RESUMO
INTRODUCTION: Periprosthetic joint infection (PJI) is a severe complication after a total knee replacement that is primarily associated with soft tissue defects. Finding an appropriate therapy for PJI is a major challenge because of the lack of guidelines and research comparing treatment options. METHODS: In this study, we retrospectively compared 78 patients who had a knee prosthetic infection within a mean follow-up period of 24 months. Group A received a soft tissue coverage in addition to orthopedic surgical therapy with or without a component replacement (CR) of the prosthesis. Group B received the same orthopedic treatment without plastic surgery for soft tissue coverage. RESULTS: Only 21% of the patients in group A received a CR compared with 70% in group B (P = 0.0001). In group A, 83% did not have a recurrent infection, and in group B, 57% of the patients had no further infection and regained joint function (P = 0.0376). In group A, only 15% of the patients who received a CR had a significant complication within the follow-up period of 2 years, whereas in group B, 75% of patients exhibiting a major complication (P = 0.0048*). CONCLUSIONS: Soft tissue coverage improves the outcome after PJI of the knee with soft tissue defects. Patients who simultaneously needed plastic surgery for defect coverage and orthopedic surgery for CR had the lowest number of complications overall. Based on the results of this study, a therapy algorithm could be identified considering the soft tissue defect grade leading to the lowest major complication rates and maximizing the outcome of knee prosthesis infection therapies.
Assuntos
Artroplastia do Joelho , Prótese do Joelho , Procedimentos de Cirurgia Plástica , Infecções Relacionadas à Prótese , Artroplastia do Joelho/efeitos adversos , Humanos , Joelho/cirurgia , Prótese do Joelho/efeitos adversos , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/cirurgia , Estudos RetrospectivosRESUMO
Conceptually, premature initiation of post-wound angiogenesis could interfere with hemostasis, as it relies on fibrinolysis. The mechanisms facilitating orchestration of these events remain poorly understood, however, likely due to limitations in discerning the individual contribution of cells and extracellular matrix. Here, we designed an in vitro Hemostatic-Components-Model (HCM) to investigate the role of the fibrin matrix as protein factor-carrier, independent of its cell-scaffold function. After characterizing the proteomic profile of HCM-harvested matrix releasates, we demonstrate that the key pro-/anti-angiogenic factors, VEGF and PF4, are differentially bound by the matrix. Changing matrix fibrin mass consequently alters the balance of releasate factor concentrations, with differential effects on basic endothelial cell (EC) behaviors. While increasing mass, and releasate VEGF levels, promoted EC chemotactic migration, it progressively inhibited tube formation, a response that was dependent on PF4. These results indicate that the clot's matrix component initially serves as biochemical anti-angiogenic barrier, suggesting that post-hemostatic angiogenesis follows fibrinolysis-mediated angiogenic disinhibition. Beyond their significance towards understanding the spatiotemporal regulation of wound healing, our findings could inform the study of other pathophysiological processes in which coagulation and angiogenesis are prominent features, such as cardiovascular and malignant disease.
Assuntos
Fibrina/metabolismo , Hemostasia , Neovascularização Fisiológica , Indutores da Angiogênese/metabolismo , Coagulação Sanguínea , Movimento Celular , Células Endoteliais/metabolismo , Matriz Extracelular , Humanos , Hipóxia/metabolismo , Oxigênio , Ligação Proteica , Transdução de Sinais , CicatrizaçãoRESUMO
EMT-6 mammary carcinoma and B16 melanoma (B16M) cells are lethal and barely immunogenic in syngeneic BALB/c and C57BL/6 mice, respectively. We show that mice vaccinated with tumor cells pulsed with a MHC class I-restricted peptide develop a T cell response, not only to the peptide, but also to the unpulsed tumor. These mice display protective immunity against the unpulsed tumor, and their T cells adoptively transfer tumor-specific protection to immunodeficient SCID mice. Our data have implications for cancer vaccine strategies. Grafting a single well-defined foreign peptide on tumor cells might suffice to trigger anti-tumor immunity.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Vacinas Anticâncer/imunologia , Neoplasias Mamárias Animais/imunologia , Melanoma Experimental/imunologia , Peptídeos/imunologia , Transferência Adotiva , Animais , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Antígenos de Histocompatibilidade Classe I/imunologia , Neoplasias Mamárias Animais/terapia , Melanoma Experimental/terapia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos SCID , Peptídeos/metabolismo , VacinaçãoRESUMO
OBJECTIVES: As interleukin (IL)-2 therapy increases CD4 cell counts in HIV infected subjects, it emerged as a candidate for the partial restoration of immune competence in this disease. METHODS: We studied the frequencies of antigen-specific T cells using single cell resolution cytokine ELISPOT assays and titers of specific antibodies before and after immunization of HIV infected subjects who were treated with HAART or HAART plus IL-2. RESULTS: Subjects seronegative to hepatitis A were vaccinated with hepatitis A antigen. In the non-IL-2 treated group, hepatitis A-specific T cells producing IL-2 and IL-4 along with specific antibodies were induced, showing that these subjects are immune competent and capable of mounting a primary immune response. Additional IL-2 treatment had no significant effect on this primary T cell response; however, booster immunizations with tetanus toxoid or the gp120 depleted HIV vaccine Remune induced higher frequencies of specific interferon (IFN)-gamma producing T cells in IL-2 treated subjects. No impact of IL-2 treatment on these secondary B cell responses was seen. CONCLUSION: Overall, our study showed that IL-2 therapy had no immune enhancing effect on the induction of a primary response, but increased the frequency of IFN-gamma producing memory cells after booster immunization.
Assuntos
Infecções por HIV/imunologia , Imunização/métodos , Interleucina-2/imunologia , Vacinas contra a AIDS/imunologia , Formação de Anticorpos/imunologia , Especificidade de Anticorpos/imunologia , Terapia Antirretroviral de Alta Atividade/métodos , Linfócitos B/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Proteína do Núcleo p24 do HIV/imunologia , Infecções por HIV/tratamento farmacológico , Hepatite A/imunologia , Antígenos da Hepatite A/imunologia , Hepatite B/imunologia , Humanos , Imunização Secundária/métodos , Interferon gama/imunologia , Interleucina-4/imunologia , Leucócitos Mononucleares/imunologia , Linfócitos T/imunologia , Toxina Tetânica/imunologia , Células Th1/imunologia , Células Th2/imunologiaRESUMO
Tumor cells are typically poorly immunogenic. The same mechanisms that evolved to avoid the induction of immune responses against self tissues, and, hence, autoimmune disease, also have to be overcome for immune therapy of cancer. Toll-like receptor-activating microbial products such as CpG motif containing DNA are among the primary stimuli that the immune system uses to distinguish between infectious nonself (that is to be attacked) and noninfectious self (that must not be attacked). We tested in a murine RMA lymphoma/C57BL/6 model whether providing the infectious nonself context in a tumor-by injecting CpG-oligodeoxynucleotides directly into the tumor-would elicit a protective antitumor response. Complete remission of established solid tumors was achieved in immune competent mice, but not in T cell/B cell-deficient RAG-1 knockout mice. Intratumor injection of CpG-oligodeoxynucleotides was shown to induce a tumor-specific CD4(+) and CD8(+) T cell response of the type 1 effector class, and T cells adoptively transferred the protection to RAG-1 knockout mice. The data show that intratumor injection of CpG-oligodeoxynucleotides is a promising strategy for rendering tumors immunogenic.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Antineoplásicos/administração & dosagem , Ilhas de CpG/imunologia , Oligodesoxirribonucleotídeos/administração & dosagem , Oligodesoxirribonucleotídeos/uso terapêutico , Linfócitos T/imunologia , Transferência Adotiva/métodos , Animais , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/uso terapêutico , Linhagem Celular Tumoral , Testes Imunológicos de Citotoxicidade , Injeções Intralesionais , Injeções Subcutâneas , Linfoma de Células T/genética , Linfoma de Células T/imunologia , Linfoma de Células T/prevenção & controle , Melanoma Experimental/genética , Melanoma Experimental/imunologia , Melanoma Experimental/prevenção & controle , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transplante de Neoplasias , Linfócitos T/transplanteRESUMO
Normal cellular prion protein (PrP(C)) and decay-accelerating factor (DAF) are glycoproteins linked to the cell surface by glycosylphosphatidylinositol (GPI) anchors. Both PrP(C) and DAF reside in detergent insoluble complex that can be isolated from human peripheral blood mononuclear cells. However, these two GPI-anchored proteins possess different cell biological properties. The GPI anchor of DAF is markedly more sensitive to cleavage by phosphatidylinositol-specific phospholipase C (PI-PLC) than that of PrP(C). Conversely, PrP(C) has a shorter cell surface half-life than DAF, possibly due to the fact that PrP(C) but not DAF is shed from the cell surface. This is the first demonstration that on the surface of the same cell type two GPI-anchored proteins differ in their cell biological properties.