Cell resistivity, differential

Most recently, a phase-I-study defined a dose of 13-ris-retinoic acid that was tolerable in patients after myeloablative therapy, and a phase-III-trial showed that postconsolidation therapy with 13-cis-retinoic acid improved EFS for patients with high-risk neuroblastoma [7]. Preclinical studies in neuroblastoma indicate that ATRA or 13-cw-RA can antagonize cytotoxic chemotherapy and radiation, such that use of 13-cis-RA in neuroblastoma is limited to maintenance after completion of cytotoxic chemotherapy and radiation. It is likely that recurrent disease seen during or after 13-cis-RA therapy in neuroblastoma is due to tumor cell resistance to retinoid-mediated differentiation induction. Studies in neuroblastoma cell lines resistant to 13-cw-RA and ATRA have shown that they can be sensitive, and in some cases collaterally hypersensitive, to the cytotoxic retinoid fenretinide. Here, fenretinide induces tumor cell cytotoxicity rather than differentiation, acts independently from RA receptors, and in initial phase-I-trials has been well tolerated. Clinical trials of fenretinide, alone and in combination with ceramide modulators, are in development. 

All of these characteristics can be under the regulation of the cell and influenced by the cell culture conditions. The age of the cell monolayer in culture can have a profound impact on the quality of the barrier. In monolayers with actively dividing cells, resistance increases with time in culture as tight junctions form (see Fig. 15, Section III.C.4). Resistance reaches a plateau, then decreases as cell viability declines (Section III.C.4). Time in culture may also be a factor in the expression of polarity, which is related to tight junction formation as well as the state of differentiation of the cells (e.g., differential gene expression). 

Vincristine resistance has been studied in Chinese hamster ovary cell lines cells resistant to vincristine also are resistant to vinblastine and vindesine. Suggestions were made that, in cells with relatively low levels of drug resistance, at least two prominent mechanisms of resistance can occur (22). In the first instance, cellular resistance may be attributable to membrane alterations that are reversible, functionally, by treatment with verapamil. In the second, resistance has been postulated to be due to an altered sensitivity of tubulin to the effects of the drugs the primary basis for postulating an altered interaction with tubulin was that a subgroup of cells resistant to vincristine showed enhanced sensitivity to taxol, a drug that can stabilize microtubules. It should be emphasized that differential sensitivities of tubulins from different tumor cells to the effects of vincristine or vinblastine has been proposed as a basis for the susceptibilities of cells to the cytotoxic effects of such drugs (23). Differences have been described in the electrophoretic patterns for tubulins obtained from vin-... 

The sequel to acute injury depends on the potency and concentration of the toxic agent and the duration of exposure. Potent gases produce a severe vascular reaction and alveolar flooding. The fluid prevents gaseous exchange, and death of the human or animal ensues. After acute mild nonlethal damage, excess fluid is removed and the resistant Type II cells proliferate and reline the alveoli. The cells subsequently differentiate into Type I cells. 

Monitoring Obtain blood cultures, white blood cell, and differential cell counts prior to initiation of therapy and at least weekly during therapy with penicillinase-resistant penicillins. Measure AST and ALT during therapy to monitor for liver function abnormalities. 

Yuspa, S.H. and Morgan, D.L. (1981). Mouse skin cells resistant to terminal differentiation associated with initiation of carcinogenesis, Nature 293, 72. 

Adult stem cells include skeletal myoblasts and bone marrow stem cells. Skeletal myoblasts are highly resistant to ischemia, they are harvested as autologous cells and differentiate efficiently into adult skeletal muscle after transplantation. Electromechanical coupling between mature skeletal grafts and cardiac muscle has yet to be demonstrated. Furthermore, arrhythmias are reported to occur with the use of skeletal myoblasts.255... 

Yuspa and Morgan (1981) reported that cells resistant to terminal differentiation can be readily isolated from skin of B ALB/c mice exposed to an initiating dose... 

Comparison of the two mutant strains of B. megaterium, resistant to bacitracin and Su 2079, respectively, revealed that the 1735 cm" band was present in both cases, while the 1176 cm" band seen in the strain resistant to the thiourea compound was absent in the curve produced by the cells resistant to bacitracin. The strain resistant to the Su 2079 had a spectrum without a band at 835 cm". The 835 cm" band was distinct in the spectrum of the bacitracin-resistant cells. Thus, infrared spectroscopy differentiated between sensitive and resistant strains. 

The sum of Eqs. (5.37) and (5.41) is a differential equation of the oxidiser mass balance with two variables—concentration and temperature. The conductivity of the cell, K, is also, in general, temperature-dependent, and this dependence should be similar to Eq. (5.38) if the migration of ions through the film at the lithium surface determines the cell resistance. 

In our model the cell polarization curve Vceii j) is linear. This approximation is quite reasonable if the cell operates in the linear resistive region of the real curve. In that case, all previous relations are valid provided that RP is replaced by the differential cell resistivity —dVceii/dj. 

In the case of A = const. Equation 5.58 can be directly differentiated, keeping fx = const. Differentiating Equation 5.58 over J, one obtains the static differential cell resistivity Fee/ = dfjo/dJ,... 

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