Medical researchers with EDP Biotech Corporation (EDP) have captured national attention with their revolutionary new technology for a simple blood test to detect early-stage colon cancer.
Following the success of its pre-clinical trials for the ColoMarker(TM) assay, EDP has filed a patent on the biomarker, CA11-19, and all aspects of its use. Via an inexpensive blood test, ColoMarker(TM) will detect colon cancer in its earliest, most curable stages.
"American Cancer Society statistics show that when colon cancer is detected in its early stages, more than 90% of patients will survive. If not detected until the later stages, fewer than 10% will survive. ColoMarker(TM) detects colon cancer in these early, highly curable stages," says Kevin Jones, Ph.D., Chief Scientific Officer of EDP.
According to American Cancer Society statistics, fewer than 20% of Americans over the age of 50 who should be screened for colon cancer, actually are. With the use of ColoMarker(TM), a simple and inexpensive blood test, the number of people being screened would likely increase dramatically, leading to a decline in deaths due to colon cancer.
In pre-clinical trials, ColoMarker(TM) successfully detected the early stages (I, II, and III) of colon cancer. In tests of 2,370 blood samples, ColoMarker(TM) showed an accuracy rate of >99% for detecting colon cancer in these early stages. "ColoMarker(TM) could lead to a radical shift in the way we detect colon cancer," adds Dr. Jones.
National researchers who study colorectal cancer are closely monitoring emerging technologies such as ColoMarker(TM). Their findings are encouraging; just last week, the American Cancer Society, the National Cancer Institute, the Centers for Disease Control and Prevention and the North American Association of Central Cancer Registries released an optimistic report about the expected decline in deaths from colon cancer due to anticipated improvements in early screening methods.
Dr. Jones states, "The use of ColoMarker(TM) as a screening test could save tens of thousands of American lives every year and billions of dollars in healthcare costs." EDP Biotech is now moving forward expeditiously to get ColoMarker(TM) through the Food and Drug Administration clearance process.
About EDP Biotech Corporation
EDP Biotech Corporation (EDP) is a medical device company focused on the development and sale of immunodiagnostic tests for both humans and animals. EDP utilizes more than 30 years of research and development in identification and purification of proteins present in the early stages of biological changes for production of in vitro diagnostic tests whose primary target is Early Detection Products.
Source: EDP Biotech Corporation
суббота, 2 июля 2011 г.
пятница, 1 июля 2011 г.
St. Jude Medical Announces U.S. Launch Of TigerWire Steerable Guidewire
St. Jude Medical, Inc. (NYSE:STJ) announced U.S. launch of the TigerWire(TM) Steerable Guidewire. The newest member of the St. Jude Medical GuideRight(TM) family of steerable guidewires, the TigerWire Steerable Guidewire is designed to enhance physicians' ability to steer through challenging peripheral arteries, the vessels that supply blood to the legs and arms.
A guidewire is a thin, flexible wire that physicians use to help guide and steer a catheter (a flexible tube) through the arteries. Catheters are used to assist in diagnosing and treating blockages caused by a build-up of plaque inside artery walls. Plaque build-up can block blood flow and lead to heart attack or stroke.
The TigerWire Guidewire's tip is designed with enhanced flexibility to aid in navigation through the vessels. Its supportive design provides distinct zones of flexibility that make it easier for physicians to track and position the guidewire through challenging anatomy.
"The TigerWire Steerable Guidewire has been engineered for improved steerability," said Frank Callaghan, president of the St. Jude Medical Cardiovascular Division. "It gives physicians a tool that can ease access to difficult-to-reach vessels when performing complex diagnostic and interventional procedures."
The insertion of a guidewire is a first step in interventional procedures in which physicians thread catheters through the arteries to diagnose the severity of disease or deliver treatments, including devices such as stents that open blockages and restore blood flow.
Each year, an estimated 4 million cardiovascular catheterization procedures are performed in the U.S., according to IMV, a research and publishing firm specializing in the medical imaging and clinical diagnostic instruments markets.
About St. Jude Medical
St. Jude Medical is dedicated to making life better for cardiac, neurological and chronic pain patients worldwide through excellence in medical device technology and services. The Company has five major focus areas that include: cardiac rhythm management, atrial fibrillation, cardiac surgery, cardiology and neuromodulation. Headquartered in St. Paul, Minn., St. Jude Medical employs more than 12,000 people worldwide. For more information, please visit sjm.
Forward-Looking Statements
This news release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that involve risks and uncertainties. Such forward-looking statements include the expectations, plans and prospects for the Company, including potential clinical successes, anticipated regulatory approvals and future product launches, and projected revenues, margins, earnings, and market shares. The statements made by the Company are based upon management's current expectations and are subject to certain risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. These risks and uncertainties include market conditions and other factors beyond the Company's control and the risk factors and other cautionary statements described in the Company's filings with the SEC, including those described in the Company's Annual Report on Form 10-K filed on February 27, 2008 (see Item 1A on pages 13-20, and page 20 of Exhibit 13 to the Company's Form 10-K). The Company does not intend to update these statements and undertakes no duty to any person to provide any such update under any circumstance.
St. Jude Medical
A guidewire is a thin, flexible wire that physicians use to help guide and steer a catheter (a flexible tube) through the arteries. Catheters are used to assist in diagnosing and treating blockages caused by a build-up of plaque inside artery walls. Plaque build-up can block blood flow and lead to heart attack or stroke.
The TigerWire Guidewire's tip is designed with enhanced flexibility to aid in navigation through the vessels. Its supportive design provides distinct zones of flexibility that make it easier for physicians to track and position the guidewire through challenging anatomy.
"The TigerWire Steerable Guidewire has been engineered for improved steerability," said Frank Callaghan, president of the St. Jude Medical Cardiovascular Division. "It gives physicians a tool that can ease access to difficult-to-reach vessels when performing complex diagnostic and interventional procedures."
The insertion of a guidewire is a first step in interventional procedures in which physicians thread catheters through the arteries to diagnose the severity of disease or deliver treatments, including devices such as stents that open blockages and restore blood flow.
Each year, an estimated 4 million cardiovascular catheterization procedures are performed in the U.S., according to IMV, a research and publishing firm specializing in the medical imaging and clinical diagnostic instruments markets.
About St. Jude Medical
St. Jude Medical is dedicated to making life better for cardiac, neurological and chronic pain patients worldwide through excellence in medical device technology and services. The Company has five major focus areas that include: cardiac rhythm management, atrial fibrillation, cardiac surgery, cardiology and neuromodulation. Headquartered in St. Paul, Minn., St. Jude Medical employs more than 12,000 people worldwide. For more information, please visit sjm.
Forward-Looking Statements
This news release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that involve risks and uncertainties. Such forward-looking statements include the expectations, plans and prospects for the Company, including potential clinical successes, anticipated regulatory approvals and future product launches, and projected revenues, margins, earnings, and market shares. The statements made by the Company are based upon management's current expectations and are subject to certain risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. These risks and uncertainties include market conditions and other factors beyond the Company's control and the risk factors and other cautionary statements described in the Company's filings with the SEC, including those described in the Company's Annual Report on Form 10-K filed on February 27, 2008 (see Item 1A on pages 13-20, and page 20 of Exhibit 13 to the Company's Form 10-K). The Company does not intend to update these statements and undertakes no duty to any person to provide any such update under any circumstance.
St. Jude Medical
четверг, 30 июня 2011 г.
MOM, Metal Ions And Lymphopenia
Metal-on-metal hip replacement and resurfacing have become the most commonly used type of procedure in the United Kingdom for patients who are < 60 years of age with osteoarthritis. Therefore, this research consisted of a cross-sectional study with analysis of demographic, clinical and laboratory characteristics of patients who had undergone metal-on-metal hip resurfacing, ceramic-on-ceramic and metal-on-polyethylene hip replacement to assess whether there was a relationship between MOM replacements and circulating metal ions in the blood, and absolute numbers of circulating lymphocytes.
There were 164 patients in the study, of which 106 had MOM hips, all were aged < 65 years and had pre-operative diagnosis of osteoarthritis and no pre-existing immunological disorders. Patients were excluded if their replacement had taken place less than six months previously, thereby avoiding the high-wearing, bedding-in phase. Blood samples were taken using a plastic needle cannula to avoid metal contamination.
The results showed that 'there were significant differences in the levels of metal ions in the whole blood and in the absolute lymphocyte counts'. A group of 10 patients of the 106 from the MOM group had circulating levels of chromium greater than 5 parts per billion. Therefore, the authors conclude that 'patients with MOM hips had reduced peripheral blood counts of T-lymphocytes in particular and B-lymphocytes when compared with control subjects with hip replacements which did not produce metal wear debris'. Although the effect of reduced lymphocytes is unknown, there has been a link between high levels of cobalt and chromium and DNA damage of lymphocytes and the authors recommend that long-term studies need to be conducted to determine whether the moderate lymphopenia associated with MOM hip replacements is detrimental or even beneficial to longevity of the replacement.
Read the full text article.
Source
The Journal of Bone and Joint Surgery
There were 164 patients in the study, of which 106 had MOM hips, all were aged < 65 years and had pre-operative diagnosis of osteoarthritis and no pre-existing immunological disorders. Patients were excluded if their replacement had taken place less than six months previously, thereby avoiding the high-wearing, bedding-in phase. Blood samples were taken using a plastic needle cannula to avoid metal contamination.
The results showed that 'there were significant differences in the levels of metal ions in the whole blood and in the absolute lymphocyte counts'. A group of 10 patients of the 106 from the MOM group had circulating levels of chromium greater than 5 parts per billion. Therefore, the authors conclude that 'patients with MOM hips had reduced peripheral blood counts of T-lymphocytes in particular and B-lymphocytes when compared with control subjects with hip replacements which did not produce metal wear debris'. Although the effect of reduced lymphocytes is unknown, there has been a link between high levels of cobalt and chromium and DNA damage of lymphocytes and the authors recommend that long-term studies need to be conducted to determine whether the moderate lymphopenia associated with MOM hip replacements is detrimental or even beneficial to longevity of the replacement.
Read the full text article.
Source
The Journal of Bone and Joint Surgery
среда, 29 июня 2011 г.
New Vascular Channel On
is pleased to announce the launch of a new Vascular channel. The section will include news on arterial diseases (aortic abdominal aneurysms, thoracic aortic aneurysms, aortic arch, dissections and ischemia, as well as peripheral arterial disease) and venous diseases (varicose veins and deep vein thrombosis).
asks that any subscribers to the tailored Newsletter or Newsalert, who would like to receive the news from this new section in their e-mails, amend their preferences using the link provided in their last/next e-mail from (or use our feedback form if you would like assistance).
Other channels that have been added recently and will also need to be updated in the e-mail subscriptions include:
Asbestos / Mesothelioma
Back Pain
COPD
Eczema / Psoriasis
Fibromyalgia
Lymphology/Lymphedema
Medical Practice Management
Melanoma / Skin Cancer
Menopause
Ovarian Cancer
Palliative Care / Hospice Care
Tuberculosis
Veterans / Ex-Servicemen
If you have a suggestion for another new channel you would like to see on our site please fill in the form at the bottom of our Contact Us page.
To sign up for one of our free e-mails please fill in the form on the relevant page:
Weekly Newsletter
Daily Newsalert
Every e-mail provides you with a link to unsubscribe or change your preferences if you wish to do so.
asks that any subscribers to the tailored Newsletter or Newsalert, who would like to receive the news from this new section in their e-mails, amend their preferences using the link provided in their last/next e-mail from (or use our feedback form if you would like assistance).
Other channels that have been added recently and will also need to be updated in the e-mail subscriptions include:
Asbestos / Mesothelioma
Back Pain
COPD
Eczema / Psoriasis
Fibromyalgia
Lymphology/Lymphedema
Medical Practice Management
Melanoma / Skin Cancer
Menopause
Ovarian Cancer
Palliative Care / Hospice Care
Tuberculosis
Veterans / Ex-Servicemen
If you have a suggestion for another new channel you would like to see on our site please fill in the form at the bottom of our Contact Us page.
To sign up for one of our free e-mails please fill in the form on the relevant page:
Weekly Newsletter
Daily Newsalert
Every e-mail provides you with a link to unsubscribe or change your preferences if you wish to do so.
вторник, 28 июня 2011 г.
2010 Merit Award Winners Announced By ASH
The American Society of Hematology (ASH) recognizes the following abstract presenters at the 52nd ASH Annual Meeting in Orlando, FL, with the highest scoring abstracts in the categories of undergraduate student, medical student, graduate student, resident physician, and post-doctoral fellow. Merit Award winners receive a $500 honorarium plus annual meeting travel reimbursement.
The 2010 Merit Award recipients are:
Undergraduate Student
Maria Virgilio
Treatment of Zebrafish Models of Ribosomopathies (Diamond Blackfan Anemia (DBA) and 5q- Syndrome) With L-Leucine Results in an Improvement of Anemia and Developmental Defects: Evidence for a Common Pathway?
Abstract #195
Medical Student
Karrune Woan
Identification of a Discrete Subpopulation of T-Cells Over-Expressing HDAC11 With a TH17 Phenotype
Abstract #588
Graduate Student
Wulan Deng
Manipulating Higher Order Chromatin Structure of the ОІ-Globin Locus by Targeted Tethering of a "Looping" Factor
Abstract #647
Post-Doctoral Fellow
Jian Xu, PhD
Reactivation of Silenced Human HbF in Adult Mice by Inactivation of BCL11A
Abstract #643
Mary Rodes Gibson Memorial Award in Hemostasis and Thrombosis
This award was established to recognize the trainee (undergraduate student, medical student, graduate student, resident physician, or post-doctoral fellow) who is the first author and presenter of the highest scoring abstract submitted in the field of hemostasis and thrombosis. This annual award is made possible by the Mary Rodes Gibson Hemostasis-Thrombosis Foundation to continue the legacy of Mary Rodes Gibson, who suffered from severe, type 3 von Willebrand disease.
The 2010 recipient is:
Louisa M. Dowal, PhD
A Chemical Genetic Analysis of Platelet Activation Identifies an Antithrombotic Allosteric Modulator That Acts Through Helix 8 of Par1
Abstract #483
Source:
Lindsey Love
American Society of Hematology
The 2010 Merit Award recipients are:
Undergraduate Student
Maria Virgilio
Treatment of Zebrafish Models of Ribosomopathies (Diamond Blackfan Anemia (DBA) and 5q- Syndrome) With L-Leucine Results in an Improvement of Anemia and Developmental Defects: Evidence for a Common Pathway?
Abstract #195
Medical Student
Karrune Woan
Identification of a Discrete Subpopulation of T-Cells Over-Expressing HDAC11 With a TH17 Phenotype
Abstract #588
Graduate Student
Wulan Deng
Manipulating Higher Order Chromatin Structure of the ОІ-Globin Locus by Targeted Tethering of a "Looping" Factor
Abstract #647
Post-Doctoral Fellow
Jian Xu, PhD
Reactivation of Silenced Human HbF in Adult Mice by Inactivation of BCL11A
Abstract #643
Mary Rodes Gibson Memorial Award in Hemostasis and Thrombosis
This award was established to recognize the trainee (undergraduate student, medical student, graduate student, resident physician, or post-doctoral fellow) who is the first author and presenter of the highest scoring abstract submitted in the field of hemostasis and thrombosis. This annual award is made possible by the Mary Rodes Gibson Hemostasis-Thrombosis Foundation to continue the legacy of Mary Rodes Gibson, who suffered from severe, type 3 von Willebrand disease.
The 2010 recipient is:
Louisa M. Dowal, PhD
A Chemical Genetic Analysis of Platelet Activation Identifies an Antithrombotic Allosteric Modulator That Acts Through Helix 8 of Par1
Abstract #483
Source:
Lindsey Love
American Society of Hematology
понедельник, 27 июня 2011 г.
Racial Differences In Risk Factors For Venous Thromboembolism And Pulmonary Embolism
A new study of 1,960 White-Americans and 368 Black-Americans with objectively diagnosed venous thromboembolism (VTE) showed that, compared to Whites, Blacks had a significantly higher proportion with pulmonary embolism (PE), including idiopathic PE among Black women, and a significantly higher proportion of Blacks with VTE were women (71% vs 61% for Whites) The study is published in the American Journal of Hematology.
VTE is blood clots in veins and consists of deep vein thrombosis (DVT), a blood clot in the "inner" or "deep" vein, typically of the leg or pelvis, and its complication, PE, a dislodged DVT that has traveled with the returning blood to the heart and become lodged in the lungs. Most epidemiologic studies of VTE risk factors have been conducted within White-American and -European populations. However, compared to Whites, Black-Americans appear to have a higher risk and incidence of VTE. Two single nucleotide polymorphisms (DNA sequence variations), factor V Leiden (G1691A) and prothrombin (G20210A), have been identified as risk factors for DVT and PE in Europeans and White-Americans, but not Black- Americans.
"VTE appears to be more common in Blacks than Whites, but while we have identified many inherited causes for VTE in Whites, no such inherited causes in Blacks have been identified," said lead researcher Prof. John Heit, of the Mayo Clinic College of Medicine, Minnesota, USA. "We wondered whether Blacks were more likely to have VTE related to common exposures that can cause VTE, such as major surgery, hospitalization for acute medical illness, trauma, fracture, or birth control pills, to account for VTE being more common in Blacks, but this does not appear to be the case. Thus, we now question whether Blacks may have some as yet unidentified inherited cause for VTE."
The researchers found that, compared to Whites with VTE, Blacks with VTE have a higher proportion of PE events, a lower proportion of VTE related to transient risk factors and a higher proportion with idiopathic VTE, i.e. from a seemingly unknown or unrelated cause.
Blacks had a significantly higher mean BMI, and a significantly lower proportion with recent surgery, trauma or infection, family history of VTE and documented thrombophilia. Conversely, Blacks had a significantly higher proportion with hypertension, diabetes mellitus, chronic renal disease and dialysis, HIV and sickle cell disease. Compared to White women, Black women had a significantly lower proportion with recent oral contraceptive use or hormone therapy
"Given the poor survival after PE, our finding of an increased prevalence of PE among Blacks (particularly idiopathic PE) is disturbing, especially when coupled with previous reports of increased complications after VTE and higher PE case-fatality among Blacks," added Heit.
The study is accompanied by an editorial by Dr. Samuel Goldhaber of Brigham and Women's Hospital and Harvard Medical School, Boston, USA.
Full citation:
JA Heit et al; Comparison of Characteristics from White- and Black-Americans with Venous Thromboembolism: A Cross Sectional Study; American Journal of Hematology, 2010; DOI: 10.1002/ajh.21735
About the author:
John A. Heit, M.D., FACP, FACC, is Director of Coagulation Laboratories and Professor of Medicine at the Mayo Clinic College of Medicine, MN, USA.
Source:
Amy Molnar
Wiley-Blackwell
VTE is blood clots in veins and consists of deep vein thrombosis (DVT), a blood clot in the "inner" or "deep" vein, typically of the leg or pelvis, and its complication, PE, a dislodged DVT that has traveled with the returning blood to the heart and become lodged in the lungs. Most epidemiologic studies of VTE risk factors have been conducted within White-American and -European populations. However, compared to Whites, Black-Americans appear to have a higher risk and incidence of VTE. Two single nucleotide polymorphisms (DNA sequence variations), factor V Leiden (G1691A) and prothrombin (G20210A), have been identified as risk factors for DVT and PE in Europeans and White-Americans, but not Black- Americans.
"VTE appears to be more common in Blacks than Whites, but while we have identified many inherited causes for VTE in Whites, no such inherited causes in Blacks have been identified," said lead researcher Prof. John Heit, of the Mayo Clinic College of Medicine, Minnesota, USA. "We wondered whether Blacks were more likely to have VTE related to common exposures that can cause VTE, such as major surgery, hospitalization for acute medical illness, trauma, fracture, or birth control pills, to account for VTE being more common in Blacks, but this does not appear to be the case. Thus, we now question whether Blacks may have some as yet unidentified inherited cause for VTE."
The researchers found that, compared to Whites with VTE, Blacks with VTE have a higher proportion of PE events, a lower proportion of VTE related to transient risk factors and a higher proportion with idiopathic VTE, i.e. from a seemingly unknown or unrelated cause.
Blacks had a significantly higher mean BMI, and a significantly lower proportion with recent surgery, trauma or infection, family history of VTE and documented thrombophilia. Conversely, Blacks had a significantly higher proportion with hypertension, diabetes mellitus, chronic renal disease and dialysis, HIV and sickle cell disease. Compared to White women, Black women had a significantly lower proportion with recent oral contraceptive use or hormone therapy
"Given the poor survival after PE, our finding of an increased prevalence of PE among Blacks (particularly idiopathic PE) is disturbing, especially when coupled with previous reports of increased complications after VTE and higher PE case-fatality among Blacks," added Heit.
The study is accompanied by an editorial by Dr. Samuel Goldhaber of Brigham and Women's Hospital and Harvard Medical School, Boston, USA.
Full citation:
JA Heit et al; Comparison of Characteristics from White- and Black-Americans with Venous Thromboembolism: A Cross Sectional Study; American Journal of Hematology, 2010; DOI: 10.1002/ajh.21735
About the author:
John A. Heit, M.D., FACP, FACC, is Director of Coagulation Laboratories and Professor of Medicine at the Mayo Clinic College of Medicine, MN, USA.
Source:
Amy Molnar
Wiley-Blackwell
воскресенье, 26 июня 2011 г.
New Clinical Study Shows RyMed InVision-Plus® IV Connector Dramatically Reduced Catheter-Related Bloodstream Infections By Over 92%
Georgia Health Sciences University, Augusta, GA exhibited a poster at the recent 11th National Conference on Cancer Nursing Research in Los Angeles, in which their clinical study showed RyMed Technologies' zero displacement InVision-Plus® IV Connector significantly decreased the incidence of catheter-related bloodstream infections (CR-BSIs) by 92.6% on average when compared to a simple split septum with negative displacement IV connector (Becton-Dickinson Q-Syte®) and a reversed split-septum device with negative displacement IV connector (ICU Medical Clave®). No clinical studies have been published comparing different types of connectors in oncology patients on CR-BSIs. CR-BSIs can cause treatment delays, add time to nursing care, increase costs, increase mortality and decrease quality of life for the patient and family.
The purpose of the study was to determine infection rates for a split septum valve, a negative reversed split-septum valve and an intraluminal protection device (IPD) with zero displacement in both critical care and medical in-patient oncology patients.
Detailed results:
-- CR-BSI incidences decreased 96.3%, from 2.9 to 0.1 infections per 1,000 catheter days, when the RyMed InVision-Plus® needleless IV connector was used compared to the Becton-Dickinson's Q-Syte® product.
-- CR-BSI incidences decreased 88.9%, from 3.7 to 0.4 infections per 1,000 catheter days, when the RyMed InVision-Plus® needleless IV connector was used compared to the ICU Medical Clave® product.
-- Overall, 92.6% decrease in infection rate was found when using the RyMed InVision-Plus® with Neutral Advantage™ technology.
Leading the study was Dr. Cynthia C. Chernecky PhD, RN, AOCN, FAAN, Jennifer Waller, PhD both from Georgia Health Sciences University; and Denise Macklin, BSN, RNC.
Dr. Chernecky stated, "Decreasing infections is essential to quality nursing care in oncology. The use of best product when added to other nursing interventions is essential as it can enable best outcomes for treatments and ultimately quality of life and a decrease in mortality".
"This new clinical data continues to demonstrate the superior design features of RyMed's InVision-Plus® needleless IV connector technology and how they have a significant positive patient safety impact among the cancer patient population," said Dana Wm. Ryan, President & CEO, RyMed Technologies, Inc.
This poster presentation by Dr. Chernecky was preceded by another in which she highlighted similar success by the RyMed product in decreasing intraluminal thrombotic occlusions compared to a negative displacement mechanical valve. Additionally, Chernecky also delivered a podium presentation discussing new data on the apparent ineffectiveness of other silver coated needleless IV connectors.
Catheter-related bloodstream infection (CR-BSI) continues to be one of the most frequent hospital acquired infections (HAIs) reported by hospitals nationwide. It has been reported that a patient that develops a CR-BSI could die up to 25% of the time, and the industry is discovering that RyMed's InVision-Plus® technology with zero fluid displacement is going to save many lives.
Source: RyMed Technologies, Inc
The purpose of the study was to determine infection rates for a split septum valve, a negative reversed split-septum valve and an intraluminal protection device (IPD) with zero displacement in both critical care and medical in-patient oncology patients.
Detailed results:
-- CR-BSI incidences decreased 96.3%, from 2.9 to 0.1 infections per 1,000 catheter days, when the RyMed InVision-Plus® needleless IV connector was used compared to the Becton-Dickinson's Q-Syte® product.
-- CR-BSI incidences decreased 88.9%, from 3.7 to 0.4 infections per 1,000 catheter days, when the RyMed InVision-Plus® needleless IV connector was used compared to the ICU Medical Clave® product.
-- Overall, 92.6% decrease in infection rate was found when using the RyMed InVision-Plus® with Neutral Advantage™ technology.
Leading the study was Dr. Cynthia C. Chernecky PhD, RN, AOCN, FAAN, Jennifer Waller, PhD both from Georgia Health Sciences University; and Denise Macklin, BSN, RNC.
Dr. Chernecky stated, "Decreasing infections is essential to quality nursing care in oncology. The use of best product when added to other nursing interventions is essential as it can enable best outcomes for treatments and ultimately quality of life and a decrease in mortality".
"This new clinical data continues to demonstrate the superior design features of RyMed's InVision-Plus® needleless IV connector technology and how they have a significant positive patient safety impact among the cancer patient population," said Dana Wm. Ryan, President & CEO, RyMed Technologies, Inc.
This poster presentation by Dr. Chernecky was preceded by another in which she highlighted similar success by the RyMed product in decreasing intraluminal thrombotic occlusions compared to a negative displacement mechanical valve. Additionally, Chernecky also delivered a podium presentation discussing new data on the apparent ineffectiveness of other silver coated needleless IV connectors.
Catheter-related bloodstream infection (CR-BSI) continues to be one of the most frequent hospital acquired infections (HAIs) reported by hospitals nationwide. It has been reported that a patient that develops a CR-BSI could die up to 25% of the time, and the industry is discovering that RyMed's InVision-Plus® technology with zero fluid displacement is going to save many lives.
Source: RyMed Technologies, Inc
суббота, 25 июня 2011 г.
New Study Reveals Genetic Link To Blood Cancers
The study, published in the journal Nature Genetics, has shown that susceptibility to a series of blood cancers, known as myeloproliferative disorders (MPDs), is linked to a particular area of the patient's DNA, which is prone to developing mutations.
Myeloproliferative disorders are characterised by the overproduction of red and white blood cells, which increases the risk of strokes and heart attacks. Many cases of MPDs are caused by a mutation in a gene called JAK2. When the JAK2 gene has mutated, it sends abnormal messages to the blood stem cells to produce more and more blood cells.
Scientists, funded by Leukaemia Research, have found that a particular region of chromosome 9 that carries the JAK2 gene is predisposed to acquiring mutations, but only in individuals with a particular genetic makeup. It is likely that this finding will lead to a much better understanding of how the JAK2 gene mutations happen and why they lead to an increased risk of someone developing an MPD.
The study, carried out at the Wessex Regional Genetics Laboratory in Salisbury and the University of Southampton, has proved that people carrying this mutation-prone region of DNA on chromosome 9 that includes the JAK2 gene have triple the risk of developing an MPD.
The chromosome 9 variant is present in 40 per cent of the UK population but only 1 in 20,000 people develop an MPD each year. Nonetheless, the new research has confirmed that the inheritance of this genetic variant can contribute to inherited susceptibility to develop an MPD.
The study found that the link was especially strong in polycythaemia vera (PV), one of the main three MPDs. Professor Nick Cross, from the University of Southampton who led the research team, says: "This research provides strong evidence that at least half of the cases of PV diagnosed each year are linked to an inherited genetic variant on chromosome 9. Whilst this risk is still very small it nonetheless confirms that individual susceptibility to acquiring cancer-causing mutations is linked to genetic inheritance. Now that we have this evidence we can carry out studies to determine exactly how the variant contributes to this risk."
Dr Shabih Syed, Scientific Director at Leukaemia Research, adds: "This is a very important step forward in our knowledge of the causes of myeloproliferative disorders. It helps us to understand why some people might be predisposed to acquiring genetic mutations that lead to cancers."
The report is published online from 15 March 2009 in the journal Nature Genetics under the title 'JAK2 haplotype is a major risk factor for the development of myeloproliferative neoplasms'. The corresponding author is Professor Nicholas Cross of the Human Genetics Division, University of Southampton and the Wessex Regional Genetics Laboratory, Salisbury. The study was funded by the cancer charity Leukaemia Research.
Southampton University
soton.ac.uk
Myeloproliferative disorders are characterised by the overproduction of red and white blood cells, which increases the risk of strokes and heart attacks. Many cases of MPDs are caused by a mutation in a gene called JAK2. When the JAK2 gene has mutated, it sends abnormal messages to the blood stem cells to produce more and more blood cells.
Scientists, funded by Leukaemia Research, have found that a particular region of chromosome 9 that carries the JAK2 gene is predisposed to acquiring mutations, but only in individuals with a particular genetic makeup. It is likely that this finding will lead to a much better understanding of how the JAK2 gene mutations happen and why they lead to an increased risk of someone developing an MPD.
The study, carried out at the Wessex Regional Genetics Laboratory in Salisbury and the University of Southampton, has proved that people carrying this mutation-prone region of DNA on chromosome 9 that includes the JAK2 gene have triple the risk of developing an MPD.
The chromosome 9 variant is present in 40 per cent of the UK population but only 1 in 20,000 people develop an MPD each year. Nonetheless, the new research has confirmed that the inheritance of this genetic variant can contribute to inherited susceptibility to develop an MPD.
The study found that the link was especially strong in polycythaemia vera (PV), one of the main three MPDs. Professor Nick Cross, from the University of Southampton who led the research team, says: "This research provides strong evidence that at least half of the cases of PV diagnosed each year are linked to an inherited genetic variant on chromosome 9. Whilst this risk is still very small it nonetheless confirms that individual susceptibility to acquiring cancer-causing mutations is linked to genetic inheritance. Now that we have this evidence we can carry out studies to determine exactly how the variant contributes to this risk."
Dr Shabih Syed, Scientific Director at Leukaemia Research, adds: "This is a very important step forward in our knowledge of the causes of myeloproliferative disorders. It helps us to understand why some people might be predisposed to acquiring genetic mutations that lead to cancers."
The report is published online from 15 March 2009 in the journal Nature Genetics under the title 'JAK2 haplotype is a major risk factor for the development of myeloproliferative neoplasms'. The corresponding author is Professor Nicholas Cross of the Human Genetics Division, University of Southampton and the Wessex Regional Genetics Laboratory, Salisbury. The study was funded by the cancer charity Leukaemia Research.
Southampton University
soton.ac.uk
пятница, 24 июня 2011 г.
Thrombolysis: An Enlarged Treatment Window And Stent Support Open Possibilities For More Patients
Professor Ferro sees better chances for stroke victims in the newest scientific findings on thrombolytic treatment. This intravenously applied medication to break up blood clots has significantly improved survival chances for stroke victims. Guidelines and regulatory approvals have hitherto recommended a time window of three hours between the onset of stroke and the beginning of therapy.
The recently published ECASS III study showed that treatment between 3 and 4.5 hours after the onset of a stroke with the thrombolytic agent alteplase can also improve clinical outcome. Data from the trial show that thrombolysis, when used in the 3 to 4.5 hour time window, is consistent with the safety profile reported for the approved time window of 0 to 3 hours. "These new insights open treatment possibilities for a variety of patients who hitherto were not able to profit from thrombolysis. Many patients today still are not able to reach a clinic within three hours," Professor Ferro says. "I assume that this will soon be reflected in the treatment guidelines and regulatory approvals."
Yet another new approach should likewise expand the possibilities of thrombolysis. Professor Ferro notes that "endovascular stent-assisted thrombolysis is a promising treatment for patients with a specific type of artery occlusions arising from internal carotid artery (ICA) dissection." Spontaneous ICA dissection is a common cause of stroke in young people. The condition mainly has thromboembolic consequences which are often resistant to intravenous thrombolysis.
Source
European Neurological Society
The recently published ECASS III study showed that treatment between 3 and 4.5 hours after the onset of a stroke with the thrombolytic agent alteplase can also improve clinical outcome. Data from the trial show that thrombolysis, when used in the 3 to 4.5 hour time window, is consistent with the safety profile reported for the approved time window of 0 to 3 hours. "These new insights open treatment possibilities for a variety of patients who hitherto were not able to profit from thrombolysis. Many patients today still are not able to reach a clinic within three hours," Professor Ferro says. "I assume that this will soon be reflected in the treatment guidelines and regulatory approvals."
Yet another new approach should likewise expand the possibilities of thrombolysis. Professor Ferro notes that "endovascular stent-assisted thrombolysis is a promising treatment for patients with a specific type of artery occlusions arising from internal carotid artery (ICA) dissection." Spontaneous ICA dissection is a common cause of stroke in young people. The condition mainly has thromboembolic consequences which are often resistant to intravenous thrombolysis.
Source
European Neurological Society
четверг, 23 июня 2011 г.
FDA Fines American Red Cross $16 Million For Prior Failures To Meet Blood Safety Laws
The FDA announced today that the American Red Cross has been fined $16 million for prior failures to comply with Federal laws and regulations related to the collection and manufacture of blood products.
Despite the compliance failures, FDA found no evidence that the Red Cross violations endangered any patients and the blood supply is believed to be safe. Multiple layers of safeguards are in place to protect and enhance the safety of blood products. However, these types of violations decrease the assurance that blood products manufactured by American Red Cross will continue to be safe and have the potential to compromise the safety of the blood supply.
The FDA assessed fines totaling $16.18 million - $9.79 million for violations related to mismanagement of certain blood products and $6.39 million for Good Manufacturing Practice violations. Blood products include red cells, plasma and platelets.
FDA is encouraged by recent efforts made by the Red Cross leadership and will work closely with them to achieve full compliance. The FDA is hopeful these fines will encourage the Red Cross to act more quickly to take the actions necessary to address and correct the issues that have contributed to these violations.
In October 2009, the agency notified the American Red Cross that FDA inspections conducted during fiscal years 2008 and 2009 revealed violations that included failure to identify problems that occur during manufacturing and failure to adequately investigate identified problems.
The fines announced today were assessed under an amended 2003 consent decree that outlines requirements for the American Red Cross to ensure safety of the nation's blood supply.
The original 1993 decree was amended in 2003 to allow the FDA to impose significant fines for failure to comply with agency regulations and provisions designed to ensure the safety of the nation's blood supply.
Since 2003, the American Red Cross has made progress addressing some of its quality issues, including standardizing procedures, upgrading its National Testing Laboratories, and increasing oversight of the organization. However, to fully comply with federal regulations and consent decree provisions, the American Red Cross must make swift, additional progress on all of the issues the FDA has identified.
The agency has previously sent 12 similar letters to the American Red Cross and imposed a total of more than $21 million in fines under terms of the amended 2003 consent decree.
The American Red Cross is one of several organizations that is responsible for the nation's blood supply.
Source:
U.S. Food and Drug Administration
Despite the compliance failures, FDA found no evidence that the Red Cross violations endangered any patients and the blood supply is believed to be safe. Multiple layers of safeguards are in place to protect and enhance the safety of blood products. However, these types of violations decrease the assurance that blood products manufactured by American Red Cross will continue to be safe and have the potential to compromise the safety of the blood supply.
The FDA assessed fines totaling $16.18 million - $9.79 million for violations related to mismanagement of certain blood products and $6.39 million for Good Manufacturing Practice violations. Blood products include red cells, plasma and platelets.
FDA is encouraged by recent efforts made by the Red Cross leadership and will work closely with them to achieve full compliance. The FDA is hopeful these fines will encourage the Red Cross to act more quickly to take the actions necessary to address and correct the issues that have contributed to these violations.
In October 2009, the agency notified the American Red Cross that FDA inspections conducted during fiscal years 2008 and 2009 revealed violations that included failure to identify problems that occur during manufacturing and failure to adequately investigate identified problems.
The fines announced today were assessed under an amended 2003 consent decree that outlines requirements for the American Red Cross to ensure safety of the nation's blood supply.
The original 1993 decree was amended in 2003 to allow the FDA to impose significant fines for failure to comply with agency regulations and provisions designed to ensure the safety of the nation's blood supply.
Since 2003, the American Red Cross has made progress addressing some of its quality issues, including standardizing procedures, upgrading its National Testing Laboratories, and increasing oversight of the organization. However, to fully comply with federal regulations and consent decree provisions, the American Red Cross must make swift, additional progress on all of the issues the FDA has identified.
The agency has previously sent 12 similar letters to the American Red Cross and imposed a total of more than $21 million in fines under terms of the amended 2003 consent decree.
The American Red Cross is one of several organizations that is responsible for the nation's blood supply.
Source:
U.S. Food and Drug Administration
среда, 22 июня 2011 г.
Incyte's Selective JAK1 / 2 Inhibitor, INCB18424, Demonstrates Rapid And Durable Clinical Benefits In Myelofibrosis Patients
Incyte Corporation (Nasdaq: INCY) will present updated results from an ongoing Phase II trial of INCB18424, its selective, orally available Janus kinase (JAK) inhibitor, in patients with myelofibrosis (MF) at the 50th American Society of Hematology (ASH) Annual Meeting.
MF is a serious neoplastic condition characterized by varying degrees of bone marrow failure, splenic enlargement and debilitating constitutional symptoms resulting in a significant loss in quality of life and reduced life-span. There are currently no approved treatments for patients with myelofibrosis.
Srdan Verstovsek, M.D., Ph.D., Associate Professor, Leukemia Department, Myeloproliferative Disorders Program Leader, University of Texas M.D. Anderson Cancer Center, and the principal investigator for the Phase II trial, stated, "Over the past 18 months, nearly 150 MF patients have been enrolled in the Phase II trial, INCB18424-251. Important and previously unachievable clinical benefits observed in this study include striking improvement in splenomegaly and the debilitating constitutional symptoms that plague the majority of these patients. INCB18424 treatment improves the systemic inflammatory state which we know characterizes advanced MF. INCB18424 results in prompt and sustained reductions in the markedly elevated levels of a broad range of pro-inflammatory cytokines that we have now documented in MF patients. Additionally, regardless of an MF patient's diagnostic subgroup or the presence or absence of JAK2 mutations which occur in subsets of MF patients, the vast majority of patients entering this trial remain on study, many for a year or more, with durable and robust clinical benefit."
Richard Levy, M.D., Incyte's Senior Vice President, Drug Development, added, "The updated data set, much of which will be summarized at ASH, confirms that long term INCB18424 treatment has been well tolerated and results in durable clinical improvement in splenomegaly, constitutional symptoms, and cachexia. New data also demonstrate improvement in exercise tolerance and confirmation of spleen size reduction as measured by MRI. Importantly, this clinical experience gives us the confidence to select registration endpoints and the dosing regimen for the Phase III program which we expect will support US and international registrations. We plan to start Phase III in the first half of 2009 following FDA approval of a special protocol assessment."
The most current data from the ongoing Phase II trial will be described in four posters to be presented at the ASH meeting (to access copies of these posters, click here.
# 1760: INCB018424, a Selective JAK1/2 Inhibitor, Significantly Improves the Compromised Nutritional Status and Frank Cachexia in Patients with Myelofibrosis (MF)
Ruben A. Mesa, MD, FACP, Srdan Verstovsek, Hagop M. Kantarjian, MD, Animesh D. Pardanani, MBBS, PhD, Steven Friedman, MD, Robert Newton, Susan Erickson-Viitanen, Deborah Hunter, John Redman, MD, Swamy Yeleswaram, Edward Bradley, MD and Ayalew Tefferi, MD
# 1762: The JAK Inhibitor, INCB018424, Demonstrates Durable and Marked Clinical Responses in Primary Myelofibrosis (PMF) and Post-Polycythemia Vera/Essential Thrombocythemia Myelofibrosis (Post PV/ET-MF)
Srdan Verstovsek, Hagop M. Kantarjian, MD, Animesh D. Pardanani, MBBS, PhD, Deborah Thomas, MD, Jorge Cortes, MD, Ruben A. Mesa, MD, FACP, William J.Hogan, MBChB, John R. Redman, MD, Sue Erickson-Viitanen, Richard Levy, MD, Kris Vaddi, PhD, DVM, Edward Bradley, MD, Jordan Fridman, PhD and Ayalew Tefferi, MD
# 2804: The Clinical Phenotype of Myelofibrosis Encompasses a Chronic Inflammatory State that is Favorably Altered by INCB018424, a Selective Inhibitor of JAK1/2
Ayalew Tefferi, MD, Hagop M Kantarjian, Animesh D. Pardanani, MBBS, PhD, Ruben A. Mesa, MD, FACP, Robert C Newton, PhD, Peggy A Scherle, PhD, Timothy Burn, PhD and Srdan Verstovsek
# 2802: Characterization of JAK2 V617F Allele Burden in Advanced Myelofibrosis (MF) Patients: No Change in V617F:WT JAK2 Ratio in Patients with High Allele Burdens despite Profound Clinical Improvement Following Treatment with the JAK Inhibitor, INCB018424
Srdan Verstovsek, MD, PhD, Hagop M. Kantarjian, MD, Animesh D. Pardanani, MBBS, PhD, Timothy Burn, PhD, Kris Vaddi, PhD, DVM, John Redman, MD, Edward C Bradley, MD, Richard Levy, MD, Steven Friedman, MD, Gregory Hollis, PhD and Ayalew Tefferi, MD
Phase II Study Design
Study INCB18424-251 is an ongoing Phase II trial in patients with primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (post-PV/MF), and post-essential thrombocythemia myelofibrosis (post-ET/MF) with both mutated JAK2 (V617F mutation) and normal JAK2 (wild type). To date, 148 patients have been enrolled in the Phase II trial, which includes several different twice-daily and once-daily doses. Primary objectives of the study include:
-- The determination of the safety and efficacy of INCB18424 treatment in MF patients
-- Evaluation of twice-daily and once-daily dosing regimens to identify an optimal dosing paradigm for use in future clinical trials
-- Prospective identification of functional measures of clinical efficacy
In this ongoing Phase II trial, INCB18424 has been well tolerated, with no off-target toxicities. Reversible thrombocytopenia is the dose-limiting toxicity and has been effectively managed by dose reduction and/or interruption of therapy. The median duration of treatment with INCB18424 is approximately 7 months.
About Myeloproliferative Disease
Myeloproliferative diseases (MPDs) are a related group of hematological neoplasms characterized by dysfunction of the bone marrow resulting in either over production of blood cells or ineffective hematopoiesis leading to production of blood cells in the spleen and resulting in massive splenomegaly. The three main MPDs are polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF). Approximately 10 to 20% of patients with PV and ET progress to MF and MF can also develop without a prior history of PV or ET. There is currently no known cure for these diseases and there are no adequately effective therapies.
About The Incyte JAK Inhibitor Program
There are four known JAK enzymes: JAK1, 2, 3 and TYK2. These enzymes are critical components of signaling mechanisms utilized by a number of cytokines and growth factors, including those that are elevated in MPD patients and which may contribute to poor quality of life in these patients. Pathways triggered by the JAKs are dysregulated in inflammation, myeloproliferative diseases, and other liquid and solid cancers.
INCB18424 is Incyte's lead internally developed JAK inhibitor. The compound is a potent JAK inhibitor that is greater than 100-fold selective against a broad panel of kinases and is being developed as an oral treatment for MF, PV and ET, multiple myeloma, hormone refractory prostate cancer, and rheumatoid arthritis and as a topical treatment for psoriasis.
Incyte has discovered multiple potent, selective and orally bioavailable JAK inhibitors from multiple distinct chemical scaffolds. A lead follow-on compound, INCB28050, is in Phase Ib development.
Webcast Information
Incyte is hosting a meeting to discuss the INCB18424 data presented at the 50th American Society of Hematology Annual Meeting. The webcast is scheduled to begin at 7:30 p.m. PT (10:30 p.m. ET) on Monday, December 8, 2008, and can be accessed at: incyte under Investor Relations, Events and Webcasts.
The discussion will feature Srdan Verstovsek, M.D., Ph.D., Associate Professor, Leukemia Department, Myeloproliferative Disorders Program Leader, University of Texas M.D. Anderson Cancer Center, and Richard Levy, M.D., Senior Vice President, Drug Development, Incyte.
A replay of this event will be available and can be assessed at: incyte.
About Incyte
Incyte Corporation is a Wilmington, Delaware-based drug discovery and development company focused on developing proprietary small molecule drugs to treat serious unmet medical needs. Incyte's pipeline includes multiple compounds in Phase I and Phase II development for oncology, inflammation and diabetes. incyte
Forward Looking Statements
Except for the historical information contained herein, the matters set forth in this press release, including statements with respect to clinical experience giving the confidence to select registration endpoints and the dosing regimen for a Phase III program which we expect will support US and international registrations, plans to start Phase III in the first half of 2009 following FDA approval of a special protocol assessment for INCB18424 for myelofibrosis, plans to describe the most current data from the ongoing Phase II clinical trial of INCB 18424 in myelofibrosis at ASH, plans to develop INCB18424 as an oral treatment for MF, PV and ET, multiple myeloma, hormone refractory prostate cancer, and rheumatoid arthritis and as a topical treatment for psoriasis, are all forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially, including the high degree of risk associated with drug development and clinical trials, the uncertainty of the FDA approval process, results of further research and development, the impact of competition and of technological advances and the ability of Incyte to compete against parties with greater financial or other resources, Incyte's ability to enroll a sufficient number of patients for its clinical trials, and other risks detailed from time to time in Incyte's filings with the Securities and Exchange Commission, including its Quarterly Report on Form 10-Q for the quarter ended September 30, 2008. Incyte disclaims any intent or obligation to update these forward-looking statements.
MF is a serious neoplastic condition characterized by varying degrees of bone marrow failure, splenic enlargement and debilitating constitutional symptoms resulting in a significant loss in quality of life and reduced life-span. There are currently no approved treatments for patients with myelofibrosis.
Srdan Verstovsek, M.D., Ph.D., Associate Professor, Leukemia Department, Myeloproliferative Disorders Program Leader, University of Texas M.D. Anderson Cancer Center, and the principal investigator for the Phase II trial, stated, "Over the past 18 months, nearly 150 MF patients have been enrolled in the Phase II trial, INCB18424-251. Important and previously unachievable clinical benefits observed in this study include striking improvement in splenomegaly and the debilitating constitutional symptoms that plague the majority of these patients. INCB18424 treatment improves the systemic inflammatory state which we know characterizes advanced MF. INCB18424 results in prompt and sustained reductions in the markedly elevated levels of a broad range of pro-inflammatory cytokines that we have now documented in MF patients. Additionally, regardless of an MF patient's diagnostic subgroup or the presence or absence of JAK2 mutations which occur in subsets of MF patients, the vast majority of patients entering this trial remain on study, many for a year or more, with durable and robust clinical benefit."
Richard Levy, M.D., Incyte's Senior Vice President, Drug Development, added, "The updated data set, much of which will be summarized at ASH, confirms that long term INCB18424 treatment has been well tolerated and results in durable clinical improvement in splenomegaly, constitutional symptoms, and cachexia. New data also demonstrate improvement in exercise tolerance and confirmation of spleen size reduction as measured by MRI. Importantly, this clinical experience gives us the confidence to select registration endpoints and the dosing regimen for the Phase III program which we expect will support US and international registrations. We plan to start Phase III in the first half of 2009 following FDA approval of a special protocol assessment."
The most current data from the ongoing Phase II trial will be described in four posters to be presented at the ASH meeting (to access copies of these posters, click here.
# 1760: INCB018424, a Selective JAK1/2 Inhibitor, Significantly Improves the Compromised Nutritional Status and Frank Cachexia in Patients with Myelofibrosis (MF)
Ruben A. Mesa, MD, FACP, Srdan Verstovsek, Hagop M. Kantarjian, MD, Animesh D. Pardanani, MBBS, PhD, Steven Friedman, MD, Robert Newton, Susan Erickson-Viitanen, Deborah Hunter, John Redman, MD, Swamy Yeleswaram, Edward Bradley, MD and Ayalew Tefferi, MD
# 1762: The JAK Inhibitor, INCB018424, Demonstrates Durable and Marked Clinical Responses in Primary Myelofibrosis (PMF) and Post-Polycythemia Vera/Essential Thrombocythemia Myelofibrosis (Post PV/ET-MF)
Srdan Verstovsek, Hagop M. Kantarjian, MD, Animesh D. Pardanani, MBBS, PhD, Deborah Thomas, MD, Jorge Cortes, MD, Ruben A. Mesa, MD, FACP, William J.Hogan, MBChB, John R. Redman, MD, Sue Erickson-Viitanen, Richard Levy, MD, Kris Vaddi, PhD, DVM, Edward Bradley, MD, Jordan Fridman, PhD and Ayalew Tefferi, MD
# 2804: The Clinical Phenotype of Myelofibrosis Encompasses a Chronic Inflammatory State that is Favorably Altered by INCB018424, a Selective Inhibitor of JAK1/2
Ayalew Tefferi, MD, Hagop M Kantarjian, Animesh D. Pardanani, MBBS, PhD, Ruben A. Mesa, MD, FACP, Robert C Newton, PhD, Peggy A Scherle, PhD, Timothy Burn, PhD and Srdan Verstovsek
# 2802: Characterization of JAK2 V617F Allele Burden in Advanced Myelofibrosis (MF) Patients: No Change in V617F:WT JAK2 Ratio in Patients with High Allele Burdens despite Profound Clinical Improvement Following Treatment with the JAK Inhibitor, INCB018424
Srdan Verstovsek, MD, PhD, Hagop M. Kantarjian, MD, Animesh D. Pardanani, MBBS, PhD, Timothy Burn, PhD, Kris Vaddi, PhD, DVM, John Redman, MD, Edward C Bradley, MD, Richard Levy, MD, Steven Friedman, MD, Gregory Hollis, PhD and Ayalew Tefferi, MD
Phase II Study Design
Study INCB18424-251 is an ongoing Phase II trial in patients with primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (post-PV/MF), and post-essential thrombocythemia myelofibrosis (post-ET/MF) with both mutated JAK2 (V617F mutation) and normal JAK2 (wild type). To date, 148 patients have been enrolled in the Phase II trial, which includes several different twice-daily and once-daily doses. Primary objectives of the study include:
-- The determination of the safety and efficacy of INCB18424 treatment in MF patients
-- Evaluation of twice-daily and once-daily dosing regimens to identify an optimal dosing paradigm for use in future clinical trials
-- Prospective identification of functional measures of clinical efficacy
In this ongoing Phase II trial, INCB18424 has been well tolerated, with no off-target toxicities. Reversible thrombocytopenia is the dose-limiting toxicity and has been effectively managed by dose reduction and/or interruption of therapy. The median duration of treatment with INCB18424 is approximately 7 months.
About Myeloproliferative Disease
Myeloproliferative diseases (MPDs) are a related group of hematological neoplasms characterized by dysfunction of the bone marrow resulting in either over production of blood cells or ineffective hematopoiesis leading to production of blood cells in the spleen and resulting in massive splenomegaly. The three main MPDs are polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF). Approximately 10 to 20% of patients with PV and ET progress to MF and MF can also develop without a prior history of PV or ET. There is currently no known cure for these diseases and there are no adequately effective therapies.
About The Incyte JAK Inhibitor Program
There are four known JAK enzymes: JAK1, 2, 3 and TYK2. These enzymes are critical components of signaling mechanisms utilized by a number of cytokines and growth factors, including those that are elevated in MPD patients and which may contribute to poor quality of life in these patients. Pathways triggered by the JAKs are dysregulated in inflammation, myeloproliferative diseases, and other liquid and solid cancers.
INCB18424 is Incyte's lead internally developed JAK inhibitor. The compound is a potent JAK inhibitor that is greater than 100-fold selective against a broad panel of kinases and is being developed as an oral treatment for MF, PV and ET, multiple myeloma, hormone refractory prostate cancer, and rheumatoid arthritis and as a topical treatment for psoriasis.
Incyte has discovered multiple potent, selective and orally bioavailable JAK inhibitors from multiple distinct chemical scaffolds. A lead follow-on compound, INCB28050, is in Phase Ib development.
Webcast Information
Incyte is hosting a meeting to discuss the INCB18424 data presented at the 50th American Society of Hematology Annual Meeting. The webcast is scheduled to begin at 7:30 p.m. PT (10:30 p.m. ET) on Monday, December 8, 2008, and can be accessed at: incyte under Investor Relations, Events and Webcasts.
The discussion will feature Srdan Verstovsek, M.D., Ph.D., Associate Professor, Leukemia Department, Myeloproliferative Disorders Program Leader, University of Texas M.D. Anderson Cancer Center, and Richard Levy, M.D., Senior Vice President, Drug Development, Incyte.
A replay of this event will be available and can be assessed at: incyte.
About Incyte
Incyte Corporation is a Wilmington, Delaware-based drug discovery and development company focused on developing proprietary small molecule drugs to treat serious unmet medical needs. Incyte's pipeline includes multiple compounds in Phase I and Phase II development for oncology, inflammation and diabetes. incyte
Forward Looking Statements
Except for the historical information contained herein, the matters set forth in this press release, including statements with respect to clinical experience giving the confidence to select registration endpoints and the dosing regimen for a Phase III program which we expect will support US and international registrations, plans to start Phase III in the first half of 2009 following FDA approval of a special protocol assessment for INCB18424 for myelofibrosis, plans to describe the most current data from the ongoing Phase II clinical trial of INCB 18424 in myelofibrosis at ASH, plans to develop INCB18424 as an oral treatment for MF, PV and ET, multiple myeloma, hormone refractory prostate cancer, and rheumatoid arthritis and as a topical treatment for psoriasis, are all forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially, including the high degree of risk associated with drug development and clinical trials, the uncertainty of the FDA approval process, results of further research and development, the impact of competition and of technological advances and the ability of Incyte to compete against parties with greater financial or other resources, Incyte's ability to enroll a sufficient number of patients for its clinical trials, and other risks detailed from time to time in Incyte's filings with the Securities and Exchange Commission, including its Quarterly Report on Form 10-Q for the quarter ended September 30, 2008. Incyte disclaims any intent or obligation to update these forward-looking statements.
вторник, 21 июня 2011 г.
Anemia elevates risk of physical decline in older people
Contact: Doug Dollemore
dollemodnia.nih
301-496-1752
NIH/National Institute on Aging
Anemia doubles the risk that an older person will develop serious physical declines that can erode the ability to live independently, according to a new epidemiological study supported by the National Institute on Aging (NIA) and others*. It is the first longitudinal research to find an association between physical decline in later life and anemia, a blood condition that affects about 13 percent of older Americans.
The study,** published in the August 1, 2003 issue of the American Journal of Medicine, also found that older people who do not yet have anemia, but whose blood tests are just above the traditional cut off point for diagnosing the condition, are 1.5 times more likely to develop physical declines than those who have normal blood hemoglobin levels.
'This study suggests that even mild anemia is a risk factor linked to reduced ability of older people to function at their fullest potential,' said Jack Guralnik, M.D., Ph.D., an NIA epidemiologist who co-authored the study. 'Further research will tell us whether the treatment of anemia can prevent the progressive decline in function that eventually results in disability.'
The investigators, led by Brenda Penninx, Ph.D., of Wake Forest University School of Medicine in Winston-Salem, North Carolina, followed a group of 1,146 people, ages 71 and older, for more than 4 years, assessing their ability to perform three physical tasks: standing balance, a timed 8-foot walk, and ability to rise from a chair.
Each of these activities was scored on a 5-point scale (0= an inability to do the test; 4=top performance). These points were added together to create a 0 to 12 overall score. These scores were correlated with blood samples obtained from the participants.
Anemia is defined by the World Health Organization (WHO) as hemoglobin levels below 12g/dL in women and below 13g/dL in men. For this study, Dr. Penninx classified men and women whose blood hemoglobin levels were within1g/dL of the WHO standard (12-13g/dL for women, 13-14g/dL for men) as having borderline anemia.
At the end of the four-year study, two-thirds of the participants had at least modest declines in physical performance scores, with 346 people (30 percent) having substantial decreases.
Overall, those who did not have anemia averaged a 1.4 point decline on the 12-point scale during the study. In contrast, those who had borderline anemia dipped an average of 1.8 points and those with anemia dropped an average of 2.3 points on the 12-point scale.
Women with anemia showed the greatest physical decline followed by women who had borderline anemia. Also, men with anemia had significantly greater physical decline than men with normal blood hemoglobin levels.
Men with borderline anemia were more likely to show physical decline than those whose hemoglobin levels were slightly higher than the WHO standard.
Excluding people who had ailments associated with anemia, such as cancer, kidney disease, and infections, did not change the findings.
In a previous study, using the same data, Dr. Penninx found that a decrease in physical performance is highly predictive of hospitalization, nursing home admission and mortality.
In his work, Dr. Guralnik has found that a 1.5 point decrease is associated with a 50 percent increased risk of developing a disability that impairs a person's ability to do activities of daily living, such as bathing, eating and dressing.
'Although no study yet shows that treating anemia in older people reduces the incidence of physical decline, our study certainly suggests that this may be the case,' Dr. Penninx said. 'Anemia deserves clinical attention. That's the take home message.'
Anemia affects at least 3.4 million Americans and is the most common blood disorder in the United States. It occurs when the body doesn't produce enough red blood cells or red blood cells are prematurely destroyed.
More specifically, it is defined as a low concentration of hemoglobin, the main component of red blood cells that transports oxygen from the lungs to other tissues and then returns carbon dioxide from the body to the lungs. A person who has anemia can feel fatigued, dizzy, apathetic or irritable.
Other common symptoms include muscle weakness, shortness of breath, rapid heart beat, and pale skin. However, the warning signs are often subtle and can be difficult for doctors to detect.
Anemia can be caused by vitamin or mineral deficiencies, particularly of iron, vitamin B12, and folic acid. Underlying diseases including cancer, rheumatoid arthritis and chronic kidney disease also can trigger anemia.
But in up to 25 percent of cases, no cause can be identified. Treatment varies, but dietary changes, nutritional supplements, and medications can help. The National Institute on Aging is one of 27 Institutes and Centers that constitute the National Institutes of Health.
The NIA leads Federal efforts to support and conduct basic, clinical, epidemiological, and social research on aging and the special needs of older people. Press releases, fact sheets, and other materials about aging and aging research can be viewed at the NIA's general information Web site, nia.nih.
* This study was funded by the National Institute on Aging and through support from Ortho Biotech Products, L.P.
** B.W.J.H. Penninx, J.M. Guralnik, G. Onder, L. Ferrucci, R.B. Wallace, and M. Pahor, 'Anemia and decline in physical performance among older persons,' American Journal of Medicine, Vol. 115, No. 2, pp. 104-110.
dollemodnia.nih
301-496-1752
NIH/National Institute on Aging
Anemia doubles the risk that an older person will develop serious physical declines that can erode the ability to live independently, according to a new epidemiological study supported by the National Institute on Aging (NIA) and others*. It is the first longitudinal research to find an association between physical decline in later life and anemia, a blood condition that affects about 13 percent of older Americans.
The study,** published in the August 1, 2003 issue of the American Journal of Medicine, also found that older people who do not yet have anemia, but whose blood tests are just above the traditional cut off point for diagnosing the condition, are 1.5 times more likely to develop physical declines than those who have normal blood hemoglobin levels.
'This study suggests that even mild anemia is a risk factor linked to reduced ability of older people to function at their fullest potential,' said Jack Guralnik, M.D., Ph.D., an NIA epidemiologist who co-authored the study. 'Further research will tell us whether the treatment of anemia can prevent the progressive decline in function that eventually results in disability.'
The investigators, led by Brenda Penninx, Ph.D., of Wake Forest University School of Medicine in Winston-Salem, North Carolina, followed a group of 1,146 people, ages 71 and older, for more than 4 years, assessing their ability to perform three physical tasks: standing balance, a timed 8-foot walk, and ability to rise from a chair.
Each of these activities was scored on a 5-point scale (0= an inability to do the test; 4=top performance). These points were added together to create a 0 to 12 overall score. These scores were correlated with blood samples obtained from the participants.
Anemia is defined by the World Health Organization (WHO) as hemoglobin levels below 12g/dL in women and below 13g/dL in men. For this study, Dr. Penninx classified men and women whose blood hemoglobin levels were within1g/dL of the WHO standard (12-13g/dL for women, 13-14g/dL for men) as having borderline anemia.
At the end of the four-year study, two-thirds of the participants had at least modest declines in physical performance scores, with 346 people (30 percent) having substantial decreases.
Overall, those who did not have anemia averaged a 1.4 point decline on the 12-point scale during the study. In contrast, those who had borderline anemia dipped an average of 1.8 points and those with anemia dropped an average of 2.3 points on the 12-point scale.
Women with anemia showed the greatest physical decline followed by women who had borderline anemia. Also, men with anemia had significantly greater physical decline than men with normal blood hemoglobin levels.
Men with borderline anemia were more likely to show physical decline than those whose hemoglobin levels were slightly higher than the WHO standard.
Excluding people who had ailments associated with anemia, such as cancer, kidney disease, and infections, did not change the findings.
In a previous study, using the same data, Dr. Penninx found that a decrease in physical performance is highly predictive of hospitalization, nursing home admission and mortality.
In his work, Dr. Guralnik has found that a 1.5 point decrease is associated with a 50 percent increased risk of developing a disability that impairs a person's ability to do activities of daily living, such as bathing, eating and dressing.
'Although no study yet shows that treating anemia in older people reduces the incidence of physical decline, our study certainly suggests that this may be the case,' Dr. Penninx said. 'Anemia deserves clinical attention. That's the take home message.'
Anemia affects at least 3.4 million Americans and is the most common blood disorder in the United States. It occurs when the body doesn't produce enough red blood cells or red blood cells are prematurely destroyed.
More specifically, it is defined as a low concentration of hemoglobin, the main component of red blood cells that transports oxygen from the lungs to other tissues and then returns carbon dioxide from the body to the lungs. A person who has anemia can feel fatigued, dizzy, apathetic or irritable.
Other common symptoms include muscle weakness, shortness of breath, rapid heart beat, and pale skin. However, the warning signs are often subtle and can be difficult for doctors to detect.
Anemia can be caused by vitamin or mineral deficiencies, particularly of iron, vitamin B12, and folic acid. Underlying diseases including cancer, rheumatoid arthritis and chronic kidney disease also can trigger anemia.
But in up to 25 percent of cases, no cause can be identified. Treatment varies, but dietary changes, nutritional supplements, and medications can help. The National Institute on Aging is one of 27 Institutes and Centers that constitute the National Institutes of Health.
The NIA leads Federal efforts to support and conduct basic, clinical, epidemiological, and social research on aging and the special needs of older people. Press releases, fact sheets, and other materials about aging and aging research can be viewed at the NIA's general information Web site, nia.nih.
* This study was funded by the National Institute on Aging and through support from Ortho Biotech Products, L.P.
** B.W.J.H. Penninx, J.M. Guralnik, G. Onder, L. Ferrucci, R.B. Wallace, and M. Pahor, 'Anemia and decline in physical performance among older persons,' American Journal of Medicine, Vol. 115, No. 2, pp. 104-110.
понедельник, 20 июня 2011 г.
New And Complex Circuitry Revealed By Global View Of Blood Cell Development
A small pool of stem cells replenishes the human body with about 200 billion new blood cells daily. But the elaborate circuitry that determines if a cell will develop into a T cell, red blood cell, or one of the nine or more other blood cell types remains largely unknown. A research team led by scientists from the Broad Institute and Brigham and Women's Hospital has taken a systematic approach to help decipher this circuitry, compiling a comprehensive catalog of the factors that determine a blood cell's fate. Their work appears in the January 21 issue of Cell.
The researchers found that blood cells are directed by a multitude of transcription factors, proteins that turn on and off genes. While many previous studies have focused on individual transcription factors or types of blood cells, this study examined the expression and regulation of all transcription factors throughout blood development. The findings point to densely, interconnected circuits that control this process, suggesting that the wiring for blood cell fate is far more complex than previously thought.
"One assumption in the field had been that there are a small number of transcription factors that orchestrate this process," said Aviv Regev, a Broad Institute core member and co-senior corresponding author of the study. "Some people have always thought there would be a lot of factors and that it would just take time to find them. It turns out there are more masters than we would have thought."
The researchers looked globally at how the expression of all 20,000 or so genes in the genome change as blood stem cells become specialized cell types (a process known as differentiation). They discovered that while a small fraction of genes are uniquely expressed in a single type of cell, other genes are more broadly expressed - present in a variety of cell types but at varying levels. Some of these genes are turned on in the blood stem cells and switched off at certain points in development while others are reused in several parallel developmental branches. The researchers found about 80 of these patterns of variable genes, called modules. Each kind of specialized cell has a unique profile, or combination, of these modules.
Looking at the genes modulated in the course of healthy cell development could give researchers clues about what events lead to blood cancers, such as leukemia, a disease where differentiation has gone wrong.
"When you look at leukemia cells beneath a microscope, they have a lack of differentiation and they look abnormal," said Broad associate member Ben Ebert, an associate physician of hematology at Brigham and Women's Hospital and a senior corresponding author of the study. "They've ended up in a place that doesn't exist in normal development." Now that the researchers have a clearer picture of the modules that normal cells exhibit, they can apply this knowledge to help identify the similarities and critical changes in leukemia cells' profiles.
"Leukemia cells have the same set of building blocks as normal blood cells - some, they keep the right way so a piece of the profile is right, and a piece of the profile is wrong," said Regev, who is also an assistant professor in the department of biology at MIT and an Early Career Scientist at Howard Hughes Medical Institute.
The research team included co-first author Noa Novershtern from the School of Computer Science at the Hebrew University of Jerusalem, co-first author Aravind Subramanian in Todd Golub's laboratory at the Broad, and Lee Lawton and other collaborators in Richard Young's laboratory at the Whitehead Institute. All of their results will be made publicly available online through a database known as the Differentiation Map Portal (or D-Map). Ebert, Regev and their colleagues intend for D-Map to be a starting point for other researchers, empowering their investigations into the biology of blood cells as well as leukemia and other human diseases.
"Already, many people are asking for the data. Other groups can now combine their data with ours to ask new questions," said Novershtern. "What's also exciting is that people can see the power of computational models, tools that can be used to find new biological insights from the data."
Notes:
This work was supported by the Richard Merkin Foundation for Stem Cell Research at the Broad Institute, the Damon Runyon-Rachleff Foundation, the Searle Scholar Program, the Burroughs Wellcome Fund, the Smith Family Foundation, the Howard Hughes Medical Institute, and the National Institutes of Health.
Paper cited: Novershtern N. et al. Densely interconnected transcriptional circuits control cell states in human hematopoiesis. Cell. Published online January 20, 2011.
Source:
Nicole Davis
Broad Institute of MIT and Harvard
The researchers found that blood cells are directed by a multitude of transcription factors, proteins that turn on and off genes. While many previous studies have focused on individual transcription factors or types of blood cells, this study examined the expression and regulation of all transcription factors throughout blood development. The findings point to densely, interconnected circuits that control this process, suggesting that the wiring for blood cell fate is far more complex than previously thought.
"One assumption in the field had been that there are a small number of transcription factors that orchestrate this process," said Aviv Regev, a Broad Institute core member and co-senior corresponding author of the study. "Some people have always thought there would be a lot of factors and that it would just take time to find them. It turns out there are more masters than we would have thought."
The researchers looked globally at how the expression of all 20,000 or so genes in the genome change as blood stem cells become specialized cell types (a process known as differentiation). They discovered that while a small fraction of genes are uniquely expressed in a single type of cell, other genes are more broadly expressed - present in a variety of cell types but at varying levels. Some of these genes are turned on in the blood stem cells and switched off at certain points in development while others are reused in several parallel developmental branches. The researchers found about 80 of these patterns of variable genes, called modules. Each kind of specialized cell has a unique profile, or combination, of these modules.
Looking at the genes modulated in the course of healthy cell development could give researchers clues about what events lead to blood cancers, such as leukemia, a disease where differentiation has gone wrong.
"When you look at leukemia cells beneath a microscope, they have a lack of differentiation and they look abnormal," said Broad associate member Ben Ebert, an associate physician of hematology at Brigham and Women's Hospital and a senior corresponding author of the study. "They've ended up in a place that doesn't exist in normal development." Now that the researchers have a clearer picture of the modules that normal cells exhibit, they can apply this knowledge to help identify the similarities and critical changes in leukemia cells' profiles.
"Leukemia cells have the same set of building blocks as normal blood cells - some, they keep the right way so a piece of the profile is right, and a piece of the profile is wrong," said Regev, who is also an assistant professor in the department of biology at MIT and an Early Career Scientist at Howard Hughes Medical Institute.
The research team included co-first author Noa Novershtern from the School of Computer Science at the Hebrew University of Jerusalem, co-first author Aravind Subramanian in Todd Golub's laboratory at the Broad, and Lee Lawton and other collaborators in Richard Young's laboratory at the Whitehead Institute. All of their results will be made publicly available online through a database known as the Differentiation Map Portal (or D-Map). Ebert, Regev and their colleagues intend for D-Map to be a starting point for other researchers, empowering their investigations into the biology of blood cells as well as leukemia and other human diseases.
"Already, many people are asking for the data. Other groups can now combine their data with ours to ask new questions," said Novershtern. "What's also exciting is that people can see the power of computational models, tools that can be used to find new biological insights from the data."
Notes:
This work was supported by the Richard Merkin Foundation for Stem Cell Research at the Broad Institute, the Damon Runyon-Rachleff Foundation, the Searle Scholar Program, the Burroughs Wellcome Fund, the Smith Family Foundation, the Howard Hughes Medical Institute, and the National Institutes of Health.
Paper cited: Novershtern N. et al. Densely interconnected transcriptional circuits control cell states in human hematopoiesis. Cell. Published online January 20, 2011.
Source:
Nicole Davis
Broad Institute of MIT and Harvard
воскресенье, 19 июня 2011 г.
News From The Journal Of Clinical Investigation
System overload: infusion of IgG helps clear therapeutic and imaging antibodies from the circulation
The use of monoclonal IgG antibodies attached to toxins or radioactive substances for treating and imaging cancer is currently limited by the ability of IgG to remain in the blood for a long time because this decreases the tumor-to-background contrast and increases normal tissue toxicity. Now, David Scheinberg and colleagues at Memorial Sloan-Kettering Cancer Center, New York, have found a way to decrease the length of time IgG stays in the blood of both mice and humans such that tumor targeting is not compromised but the negative side effects of radiolabeled IgG are substantially diminished.
IgG hangs around in the blood for a long time because it is protected from degradation by the neonatal Fc receptor (FcRn). Infusing mice and humans with large amounts of polyclonal IgG after they had received a radiolabeled monoclonal antibody increased the rate of clearance of the radiolabeled monoclonal antibody from the blood. For both mice and humans, uptake of the radiolabeled monoclonal antibody by the tumor was the same with or without IgG infusion. However, the contrast between the labeled tumor and blood was much better with IgG infusion. Further analysis in mice also showed that IgG infusion decreased the normal tissue toxicity caused by the radiolabeled monoclonal antibody. The authors therefore suggest that polycloncal IgG infusion provides a new way to enhance the therapeutic and imaging efficacy of radiolabeled and toxin-conjugated monoclonal antibodies.
TITLE: Improved tumor imaging and therapy via i.v. Ig-mediated time-sequential modulation of neonatal Fc receptor
AUTHOR CONTACT:
David A. Scheinberg
Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Uncovering the molecules behind B cell lymphomagenesis
New data produced by Andrei Thomas-Tikhonenko and colleagues at the University of Pennsylvania, Philadelphia, provides a molecular mechanism by which a protein known as PAX5 promotes the growth of a number of types of lymphoma.
Overexpression of PAX5 in mouse B cell lymphoma cell lines increased tumor growth when these cells were transplanted into mice. Conversely, knocking down expression of PAX5 in these cell lines decreased tumor growth when the cells were transplanted into mice. Further analysis revealed that PAX5 promoted B cell lymphomagenesis by increasing the level of expression of molecules involved in B cell receptor signaling and decreasing the level of expression of molecules that inhibit B cell receptor signaling. Inhibitors of the BCR signaling pathway blocked tumor growth further highlighting the importance of BCR signaling in PAX5-driven growth of B cell lymphomas.
TITLE: B cell activator PAX5 promotes lymphomagenesis through stimulation of B cell receptor signaling
AUTHOR CONTACT:
Andrei Thomas-Tikhonenko
University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Building muscle requires Foxo1
The mechanisms by which Foxo proteins regulate metabolism are relatively well characterized. However, little was known about the mechanisms by which these same proteins regulate cellular differentiation. New data generated by Domenico Accili and colleagues at Columbia University, New York, now indicates that Foxo1 cooperates with Notch to control muscle cell differentiation in vitro.
Overexpression of either a constitutively active form of Foxo1 or a constitutively active form of Notch was found to inhibit the in vitro differentiation of a mouse myoblast cell line. Further analysis revealed that Foxo1 binds to the effector of Notch signaling Csl and that this is required for Notch activation of its target gene Hes1, which suppresses the expression of the myoblast differentiation factor MyoD. Consistent with this, mice lacking Foxo1 in skeletal muscle cells have more MyoD-containing muscle fibers. The authors therefore suggest that Notch and Foxo1 cooperation might allow environmental and metabolic cues, respectively, to be integrated into the muscle cell differentiation decision.
TITLE: A Foxo/Notch pathway controls myogenic differentiation and fiber type specification
AUTHOR CONTACT:
Domenico Accili
Columbia University College of Physicians and Surgeons, New York, New York, USA.
Making blood cells requires tescalcin
The recently identified protein tescalcin is known to be highly expressed in hematopoietic cells, but its function in these cells had not been determined. In a new study, Konstantin Levay and Vladlen Slepak at the University of Miami now show that tescalcin has a central role in the in vitro differentiation of megakaryocytes, the cells responsible for producing platelets.
The expression of tescalcin was found to dramatically increase when a hematopoietic progenitor cell line was induced to differentiate into megakaryocytes and overexpression of tescalcin in this cell line induced the spontaneous initiation of megakaryocyte differentiation. Conversely knockdown of tescalin expression in this cell line and in primary hematopoietic progenitors inhibited the induction of megakaryocyte differentiation. Further analysis showed that tescalcin couples the ERK signaling cascade with the expression of Ets family transcription factors. This study therefore identifies a cellular and molecular function for tescalcin in terminal differentiation in the hematopioetic system.
TITLE: Tescalcin is an essential factor in megakaryocytic differentiation associated with Ets family gene expression
AUTHOR CONTACT:
Konstantin Levay
University of Miami Miller School of Medicine, Miami, Florida, USA.
Vladlen Z. Slepak
University of Miami Miller School of Medicine, Miami, Florida, USA.
Risk factor for heart disease: Just say NO
Nitric oxide (NO) acts as a biological mediator throughout the body; for example, if the pressure in a blood vessel increases, the cells that line the blood vessel produce NO, which causes the surrounding smooth muscle cells to relax so that the blood vessels dilate and the pressure in the vessel drops. In a new study, Daniel O'Connor and colleagues from UCSD School of Medicine, San Diego, show that in humans a common variant of the GCH1 gene predicts NO excretion in the urine, which they used as a correlate for NO production in the body. The same GCH1 genetic variant was associated with increased blood pressure, a risk factor for developing heart disease. This study led the authors to suggest that "the NO pathway is centrally involved in the early pathogenesis of cardiac diseases" and that "treatments targeting the pathway might be beneficial in preventing later cardiac diseases if administered to subjects at specific genetic risk."
TITLE: Discovery of common human genetic variants of GTP cyclohydrolase 1 (GCH1) governing NO, autonomic activity, and cardiovascular risk
AUTHOR CONTACT:
Daniel T. O'Connor
Michael G. Ziegler
University of California at San Diego School of Medicine, San Diego, California, USA.
Source: Karen Honey
Journal of Clinical Investigation
The use of monoclonal IgG antibodies attached to toxins or radioactive substances for treating and imaging cancer is currently limited by the ability of IgG to remain in the blood for a long time because this decreases the tumor-to-background contrast and increases normal tissue toxicity. Now, David Scheinberg and colleagues at Memorial Sloan-Kettering Cancer Center, New York, have found a way to decrease the length of time IgG stays in the blood of both mice and humans such that tumor targeting is not compromised but the negative side effects of radiolabeled IgG are substantially diminished.
IgG hangs around in the blood for a long time because it is protected from degradation by the neonatal Fc receptor (FcRn). Infusing mice and humans with large amounts of polyclonal IgG after they had received a radiolabeled monoclonal antibody increased the rate of clearance of the radiolabeled monoclonal antibody from the blood. For both mice and humans, uptake of the radiolabeled monoclonal antibody by the tumor was the same with or without IgG infusion. However, the contrast between the labeled tumor and blood was much better with IgG infusion. Further analysis in mice also showed that IgG infusion decreased the normal tissue toxicity caused by the radiolabeled monoclonal antibody. The authors therefore suggest that polycloncal IgG infusion provides a new way to enhance the therapeutic and imaging efficacy of radiolabeled and toxin-conjugated monoclonal antibodies.
TITLE: Improved tumor imaging and therapy via i.v. Ig-mediated time-sequential modulation of neonatal Fc receptor
AUTHOR CONTACT:
David A. Scheinberg
Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Uncovering the molecules behind B cell lymphomagenesis
New data produced by Andrei Thomas-Tikhonenko and colleagues at the University of Pennsylvania, Philadelphia, provides a molecular mechanism by which a protein known as PAX5 promotes the growth of a number of types of lymphoma.
Overexpression of PAX5 in mouse B cell lymphoma cell lines increased tumor growth when these cells were transplanted into mice. Conversely, knocking down expression of PAX5 in these cell lines decreased tumor growth when the cells were transplanted into mice. Further analysis revealed that PAX5 promoted B cell lymphomagenesis by increasing the level of expression of molecules involved in B cell receptor signaling and decreasing the level of expression of molecules that inhibit B cell receptor signaling. Inhibitors of the BCR signaling pathway blocked tumor growth further highlighting the importance of BCR signaling in PAX5-driven growth of B cell lymphomas.
TITLE: B cell activator PAX5 promotes lymphomagenesis through stimulation of B cell receptor signaling
AUTHOR CONTACT:
Andrei Thomas-Tikhonenko
University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Building muscle requires Foxo1
The mechanisms by which Foxo proteins regulate metabolism are relatively well characterized. However, little was known about the mechanisms by which these same proteins regulate cellular differentiation. New data generated by Domenico Accili and colleagues at Columbia University, New York, now indicates that Foxo1 cooperates with Notch to control muscle cell differentiation in vitro.
Overexpression of either a constitutively active form of Foxo1 or a constitutively active form of Notch was found to inhibit the in vitro differentiation of a mouse myoblast cell line. Further analysis revealed that Foxo1 binds to the effector of Notch signaling Csl and that this is required for Notch activation of its target gene Hes1, which suppresses the expression of the myoblast differentiation factor MyoD. Consistent with this, mice lacking Foxo1 in skeletal muscle cells have more MyoD-containing muscle fibers. The authors therefore suggest that Notch and Foxo1 cooperation might allow environmental and metabolic cues, respectively, to be integrated into the muscle cell differentiation decision.
TITLE: A Foxo/Notch pathway controls myogenic differentiation and fiber type specification
AUTHOR CONTACT:
Domenico Accili
Columbia University College of Physicians and Surgeons, New York, New York, USA.
Making blood cells requires tescalcin
The recently identified protein tescalcin is known to be highly expressed in hematopoietic cells, but its function in these cells had not been determined. In a new study, Konstantin Levay and Vladlen Slepak at the University of Miami now show that tescalcin has a central role in the in vitro differentiation of megakaryocytes, the cells responsible for producing platelets.
The expression of tescalcin was found to dramatically increase when a hematopoietic progenitor cell line was induced to differentiate into megakaryocytes and overexpression of tescalcin in this cell line induced the spontaneous initiation of megakaryocyte differentiation. Conversely knockdown of tescalin expression in this cell line and in primary hematopoietic progenitors inhibited the induction of megakaryocyte differentiation. Further analysis showed that tescalcin couples the ERK signaling cascade with the expression of Ets family transcription factors. This study therefore identifies a cellular and molecular function for tescalcin in terminal differentiation in the hematopioetic system.
TITLE: Tescalcin is an essential factor in megakaryocytic differentiation associated with Ets family gene expression
AUTHOR CONTACT:
Konstantin Levay
University of Miami Miller School of Medicine, Miami, Florida, USA.
Vladlen Z. Slepak
University of Miami Miller School of Medicine, Miami, Florida, USA.
Risk factor for heart disease: Just say NO
Nitric oxide (NO) acts as a biological mediator throughout the body; for example, if the pressure in a blood vessel increases, the cells that line the blood vessel produce NO, which causes the surrounding smooth muscle cells to relax so that the blood vessels dilate and the pressure in the vessel drops. In a new study, Daniel O'Connor and colleagues from UCSD School of Medicine, San Diego, show that in humans a common variant of the GCH1 gene predicts NO excretion in the urine, which they used as a correlate for NO production in the body. The same GCH1 genetic variant was associated with increased blood pressure, a risk factor for developing heart disease. This study led the authors to suggest that "the NO pathway is centrally involved in the early pathogenesis of cardiac diseases" and that "treatments targeting the pathway might be beneficial in preventing later cardiac diseases if administered to subjects at specific genetic risk."
TITLE: Discovery of common human genetic variants of GTP cyclohydrolase 1 (GCH1) governing NO, autonomic activity, and cardiovascular risk
AUTHOR CONTACT:
Daniel T. O'Connor
Michael G. Ziegler
University of California at San Diego School of Medicine, San Diego, California, USA.
Source: Karen Honey
Journal of Clinical Investigation
суббота, 18 июня 2011 г.
EBMT Hosts Gathering Of Over 3,700 Top Scientists, Physicians, Nurses And Patients From More Than 75 Countries
EBMT, the European Group for Blood and Marrow Transplantation, is pleased to announce its 35th Annual Congress in Gothenburg, Sweden, from 29th March to 1st April. This meeting is a forum to promote all activity aimed at improving stem cell transplantation (SCT) and cellular therapy. The meeting fosters exchange of the latest scientific findings between researchers, physicians, nurses, and data managers, as well as provides a forum for families, patients and others to meet, network, and exchange their experiences related to SCT and cellular therapy.
The congress has been carefully prepared to offer a scientifically stimulating and highly informative meeting. The Scientific Programme encompasses symposia, educational sessions and workshops covering issues related to the specific problems of stem cell transplantation in clinical practice, indications for transplantation, as well as basic and translational science relevant to the field. The sessions will be led by experts in the field of blood and marrow transplantation.
This year, the two plenary sessions focus on the cutting edge topics of the use of stem cells in the field of Regenerative Medicine - presented in three exciting talks on how stem cells can be used for organ repair - and on Immune Regeneration and Infection, which will address one of the historical limitations of stem cell transplantation and how knowledge about the regeneration of the immune system can help combat the threat of infection. The latest findings in the use of cord blood in the treatments of haematological malignancies will also be an important part of the programme. All of these issues will be discussed taking into account the paediatric perspectives.
The 25th Meeting of the EBMT Nurses Group
The topic this year is "Quality of life lessons - into the future". Physicians and nurses will discuss the late effects of Bone Marrow Transplantations on sexuality and quality of life.
The 3rd EBMT Patient & Family Day
The third EBMT Patient & Family Day will take place in Gothenburg on Saturday 28th March. This event is now an established and integral part of the annual EBMT meeting and takes place the day before the scientific meeting each year. It is a unique opportunity for patients to share their experience. The programme will consist of three presentations, three plenary sessions and four workshops led by physicians, nurses and patients. The morning programme addresses important questions regarding the integrity of the sibling stem cell donors, and the problems that may occur when two family members meet the challenge of a stem cell transplantation; one as a patient and one as a potential donor. The second plenary session discusses the consequences of a cancer diagnosis for the patient's body image, and the frequently overlooked problem of genital chronic Graft-versus-Host disease. In the afternoon, popular science lectures will be given on news and developments in the field of transplantation for leukemias, lymphomas and multiple myeloma.
For more information on the Congress and to see the full schedule, please visit
congrex.ch/ebmt2009
About the European Group for Blood and Marrow Transplantation
Bone marrow or stem cell transplantation is often the only curative treatment for different malignant
diseases and is currently performed on more than 50,000 patients worldwide each year. The
European Group for Blood and Marrow Transplantation (EBMT) as the leading non-profit, scientific
society representing 527 transplant centres in and outside Europe, promotes all activity aiming to
improve stem cell transplantation or cellular therapy. This includes registering all the activity relating
to stem cell transplants with a view to improving treatment outcomes for patients. EBMT has set
standards for indication and treatment for malignant and non-malignant diseases, along with running
training programmes for continual professional development. These are continually audited and
updated. EBMT is also responsible for accrediting the transplant centres based on their performance
and data reporting.
Source
European Group for Blood and Marrow Transplantation
The congress has been carefully prepared to offer a scientifically stimulating and highly informative meeting. The Scientific Programme encompasses symposia, educational sessions and workshops covering issues related to the specific problems of stem cell transplantation in clinical practice, indications for transplantation, as well as basic and translational science relevant to the field. The sessions will be led by experts in the field of blood and marrow transplantation.
This year, the two plenary sessions focus on the cutting edge topics of the use of stem cells in the field of Regenerative Medicine - presented in three exciting talks on how stem cells can be used for organ repair - and on Immune Regeneration and Infection, which will address one of the historical limitations of stem cell transplantation and how knowledge about the regeneration of the immune system can help combat the threat of infection. The latest findings in the use of cord blood in the treatments of haematological malignancies will also be an important part of the programme. All of these issues will be discussed taking into account the paediatric perspectives.
The 25th Meeting of the EBMT Nurses Group
The topic this year is "Quality of life lessons - into the future". Physicians and nurses will discuss the late effects of Bone Marrow Transplantations on sexuality and quality of life.
The 3rd EBMT Patient & Family Day
The third EBMT Patient & Family Day will take place in Gothenburg on Saturday 28th March. This event is now an established and integral part of the annual EBMT meeting and takes place the day before the scientific meeting each year. It is a unique opportunity for patients to share their experience. The programme will consist of three presentations, three plenary sessions and four workshops led by physicians, nurses and patients. The morning programme addresses important questions regarding the integrity of the sibling stem cell donors, and the problems that may occur when two family members meet the challenge of a stem cell transplantation; one as a patient and one as a potential donor. The second plenary session discusses the consequences of a cancer diagnosis for the patient's body image, and the frequently overlooked problem of genital chronic Graft-versus-Host disease. In the afternoon, popular science lectures will be given on news and developments in the field of transplantation for leukemias, lymphomas and multiple myeloma.
For more information on the Congress and to see the full schedule, please visit
congrex.ch/ebmt2009
About the European Group for Blood and Marrow Transplantation
Bone marrow or stem cell transplantation is often the only curative treatment for different malignant
diseases and is currently performed on more than 50,000 patients worldwide each year. The
European Group for Blood and Marrow Transplantation (EBMT) as the leading non-profit, scientific
society representing 527 transplant centres in and outside Europe, promotes all activity aiming to
improve stem cell transplantation or cellular therapy. This includes registering all the activity relating
to stem cell transplants with a view to improving treatment outcomes for patients. EBMT has set
standards for indication and treatment for malignant and non-malignant diseases, along with running
training programmes for continual professional development. These are continually audited and
updated. EBMT is also responsible for accrediting the transplant centres based on their performance
and data reporting.
Source
European Group for Blood and Marrow Transplantation
пятница, 17 июня 2011 г.
African-Americans' Lack Of Trust In Hospitals A Major Deterrent For Blood Donation
Disparities in healthcare between races exist in the United States. A new study published in the journal Transfusion explores why African Americans donate blood at lower rates than whites. The findings reveal that there is a significant distrust in the healthcare system among the African American community, and African Americans who distrust hospitals are less likely to donate.
Led by Beth H. Shaz, MD, Chief Medical Officer of the New York Blood Center in New York, New York, researchers created a survey to explore reasons for low likelihood of blood donation in African Americans. Fifteen African American churches in metropolitan Atlanta participated in an 81-item self-administered survey, with 930 people responding to the survey.
The study's results demonstrate that about 1 in 5 African American individuals (17 percent) do not trust hospitals. This lack of trust was positively correlated with not donating blood even compared against other risk factors. Lack of trust in hospitals was also associated with not wanting to participate in research and less knowledge about the blood supply.
Respondents who did trust hospitals had more knowledge of the blood supply, less fear of donation, and were more likely to respond to blood needs of the community.
"Blood centers and hospitals need to build trust with the African American community," Shaz notes. "Increased trust will result in increased blood donor rates, increased participation in research, and increased medical knowledge."
Source:
Amy Molnar
Wiley-Blackwell
Led by Beth H. Shaz, MD, Chief Medical Officer of the New York Blood Center in New York, New York, researchers created a survey to explore reasons for low likelihood of blood donation in African Americans. Fifteen African American churches in metropolitan Atlanta participated in an 81-item self-administered survey, with 930 people responding to the survey.
The study's results demonstrate that about 1 in 5 African American individuals (17 percent) do not trust hospitals. This lack of trust was positively correlated with not donating blood even compared against other risk factors. Lack of trust in hospitals was also associated with not wanting to participate in research and less knowledge about the blood supply.
Respondents who did trust hospitals had more knowledge of the blood supply, less fear of donation, and were more likely to respond to blood needs of the community.
"Blood centers and hospitals need to build trust with the African American community," Shaz notes. "Increased trust will result in increased blood donor rates, increased participation in research, and increased medical knowledge."
Source:
Amy Molnar
Wiley-Blackwell
четверг, 16 июня 2011 г.
Severe Hypoglycemia Associated With Increased Risk Of Dementia For Older Adults With Type 2 Diabetes
Having hypoglycemic (low blood sugar level) episodes that are severe enough to require hospitalization are associated with a greater risk of dementia for older adults with type 2 diabetes, according to a study in the April 15 issue of JAMA, a theme issue on diabetes.
Rachel A. Whitmer, Ph.D., of Kaiser Permanente, Oakland, Calif., presented the findings of the study at a JAMA media briefing at the National Press Club in Washington, D.C.
Hypoglycemic episodes may include dizziness, disorientation, fainting or seizures. While most hypoglycemia is mild and self-managed, more severe hypoglycemia can require hospitalization. Although some studies have reported an association between history of hypoglycemia and impaired cognitive functioning in children and young adults with type 1 diabetes, no studies have evaluated whether or to what extent hypoglycemic episodes are a risk factor for the development of dementia in populations of older patients, who are more likely to have type 2 diabetes than type 1. "With the increasing prevalence of type 2 diabetes worldwide, and potentially of hypoglycemia and dementia among patients with diabetes, the relationship between these conditions should be evaluated," the authors write.
Dr. Whitmer and colleagues conducted a study to determine whether prior episodes of hypoglycemia that required hospitalization or emergency department (ED) visits are associated with an increased risk of dementia. The study, that included 22 years (1980-2002) of follow-up for hypoglycemic episodes and more than 4 years (starting in 2003) of follow-up for diagnosis of dementia, included 16,667 patients with type 2 diabetes (average age, 65 years).
The researchers found that a total of 1,822 patients (11 percent) had a diagnosis of dementia and 1,465 patients (8.8 percent) had at least 1 episode of hypoglycemia; 250 patients had both dementia and at least 1 episode of hypoglycemia (16.95 percent). Age-adjusted incidence rates of dementia by frequency of hypoglycemic episodes were significantly elevated for patients with at least 1 episode compared with patients with no episodes. "Specifically, we observed a 2.39 percent increase in absolute risk of dementia per year of follow-up for patients with history of hypoglycemia, compared with patients without a history. Although this 1-year absolute risk difference is modest, the cumulative effects would be sizeable," the authors write.
Compared with patients with no hypoglycemia, patients with single or multiple episodes had a graded increase in risk of dementia. Patients with 1 hypoglycemic episode had a 26 percent increased risk; 2 episodes, an 80 percent increased risk; and 3 or more hypoglycemic episodes were associated with nearly double the risk for dementia.
"Our results suggest that hypoglycemic episodes severe enough to require hospitalization or an ED visit are associated with increased risk of dementia, particularly for patients who have a history of multiple episodes," the researchers write.
"A large body of evidence suggests that individuals with diabetes are at an increased risk of dementia, yet exact mechanisms are not known; our study suggests a potentially modifiable mechanism. Pharmacologically induced severe hypoglycemia may be associated with neurological consequences in an older population already susceptible to dementia. More scientific studies examining hypoglycemia and cognitive performance and brain-imaging sequelae in populations of older patients with type 2 diabetes are needed."
JAMA. 2009;301[15]:1565-1572.
Journal of the American Medical Association
Rachel A. Whitmer, Ph.D., of Kaiser Permanente, Oakland, Calif., presented the findings of the study at a JAMA media briefing at the National Press Club in Washington, D.C.
Hypoglycemic episodes may include dizziness, disorientation, fainting or seizures. While most hypoglycemia is mild and self-managed, more severe hypoglycemia can require hospitalization. Although some studies have reported an association between history of hypoglycemia and impaired cognitive functioning in children and young adults with type 1 diabetes, no studies have evaluated whether or to what extent hypoglycemic episodes are a risk factor for the development of dementia in populations of older patients, who are more likely to have type 2 diabetes than type 1. "With the increasing prevalence of type 2 diabetes worldwide, and potentially of hypoglycemia and dementia among patients with diabetes, the relationship between these conditions should be evaluated," the authors write.
Dr. Whitmer and colleagues conducted a study to determine whether prior episodes of hypoglycemia that required hospitalization or emergency department (ED) visits are associated with an increased risk of dementia. The study, that included 22 years (1980-2002) of follow-up for hypoglycemic episodes and more than 4 years (starting in 2003) of follow-up for diagnosis of dementia, included 16,667 patients with type 2 diabetes (average age, 65 years).
The researchers found that a total of 1,822 patients (11 percent) had a diagnosis of dementia and 1,465 patients (8.8 percent) had at least 1 episode of hypoglycemia; 250 patients had both dementia and at least 1 episode of hypoglycemia (16.95 percent). Age-adjusted incidence rates of dementia by frequency of hypoglycemic episodes were significantly elevated for patients with at least 1 episode compared with patients with no episodes. "Specifically, we observed a 2.39 percent increase in absolute risk of dementia per year of follow-up for patients with history of hypoglycemia, compared with patients without a history. Although this 1-year absolute risk difference is modest, the cumulative effects would be sizeable," the authors write.
Compared with patients with no hypoglycemia, patients with single or multiple episodes had a graded increase in risk of dementia. Patients with 1 hypoglycemic episode had a 26 percent increased risk; 2 episodes, an 80 percent increased risk; and 3 or more hypoglycemic episodes were associated with nearly double the risk for dementia.
"Our results suggest that hypoglycemic episodes severe enough to require hospitalization or an ED visit are associated with increased risk of dementia, particularly for patients who have a history of multiple episodes," the researchers write.
"A large body of evidence suggests that individuals with diabetes are at an increased risk of dementia, yet exact mechanisms are not known; our study suggests a potentially modifiable mechanism. Pharmacologically induced severe hypoglycemia may be associated with neurological consequences in an older population already susceptible to dementia. More scientific studies examining hypoglycemia and cognitive performance and brain-imaging sequelae in populations of older patients with type 2 diabetes are needed."
JAMA. 2009;301[15]:1565-1572.
Journal of the American Medical Association
среда, 15 июня 2011 г.
New Tool For Diagnosing Anemia Of Chronic Disease
University of Utah School of Medicine researchers have developed a new tool that facilitates diagnosis of anemia related to chronic illness, as well as diseases of iron overload. The results of a study detailing the new tool are published in the August 2008 issue of the journal Cell Metabolism, a publication of Cell Press.
Iron balance in the body is regulated by the interaction between a liver-produced hormone called hepcidin and the iron transporting receptor ferroportin. Hepcidin binds to ferroportin resulting in decreased export of iron out of cells. An excess of hepcidin in the blood can result in anemia and a deficiency of hepcidin causes a build-up of iron that is damaging to body organs.
Since both anemia and iron overload have various causes, it is often difficult to distinguish among those causes. "It is hard to diagnose the anemia of chronic disease," said senior author Jerry Kaplan, Ph.D., University of Utah professor of pathology and assistant vice president for research at University of Utah Health Sciences. "Having an assay for hepcidin would make it much easier and it would also help in diagnosing iron overload diseases."
Identification of the Hepcidin-Binding Domain
In the study, Kaplan and researchers from the University of Utah and University of California, Los Angeles report that they have identified the hepcidin-binding domain (HBD), the specific site where hepcidin binds to ferroportin. By placing a synthetic version of that binding site on agarose beads, the researchers developed a rapid, sensitive test, called the HBD assay, for measuring the concentration of active hepcidin in the blood.
The ability to detect and measure hepcidin has important implications for the diagnosis of anemias and iron overload disorders related to hepcidin. Anemia is a deficiency of the oxygen-carrying molecules inside red blood cells which can be caused by iron deficiency, vitamin B12 or folate deficiency, or chronic illnesses. Anemia of chronic disease, or anemia of inflammation, is a form of anemia that is thought to be related to abnormally high levels of hepcidin.
The most common human disorder of iron overload is hereditary hemochromatosis, which leads to abnormal accumulation of iron in the liver, heart, skin, and other organs. Some types of hereditary hemochromatosis are associated with inappropriately low levels of hepcidin in the blood.
The HBD assay developed by Kaplan and his colleagues detects biologically active hepcidin. This assay can readily detect variations in hepcidin levels in the blood due to mutations in genes that are known to affect hepcidin levels, as well as mutations in other genes involved in iron metabolism. It can also measure hepcidin concentration in response to inflammation. This novel test would allow doctors to distinguish anemias and diseases of iron metabolism that arise from abnormalities in hepcidin from those that have other causes.
Hepcidin was first reported for its role in the body's defense against bacterial and fungal infections. Current scientific evidence, however, suggests that hepcidin's primary role in the body is to regulate iron balance.
Kaplan and his colleagues found that even very small changes to the composition of the HBD had significant effects on the ability of the binding site to bind hepcidin. They also discovered that hepcidin's ability to bind to the HBD decreases at temperatures below the normal human body temperature of 37°C due to structural changes in the hepcidin molecule at lower temperatures. This change in structure also affected the ability of hepcidin to bind to bacteria. This raised questions about the effect of low temperatures on iron metabolism and antibacterial activity.
Evolutionary Insight
The hepcidin-binding domain of fish is nearly identical to the human HBD. The researchers looked at hepcidin in fish such as the brown trout from the Middle Provo River, which routinely live in very cold waters. Most mammals have only one hepcidin gene, but fish have multiple hepcidin genes that encode hepcidin molecules of different lengths. In this study, Kaplan and his colleagues found that the fish hepcidin which is the same length as human hepcidin was able to bind to the HBD at temperatures as low as 4°C but had very little antibacterial activity at both 4°C and 37°C. This discovery provides insight into the evolution of hepcidin among vertebrates. Human hepcidin has both iron- and bacteria-related activities, while fish hepcidin genes evolved to separate these functions.
Due to the similarity of the hepcidin binding site among vertebrates, the usefulness of the novel HBD assay described in this study is not limited to humans. "The assay can be used to easily measure hepcidin in the blood of all vertebrates," says Kaplan.
University of Utah School of Medicine
Iron balance in the body is regulated by the interaction between a liver-produced hormone called hepcidin and the iron transporting receptor ferroportin. Hepcidin binds to ferroportin resulting in decreased export of iron out of cells. An excess of hepcidin in the blood can result in anemia and a deficiency of hepcidin causes a build-up of iron that is damaging to body organs.
Since both anemia and iron overload have various causes, it is often difficult to distinguish among those causes. "It is hard to diagnose the anemia of chronic disease," said senior author Jerry Kaplan, Ph.D., University of Utah professor of pathology and assistant vice president for research at University of Utah Health Sciences. "Having an assay for hepcidin would make it much easier and it would also help in diagnosing iron overload diseases."
Identification of the Hepcidin-Binding Domain
In the study, Kaplan and researchers from the University of Utah and University of California, Los Angeles report that they have identified the hepcidin-binding domain (HBD), the specific site where hepcidin binds to ferroportin. By placing a synthetic version of that binding site on agarose beads, the researchers developed a rapid, sensitive test, called the HBD assay, for measuring the concentration of active hepcidin in the blood.
The ability to detect and measure hepcidin has important implications for the diagnosis of anemias and iron overload disorders related to hepcidin. Anemia is a deficiency of the oxygen-carrying molecules inside red blood cells which can be caused by iron deficiency, vitamin B12 or folate deficiency, or chronic illnesses. Anemia of chronic disease, or anemia of inflammation, is a form of anemia that is thought to be related to abnormally high levels of hepcidin.
The most common human disorder of iron overload is hereditary hemochromatosis, which leads to abnormal accumulation of iron in the liver, heart, skin, and other organs. Some types of hereditary hemochromatosis are associated with inappropriately low levels of hepcidin in the blood.
The HBD assay developed by Kaplan and his colleagues detects biologically active hepcidin. This assay can readily detect variations in hepcidin levels in the blood due to mutations in genes that are known to affect hepcidin levels, as well as mutations in other genes involved in iron metabolism. It can also measure hepcidin concentration in response to inflammation. This novel test would allow doctors to distinguish anemias and diseases of iron metabolism that arise from abnormalities in hepcidin from those that have other causes.
Hepcidin was first reported for its role in the body's defense against bacterial and fungal infections. Current scientific evidence, however, suggests that hepcidin's primary role in the body is to regulate iron balance.
Kaplan and his colleagues found that even very small changes to the composition of the HBD had significant effects on the ability of the binding site to bind hepcidin. They also discovered that hepcidin's ability to bind to the HBD decreases at temperatures below the normal human body temperature of 37°C due to structural changes in the hepcidin molecule at lower temperatures. This change in structure also affected the ability of hepcidin to bind to bacteria. This raised questions about the effect of low temperatures on iron metabolism and antibacterial activity.
Evolutionary Insight
The hepcidin-binding domain of fish is nearly identical to the human HBD. The researchers looked at hepcidin in fish such as the brown trout from the Middle Provo River, which routinely live in very cold waters. Most mammals have only one hepcidin gene, but fish have multiple hepcidin genes that encode hepcidin molecules of different lengths. In this study, Kaplan and his colleagues found that the fish hepcidin which is the same length as human hepcidin was able to bind to the HBD at temperatures as low as 4°C but had very little antibacterial activity at both 4°C and 37°C. This discovery provides insight into the evolution of hepcidin among vertebrates. Human hepcidin has both iron- and bacteria-related activities, while fish hepcidin genes evolved to separate these functions.
Due to the similarity of the hepcidin binding site among vertebrates, the usefulness of the novel HBD assay described in this study is not limited to humans. "The assay can be used to easily measure hepcidin in the blood of all vertebrates," says Kaplan.
University of Utah School of Medicine
вторник, 14 июня 2011 г.
Slowing Down The Development Of Heart Disease
Scientists report in the November 2007 issue of the Journal of Lipid Research that a protein called transthyretin (TTR) that is present in the blood may accelerate the development of atherosclerosis a potentially fatal heart disease in which the arteries are progressively narrowed and hardened over time, reducing blood flow to the heart.
TTR has been shown to cleave a blood compound called apolipoprotein A I (ApoA I), which can produce structures called fibrils that are shaped like strands and accumulate in blood vessels. These fibrils have been observed in people with a mutation of the gene that makes ApoA-I, but whether cleavage by TTR promotes the formation of such fibrils has not been assessed yet.
Monica Mendes Sousa and colleagues determined that when ApoA I is cleaved by TTR, it tends to form fibrils faster than the uncleaved ApoA-I. This discovery may provide new ways to treat people with atherosclerosis by stopping TTR from cleaving ApoA-I and slowing down the formation of fibrils in blood vessels
Article: "ApoA-I cleaved by transthyretin has reduced ability to promote cholesterol efflux and increased amyloidogenicity," by Marcia Almeida Liz, Claudio M. Gomes, Maria Joao Saraiva, and Monica Mendes Sousa
The American Society for Biochemistry and Molecular Biology is a nonprofit scientific and educational organization with over 11,900 members in the United States and internationally. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, nonprofit research institutions and industry. The Society's student members attend undergraduate or graduate institutions.
Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for Experimental Biology. The Society's purpose is to advance the science of biochemistry and molecular biology through publication of the Journal of Biological Chemistry, the Journal of Lipid Research, and Molecular and Cellular Proteomics, organization of scientific meetings, advocacy for funding of basic research and education, support of science education at all levels, and promoting the diversity of individuals entering the scientific work force.
For more information about ASBMB, see the Society's Web site at asbmb.
American Society for Biochemistry and Molecular Biology (ASBMB)
9650 Rockville Pike
Bethesda, MD 20814-3996
United States
asbmb
TTR has been shown to cleave a blood compound called apolipoprotein A I (ApoA I), which can produce structures called fibrils that are shaped like strands and accumulate in blood vessels. These fibrils have been observed in people with a mutation of the gene that makes ApoA-I, but whether cleavage by TTR promotes the formation of such fibrils has not been assessed yet.
Monica Mendes Sousa and colleagues determined that when ApoA I is cleaved by TTR, it tends to form fibrils faster than the uncleaved ApoA-I. This discovery may provide new ways to treat people with atherosclerosis by stopping TTR from cleaving ApoA-I and slowing down the formation of fibrils in blood vessels
Article: "ApoA-I cleaved by transthyretin has reduced ability to promote cholesterol efflux and increased amyloidogenicity," by Marcia Almeida Liz, Claudio M. Gomes, Maria Joao Saraiva, and Monica Mendes Sousa
The American Society for Biochemistry and Molecular Biology is a nonprofit scientific and educational organization with over 11,900 members in the United States and internationally. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, nonprofit research institutions and industry. The Society's student members attend undergraduate or graduate institutions.
Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for Experimental Biology. The Society's purpose is to advance the science of biochemistry and molecular biology through publication of the Journal of Biological Chemistry, the Journal of Lipid Research, and Molecular and Cellular Proteomics, organization of scientific meetings, advocacy for funding of basic research and education, support of science education at all levels, and promoting the diversity of individuals entering the scientific work force.
For more information about ASBMB, see the Society's Web site at asbmb.
American Society for Biochemistry and Molecular Biology (ASBMB)
9650 Rockville Pike
Bethesda, MD 20814-3996
United States
asbmb
понедельник, 13 июня 2011 г.
Osteoarthritis Could Be Indication Of Faster "Biological Ageing"
Osteoarthritis, the degenerative inflammatory bone disease, may be a sign of faster "biological ageing," suggests research published ahead of print in the Annals of the Rheumatic Diseases.
The authors base their findings on a study of almost 1100 people, aged between 30 and 79. Most of them were female twins.
X-rays of both hands were taken of all participants to check for signs of osteoarthritis and a blood sample was taken to assess "biological ageing" in white cell DNA.
Biological ageing is likely to be reflected by the gradual shortening of telomeres, the length of DNA which caps the tips of chromosomes. A host of factors make them shorten over time, including insufficient repair of the damage caused by oxygen free radicals (oxidative stress).
Oxygen free radicals are the unstable molecules produced as a by-product of normal bodily processes, as well as external factors, such as tobacco, alcohol, and sunlight.
Osteoarthritis is the most common form of arthritis, with the hands being one of the sites most often affected. Its frequency rises dramatically with age, but it is still not known exactly what causes it.
Unsurprisingly, the findings showed that white cell telomere lengths were associated with chronological age. The older a person was, the shorter they were.
But among the 160 people with hand osteoarthritis, the telomere length was significantly shorter than among those without the disease, even after taking account of influential factors, such as obesity, age, sex, and smoking.
All those with hand osteoarthritis were over 50, and the amount of telomere shortening was equivalent to that accrued over 11 years in healthy people (178 base pairs).
Telomere length was also significantly associated with the severity of osteoarthritis. The more severe the disease, the shorter was the telomere length.
The authors suggest that both the ageing process and osteoarthritis share biological factors in common, including oxidative stress and low level chronic inflammation.
Contact: Emma Dickinson
BMJ Specialty Journals
The authors base their findings on a study of almost 1100 people, aged between 30 and 79. Most of them were female twins.
X-rays of both hands were taken of all participants to check for signs of osteoarthritis and a blood sample was taken to assess "biological ageing" in white cell DNA.
Biological ageing is likely to be reflected by the gradual shortening of telomeres, the length of DNA which caps the tips of chromosomes. A host of factors make them shorten over time, including insufficient repair of the damage caused by oxygen free radicals (oxidative stress).
Oxygen free radicals are the unstable molecules produced as a by-product of normal bodily processes, as well as external factors, such as tobacco, alcohol, and sunlight.
Osteoarthritis is the most common form of arthritis, with the hands being one of the sites most often affected. Its frequency rises dramatically with age, but it is still not known exactly what causes it.
Unsurprisingly, the findings showed that white cell telomere lengths were associated with chronological age. The older a person was, the shorter they were.
But among the 160 people with hand osteoarthritis, the telomere length was significantly shorter than among those without the disease, even after taking account of influential factors, such as obesity, age, sex, and smoking.
All those with hand osteoarthritis were over 50, and the amount of telomere shortening was equivalent to that accrued over 11 years in healthy people (178 base pairs).
Telomere length was also significantly associated with the severity of osteoarthritis. The more severe the disease, the shorter was the telomere length.
The authors suggest that both the ageing process and osteoarthritis share biological factors in common, including oxidative stress and low level chronic inflammation.
Contact: Emma Dickinson
BMJ Specialty Journals
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