ABSTRACT
Postulated cytoprotective action of (-)-deprenyl (D), (-)-desmethyl-deprenyl (DD) and (-)-deprenyl-N-oxide (DNO) on L-buthionine-(S,R)-sulfoximine (BSO) toxicity was investigated using in vitro cultures of serum-deprived A-2058 melanoma cells. BSO (10 microM/l) decreased viable cell number and mitotic rate, while increased the apoptotic index. D and both of its metabolites, given together with BSO in the concentration of 50 microM/l, mitigated cell loss and decreased the apoptotic ratio. DD was the most effective compound in decreasing apoptotic activity, while DNO stabilized the cell number on control level and increasing the ratio of mitotic cells above the only serum-deprived control. Surveillance on mitochondrial membrane stability and antioxidant properties may play an important role in these processes.
Subject(s)
Amphetamines/pharmacology , Cytoprotection/drug effects , Glutathione/pharmacology , Monoamine Oxidase Inhibitors/pharmacology , Selegiline/analogs & derivatives , Buthionine Sulfoximine/pharmacology , Cell Death/drug effects , Cell Line, Tumor , Drug Interactions , Flow Cytometry/methods , Humans , Melanoma/pathology , Radiation-Sensitizing Agents , Selegiline/pharmacology , Serum/metabolismABSTRACT
Dysregulation of the Notch-pathway has been implicated in the pathogenesis of chronic lymphocytic leukaemia (B-CLL). We characterized the mRNA expression of Notch pathway elements in circulating normal B- and B-CLL cells, and compared expression profiles with clinical and prognostic data. Similar expression profiles were found in normal B-cells and B-CLL cells, however, most B-CLL samples showed lower Hairy/Enhancer of Split-1 expression than normal B-cells, which suggests that the pathway is not over-activated in B-CLL. The expression of Notch-pathway genes did not correlate with other prognostic factors of B-CLL. The importance of Notch-signalling in CLL cells in lymphatic tissue microenvironments remains to be determined.
Subject(s)
B-Lymphocytes/metabolism , Leukemia, Lymphocytic, Chronic, B-Cell/metabolism , Receptors, Notch/metabolism , Signal Transduction/immunology , ADP-ribosyl Cyclase 1/metabolism , B-Lymphocytes/immunology , Blotting, Western , Flow Cytometry , Gene Expression , Gene Expression Profiling , Humans , Immunoglobulin Heavy Chains , Prognosis , RNA, Messenger/analysis , Reverse Transcriptase Polymerase Chain Reaction , Somatic Hypermutation, ImmunoglobulinABSTRACT
Transforming growth factor beta 1 (TGF beta 1) is an antiproliferative and proapoptotic cytokine for normal B-cells, however many B-cell lymphomas have lost their response to TGF beta 1. The aim of this study was to identify the sequence of events in apoptosis induced by TGF beta 1 in an EBV negative, human B-cell lymphoma line (HT58). The proportion of apoptotic cells increased gradually (up to 72 hr) at an optimal dose range of 0.5-1.0 ng/ml. The induced cell death required the action of downstream caspases. Caspase activation was accompanied by an increase in the permeability of mitochondrial membranes, but there was no change in the expression of certain members of Bcl-2 family (Bcl-2, Bax, Bcl-XL). Similarly, none of the death receptors or ligands were involved in apoptosis induction. Further study will include the participation of TGF beta 1 target genes in the pore formation of mitochondrial membranes and/or the elimination of a putative survival signal.
Subject(s)
Apoptosis , Caspases/metabolism , Lymphocytes/cytology , Transforming Growth Factor beta/metabolism , Caspase 3 , GPI-Linked Proteins , Humans , Receptors, TNF-Related Apoptosis-Inducing Ligand , Receptors, Tumor Necrosis Factor/genetics , Receptors, Tumor Necrosis Factor/metabolism , Receptors, Tumor Necrosis Factor, Member 10c , Signal Transduction , Transforming Growth Factor beta1 , Tumor Cells, Cultured , Tumor Necrosis Factor Decoy ReceptorsABSTRACT
A model with intermediate complexity is introduced to reproduce the basic firing modes of the CA3 pyramidal cell. Our model consists of a single compartment, has two variables (membrane potential and internal calcium concentration), and involves two separate stages for interspike mechanisms and firing. Interspike dynamics is governed by voltage- and calcium-dependent ionic channels but no channel kinetics are provided. This model is suitable to be included in our statistical population model (Part II, following paper). Bifurcation analysis reveals that interspike dynamics rather than sodium firing has the dominant role in the control of bursting/nonbursting behavior.
Subject(s)
Computer Simulation , Hippocampus/physiology , Models, Neurological , Periodicity , Pyramidal Cells/physiology , Action Potentials/physiology , Animals , Hippocampus/cytology , Humans , Neural Inhibition/physiologyABSTRACT
A statistical model is given to describe the electrical activity patterns of large neural populations of the hippocampal CA3 region. A continuous model has been formalized to describe the statistical processes governing the interactions within and between neural fields. The system of partial differential equations contains diffusion terms which determine the evolution of second moments of the probability distribution functions. The model is supplemented with a differential description of post-synaptic potentials. The discretization procedure has been designed so as to make the discrete equations scaling invariant. Population activities as well as underlying single-cell voltages are simulated during normal and epileptiform activities in the hippocampal CA3 slice. It is demonstrated that our model can reproduce electrophysiological phenomena characteristic to both single-cell and population activities. Specifically, fully synchronized population bursts, synchronized synaptic potentials, and low amplitude population oscillation were obtained.
Subject(s)
Hippocampus/physiology , Models, Neurological , Models, Statistical , Neurons/physiology , Periodicity , Action Potentials/physiology , Animals , Hippocampus/cytology , Organ Culture Techniques , Time FactorsSubject(s)
Epilepsy/physiopathology , Hippocampus/physiology , Models, Neurological , Pyramidal Cells/physiology , Animals , Hippocampus/anatomy & histology , Hippocampus/physiopathology , Models, Theoretical , Pyramidal Cells/cytology , Pyramidal Cells/pathology , Rats , Receptors, GABA-A/physiology , Reference Values , Synapses/physiology , Synaptic TransmissionABSTRACT
A mathematical model for describing dynamic phenomena in the olfactory bulb is presented. The nature of attractors and the bifurcation sequences in terms of the lateral connection strength in the mitral layer are studied numerically. Chaotic activity has only been found in the case of strong excitatory coupling. Synaptic modification-induced transition from oscillation to chaos is demonstrated. A model for a simple associative memory is also presented.
Subject(s)
Learning/physiology , Memory/physiology , Models, Neurological , Neurons/physiology , Olfactory Bulb/physiology , Animals , Association Learning/physiology , Mammals , Mathematics , Membrane Potentials , Smell/physiologyABSTRACT
A model for the formation of ordered neural mappings in general, and of retinotectal connections, in particular is given. The main point came from the theory of "noise induced transitions", i.e. order may be the result of the interplay between deterministic and random interactions. An activity-dependent self-organizing mechanism is presented in terms of modifiable synapses. Simulation experiments were done not only for the normal ontogenetic development but also for the plastic behaviour of the retinotopic connections.
Subject(s)
Models, Neurological , Neural Pathways/growth & development , Animals , Photic Stimulation , Physical Stimulation , Retina/growth & development , Stochastic Processes , Superior Colliculi/growth & development , Visual Pathways/growth & developmentABSTRACT
A study was undertaken to evaluate the influence of light intensity on the ability to discriminate color differences within the color range of natural teeth. The results show that shade selection is not significantly affected within the range of 75 to 300 fc. Neither the specialty of the dentist nor the amount of time in practice appeared to be a factor in making color discriminations. However, 7 of the 50 dentists serving as subjects were found to be color defective, and a difference was found between their color discrimination abilities and those of normal persons. This suggests that color-defective dentists should obtain assistance when matching tooth shades.
