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Objective To explore the causes of postoperative recurrence in patients of nodular goiter,the selection of method for reoperation and the postoperative complications. Methods The clinical data of 278 nodular goiter patients admitted in the first affiliated hospital of Harbin Medical University between 2001 and 2008 were analyzed retrospectively,including the methods and complications for first operation and reoperation. Results In the first operation,79 eases received simple eminectomy and 167 cases received partial lobectomy,accounted for 28.4% and 60.1%,respectively. Unilateral subtotal lobectomy plus contralateral eminectomy was performed in 23 cases and subtotal thyroideetomy was conducted in 9 cases,accounted for 8.3% and 3.2%,respectively. Postoperative complications occurred in one hundred and twenty-three cases,the incidence being 8.2% (23/278). Unilateral subtotal Iobectomy plus contralateral partial iobectomy was reperformed in 37 cases and bilateral subtotal thyroidectomy in 241 cases. Postoperative complications occurred in 12 cases,the incidence being 4.2%(12/278). No postoperative recurrence of nodular goiter was found. Conclusions Recurrence of nodular goiter is closely associated with the scope of previous surgical treatment,and correct operative manipulation may reduce the recurrent rate.
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OBJECTIVE: To explore the effects of adenovirus vector-mediated gene transfer of CTLA4Ig fusion protein on CD4+CD25+ T cells in experimental autoimmune myocarditis (EAM). METHODS: EAM was induced by porcine cardiac myosin as previously described. Adenovirus vector-mediated CTLA4Ig gene was administrated intravenously in EAM rats on days 1, 4 and 7, with EGFP as control. On day 21, myocardium histopathology was examined and CD4+CD25+ T cells were isolated. Proliferation and suppression assays were used to evaluate the suppressive capacity of CD4+CD25+ T cells in vitro. Relative mRNA level of Foxp3 and TGF-beta was determined by quantitative real-time RT-PCR; expression of CTLA-4, B7-1 and B7-2 protein was compared with Western blot in CD4+CD25+ Tregs. RESULTS: Severe inflammatory lesions were observed in the hearts of EGFP-treated EAM rats and the untreated ones, while Ad-CMV-CTLA4Ig alleviated the myocarditis histologically. Adenovirus vector-mediated CTLA4Ig gene transfer up-regulated the proportion of CD4+CD25+ Tregs significantly. T cell proliferation was greatly inhibited in the CTLA4Ig group compared with the untreated and EGFP-treated groups in vitro. CTLA-4 and B7-2 proteins were down-regulated in the CTLA4Ig group, Foxp3 and TGF-beta mRNA was up-regulated significantly by CTLA4Ig treatment. CONCLUSIONS: Adenovirus vector-mediated CTLA4Ig gene transfer alleviated inflammation in EAM, one of the potential mechanisms is up-regulation of CD4+CD25+ Tregs.
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Enfermedades Autoinmunes/inmunología , Terapia Genética/métodos , Inmunoconjugados/inmunología , Miocarditis/inmunología , Linfocitos T Reguladores/inmunología , Abatacept , Adenoviridae/genética , Animales , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/terapia , Antígeno B7-1/biosíntesis , Antígeno B7-1/inmunología , Antígeno B7-2/biosíntesis , Antígeno B7-2/inmunología , Western Blotting , Antígenos CD4/sangre , Antígenos CD4/inmunología , Proliferación Celular , Factores de Transcripción Forkhead/biosíntesis , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/inmunología , Vectores Genéticos/genética , Humanos , Inmunoconjugados/sangre , Inmunoconjugados/genética , Activación de Linfocitos , Masculino , Miocarditis/genética , Miocarditis/terapia , Miocardio/patología , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Ratas , Ratas Endogámicas Lew , Receptores de Interleucina-2/sangre , Receptores de Interleucina-2/inmunología , Linfocitos T Reguladores/citología , Factor de Crecimiento Transformador beta/biosíntesis , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/inmunologíaRESUMEN
<p><b>BACKGROUND</b>Experimental autoimmune myocarditis (EAM) in rats is a T-cell-mediated disorder. The initiation and maintenance of autoimmune responses in EAM depend on the maturation state of dendritic cells. IL-10 is a pleiotrophic immunomodulatory cytokine that functions at different levels of the immune response, so it has emerged as a promising therapeutic factor for the treatment of autoimmune/inflammatory diseases. This study was designed to test the hypothesis that IL-10 gene modified bone marrow-derived immature dendritic cells (iDCs) ameliorate EAM and to explore the underlying mechanisms.</p><p><b>METHODS</b>EAM was induced using the methods of cardiac myosin immunization on day 0 and day 7. Immature and mature bone marrow-derived dendritic cells (BMDCs) were generated without or with the stimulation by lipopolysaccharide (LPS) and the phenotype was analyzed by flow cytometry. Some of the iDCs were transfected by pcDNA3-IL-10 plasmid. 2 x 10(6)/per rat mature DC (mDC), immature DC (iDC), pcDNA3 transfected iDC, pcDNA3-IL-10 transfected iDC or phosphate buffered saline (PBS) were injected intravenously for treatment 5 days after the first immunization. On day 21, HE staining was performed to detect the myocardial inflammation and T lymphocyte proliferation assay was used to determine the effects of IL-10 gene transfected iDC on autoreactive T cell proliferation. Expression of IkappaB, the inhibitor of NF-kappaB pathway, was determined by Western blot.</p><p><b>RESULTS</b>BMDCs generated in a medium supplemented with granulocyte-macrophage-colony-stimulating factor (GM-CSF) were relatively immature, as determined by flow cytometry. However, stimulation with LPS induced these cells to become mature (m) DCs with higher levels of surface major histocompatibility complex (MHC)-II and costimulatory molecules. Intravenous administration of iDCs, especially pcDNA3-IL-10 transfected iDC, ameliorated the histopathological severity of the myosin induced-EAM, and the effect was lost after the DCs underwent maturation induced by in vitro exposure to LPS. IL-10 gene modified iDC inhibited the antigen specific T cell responses towards cardiac myosin. IkappaB protein was up-regulated significantly in the IL-10 gene modified iDC group.</p><p><b>CONCLUSIONS</b>IL-10 gene modified iDC induced antigen-specific tolerance in EAM. The underlying mechanisms may be related to costimulatory molecules down-regulation and NF-kappaB pathway inhibition.</p>
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Animales , Masculino , Ratas , Enfermedades Autoinmunes , Alergia e Inmunología , Células Dendríticas , Fisiología , Tolerancia Inmunológica , Interleucina-10 , Genética , Activación de Linfocitos , Miocarditis , Alergia e Inmunología , Miosinas , Alergia e Inmunología , FN-kappa B , Fisiología , Ratas Endogámicas Lew , Transducción de Señal , TransfecciónRESUMEN
<p><b>OBJECTIVE</b>To investigate whether IL-10 gene modification on immature dendritic cells (iDC) could induce autoimmune tolerance in rat experimental autoimmune myocarditis (EAM).</p><p><b>METHODS</b>EAM was induced by cardiac myosin immunization on day 0 and day 7 in rats. A total of 2 x 10(6) mature DC (mDC), iDC, pcDNA3 transfected iDC, pcDNA3-IL-10 transfected iDC or PBS were injected intravenously at 5th immunization day. Three weeks later, echocardiography and HE staining were performed to observe the cardiac function and myocardial inflammation. Th1/Th2 cytokines were detected by ELISA and MHC-II molecules, costimulatory molecules were identified by flow cytometry. In vitro T lymphocyte proliferation assay and adoptive transfer of DCs were performed to determine the antigen specific tolerance induced by IL-10 gene modification on iDCs.</p><p><b>RESULTS</b>EAM rats treated with pcDNA3-IL-10 transfected iDC showed improved cardiac function and reduced inflammatory cells infiltration into myocardium. Moreover, lower Th1 and higher Th2-type response was induced, MHC-II and costimulatory molecules down-regulated and antigen specific immunological responses towards cardiac myosin inhibited in pcDNA3-IL-10-iDC treated EAM rats.</p><p><b>CONCLUSION</b>Treatment with IL-10 gene modified iDCs could ameliorates EAM by inducing Th2 polarization and down-regulation of MHC-II molecules and costimulatory molecule expressions.</p>