Benign peripheral nerve tumors: treatment algorithm and reconstructive options.

Peripheral nerve tumors are mostly benign; however, their excision can result in profound deficits. Nerve reconstruction strategies offer techniques to minimize morbidity. In this prospective study, 20 consecutive patients with benign peripheral nerve tumors were treated using a single-stage surgical paradigm between 2003 and 2007. Nerve fascicles were microdissected off of the tumor; any fascicle that gave origin to the tumor (was inseparable from tumor) was reconstructed using nerve conduits. Patients were followed from 6 to 24 months. All patients had neuropathic pain before tumor excision; only 1 patient had pain persist postoperatively. Seventeen patients had complete functional recovery after nerve reconstruction. No perioperative complications occurred. Benign peripheral nerve tumors require highly specialized surgical care. Tumor excision with immediate nerve reconstruction, for fascicles inseparable from the tumor, optimizes outcomes. Nerve reconstruction with available conduits or allografts should be attempted to restore anatomic integrity to any killed fascicles, thereby minimizing possible deficits.

Inhibition of protein-tyrosine phosphatases by mild oxidative stresses is dependent on S-nitrosylation.

Previous studies have shown that a Ca(2+)-dependent nitric-oxide synthase (NOS) is activated as part of a cellular response to low doses of ionizing radiation. Genetic and pharmacological inhibitor studies linked this NO signaling to the radiation-induced activation of ERK1/2. Herein, a mechanism for the radiation-induced activation of Tyr phosphorylation-dependent pathways (e.g. ERK1/2) involving the inhibition of protein-Tyr phosphatases (PTPs) by S-nitrosylation is tested. The basis for this mechanism resides in the redox-sensitive active site Cys in PTPs. These studies also examined oxidative stress induced by low concentrations of H(2)O(2). S-Nitrosylation of total cellular PTP and immunopurified SHP-1 and SHP-2 was detected as protection of PTP enzymatic activity from alkylation by N-ethylmaleimide and reversal by ascorbate. Both radiation and H(2)O(2) protected PTP activity from alkylation by a mechanism reversible by ascorbate and inhibited by NOS inhibitors or expression of a dominant negative mutant of NOS-1. Radiation and H(2)O(2) stimulated a transient increase in cytoplasmic free [Ca(2+)]. Radiation, H(2)O(2), and the Ca(2+) ionophore, ionomycin, also stimulated NOS activity, and this was associated with an enhanced S-nitrosylation of the active site Cys(453) determined by isolation of S-nitrosylated wild type but not active site Cys(453) --> Ser SHP-1 mutant by the "biotin-switch" method. Thus, one consequence of oxidative stimulation of NO generation is S-nitrosylation and inhibition of PTPs critical in cellular signal transduction pathways. These results support the conclusion that a mild oxidative signal is converted to a nitrosative one due to the better redox signaling properties of NO.