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We previously showed in vivo that coding-end processing is specific for each coding end, suggesting that specific motifs in a coding-end sequence influence nucleotide deletion and P-region formation. In this study, we created a panel of recombination substrates containing actual immunoglobulin and T-cell receptor coding-end sequences and dissected the role of each motif by comparing its processing pattern with those of variants containing minimal nucleotide changes from the original sequence.

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Using colony formation in soft agar as a measure of full transformation, we report here that R- cells can be transformed by v-src, although they still cannot be transformed by the activated c-src577 (mutation at tyrosine 577 to phenylalanine), which readily transforms mouse embryo cells with a wild-type number of IGF-I receptors (W cells). Although v-src is a more potent inducer of tyrosine phosphorylation than c-src577, the extent of phosphorylation of either insulin receptor substrate 6 or Shc, two of the major substrates of the IGF-I receptor, does not seem sufficiently different to explain the qualitative difference in soft agar growth.

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We have used epidural SCS for pain control during the past 65 years. An analysis of our records revealed 67 consecutive patients diagnosed as having RSD before undergoing SCS. Eight of the 67 patients had undergone previous ablative sympathectomy. All 67 patients experienced relief of pain after trial stimulation and had their systems permanently implanted.

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The results suggest that leptomeningeal fibrosis is not the only pathoanatomic basis of increased R(out) and/or B-wave activity in patients with NPH and that various degenerative changes in the parenchyma may be responsible for the altered cerebrospinal fluid dynamics characteristic of NPH. The purpose of this study was to determine the efficacy of spinal cord stimulation (SCS) in patients with symptoms of reflex sympathetic dystrophy (RSD), a disabling clinical condition with significant consequences of morbidity and loss of productivity.

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v-src, however, is considerably more efficient than c-src577 in its ability to tyrosyl phosphorylate, in R- cells, the focal adhesion kinase, Stat6, and p685cas. These results indicate that v-src, but not c-src577, can bypass the requirement for a functional IGF-I receptor in the full transformation of mouse embryo fibroblasts and suggest that qualitative and quantitative differences between the two oncogenes can be used to identify some of the signals relevant to the mechanism(s) of transformation.

Our results demonstrate the determinant role of specific sequence motifs on coding-end processing and also the importance of the context in which they are found. We propose that each coding-end sequence dictates a unique hairpin structure, the result of a particular energy conformation between nucleotides organizing the loop and the stem, and that the interplay between this structure and specific sequence motifs influences the frequency and location of nicks which open the coding-end hairpin. These findings indicate that the sequences of the coding ends determine their own processing and have a profound impact on the development of the primary B- and T-cell repertoires.

Eight patients reported excellent pain relief, and four patients described good results. SCS is an effective treatment for the pain of RSD, including recurrent pain after ablative sympathectomy. The low morbidity of this procedure and its efficacy in patients with refractory pain related to RSD suggest that SCS is superior to ablative sympathectomy in the management of RSD.

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