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1.
Int Endod J ; 50(1): 15-23, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26609804

RESUMO

AIM: To investigate the effects of mammalian homologue of Drosophila diaphanous-1(mDia1) and Rho-associated coiled-coil-containing protein kinase (ROCK) on the migration and adhesion of dental pulp cells (DPCs). METHODOLOGY: Lysophosphatidic acid (LPA) was used to activate Rho signalling. mDia1 and ROCK were inhibited by short interfering RNA and the specific inhibitor, Y-27632, respectively. The migration of DPCs was assessed using the transwell migration assay and scratch test. Formation of cytoskeleton and focal adhesions(FAs) was observed by confocal laser scanning microscopy. Cell adhesion and spreading assays were performed. Phosphorylation of focal adhesion kinase (FAK) and paxillin was detected by Western blotting, and the bands were analysed using Adobe Photoshop CS5 software. All experiments were performed at least three times, and data were analysed with one-way anova and a post hoc test. RESULTS: LPA-triggered activation of Rho and inhibition of ROCK significantly increased the cell migration rate. Cell migration was inhibited by silencing mDia1. mDia1 silencing and ROCK inhibition suppressed the LPA-induced formation of the cytoskeleton, FA and phosphorylation of FAK and paxillin. Inhibition of ROCK or mDia1 facilitated early cell adhesion and spreading; by contrast, the combined inhibition of ROCK and mDia1 neutralized these effects. CONCLUSIONS: mDia1 promoted RhoA-induced migration of DPCs, but ROCK had an opposite effect. Both mDia1 and ROCK participated in cytoskeleton formation and adhesion of DPCs. The interactions between mDia1 and ROCK might influence dental pulp repair by determining the migration and adhesion of DPCs.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Polpa Dentária/citologia , Quinases Associadas a rho/metabolismo , Adolescente , Adulto , Amidas/farmacologia , Animais , Células Cultivadas , Forminas , Humanos , Lisofosfolipídeos/farmacologia , Piridinas/farmacologia , RNA Interferente Pequeno/farmacologia , Adulto Jovem
2.
J Hum Nutr Diet ; 29(5): 643-51, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27230729

RESUMO

BACKGROUND: Being small for gestational age (SGA), a foetal growth abnormality, has a long-lasting impact on childhood health. Its aetiology and underlying mechanisms are not well understood. Underlying epigenetic changes of imprinted genes have emerged as a potential pathological pathway because they may be associated with growth, including SGA. As a common methyl donor, folic acid (FA) is essential for DNA methylation, synthesis and repair, and FA supplementation is widely recommended for women planning pregnancy. The present study aimed to investigate the inter-relationships among methylation levels of two imprinted genes [H19 differentially methylated regions (DMRs) and MEST DMRs], maternal FA supplementation and SGA. METHODS: We conducted a case-control study. Umbilical cord blood was taken from 39 SGA infants and 49 controls whose birth weights are appropriate for gestational age (AGA). DNA methylation levels of H19 and MEST DMRs were determined by an analysis of mass array quantitative methylation. RESULTS: Statistically significantly higher methylation levels were observed at sites 7.8, 9 and 17.18 of H19 (P = 0.030, 0.016 and 0.050, respectively) in the SGA infants compared to the AGA group. In addition, the association was stronger in male births where the mothers took FA around conception at six H19 sites (P = 0.004, 0.005, 0.048, 0.002, 0.021 and 0.005, respectively). CONCLUSIONS: Methylation levels at H19 DMRs were higher in SGA infants compared to AGA controls. It appears that the association may be influenced by maternal peri-conception FA supplementation and also be sex-specific.


Assuntos
Metilação de DNA , Suplementos Nutricionais , Epigênese Genética , Retardo do Crescimento Fetal/prevenção & controle , Ácido Fólico/uso terapêutico , Fenômenos Fisiológicos da Nutrição Materna , RNA Longo não Codificante/metabolismo , Adulto , Estudos de Casos e Controles , China/epidemiologia , Estudos de Coortes , Feminino , Sangue Fetal/metabolismo , Desenvolvimento Fetal , Retardo do Crescimento Fetal/sangue , Retardo do Crescimento Fetal/epidemiologia , Retardo do Crescimento Fetal/metabolismo , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Masculino , Cuidado Pré-Concepcional , Gravidez , Cuidado Pré-Natal , Proteínas/genética , Proteínas/metabolismo , RNA Longo não Codificante/genética , Fatores de Risco , Fatores Sexuais
3.
Zhonghua Yi Xue Za Zhi ; 96(20): 1566-9, 2016 May 31.
Artigo em Chinês | MEDLINE | ID: mdl-27266683

RESUMO

OBJECTIVE: To evaluate the safety and effectiveness of retroperitoneoscopic donor nephrectomy in elderly donors for renal transplantation. METHODS: A retrospective analysis was conducted with 123 cases of retroperitoneoscopic living donor kidney transplantation in 309th Hospital of PLA from March 2011 to March 2014, including 44 elderly donors (age≥55 years) and 79 young to middle-aged donors (age <55 years). Comparisons were made in terms of postoperative complications in both donors and recipients, renal function recovery in the donors and function of graft in the recipients. RESULTS: The clinical baseline data of the two groups shows that glomerular filtration rate (GFR) of donors in the elderly donor group was lower than the young donor group (P=0.04). The 123 donors all underwent retroperitoneoscopic donor nephrectomy successfully. Postoperative complications in donors and recipients of both groups had no significant differences (P=0.60; P=1.00). In the elderly donor group, the mean serum creatinine level of donors was significantly higher than that in the young donors group [(115.8±22.3) vs (102.5±16.3) µmol/L, P<0.01] 3 days after operation; and estimated GFR (eGFR) was lower [(53.0±9.1)vs(59.6±8.3)ml·min(-1)·(1.73 m(2))(-1,) P<0.01]. Serum creatinine and eGFR of the two groups showed no significant differences one week and six months after surgery (all P>0.05). Four recipients in the elderly donor group had delayed graft function (DGF), 3 had acute rejection; 8 recipients in the young donor group had DGF, 5 had acute rejection; no statistically significant differences were observed between the 2 groups (both P=1.00). Recipients' eGFR were higher in the young donor group than in the elderly donor group at 1 week, 1 month, 3 months, 6 months and 12 months after surgery, but with no statistically significant differences(all P>0.05). After (27.8±12.6) months follow-up, 1 recipient in the elderly donor group died from pulmonary infection; two recipients in the young donor group had kidney dysfunction. Graft survival in the two groups showed no significant difference(P=0.95). CONCLUSIONS: Retroperitoneoscopic donor nephrectomy is safe and feasible for elderly donors. With careful preoperative evaluation, precise operation, and close postoperative monitoring and follow-up, it could provide satisfactory clinical outcome.


Assuntos
Endoscopia , Transplante de Rim , Nefrectomia , Idoso , Função Retardada do Enxerto , Taxa de Filtração Glomerular/fisiologia , Sobrevivência de Enxerto , Humanos , Complicações Intraoperatórias , Testes de Função Renal , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , Pessoa de Meia-Idade , Nefrectomia/efeitos adversos , Nefrectomia/métodos , Complicações Pós-Operatórias , Estudos Retrospectivos , Doadores de Tecidos , Resultado do Tratamento
4.
J Dent Res ; 103(3): 298-307, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38197150

RESUMO

Periodontitis (PD) is the primary cause of tooth loss in adults. Porphyromonas gingivalis (P.g), a keystone pathogen, has been identified as a crucial contributor to this process. Pyroptosis activation in PD is acknowledged, with accumulating evidence underscoring the crucial role of Caspase-11 (described as Caspase-4/5 in humans)-mediated noncanonical pyroptosis. However, the mechanism behind its impact on PD remains unclear. In this study, we delved into the interplay between the Caspase-11-mediated noncanonical pyroptosis, subgingival microbiota alteration, and macrophage polarization. Clinical samples from PD patients revealed heightened expression of Caspase-4, gasdermin-D, and their active fragments, pointing to the activation of the noncanonical pyroptosis. Single-cell sequencing analysis linked Caspase-4 with gingival macrophages, emphasizing their involvement in PD. In vitro cell experiments confirmed that P.g-induced pyroptosis was activated in macrophages, with Casp11 deficiency attenuating these effects. In an experimental PD mouse model, Casp11 deficiency led to an alteration in subgingival microbiota composition and reduced alveolar bone resorption. Casp11-/- mice cohousing with wild-type mice confirmed the alteration of the subgingival microbiota and aggravated the alveolar bone resorption. Notably, Casp11 deficiency led to decreased M1-polarized macrophages, corresponding with reduced alveolar bone resorption, uncovering a connection between subgingival microbiota alteration, macrophage M1 polarization, and alveolar bone resorption. Taken together, we showed that Caspase-11 fulfilled a crucial role in the noncanonical pyroptosis in PD, potentially influencing the subgingival microbiota and linking to M1 polarization, which was associated with alveolar bone resorption. These findings underscored the pivotal role of the Caspase-11-mediated noncanonical pyroptosis in PD pathogenesis and may provide critical insights into potential therapeutic avenues for mitigating PD.


Assuntos
Perda do Osso Alveolar , Microbiota , Periodontite , Adulto , Animais , Humanos , Camundongos , Perda do Osso Alveolar/complicações , Caspases , Periodontite/complicações , Porphyromonas gingivalis
5.
Zhonghua Er Ke Za Zhi ; 62(8): 741-746, 2024 Aug 02.
Artigo em Chinês | MEDLINE | ID: mdl-39039876

RESUMO

Objective: To explore the genetic etiology of pediatric intensive care unit (PICU) mortality cases and summarize their clinical characteristics. Methods: This was a retrospective cohort study. The study population consisted of 234 children who died within 7 d after admitted to the PICU of Children's Hospital of Fudan University from January 2017 to December 2021. The clinical diagnoses, laboratory test results, and genetic testing results were collected. These patients were divided into the pathogenic gene variation positive (PGVP) group and the pathogenic gene variation negative (PGVN) group according to the results of genetic testing. The Mann-Whitney U test and Pearson's chi-square test or Fisher's exact probability method were used to compare the clinical characteristics between the groups. Results: A total of 234 cases were enrolled, including 139 (59.4%) males and 95 (40.6%) females. The age at death was 1.0 (0.4, 3.7) years old and the length of PICU stay was 16 (6, 33) days. There were 62 cases (26.5%) PGVP, and the mutated pathogenic genes included immune genes (23 cases (37.1%)), metabolic genes (11 cases (17.7%)), neuromuscular genes (11 cases (17.7%)), cardiovascular genes (4 cases (6.5%)), and genes of other systems (13 cases (21.0%)). The age at death in PGVP cases was significantly lower than in PGVN cases (0.6 (0.3, 1.4) vs. 1.3(0.5, 4.3) years old, Z=3.85, P<0.001). Compared with the PGVN group, the PGVP group had a higher incidence of family history and chronic complex conditions (CCC) than the PGVN group (6.5% (4/62) vs. 0.6% (1/172) and 93.5% (58/62) vs. 76.2% (131/172), χ2=8.87, P=0.018 and 0.003, respectively). Children in the PGVP group were admitted with higher incidence of severe infection, decreased consciousness or coma, moderate-to-severe anemia, thrombocytopenia, protracted diarrhea, and abnormalities in muscle strength or tone than those in the PGVN group (74.2%(46/62) vs. 45.9%(79/172), 50.0%(31/62) vs. 35.5%(61/172), 32.3%(20/62) vs. 18.0%(31/172), 21.0%(13/62) vs. 10.5%(18/172), 25.8%(16/62) vs. 4.1%(7/172), 16.1%(10/62) vs. 5.2%(9/172), χ2=14.63, 4.04, 5.41, 4.37, 24.30, 7.25, all P<0.05). Pathogenic genes that occurred more than twice included IL2RG (5 cases), SMN1 (4 cases), and SH2D1A (3 cases, including 2 single gene varients and 1 copy number varient). Conclusions: Among the deceased cases in the PICU, the main genetic causes are immune-related, metabolic, and neuromuscular genetic disorders. Critically ill children with a family history, CCC, and early features such as severe infections, decreased consciousness or coma, moderate to severe anemia, thrombocytopenia, protracted diarrhea, or abnormalities in muscle strength or tone should be closely monitored and undergo early genetic testing.


Assuntos
Doenças Genéticas Inatas , Unidades de Terapia Intensiva Pediátrica , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pré-Escolar , Lactente , Doenças Genéticas Inatas/mortalidade , Doenças Genéticas Inatas/genética , Mutação , Testes Genéticos , Criança , Tempo de Internação , Mortalidade Hospitalar
6.
Genet Mol Res ; 9(3): 1606-14, 2010 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-20730712

RESUMO

The cDNA encoding noggin2 protein was obtained from the brain and spinal cord cDNA library of Gekko japonicus. The size of the noggin2 transcript and its expression in different tissues were analyzed by Northern blot analysis. In situ hybridization revealed positive hybridization signals in both gray and white matter of the spinal cord. Changes in noggin2 expression in the spinal cord after tail amputation were examined by real-time PCR. The noggin2 was expressed in the normal spinal cord and down-regulated three days after tail amputation, reaching the lowest level at two weeks, during the time course when we followed the expression levels. We concluded that the expression of noggin2 is affected by the process of spinal cord injury and regeneration.


Assuntos
Amputação Cirúrgica , Proteínas de Transporte/genética , Lagartos/genética , Proteínas de Répteis/genética , Medula Espinal/metabolismo , Cauda/lesões , Animais , Regulação da Expressão Gênica
7.
Clin Exp Immunol ; 155(3): 496-503, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19141125

RESUMO

CD4(+)CD25(+) forkhead box P3 (FoxP3)(+)regulatory T (T(reg)) cells are generated and play a key role in the induction and maintenance of transplant tolerance in organ recipients. It has been proposed that interleukin (IL)-2/IL-2 receptor (IL-2R) signalling was essential for the development and proliferation of antigen-activated T cells that included both effector T cells and T(reg) cells. Basiliximab (Simulect), a chimeric monoclonal antibody directed against the alpha-chain of the IL-2R (CD25), can be expected to not only affect alloreactive effector T cells, but also reduce the number and function of T(reg) cells. We therefore examined the effect of basiliximab induction therapy on the number and function of the T(reg) cells in renal recipients. Basiliximab decreased the percentage of CD4(+)CD25(+)T cells, but failed to influence the percentage of CD4(+)FoxP3(+) T(reg) cells. The cellular CD25 expression was decreased significantly by basiliximab injection, but CD4(+)CD25(+) T cells was not depleted from the circulating pool through monoclonal antibody activation-associated apoptosis. Functional analysis revealed that inhibitory function of T(reg) cells from recipients with basiliximab injection was not significantly different from recipients without injection. These data indicate that the functional T(reg) population may not be influenced by short-term basiliximab treatment.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Imunossupressores/uso terapêutico , Transplante de Rim/imunologia , Proteínas Recombinantes de Fusão/uso terapêutico , Linfócitos T Reguladores/imunologia , Adulto , Basiliximab , Biomarcadores/análise , Antígenos CD4/análise , Antígenos CD4/imunologia , Proliferação de Células/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Fatores de Transcrição Forkhead/análise , Fatores de Transcrição Forkhead/imunologia , Expressão Gênica , Sobrevivência de Enxerto , Humanos , Interferon gama/análise , Interleucina-2/metabolismo , Subunidade alfa de Receptor de Interleucina-2/análise , Subunidade alfa de Receptor de Interleucina-2/imunologia , Teste de Cultura Mista de Linfócitos , Masculino , Estudos Prospectivos , Receptores de Interleucina-2/metabolismo , Estatísticas não Paramétricas , Tolerância ao Transplante , Transplante Homólogo
8.
Transplant Proc ; 38(10): 3430-3, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17175294

RESUMO

BACKGROUND: The blood vessels of a transplanted organ are an interface between the donor and the recipient. The endothelium is believed to be a major target for graft rejection. After transplantation endothelial cells of a transplanted organ may be of recipient origin. OBJECTIVES: In this study we sought to determine whether endothelial chimerism correlates with graft rejection. METHODS: Biopsy samples from 34 renal transplants of female recipients who received kidneys from male donors were studied for the presence of endothelial cells of recipient origin. Formalin-fixed, paraffin-embedded tissue sections of renal biopsy samples were examined by fluorescence in situ hybridization (FISH) for the presence of endothelial cells containing two X chromosomes, using a biotinylated Y-chromosome probe and digoxigenin-labeled X-chromosome probe. RESULTS: The FISH methods identified endothelial cells of recipient origin. Endothelial chimerism was common, irrespective of rejection. Its presence was focal with these elements, coexisting in the biopsy. CONCLUSIONS: We observed no correlation between the percentage of recipient endothelial cells among vascular elements and the type of graft rejection (P > .05).


Assuntos
Endotélio Vascular/imunologia , Rejeição de Enxerto/imunologia , Transplante de Rim/imunologia , Quimeras de Transplante , Biópsia , Cromossomos Humanos X , Cromossomos Humanos Y , Endotélio Vascular/patologia , Feminino , Rejeição de Enxerto/patologia , Humanos , Hibridização in Situ Fluorescente , Transplante de Rim/patologia , Linfócitos/imunologia , Linfócitos/patologia , Masculino , Transplante Homólogo
9.
Transplant Proc ; 47(2): 319-22, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25769566

RESUMO

This study was designed to explore the clinical significance of dynamically monitoring the serum level of matrix metalloproteinase 9 (MMP-9) before and after renal transplantation. Before transplantation and 1, 3, 5, 7, 10, 15, and 20 days after transplantation, the peripheral blood was collected from 102 renal transplant recipients, including 8 with acute rejection (ARs) and 94 non-ARs. The serum MMP-9 level was detected by Luminex 200 analyzer (Luminex Corporation, Austin, TX, USA). By day 3 post-transplantation, the serum MMP-9 level in non-ARs had significantly reduced as compared to the pretransplantation level, and reached the lowest value on day 20 post-transplantation. In contrast, the serum MMP-9 level in ARs had significantly increased by day 3, reached the highest value on day 7, and remained significantly higher on day 20 as compared to the pretransplantation level. The receiver operating characteristic curve was plotted to evaluate the power of serum MMP-9 level on day 20 post-transplantation to differentiate the non-AR and AR groups. Our data revealed that with a threshold of 8473.26 pg/mL, the area under the curve was 0.758 (0.661, 0.856); the sensitivity and specificity of the diagnostic were 78.40% and 61.30%, respectively; the positive and the negative predictive values were 74.60% and 66.67%, respectively; and the accuracy rate was up to 71.57%. Taken together, the results indicated that dynamically monitoring serum MMP-9 levels in renal allograft recipients might be a convenient and safe method to diagnose ARs.


Assuntos
Rejeição de Enxerto/enzimologia , Falência Renal Crônica/enzimologia , Falência Renal Crônica/cirurgia , Transplante de Rim , Metaloproteinase 9 da Matriz/sangue , Doença Aguda , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Fatores de Tempo
10.
Biomed Mater Eng ; 6(6): 389-403, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-9138650

RESUMO

Shape memory alloys (SMA) are being increasingly used in various industrial applications as actuators, connectors, or damping materials. In the medical field, superelastic devices such as eyeglass frames, stents or guide catheters have come to market in the recent years. The design of SMA devices has usually been based on trial and error, since until recently no general simulation model was available to assist application engineers. The purpose of this article is to describe the computational methodology developed, validated and used for several industrial projects at Ecole Polytechnique of Montréal to simulate the thermomechanical behavior of shape memory materials. This new approach includes three main stages: experimental characterization, construction of a nonlinear material law based on dual kriging interpolation and finally, calculation of the thermomechanical response of SMA devices. For complex geometry, finite element analysis is used, but for simple devices such as springs or electrically activated SMA wires, simplified calculation methods are satisfactory. Validation results recently obtained will also be presented, and examples of industrial applications briefly reviewed.


Assuntos
Ligas/química , Materiais Biocompatíveis/química , Modelos Químicos , Algoritmos , Engenharia Biomédica , Cateterismo/instrumentação , Fenômenos Químicos , Físico-Química , Simulação por Computador , Equipamentos e Provisões , Óculos , Humanos , Indústrias , Metalurgia , Dinâmica não Linear , Reprodutibilidade dos Testes , Stents , Estresse Mecânico , Tecnologia , Termodinâmica
11.
Zhonghua Zhong Liu Za Zhi ; 12(4): 307-9, 1990 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-2272270

RESUMO

Lymphoscintigraphy was performed in 50 cases of breast cancer using 99mTc-colloid as a tracer. The results indicated that 277 lymph nodes, 128 on the right side and 149 on the left, were imaged. Most of the lymph nodes were located in the second and third intercostal spaces. The mean distance between these lymph nodes and mid line was 1.93 +/- 1.05 cm-2.70 +/- 0.93 cm. The mean depth was 2.42 +/- 0.52 cm-3.07 +/- 0.72 cm. It was over 4.0 cm in isolated cases. The lymph nodes which were not showed after repeated examination could have been involved by the cancer. Radionuclide lymphoscintigraphy, being safe, easily repeated and having low radiation dose and good image, is very useful for radiotherapy.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Linfonodos/diagnóstico por imagem , Adulto , Idoso , Feminino , Câmaras gama , Humanos , Linfonodos/patologia , Pessoa de Meia-Idade , Cintilografia , Coloide de Enxofre Marcado com Tecnécio Tc 99m
12.
Biochem Pharmacol ; 87(4): 562-70, 2014 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-24345332

RESUMO

miR-30d has been observed to be significantly down-regulated in human anaplastic thyroid carcinoma (ATC), and is believed to be an important event in thyroid cell transformation. In this study, we found that miR-30d has a critical role in modulating sensitivity of ATC cells to cisplatin, a commonly used chemotherapeutic drug for treatment of this neoplasm. Using a mimic of miR-30d, we demonstrated that miR-30d could negatively regulate the expression of beclin 1, a key autophagy gene, leading to suppression of the cisplatin-activated autophagic response that protects ATC cells from apoptosis. A reporter gene assay demonstrated that the binding sequences of miR-30d in the beclin 1-3' UTR was the region required for the inhibition of beclin 1 expression by this miRNA. We further showed that inhibition of the beclin 1-mediated autophagy by the miR-30d mimic sensitized ATC cells to cisplatin both in vitro (cell culture) and in vivo (animal xenograft model). These results suggest that dysregulation of miR-30d in ATC cells is responsible for the insensitivity to cisplatin by promoting autophagic survival. Thus, miR-30d may be exploited as a potential target for therapeutic intervention in the treatment of ATC.


Assuntos
Antineoplásicos/farmacologia , Proteínas Reguladoras de Apoptose/antagonistas & inibidores , Proteínas Reguladoras de Apoptose/genética , Autofagia/genética , Cisplatino/farmacologia , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , MicroRNAs/genética , Neoplasias da Glândula Tireoide/genética , Regiões 3' não Traduzidas/efeitos dos fármacos , Regiões 3' não Traduzidas/fisiologia , Animais , Antineoplásicos/uso terapêutico , Proteínas Reguladoras de Apoptose/biossíntese , Autofagia/efeitos dos fármacos , Proteína Beclina-1 , Linhagem Celular Tumoral , Cisplatino/uso terapêutico , Humanos , Proteínas de Membrana/biossíntese , Camundongos , Camundongos Endogâmicos BALB C , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/fisiologia , Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
14.
Transplant Proc ; 41(5): 1574-6, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19545682

RESUMO

The biology and function of induced CD4(+)CD25(high) regulatory T (Treg) cells have not been clarified for their specificity to a foreign antigen. To test whether the regulatory functions of the induced CD4(+)CD25(high) Treg cells after transplantation require antigen-specific triggering, we analyzed the capacity of induced CD4(+)CD25(high) Treg cells to inhibit the proliferation of conventional CD4(+)CD25(-) T cells in response to T-cell receptor stimulation using donor cells or HLA-mismatched third-party cells in vitro. CD4(+)CD25(high) Treg cells did not proliferate in response to allogeneic stimulation and suppressed proliferation of the co-cultured autologous CD4(+)CD25(-) populations in a dose-dependent manner. The proliferation of CD4(+)CD25(-)T cells from the same donor in mixed lymphocyte reactions was significantly inhibited at a 1:8 ratio of conventional T cells:Treg cells: 14,404 +/- 673 cpm without CD4(+)CD25(high) Treg cells versus 10,781 +/- 539 cpm with CD4(+)CD25(high) Treg cells P = .01). At the same 1:8 ratio, the proliferation of CD4(+)CD25(-) cells derived from major histocompatibility complex-mismatched patients was not significantly inhibited: 14,404 +/- 673 cpm without CD4(+)CD25(high) Treg cells versus 12,471 +/- 709 cpm with CD4(+)CD25(high) Treg cells (P = .06). Antigen specificity of the induced CD4(+)CD25(high) Treg cells was demonstrated, after transplantation, supporting the use of antigen-specific Treg cells as a therapeutic strategy.


Assuntos
Transplante de Rim/imunologia , Linfócitos T Reguladores/imunologia , Quimioterapia Combinada , Genótipo , Antígenos HLA/genética , Antígenos HLA-A/genética , Antígeno HLA-DR1/genética , Antígenos HLA-G , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Imunossupressores/uso terapêutico , Doadores Vivos , Ativação Linfocitária , Teste de Cultura Mista de Linfócitos , Doadores de Tecidos
15.
J Immunol ; 142(12): 4225-32, 1989 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-2470822

RESUMO

Cyclosporin A (CsA) is an undecapeptide fungal metabolite and is generally regarded as a new generation of immunosuppressive drugs. We uncovered a novel immunomodulatory property of CsA as a potent immunologic stimulator in the murine IgE antibody system. The enhancement of IgE responses was observed in mice receiving as few as three daily i.m. injections before Ag priming. Our studies demonstrate the three points listed below. First, CsA potentiates murine IgE responses regardless of Ag specificities in inbred mice. A hierarchy of immunopotentiation by CsA follows the order of low, intermediate, and high IgE responder mice. Second, CsA, when administered along with Ag, exerts a thorough and long lasting impact on the Ag-specific IgE antibody response, and leads to an Ag-specific breakthrough of IgE antibody synthesis in mice rendered tolerant in the IgE antibody system by soluble Ag pretreatment or neonatal IgE treatment. Third, IgE enhancer cells become sensitive to a low dose of irradiation. Two enhancer cellular components are identified, those of the Th cells and B cells, which appear to favor the induction of IgE responses. Understanding the cellular basis of the immunopotentiating effect of CsA will provide further insight into the murine IgE antibody system.


Assuntos
Adjuvantes Imunológicos/farmacologia , Ciclosporinas/farmacologia , Imunoglobulina E/biossíntese , Animais , Animais Recém-Nascidos/crescimento & desenvolvimento , Animais Recém-Nascidos/imunologia , Linfócitos B/efeitos dos fármacos , Linfócitos B/metabolismo , Dinitrofenóis/administração & dosagem , Relação Dose-Resposta Imunológica , Relação Dose-Resposta à Radiação , Epitopos/imunologia , Feminino , Haptenos/administração & dosagem , Hemocianinas/administração & dosagem , Tolerância Imunológica/efeitos dos fármacos , Imunoglobulina E/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Pré-Medicação , Ratos , Ratos Endogâmicos Lew , Ratos Endogâmicos , Soroalbumina Bovina/administração & dosagem , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/efeitos da radiação
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