Introduction: B cell chronic lymphocytic leukemia (B-CLL) is a hematological malignancy considered as the most common leukemia in the Western world. The understanding of B cell differentiation is crucial for the diagnosis, prognosis, and treatment of the disease.
Areas covered: In this review, B-cell ontogeny and its relation with the CLL development, in combination with the proteomic approaches which could provide a deep characterization of the disease through the characterization of the cellular signaling pathways involved in the pathological cells is described.
Expert commentary: Although conventional strategies (genome sequencing, morphology assays, and immunophenotyping by flow cytometry and/or immunochemistry) have allowed the establishment of the disease stage based on different parameters, it is still necessary to utilize novel approaches (e.g., proteomics) that have the potential to simultaneously analyze thousands of molecules to improve understanding of CLL. 相似文献
It has taken more than 40 years for the fields of immunology and neuroscience to capture the potential impact of the mechanistic understanding of how an active immune signalling brain might function. These developments have grown an appreciation for the immunocompetent cells of the central nervous system and their key role in the health and disease of the brain and spinal cord. Moreover, the understanding of the bidirectional communication between the brain and the peripheral immune system has evolved to capture an understanding of how mood can alter immune function and vice versa. These concepts are rapidly evolving the field of psychiatry and medicine as a whole. However, the advances in human medicine have not been capitalised upon yet in animal husbandry practice. Of specific attention are the implications that these biological systems have for creating and maintaining heightened pain states. This review will outline the key concepts of brain–immune communication and the immediate opportunities targeting this biology can have for husbandry practices, with a specific focus on pain. 相似文献
Radiosynoviorthesis is used for the local treatment of recurrent joint effusions and leads to synovial pannus necrosis after radionuclide administration. This procedure provides the opportunity to full recovery of normal synovium function after local corticosteroids and systemic modifying drugs failure. 相似文献
Pain sensation has been studied extensively, over a range of scales, from the molecular level to the entire human neural system. Thermal stimulation of pain has been widely used in the study of pain sensation. Skin thermal pain is induced through both direct (an increase/decrease in temperature) and indirect (thermomechanical and thermochemical) ways, and is governed by complicated thermomechanical–chemical–neurophysiologic responses. This paper is focused on the theoretical modeling of the underlying mechanisms in the process of skin thermal pain. A holistic model has been developed, which is composed of three sub-models, namely, transduction, transmission, and modulation and perception. The model can contribute to the understanding of thermally related pain phenomena in skin tissue and to improvements in a range of thermal therapeutic methods. 相似文献
We examined stimulus-response relationships of vibrissa-activated mechanosensory neurons of the rat's fifth (trigeminal) ganglion. Single-unit activity was recorded with tungsten microelectrodes. The vibrissae were deflected with a variety of parametrically controlled stimulus waveforms.We found that the receptive field of each vibrissa-activated neuron consisted of a single vibrissa. Few, if any, unambiguous examples of spontaneous activity were observed in these neurons. Even if true spontaneous activity was present, its observed incidence was low, as were the measured discharge rates.Thresholds of individual neurons were usually quite discrete; often a 1-2% increase in pulse magnitude (angular displacement) above a level to which the neuron did not respond caused it to discharge on every trial. The distribution of thresholds for the sample was continuous with a median of about 1° and a range of over three orders of magnitude. The most sensitive neurons responded to deflections of less than 0.1°. Many neurons responded to a single suprathreshold pulse with more than one spike. We found no consistent relationships among the thresholds of the additional evoked discharges of an individual neuron other than that the total number of evoked spikes either increased or stayed the same, but never decreased, as stimulus magnitude increased.About one-third of the neurons examined had velocity thresholds below 3°/sec. Above that value, thresholds were distributed continuously throughout a range of over three orders of magnitude. The median velocity threshold was about 100°/sec. The broad and continuous distributions of both magnitude and velocity thresholds suggest that a population of vibrissa-activated neurons can code stimulus strength smoothly and continuously over a wide range, even though individual neurons may be poorly suited to do so. 相似文献
The X+-linked chronic granulomatous disease (X+-CGD) variants are natural mutants characterized by defective NADPH oxidase activity but with normal Nox2 expression. According to the three-dimensional model of the cytosolic Nox2 domain, most of the X+-CGD mutations are located in/or close to the FAD/NADPH binding regions. A structure/function study of this domain was conducted in X+-CGD PLB-985 cells exactly mimicking 10 human variants: T341K, C369R, G408E, G408R, P415H, P415L, Δ507QKT509-HIWAinsert, C537R, L546P, and E568K. Diaphorase activity is defective in all these mutants. NADPH oxidase assembly is normal for P415H/P415L and T341K mutants where mutation occurs in the consensus sequences of NADPH- and FAD-binding sites, respectively. This is in accordance with their buried position in the three-dimensional model of the cytosolic Nox2 domain. FAD incorporation is abolished only in the T341K mutant explaining its absence of diaphorase activity. This demonstrates that NADPH oxidase assembly can occur without FAD incorporation. In addition, a defect of NADPH binding is a plausible explanation for the diaphorase activity inhibition in the P415H, P415L, and C537R mutants. In contrast, Cys-369, Gly-408, Leu-546, and Glu-568 are essential for NADPH oxidase complex assembly. However, according to their position in the three-dimensional model of the cytosolic domain of Nox2, only Cys-369 could be in direct contact with cytosolic factors during oxidase assembly. In addition, the defect in oxidase assembly observed in the C369R, G408E, G408R, and E568K mutants correlates with the lack of FAD incorporation. Thus, the NADPH oxidase assembly process and FAD incorporation are closely related events essential for the diaphorase activity of Nox2. 相似文献