Physician-scientist training.
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Biomedical Research↗
Biomedical subjects
Richard L Haspel
Publications and source records attributed to Richard L Haspel.
The "cutting" edge: von Willebrand factor-cleaving protease activity in thrombotic microangiopathies.
The thrombotic microangiopathies (TMAs), including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), are classically defined by constellations of clinical findings. In the late 1990's, several groups reported that a single test might be able to diagnose TTP and distinguish it from HUS. This test was an assay to detect von Willebrand factor-cleaving protease activity. Although there has been debate in the literature as to the utility of this assay, review of the available data suggests that this test can separate the idiopathic TMAs into three distinct categories: (1) patients who are protease positive with severe renal failure (similar to classic HUS), (2) patients who are protease positive without severe renal failure and (3) patients who are protease negative. While the latter two categories may appear similar to TTP at presentation, the prognosis differs in each of these groups of patients. Through use of the protease assay clinicians will be better able to diagnose, treat, predict outcome and design clinical trials.
ADAM Proteins↗
Platelet transfusion in an infant leading to formation of anti-D: implications for immunoprophylaxis.
BACKGROUND: The immature infant immune system rarely makes RBC alloantibodies; however, most studies confirming the absence of alloantibodies in infants have involved transfusions that were matched for one of the most immunogenic antigens, rhesus D. The potential for D- infants to develop anti-D is unknown. Specifically, this issue has not been analyzed for infants receiving whole-blood-derived PLTs from D+ donors. The importance of understanding such risk is underscored by the fact that anti-D formation can be prevented by the administration of Rh immunoglobulin. CASE REPORT: A D- infant with congenital heart disease received two D-mismatched whole-blood-derived PLT units at 17 weeks of age. He did not receive Rh immunoglobulin prophylaxis. Upon a subsequent admission 13 months later, anti-D was identified in his plasma sample. CONCLUSION: The case presented here demonstrates that a young infant can respond to less than 0.6 mL of D+ RBCs and documents the youngest patient to have developed a RBC alloantibody from a PLT transfusion. To prevent anti-D formation, we recommend administering Rh immunoglobulin to all D- pediatric patients that receive PLT transfusions from D+ donors [correction].
Humans↗
The Krüppel-like factor KLF2 inhibits peroxisome proliferator-activated receptor-gamma expression and adipogenesis.
Obesity is an important public health problem associated with a number of disease states such as diabetes and arteriosclerosis. As such, an understanding of the mechanisms governing adipose tissue differentiation and function is of considerable importance. We recently reported that the Krüppel-like zinc finger transcription factor KLF15 can induce adipocyte maturation and GLUT4 expression. In this study, we identify that a second family member, KLF2/Lung Krüppel-like factor (LKLF), as a negative regulator of adipocyte differentiation. KLF2 is highly expressed in adipose tissue, and studies in cell lines and primary cells demonstrate that KLF2 is expressed in preadipocytes but not mature adipocytes. Constitutive overexpression of KLF2 but not KLF15 potently inhibits peroxisome proliferator-activated receptor-gamma (PPARgamma) expression with no effect on the upstream regulators C/EBPbeta and C/EBPdelta. However, the expression of C/EBPalpha and SREBP1c/ADD1 (adipocyte determination and differentiation factor-1/sterol regulatory element-binding protein-1), two factors that feedback in a positive manner to enhance PPARgamma function, was also markedly reduced. In addition, transient transfection studies show that KLF2 directly inhibits PPARgamma2 promoter activity (70% inhibition; p < 0.001). Using a combination of promoter mutational analysis and gel mobility shift assays, we have identified a binding site within the PPARgamma2 promoter, which mediates this inhibitory effect. These data identify a novel role for KLF2 as a negative regulator of adipogenesis.
Adipocytes↗