Cellular studies

Evidence from cellular studies in vitro initially showed how oxidative processes could play a central role in the pathological changes involved in the genesis of atherosclerosis. LDL can be oxidatively modified in culture by a range of cell types including endothelial cells (Henriksen et a.1., 1981), arterial smooth muscle cells... 

Molsidomine and pirsidomine, are both stable as solids at room temperature in the absence oflight [137]. However the ring opened metabolites SIN-1A and C87-3786 are both photo labile and sensitive to an oxidising environment resulting ultimately in the release of superoxide and NO in stoichiometric quantities [138]. Generation of these two species is an obvious problem due to the resulting formation of peroxynitrite and the generation of OH, which may initiate lipid peroxidation [139-141] (see Eq. (19)). Such concerns over the formation of peroxynitrite from SIN-1A or C87-3786 are warranted since their cytotoxic effects show close consistency with cellular studies doped with neat peroxynitrite [142, 143]. 

ErbB inhibitors in development differ in several aspects, including potency, selectivity, and mechanism of inhibition. Fortunately, there are data that compare erlotinib, gefitinib, lapatinib, canertinib, HKI-272, and BIBW 2992 directly in enzymatic and cellular studies, as shown in Tables 2 and 3 [89,95]. 

Caboche, M. Rouze, P. (1990). Nitrate reductase a target for molecular and cellular studies in higher plants. Trends in Genetics 6,187-92. 

Cellular studies are facilitated in the microfluidic chips because of their small dimensions. In addition, the chip provides excellent optical properties for observation and flexible fluidic control capabilities for reagent delivery. 

In order to fully understand the antidiabetic effects of vanadium, or any other drug, cellular studies are extended to mammalian models of diabetes, frequently in rodents. Models exist and have been used for vanadium studies of both type 1 and type 2 diabetes. Below, general results observed with vanadium compounds in the various model systems are described. More detailed descriptions of the molecular signal transduction systems affected are given in references [12,13,100,133],... 

Unanue ER (1992) Cellular studies on antigen presentation by class II MHC molecules. Curr Opin Immunol 4 63-69... 

Although slightly attenuated, the rise in cytosolic calcium proceeds in the absence of extracellular calcium (as mentioned above), indicating that upon All stimulation calcium is released into the cytosol from an internal pool. The identity of this mobilized internal pool was initially inferred from cellular studies in which treatment with dantrolene inhibited the redistribution of intracellular calcium [39,40], Be-... 

TEER, normalized to surface, was 188-221 Ohm/cm2 in CACO-2 cells and 78-125 Ohm/cm2 in colon (Rubas et al. 1996). The presence of villi and crypts in vivo with a higher surface and a different cellular composition (goblet cells, M cells, higher permeability in crypts) compared to a cell mono-layer might lead to higher permeability. Tanaka et al. (1995) compared permeability of FITC-Dextran (MW 4000) in CACO-2 cells and rat jejunum and colon the permeability was 10 fold decreased in CACO-2 compared to jejunum and 5 fold lower than in colon. TEER in CACO-2 was 470 Ohm x cm2 in this study, 40 Ohm x cm2 in rat jejunum and 80 Ohm x cm2 in rat colon. Permeability of standard markers like PEG was compared between CACO-2 cells and colon (Artursson et al. 1993). The conclusion for cellular studies is to select cells with acceptable TEER and permeability values and to perform quality assurance tests on a regular basis. 

CELLULAR STUDIES IN INTACT TISSUE 8.2.1 Whole-Animal Studies... 

Tanke HJ, Brouwer J, Reedijk J. Dinuclear platinum complexes with N,N -bis(aminoalkyl)-l,4-diaminoanthraquinones as linking ligands. Part I. Synthesis, cytotoxicity, and cellular studies in... 

If the extracellular Rb+ concentration changes with time, the solution is more complicated, but we will not discuss this here. If the NMR experiment allows sufficient time resolution, we can mirror radioactive tracer experiments and use the data acquired in the linear part of the exponential curve, i.e. where t < 1 /k, as this eliminates any need to model the passive efflux part of the transport process correctly. For cellular studies at high field this is possible, but for perfused organ studies at lower field the sensitivity of the NMR experiment does not permit this, and we are forced to acquire data over a longer time period and fit equation (85) to the resulting spectral areas. 

Studies with PNA analogs have shown that these analogs can inhibit translation in cell-free systems, but to date no data have been reported from cellular studies (114,115). For morpholino oligomers, antisense activity has been reported in both cell-free and cellular assays (116, 117). Numerous oligonucleotides... 

Despite their high affinity, these peptide-based compounds were not useful for cellular studies, primarily due to their poor cell permeability. To enhance their permeability, compounds were tethered to carrier peptides, which resulted in compounds that activated p53 function in cells at concentrations of 100-500 pM. Although such weak cellular activity clearly makes them unsuitable as potential therapeutic agents, they nevertheless provided the initial proof-of-concept that blocking the interaction between MDM2 and p53 can indeed be an effective means of activating p53. 

Summary what do cellular studies say about the molecular nature of axon guidance factors ... 

Cellular studies of axon growth in invertebrates have shown that axons acquire their stereotypic, mature morphologies by both accurate growth... 

The cellular studies outlined in Section 3.5 point to a role for factors in the extracellular matrix, and particularly the basal lamina, in axon guidance. A number of studies in invertebrate species have begun to characterize molecules that may subserve axon guidance on such substrates. 

The cellular studies discussed in Section 3.4.3 provide evidence for a role for glia in guiding axons in insect embryos. To date, however, there are no well-documented examples of molecules that may subserve this function. The case of the DER protein in the Drosophila embryo has been discussed above. Some proteins, such as fasciclin in (see Section 5.1.1) and neuroglian (Section 5.3), are expressed on glia as well as on neurons, but their glial function has not been determined. Oth-... 

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