Extreme Peripheral Blood Plasmacytosis Mimicking Plasma Cell Leukemia as a Presenting Feature of Angioimmunoblastic T-Cell Lymphoma (AITL).

Angioimmunoblastic T-cell lymphoma (AITL) is one of four major subtypes of nodal peripheral T cell lymphoma, characterized by its cell of origin, the follicular helper T-cell (TFH). Patients typically present with prominent constitutional (B) symptoms, generalized lymphadenopathy, hepatosplenomegaly, cytopenias, and rash. Here we present a case of a 62-year-old male with progressive cervical adenopathy, fevers and weight loss presenting with extreme polyclonal plasmacytosis and high plasma EBV viral load. While the initial presentation appeared to mimic plasma cell leukemia or severe infection, lymph node biopsy and bone marrow biopsy confirmed a diagnosis of AITL. This case highlights the heterogeneity of the clinical presentation of AITL to enable physicians to more promptly recognize, diagnose and initiate treatment

Nonequilibrium phase transition in the kinetic Ising model: Is transition point the maximum lossy point ?

The nonequilibrium dynamic phase transition, in the kinetic Ising model in presence of an oscillating magnetic field, has been studied both by Monte Carlo simulation (in two dimension) and by solving the meanfield dynamical equation of motion for the average magnetization. The temperature variations of hysteretic loss (loop area) and the dynamic correlation have been studied near the transition point. The transition point has been identified as the minimum-correlation point. The hysteretic loss becomes maximum above the transition point. An analytical formulation has been developed to analyse the simulation results. A general relationship among hysteresis loop area, dynamic order parameter and dynamic correlation has also been developed.Comment: 8 pages Revtex and 4 Postscript figures; To appear in Phys. Rev.

Collective dynamics of two-mode stochastic oscillators

We study a system of two-mode stochastic oscillators coupled through their collective output. As a function of a relevant parameter four qualitatively distinct regimes of collective behavior are observed. In an extended region of the parameter space the periodicity of the collective output is enhanced by the considered coupling. This system can be used as a new model to describe synchronization-like phenomena in systems of units with two or more oscillation modes. The model can also explain how periodic dynamics can be generated by coupling largely stochastic units. Similar systems could be responsible for the emergence of rhythmic behavior in complex biological or sociological systems.Comment: 4 pages, RevTex, 5 figure

Prostate Field Cancerization and Exosomes: Association Between CD9, Early Growth Response 1 and Fatty Acid Synthase

Intracapsular and well‑defined adenocarcinomas of the prostate are often surrounded by tissue areas that harbor molecular aberrations, including those of genetic, epigenetic and biochemical nature. This is known as field cancerization, or a field effect and denotes a state of pre‑malignancy. Such alterations in histologically normal tumor‑adjacent prostatic tissues have been recognized as clinically important and are potentially exploitable as biomarkers of disease and/or targets for preventative/therapeutic intervention. The authors have previously identified and validated two protein markers of field cancerization: The expressional upregulation of the transcription factor early growth response 1 (EGR‑1) and the lipogenic enzyme fatty acid synthase (FASN). However, the molecular etiology of prostate field cancerization, including EGR‑1 and FASN upregulation, remains largely unknown. It was thus hypothesized that extracellular vesicles, notably exosomes, released by tumor lesions may induce molecular alterations in the surrounding tissues, resulting in field cancerization, priming the tissue, and ultimately promoting multifocal tumorigenesis, which is often observed in prostate cancer. Towards testing this hypothesis, the current study, to the best of our knowledge, for the first time, presents correlative protein expression data, generated in disease‑free, tumor‑adjacent and cancerous human prostate tissues by quantitative immunofluorescence, between the exosomal marker CD9, and EGR‑1 and FASN. Despite the pilot character of the present study, and the static nature and heterogeneity of human tissues, the data suggest that CD9 expression itself is part of a field effect. In support of this hypothesis, the results suggest a possible contribution of exosomes to the induction of field cancerization in the prostate, particularly for EGR‑1. These findings were corroborated in established cell models of cancerous (LNCaP) and non‑cancerous (RWPE‑1) human prostate epithelial cells. The findings of this study warrant further investigation into the functional interface between exosomes and field cancerization, as a detailed understanding of this characterization may lead to the development of clinical applications related to diagnosis and/or prognosis and targeted intervention to prevent progression from pre‑malignancy to cancer

Correlative High-Resolution Imaging of Iron Uptake in Lung Macrophages

Detection of iron at the subcellular level in order to gain insights into its transport, storage, and therapeutic prospects to prevent cytotoxic effects of excessive iron accumulation is still a challenge. Nanoscale magnetic sector secondary ion mass spectrometry (SIMS) is an excellent candidate for subcellular mapping of elements in cells since it provides high secondary ion collection efficiency and transmission, coupled with high-lateral-resolution capabilities enabled by nanoscale primary ion beams. In this study, we developed correlative methodologies that implement SIMS high-resolution imaging technologies to study accumulation and determine subcellular localization of iron in alveolar macrophages. We employed transmission electron microscopy (TEM) and backscattered electron (BSE) microscopy to obtain structural information and high-resolution analytical tools, NanoSIMS and helium ion microscopy-SIMS (HIM-SIMS) to trace the chemical signature of iron. Chemical information from NanoSIMS was correlated with TEM data, while high-spatial-resolution ion maps from HIM-SIMS analysis were correlated with BSE structural information of the cell. NanoSIMS revealed that iron is accumulating within mitochondria, and both NanoSIMS and HIM-SIMS showed accumulation of iron in electrolucent compartments such as vacuoles, lysosomes, and lipid droplets. This study provides insights into iron metabolism at the subcellular level and has future potential in finding therapeutics to reduce the cytotoxic effects of excessive iron loading