- Activation of Prothrombin by a Potential Staphylococcus Aureus Virulence Factor: A Lesson in Classical EnzymologySeptember 01, 2009 | Pete Lollar, MD
Most of the trypsin-like serine proteases in the coagulation and fibrinolytic mechanisms are formed by proteolytic activation from an inactive precursor, called the zymogen. During this process, a peptide at the NH
-terminus of the zymogen is cleaved. In a process referred to as molecular sexuality, the newly formed NH
-terminus of the nascent enzyme forms an internal salt bridge that results in conformational activation of the catalytic site.
- Bad FatSeptember 01, 2009 | Nelson Chao, MD, MBA
In our current epidemic of obesity, fat is a dreaded word. By some estimates, Americans spend $40 billion per year on weight-loss programs and diets. Now comes yet more evidence that fat is bad … for hematopoiesis.
- Bugs and the Vasculature: 60 Trillion Endothelial Cells Can Save Your LifeSeptember 01, 2009 | Gregory M. Vercellotti, MD
Twenty years ago Charles Janeway proposed the concepts of innate immunity that transformed immunology.
These ideas suggested that innate immune recognition of microbes depended upon receptors that detected conserved microbial products using pathogen-associated molecular patterns. This evolutionarily conserved mechanism led to the discovery in drosophila of Toll-like receptors (TLR) that could bind ligands of bacteria, viruses, and fungi that were non-self.
- Bypass Gene Therapy for HemophiliaSeptember 01, 2009 | Robert Flaumenhaft, MD, PhD
The formation of inhibitory antibodies to factor VIII or IX following therapy with either plasma-derived or recombinant factors remains a challenging problem in hemophilia management. Recombinant human activated factor VIIa (rhFVIIa) could potentially provide secondary prophylaxis as a bypass agent in hemophilia complicated by inhibitor formation.
- F18-Fluorodeoxyglucose PET Scanning in Multiple MyelomaSeptember 01, 2009 | Kenneth C. Anderson, MD
In this paper, Bartel et al., from Barlogie's group at the University of Arkansas for Medical Sciences, compared the utility of F18-fluorodeoxyglucose positron emission tomographic (FDG-PET) imaging to skeletal x-ray survey and magnetic resonance imaging in multiple myeloma (MM). In the context of their Total Therapy (TT)-3 program, FDG-PET was the leading independent factor predictive of decreased event-free and overall survival.
- Lenalidomide and Pomalidomide Meet RhoASeptember 01, 2009 | John C. Byrd, MD
The immune-modulating therapeutic agent lenalidomide is a broadly active therapeutic agent for a variety of hematologic malignancies including multiple myeloma, del(5q-) myelodysplastic syndrome, acute myeloid leukemia, non-Hodgkin lymphoma, Hodgkin disease, and chronic lymphocytic leukemia. This has prompted considerable interest in developing third-generation immune modulation agents, such as pomalidomide. Several of these are currently in clinical trials for multiple myeloma where promising responses have been observed.
- Loss-of-Function TET2 Mutations: Adding Fire to Hematologic Malignancies?September 01, 2009 | Josef Prchal, MD
Somatic mutations in
in Philadelphia-chromosome-negative (Ph-) myeloproliferative disorders (MPD), FLT 3 and other genes in acute myelocytic leukemias (AML), and numerous others reported in myelodysplastic syndromes (MDS) are clearly not sufficient to explain the full genesis of these disorders. Thus, the recent finding of a multitude of mutations of the tumor suppressive gene
in numerous malignant hematologic entities has created a lot of excitement.
- Molecular Profiling in Lymphoma Comes of AgeSeptember 01, 2009 | Steven Grant, MD
The emergence of gene-expression analysis has added a powerful new weapon to the oncologist's armamentarium in the classification of neoplastic diseases and in the identification of prognostic indicators. The basic premise underlying this approach is that tumors that appear to be identical from a purely morphologic standpoint may in fact harbor highly disparate genetic profiles.
- Proof of Principle for Combined Cell and Gene Therapy for Fanconi AnemiaSeptember 01, 2009 | Diane Krause, MD, PhD
Optimal therapy for patients with genetic hematologic diseases would be to take the patient's own cells, correct the genetic abnormality, and return the cells to the patient for long-term functional engraftment. Such therapy would require a combination of cell and gene therapy. In this paper, investigators from the laboratories of Juan Carlos Izpisúa-Belmonte in Barcelona and Juan Antonio Bueren in Madrid published proof-of-principle studies showing that cells from patients with Fanconi anemia (FA) can be genetically repaired and reprogrammed into inducible pluripotent stem (iPS) cells, which can then be guided to differentiate down the hematopoietic lineage