MaryO

These are still up from 2002 LOL

Remember, if you want the teddy bear or the coffee mug for Valentine's Day, they need to be ordered by:

Flat Fee Feb. 2nd

Standard Feb. 4th

USPS Feb. 5th

2-Day Feb. 7th

Next Day Feb. 11th

International/Canada Jan. 29th

The bear's TShirt looks like:

I'm not sure if they'll give away the candy again or not.

The coffee mug image is similar but with a larger design:

These and other stuff is available in the Cushie Store

Here's another possible back

Unfortunately, to put the ribbon that high up on the back, there was only 4 inches high allotted to that space. It is 10 inches wide, if you wanted to put something off to the side or maybe the web info very small underneath. Of the 4 inches, I made the ribbon about 3.8 inches high. That could be smaller, but it still wouldn't be possible to move the url any lower than the 4 inch limit.

If it were a regular back, there would be 10 inches of height to play with - but the ribbon wouldn't be over the hump anymore

The web address doesn't have to be on there at all, though.

Good ideas! To put it under the hump would mean that the ribbon would have to be a bit smaller, but that's ok.

Other ideas?

Image changed to make it higher on the front. How's that for speedy service? LOL

So far on the ribbon magnets - I'd have to get a minimum of 125 but there can be 2 colors and a logo on that.

Here's how the images look on a *few* items http://www.cafepress.com/cushingshelp

That neon green looks ghastly! LOL

And a possible front...

I can move the web address up like Jen did. Thoughts?

Here's a back sample. Unfortunately, that's as high as I can get the hump using the CafePress site.

What do you think?

Jayne and I were just talking about doing something here in the metro DC area for the week (or so) after Cushing's Awareness Day. The week before is also Palm Sunday and that's also an incredibly busy time for me with my handbell ringing.

So...if anyone wants to come to the DC area to celebrate, let me know!

Anyone who is planning a Cushing's Awareness Day please post here or let me know so I can add it to the newsletter and the main site - and the calendar on here.

It worked Mary - and I made up a prototype for ya!

 

Thanks, Jen - I was thinking of doing something like that for the front, then a ribbon on the hump like Amber's tattoo.

The question that I have is would people want one that said "survivor" on it or just the ribbon on the hump?

If it said survivor and the hump, would you want the year? That would be a little more tricky, like a special order.

I could make ones with just the ribbon, just the ribbon and survivor and then a series of years but I could only put those up one at a time, unless I opened a "professional" store which, of course, co$t$ and we don't do that kind of volume to make it worthwhile.

I have 2 thoughts on the survivor + year... there could be a week that the number was 2000, then 2001 the next week etc and cycle around.

OR they could be more by special order. Like Jen writes that she wants her year, she orders that and writes to me that the order is complete.

Then I take the next special request, put that up for awhile, then when that is ordered move on to the next one.

I'm more inclined to go with # 1. Then, everyone from the last 52 years could at least get one this year

I think I'd start with my year, though, 1987 since I don't know of anyone here earlier than that. I'd guess there's a big jump, too up to about 1996 or so.

Any thoughts? Or I'll start collecting year numbers to work on if people want those

~~~~~~~~~~~~~~~~~~~~~

Car magnets - it seems fairly expensive to do the 2 color ones Yellow seems to indicate Support Our Troops. Is there interest for the light blue?

An alternative, if you have an inkjet printer that feeds fairly straight through rather than curving the paper around.

There is magnetic paper that you can print on but it's a little too thick to curve around in the nonstraight printer because the backing peels off.

But, if you want to experiment with printing your own magnets, I could do an image...

I'm still looking for a reasonable place to get 2-color ribbons, though. It looks like there would have to be a pre-order at least from what I've seen so far.

http://www.blackwell-synergy.com/doi/abs/1...65.2004.02003.x

Clinical Endocrinology

Volume 60 Issue 4 Page 470 - April 2004

To cite this article: Maria Alba, Catherine M. Hall, Andrew J. Whatmore, Peter E. Clayton, David A. Price, Roberto Salvatori (2004)

Variability in anterior pituitary size within members of a family with GH deficiency due to a new splice mutation in the GHRH receptor gene

Clinical Endocrinology 60 (4), 470?475.

doi:10.1111/j.1365-2265.2004.02003.x

Original Article

Variability in anterior pituitary size within members of a family with GH deficiency due to a new splice mutation in the GHRH receptor gene

* Maria Alba**Division of Endocrinology, and The Ilyssa Center for Molecular and Cellular Endocrinology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA and ,

* Catherine M. Hall??Department of Paediatric Endocrinology, The Royal Manchester Children's Hospital, Manchester, UK,

* Andrew J. Whatmore??Department of Paediatric Endocrinology, The Royal Manchester Children's Hospital, Manchester, UK,

* Peter E. Clayton??Department of Paediatric Endocrinology, The Royal Manchester Children's Hospital, Manchester, UK,

* David A. Price??Department of Paediatric Endocrinology, The Royal Manchester Children's Hospital, Manchester, UK and

* Roberto Salvatori**Division of Endocrinology, and The Ilyssa Center for Molecular and Cellular Endocrinology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA and

* *Division of Endocrinology, and The Ilyssa Center for Molecular and Cellular Endocrinology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA and ?Department of Paediatric Endocrinology, The Royal Manchester Children's Hospital, Manchester, UK

Summary

objective Mutations in the GHRH receptor (GHRHR) gene (GHRHR) cause autosomal recessive isolated GH deficiency (IGHD), and are usually associated with anterior pituitary hypoplasia (APH) (defined as pituitary height more than 2 SDS below normal). We searched for GHRHR mutations and studied pituitary morphology in three prepubertal sibs with severe IGHD, who were born from consanguineous parents.

design We sequenced the 13 exons and the intron?exon boundaries of the GHRHR of the index patient. After identifying a novel mutation, we sequenced the same area in the other family members. In addition, we performed magnetic resonance imaging (MRI) study of the pituitary (at age 8, 4 and 3 years) in the three affected subjects.

results The three children were homozygous for a new GHRHR mutation that alters the second base of the invariant 5' splice site (GT) of intron 12 [iVS12 + 2T→A]. The parents and an unaffected sibling were heterozygous for the same change. MRI did not show frank APH (by height criteria) in any of the subjects: pituitary height was normal (5?6 mm, +1?8 SDS) in the oldest sibling, and it was low but not below 2 SDS by age-adjusted criteria in the second (3 mm, −1?4 SDS), and third sibling (2?8 mm, −1?7 SDS). Calculated pituitary volume was below −2 SDS in the youngest patient.

conclusions These data demonstrate that pituitary height may fall within 2 SDS from the norm in patients with severe IGHD due to a homozygous GHRHR mutation, and that pituitary size may vary within patients with identical mutations who belong to the same family.

It's nice to see that someone is working on stuff that might be beneficial to us...someday!

At least we got a mention

This was in Today's Email Newsletter

from http://ott.od.nih.gov/db/abstractdetails.asp?RefNo=1033

Description of Invention:

Nuclear receptors are ligand-activated transcription factors that regulate a wide range of biological processes and dysfunction of these receptors can lead to proliferative, reproductive and metabolic diseases, such as cancer, infertility, obesity and diabetes. Nuclear receptors are the second largest class of drug targets and the market for nuclear receptor targeted drugs is estimated to be almost 15% of the $400 billion global pharmaceutical market. Researchers at the National Institute of Diabetes and Digestive and Kidney Disease have isolated a novel protein termed STAMP (SRC-1 and TIF-2 Associated Modulatory Protein) that interacts with the biologically active domains of the coactivators TIF-2 and SRC-1 (J. Biol. Chem. (2002) 51,49256-66) and present data which support a role for STAMP as an important new factor in the glucocorticoid regulatory network. There remains a need for novel therapeutics that specifically block or enhance specific genes and an emerging therapeutic goal is the discovery of agents that modulate co-activators or co-repressors in a tissue specific manner.

The invention is a novel protein that plays a key role in modulating transcriptional properties of glucocorticoid receptor (GR)-steroid complexes during both gene induction and gene repression, and is likely to modulate the transcriptional properties of all the steroid receptors including androgen, mineralocorticoid and progesterone receptors. The inventors have shown that ectopically expressed STAMP protein both modulates the EC50 of glucocorticoid receptor-agonist complexes for induced genes and increases glucocorticoid receptor-repressive activity of suppressed genes in a manner that is inhibited by specific siRNAs under physiologically relevant conditions. The modulation of STAMP levels at the cell or organism level could possibly be used as a therapeutic able to modify inappropriate gene expression that occurs in certain diseases or as a result of long-term steroid treatment.

Available for licensing are claims directed to compositions which are capable of modulating the GR gene expression in a mammalian cell using DNA, siRNA or antibodies and to methods of shifting a steroid dose-response curve, where less of the steroid needs to be administered because the composition contains the STAMP polypeptide. The novel STAMP functional sequence can be used in a composition of matter claim or as a target that could be regulated by an antibody or perhaps other modulator that would vary the ability of STAMP to either induce or repress the activity of glucocorticoid receptors. Diseases that could be treated include: hypertension, diabetes, cardiovascular disease, osteoporosis, Cushing's Disease as well as any disease requiring chronic steroid treatment such as Rheumatoid Arthritis, Asthma, inflammatory and auto-immune diseases. The present invention provides a broad, flexible IP platform that should be of interest to companies which focus on nuclear receptors as drug target and lead discovery generators, as well as to companies which have the capability to develop STAMP's potential as a therapeutic.

Inventors:

S. Stoney Simons and Yuanzheng He (NIDDK)

Patent Status:

DHHS Reference No. E-056-2004/0 --

U.S. Provisional Application No. 60/548,039 filed 26 Feb 2004

PCT Application No. PCT/US2005/006393 filed 25 Feb 2005, which published as WO 2005/082935 on 09 Sep 2005

Licensing Status:

In addition to licensing, the technology is available for further development through collaborative research with the inventors via a Cooperative Research and Development Agreement (CRADA).

Portfolios:

Internal Medicine

Internal Medicine-Therapeutics-Cardiology-Other

Internal Medicine-Therapeutics

Internal Medicine-Other

For Additional Information Please Contact: Susan Carson D.Phil.

NIH Office of Technology Transfer

6011 Executive Blvd, Suite 325

Rockville, MD 20852-3804

Phone: (301) 435-5020

Email: carsonsu@mail.nih.gov

Fax: (301) 402-0220

Web Ref: 1033

Last Updated On: 1/05

Count me in on 3-4 of the magnetic ribbons and the same for the wrist bands.

 

Kathy Z

The wrist bands are available now, and have been for at least a year or two, from http://cushings-interactive.com/oscommerce2/

Still working on the magnetic ribbons, though. Like the bracelets, that is something I would have to order in quantity and ship out from my home

We could put the Amber Tattoo on the back - if she agreed! - but that has the year on it, and we all have different years

If Amber agrees, we could do that and take out the year, though...

Cute! I like that

I thought you wanted that on the back, by the hump - or not?

I see that Cafe Press is back up, too, so the link I posted earlier should work

There are already bracelets available - they've been around for at least a couple years and I've had to reorder them several times. There's a link at the top of every page here that ways "WristBands" and the link is http://www.cushings-interactive.com/oscommerce2/

I haven't yet found a place that is reasonable to do the car magnets yet unless we were to go with one color.

I can put any saying that anyone wants on a T-Shirt, etc if you let me know what you want.

Right now it looks like the site where the T-shirts are is down or there's something weird going on with the internet. The usual link is http://www.cafepress.com/cp/store/store.as...rt,cushpersonal and I'm not sure what is going to happen, if they went out of business or what

Sam's mom posts here quite regularly. If you search for her posts (samsmom) you can get updates and current pictures on how well Same is doing now

Sunday, December 3, 2006

Video: Transnasal Pituitary Surgery

Removal of a pituitary tumor using only an endoscope through the nostril. The video also demonstrates several newly developed techniques and surgical tools. This surgery is very gentle for the patients and the hospital stay will be shortened drastically.

See the video here http://medicalvideos.blogspot.com/2006/12/...using-only.html

Kind of reminds me of this article from Men's Health Magazine http://www.cushings-help.com/youd-rather.htm

You'd Rather Be Dead ...

 

SWIERCZYNSKI, DUANE

Men's Health

December 1, 1999

 

... than have any one of these 10 horrifying and peculiar afflictions

 

THE PHILOSOPHER Mel Brooks once said, "Tragedy is when you cut your finger. Comedy is when you fall down an open sewer and die." If this is true, then the following story contains the most comedic material you've ever read.

 

We're about to present the 10 most miserable diseases on the face of the earth. They're hideous, painful, and in some cases downright phantasmagoric. Their symptoms make you long for a comparatively pleasant malady, such as a brain tumor or paralyzing stroke.

 

You may ask yourself, "Why, God? Why is Men's Health printing this collection of biological atrocities?" Well, we hope you'll scan this list of horrifying maladies and thank the Higher Powers that you don't have them. What was it you were saying earlier about the sniffles?

 

....

 

Affliction 4

 

Your head swells to the size of a basketball

 

* Possible cause: Cushing's syndrome (a.k.a. hypercortisolism)

 

When most people worry about gaining weight, the parts they usually think about are below the neck. But for victims of Cushing's syndrome, a hormonal disorder, it's the opposite: Their heads and necks swell to a John Goodman-like degree.

 

To blame is an overabundance of the hormone cortisol--either produced by your body or from hormone therapy used to treat certain ailments, such as rheumatoid arthritis. Ordinarily cortisol is your friend: It helps your body maintain its blood pressure, keeps your inflammatory response in check, helps balance the effects of insulin, and regulates the metabolism of proteins. Too much of the hormone, however, and the body goes wacky, allowing huge amounts of fat to deposit from the neck up, and rendering your skin fragile and easily bruised from the neck down.

 

* Chances of contracting it: Slim. Cushing's syndrome affects about 10 people per million. Fortunately, there are several treatments and therapies available to keep the Spalding endorsement people away.

I know that all they say is true, but I'm not (always!) sure that I'd rather be dead.

http://www.seacoastonline.com/news/1130200...shings-n29.html

11-30-2006

'The ugly disease'

By Toby Hatchett

features@seacoastonline.com

When Fedela Vincent, 68, of Rye, was diagnosed with Cushing's disease, she was relieved, almost happy. After more than three years, she knew what was wrong with her.

Vincent had spent years trying to figure out what was wrong with her, what was happening to her and her body. A petite woman, of 5 feet, she had always been trim and fit. She ate right, worked out at the gym and led a healthy lifestyle.

But, for no apparent reason, she began to gain weight. Lots of weight, primarily in the upper body.

"I looked like an apple, with a moon face," Fedela says. "Cushing's is not called ?the ugly disease' for nothing."

Cushing's disease victims don't share the same symptoms, but many of the symptoms are physically noticeable: the extreme weight gain in the upper body, the moon face, a buffalo hump on the back, hair loss and blotchy, red skin with breakouts.

"Feeling constantly cruddy" is the polite description of being a Cushie," Fedela says.

Then there are the other symptoms, those not visible on the outside. Fedela says the worst for her was the insomnia, the anxiety, the fear of abandonment and pain. The joints hurt, the muscles lose their mass and walking is difficult.

When Fedela was at her worst, she couldn't walk up the stairs, let alone cook or shop. She was as weak as a kitten, she says.

Her doctors at this time urged her to lose weight, giving medications that often made her sick in an effort to solve the problem.

Bob Vincent, her husband of 48 years, never left her side during this difficult time. Cushing's disease is such a traumatic disease that it is estimated more than half of husbands leave their wives. The mood swings can be dramatic.

"When Bob would bring me coffee," says Fedela, "he never knew what to expect."

Then Fedela decided to try a different kind of doctor. She went to Dr. Jennifer Warren, in Hampton, who specializes in weight control. In Warren, she found someone who listened to her and paid attention. Warren was the first doctor to suggest Cushing's disease might be the cause of Fedela's weight gain.

From that moment on, things began to happen. Fedela went to Dr. Daniel Nadeau who put her on a diabetes-related medication for weight loss. This didn't work and after a month, she was given a simple urinalysis test. Within 24 hours, she had her diagnosis.

Nadeau referred Fedela to the Lahey Clinic, in Burlington, Mass. There she met the doctor she now calls her "savior," Dr. Nicholas Tritos. This clinic is world-renowned for its work in pituitary malfunctions.

What is Cushing's disease? It is the body reacting to a constant overdose of steroids being released by the adrenal glands. The pituitary gland over-stimulates the adrenal glands, which in turn send crisis-level chemical messages to all the other endocrine glands.

"The body reacts to the hyper-stimulation by constantly being in a state of fight or flight," says Fedela. "It's 24/7 with no relief."

Cushing's disease affects an estimated 10 to 15 out of every million people. The fact that it is relatively rare in numbers is one cause of the lack of public knowledge and awareness of this disease.

Non-diagnosed, Cushing's disease can lead to uncontrollable diabetes, and eventually, death. The symptoms can be so varied and mimic so many other conditions, that Cushing's disease is often not diagnosed or misdiagnosed.

"The not knowing what is wrong with you is awful," Fedela says, "and the way people look at you when you're not what society calls ?normal.'"

"People would tell me ?you are what you eat' and suggest I try Weight Watchers, things like that."

But Fedela was carefully watching what she ate, often eating less than her doctors prescribed. Even when her energy level was almost non-existent, she and her husband would go to the gym.

"Bob wouldn't let me stay inside. We kept going out, for drives, to Market Square and lunch with friends."

After the initial diagnosis, Fedela spent six months undergoing various tests.

Then, on Mother's Day of this year, during the New Hampshire floods, she was operated on. Fifty percent of one side of the pituitary was removed and 25 percent of the other side to remove the offending tumorous tissues.

Fedela spent five days recovering at the Lahey Clinic.

"The whole staff was just wonderful. The nurses would pop in to see what a Cushie looked like. They never left me alone."

When she came out of the surgery, Bob was there beside her, along with a very special teddy bear.

"The teddy bear was hugged by members of South Church, including the children Fedela taught in her kindergarten class," he said.

The blessing of this disease, as Fedela describes it, is in learning how to receive. Having long been a giver herself, this was not an easy lesson to learn. South Church, in Portsmouth, put together a Fedela Vincent Support Group, with people from Portsmouth, Rye, Salem, Mass., and Greenland, to provide moral support, company and meals. For six weeks, day and night, someone was there.

"South Church is an amazing institution," Bob says. "The support group was invaluable. Fedela received over 250 cards from all over the country."

This support group is still there for Vincent as she continues to recover and regain her health. She still has problems, but she can now lead a more normal life. "I can shop!" she says with a grin.

"I wanted to do this interview as a call to the medical community to be alert to the symptoms of Cushing's disease and to really listen to their patients."

Fedela also hopes that by sharing her story, others may learn that diet alone is not always the cause of weight gain. America's obsession with skinny bodies and the resulting negative judgmental views on those who do not fit this picture is something she hopes people may think twice about before making judgments.

Lastly, Fedela wants to publicly thank her husband, family, friends and physicians who have stood by her during this difficult struggle. She still has a long way to go, but she is on the mend now and knows what was wrong with her.

"The not knowing what was happening to me was the worst of all."

"If by telling my story, I can help even one person not go through what I did, then it's worth it."

Tritos, a leading endocrinologist at the Lahey Clinic, says it is common for Cushing's disease to not be immediately diagnosed.

"It is common because the condition itself is uncommon. The symptoms are subtle and can be attributed to other causes."

"In Fedela's case, her own body was producing an overload of steroids."

There is a peculiar type of weight gain, in the face, neck and upper torso. Unfortunately, it can take awhile to be diagnosed.

"Most patients go from one doctor to another before Cushing's disease is diagnosed."

Also, Tritos says, sometimes the tests are inconclusive.

But once on the appropriate path, most patients can be helped.

Tritos also notes the value of a good support system, which Fedela had in place.

"The support of family and friends is very important. By telling her story, Mrs. Vincent will increase the public's awareness of Cushing's disease."

http://neuro.psychiatryonline.org/cgi/cont...stract/18/4/450

J Neuropsychiatry Clin Neurosci 18:450-459, November 2006

doi: 10.1176/appi.neuropsych.18.4.450

? 2006 American Psychiatric Publishing, Inc.

Special Article

The Neuropsychiatric Profile of Addison?s Disease: Revisiting a Forgotten Phenomenon

Rebecca E. Anglin, B.Sc., M.D., Patricia I. Rosebush, M.Sc.N., M.D., F.R.C.P.(C.) and Michael F. Mazurek, M.D., F.R.C.P.(C.)

Received November 2, 2005; revised January 8, 2006; accepted January 19, 2006. Drs. Anglin and Mazurek are affiliated with the Department of Medicine and Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, Ontario, Canada. Dr. Rosebush is affiliated with the Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, Ontario, Canada. Address correspondence to Dr. Rosebush, 3G15, Health Sciences Center, 1200 Main St.W, Hamilton, Ontario, L8Z 3N5, Canada; rosebush@hhsc.ca (E-mail).

One hundred fifty years since Thomas Addison?s original description of the disease, it is not commonly appreciated that patients with Addison?s disease may present with psychiatric symptoms. A review of the literature indicates that disturbances in mood, motivation, and behavior are associated with Addison?s disease. Psychosis occurs less frequently, but can be the presenting symptom of a life-threatening adrenal crisis. Potential mechanisms for the neuropsychiatric symptoms of Addison?s disease include electrophysiological, electrolyte and metabolic abnormalities, glucocorticoid deficiency, increased endorphins, and an associated Hashimoto encephalopathy. Physicians must be aware that Addison?s disease may present solely with psychiatric symptoms and maintain a high index of suspicion for this potentially fatal condition.

~~~~~~~~~~~

You may access this article (from the computer you are currently using) for 1 day for US$15.00 at http://neuro.psychiatryonline.org/cgi/reprint/18/4/450

http://www.irishhealth.com/?level=4&id=10614

Pituitary patients missing out

[Posted: Tue 21/11/2006]

The absence of a national register of patients with pituitary conditions is preventing hundreds, perhaps even thousands of people, from the getting the treatment and medication they need, some of the country's leading endocrinologists have claimed.

The pituitary gland is a pea-sized gland located at the base of the brain. It produces hormones, which in turn control the hormone production of many other glands in the body.

There are a number of conditions caused by problems with the pituitary gland, including pituitary tumours and Cushing's disease, the symptoms of which include depression, weight gain and a round 'moon face'.

According to experts, a large number of pituitary conditions remain under-diagnosed here.

"There is no comprehensive database in Ireland of patients suffering from pituitary disease. This is a situation which requires immediate remedy. Extrapolating from European and other studies, we would estimate that there are several thousand patients with pituitary disease in this country", explained Dr Domhnall O'Halloran of Cork University Hospital.

He emphasised that in order to alleviate the significant morbidity and increased mortality associated with pituitary disease, a dedicated team approach from both primary and secondary care is required.

"Patients with pituitary disease require long-term supervision by a dedicated multidisciplinary hospital service working in collaboration with their family doctor. They will require pituitary hormone treatment, as well as management of heart risk factors, such as blood pressure and cholesterol. For their underlying pituitary conditions, they may require complex treatments including drug therapies and pituitary surgery", Dr O'Halloran said.

These treatments, he explained, must be tailored to an individual patient's requirements and supervised by a team with expertise in this area.

Also commenting on this issue, Dr Chris Thompson, a consultant endocrinologist in Beaumont Hospital, pointed out that new causes of pituitary dysfunction, such as traumatic brain injury (TBI) and the effects of radiation, have only recently been recognised.

"The pituitary unit in Beaumont Hospital is a world leader in research on pituitary dysfunction following TBI. This opens up the possibility of hormonal treatment to improve outcomes for some patients with severe head injuries", he said.

The endocrinologists made their comments to coincide with National Pituitary Awareness Day, which takes place on November 24.

"We hope that this day will heighten awareness about the conditions and encourage healthcare providers and the public to be mindful of the many patients throughout Ireland affected by pituitary problems", said Brian and Ronnie Lawler, the Irish coordinators for the UK-based Pituitary Foundation, which provides support, advice and information to pituitary patients.

Patient information leaflets are available from the foundation on a range of pituitary-related issues and conditions. For more information, call (01) 283 1060, email rep-ireland@pituitary.org.uk or log on to...

http://www.pituitary.org.uk

http://journals.endocrinology.org/joe/fca/JOE06925.htm

Changes in thrombospondin-1 levels in the endothelial cells of the anterior pituitary during estrogen-induced prolactin-secreting pituitary tumors

Abby J Sarkar, Kirti Chaturvedi, Cui Ping Chen and Dipak K Sarkar

Endocrinology Program and Department of Animal Sciences, Rutgers, The State University of New Jersey, 84 Lipman Drive, New Brunswick, NJ 08901, USA

(Requests for offprints should be addressed to D K Sarkar)

Abstract

Thrombospondin-1 (TSP-1), a multifunctional matrix glycoprotein, has been shown to control tumor growth by inhibiting angiogenesis in various tissues. However, the role of this glycoprotein in pituitary angiogenesis is not well studied. In this report, we determined the changes in the production and action of TSP-1 on endothelial cells in anterior pituitary following estradiol treatment, which is known to increase prolactin-secreting tumor growth and vascularization in this tissue. We showed that TSP1 immunoreactive protein is distributed in the anterior pituitary, particularly in the endothelial cells. Estradiol treatment for 2 and 4 weeks decreased the total tissue immunoreactive level of TSP1 as well as the endothelial cell specific immunoreactive level of this protein in the anterior pituitary. The steroid treatment also decreased the protein levels of TSP1 in anterior pituitary tissues and in purified pituitary endothelial cells in primary cultures. Determination of the effects of TSP-1 on proliferation and migration of pituitary-derived endothelial cells in primary cultures elucidated an inhibitory action of TSP-1 on this vascular cell functions. These results suggest that locally produced TSP-1 may regulate estrogen angiogenic action on the pituitary.

Journal of Endocrinology

Download the ACCEPTED PREPRINT (i.e. full text) of this article in Acrobat PDF format.

http://www.sun-herald.com/NewsArchive2/111...p;story=hn1.htm

11/16/06

TOO MUCH IRON RUSTS THE LIVER

DEAR DR. DONOHUE: My husband died at age 62 of liver cancer. I have a feeling that it might have been caused by the undiagnosed complications of hemochromatosis. I think this is so because three of my five children over the age of 40 have just been diagnosed with hemochromatosis and are presently under treatment for it. Could there be a connection between it and my husband's cancer? -- P.F.

ANSWER: Hemochromatosis (HE-moe-CROW-muh-TOE-suss) is an inherited disorder with an unfortunately unusual name that makes people think it's a rarity. It is not. It has to do with an inappropriate absorption of iron.

Humans have a built-in mechanism that allows the digestive tract to absorb only the amount of iron that is lost every day. People with hemochromatosis don't have this mechanism. They absorb far too much iron, which deposits in many tissues and organs. The liver is the principal organ affected, and the iron rusts it, so to speak.

Excess liver iron leads to cirrhosis. Iron in the heart brings on heart failure. In the pancreas it causes diabetes. Joints filled with iron become arthritic. Iron infiltrating the skin turns it a bronze color. Iron can invade the testicles and the pituitary gland and greatly damage them.

Although the defect is present from birth, signs don't develop until sometime between 40 and 60. If the illness is diagnosed before organ damage takes place, treatment by removing blood keeps organs healthy. Blood is the body's storehouse of iron.

Liver cancer can be a consequence of hemochromatosis. It happens to about 30 percent of those hemochromatosis patients who develop cirrhosis.

Since hemochromatosis is a genetic illness, all your children should be checked so that early treatment can keep organs healthy.

http://jcem.endojournals.org/cgi/content/abstract/91/11/4528

Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2006-0426

The Journal of Clinical Endocrinology & Metabolism Vol. 91, No. 11 4528-4536

Copyright ? 2006 by The Endocrine Society

Novel HESX1 Mutations Associated with a Life-Threatening Neonatal Phenotype, Pituitary Aplasia, but Normally Located Posterior Pituitary and No Optic Nerve Abnormalities

Marie-Laure Sobrier, Mohamad Maghnie, Marie-Pierre Vi?-Luton, Andrea Secco, Natascia di Iorgi, Renata Lorini and Serge Amselem

Institut National de la Sant? et de la Recherche M?dicale U654 H?pital Henri-Mondor (M.-L.S., M.-P.V.-L., S.A.), 94000 Cr?teil, France; Department of Pediatrics (A.S.), University of Pavia, 27100 Pavia, Italy; and Department of Pediatrics (M.M., N.d.I., R.L.), Instituto di Ricovero e Cura a Carattere Scientifico G. Gaslini, University of Genova, 16147 Genova, Italy

Address all correspondence and requests for reprints to: Serge Amselem, M.D., Ph.D., Institut National de la Sant? et de la Recherche M?dicale, U654, H?pital Henri-Mondor, Cr?teil F-94010, France. E-mail: serge.amselem@creteil.inserm.fr.

Context: Hesx1 is one of the earliest homeodomain transcription factors expressed during pituitary development. Very few HESX1 mutations have been identified in humans; although in those cases the disease phenotype shows considerable variability, all but one of the patients display an ectopic posterior pituitary and/or optic nerve abnormalities.

Objective: The objectives of the study were to describe the complex phenotype associated with the panhypopituitarism of two unrelated Italian patients who, at birth, presented with hypoglycemic seizures and respiratory distress complicated by shock, in a familial context of neonatal death in one family and spontaneous miscarriage in both families and to identify the molecular basis of this unusual syndrome.

Main Outcome Measures: Magnetic resonance imaging of the pituitary region, study of HESX1 gene and transcripts, and assessment of the ability of mutated HESX1 proteins to repress transcription were measured.

Results: Magnetic resonance imaging examination showed an anterior pituitary aplasia in a flat sella turcica and a normally located posterior pituitary in both patients. A constellation of extrapituitary developmental defects were found in the two patients, but without any optic nerve abnormalities. Sequencing of HESX1 exons and their flanking intronic regions revealed two different homozygous mutations. A frameshift (c.449_450delAC) was identified in one case, whereas the other patient carried a splice defect (c.357 + 2T>C) confirmed by the study of HESX1 transcripts. If translated, these mutations would lead to the synthesis of truncated proteins partly or entirely lacking the homeodomain, with no transcriptional repression, as shown by their inability to inhibit PROP1 activity.

Conclusions: These observations reveal two novel HESX1 mutations in a so-far-undescribed disease phenotype characterized by a life-threatening neonatal condition associated with anterior pituitary aplasia, in the absence of ectopic posterior pituitary

Full Text (PDF): http://jcem.endojournals.org/cgi/reprint/91/11/4528