A Novel F45S SOD1 Mutation in Amyotrophic Lateral Sclerosis Coexisting with Bullous Pemphigoid

BACKGROUND: The coexistence of an autoimmune disease and amyotrophic lateral sclerosis (ALS) has led to the hypothesis that immune-mediated pathological mechanisms are overlapping in the two diseases. We report herein a rare coexistence of bullous pemphigoid (BP) in a novel mutation (F45S) of the gene encoding Cu/Zn superoxide dismutase (SOD1) in an ALS patient, and discuss a role for the SOD1 mutation in this unusual overlap. CASE REPORT: A 57-year-old male with familial ALS, including vesicles and tense bullae on erythematous bases, was diagnosed with BP. Direct immunofluorescence revealed deposits of C3 and immunoglobulin G in the basement membrane zone. Direct sequencing of SOD1 in the patient revealed a novel mutation (c.137T>C; F45S). CONCLUSIONS: We report a novel SOD1 mutation in ALS, which was combined with BP. This novel SOD1 mutation could affect the phenotype of a combined autoimmune disease and matrix metalloproteinase-9. There may therefore be common factors linking BP and ALS with the SOD1 mutation.

The Effect of Atorvastatin and Simvastatin on NIS Expression of the TPC-1 Cell under the Therapeutic Blood Concentrations

BACKGROUND: Although so many experimental trials have been done to improve the redifferentiation and responsiveness of radioiodide therapy, they have not yet yielded any satisfactory results. As statins inhibit both farnesylation and geranylgeranylation, they have been reported to have an antineoplastic and redifferentiation effect in experimental and clinical studies. In this study, we investigated the relationship between statins and the alteration of the NIS expression and, TPC-1 cell apotosis to evaluate the possibility of using statins as adjuvant therapeutic agents for papillary thyroid cancer. METHODS: We used the TPC-1 cell lines for our experiments. Cell viabilities were measured by CCK-8. The degrees of apoptosis and, the expressions of NIS mRNA and NIS protein were measured by flow cytometry, semi quantitative RT-PCR and Western blot assay. RESULTS: Increased levels of NIS mRNA and NIS protein were observed under therapeutic blood concentrations (concentrations of simvastatin: 20, 50, 80 nM, concentrations of atorvastatin: 50, 80,110 nM), but the dose-response relationship was only manifested within simvastatin. The TPC-1 cells showed a concentration dependent decrease of viability and an increase of apoptosis not under therapeutic blood concentrations, but under excessively high concentrations (after treatment with 10-50 microM of atorvastatin and with 1-10 microM of simvastatin). CONCLUSION: The results of this study show that effective therapeutic blood concentrations of simvastatin and atorvastatin can give a favorable effect on the NIS expression under effective therapeutic blood concentrations. Therefore, we demonstrated the possibility that simvastatin and atorvastatin might have an important role as adjuvant therapeutic agents to improve the responsiveness of radioiodide therapy for papillary thyroid cancer. Further studies are needed to clarify this issue.