Citations

Objective— Left atrial blood stasis is associated with increased risk for left atrial appendage thrombus (LAAT) and stroke in atrial fibrillation (AF). Von Willebrand factor (VWF) is associated with thromboembolism in AF. VWF thrombogenic activity is proportional to multimer size, which is regulated by VWF-cleaving protease (ADAMTS13). Methods and Results— To assess the association between left atrial blood stasis and VWF-ADAMTS13 system, plasma VWF antigen (VWF:Ag), VWF activity (VWF:Act), and ADAMTS13 activity were measured in 414 consecutive patients with nonvalvular AF (age 63±13 years; 25% women) and in 100 patients (age 64±14 years; 39% women) with normal sinus rhythm. Spontaneous echocardiographic contrast (SEC), left atrial appendage emptying velocity, and LAAT were assessed by transesophageal echocardiography. Presence and intensity of SEC varied directly with VWF:Ag and VWF:Act but not with ADAMTS13 activity. AF patients with LAAT had higher VWF:Ag (200±61 versus 155±52, P =0.0006) and VWF:Act (179±57 versus 141±51 P =0.0026) compared with those without LAAT. VWF:Ag and VWF:Act were independent predictors of LAAT after adjustment for CHADS 2 score ( P =0.0179 and P =0.0497, respectively). Conclusion— The association between VWF and SEC may explain the thrombotic propensity in AF. Elevated VWF:Ag may help identify AF patients at risk for LAAT.

A rapid progression from conventional open surgery to minimally invasive approaches in the surgical management of colorectal cancer has occurred over the last 2 decades. Initial concerns that this new approach was oncologically inferior to open surgery were ultimately refuted when several prospective randomized trials concluded that laparoscopic colectomy could achieve similar oncologic outcomes to open surgery. On the contrary, level 1 data has not yet matured regarding the oncologic safety of minimally invasive approaches for rectal cancer. We review the published literature pertaining to the evolution of minimally invasive techniques used to treat colorectal cancer surgery, including barriers to adoption, and the prospects for future advances related to innovative techniques.

AbstractPneumocystis carinii (Pc) undergoes morphological transitions between cysts and trophic forms. We have previously described two Pc serine/threonine kinases, termed PcCbk1 and PcSte20, with PcSte20 belonging to a family of kinases involved in yeast mating, while PcCbk1 is a member of a group of protein kinases involved in regulation of cell cycle, shape, and proliferation. As Pc remains genetically intractable, knowledge on specific substrates phosphorylated by these kinases remains limited. Utilizing the phylogenetic relatedness of Pc to Saccharomyces cerevisiae, we interrogated a yeast proteome microarray containing >4000 purified protein based peptides, leading to the identification of 18 potential PcCbk1 and 15 PcSte20 substrates (Z‐score > 3.0). A number of these potential protein substrates are involved in bud site selection, polarized growth, and response to mating α factor and pseudohyphal and invasive growth. Full‐length open reading frames suggested by the PcCbk1 and PcSte20 protoarrays were amplified and expressed. These five proteins were used as substrates for PcCbk1 or PcSte20, with each being highly phosphorylated by the respective kinase. Finally, to demonstrate the utility of this method to identify novel PcCbk1 and PcSte20 substrates, we analysed DNA sequence data from the partially complete Pc genome database and detected partial sequence information of potential PcCbk1 kinase substrates PcPxl1 and PcInt1. We additionally identified the potential PcSte20 kinase substrate PcBdf2. Full‐length Pc substrates were cloned and expressed in yeast, and shown to be phosphorylated by the respective Pc kinases. In conclusion, the yeast protein microarray represents a novel crossover technique for identifying unique potential Pc kinase substrates. Copyright © 2011 John Wiley & Sons, Ltd.

Abstract Annexin-1 and T-bet are recently described immunohistochemical stains that reportedly assist in the diagnosis of hairy cell leukemia (HCL). Our objective was to assess the sensitivity and specificity of a panel of immunohistochemical stains in distinguishing HCL from other B-cell neoplasms, particularly splenic and extranodal marginal zone lymphomas (SMZL and ENMZL, respectively). The study included 234 bone marrow biopsy specimens: 101 HCL, 13 SMZL, and 10 ENMZL cases were assessed with CD20, tartrate-resistant acid phosphatase (TRAP), DBA.44, a-1, T-bet, and cyclin D1, and 110 control cases were assessed with annexin-1 and T-bet. Our study showed that annexin-1 is a specific and sensitive marker for HCL; however, interpretation is limited by positivity within myeloid precursors. T-bet, DBA.44, and TRAP immunohistochemical stains lack sufficient sensitivity and specificity to differentiate HCL from either form of marginal zone lymphoma. However, our data suggest that the addition cyclin D1 to the immunostaining panel will increase the sensitivity and specificity of HCL diagnosis.