Unique Scanning Electron Microscopic Features of Hairy Cells in Hairy-Cell Leukemia. A Review and Current Status

Past scanning electron microscopy (SEM) reports demonstrated cell surface undulations, ridges, folds, and ruffles to support the monocytic/histiocytic nature of hairy-cell leukemia (HCL) cells. On the other hand, SEM studies illustrating spikes, villi, and microvilli on the cell surfaces favored the lymphocytic nature of hairy cells (HCs). The evidence for the \u27hybrid\u27 nature of the HCs has emerged from the demonstration of concurrent display of monocytic (ruffles) and lymphocytic (microvilli) surface features on each cell. Utilizing improved methods of sampling, fixation, and drying, the current status is that all HCs display microvilli and ruffles simultaneously. However, two distinct morphological types of HCs are acknowledged: cells showing ruffled areas next to clumps of microvilli (type A), and cells displaying microvilli interspersed among ruffles (type B) . Each of the HCL cases reported in our studies had cells with either type A or type B surface features. Amazingly, these unique SEM features correlate well with the prevalent trend to classify HCs as malignant (villous) B-lymphocytes imitating (ruffled) monocytes in some functional respects

Interferon-Induced Surface Alterations in Hairy Cells. A Review

Hairy cells (HCs), derived from the peripheral blood and spleen of hairy cell leukemia (HCL) patients, constantly displayed both ruffles and microvilli. HCs which were kept in culture for up to three days exhibited extremely polarized and active surfaces with elongated microvilli and exaggerated spiked ruffles. Cells derived from 11 cases of HCL were treated with alpha-interferon (IFN) in-vitro and examined by immuno -scanning electron microscopy (immuno-SEM). In 8 cases, up to one-third of the IFN-treated hairy cells displayed deformed surfaces with bubbling membrane and markedly villous bud-like formations. Monoclonal antibodies (MoAb), used in conjunction with immuno-qold labeling, facilitated better correlation between these morphological changes and the immunological profiles of the cells before and after interferon treatment in-vitro. Immuno-SEM analyses revealed no remarkable changes in the labeling of HCs with Leu-14 and Leu-MS MoAbs before and after IFN treatment, even in cases showing membrane changes. However, a significant increase in the labeling intensity for HLA-DR and HLA-DQ was noticed in HCs from cases where IFN-induced membrane changes were evident. A review of the literature on membrane changes in IFN-treated cells proposes that such immuno-ultrastructural alterations might reflect unique interferon-induced membrane reorganization in the target malignant cells

Topical Modes in the Preparation of Human Spleen Specimens for Routine Scanning Electron Microscopy Studies

Various preparatory techniques were used to improve scanning electron microscopy images of the fine structure of vascular, cellular, and cordal-reticular components of normal human spleens. The progressive method of fixation (GTGO) applied in the present study, allowed air drying of the tissues and rendered the specimens conductive even in newly fractured surfaces. Vascular perfusion proved necessary only in studies of the splenic blood vessels, while a simple immersion of tissue blocks in the washing solution resulted in better images of the white pulps. Interstitial (trans-splenic) perfusion was found to be superior to vascular perfusion for routine preparation of spleen tissues, and freeze-cracking did not necessarily lead to improved images of the specimen\u27s surfaces. Combined with proper washing and shaping protocols, the GTGO procedure is shown to be a superior mode of specimen preparation, abolishing most traditional artifacts and obtaining clear images of the complex splenic tissue

Membrane Properties and the Balance between Excitation and Inhibition Control Gamma-Frequency Oscillations Arising from Feedback Inhibition

Computational studies as well as in vivo and in vitro results have shown that many cortical neurons fire in a highly irregular manner and at low average firing rates. These patterns seem to persist even when highly rhythmic signals are recorded by local field potential electrodes or other methods that quantify the summed behavior of a local population. Models of the 30–80 Hz gamma rhythm in which network oscillations arise through ‘stochastic synchrony’ capture the variability observed in the spike output of single cells while preserving network-level organization. We extend upon these results by constructing model networks constrained by experimental measurements and using them to probe the effect of biophysical parameters on network-level activity. We find in simulations that gamma-frequency oscillations are enabled by a high level of incoherent synaptic conductance input, similar to the barrage of noisy synaptic input that cortical neurons have been shown to receive in vivo. This incoherent synaptic input increases the emergent network frequency by shortening the time scale of the membrane in excitatory neurons and by reducing the temporal separation between excitation and inhibition due to decreased spike latency in inhibitory neurons. These mechanisms are demonstrated in simulations and in vitro current-clamp and dynamic-clamp experiments. Simulation results further indicate that the membrane potential noise amplitude has a large impact on network frequency and that the balance between excitatory and inhibitory currents controls network stability and sensitivity to external inputs

In Support of a Patient-Driven Initiative and Petition to Lower the High Price of Cancer Drugs

Comment in Lowering the High Cost of Cancer Drugs--III. [Mayo Clin Proc. 2016] Lowering the High Cost of Cancer Drugs--I. [Mayo Clin Proc. 2016] Lowering the High Cost of Cancer Drugs--IV. [Mayo Clin Proc. 2016] In Reply--Lowering the High Cost of Cancer Drugs. [Mayo Clin Proc. 2016] US oncologists call for government regulation to curb drug price rises. [BMJ. 2015