterococci were found in 40 percent of the stool samples. No association was found between colonization with enterococci and colorectal cancer. The study had limitations. The patients were not tracked long enough to study chronic infection and genomic instability that occurs over decades instead of years. In addition, the presence of any enterococci was evaluated instead of focusing on E. faecalis. It is possible that E. faecalis differs significantly from other enterococci in the ability to cause colorectal cancer. [6]

Much remains unknown about the cause of colorectal cancer. Research linking lifestyle factors and infectious causes is lacking. There is a need for more epidemiological studies and studies describing potential pathways leading to the development of cancer. E. faecalis, or any other infectious cause, has not yet been definitively associated with colorectal cancer. Lifestyle factors and family history will remain important risk factors regardless of an infectious cause, but these factors may interact with bacteria found in the colon and help explain why some individuals are at an increased risk for colorectal cancer.

1. Colorectal Cancer Overview. (1999) Colon Cancer (Colorectal Cancer). Retrieved 4/10/2010, from

2. Sandler RS. (1996) Epidemiology and risk factors for colorectal cancer. Gastroenterol Clin North Am; 25(4):717-735.

3. Balish E and Warner T. (2002) Enterococcus faecalis induces inflammatory bowel disease in interleukin-10 knockout mice. Am J of Path; 160:2253-2257.

4. Huycke MM, Abrams V, and Moore DR. (2002) Enterococcus faecalis produces extracellular superoxide and hydrogen peroxide that damages colonic epithelial cell DNA. Carcinogenesis; 23(3):529-536.

5. Darjee R and Gibb AP. (1993) Serological investigation into the association between Streptococcus bovis and colonic cancer. J Clin Pathol; 46:1116-1119.

6. Winters MD, Schlinke TL, Joyce WA, Glore SR, Huycke MM. (1998) Prospective case-control study of intestinal colonization with enterococci that produce extracellular superoxide and the risk for colorectal adenomas or cancer. Am J Gastroenterol; 93(12):2491-2500.

Malignant Mesothelioma and Simian Virus 40 (SV40)

Student guest post by Andrew Behan

Malignant Mesothelioma (MM) is a rare type of cancer which manifests itself in the thin cells lining the human body’s internal organs. There are three types of MM; pleural mesothelioma, peritoneal mesothelioma, and pericardial mesothelioma, affecting the lining of the lungs, abdominal cavity, and lining of the heart, respectively (1). Pleural mesothelioma is most common, consisting of about 70% of all MM cases and has a poor prognosis; patients live a median time of 18 months after diagnosis. (Note: for the purposes of this article, MM will be used to represent pleural mesothelioma exclusively.) Despite its discovery in the mid-1800’s, MM was not linked to asbestos until the late 1900’s, when case reports of fast-growing lung cancers, different from previously described lung cancers, motivated investigators to uncover undisputed evidence linking asbestos to MM. Measures to reduce/eliminate asbestos from buildings reduced exposure to the cancer-causing agents found within the material, and public health officials remained confident by the year 2000 MM cases would decline in the U.S. and parts of Europe. Despite these predictions, MM cases have not declined. In fact, the incidence of MM is on the rise (1). Consequently, investigators have focused their attention on other factors to explain the steady incidence of MM in the U.S., eventually naming Simian Virus 40 (SV40) as a potential cause of MM.

You might be asking, “SV40? What’s that?” SV40 is a virus originally discovered in 1960 in kidney cells of rhesus monkeys. SV40 is dormant and asymptomatic in rhesus monkeys, but was later found to cause kidney disease, sarcoma, and other cancers in animal models. Later on, it was found SV40 attacks p53 gene (a tumor suppressor) and can interrupt the cell’s ability to perform apoptosis, or cell death. This makes the cells immortal, leading to tumor formation, or cancer (2). Controversy arose when the discovery of SV40 was found in the rhesus monkey kidney cells because these same cells were being utilized to form the polio vaccine. Consequently, many polio vaccines were contaminated with SV40 and when the vaccine was used to inoculate humans, SV40 was passed to humans along with the inactive form of the polio virus. It was estimated over 98 million Americans received the vaccine from 1955-1963, when a proportion of the vaccine was contaminated with SV40. Of the 98 million vaccinated during this time period, it was estimated 10-30 million of those individuals were exposed to SV40. Naturally, people who received contaminated forms of the vaccine were afraid they would develop cancer from exposure to SV40.

Since the controversy began in 1960, research has been devoted to confirming its role in cancer development in humans, as well as many animal models. As I mentioned above, presence of SV40 in animals has led to tumors and other cancers, and a few studies have found presence of SV40 in humans who have developed MM. For example, Carbone et al. found SV40 in mesothelial cells of humans who had developed MM, but not in the surrounding tissue (3). They did not find SV40 in patients who had other lung cancers, possibly reinforcing the specificity of their findings (3). Overall, 54% of MM cases were found to have SV40 infection within the mesothelial cells (3). The investigators determined more research needed to be done to see if SV40 infection alone could cause MM, or if other factors, such as immunosuppression or exposure to asbestos, were necessary for development of MM.

Other studies were not as convincing. For example, Lopez-Rios et al. reported that initially they detected SV40 in about 60% of MM specimens, and then they determined that most of the positive results were caused by plasmid PCR contamination, and that only 6% of the initially positive samples were confirmed to contain SV40 DNA (4). However, studies have shown the presence of SV40 in human specimens by using several other techniques besides PCR, including Southern blotting, immunostaining, RNA in situ hybridization, microdissection, and electron microscopy” (5).

Thus, the question remains: does SV40 cause MM, or does SV40 infection, in conjunction with asbestos exposure, generate a greater risk for the development of MM? This is a tough question to answer, because although asbestos is no longer mined in the U.S., it is still being imported; workers are still continually being exposed to asbestos. However, the use of asbestos has nearly ceased, decreasing from 813,000 metric tons in 1973, to 1700 metric tons in 2007 (6). The other problem in teasing out SV40 as a cause of MM from asbestos lies in the latency period between asbestos exposure and MM clinical diagnosis. According to the CDC, the latency period for someone who is first exposed to asbestos and clinical disease is 20-40 years. It may be, given asbestos still remains in many buildings, and exposure to it is inevitable when removal is completed, in addition to the long latency period between exposure and disease, that we have not yet come to the dramatic decrease in MM health officials have predicted. Or, is SV40 infection the culprit and the increase in incidence of MM will continue to rise? According to the SV40 Foundation, “SV40 is a problem that federal government authorities have not addressed responsibly because the government’s own vaccine programs are responsible for the spread of the virus throughout the western world”.(2) It is no question the public has not forgotten, even after almost 50 years, and much more research into this area is needed, to attempt to confirm SV40’s causal role, if any, in the development of MM.


(1) Mesothelioma. Retrieved April 2010.

(2) “Treating SV40 Cancers.” Retrieved April 2010.

(3) Carbone, M. “Simian virus 40 and human tumors: It is time to study mechanisms.” Retrieved from PubMed April 2010.

(4) López-Ríos F, Illei PB, Rusch V, et al. “Evidence against a role for SV40 infection in human mesotheliomas and high risk of false-positive PCR results owing to presence of SV40 sequences in common laboratory plasmids”. Lancet. 2004;364:1157-1166.

(5) Yang, Haining et al. “Mesothelioma Epidemiology, Carcinogenesis, and Pathogenesis.” Retrieved from PubMed April 2010

(6) CDC. “Mesothelioma.” Retrieved from PubMed April 2010.

Chronic Fatigue Syndrome: a Legitimate Excuse for Missing Work

Student guest post by Jay Watson

Tired again? Perhaps it’s the crappy weather, because you’re sure that you’ve been getting enough sleep. After all, you can’t remember the last time you spent less than ten hours in bed per night. Hopefully it’s not mono; one of your friends had it a few months ago and it’s all but knocked her out. However, you soon realize that you’ve only talked to her on the phone since she got engaged, so there’s no way that’s it. It’s strange, even everyday activities like running errands has turned into something utterly exhausting. As you consider the reasons as to why you’ve felt so drained for… well for as long as you can remember, you whittle your way down through all the likely suspects. Worried, you finally make a trip into the doctor’s office. After seeing a couple doctors and explaining your medial history in depth each time, a specialist eventually mentions that you might be suffering from chronic fatigue syndrome.

According to the CDC, Chronic fatigue syndrome (or CFS) is a complex disorder that is characterized by severe chronic fatigue that lasts at least six months, as well as at least four of the following symptoms: impairment of short-term memory or concentration, sore throat, tenderness in lymph nodes, muscle or joint pain without swelling or redness, headaches, unrefreshing sleep, and post exertional malaise. In addition to the symptoms listed above, patients diagnosed with CFS have noted several other commonly observed symptoms. Because the laundry list of symptoms can be long, and due to the fact that ‘fatigue’ itself accompanies numerous other illnesses, diagnosis can only be made after eliminating other causes. Diagnosis includes more than one specialist, which typically involves detailed physical examinations and medical histories. Also, it is important to note that there is no laboratory technique currently available to test for chronic fatigue syndrome. Treatment for CSF focuses on the symptoms experienced by individual patients. Though there are plenty of gaps in the knowledge base for this disease, what is known is that CSF affects over one million Americans, and it occurs four times more frequently in women than men. Worldwide, CSF is estimated to affect 17 million, with a majority of people still undiagnosed. Also, CSF is a disease associated with adulthood, with people between forty and fifty most likely to have it. However, true to its name, the specific cause for this syndrome has not been established… yet!

Recently, actually very recently in fact, there has been much attention diverted to a potential factor involved with CSF: Xenotropic murine leukemia virus-related virus (or XMRV for short). Also according to the CDC, this virus is similar to a known mouse retrovirus. However, beyond knowledge of XMRV at the molecular level, little is known about the virus and its mode(s) of transmission. Even the CDC admits that the manner in which XMRV is transmitted is still uncertain and that more information is needed. Initially thought to be only associated with human prostate cancer, a study done by Vincent Lombardi and colleagues in October of 2009 found that approximately 67% of cases in the study diagnosed with CSF had detectible levels of XMRV versus about 4% of controls. Very quickly, additional studies to test this hypothesis have arisen. In contrast with Lombardi’s results, none of the subsequent studies have found an association between XMRV and chronic fatigue syndrome, including a both a case control study and a cohort study in the UK and a small cohort study done in the Netherlands. However, research is so incomplete regarding the association between these two factors that currently researches do not have the ability to say things are one way or the other.

Regardless of the complexity of CSF and the novelty of XMRV, research has undoubtedly unveiled some very important implications that I conclude with:

• Is/will there ever be a method developed so that we can prevent chronic fatigue syndrome rather than treat the symptoms of it alone?

• Why are women more likely than men to have it? What other epidemiologic factors play into CFS?

• Is there significant evidence to associate XMRV with CSF? How much is enough?

• What about XMRV and prostate cancer, as initially theorized?

• Is XMRV actually infectious? How is it transmitted? How virulent is it?

• If XMRV actually is a cause, or at least a within the causal pathway of CFS, what are some of the implications there? Would there be a cure? Can eventually eliminate chronic fatigue syndrome?

Obviously this is not an exhaustive list, but something worth pondering. Perhaps tomorrow’s research will lend insight into this intriguing disease and it’s mysterious cause(s).


Chronic Fatigue Syndrome. Center for Disease Control and Prevention. U.S. Department of Health and Human Services. Revised 5 May 2006.

Erlwein O, Kaye S, McClure MO, Weber J, Wills G, et al. 2010 Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome. PLoS ONE. 5(1).

Groom HC, Boucherit VC, Makison K, Randal E, Baptista S, Hagan S, Gow JW, Mattes FM, Breurer J, Kerr JR, SToye JP, Bishop KN. 2010. Absence of xenotropic murine leukaemia virus-related virus in UK patients with chronic fatigue syndrome. Retrovirology. 7(10).

Infectious Mononucleosis. WebMD. Healthwise, Inc. Revised 8 September 2009.

van Kuppeveld FJM, de Jong AS, Lanke KH, Verhaegh GW, Melchers WJ, Swanink CMA, Bleijenberg G, Netea MG, Galama JMD, van der Meer JWM. 2010. Prevalence of xenotropic murine leukaemia virus-related virus in patients with chronic fatigue syndrome in the Netherlands: retrospective analysis of samples from an established cohort. British Medical Journal. 340(1018).

Lombardi VC, Ruscetti FW, Gupta JD, Pfost, MA, Hagen KS, Peterson DL, Ruscetti SK, Bagni RK, Petro-Sadowski R, Gold B, Dean M, Silverman RH, and Mikovits JA. 2009. Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome. Science. 326(5952): 585-589

Malaise. 2010. Merriam-Webster Dictonary Online.

Retrovirus. 2010. Merriam-Webster Dictonary Online.

Xenotropic Murine Leukemia Virus-related Virus (XMRV). Center for Disease Control and Prevention. U.S. Department of Health and Human Services. Revised 18 February 2010.

Aspirin for Heart Attack: What’s Next, Tylenol for Alzheimer’s Disease?

Student guest post by Ron Bedford

The NYT (Kolata, 2010) recently published a story we’d all like to believe in. After their “lab’s usual end-of-the-week beer hour,” two Harvard neurology researchers noticed similarities between not only genes associated with both the innate immune system and Alzheimer’s disease (AD), but structures, characteristics, and actions of selected proteins as well. Dr. Rudolph E. Tanzi, Dr. Robert D. Moir, and their team found “striking similarities” between the well-known innate immune system protein, LL-37, and amyloid β-protein (Aβ), long considered a waste product with no apparent function, which “is believed to be the key mediator of AD pathology” (Soscia et al., 2010) What a heart-warming, at least to research scientists, story: after beers, a couple of smart guys put two and two together to notice that a protein of no apparent purpose may be associated with both the innate immune system and AD, the most common form of dementia, affecting 5.3 million patients, with costs of 172 billion dollars annually, and the seventh-leading cause of death (all U.S. statistics) (Alzheimer’s Association, 2010).

But wait, it may get even better. In BioMed Central’s Journal of Neuroinflammation, Debjani Tripathy and Paula Grammas report research suggesting that acetaminophen, a very common over-the-counter medication in the U.S., may have “a heretofore unappreciated therapeutic potential … in neurodegenerative diseases such as AD that are characterized by oxidant and inflammatory stress” (Tripathy & Grammas, 2009) A couple smart women at Texas Tech University may be onto something, too.

Soscia et al. conducted in vitro experiments to determine whether Aβ could have antimicrobial properties similar to LL-37. Their results support the hypothesis that Aβ may function in the innate immune system as an antimicrobial peptide (AMP) effective against “at least eight common and clinically relevant microorganisms.” While their research focused on the potential of β-amyloid as an AMP, the authors also acknowledge the large body of literature on the role of the innate immune system in mediating neuroinflammation related to AD and its possible association with Aβ. This is where the acetaminophen research may come in.

Tripathy and Grammas report that in addition to its association with neuroinflammation, β-amyloid evokes oxidative stress and directly damages neurons. They also state that while the interactions of all these mechanisms are not fully understood, current AD treatments focus on reducing oxidative stress and inflammation. The Texas Tech researchers pretreated rat neuronal cultures with acetaminophen and treated the cultures with menadione, “an agent that releases superoxide” or hydrogen peroxide (H2O2). The cultures pretreated with acetaminophen showed significantly improved survival compared to cultures not treated with acetaminophen (Tripathy & Grammas, 2009).

The research by Tripathy and Grammas also measured the effectiveness of acetaminophen at reducing inflammatory protein (cytokine and chemokine) release brought about by menadione treatment. Acetaminophen treated cultures showed significant reductions in the release of each of the cytokines and chemokines tested. Additionally, acetaminophen was shown to down-regulate expression of apoptotic proteins and up-regulate expression of anti-apoptotic proteins in response to menadione treatment.

Tripathy and Grammas acknowledge that much remains to be learned about the complex interactions of the innate immune system in the setting of neurodegenerative diseases. Certainly there are trade-offs to be weighed and measured between the hypothesized protective antimicrobial effects of Aβ, which was until recently regarded as a waste product, and the potential benefits of decreasing its inflammatory and oxidative effects on neuronal tissue.

No one is suggesting that in vitro rat brain cultures are the same as live human AD brain or that menadione or H2O2 perfectly represent the oxidative and inflammatory stressors that occur in conjunction with AD. But the possibility that a medication as ubiquitous as acetaminophen could potentially hold promise for the treatment of AD has to at least pique the interest of researchers in the field, except maybe those pursuing the next “latest and greatest” million dollar medication.

As always, more research is called for, both in new and cutting edge technologies as well as application of more traditional treatments in novel methodologies.


Alzheimer’s Association. (2010). 2010 alzheimer’s disease facts and figures. Retrieved 04/14, 2010, from

Kolata, G. (2010, 3/8/2010). Infection defense may spur Alzheimer’s. The New York Times, from

Soscia, S. J., Kirby, J. E., Washicosky, K. J., Tucker, S. M., Ingelsson, M., Hyman, B., et al. (2010). The alzheimer’s disease-associated amyloid beta-protein is an antimicrobial peptide. PloS One, 5(3), e9505.

Tripathy, D., & Grammas, P. (2009). Acetaminophen inhibits neuronal inflammation and protects neurons from oxidative stress. Journal of Neuroinflammation, 6, 10.

What’s in Your Genes?

Student guest post by Liz Stepniak

In the field of chronic disease, genetics has long been determined as a component of disease susceptibility. Infectious disease was believed to be caused by an agent of infection, such as a virus or bacteria which comprises a large environmental factor. In the past decade or so, this view has been expanded to include an important genetic factor as well.

There has been scientific evidence supporting the controversial idea that one error in a single gene can significantly alter the individual’s risk of obtaining a bacterial infection. Can infectious disease develop as a result of such genetic vulnerabilities? This idea was met with resistance from the microbiology field, which stresses that infectious diseases are strictly environmental. Immunologists have also viewed this idea with skepticism; since adding this component opens a large area of re-exploration for the possibilities of interactions between a range of microbes and certain immunological molecules. The positive implications of further research in this area is that it allows for a more complete and accurate way of treating infection. This also opens the door to further explanation of the immune system as a target for treatment instead of just the bacteria causing the infection.

There are many important components of infectious disease, but I’m going to focus on disease severity for the research I’m going to discuss further. This is by no means an exhaustive commentary, merely a discussion of a few papers I found interesting while I was looking into this topic and what it could bring to the scientific and medical worlds:
A study published in December 2008 took the first look into genetic determinants of severity of acute infectious illnesses. These researchers found that high-risk gene combinations made certain individuals 8 times more likely to suffer from a severe and prolonged illness. Another interesting result from this paper was that the converse was also true, a certain gene combination acted protectively; with these individuals having a less severe, shorter illness. I thought this was an interesting paper because in the future, it may be possible to identify those individuals at high-risk and provide prevention and more appropriate treatment for common infectious disease.

Recent research findings from Rockefeller University and the Necker Medical School that supports this idea has identified a new gene mutation that causes children to be more susceptible to mycobacterial diseases. Mycobacterium infection can lead to diseases like leprosy or tuberculosis. This January 2010 paper suggested that this mutation disrupts IFN- γR1, which is responsible for making a receptor for interferon γ, a molecule that leads the immune cells to form an attack on a foreign organism. It has been found that when this receptor is absent or not fully functional, an immune system pathway that specifically targets mycobacterium is disrupted. This was a small study, only done in 118 patients with complete or partial IFN-γR1 deficiency; but 33 different IFN-γR1 mutations were found among these patients.

A researcher conducting this study explained that the severity of the disease depended on the severity of the deficiency, and that for this deficiency; there was little difference between partial and complete deficiency leading to a dramatic increase in the severity of the mycobacterial disease. For one young patient, the researchers sequenced the genes of this patient and her healthy family members. They found that each parent had one copy of the mutation located on the initiation codon. This article also provided further evidence to the idea that an error in a single gene may be enough to radically alter individual risk for bacterial disease. This research group, led by Jean Laurent Casanova has also conducted research studies showing underlying genetic vulnerabilities to other infectious diseases including pneumococcal disease and herpes simplex encephalitis.

I found this topic interesting because a lot of important efforts focus on altering environmental factors that cause disease but the strong presence of a genetic component just keeps sneaking into all forms of disease and illness and adding a complexity to understanding and treatment. It just goes to show how interactive the battle between the human body and infectious agents has become! While there have been multiple studies demonstrating the important role of genetics in infectious disease, there is further evidence needed to better understand the multifaceted puzzle that results from the interactions of genetics, environments, and infectious agents with regards to all disease components. As with most research, the more discoveries investigators make, the more it makes us realize is still out there to be uncovered and understood. Even though this may add to the difficulty of understanding infectious diseases; with more research in this area, the outcome can lead to better treatments and prevention efforts of infectious diseases and more lives saved.

Works Cited:

Kong et al. (2010). A novel form of cell type-specific partial IFN-γR1 deficiency caused by a germ line mutation of the IFNGR1 initiation codon. Human Molecular Genetics, 19 (3): 434-444

Rockefeller University (2010, February 21). Human genetic vulnerabilities may underlie infectious diseases, scientist argues. ScienceDaily

Rockefeller University (2010, January 1). Mutation leads to new and severe form of bacterial disease. ScienceDaily.

University of New South Wales (2008, December 9). Blame Your Genes: Some People Eight Times More Likely To Suffer From Prolonged Illness With Infection. ScienceDaily.

Campylobacter jejuni-Associated Guillain-Barré Syndrome: It’s No Picnic

Student guest post by D.F. Johnston

As the year marches forward, ever closer to that summer sun we missed so much during dreary winter days, we also get closer to the traditional summer picnics and barbecues. Sometimes, in our hurry to enjoy quality time with friends and family, we get distracted from our usual practices for proper food handling. We might try to get little Billy his hamburger before he has time for a full-fledged temper tantrum, so we hurry it along, figuring a tiny bit of pink in the middle won’t be the end of the world. Or we might realize that we’re short a couple of serving spoons and re-use the meat fork for the raw fruit or veggie tray. After all, even if we’re thinking about foodborne illness, a little diarrhea is our biggest worry, right?

Actually, amongst the wide range of microbes that can cause foodborne illness, one of the more common is a Gram-negative bacterium called Campylobacter jejuni, which lives in the intestines (where the name “jejuni” comes from) and it is most often encountered in undercooked poultry or via cross-contamination. This bacterium does cause the well-known symptom of short-term diarrhea and usually resolves on its own over the course of two to ten days or with antibiotic treatment (1). Many people who worry about foodborne illness worry about the well-known salmonellosis or the dreaded E. coli O157:H7. According to the National Center for Zoonotic, Vector-Borne, and Enteric Diseases estimates for the number of cases of shiga-toxin producing E. coli, enterohemorrhagic E. coli, salmonellosis and an Institute of Medicine estimate for enterotoxigenicE. coli, the combined total number of cases occurring each year in the United States is approximately 880,000 (2-5). Ironically, cases of Campylobacter are over 2.5 times more common, as there are approximately 2.4 million cases in the United States each year (6). Campylobacter probably isn’t as infamous as it tends to occur in small clusters like at family picnics, rather than in high-profile outbreaks and recalls.

Unfortunately, discomfort and dehydration are not the only possible consequences of campylobacteriosis. Lindsay mentions temporary arthritis and hemolytic uremic syndrome, which can result in renal failure, as potential consequences of C. jejuni infection (7). Additional chronic conditions associated with prior infection with C. jejuni are mentioned by the Food Research Institute at the University of Wisconsin-Madison and include appendicitis, carditis, Reiter syndrome, and Miller Fisher syndrome, which is a subtype of Guillain-Barré syndrome (8). There are several forms of Guillain-Barré syndrome (GBS), making the range of symptoms wide as well, but some of the more commonly encountered effects are limb and respiratory weakness, and loss of reflexes (9). Several organisms may precipitate GBS, in addition to C. jejuni, such as cytomegalovirus, Epstein-Barr virus, and Mycoplasma pneumoniae, although Campylobacter-associated forms may be more severe in clinical presentation (10, 11). Typically, GBS associated with C. jejuni follows 1-3 weeks after infection and patients generally recover within weeks to months (11). However, there is a 2-3% mortality rate and 20% of GBS cases may have significant and lasting neurologic effects (12). Between 30-50% of all GBS cases are linked to C. jejuni infection (12).

Since there are several forms of clinical presentation for GBS, the forms also differ in hypothesized mechanisms for how the disease is caused or what part of the nerve cell is directly affected (i.e. the myelin sheath versus the axon or T-cell mediated versus antibody-mediated) (11). Despite this, the current conception for all types is of GBS being caused by the immune system reacting to an external factor (such as C. jejuni) to the degree that human cells become collateral damage in one form or another. One of the more popular theories is that part of a molecule on the surface of the bacterium is very similar to those found on nerve cells in the human body, leading to an antibody attack on nerve cells even after the Campylobacter has been eliminated. This mechanism is further supported by the other agents suspected in causation of GBS since they also have a similarly-shaped molecule on their surface (11). The paralysis or muscle weakness may occur because the immune system breaks open the protective Schwann cells surrounding the nerves, allowing enzymes to begin breaking down the myelin “insulation” of nerve axons that help ensure reception and speed of nerve impulses (11).

The first causal relationship for C. jejuni and GBS was hypothesized in 1982 based on a case report and similar reports continued after this (11). Isolation and growth of Campylobacter from the stool of GBS patients also supported such a relationship, but was assumed to underestimate bacterial presence, as time from initial infection to culture and culture methodology could strongly influence recovery of the bacterium (11). Lab techniques to detect antibodies to C. jejuni have also been used to demonstrate presence of the organism in GBS patients, although this technique is subject to cross-reaction with closely related bacteria (11). That GBS appears 1-3 weeks after bacterial infection (the time it takes to produce an antibody response) also supports an infectious event leading to GBS. Animal models have strengthened support for the association, as rabbits and mice have been injected with molecules similarly shaped to those of C. jejuni and have developed high titers of antibodies that also react against nerve cells (11, 12). The NIH appears to accept the role of Campylobacter in GBS etiology and has moved to outlining steps for improving mechanistic knowledge (11); the published literature also reflects this general acceptance.

This summer, my family reunion is going to use safe food handling techniques in an attempt to lower my family’s risk for the unpleasantness of campylobacteriosis and the subsequent risk for Guillain-Barré syndrome and other Campylobacter-associated chronic conditions. Have a look at the USDA guidelines for proper food handling and enjoy your summer pursuits (13).

Works Cited

1. Ang, J.Y. & Nachman, S. 2009. “Campylobacter Infections.” eMedicine.

2. National Center for Zoonotic, Vector-Borne, and Enteric Diseases. 2009. “Escherichia coli O157:H7.” Centers for Disease Control and Prevention.

3. National Center for Zoonotic, Vector-Borne, and Enteric Diseases. 2009. “Enterohemorrhagic Escherichia coli: Technical Information.” Centers for Disease Control and Prevention.

4. National Center for Zoonotic, Vector-Borne, and Enteric Diseases. 2009. “Salmonellosis.” Centers for Disease Control and Prevention.

5. Stratton, K.R., Durch, J.S., & Lawrence, R.S (Institute of Medicine). 2000. “Vaccines for the 21st Century: A Tool for Decisionmaking–Appendix 5: Enterotoxigenic E. coli.” National Academies Press.

6. National Center for Zoonotic, Vector-Borne, and Enteric Diseases. 2009. “Campylobacter, General Information.” Centers for Disease Control and Prevention.

7. Lindsay, J.A. 1997. “Chronic Sequelae of Foodborne Disease.” Emerg Infect Dis, 3(4): 443-452.

8. Doyle, M.E. 1998. “Campylobacter–Chronic Effects.” UW-FRI Briefings.

9. Davids, H.R. & Oleszek, J.L. 2010. “Guillain-Barré Syndrome.” eMedicine.

10. Yu, R.K., Usuki, S., & Ariga, T. 2006. “Ganglioside Molecular Mimicry and Its Pathological Roles in Guillain-Barré Syndrome and Related Diseases.” Infect Immun, 74(12): 6517-6527.

11. Nachamkin, I., Allos, B.M., & Ho, T. 1998. “Campylobacter Species and Guillain-Barré Syndrome.” Clin Microbiol Rev, 11(3): 555-567.

12. Moore, J.E., Corcoran, D., Dooley, J.S.G., Fanning, S., Lucey, B., Matsuda, M., McDowell, D.A., Megraud, F., Millar, B.C., O’Mahony, R., O’Riordan, L., O’Rourke, M., Rao, J.R., Rooney, P.J., Sails, A., & Whyte, P. 2005. Campylobacter.” Vet Res, 36(3): 351-382.

13. USDA: Food Safety and Inspection Service. 2010. “Safe Food Handling Fact Sheets.”

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Psychological Disorders Associated with Cerebral Malaria

Student guest post by Laura Vonnahme

As a part of traveling to a developing nation, we are often required to take medical precautions. This generally includes a line-up of shots for various diseases, a few other tests, and various regimens of prophylaxis for possible diseases. I have often left these doctors appointments with a line of band-aids on my arm, a handful of prescriptions and a little weakness in my knees. However, I will readily admit that my malaria prophylaxis is often pushed to the back burner; in fact the last time I went to a developing nation, I didn’t even get the malaria prophylaxis until I was in the country and I didn’t even bother taking it for the prescribed amount of time. However, as I readily admit my shortsightedness in the past, I have become more aware of the chronic conditions that can be caused by a single malaria infection.

Malaria is a mosquito-borne disease caused by a parasite, and there are four different species of parasites that cause malaria, Plasmodium falciparum (which is the most fatal), P. vivax, P. malariae, and P. ovale. When initially infected, parasites first enter the liver, then multiply quickly and enter the bloodstream, where they continue to multiply and rupture blood cells2. While P. falciparum causes the most severe symptoms, P. vivax and P. ovale can cause chronic malaria which is characterized by profound anemia, enlargement of the spleen, emaciation, mental depression, sallow complexion, edema of ankles, feeble digestion, and muscular weakness.

In addition, there is a more serious form of malaria caused by P. falciparum, called cerebral malaria, which can be deadly quickly if left untreated. However, a more controversial disease has been linked to malaria as of late. Recently there have been links to cerebral malaria, posttraumatic stress disorder (PTSD) and other psychological disorders in soldiers who have returned from service in areas where malaria is endemic. In particular several studies have been conducted on soldiers who had contracted malaria while in service during the Vietnam War. Dr. Nils R. Varney conducted one of these first studies here at the University of Iowa and reported that many cerebral malaria survivors from the Vietnam War have a number of neuropsychiatric symptoms that can persist for years after the acute illness has been treated. “Cerebral malaria does a number of different things to a patient’s brain that cause a variety of neurological problems,” Varney says. “…patients who survived the illness frequently developed depression, impaired memory loss, personality change and proneness to violence as long-term effects of the disease. These are symptoms that have been reported by many Vietnam veterans for years and are often treated strictly as PTSD.”

The journal article compared the neuropsychiatric status of 40 Vietnam combat veterans who contracted cerebral malaria between 1966-1969 with 40 Vietnam veterans with similar wartime experience who suffered gunshot or shrapnel wounds during the same period. The participants underwent numerous tests for sensory, cognitive and behavioral symptoms. Findings indicate that cerebral malaria results in multiple, major, substantially underappreciated neuropsychiatric symptoms in Vietnam veterans, including poor dichotic listening, “personality change,” depression, and, in some cases, partial seizure-like symptoms. Findings strongly suggest that history of malaria should be considered in any medical, psychological, or psychiatric workup of a Vietnam War veteran because a positive response could result in substantial changes in diagnosis and treatment. Interestingly, these results seen in Vietnam veterans are similar to those seen in British troops stationed in India during in the 19th century during the height of the British Empire. Nineteenth-century physicians documented these cases and considered malaria a leading cause of mental illness in British-occupied regions

Therefore, continued prophylaxis is extremely important for anyone traveling to an area where malaria is thought to be endemic. Thus, while you may think prophylaxis is a nuisance, the pills make you have weird dreams, you cant remember to take the pill every week or you just plain think your invincible, none of these are valid excuses for skipping a necessary malaria prophylaxis.


1. CDC – Malaria. (n.d.). Centers for Disease Control and Prevention. Retrieved April 11, 2010, from

2. Malaria. (n.d.). Penn State Hershey. Retrieved April 11, 2010, from

3. UI/VAMC study says patient’s history of malaria may be a clue to many Vietnam vets’ psychological and other health problems. (n.d.). Retrieved April 11, 2010, from

4. Varney, N., Roberts, R., & Springer, J. (1997). Neuropsychiatric Sequelae of Cerebral Malaria in Vietnam Veterans. The Journal of Nervous & Mental Disease, 185(11), 695-703. Retrieved April 11, 2010, from