The Diamond Blackfan Anemia Foundation relies on the support of our friends and families to continue our mission of supporting DBA patients, families, and research.
Once again we are asking for your help. Many employers and companies offer their employees an opportunity to donate to an organization through a payroll deduction program or participate in a matching gift program. The payroll deduction programs and United Way payroll designation programs make donating easy. The matching gift programs are a great way to double your contribution! The DBA Foundation is a 501(c)(3) organization and is eligible to take advantage of these generous company-based programs.
To find out if your employer participates in a charitable giving program, it's as easy as visiting your Human Resources Department or checking the company's website. The DBAF is happy to assist you in filling out the necessary paperwork.
Over the last few years, donations received through payroll deductios and matched gifts have markedly increased. We are grateful to our donors and their employers for their continued support. We encourage everyone to take advantage of these workplace options to help maximize your charitable giving.
Please contact the DBA Foundation for further information at DBAFoundation@juno.com
DBA Fishing Tournament
October 9, 2011
1:00 - 5:00pm
Four Oaks, NC
Blood Drive & DBA Fundraiser
October 14, 2011
Schumacher Elementary School
1:00 - 7:00pm
Lea Ann Soto
Kevin J. Gately Foundation
Black Swan Country Club
Shopping Day for DBA
Retail Therapy for a Cure
October 19, 2011
11:00am - 6:30pm
Jack's Fight for a Cure
DBA Dinner & Dance Gala
to benefit DBAC
Orangeville Agricultural Center
Tribute Cards Available
In honor of...
In memory of...
DBA Cookbooks Available
To download your order form:http://issuu.com/bhivemom/docs/cookbook_order_form-pdf
Good Search/Good Shop
Raise money for DBAF just by searching the web and shopping online!
|The Diamond Blackfan Anemia Foundation (DBAF) is committed to keeping you updated and connected to the entire DBA community. The Diamond Blackfan Anemia Foundation is YOUR Foundation! We encourage you to share your ideas, photos, and stories for our website and upcoming newsletters. Contact us at DBAFoundation@juno.com.|
Oral Steroids Linked to Severe Vitamin D Deficiency in Nationwide Study
(reprinted with permission from Albert Einstein School of Medicine)
September 29, 2011 (BRONX, NY) - People taking oral steroids are twice as likely as the general population to have severe vitamin D deficiency, according to a study of more than 31,000 children and adults by scientists at Albert Einstein College of Medicine of Yeshiva University. Their findings, in the September 28 online edition of The Journal of Clinical Endocrinology and Metabolism, suggest that physicians should more diligently monitor vitamin D levels in patients being treated with oral steroids.
"When doctors write that prescription for steroids
Amy Skversky, M.D., M.S.
and they're sending the patients for lab tests, they should also get thevitamin D level measured," said study lead author Amy Skversky, M.D., M.S., assistant professor of pediatrics at Einstein and Montefiore Medical Center, the University Hospital for Einstein.
The severe vitamin D deficiency assessed in this study (defined as levels below 10 nanograms per milliliter of blood) is known to be associated with osteomalacia (softening of the bones), rickets (softening of bones in children) and clinical myopathy (musc le weakness). While there is much debate on the issue, vitamin D levels between 20 and 50 ng/ml are generally considered adequate for bone and overall health in healthy individuals. Steroids have been shown to cause vitamin D deficiency, possibly by increasing levels of an enzyme that inactivates the vitamin.
Smaller studies involving people often prescribed steroids (i.e., children with asthma and patients with Crohn's disease and lupus) have found significantly reduced vitamin D levels in these patients. To further assess this association between steroid use and vitamin D levels, the Einstein researchers carried out the first-ever study of a large, nationally representative sample of people.
The researchers examined data collected from participants who had participated in the National Health and Nutrition Examination Survey 2001-2006. About one percent of the participants answered "yes" when asked if they had used oral steroids during the previous 30 days.
Eleven percent of the self-reported steroid users had severely low vitamin D levels compared with a severe vitamin D deficiency of 5 percent for people not taking steroids - a two-fold increased risk for severe vitamin D deficiency. The risk was particularly pronounced for steroid users under 18, who were 14 times more likely to have a severe vitamin D deficiency compared with young non-steroid users. (Participants who reported using inhaled steroids were not included in the steroid-user group.)
The paper is titled "Association of Glucocorticoid Use and Low 25-Hydroxyvitamin D Levels: Results from the National Health and Nutrition Examination Survey (NHANES): 2001-2006." Co-authors include senior author Michal Melamed, M.D., M.H.S., Matthew Abramowitz, M.D., M.S., and Frederick Kaskel, M.D., Ph.D., all at Einstein; and Juhi Kumar, M.D., M.P.H. at Weill Cornell Medical Center. This research was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institutes of Health and National Center for Research Resources, both part of the National Institutes of Health.
Coming Soon to a Window Near You!
Coming soon! This awesome 5" x 5" window sticker will be available to display on your car, windows, and mirrors. Help spread our message and support our mission.
Michelle Holdren, mother to 11 month old Ethan, will be announcing details shortly. Thanks, Michelle!
Donating is easy and all contributions are tax-deductable. Please visit our Donate Page for details. If you are interested in organizing a fundraiser to benefit the DBAF, please contact us at DBAFoundation@juno.com. THANK YOU!
The DBAF is reaching out to our families and friends to help us to grow and to fulfill our mission. Your gifts of time, talents, and treasure are appreciated and necessary for our continued success.
If you have a talent or area of expertise that you feel may benefit the DBAF, please contact us at DBAFoundation@juno.com. We welcome your ideas!
Take the Challenge ~ Show Us Your Logo
T-shirts, hats, coffee mugs, face paintings, tattoos, bags, pumpkins ... our logo is showing up everywhere! We are thrilled that our beautiful logo is proudly being worn and displayed by patients, families, and friends.
Maddy Lapierre, mom to DBA patient Mark Lapierre, dedicated her time and talent to craft a beautiful hand-made quilt for Camp Sunshine. DBA patients and families signed their names and messages of gratitude and appreciate in every quilted heart, and proudly presented it to Camp Sunshine. The quilt, made with love, will wrap many Camp families in DBA compassion and warm wishes. Thank you Maddy for making this treasured gift possible.
Here's the challenge: we'd like to see how many places we can show off our logo! Snap a picture sporting our logo and send us your story. Draw it, print it out, wear it, wave it, tattoo it, carve it... be creative! Take us to school, on vacation, to the hospital, on a plane, to the game, in your home... anywhere! Show us your logo! Send your photos and stories to DBAFoundation@juno.com.
Our Facebook page posts DBA facts written by DBA nurse, Ellen Muir, RN, MSN, CPON. We are pleased to share these facts with our patients and families. Thanks, Ellen!
We have been working closely with an adult endocrinologist, Dr. Irwin Klein, at the Feinstein Institute for Medical Research, who has done a lot of research studying heart disease in relation to thyroid dysfunction. Being that DBA patients who are chronically transfused have thyroid issues due to iron overload, he has taken an interest in working with us to prevent thyroid disease as well as cardiac failure due to thyroid dysfunction. As we know, other endocrine organs are also affected - pancreas, gonads, pituitary, as well as linear height. Here is a list of recommended labs to monitor and prevent the devastating effects of iron overload in the thyroid, heart, and the effects of diabetes:
T3 uptake (instead of free T4)
IGF-1(monitors acute fluctuations in insulin action and determines inadequate insulin treatment or poor control of dietary intake) NT-proBNP (aids in diagnosis of left ventricular dysfunction in heart failure)
Antithyroid Abs (Antithyroglobulin and AntiThyroperoxidase)
Fructosamine (useful in situations where the A1C cannot be reliably measured - as with transfused persons)
Any questions, please feel free to e-mail me firstname.lastname@example.org or call
Get all the News
To stay "in the know" and to receive all the DBAF's updates, please ensure we have your correct contact information. Complete the secure form at http://www.dbafoundation.org/registration.php
Help us to reach all our families. If you are aware of other DBA families in your area, please encourage them to contact to the DBA Foundation.
Please note that the Diamond Blackfan Anemia Registry (DBAR) and the Diamond Blackfan Anemia Foundation (DBAF), are not allowed to share your personal information. It is necessary to register with both the DBAR and the DBAF.
If you have any questions, or to check on the status of your information, contact Dawn at DBAFoundation@juno.com.
| Steven R. Ellis, PhD|
This month's Journal Club is not a Journal Club per se, as no single manuscript prompted this discourse. Instead, I will use this space to expand on a subject that has been raised before on numerous occasions... p53. I've mentioned p53 in the context of how haploinsufficiency for ribosomal proteins leads to its activation, and how this could account, in part, for the premature death of erythroid progenitors in the marrow of DBA patients (DBAF newsletters; November 2010, April 2011).
What then is p53?
Let us begin with the name. p53... rather dull, don't you think? The p of p53 stands for protein; so alas, p53 is a protein. Proteins in turn are polymers of amino acids that fold into complex three dimensional structures that are capable of a wide range of functions. These functions include antibodies of the immune system, the light harvesting proteins of vision, proteins involved in muscle contraction, thousands of enzymes involved in intermediary metabolism, ribosomal proteins, and the list goes on and on. Proteins are capable of a wide range of functions because of the astronomically large number of structures they can assume. These structures are ultimately dictated by the order of 20 common amino acids along the length of a protein as they are polymerized during protein synthesis. The order of amino acids in a protein is dictated by the gene encoding that protein. The number of amino acids which comprise a protein brings me to the 53 in p53's name. The 53 refers to p53's size, or at least its apparent size, of 53,000 Daltons when analyzed by a routine laboratory gel electrophoresis technique. It is composed of 393 amino acids. This size is not unduly large or small for a protein, and so from a size perspective, p53 is fairly average. Despite its fairly average size there is really nothing average at all about what p53 does. To give you a feel for just how important p53 is, a search for p53 in the scientific literature compiled in PubMed gave 59,781 manuscripts that touched on this protein. For a frame of reference, a similar search for Diamond Blackfan anemia gave 578 hits.
So, what is the function of p53 within a cell? One of the major functions for p53 is as a transcription factor. Transcription is the process by which a sequence of bases in DNA (genes) is converted to a sequence of bases in RNA. RNA then dictates the sequence of amino acids in a protein, through a process known as translation. Transcription factors play a central role in turning genes on and off in response to a vast array of physiological, developmental, and environmental signals 1. The p53 protein gets activated through a variety of signals emanating from various cell stressors including DNA damage, oxidative stress, oncogenic stress, and yes, now even ribosome stress. In response to these stress signals, p53 stimulates the expression of a number of genes, some of which arrest cell division and others of which may function to resolve the stress imposed on the cell. If the stress is too great for the cell to resolve, p53 may also initiate a cell death program. In responding to oncogenic (or cancer promoting) stresses, one can think of the p53 response as putting the brakes on cancer. As such, p53 is classified as a tumor suppressor. It should come as no surprise therefore that p53 is frequently inactivated in human cancers.
So having p53 around is a good thing right? Well yes... and no. Activation of p53 in response to DNA damage or oncogenic stress protects against cancer. But, it has also been proposed that activation of p53 in response to oxidative stress plays a role in aging 2, and as mentioned above, activation of p53 in response to ribosome stress likely contributes to the pathophysiology of
DBA 3. Consequently, just as in the Goldilocks story, p53 has to be maintained at levels that are just right... responding to appropriate signals in its protective role while at the same time being held in check to temper its contribution to pathogenic states.
To maintain p53 at levels that are "just right" while still allowing p53 to fulfill its critical functions, this remarkable protein is shackled with numerous levels of control that often have layers of redundancy. One such level of control is mediated by the protein MDM2, which modifies p53 with a molecule known as ubiquitin. Ubiquitinated p53 is then directed to cellular garbage disposals where p53 is degraded 4. The action of MDM2 on p53 keeps p53 levels relatively low in normal cells that are not exposed to stress. While making and degrading p53 under non-stressful conditions may seem wasteful, this control strategy allows for a rapid response in times of stress. For example, signals resulting from DNA damage disrupt the MDM2/p53 interaction, so p53 is no longer labeled for degradation allowing p53 levels to quickly rise in response to this environmental insult.
The action of MDM2 however, represents only one level of control of p53 function. In addition to ubiquitination, p53 is subject to a large number of chemical modifications that also regulate its function. These modifications include phosphorylation, acetylation, methylation, sumoylation, and neddylation (yes, neddylation) 1. A conservative estimate in a recent publication places the number of confirmed modifications of p53 at 52 5. These various modifications superimpose additional, sometimes overlapping, layers of control on p53 and allow its function to be fine tuned to cellular demands. By dissecting the different signaling pathways that direct these various modifications it may be possible to develop drugs that target a specific pathway of p53 activation while leaving others essentially intact. This approach may allow the development of treatments for pathologies linked to inappropriate activation of p53 without having an unduly high risk of promoting cancer.
By targeting the enzymes that modify p53, the DBA community could tap into a very robust area of drug development. Drugs targeting enzymes that carry out protein phosphoryation have transformed certain deadly cancers to chronic diseases 6. Less specific drugs targeting protein acetylation and methylation have also shown promise in cancer clinical trials with the hope that these drugs will show improved success as they are refined to target more specific modifying enzymes 7.
By learning more about the signaling pathway from ribosome stress to p53 activation, it may be possible to specifically target this pathway, while leaving other pathways to p53 activation largely intact, thereby reducing the cancer risks associated with targeting p53 activation as a possible therapy for DBA.
1. Brooks CL, Gu W. New insights into p53 activation. Cell Res;20:614-621.
2. Yi J, Luo J. SIRT1 and p53, effect on cancer, senescence and beyond. Biochim Biophys Acta;1804:1684-1689.
3. Dutt S, Narla A, Lin K, et al. Haploinsufficiency for ribosomal protein genes causes selective activation of p53 in human erythroid progenitor cells. Blood;117:2567-2576.
4. Vucic D, Dixit VM, Wertz IE. Ubiquitylation in apoptosis: a post-translational modification at the edge of life and death. Nat Rev Mol Cell Biol;12:439-452.
5. Dai C, Gu W. p53 post-translational modification: deregulated in tumorigenesis. Trends Mol Med;16:528-536.
6. Santos FP, Quintas-Cardama A. New drugs for chronic myelogenous leukemia. Curr Hematol Malig Rep;6:96-103.
7. Wanczyk M, Roszczenko K, Marcinkiewicz K, Bojarczuk K, Kowara M, Winiarska M. HDACi--going through the mechanisms. Front Biosci;16:340-359.