There has been an explosion of interest in mindfulness-based programs (MBPs) such as Mindfulness-Based Stress Reduction (MBSR) and Mindfulness-Based Cognitive Therapy. This is demonstrated in ...increased research, implementation of MBPs in healthcare, educational, criminal justice and workplace settings, and in mainstream interest. For the sustainable development of the field there is a need to articulate a definition of what an MBP is and what it is not. This paper provides a framework to define the essential characteristics of the family of MBPs originating from the parent program MBSR, and the processes which inform adaptations of MBPs for different populations or contexts. The framework addresses the essential characteristics of the program and of teacher. MBPs: are informed by theories and practices that draw from a confluence of contemplative traditions, science, and the major disciplines of medicine, psychology and education; underpinned by a model of human experience which addresses the causes of human distress and the pathways to relieving it; develop a new relationship with experience characterized by present moment focus, decentering and an approach orientation; catalyze the development of qualities such as joy, compassion, wisdom, equanimity and greater attentional, emotional and behavioral self-regulation, and engage participants in a sustained intensive training in mindfulness meditation practice, in an experiential inquiry-based learning process and in exercises to develop understanding. The paper's aim is to support clarity, which will in turn support the systematic development of MBP research, and the integrity of the field during the process of implementation in the mainstream.
Although it is accepted that particulate Ags are more immunogenic than soluble Ags in vivo, it is unclear whether this effect can be explained solely through enhanced uptake by APCs. In this study we ...demonstrate that vesicle size modulated the efficiency of Ag presentation by murine macrophages and that this effect was accompanied by a profound change in trafficking of Ag. Ag prepared in large particles (560 nm) was delivered into early endosome-like, immature phagosomes, whereas smaller vesicles (155 nm) and soluble Ags localized rapidly to late endosomes/lysosomes. However, peptide/class II complexes could be detected in both compartments. Phagosomes formed on uptake of large vesicles recruit Ag-processing apparatus while retaining the characteristics of early endosomes. In contrast, smaller vesicles bypassed this compartment, appeared to go more rapidly to lysosomal compartments, and exhibited reduced Ag-presenting efficiency. We conclude that the ability of phagocytosed, particulate Ag to target early phagosomes results in more efficient Ag presentation.
Copper in medicine Brewer, George J
Current opinion in chemical biology,
04/2003, Volume:
7, Issue:
2
Journal Article
Peer reviewed
Copper has been found to be causative in several diseases. New findings with the greatest potential for impact in medicine include the use of copper-lowering therapy for antiangiogenesis, ...antifibrotic and anti-inflammatory purposes. The indication of the role of copper in formation of amyloid plaques in Alzheimer’s disease, and successful treatment of an Alzheimer’s rodent model by copper chelation are also potentially important. There have also been recent developments in the genetic and non-genetic abnormalities of copper, including the finding of new copper-related genes that potentially could cause disease if mutated.
Two fundamental questions about neuron cell culture were addressed. Can one serum-free medium that was developed for optimum growth of hippocampal neurons support the growth of neurons from other ...regions of the brain? Is the region specific state of differentiation maintained in culture? To answer these questions, we isolated neurons from six other rat brain regions, placed them in culture in B27/Neurobasal defined medium, and analyzed their morphology and growth dependence on cell density after 4 days in culture. Neuronal identity was confirmed by immunostaining with antibodies to neurofilament 200. Neurons from each brain region maintained distinctive morphologies in culture in the virtual absence of glia. Cells isolated from embryonic day 18 cerebral cortex by digestion with papain showed the same high survival as hippocampal neurons, e.g., 70% survival for cells plated at 160/mm2. At this age and density, neurons from the septum showed slightly lower survival, 45%. Survival of dentate granule neurons from postnatal day four brains was 30-40%, significantly lower, and relatively independent of plating density. This suggests an absence of dependence on trophic factors or contact for dentate granule neurons. Growth of cerebellar granule neurons isolated from postnatal day 7, 8, or 9 brains in B27/Neurobasal was compared to growth in BME/10% serum. Viability in serum-free medium at 4 days was much better than that in serum, did not require KCl elevated to 25 mM, and occurred without substantial growth of glia. Cerebellar granule neurons plated at 1,280 cells/mm2 were maintained in culture for three weeks with 17% of the original cell density surviving. Survival of cells isolated from embryonic day 18 substantia nigra was 50% at 160 cells/mm2 after 4 days, similar to that of striatum, but slightly less than hippocampal neuron survival. The dopaminergic phenotype of the substantia nigral neurons was maintained over 2 weeks in culture as judged by immunoreactivity with antibodies to tyrosine hydroxylase. During this time, immunoreactivity was found in the processes as they grew out from the soma. Together, these studies suggest that B27/Neurobasal will be a useful medium for maintaining the differentiated growth of neurons from many brain regions. Potential applications of a common growth medium for different neurons are discussed.
Inability to culture adult central neurons and the failure of injured neurons to regenerate in the brain could be due to genetic controls or environmental inhibitors. We tested the environmental ...inhibitor hypothesis by attempting to regenerate adult rat neurons in B27/Neurobasal™ culture medium, a medium optimized for survival of embryonic neurons. To isolate neurons from their numerous connections, papain was the best of six different proteases screened on slices of hippocampus for survival of isolated cells after 4 days of culture. Use of a density gradient enabled separation of oligodendroglia and some enrichment of neurons and microglia from considerable debris which was inhibitory to sprouting and viability. With these techniques, about 900 000 viable neurons were isolated from each hippocampus of any age rat from birth to 24–36 months, near the median mortality. FGF2 was found to enhance viability at least 3-fold to 40–80%, independent of age, without affecting the length of the processes. Neurons were cultured for more than 3 weeks. These methods demonstrate that hippocampal neurons can regenerate axons and dendrites if provided with adequate nutrition and if inhibitors are removed. They also will enable aging studies. Therefore, the concept of environmental growth restriction may be more appropriate for neurons in the brain than the concept of a genetic block that precludes regeneration of processes.
Copper is a tightly regulated trace element. Disruptions of copper homeostasis are rare and they cause serious disorders such as Wilson's disease and Menkes disease. Copper also plays an important ...role in promoting physiological and malignant angiogenesis. Formation of new blood vessels by a tumor enables tumor growth, invasion and metastasis. The copper chelator tetrathiomolybdate (TM), which quickly and effectively depletes copper stores, is under investigation as an anti-angiogenic agent. Promising results in vitro, in pre-clinical animal models and in an early (phase I) clinical trial have led to ongoing phase II evaluation of TM in patients with advanced cancers.
We have systematically optimized the concentrations of 20 components of a previously published serum-free medium (Brewer and Cotman, Brain Res 494: 65-74, 1989) for survival of rat embryonic ...hippocampal neurons after 4 days in culture. This serum-free medium supplement, B27, produced neuron survival above 60%, independent of plating density above 160 plated cells/mm2. For isolated cells (< 100 cells/mm2), survival at 4 days was still above 45%, but could be rescued to the 60% level at 40 cells/mm2 by simply applying a coverslip on top of the cells. This suggests a need for additional trophic factors. High survival was achieved with osmolarity lower than found in Dulbecco's Modified Eagle's Medium (DMEM), and by reducing cysteine and glutamine concentrations and by the elimination of toxic ferrous sulphate found in DME/F12. Neurobasal is a new medium that incorporates these modifications to DMEM. In B27/Neurobasal, glial growth is reduced to less than 0.5% of the nearly pure neuronal population, as judged by immunocytochemistry for glial fibrillary acidic protein and neuron-specific enolase. Excellent long-term viability is achieved after 4 weeks in culture with greater than 90% viability for cells plated at 640/mm2 and greater than 50% viability for cells plated at 160/mm2. Since the medium also supports the growth of neurons from embryonic rat striatum, substantia nigra, septum, and cortex, and neonatal dentate gyrus and cerebellum (Brewer, in preparation), support for other neuron types is likely. B27/Neurobasal should be useful for in vitro studies of neuronal toxicology, pharmacology, electrophysiology, gene expression, development, and effects of growth factors and hormones.
The search for new anticopper drugs for Wilson's disease is culminating in two excellent new drugs: zinc for maintenance therapy and tetrathiomolybdate (TM) for initial therapy. Both are effective ...and nontoxic. TM is a very potent, fast-acting new anticopper drug and its properties may be useful well beyond Wilson's disease. Angiogenesis (new blood vessel growth) is required for tumor growth, and a sufficient level of copper appears to be required for angiogenesis. We hypothesize that there is a "window" to which the copper level can be reduced that inhibits angiogenesis in tumors, but does not interfere with vital cellular functions of copper. Using TM therapy, this approach has worked to slow or stabilize tumor growth in several animal tumor models, and preliminary results are also very encouraging in human patients with a variety of advanced and metastatic malignancies. A hypothesis is advanced that copper availability has played a fundamental role in growth regulation throughout evolution and that is the reason that so many angiogenic promoters appear to be dependent upon copper levels.
We have utilized an experimental model of human zinc deficiency for study of cytokines production by TH1 and TH2 cells. Additionally, we determined ratios of CD4+ to CD8+ and CD4+CD45RA+ to ...CD4+CD45RO+ cells and percentages of CD73+ T cytolytic cells in the CD8+ subset. The data were collected during baseline, at the end of the zinc-restricted period, and following zinc repletion. Our results showed that functions of TH1 cells, as evidenced by production of interferon-gamma, interleukin-2 (IL-2), and tumor necrosis factor-alpha, were decreased, whereas functions of TH2 cells (production of IL-4, IL-6, and IL-10) were unaffected by zinc deficiency. Thus an imbalance between TH1 and TH2 cells resulted because of zinc deficiency in humans. Our studies also showed that zinc may be required for regeneration of new CD4+ T lymphocytes and maintenance of T cytolytic cells. We conclude that an imbalance between TH1 and TH2 cells, decreased recruitment of T naive cells, and decreased percentage of T cytolytic cells may account for decreased cell-mediated immune functions in zinc-deficient subjects.
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