Pic Of The Day
Posted by rob on August 29, 2005 under Uncategorized | 
Be the First to Comment
Copa Casino uses it’s electronic billboard to tell customers that it is closed due to Hurricane Katrina,
Pic Of The Day
Posted by rob on August 28, 2005 under Uncategorized | Be the First to Comment
Seagulls fly around a dumping area in Oulu, some 600 km north of Helsinki.
Pretreated Bone Marrow Grafts Don’t Lower GvHD Risk
Posted by rob on August 27, 2005 under Uncategorized | Be the First to Comment
Patients who had bone marrow transplants for hematologic cancers did not have a lower risk of graft-versus-host disease (GvHD) when the marrow was pretreated to remove most of the donors’ T cells.
So it emerged in a study by researchers at the University of Minnesota here and other centers of 405 patients with hematologic malignancies, according to a report in the Aug. 27 issue of The Lancet.
The investigators also found that patients who received bone marrow grafts that were depleted of T cells prior to transplant did not have improved disease-free survival at three years, reported John E. Wagner, M.D., and colleagues. The patients were compared with those who received T-cell replete grafts and GvHD prophylaxis with methotrexte and cyclosporine.
But despite results of this study, “T-cell depletion of donor graft is the most effective method for prevention of GvHD,” wrote Franco Locatelli, M.D., and Piero De Stefano, M.D., of the IRCCS Policlinco San Matteo in Pavia, Italy, in an accompanying editorial.
T-cell depletion of donor bone marrow has been shown to reduce the risk of severe GvHD after transplant in patients who received marrow from a sibling, and to reduce the risk of acute GvHD and improve survival in patients who receive marrow from unrelated donors, Dr. Wagner and colleagues noted.
To determine whether T-cell depletion could reduce transplant-related mortality, improve survival, and enhance health-related quality of life after bone marrow transplantation from an unrelated donor, the investigators conducted a randomized study comparing pre-transplant T-cell depletion with post-transplant GvHD prophylaxis with methotrexate and cyclosporine A.
A total of 405 patients from 15 centers were enrolled. All patients were candidates for unrelated donor transplants. The diagnoses included chronic myelogenous leukemia, acute myelogenous leukemia, biphenotypic leukemia, juvenile myelomonocytic leukemia, myelodysplastic syndrome, lymphoblastic lymphoma, and non-Hodgkin’s lymphoma.
Patients were randomly assigned to be treated with either T-cell depleted bone marrow, or T-cell replete bone marrow, followed by GvHD prophylaxis with methotrexate and cyclosporine A.
T-cell depletion was accomplished with either centrifuging of donor grafts to separate T cells from hematopoietic stem cells and progenitor cells, or with antibodies targeted to T-cell receptors.
The primary endpoint was disease-free survival at three years, defined as the minimum time to relapse, death, or last follow-up. Analysis was by intention-to-treat.
In all, five patients died before the transplant took place, and seven patients in the T-cell depletion arm ended up receiving T-cell replete grafts, because of inadequate marrow harvest, problems with total body irradiation, and complications with the conditioning regimen.
The investigators found that disease-free survival at three years in the patients who received the pretreated T-cell depleted grafts was 27% (95% CI 21-33) compared with 34% (27-40) of the methtrexate/cyclosporine recipients (p=0.16).
T-cell depletion was associated with significantly faster neutrophil recovery (15 days vs. 20 days, p
However, these advantages of T-cell depletion over methotrexate/cyclosporine were offset by a higher risk of relapse in patients with chronic myelogenous leukemia (20% in the T-cell group vs. 7%, p=0.009). In addition cytomegalovirus infections occurred in 28% of patients with T-cell depleted grafts, compared with 17% of those in the post-transplant immunosuppressant group (p=0.023).
“Major drawbacks of T-cell depletion are an enhanced risk of graft rejection and leukemia relapse, as well as delayed immune reconstitution, with a consequent increased risk of viral and fungal infections, and lymphoproliferative disorders associated with Epstein-Barr virus,” Drs. Locatelli and De Stefano wrote in their editorial. “All these complications reduce or even offset the advantage offered by T-cell depletion, so that a better outcome in patients given a T-cell-depleted allograft has not been consistently found.”
T-cell depletion could play a role, however, in the treatment of patients at higher risk for GvHD, such as elderly people with acute leukemia who receive marrow from a donor who a less than ideal HLA match.
“Use of T-cell depletion together with strategies aimed at restoring immune competence towards widespread pathogens, and at strengthening the specific [graft-versus-leukemia] response, could be a more effective and attractive approach for GvHD prevention,” they wrote. “Selective removal and/or immunomodulation of alloreactive T cells, activated by recipient histocompatibility antigens, could also overcome the problems of prolonged immunosuppression associated with T-cell depletion.”
The Wagner study was funded by the National Heart, Lung, and Blood Institute.
Primary source: The Lancet
Source reference:
Lancet 2005; 366: 733-41
Additional source: The Lancet
Source reference:
Lancet 2005; 366: 692-693
Pretreated Bone Marrow Grafts Don’t Lower GvHD Risk – CME Teaching Brief – MedPage Today
Pic Of The Day
Posted by rob on under Uncategorized | Read the First Comment
The ‘Homo Sapiens’ exhibit at the London Zoo. The exhibit is intended to show the basic nature of human beings as they frolick throughout the August bank holiday weekend.(
Ph-Chromosome-positive chronic myeloid leukemia with associated bone marrow mastocytosis.
Posted by rob on August 26, 2005 under Uncategorized | Be the First to Comment
Agis H, Sotlar K, Valent P, Horny HP
Leuk Res. 2005 Oct ; 29(10): 1227-32
The concurrent development of chronic myeloid (CML) or myelomonocytic (CMML) leukemia in patients with systemic mastocytosis (SM) is a well recognized phenomenon. Although the leukemia often resembles CML in morphological and in clinical terms, a Ph-Chromosome-positive variant has not been reported in SM so far. We here describe a 43-year-old female patient with typical Ph-Chromosome-positive CML in whom a co-existing bone marrow mastocytosis, a special subvariant of SM, was diagnosed. RT-PCR analysis revealed the typical p210kDa form of BCR/ABL in leukemic cells. The diagnosis SM was based on the typical focal aggregates of spindle-shaped mast cells (MC) in the bone marrow, expression of CD25 in MC, and the c-kit mutation D816V, which was detectable in microdissected bone marrow MC, but not in microdissected leukemic cells, suggesting the presence of two different (sub)clones of neoplastic cells. Therapy with the BCR/ABL-targeting drug Imatinib (STI571) resulted in complete cytogenetic remission of CML. Together, our case provides further evidence for the biologic diversity of leukemias that may occur in patients with SM. The exact knowledge of the pathology and target-profile of the associated leukemias in SM have important therapeutic implications.
Ph-Chromosome-positive chronic myeloid leukemia with associated bone marrow mastocytosis.
High expression of RbAp46 gene in patients with acute leukemia or chronic myelogenous leukemia in blast crisis.
Posted by rob on under Uncategorized | Be the First to Comment
Hu SY, Chen ZX, Gu WY, Cen JN, Zhao Y
Chin Med J (Engl). 2005 Aug 5; 118(15): 1295-8
No abstract yet
Pic Of The Day
Posted by rob on under Uncategorized | Be the First to Comment
A pelican dives into the water to go after a fish as high surf and thunderstorms roll in from tropical storm Katrina in Boca Raton, Florida, August 25, 2005. Tropical storm Katrina formed off the coast of the Bahamas and is packing 50mph winds as it heads for Florida’s southern Atlantic coast with the potential of becoming a hurricane and making landfall by Friday morning.
Pic Of The Day
Posted by rob on August 25, 2005 under Uncategorized | Be the First to Comment
Zebra mother Mabuki(R) stands beside her foal at the Berlin zoo.
Mitochondria-dependent apoptosis induced by a novel amphipathic photochemotherapeutic agent ZnPcS2P2 in HL60 cells.
Posted by rob on August 24, 2005 under Uncategorized | Be the First to Comment
Acta Pharmacol Sin. 2005 Sep ; 26(9): 1138-44
Aim: To investigate the mechanism underlying the killing effects of a novel amphipathic photosensitizer, disulfonated diphthalimidomethyl phthalocyanine zinc (ZnPcS2P2), mediated photodynamic therapy (ZnPc-PDT) in human myelogenous leukemia HL60 cells. Methods: After incubation for 5 h with 0.5 mumol/L ZnPcS2P2, the HL60 cells were exposed to a light source of 670 nm wavelength. Thereafter, the cells were detected at different time intervals after PDT. The characteristics of apoptosis were detected by observation of ultrastructure assay, DNA fragmentation assay and terminal deoxynucleotidyl transferase deoxyuridine nick-end labeling method (TUNEL). Mitochondria-dependent apoptosis was determined by the detection of mitochondrial membrane potential (deltaPhim), activities of caspase family protease and of caspase-3, cytosol cytochrome c. Proteins Bcl-2 and Bax were detected by immunoblot analysis. Results: Evident characteristics of apoptosis were observed post-ZnPc-PDT with ultrastructure assay, DNA fragmentation assay and TUNEL staining. TUNEL assay showed that apoptotic rates in the cells collected from 6 h, 12 h and 24 h after PDT were 9.6%, 24.4%, and 33.0%, respectively. HL60 cells underwent mitochondria-dependent apoptosis as a result of cytochrome c release from mitochondria into cytosol accompanied by a reduction of deltaPhim. The activities of caspase family protease and of caspase-3 were elevated. Furthermore, ZnPc-PDT could remarkably down-regulate the Bcl-2 pro-apoptotic protein and up-regulate the anti-apoptotic Bax protein. Conclusion: ZnPc-PDT could induce mitochondria-dependent apoptosis in HL60 cells.
Vesicular Monoamine Transporter 2 (VMAT2) Expression in Hematopoietic Cells and in Patients with Systemic Mastocytosis
Posted by rob on under Uncategorized | Be the First to Comment
Anlauf M, Sch?fer MK, Schwark T, von Wurmb-Schwark N, Brand V, Sipos B, Horny HP, Parwaresch R, Hartschuh W, Eiden LE, Kl?ppel G, Weihe E
J Histochem Cytochem. 2005 Aug 22;
Uptake of monoamines into secretory granules is mediated by the vesicular monoamine transporters VMAT1 and VMAT2. In this study we analyzed their expression in inflammatory and hemotopoietic cells and in patients suffering from systemic mastocytosis (SM) and chronic myelogenous leukemia (CML). Normal human and monkey tissue specimens and tissues from patients suffering from SM and CML were analyzed by means of immunohistochemistry, radioactive in situ hybridization, real time RT-PCR, double fluorescence confocal laser scanning microscopy and immunoelectron microscopy. In normal tissue specimens, VMAT2, but not VMAT1, was expressed in mast cells, megakaryocytes, thrombocytes, basophil granulocytes and cutaneous Langerhans cells. Further hematopoietic and lymphoid cells showed no expression of VMATs. VMAT2 was expressed in all types of SM, as indicated by coexpression with the mast cell marker tryptase. In CML VMAT2 expression was retained in neoplastic megakaryocytes and basophil granulocytes. In conclusion, the identification of VMAT2 in mast cells, megakaryocytes, thrombocytes, basophil granulocytes and cutaneous Langerhans cells provides evidence that these cells possess molecular mechanisms for monoamine storage and handling. VMAT2 identifies normal and neoplastic mast cells, megakaryocytes and basophil granulocytes and may therefore become a valuable tool for the diagnosis of mastocytosis and malignant systemic diseases involving megakaryocytes and basophil granulocytes.
Pic Of The Day
Posted by rob on under Uncategorized | Be the First to Comment
Jordanne Dervaes, left, picks lettuce as her sister Anais gathers lemon cucumbers in the organic garden at their home Monday, Aug. 15, 2005, in Pasadena, Calif. On one tenth of an acre, the urban garden at the their home produces about 6,000 pounds of food a year, enough to feed the Dervaes, their menagerie of ducks, chickens and bunnies and even some diners who seek out organic meals at local restaurants.
Pic Of The Day
Posted by rob on August 23, 2005 under Uncategorized | Be the First to Comment
A dove looks for insects among flowers in Bangkok’s Suan Luang Rama IX park
Pic Of The Day
Posted by rob on August 22, 2005 under Uncategorized | Be the First to Comment
A horse grazes as a rainbow appears in the sky on the Son-Kul plateau, 3013 metres above sea level located on the ancient Great Silk Road from Kashgar to Bishkek.
Molecular diagnosis of cancer: methods and protocols, second edition.
Posted by rob on under Uncategorized | Be the First to Comment
Racevskis J
Med Oncol. 2005; 22(3): 325-6
Dramatic advances in molecular biology over the past decades have led to an unprecedented understanding of cancer at a very detailed molecular level. The application of microarray technology, for example, has made it possible to characterize the expression of every human gene in any specific tumor. As a result of this detailed characterization of cancers, novel therapies that target specific gene products characteristic of a given tumor have been developed, and are being introduced at a rapid rate. Three therapeutic agents of this class, which are currently in clinical use and can be dramatically effective in some patients, are Glivec, a tyrosine kinase inhibitor that targets the fusion gene product BCR/ABL common to chronic myelogenous leukemia; Herceptin, which targets the HER-2/neu antigen expressed in about a quarter of breast cancers; and Iressa an inhibitor of receptor tyrosine kinases, which is spectacularly effective in a subgroup of lung cancer patients with mutations in their epidermal growth factor receptor genes.As more and more of these molecularly targeted therapies come into use for treatment and management of cancers, there will be a surge in the demand for very precise molecular diagnostic techniques that can identify those cancers that are treatable and susceptible to each specific therapy. It is the editors’ contention that many diagnosticians are not trained in this new and expanding field of molecular cancer diagnosis and would therefore benefit from a compilation of the most current techniques.A selection of techniques that are currently available to attain a detailed molecular characterization of various cancers is compiled in this volume. Given the vastness of this field and rapid rate of advances, it was obviously not possible to cover all possible aspects of molecular cancer diagnosis; however, the specific techniques described cover most areas of molecular diagnosis and todays’ most powerful technologies. Although some of the techniques covered in this volume are quite standard and not new, such as RT-PCR, nucleic acid extraction, etc., it is useful to have them all included in one volume along with the more cutting edge technologies. Some of the techniques covered in this volume include FISH (fluorescence in situ hybridization)-based methodologies currently in use for diagnosis of tumors, genetic abnormality detection by DNA and sequence-specific oligonucleotide array technologies, quantitative PCR, and many others.
Molecular diagnosis of cancer: methods and protocols, second edition.
Pic Of The Day
Posted by rob on August 21, 2005 under Uncategorized | Be the First to Comment
Writer and journalist Hunter S. Thompson’s ashes is fired into the sky amid fireworks after a memorial service attended by relatives and a star-studded crowd at his home in Woody Creek, Colorado, August 20, 2005. Thompson was found dead by his son Juan on February 20 with a gunshot wound to the head.
Pic Of The Day
Posted by rob on August 20, 2005 under Uncategorized | Be the First to Comment
A young girl enjoys a bath in the Baltic Sea at the Hiddensee island where a tall ship is anchoring.
Pic Of The Day
Posted by rob on August 19, 2005 under Uncategorized | Be the First to Comment
A monarch butterfly rests on a purple cone flower in Arrowsic, Maine, Thursday, Aug. 18, 2005.
Pic Of The Day
Posted by rob on August 18, 2005 under Uncategorized | Be the First to Comment
A line bearing 500 kites printed with the colors of the Indian national flag at the National Kite Flying Festival in Bangalore, India
Pic Of The Day
Posted by rob on August 17, 2005 under Uncategorized | Be the First to Comment
Performers dance during the opening ceremony of the Arirang Festival in Pyongyang, capital of North Korea.
Largest Study Of Unrelated Bone Marrow Transplantation For Leukemia Serves As Benchmark
Posted by rob on under Uncategorized | Be the First to Comment
Together with 16 other institutions in the United States, University of Minnesota researchers led the largest study to date in patients with leukemia and related disorders undergoing bone marrow transplantation from unrelated donors. The study was designed to determine whether one of two general approaches to prevent graft-versus-host-disease (GVHD), a potentially lethal complication, might result in improved survival.
While the trial demonstrated similar survival rates, the study was the most comprehensive to date, evaluating various clinical outcomes, resource utilization, costs, and health quality of life. The study, published in the Aug. 3, 2005 online issue of The Lancet, will likely serve as the benchmark for all future studies in this patient population.
Graft-versus-host-disease is a common complication after bone marrow transplantation in which the immune cells from the donated marrow attack the body of the patient who received the transplant. Severity ranges from mild to life threatening, and the disease and its treatment can have a profound effect on quality of life.
The two primary strategies for preventing GVHD, the removal of T-cells (the cell that causes GVHD) and immunosuppressive drug therapy (suppression of T-cell function), were studied in this trial. While the primary aim of the study was to demonstrate whether one approach might be better than the other in terms of disease-free survival three years after transplantation, the study also systematically compared the incidence of various complications (GVHD, graft failure, therapy-related side effects, disease recurrence) as well as utilization of blood products, nutritional supplementation, number of admissions to the hospital and intensive care unit, hospital costs, and health quality of life.
“While the T-cell depletion approach was very effective in reducing the risk of GVHD, a higher risk of viral infection in general and higher risk of disease recurrence specifically in patients with chronic myelogenous leukemia, eliminated the potential benefit of reduced GVHD,” ,” said John E. Wagner, M.D., professor of pediatrics and scientific director of clinical research, Blood and Marrow Transplantation Program and Stem Cell Institute, and lead author of the study. “Overall, we observed no differences in survival at three years and no appreciable differences in cost or quality of life.”
These results counter what investigators might have guessed and reflect the critical importance of performing large randomized trials. “Prior to this study, colleagues promoting T-cell depletion, like myself, predicted that T-cell depletion would have offered a better chance of survival,” Wagner said. “What is abundantly clear is that T-cell depletion and GVHD prevention is only one step in figuring out how to improve upon the chance of cure in unrelated marrow transplant patients. The next hurdle is to find ways to fix the crippled immune system.”
Despite the lack of evidence that one approach was better than the other, “the results clearly point out the limitations of bone marrow transplants,” Wagner said. However, he added that the methodological approaches used and study results will be valuable benchmarks for future studies of novel treatments for leukemias and other blood-related cancers.
###
The study was sponsored by the National Heart, Lung and Blood Institute.
Largest Study Of Unrelated Bone Marrow Transplantation For Leukemia Serves As Benchmark