Vol 12 Issue 1, March 2003
Dr. Ausio contacted CLSF for permission to use Davis’s picture for an upcoming paper on chromatin remodeling.
In his words to me in email, “Although [the web site article] only talks about Rett syndrome , all what it says on it could be applied to the Coffin-Lowry syndrome. It will give you a good idea of the kind of research that we do in my lab. I am a biochemist who works with chromatin (chromosomes) and therefore my research is at a very basic fundamental level (as opposed to some of the other co-authors in the paper who are Medical Doctors) but we are trying to understand together how this genetic material affects all these syndromes such as Rett, Coffin Lowry and others that affect at children at young age.”
As posted on http://communications.uvic.ca/Ring/03feb06/features/ausio.html
Understanding how DNA and associated proteins interact could revolutionize the prevention and treatment of disease
by Kristi Skebo
You could say that Dr. Juan Ausió works on jigsaw puzzles of infinitesimal dimensions.
His jigsaw board is a cell nucleus—only two millionth of a metre in diameter—and the pieces he works with are strands of DNA and the special proteins associated with them. How the pieces fit together determines who we each are, and what diseases we might be susceptible to in our lifetimes.
Putting the pieces of this puzzle together is Ausió’s life work. The UVic molecular biologist recently received a $500,000 grant from the Canadian Institutes of Health Research (CIHR) to study how structural changes in the DNA and its associated proteins relate to cell function. The work has implications for our understanding of diseases such as cancer and Rett Syndrome.
“How DNA is packaged in a cell nucleus is one of the miracles of life,” says Ausió. In a nucleus, there are 46 chromosomes consisting of two sets of double-stranded DNA. Portions of each DNA molecule are wrapped around specific proteins known as histones. This wrapping causes the DNA to twist around itself, forming coils.
To visualize this structure, think of a telephone cord—each loop represents DNA wrapped around a set of histones. If you stick your finger in a loop and twist it, the cord loops around itself. DNA spends most of its time in the cell in this coiled state known as chromatin.
When a section of chromatin unfolds, it exposes genes and allows them to be switched on, their DNA is read and the corresponding protein is synthesized. What causes a section of chromatin to unravel and which parts of the DNA are read can significantly affect how the cell functions.
“Different chemical changes to the DNA or histones can cause the chromatin to either unfold or to wrap more tightly around itself,” says Ausió. “Genes that are in tightly folded regions of chromatin can’t be expressed.”
Sometimes, mistakes happen. “Genes that are switched on as the result of a chemical miscue can be expressed at the wrong time,” he says. “Mistakes of this sort can lead to unchecked cell proliferation and the formation of tumours.”
In disorders caused by altered hormonal balance, such as breast and prostate cancer, the disease can often be halted if the source of the hormone is removed or by chemotherapy, which interferes with the hormones. But sometimes, several years after treatment, the cancer can reoccur.
“One reason why chemotherapy may fail is that some histones may shift their
position in chromatin during treatment,” says Ausió. “If this happens, the
affected region of the chromatin will likely change its folding configuration,
which may lead to inactive genes becoming active once again, or the opposite.”
To find out if this has occurred, Ausió uses a process known as DNA footprinting.
The unfolded portions of the DNA strand are broken apart and what’s left behind
are regions of DNA that are wrapped around the proteins.
“If we compare the footprint of an unhealthy cell to that of a healthy one and find that the footprints don’t match, then we know that the proteins in the unhealthy cell have moved to a spot on the chromatin fibre where they shouldn’t normally be. This means that chromatin may play a greater role in genetically linked diseases than we originally thought,” says Ausió.
Sometimes, chemical modifications to the DNA or proteins can lead to the chromatin fibre being folded even more tightly, suppressing the expression of genes required for normal cell function. “By studying chemical modifications made to the DNA and proteins, we can determine what causes the chromatin to coil even more tightly and hide genes, or to unfold and expose genes.”
To detect changes in chromatin folding, Ausió uses an analytical ultra-centrifuge, a state-of-the-art instrument purchased with a $1.3 million grant from the Canadian Foundation for Innovation (CFI) and the B.C. Knowledge and Development Fund.
In his work with Rett syndrome, a fatal disease that affects the motor skills of young girls, Ausió studies the chromatin misfolding that alters the expression of genes needed for nerve cells to function properly.
“A mutation to a highly specialized chromatin-binding protein is involved in this disease. This mutated protein is found in every cell in the body, so the same mistake is made in every cell, but it affects only the function of nerve cells. Most cells don’t need the genes encoded in the chromatin region affected by this protein, but nerve cells do.”
The potential for Ausio’s work is enormous. “If we can precisely determine what chemical modifiers cause chromatin to change its structure, ultimately activating or hiding certain genes, then pharmaceutical companies will be able to design drugs that target the proteins that make incorrect chemical modifications.”
Kristi Skebo wrote this story as a participant in the SPARK program (Students Promoting Awareness of Research Knowledge), funded by UVic, the Natural Sciences and Engineering Research Council, and the Social Sciences and Humanities Research Council.
Finish each day and be done with it. You have done what you could; some blunders and absurdities have crept in; forget them as soon as you can. Tomorrow is a new day; you shall begin it serenely and with too high a spirit to be encumbered with your old nonsense.
~Ralph Waldo Emerson
Circle of Friends
In a wonderful gesture of parents reaching out to other parents, Greg and Lissa Walter worked with their local Lions Club, of which Greg is a member, to collect $350 for Jacqueline Blyth in Bedford, UK. Jacqueline’s son Mark has CLS and was in need of funds for transportation to London for her son’s visit to a specialist.
The Walters worked with a Lions club contact in the UK, Giorgio Garofalo, and got the funds to Jacqueline through him. They are holding any excess funds for Jacqueline’s future medical expenses.
-MCH
From the Bedford Lions Club 105A in England
12/23/2002
To Greg [and Lissa] Walter & to all the members of Ham Lake Lions Club of
Minnesota, USA.
It is my pleasure to report to you that Bill Jennison, our Welfare Chairman from
the Bedford Lions Club, last night visited Jaqueline Blythe, whose young son
needs hospital care. Bill informed her that the funds for her and her son
[Mark—age 7] are now available, thanks to your remittance of 350 USD. So she can
make definite arrangements for visiting the hospital in London.
As a result of the generosity of the Ham Lake Lions Club and Lions International
co-operation, this family, consisting of a mother and two young children, can
now enjoy a more serene Christmas. Because they know that the travel costs for
attending the hospital in London, is covered.
On behalf of Bedford Lions Club, please accept our gratitude for your kind
gesture.
We also send you our Greetings. Wishing you joy and serenity during the Festive
Season, for you and your families, with even more prosperity and happiness in
2003.
Giorgio Garofalo
Ila Alldredge
Minden, NV
This is
a picture of Zenny and younger brother, Blaze, taken with Santa, Christmas before last, Dec. 2001. He has grown a lot
now and is quite a young man with a very deep laugh. He is still hanging in
there with his bum heart and trying very hard to be the same old perpetual
motion machine that he has always been. However he really gets tired now and
usually goes to bed very early.
He dearly loves his family, especially the youngest brother, Jett, now 15 mo. Zen has another doctor appt. March 19, his dad's birthday. And if he can hang on long enough he'll have another little brother about the third week in June. They recently finished building their new house and moved in. It's on ten acres so they have plenty of room. The views of the mountains all around are awesome from there. Thought you might like to see what Prince Charming looks like!
Mark & Christine Hawthorne
Bangor , Co. Down, Northern Ireland
Hi Mary
Just to let you know that we got the results that Christine my wife is a carrier. Also our concerns for my daughter Rebekah who is 3 that she also has CLS. She has been refered to the geneticist and that will confirm if she is or not. She has the facial features and hands etc. At the end of the day you just get on with it.
I have had contact with a lady from Wales, Kerrie Ann Thomas.
Still lonely here as we are on our own.
Matthew is doing well.
The Hiryama's shared a picture of their two children:
Davis is starting a trial of Lamictal (limotrigine) for his drop attacks. Sherry Barber has reported that a combination of Lamictal and Clorazepate is 100% effective in treating drop attacks in one of her two children with CLS. It is only about 80% effective in the other. Lamictal and Clorazepate have different mechanisms and it may be that a combination of drugs might be the answer, although it might not be exactly the same combination for everyone. - MCH
Vince Daniels, age 10, died on February 12, 2003 at the Southland Villa nursing home in Temple, Texas where he was a resident. He is survived by his parents, Francis and Cecil Daniels, and his brother, Eric.
The cause of death is under investigation, but is an apparent cardiac arrest.
If you wish to send condolences, the family may be reached at:
Francis & Cecil Daniels
301 S. Hill Street
Burnet, TX 78611
512-756-8217
cfev4@281.com
Pronounced: LAM-ic-tal
Generic name: Lamotrigine
Lamictal is prescribed to control partial seizures in people with epilepsy. It is used in combination with other antiepileptic medications or as a replacement for a medication such as Tegretol, Dilantin, phenobarbital, or Mysoline.
You may develop a rash during the first 2 to 8 weeks of Lamictal therapy, particularly if you are also taking Depakene. If this happens, notify your doctor immediately. The rash could become severe and even dangerous, particularly in children. A slight possibility of this problem remains for up to 6 months.
Take Lamictal exactly as prescribed by your doctor. Taking more than the prescribed amount can increase your risk of developing a serious rash. Do not stop taking this medication without first discussing it with your doctor. An abrupt halt could increase your seizures. Your doctor can schedule a gradual reduction in dosage.
Side effects cannot be anticipated. If any develop or change in intensity, tell your doctor as soon as possible. Only your doctor can determine if it is safe for you to continue taking Lamictal.
More common side effects may include:
Blurred vision, dizziness, double vision, headache, nausea, rash, sleepiness,
uncoordinated movements, vomiting
Less common side effects may include:
Abdominal pain, accidental injury, anxiety, constipation, depression, diarrhea,
fever, "flu-like" symptoms, increased cough, inflammation of vagina,
irritability, painful menstruation, sore throat, tremor
Rare side effects may include:
Absence of menstrual periods, chills, confusion, dry mouth, ear pain, emotional
changes, heart palpitations, hot flashes, joint disorders, memory decrease, mind
racing, muscle weakness, muscle spasm, poor concentration, ringing in ears,
sleep disorder, speech disorder
If you are sensitive to or have ever had an allergic reaction to Lamictal, you should not take this medication. Make sure your doctor is aware of any drug reactions you have experienced.
Lamictal may cause some people to become drowsy, dizzy, or less alert. Remember to be alert for development of any type of rash, especially during the first 2 to 8 weeks of treatment.
Be sure to tell your doctor about any medical problems you have before starting therapy with Lamictal. If you have kidney or liver disease, or heart problems, Lamictal should be used with caution.
Lamictal may cause vision problems. If any develop, notify your doctor immediately. Also be quick to call your doctor if you develop a fever or have any other signs of an allergic reaction. Notify your doctor, too, if your seizures get worse.
Lamictal is often combined with other medications
used to treat epilepsy, including the following: Carbamazepine (Tegretol)
Phenobarbital (Donnatal, Quadrinal, others), Phenytoin (Dilantin), Primidone (Mysoline),
Valproic acid (Depakene)
Be sure to check with your doctor before combining any other drugs with your seizure medications. Lamictal, in particular, may inhibit the action of sulfa drugs such as Bactrim, Proloprim, and Septra.
CHILDREN Doses for children under 12 are based on the child's weight. Children 12 to 16 receive the adult dose. Doses are increased gradually from a low starting level to limit the risk of severe rash. Lamictal is not used as a replacement drug for children under 16.
A massive overdose of Lamictal can be fatal. If you suspect an overdose, seek medical treatment immediately. Symptoms of Lamictal overdose may include: Lack of coordination, rolling eyeballs, increased seizures, decreased level of consciousness, coma, delayed heartbeat
Everybody can be great. Because anybody can serve. You don't have to have a college degree to serve. You don't have to make your subject and your verb agree to serve.... You don't have to know the second theory of thermodynamics in physics to serve. You only need a heart full of grace. A soul generated by love.
- Martin Luther King, Jr.
Remembering Carolyn Scowcroft
Carolyn Stokes Kenney Scowcroft, wife of Milton W. Scowcroft of Mount
Pleasant, SC died Saturday evening, February 1, 2003 in a local hospital. A
private memorial service will be held at a later date in Bristol, Rhode island.
Mrs. Scowcroft was born August 10, 1924 in Bristol, Rhode Island, daughter of Pardon R. and Marguerite Stokes Kenney.
She attended the University of Vermont for two years and later graduated from Katherine Gibbs Secretarial School in Providence, R.I. She then was Secretary to the Librarian of the Rhode island School of Design. Her love of books later led her to volunteer work in public libraries in Orange, Ct, Lancaster, PA, Weston CT and Summerville, SC. She loved all sports (particularly as a devoted little-league mom). She especially loved baseball and golf. She was totally dedicated to her two grandchildren.
Surviving are her husband of Mount Pleasant, SC, two sons, Robert J. Scowcroft and his wife, Judith Fried of Santa Cruz, CA and Peter K. Scowcroft and his wife, Nancy Lafargue of Crosby, TX, two grandchildren, Katy Scowcroft and Ian Scowcroft, both of Santa Cruz, CA.
In lieu of flowers, gifts may be made to the Coffin-Lowry Syndrome foundation, c/o Mary C. Hoffman, 3045 255th Avenue, S.E., Sammamish, WA 98075.
I would like to thank the following families who have donated generously towards CLSF operating expenses:
The following families made gifts in memory of Caroyln Scowcroft, grandmother of Ian Scowcroft who has CLS:
Send your donations to:
Coffin-Lowry Syndrome Foundation
c/o Mary Hoffman
3045 255th Ave SE
Sammamish, WA 98075
(U.S. Funds, please)
Your child’s neurologist may recommend one or both of the following tests. Davis
is currently undergoing both, so I thought this information might be useful to
others. I will let you know the results when I have them.—MCH
What are somatosensory evoked potentials (SSEP)?
Somatosensory evoked potentials evaluate the nerve pathway from the peripheral
nerve in the arms and legs through the spine to the brain. Electrodes are
attached to the scalp and at various other points along the nerve pathway. A
small electrical current is applied to the skin near a nerve. This current
creates a twitching/pulsating sensation at the patient’s wrist and ankle region.
The current is not painful. Each arm and leg is tested separately.
Why is the SSEP test performed?
Somatosensory evoked potentials evaluate spinal cord injuries or diseases,
neuromuscular disease and demyelineating diseases. It also is used to monitor
the patient during surgical procedures. Test time: 2-3 hours (Length of time
depends on whether the arms, legs or both are tested.)
Patient Preparation
The patient should eat regular meals. The patient should NOT consume coffee
or tea four hours before the test.
The patient should wear comfortable clothes, avoiding things such as pantyhose.
The patient needs to continue taking prescribed medications regularly, unless
otherwise instructed by their physicians.
Removing Electrodes
After the test the electrodes and paste that was used will be removed with
warm water and a washcloth. Normal washing of the hair will remove any leftover
residue of paste.
Test Results
The patient will learn the test results from either their neurologist or
from the copy of the SSEP report sent to their personal physician.
For more information, visit http://www.vmmc.org/dbNeurophysiology/sec1827.htm
Electrodiagnostic medicine studies diseases of the nerves and muscles. The
EMG your doctor has recommended is a test that studies if your muscles and
nerves are working right. You can have problems with your muscles and nerves in
only one part of your body or throughout your body. The EMG doctor examines you
to decide what tests to do. The results of the tests will help your doctor
decide what is wrong with you and how it can be treated.
Who does the testing?
The American Association of Electrodiagnostic Medicine’s policy is that an
appropriately trained doctor should do all needle EMG (electro-myography)
testing. A trained assistant, a technologist, under a doctor’s supervision can
do nerve conduction studies (NCSs).
What kind of medical training do doctors who do EMGs have?
Doctors who do EMGs go to 4 years of medical school; and then have 3 or 4
more years training in a residency program. Most work as neurologists or
physical medicine and rehabilitation doctors. Medical training helps the doctor
decide which tests to perform based on your problems. It teaches doctors the
many things that can go wrong with the human body and how to tell the difference
between these things.
Why am I being sent to the EMG Lab for tests?
You are being sent to the lab because you have numbness, tingling, pain,
weakness, and/or muscle cramping. Tests that are used by the doctors in the lab
are NCSs, needle EMG, and evoked potentials.
Nerve Conduction Studies
NCSs show how the body’s electrical signals are traveling to a nerve. This
is done by applying small electrical shocks to the nerve and recording how the
nerve works. These shocks cause a quick, mild tingling feeling. Several nerves
may be tested.
Needle EMG (Electromyography)
For this part of the exam, a small, thin needle is inserted into several
muscles to see if there are any problems. Disposable needles are used for each
patient. There may be a small amount of pain when the needle is put in. The
doctor examines only the muscles necessary to decide what is wrong. The doctor
will look at and listen to the electrical signals that travel from the needle to
the EMG machine. The doctor then reads these signals.
Evoked Potentials
Evoked potentials are painless tests that check the nerve pathways through
the spinal cord or from the eyes and ears. The signals for these tests can come
from small electrical shocks, light pulses, or clicks of sound in the ears. The
nerve responses are recorded over the scalp and other areas of skin.
How long will these tests take?
The tests usually take 20 to 90 minutes. You can do any of your normal
activities, like eating, driving and exercising, before the tests. You also can
do your normal activities after the tests. There are no lasting side effects.
How should I prepare for the tests?
Tell the EMG doctor if you are taking aspirin, blood thinners like Coumadin,
have a pacemaker, or have hemophilia. Take a bath in order to remove oil on your
skin. Do not use body lotion on the day of the test. If you have Myasthenia
Gravis, ask your EMG doctor if you should take any medications before the test.
When will I know the test results?
The EMG doctor will send your test results to your referring doctor. After
the exam, check with the doctor who sent you to the lab for the next step in
your care.
Copyright © revised September 1999. American Association of Electrodiagnostic Medicine. All rights reserved.
For more information, visit http://www.aaem.net/aaem/patientinfo/patientinfo.cfm
If you want to be happy, be. ~Leo Tolstoy