Cytogenetics Definition

Cytogenetics is a branch of genetics that is concerned with the study of the structure and function of the cell, especially the chromosomes. It includes routine analysis of G-Banded chromosomes, other cytogenetic banding techniques, as well as molecular cytogenetics such as fluorescent in situ hybridization (FISH) and comparative genomic hybridization (CGH).





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Targeted Radiotherapy for BMT - clinical trial

http://www.virtualmedicalcentre.com/news.asp?artid=13100&title=World-first-as-myeloma-patient-in-new-clinical-trial-is-given-targeted-radiotherapy-treatment

World first as myeloma patient in new clinical trial is given targeted radiotherapy treatment
21 Jan 2009

A patient from the Isle of Wight with the blood cancer multiple myeloma has become the first person in the world to receive a new form of radiotherapy which targets cancer cells without damaging healthy organs. In a clinical trial funded by Leukaemia Research, Pauline Pain has received a much higher dose of radioactivity delivered accurately to the bone marrow than would otherwise have been possible.
High doses of radioactivity are needed to completely eradicate cancer cells in the bone marrow. This cannot be risked with standard treatments such as total body irradiation, which cause “collateral damage” to healthy tissues, specifically the liver, and may be fatal. The new treatment uses a radioactive isotope attached to an antibody that specifically targets a protein present on myeloma tumour cells in the bone marrow.
Pauline Pain, age 58, from the Isle of Wight is the first person to be treated in the clinical trial, which is assessing the effect of the new radiotherapy treatment on patients with myeloma – an as yet incurable bone marrow cancer that causes extensive bone damage and a failure of the bone marrow to make healthy blood cells.
Following the new targeted radiotherapy treatment, Pauline was able to return home to await her bone marrow transplant (BMT). Conventional total body irradiation would have meant a long stay in hospital.
Pauline says: “The only side-effects of the radiotherapy were a little temporary tiredness and mild sickness; other than that I felt very, very well. It was incredible to be walking around knowing that something inside me was fighting the cancer, but I couldn’t feel it at all”.
Dr Kim Orchard, senior lecturer in the University of Southampton’s School of Medicine, who is leading the trial at Southampton General Hospital explains: "Radiotherapy is used to clear the bone marrow of myeloma cells before a stem cell transplant. Current treatment uses high doses of radiation, which are delivered by X-rays but the sensitivity of healthy organs limits the dose that can be tolerated. “
“Previous attempts to use antibodies to deliver the radioactivity have been frustrated by their accumulation in the liver, lungs and kidneys, which can cause serious complications and may be fatal. The key to this promising new treatment is that the antibody only accumulates in the bone marrow and not in other tissues.”
The new type of radiotherapy works by delivering the radio-isotope Yttrium-90 attached to an antibody which targets a protein called CD-66, found on the surface of bone marrow cells and myeloma tumour cells. The radioactive Yttrium-90 delivers radiation specifically to sites of disease in the bone marrow and as a result, destroys the bone marrow and any tumour cells. This is followed by a transplant of healthy stem cells collected from the patient at an earlier time.
Dr Orchard said: “The early results using this new approach to bone marrow transplantation are very encouraging with high doses of radiation targeted to the bone marrow without any side-effects. We are currently using the targeted radiation in addition to chemotherapy and we hope that the trial will show a clear benefit in better and longer remissions from myeloma. If we are successful, then this approach offers great promise for the treatment of patients who need a bone marrow transplant for a range of other blood cancers such as leukaemia.”
Dr David Grant, Scientific Consultant at Leukaemia Research, said: “This trial is very exciting. One of the main reasons why stem cell transplants have been less successful in the long-term treatment of myeloma is that patients are not cleared of all the cancer cells before the transplant. This new radiotherapy is not only more effective and potentially cheaper than existing treatments, it is far less toxic for the patient. It also enables patients to go home immediately after the procedure, reducing time spent in hospital.”
(Source: Leukaemia Research: January 2009)



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White Blood Cell normal ranges for age with mean value

http://www.fpnotebook.com/Hemeonc/Lab/WhtBldCl.htm

Normal Range
Age 6 Months to 2 years: 6.0 to 17.5 (Mean 11.0)
Age 4 Years: 5.5 to 15.5 (Mean 9.1)
Age 6 Years: 5.0 to 14.5 (Mean 8.5)
Age 8 to 16 Years: 4.5 to 13.5 (Mean 8.1)
Age over 21 Years: 4.5 to 11.0 (Mean 7.4)




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Inspiration for Today

My son's article appeared along with mine in the recent issue of the Shwachman-Diamond America eNewsletter

http://shwachmandiamondamerica.org/cgi/wp/wp-content/uploads/2009/01/sdajanfeb09-newsletter.pdf

I post this not for our articles…but there are several very good articles in this newsletter—one is Brooke’s story. She developed sepsis as an infant and almost died. She survived and had to have her toes amputated and the sepsis caused damage…her one leg turned, etc. She had a bone marrow transplant several years ago and this past summer had her leg amputated. She is doing amazingly well and I think you will find her Shwachman-Diamond story inspiring.

I have been blessed to meet so many amazing people on the journey we call SDS Highway 101. God has blessed us with an amazing Shwachman-Diamond family and I wanted to share them with you this morning! Perhaps you are dealing with a life-threatening illness or know someone who is….these children are an inspiration to us all. If you would like to read past issues, we have the back issues of the newsletters posted on our website (link to follow). We have many children who have written articles—the SDS children themselves and their siblings. http://shwachmandiamondamerica.org/newsletter.html

For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Shwachman-Diamond Syndrome Registry

North American Shwachman-Diamond Syndrome Registry

The North American Shwachman-Diamond Syndrome Registry is now enrolling patients!
The Shwachman-Diamond Syndrome Registry (SDSR) was established to collect medical information and clinical samples on all individuals with Shwachman-Diamond Syndrome across the United States and Canada with the goal of improving diagnosis and treatment. The SDSR is a research organization dedicated to gathering and analyzing information about SDS. Scientific studies will focus on elucidating the causes of SDS and its complications in order to develop better treatments.

Patients must contact the registry directly to receive the enrollment packets and questionnaires. For more information or to join the registry, please contact the Shwachman-Diamond Syndrome Registry Coordinator, Melissa Alvendia, at 206-667-6965 or 866-792-5876 or malvendi@fhcrc.org


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Dr. Shimamura's Lab

http://labs.fhcrc.org/shimamura/projects.html

SDS research lab.






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Growth Hormone in Shwachman-Diamond Syndrome

I cut and pasted from the eMedicine article. Such a shame that medical professionals still cannot SPELL the disease. SIGH.


Growth hormone has been used to treat children with Schwachman-Diamond syndrome who have growth hormone deficiency. The initial response is good; however, long-term therapy with growth hormone is unsuccessful.

It comes from the eMedicine article on SDS found here: http://www.emedicine.com/ped/topic2060.htm

The reference is gives is: Marseglia GL, Bozzola M, Marchi A, et al. Response to long-term hGH therapy in two children with Schwachman- Diamond syndrome associated with GH deficiency. Horm Res. 1998;50(1):42-5




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Shwachman-Diamond Syndrome Registry

You can contact the SDS registry for info on how to register. Melissa Alvendia malvendi@fhcrc.org Questionnaires are available, but the website is not up and running yet. It will hopefully be on-line soon. They also have pamphlets in PDF…but the margins are off when they are printed. They are working on getting all the supporting organizations a flyer that is easier to print. I just got an email about the flyer last night—so hopefully it will be soon.

The website for the registry will be located at www.SDSRegistry.org



For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

SBDS-deficiency results in specific hypersensitivity to Fas stimulation and accumulation of Fas at the plasma membrane.

Apoptosis. 2008 Nov 14.

SBDS-deficiency results in specific hypersensitivity to Fas stimulation and accumulation of Fas at the plasma membrane.
Watanabe KI, Ambekar C, Wang H, Ciccolini A, Schimmer AD, Dror Y.

Shwachman-Diamond syndrome (SDS) is an inherited disorder characterized by reduced cellularity in the bone marrow and exocrine pancreas. Most patients have mutations in the SBDS gene, whose functions are unknown. We previously showed that cells deficient in the SBDS protein are characterized by accelerated apoptosis and Fas hypersensitivity, suggesting that the protein might play an important role in Fas-mediated apoptosis. To study the mechanism of Fas hypersensitivity, we compared shRNA-mediated SBDS-knockdown HeLa cells and SDS marrow CD34+ cells for their sensitivity to several groups of apoptosis inducers. Marked hypersensitivity was noticed in response to Fas stimulation, but not to tumor necrosis factor-alpha, DNA-damaging agents, transcription inhibition or protein synthesis inhibition. To identify the Fas signaling factors that cause hypersensitivity, we analyzed the expression of the pathway's proteins. We found that Fas accumulated at the plasma membrane in SBDS-knockdown cells with corresponding expression of Fas transcript 1, the main Fas transcript which contains both the transmembrane domain and the death domain. However, the total levels of Fas protein and mRNA were comparable to controls, and Fas internalization occurred normally. Expression of FADD, caspase-8 and -3 were not elevated and the pathway inhibitors: ERK, c-FLIP and XIAP were not decreased. These results suggest that SBDS loss results in abnormal accumulation of Fas at the plasma membrane, where it sensitizes the cells to stimulation by Fas ligand.


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Depletion of the Shwachman-Diamond syndrome gene product, SBDS, leads to growth inhibition and increased expression of OPG and VEGF-A.

I have the full-text of this one-- very interesting article!

Blood Cells Mol Dis. 2008 Nov 15.

Depletion of the Shwachman-Diamond syndrome gene product, SBDS, leads to growth inhibition and increased expression of OPG and VEGF-A.
Nihrane A, Sezgin G, Dsilva S, Dellorusso P, Yamamoto K, Ellis SR, Liu JM.

Shwachman-Diamond syndrome (SDS) is an autosomal recessive disorder characterized by bone marrow failure and leukemia predisposition, pancreatic exocrine dysfunction, and skeletal abnormalities, manifesting as skeletal dysplasia and osteoporosis. Mutations in SBDS have been shown to cause SDS, but the function of the SBDS gene product is unclear. Accelerated angiogenesis has recently been described in bone marrow cells from SDS patients. To clarify the unknown function of SBDS, we performed experiments analyzing the cellular effects of depleting SBDS by RNA interference. The growth of HeLa cells constitutively depleted of SBDS was markedly hindered when compared to cells stably transfected with siRNA against an irrelevant control gene. Similarly, growth of HeLa cells induced to express siRNA against SBDS was specifically inhibited. Inducible SBDS knockdown was associated with modestly increased levels of apoptosis, suggesting a partial contribution of this process to growth inhibition. By microarray analysis of knockdown cells, we found marked differences in expression of genes in multiple pathways, and we chose to examine a selected subset more closely using quantitative PCR arrays. In constitutive and inducible SBDS-depleted HeLa cell clones, we found 3- to 6-fold elevated mRNA levels of osteoprotegerin (OPG or TNFRSF11B) and vascular endothelial growth factor-A (VEGF-A). We confirmed significant overexpression of both secreted proteins by ELISA from supernatants of SBDS-depleted HeLa cells. Osteoprotegerin and VEGF-A are known to have diverse effects on osteoclast differentiation, angiogenesis, and monocyte/macrophage migration, all processes that may be aberrant in SDS, and we propose that overexpression of these factors may contribute to its pathology.

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Totipotent stem cells bearing del(20q) maintain multipotential differentiation in Shwachman Diamond syndrome.

Br J Haematol. 2008 Nov 11.
Totipotent stem cells bearing del(20q) maintain multipotential differentiation in Shwachman Diamond syndrome.

Crescenzi B, La Starza R, Sambani C, Parcharidou A, Pierini V, Nofrini V, Brandimarte L, Matteucci C, Aversa F, Martelli MF, Mecucci C.

Summary SBDS/7q11 gene mutations underlie the congenital Shwachman Diamond syndrome (SDS), characterized by bone marrow failure and high risk of haematological malignancies. In two cases of SDS with bone marrow failure and isolated del(20q) interphase fluorescence in situ hybridization (I-FISH) found no abnormalities in FHIT/3p14.2, IKZF1/7p13, D7S486/7q31, PTEN/10q23.3, WT1/11p13, ATM/11q23, D13S25/13q14, TP53/17p13, NF1/17q11, SMAD2/18q21, RUNX1/21q22. Fluorescence immunophenotype combined with I-FISH found del(20q) in a totipotent haematopoietic stem cell (CD34(+), CD133(+)) and downstream myelocyte (CD33(+), CD14(+), CD13(+)), erythrocyte (Glycophorin A(+)) and lymphocyte lineages (CD19(+), CD20(+), CD3(+), CD7(+)). These findings and clinical follow-ups confirm the benign course of SDS with isolated del(20q).


For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Fecal fat

here are a few good links for information on fecal fat tests and results:
http://www.medhelp.org/perl6/gastro/archive/2847.html

http://pediatrics.aappublications.org/cgi/content/abstract/46/5/690

This site has pediatric reference ranges:

http://www.aruplab.com/guides/ug/tests/0020386.jsp



For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

Shwachman-Diamond Syndrome Information

This site has information on SDS including the common cytogenetic findings in SDS, telomeres, and information on P53 protein overexpression. http://atlasgeneticsoncology.org/Kprones/ShwachmanID10058.html




For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America

GREAT UK SDS video

Thank you to all who made this video possible-- the camera crews, the doctors who spoke and Jules who jumped out of the airplane! Great awareness video!

Iron Deficiency Anemia - Iron Stores

Great site about Iron Deficiency Anemia. Also has info on iron stores in the marrow along with pictures.

http://www.med-ed.virginia.edu/courses/path/innes/rcd/iron.cfm

Shwachman-Diamond Syndrome on Mystery Diagnosis

Part one:



Part two:

Bone Scans

Here are a few articles that will be helpful in understanding bone scans:

http://www.lifesteps.com/gm/Atoz/ency/bone_nuclear_medicine_scan.jsp


http://www.webmd.com/a-to-z-guides/bone-scan

Bone scans detect inflammation, cancer and new bone growth......



For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America