Despite their heavyweight name, SUMO proteins are a family of small proteins found in our cells, which, by sticking to other proteins, can regulate all sorts of cellular goings-on.
For example, sticking a SUMO protein onto another protein can shuttle it to a different location in the cell, or alter how it works.
And there’s tantalising evidence [...]... Read more »
Morris, J., Boutell, C., Keppler, M., Densham, R., Weekes, D., Alamshah, A., Butler, L., Galanty, Y., Pangon, L., Kiuchi, T.... (2009) The SUMO modification pathway is involved in the BRCA1 response to genotoxic stress. Nature, 462(7275), 886-890. DOI: 10.1038/nature08593
Galanty, Y., Belotserkovskaya, R., Coates, J., Polo, S., Miller, K., & Jackson, S. (2009) Mammalian SUMO E3-ligases PIAS1 and PIAS4 promote responses to DNA double-strand breaks. Nature, 462(7275), 935-939. DOI: 10.1038/nature08657
It’s been a bumper week for cancer research. As we report elsewhere, scientists have been delving deep into our cells’ DNA repair mechanisms, and finding out how they tick.
At the opposite end of the spectrum, two more papers published in Nature today look at what happens when DNA repair goes wrong, by mapping DNA damage [...]... Read more »
Pleasance, E., Cheetham, R., Stephens, P., McBride, D., Humphray, S., Greenman, C., Varela, I., Lin, M., Ordóñez, G., Bignell, G.... (2009) A comprehensive catalogue of somatic mutations from a human cancer genome. Nature. DOI: 10.1038/nature08658
Pleasance, E., Stephens, P., O’Meara, S., McBride, D., Meynert, A., Jones, D., Lin, M., Beare, D., Lau, K., Greenman, C.... (2009) A small-cell lung cancer genome with complex signatures of tobacco exposure. Nature. DOI: 10.1038/nature08629
Shah, S., Morin, R., Khattra, J., Prentice, L., Pugh, T., Burleigh, A., Delaney, A., Gelmon, K., Guliany, R., Senz, J.... (2009) Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution. Nature, 461(7265), 809-813. DOI: 10.1038/nature08489
One of my personal interests is the relationship between sedentary time (e.g. the amount of time that we spend sitting) and chronic disease risk. Several interesting papers have come out in the past few years suggesting that spending too much time sitting down is a risk factor for obesity, chronic disease, and even death, independent of physical activity levels. In other words, no matter how physically active you are, the more time you spend sitting, the greater your risk of death and disease.
This is a very new area of study, so a lot of questions remain unanswered. For example, consider two situations:
1) An individual who does a 60 minute run every morning, but spends the rest of the day being completely sedentary.
2) An individual who spends all day on their feet, walking and moving at a slow pace, but never raising their heart rate above 100 beats per minute.... Read more »
Dunton, G., Berrigan, D., Ballard-Barbash, R., Graubard, B., & Atienza, A. (2009) Joint associations of physical activity and sedentary behaviors with body mass index: results from a time use survey of US adults. International Journal of Obesity, 33(12), 1427-1436. DOI: 10.1038/ijo.2009.174
The relationship between personality and political preferences is not the simple relation between conservatism and negative personality traits on the one hand and liberalism and positive personality traits on the other hand. Personality is understood as the combination of innate dispositions and personal experiences that guides behavior in a stable and predictive manner. Behavior is [...]
Related posts:Maturation of Personality in Adolescence Haven’t written about adolescence for some time now. The...Are Facebook Users Different? Characteristics of social networking sites It can allow an...The Technology Profile Inventory for Nerds, Geeks, Medbloggers? You have a personality profile but you also have...
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Verhulst, B., Hatemi, P., & Martin, N. (2009) The nature of the relationship between personality traits and political attitudes. Personality and Individual Differences. DOI: 10.1016/j.paid.2009.11.013
Is the research community doing as much as it might to extract value from the diversity in life span amongst mammals? Certainly there are those scientist who would like to be engaged in a great deal more sequencing and biochemical deciphering of long-lived animals. But on the whole, I think that less is taking place in this area of study than might be. See this paper from a noted gerontologist, for example: As impressive as the accomplishments of modern molecular biologists have been in finding genetic alterations that lengthen life in short-lived model organisms, they pale in comparison to the remarkable diversity of lifespans produced by evolution. Some animal species are now firmly documented to live for more than four centuries and even some mammals, like the bowhead whale, appear to survive 200 years or more. Another group of species may not be as absolutely long-lived, but they are remarkably long-lived for their body size and metabolic rate. These species include a number of bats, some of which live for at least 40 years in the wild, as well as the naked mole-rat, which is the same size, but lives nearly 10 times as long as the laboratory mouse. Together...... Read more »
Austad SN. (2009) Methusaleh's Zoo: How Nature provides us with Clues for Extending Human Health Span. Journal of comparative pathology. PMID: 19962715_id
Previously we discussed the neurobiology of falling in love. But this is only the beginning, the process of attraction followed by the attachment process. This process can develop and last for a while or in some cases for ever. Biologically is falling in love the first step in pair formation.
Falling in love is more accompanied [...]
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Sci saw this post recently at Dr. Pal's place, and it rang some major bells in her head. So, I figure, I've got to cover it myself, now don't I.
Lim et al. "Zican-induced damage to mouse and human nasal tissue" PLoS ONE, 2009.
So let's start with a couple of things:
1) What is Zicam?
2) Why was it recalled?
3) What are the possible effects of zinc on the common cold? Read the rest of this post... | Read the comments on this post...... Read more »
Lim JH, Davis GE, Wang Z, Li V, Wu Y, Rue TC, & Storm DR. (2009) Zicam-induced damage to mouse and human nasal tissue. PloS one, 4(10). PMID: 19876403
by David Gorski in Science-Based Medicine
It’s been about a year and a half since I’ve written about this topic; so I thought I’d better update the disclaimer that I wrote at the beginning:
Before I start into the meat of this post, I feel the need to emphasize, as strongly as I can, four things:
I do not receive any funding from [...]... Read more »
Myung, S., Ju, W., McDonnell, D., Lee, Y., Kazinets, G., Cheng, C., & Moskowitz, J. (2009) Mobile Phone Use and Risk of Tumors: A Meta-Analysis. Journal of Clinical Oncology, 27(33), 5565-5572. DOI: 10.1200/JCO.2008.21.6366
Deltour, I., Johansen, C., Auvinen, A., Feychting, M., Klaeboe, L., & Schuz, J. (2009) Time Trends in Brain Tumor Incidence Rates in Denmark, Finland, Norway, and Sweden, 1974-2003. JNCI Journal of the National Cancer Institute. DOI: 10.1093/jnci/djp415
The statistics are everywhere: most of the adults in the United States are overweight or obese. These conditions are, of course, responsible for increased health care costs owing to chronic diseases such as diabetes, high blood pressure, high cholesterol, and heart disease. The patient may pick up some of these excess expenses, but society incurs [...]... Read more »
Anderson, L., Quinn, T., Glanz, K., Ramirez, G., Kahwati, L., Johnson, D., Buchanan, L., Archer, W., Chattopadhyay, S., & Kalra, G. (2009) The Effectiveness of Worksite Nutrition and Physical Activity Interventions for Controlling Employee Overweight and ObesityA Systematic Review. American Journal of Preventive Medicine, 37(4), 340-357. DOI: 10.1016/j.amepre.2009.07.003
Lightwood, J., Bibbins-Domingo, K., Coxson, P., Wang, Y., Williams, L., & Goldman, L. (2009) Forecasting the Future Economic Burden of Current Adolescent Overweight: An Estimate of the Coronary Heart Disease Policy Model. American Journal of Public Health, 99(12), 2230-2237. DOI: 10.2105/AJPH.2008.152595
Clarke, P., O'Malley, P., Johnston, L., & Schulenberg, J. (2008) Social disparities in BMI trajectories across adulthood by gender, race/ethnicity and lifetime socio-economic position: 1986-2004. International Journal of Epidemiology, 38(2), 499-509. DOI: 10.1093/ije/dyn214
Heraclides, A., & Brunner, E. (2009) Social mobility and social accumulation across the life-course in relation to adult overweight and obesity: The Whitehall II study. Journal of Epidemiology . DOI: 10.1136/jech.2009.087692
I’ve had two children – now 19 and 16, and wonderful. At the time of their delivery I can remember both times thinking ‘as long as they’re healthy’ and being not at all worried about having medical intervention if it was needed. My eldest was born with epidural anaesthesia, and my youngest was [...]... Read more »
Lavand’homme, P. (2009) Chronic pain after vaginal and cesarean delivery: a reality questioning our daily practice of obstetric anesthesia. International Journal of Obstetric Anesthesia. DOI: 10.1016/j.ijoa.2009.09.003
Some nagging uncertainties remain on progress in stem cell medicine - and especially progress in reprogramming easily obtained somatic cells into patient-specific pluripotent stem cells. These uncertainties will be answered and addressed in the years ahead, but this one springs to mind today: it is possible that cells from older people may be altered or damaged in ways that prevent their effective use as-is in the sort of autologous stem cell therapies presently envisaged. That would be a setback for the first generation therapies: an entire additional industry would be required to fix or generate cells for use. We'd like to be able to repair arbitrary issues in stem cells anyway, but to have to do it to even get therapies running at all in the elderly would be a blow. So it is reassuring to see papers appearing to show that cells from the old are as good by some measures as cells from the young, once reprogrammed: Human induced pluripotent stem cells (IPSCs) have enormous potential in the development of cellular models of human disease and represent a potential source of autologous cells and tissues for therapeutic use. A question remains as to the biological age of IPSCs,...... Read more »
Suhr, S., Chang, E., Rodriguez, R., Wang, K., Ross, P., Beyhan, Z., Murthy, S., & Cibelli, J. (2009) Telomere Dynamics in Human Cells Reprogrammed to Pluripotency. PLoS ONE, 4(12). DOI: 10.1371/journal.pone.0008124
Very recently, an interesting study was published looking at the risk of early mortality among metabolically-healthy obese individuals – a topic we’ve covered on a number of occasions on Obesity Panacea. The authors of this landmark study published in the journal Diabetes Care are actually close friends of ours (Dr. Jennifer Kuk and Dr. Christopher Ardern), and both are alumni of Queen’s university. Now that the media frenzy surrounding their recent study has subsided, Dr. Kuk was kind enough to answer a few questions about the study and enlighten our readers.
Dr. Kuk is currently an Assistant Professor at the School of Kinesiology and Health Science at York University. Before Dr. Kuk was at York University, she did her PhD in the same lab that I am currently in (Queen’s university). Dr. Kuk has been instrumental in shaping my research interests while at Queen’s and beyond, and over the years has provided tremendous guidance in many areas. I could not be happier to showcase some of her pioneering research on Obesity Panacea.... Read more »
Kuk, J., & Ardern, C. (2009) Are Metabolically Normal but Obese Individuals at Lower Risk for All-Cause Mortality?. Diabetes Care, 32(12), 2297-2299. DOI: 10.2337/dc09-0574
For Sci, the weird science tends to come in spurts (heh heh...heh). There will be times when I am literally digging through Pubmed trying to find ANYTHING ODD AT ALL, and then there are times, like now, when people are tweeting and emailing and g-chatting and all but screaming in my ear with the weird. Got enough crazy sexual crap around here to last for WEEKS.
And a good thing, too, cause it's all about premature ejaculation, and don't we all wish we could last for weeks...
So we get to this week. I was going to cover an amazing dog caper, but this one is so very relevant to LAST week's weird science that I felt they had to follow in sequence. Dog capers next week. Stay tuned.
Waldinger et al. "A multinational population survey of intravaginal ejaculation latency time." J. Sex. Med. 2005.
And I hereby dedicate this post (for better or worse...) to Miriam of the Oyster's Garter (and Seaplex!), who sent Sci the paper within TWO MINUTES of me sending out a desperate tweet for journal access. She was not a bit premature. :) Also, yay Twitter.
Read the rest of this post... | Read the comments on this post...... Read more »
Waldinger, M., Quinn, P., Dilleen, M., Mundayat, R., Schweitzer, D., & Boolell, M. (2005) A Multinational Population Survey of Intravaginal Ejaculation Latency Time. The Journal of Sexual Medicine, 2(4), 492-497. DOI: 10.1111/j.1743-6109.2005.00070.x
Arguably, the genesis of the most recent iteration of the anti-vaccine movement dates back to 1998, when a remarkably incompetent researcher named Andrew Wakefield published a trial lawyer-funded "study" in the Lancet that purported to find a link between "autistic enterocolitis" and measles vaccination with the measles-mumps-rubella (MMR) trivalent vaccine. In the wake of that publication was born a scare over the MMR that persists to this day, 11 years later. Although peer reviewers forced the actual contents of the paper to be more circumspect, in the press Wakefield promoted the idea that the MMR vaccine either predisposes, causes, or triggers autistic regressions. Even though over the next several years, investigations by investigative journalist Brian Deer revealed that not only was Wakefield's research funded by trial lawyers looking to sue vaccine manufacturers for "vaccine injury" when he did his research (for which he is now being charged by the U.K.'s General Medical Council with scientific misconduct), but during the Autism Omnibus trial testimony by a world-renowed expert in PCR technology showed that he was incompetent. Even worse for Wakefield, in February 2009 Brian Deer published a news expose based on strong evidence that Wakefield may very well have falsified data for his Lancet paper.
None of this mattered. Andrew Wakefield still enjoys a cult of personality among the anti-vaccine crowd that no revelation seems able to dislodge, even the revelation that at the time he was both in the pay of trial lawyers and working on his study, Andrew Wakefield was also applying for a patent for a rival measles vaccine. Indeed, the anti-vaccine propaganda blog Age of Autism bestowed upon him last year its "Galileo Award" as the "persecuted" scientist supposedly fighting for truth, justice, and anti-vaccinationism against the pharma-funded or brainwashed minions of the "Church of the Immaculate Vaccination." In the meantime, MMR uptake rates in the U.K. have plummeted over the last decade, far below the level needed for herd immunity, to the point where, last year the Health Protection Agency declared measles to be once again endemic in the U.K., 14 years after the local transmission of measles had been halted.
Since Wakefield's study was released, a number of studies have shown that there is no epidemiologically detectable link between vaccination with MMR and autism, including one by a researcher who once appeared to be a believer in the idea that vaccines are somehow linked with autism, Mady Hornig. Hornig actually tried very hard to replicate Wakefield's 1998 Lancet study, only this time with more children, and she found no link between MMR and autism using methodology similar to Wakefield's. None of this has had any effect on the anti-vaccine movement, except to motivate them to circle the wagons even more, as J.B. Handley of Generation Rescue did when he launched a website called Fourteen Studies, whose sole purpose is to launch fallacious and pseudoscientific attacks on studies failing to find a link between vaccines and autism and to promote the lousy science that gives the appearance of supporting the hypothesis that there is a link between the MMR vaccine and autism and then sliming anyone who points out how deceptive their attacks were.
Last week, yet another study was released investigating whether there is a link between MMR vaccination and autism. Last week, yet another study failed to find a link between MMR vaccination and autism. This week, yet another study is all set to be attacked by Generation Rescue and the anti-vaccine movement. The sad and sordid history of reactions of the anti-vaccine movement to studies that do not support its belief in the unsinkable rubber duck of a myth that vaccines cause autism. This study was published online in The Pediatric Infectious Disease Journal by a group from Department of Epidemiology and Preventive Medicine, Jagiellonian University, Collegium Medicum, Krakow, Poland (a Polish group, my people!) and entitled Lack of Association Between Measles-Mumps-Rubella Vaccination and Autism in Children: A Case-Control Study. It's yet another nail in the coffin of the myth that the MMR causes or contributes to autism. Indeed, this study not only shows that MMR vaccination is not associated with autism but that it may even be protective against autism. True, for reasons I will discuss shortly, I doubt that that latter interpretation is true, but there's no doubt that this study is powerful evidence against the view that there is an association between MMR and autism. Unfortunately, I fear that all the nails in my local Home Depot would not be enough to keep the zombie of this pseudoscience from rising from its grave yet again. Read the rest of this post... | Read the comments on this post...... Read more »
Mrożek-Budzyn D, Kiełtyka A, & Majewska R. (2009) Lack of Association Between Measles-Mumps-Rubella Vaccination and Autism in Children: A Case-Control Study. The Pediatric infectious disease journal. PMID: 19952979
I have no idea how many wrist and ankle fractures occur every year, but I can bet it’s not a small number by any imagination. For most of us, I’m guessing we’d expect to have a fracture, wield a wonderfully-autographed cast, get it removed and go on our merry way – but after reading [...]... Read more »
Linton, S., Buer, N., Samuelsson, L., & Harms-Ringdahl, K. (2010) Pain-related fear, catastrophizing and pain in the recovery from a fracture. Scandinavian Journal of Pain, 1(1), 38-42. DOI: 10.1016/j.sjpain.2009.09.004
Whatever you do, don’t think of a white bear. Go on, close your eyes, relax, but don’t think of a white bear… So, what happened? Most likely, you were overwhelmed by thoughts of a white bear. This mini-experiment highlights the fascinating paradox of thought suppression. That is, once we explicitly try not to think of [...]... Read more »
With the world's leaders currently meeting in Copenhagen to discuss strategies to reduce climate change, one of the world's most prestigious medical journals, The Lancet, has released a series examining the public health benefits of various strategies aimed at reducing greenhouse gas emissions. One of these papers focuses on the impact of widespread adoption of active transportation, and the estimated public health benefit is nothing short of astonishing.... Read more »
Wilkinson, P., Smith, K., Davies, M., Adair, H., Armstrong, B., Barrett, M., Bruce, N., Haines, A., Hamilton, I., & Oreszczyn, T. (2009) Public health benefits of strategies to reduce greenhouse-gas emissions: household energy. The Lancet, 374(9705), 1917-1929. DOI: 10.1016/S0140-6736(09)61713-X
Regular listeners will remember the Science Online London gathering back in August. The day before, Mendeley hosted a pre-conference ‘fringe’ event, organized by Jenny. It turned out to be quite a wild evening, and there is video evidence of shenanigans.
One thing I remember clearly (some of you might be surprised I remember anything from that evening, but anyway) is David Colquhoun getting a tad rabid about PR. The gist was that science doesn’t need PR, it’s a waste of time and money; I don’t remember him saying explicitly PR people are professional liars but that was the impression I came away with.
I thought that was bollocks, and I still do.
PR is necessary not simply because scientists like to eat, and therefore need to be funded, and therefore need to convince various bodies (and by extension the people who influence those bodies) to give them money (and I want to talk a little about about ‘justification’ of research in another post) but also because there are crucial social and public health aspects of what we do. We don’t just have to convince the wider community that a particular piece of research is ‘correct’, but we need to demonstrate—somehow—that it directly affects their health (or their wallet, or whatever).
I’m reminded of this because a friend of mine sent me a link via Facebook last week, saying
Some (including me) would argue that the greatest battles against illness and suffering should be fought on the PR/HR front, rather than purely in the arena of science. You, O Great Stream Feeder in the Gyre of Science Publication, may well have already seen this: RT David McCandless RT @GreatDismal: Emotional Epidemiology Of H1N1
The article is from a medical doctor (or possibly here), and describes the reactions, preconceptions and attitudes of visitors to her clinic in the face of the H1N1 epidemic; or, as she describes it, Emotional Epidemiology. In brief, her patients at first demanded a vaccine against H1N1 (despite not wanting the seasonal jab…) and then, when the vaccine became available, refused it.
It certainly isn’t related to logic or facts, since few new medical data became available during this period. It seems to reflect a sort of psychological contagion of myth and suspicion.
Another report last week backs up my claim. The Daily Express reported that taking aspirin could “significantly reduce” age-related macular degeneration. Sounds great. But let’s see what the NHS has to say:
This is a well-designed and well-conducted study, the results of which have been incorrectly reported in the press. This study found that low-dose aspirin had no effect in preventing age-related macular degeneration, a common cause of sight loss in the elderly.
Far from being a significant reduction, the authors of the reported (large, double-blind) randomized controlled trial took pains to stress that there is no benefit. Indeed,
There are risks associated with taking daily or alternate-day aspirin, which should be weighed against the benefits. Elderly people, to whom this research will be most relevant, are most at risk of gastric irritation if they regularly use aspirin.
What’s going on, here?
In both cases, it’s a failure of PR. It’s not simply a matter of education. It’s a matter of getting things right, and getting that information out there, to the public—via the newspapers or schools or physicians in surgeries. Just as with anthropogenic global warming there is no (serious) debate about the science; it’s a matter of PR. And I know it’s difficult. I have no idea who Jo Willey is (apart from Health Correspondent for the Daily Trainwreck), but I would love to see the press release that she read. Because I also know that they are difficult to get right. On Monday I had to completely re-write a release that we were about to publish because the person who produced the copy got the message of the research completely wrong.
PR is necessary. And it’s hard; perhaps even harder than the science.
... Read more »
Christen, W., Glynn, R., Chew, E., & Buring, J. (2009) Low-Dose Aspirin and Medical Record–Confirmed Age-related Macular Degeneration in a Randomized Trial of Women. Ophthalmology, 116(12), 2386-2392. DOI: 10.1016/j.ophtha.2009.05.031
Empathy is an important asset for a doctor. This ability to appreciate patients’ emotions and express this emotional awareness improves clinical outcomes, professional satisfaction, and patient adherence to medical recommendations, and is believed to significantly improve patient satisfaction. More on empathy and what it is can be read here
There is a significant decline in empathy [...]
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William Bunn, D.O. and Jan Terpstra, M.D. (2009) Cultivating Empathy for the Mentally Ill Using Simulated Auditory Hallucinations. Academic Psychiatry. DOI: 10.1176/appi.ap.33.6.457
The arthritic form of Lyme disease was first reported in the 1970s by Allen Steere, who described the condition in a group of children (and a few adults) residing in and around the town of Lyme, Connecticut. Lyme arthritis can strike when Borrelia burgdorferi introduced into the skin by an Ixodes tick burrows into deeper tissues and ends up in the joints, usually the knee. Swelling results from an inflammatory response to B. burgdorferi residing in the joint. Lyme arthritis is treated with antibiotics, which destroy the bacteria driving inflammation. Unfortunately, arthritic symptoms endure in ~10% of treated patients despite the complete or almost complete eradication of the infection, as determined by negative PCR tests for B. burgdorferi DNA in joint fluid. Such cases are called antibiotic-refractory Lyme arthritis, which can persist for months or sometimes years. In severe cases cartilage and bone erode. Although the pathogenesis of antibiotic-refractory Lyme arthritis could involve persistence of small numbers of B. burgdorferi (or their antigens) in the joints, investigators have been seeking an autoimmune mechanism to explain the prolonged attack on joint tissue by the immune system after the spirochetes have been cleared.Many autoimmune diseases are linked to variants of HLA (immunity) genes such as those encoding the MHC class II complex. Antibiotic-refractory Lyme arthritis is associated with MHC class II variants that are able to bind to fragments of the B. burgdorferi protein OspA (outer surface protein A) encompassing amino acid residues 165 through 173. Antigen-presenting cells whose MHC class II molecules display OspA165-173 peptides on their surface stimulate T cells that recognize the OspA peptide. How OspA165-173-reactive T cells cause autoimmunity has been an area of intensive research, yet a clear answer has not emerged.One potential pathway to autoimmunity is molecular mimicry, in which a cross-reactive host protein in the joint continues to stimulate OspA165-173-specific T cells even after the eradication of B. burgdorferi by antibiotics. Although the simplicity of the molecular mimicry model is appealing, exhaustive efforts to find a cross-reactive autoantigen that stimulates OspA165-173-specific T cells have failed. Moreover, levels of OspA165-173-reactive T cells decline soon after initiation of antibiotic therapy despite continuing arthritis following treatment. Thus, chronic arthritis does not seem to involve molecular mimicry driven by a cross reaction between the OspA165-173 epitope and a self-antigen in the joint. It is possible that molecular mimicry involves another B. burgdorferi antigen that is able to bind the MHC class II variants found in genetically susceptible individuals.Other potential routes to autoimmunity in antibiotic-refractory Lyme arthritis patients emphasize the role of the high levels of key proinflammatory cytokines and chemokines found in their joint fluid, levels even higher than those found in treatment-responsive patients prior to initiation of antibiotic therapy:In a model known as bystander activation, the immune response to OspA165-173 (or another B. burgdorferi antigen) causes an excessive inflammatory response that activates other T cells that react to autoantigens in the joint.The immune system is unable to turn off the intense inflammatory response associated with OspA165-173 after the spirochetes are cleared from the joint.Although much attention has been focused on the role of host genetics, a recent study indicates that the genetics of the pathogen also influences the course of Lyme arthritis. In the July 2009 issue of Arthritis and Rheumatism, Allen Steere and his collaborators showed that antibiotic-refractory Lyme arthritis is associated with different strains of B. burgdorferi. The strains were typed from joint fluid samples collected before or during antibiotic treatment. Among the methods available to group B. burgdorferi isolates, they used the 16S-23S ribosomal RNA intergenic spacer type (RST), of which there are three. Antibiotic-refractory arthritis was defined as joint swelling lasting for at least 3 months after the start of antibiotic treatment. Antibiotic treatment consisted of 8 weeks of oral antibiotics or up to 4 weeks of antibiotics administered intravenously. Joint fluid from all 17 patients in the study tested positive by PCR for B. burgdorferi DNA prior to or during antibiotic treatment.The authors found that all 7 Lyme arthritis patients infected with RST1 strains had the antibiotic-refractory form. Joint fluid was obtained after antibiotic treatment from 5 of the 7 patients; all 5 samples tested negative for B. burgdorferi DNA by PCR. In contrast, 2 of 6 and 3 of 4 infected with RST2 and RST3 strains, respectively, were successfully treated with antibiotics (see the table below from the Jones et al. 2009 article). A larger number of samples is needed to demonstrate that the difference observed between RST1 and RST2 strains is statistically significant, but there is a clear trend towards RST1 infections having the greatest association with antibiotic treatment failure and RST3 having the least, with RST2 having an intermediate effect. The duration of arthritis also depended on the infecting RST strain.How do RST1 strains cause arthritis to persist even after the apparent eradication of the spirochetes by the recommended course of antibiotics? The investigators proposed that RST1 strains provoke a stronger inflammatory response in the joint than RST2 or RST3 strains. Coupled with an immune response to OspA165-173 in genetically susceptible patients, this could cause inflammation to continue at high levels even after elimination of the spirochetes from the joints. RST1 strains may be more likely than the other genotypes to spark intense joint inflammation even in patients who are not genetically prone to antibiotic-refractory arthritis.In future studies, it would be interesting to see if proinflammatory cytokine levels are related to the RST type that infects the joint. Ultimately, researchers need to identify the B. burgdorferi gene or genes whose variation among the RSTs causes the different treatment outcomes of Lyme arthritis.Featured paperJones, K.L., McHugh, G.A., Glickstein, L.J., & Steere, A.C. (2009). Analysis of Borrelia burgdorferi genotypes in patients with Lyme arthritis: High frequency of ribosomal RNA intergenic spacer type 1 strains in antibiotic-refractory arthritis Arthritis & Rheumatism, 60 (7), 2174-2182 DOI: 10.1002/art.24812Other referencesDrouin E.E., Glickstein, L., Kwok, W.W., Nepom, G.T., and Steere, A.C. (2008). Human homologues of a Borrelia T cell epitope associated with antibiotic-refractory Lyme arthritis. Molecular Immunology 45(1):180-189. DOI: 10.1016/j.molimm.2007.04.017Kannian, P., Drouin, E.E., Glickstein, L., Kwok, W.W... Read more »
Jones, K.L., McHugh, G.A., Glickstein, L.J., & Steere, A.C. (2009) Analysis of Borrelia burgdorferi genotypes in patients with Lyme arthritis: High frequency of ribosomal RNA intergenic spacer type 1 strains in antibiotic-refractory arthritis . Arthritis , 60(7), 2174-2182. DOI: 10.1002/art.24812
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