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Brown recluse spider bites can lead to severe reactions such as skin necrosis,hemolytic anemia, and multiorgan failure, which can be life-threatening. Therapeutic plasma exchange has been reported to provide clinical benefit for such cases. In thisreport, we present a case of a brown recluse spider bite that was successfully treated with therapeutic plasma exchange and compare it with previous case reports.
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Anemia Hemolítica , Araña Reclusa Parda , Intercambio Plasmático , Picaduras de Arañas , Humanos , Intercambio Plasmático/métodos , Picaduras de Arañas/terapia , Anemia Hemolítica/terapia , Masculino , Femenino , AnimalesRESUMEN
The role of glycan-binding proteins as an activator of immune regulatory receptors has gained attention recently. We report that galectin 7 reduced CD4+ T cell percentage in both in vitro culture and mouse tumor models. Immunohistochemical staining of esophageal cancer patient samples showed a lower percentage of CD4+ cells in the galectin 7 high area. The lack of CD4+ T cell depletion by galectin 7 in PD-1 knockout mice supports the role of PD-1 in mediating the effects of galectin 7. The binding assays demonstrate that galectin 7 binds to the N-glycosylation of PD-1 on N74 and N116 sites and leads to the recruitment of SHP-2. NFAT suppressive activity of galectin 7 was abrogated upon overexpression of the dominant negative SHP-2 mutant or inhibition of PD-1 by siRNA. Glycosylation of PD-1 has been reported to play a critical role in surface expression, stability, and interaction with its ligand PD-L1. This report further expands the significance of PD-1 glycosylation and suggests that galectin 7, a glycan-binding protein, interacts with the immune regulatory receptor PD-1 through glycosylation recognition.
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Linfocitos T CD4-Positivos , Receptor de Muerte Celular Programada 1 , Animales , Humanos , Ratones , Galectinas/metabolismo , Glicosilación , Polisacáridos/metabolismo , Receptor de Muerte Celular Programada 1/genética , Receptor de Muerte Celular Programada 1/metabolismoRESUMEN
The existing T cell-centered immune checkpoint blockade therapies have been successful in treating some but not all patients with cancer. Immunosuppressive myeloid cells, including myeloid-derived suppressor cells (MDSC), that inhibit antitumor immunity and support multiple steps of tumor development are recognized as one of the major obstacles in cancer treatment. Leukocyte Ig-like receptor subfamily B3 (LILRB3), an immune inhibitory receptor containing tyrosine-based inhibitory motifs (ITIM), is expressed solely on myeloid cells. However, it is unknown whether LILRB3 is a critical checkpoint receptor in regulating the activity of immunosuppressive myeloid cells, and whether LILRB3 signaling can be blocked to activate the immune system to treat solid tumors. Here, we report that galectin-4 and galectin-7 induce activation of LILRB3 and that LILRB3 is functionally expressed on immunosuppressive myeloid cells. In some samples from patients with solid cancers, blockade of LILRB3 signaling by an antagonistic antibody inhibited the activity of immunosuppressive myeloid cells. Anti-LILRB3 also impeded tumor development in myeloid-specific LILRB3 transgenic mice through a T cell-dependent manner. LILRB3 blockade may prove to be a novel approach for immunotherapy of solid cancers.
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Células Supresoras de Origen Mieloide , Neoplasias , Ratones , Animales , Humanos , Células Mieloides , Neoplasias/terapia , Linfocitos T , Receptores Inmunológicos , Microambiente Tumoral , Antígenos CDRESUMEN
BACKGROUND: Sickle cell disease (SCD) patients with a history of stroke are encouraged to receive chronic red blood cell exchange (RBCx) for stroke prevention. The American Society of Hematology guideline published in 2020 recommends an HbS target of <30%. However, this approach necessitates more frequent RBCx and more RBC units. UT Southwestern has devised a chronic exchange protocol that elevates the HbS target to <50% in patients with a low risk of stroke. STUDY DESIGN: This retrospective chart review study reviewed the medical records of patients receiving chronic RBCx with a target of HbS <50% over the past 10-year period to assess the safety of maintaining higher HbS targets in SCD patients with a low risk of cerebrovascular accidents (CVA). RESULTS: Among 49 SCD patients in the chronic RBCx program for secondary stroke prevention, 33 patients were maintained on an HbS target of <50% (average measured: 35.4%) for the duration of RBCx program enrollment (median 93.0 months, 95% CI, 83-99). Stroke or transient ischemic attack (TIA) clearly attributable to changing target HbS had not been identified among the 33 study subjects. Seven patients experienced conversion between the HbS targets of <50% and <30% HbS target. Significant reductions were observed in the frequency of RBCx and usage of blood volume in four of them. CONCLUSION: The findings suggest that liberalizing the HbS target could confer clinical flexibility without increasing the risk of CVA in a selective population. Further studies to fully evaluate the potential benefits of this approach are indicated.
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Anemia de Células Falciformes , Accidente Cerebrovascular , Humanos , Hemoglobina Falciforme , Estudios Retrospectivos , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/terapia , Eritrocitos , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & controlRESUMEN
INTRODUCTION: Owing to its distinct biomechanical properties, nonunion is common (7-20%) after intramedullary (IM) nailing of subtrochanteric femoral fractures. Unlike diaphyseal nonunion, it is difficult to provide sufficient stability by exchanging nailing alone in subtrochanteric nonunion. This study investigated the clinical outcomes of femoral subtrochanteric nonunion initially treated with an IM nail and subsequently managed with minimally invasive augmentative plate fixation. MATERIALS AND METHODS: Nineteen patients were enrolled retrospectively. The mechanisms of initial injury were traffic accidents in 8, falls from a height in seven, and slipping in two patients. Two patients with atypical subtrochanteric femoral fractures without a specific trauma history were further included. All patients underwent IM nailing as the index operation. Nonunion surgery was performed an average of 45.2 weeks after the initial surgery. In cases of hardware damage and/or atrophic nonunion, exchange nailing and bone grafting were performed in addition to augmentative plating, as necessary. Conversely, augmentative plating alone was performed in cases of hypertrophic nonunion without any failure of the preexisting IM nail or malalignment. A narrow locking compression plate was fixed after contouring according to the shape of the proximal femur. The mean follow-up period was 36.1 months. RESULTS: Bony union was achieved in 18/19 patients (94.7%), at an average of 19.8 weeks after nonunion surgery. In the case that did not heal even after exchange nailing, additional plating and bone grafting, further autogenous bone grafting was required after 11 months, which healed uneventfully. There were 2 cases of soft tissue irritation over the plate, but no major complications were observed. CONCLUSIONS: Additional plate augmentation over a retained IM nail yields satisfactory outcomes in terms of the bony union in subtrochanteric nonunion. Given its expected biomechanical superiority and relatively easy surgical technique, it may be a reasonable option for the management of femoral subtrochanteric nonunion.
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Fracturas del Fémur , Fijación Intramedular de Fracturas , Fracturas no Consolidadas , Fracturas de Cadera , Humanos , Estudios Retrospectivos , Resultado del Tratamiento , Fijación Intramedular de Fracturas/métodos , Fracturas no Consolidadas/cirugía , Fracturas de Cadera/cirugía , Fracturas del Fémur/cirugía , Fémur , Placas Óseas , Clavos OrtopédicosRESUMEN
BACKGROUND: Current immune checkpoint blockade strategies have been successful in treating certain types of solid cancer. However, checkpoint blockade monotherapies have not been successful against most hematological malignancies including multiple myeloma and leukemia. There is an urgent need to identify new targets for development of cancer immunotherapy. LILRB1, an immunoreceptor tyrosine-based inhibitory motif-containing receptor, is widely expressed on human immune cells, including B cells, monocytes and macrophages, dendritic cells and subsets of natural killer (NK) cells and T cells. The ligands of LILRB1, such as major histocompatibility complex (MHC) class I molecules, activate LILRB1 and transduce a suppressive signal, which inhibits the immune responses. However, it is not clear whether LILRB1 blockade can be effectively used for cancer treatment. METHODS: First, we measured the LILRB1 expression on NK cells from cancer patients to determine whether LILRB1 upregulated on NK cells from patients with cancer, compared with NK cells from healthy donors. Then, we developed specific antagonistic anti-LILRB1 monoclonal antibodies and studied the effects of LILRB1 blockade on the antitumor immune function of NK cells, especially in multiple myeloma models, in vitro and in vivo xenograft model using non-obese diabetic (NOD)-SCID interleukin-2Rγ-null mice. RESULTS: We demonstrate that percentage of LILRB1+ NK cells is significantly higher in patients with persistent multiple myeloma after treatment than that in healthy donors. Further, the percentage of LILRB1+ NK cells is also significantly higher in patients with late-stage prostate cancer than that in healthy donors. Significantly, we showed that LILRB1 blockade by our antagonistic LILRB1 antibody increased the tumoricidal activity of NK cells against several types of cancer cells, including multiple myeloma, leukemia, lymphoma and solid tumors, in vitro and in vivo. CONCLUSIONS: Our results indicate that blocking LILRB1 signaling on immune effector cells such as NK cells may represent a novel strategy for the development of anticancer immunotherapy.
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Anticuerpos Monoclonales/uso terapéutico , Células Asesinas Naturales/inmunología , Receptor Leucocitario Tipo Inmunoglobulina B1/antagonistas & inhibidores , Animales , Anticuerpos Monoclonales/farmacología , Femenino , Humanos , Ratones , Ratones Endogámicos NODRESUMEN
Immune checkpoint blockade therapy has been successful in treating some types of cancer but has not shown clinical benefits for treating leukaemia1. This result suggests that leukaemia uses unique mechanisms to evade this therapy. Certain immune inhibitory receptors that are expressed by normal immune cells are also present on leukaemia cells. Whether these receptors can initiate immune-related primary signalling in tumour cells remains unknown. Here we use mouse models and human cells to show that LILRB4, an immunoreceptor tyrosine-based inhibition motif-containing receptor and a marker of monocytic leukaemia, supports tumour cell infiltration into tissues and suppresses T cell activity via a signalling pathway that involves APOE, LILRB4, SHP-2, uPAR and ARG1 in acute myeloid leukaemia (AML) cells. Deletion of LILRB4 or the use of antibodies to block LILRB4 signalling impeded AML development. Thus, LILRB4 orchestrates tumour invasion pathways in monocytic leukaemia cells by creating an immunosuppressive microenvironment. LILRB4 represents a compelling target for the treatment of monocytic AML.
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Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Leucemia Mieloide Aguda/inmunología , Leucemia Mieloide Aguda/patología , Receptores de Superficie Celular/metabolismo , Transducción de Señal , Escape del Tumor/inmunología , Animales , Apolipoproteínas E/metabolismo , Arginasa/metabolismo , Linfocitos T CD4-Positivos/citología , Linfocitos T CD8-positivos/citología , Movimiento Celular , Proliferación Celular , Femenino , Humanos , Tolerancia Inmunológica/inmunología , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/metabolismo , Masculino , Glicoproteínas de Membrana , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Ratones SCID , Unión Proteica , Proteína Tirosina Fosfatasa no Receptora Tipo 11/metabolismo , Receptores de Superficie Celular/deficiencia , Receptores de Superficie Celular/genética , Receptores Inmunológicos , Receptores del Activador de Plasminógeno Tipo Uroquinasa/metabolismo , Escape del Tumor/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Transfusion of donor red blood cells (RBCs) remains an important part of management of sickle cell disease (SCD). However, the survival characteristics of transfused donor RBCs in SCD patients have not been well studied. We sought to calculate survival kinetics of transfused RBCs in SCD patients since it is unclear whether transfused RBCs get destroyed at faster rate as innocent bystander or persist longer due to decreased destruction capacity such as functional splenectomy. STUDY DESIGN: and methods Forty-one SCD patients who had undergone at least 3 RBC exchange procedures were inlcuded. Interval between the procedures, both pre-procedure and post procedure hematocrits, HbA% and HbS% were collected. We developed a mathematical model to calculate RBC lifespan for donor RBCs. RESULTS: Donor RBCs exhibited average lifespan of about 120days (121.1±13.9 days), which was similar to reported survival of RBCs in normal recipients. However, significant variation between patients were observed with lifespan ranging from 75.6-148.5 days. Intrapersonal variations were small in most cases. CONCLUSION: The calculated survival of donor RBCs in SCD recipient, based on certain laboratory values, appears to be similar to that of normal recipient. However, inter-personal variations were large, suggesting different RBC kinetics in a subset of patients, which calls for further research to better understand underlying pathophysiology. This knowledge of RBC survival would be very helpful in individualized management of patients on chronic RBCx.
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Anemia de Células Falciformes/sangre , Transfusión de Eritrocitos , Eritrocitos/metabolismo , Modelos Cardiovasculares , Anemia de Células Falciformes/terapia , Supervivencia Celular , Femenino , Humanos , Masculino , Estudios RetrospectivosRESUMEN
Colloidal assemblies of nanoparticles possess both the intrinsic and collective properties of their constituent nanoparticles, which are useful in applications where ordinary nanoparticles are not well suited. Here, we report an immunoassay technique based on colloidal nanoparticle assemblies made of iron oxide nanoparticles (magnetic substrate) and manganese-doped zinc sulfide (ZnS:Mn) nanoparticles (photoluminescent substrate), both of which are functionalized with antibodies to capture target proteins in a sandwich assay format. After magnetic isolation of the iron oxide nanoparticle assemblies and their bound ZnS:Mn nanoparticle assemblies (MZSNAs), photoluminescence of the remaining MZSNAs is measured for the protein quantification, eliminating the need for washing steps and signal amplification. Using human C-reactive protein as a model biomarker, we achieve a detection limit of as low as 0.7 pg/mL, which is more than 1 order of magnitude lower than that of enzyme-linked immunosorbent assay (9.1 pg/mL) performed using the same pair of antibodies, while using only one-tenth of the antibodies. We also confirm the potential for multiplex detection by using two different types of photoluminescent colloidal nanoparticle assemblies simultaneously.
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Coloides/química , Inmunoensayo/métodos , Magnetismo , Nanopartículas/química , Ensayo de Inmunoadsorción EnzimáticaRESUMEN
The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.actbio.2017.06.005. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.
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Mesenchymal stem cells (MSCs) have immunosuppressive and tissue repair properties, but clinical trials using MSCs to prevent or treat graft-versus-host disease (GVHD) have shown mixed results. Macrophages (MØs) are important regulators of immunity and can promote tissue regeneration and remodeling. We have previously shown that MSCs can educate MØs toward a unique anti-inflammatory immunophenotype (MSC-educated MØs [MEMs]); however, their implications for in vivo models of inflammation have not been studied yet. We now show that in comparison with MØs, MEMs have increased expression of the inhibitory molecules PD-L1, PD-L2, in addition to markers of alternatively activated MØs: CD206 and CD163. RNA-Seq analysis of MEMs, as compared with MØs, show a distinct gene expression profile that positively correlates with multiple pathways important in tissue repair. MEMs also show increased expression of IL-6, transforming growth factor-ß, arginase-1, CD73, and decreased expression of IL-12 and tumor necrosis factor-α. We show that IL-6 secretion is controlled in part by the cyclo-oxygenase-2, arginase, and JAK1/STAT1 pathway. When tested in vivo, we show that human MEMs significantly enhance survival from lethal GVHD and improve survival of mice from radiation injury. We show these effects could be mediated in part through suppression of human T cell proliferation and may have attenuated host tissue injury in part by enhancing murine fibroblast proliferation. MEMs are a unique MØ subset with therapeutic potential for the management of GVHD and/or protection from radiation-induced injury.
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Comunicación Celular/inmunología , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Enfermedad Injerto contra Huésped/terapia , Macrófagos/inmunología , Células Madre Mesenquimatosas/inmunología , Traumatismos por Radiación/terapia , Animales , Humanos , Inflamación/inmunología , Interleucina-6/biosíntesis , Activación de Macrófagos/inmunología , Macrófagos/citología , Células Madre Mesenquimatosas/citología , RatonesRESUMEN
Tumor stroma-secreted growth factors, cytokines, and reactive oxygen species (ROS) influence tumor development from early stages to the metastasis phase. Previous studies have demonstrated downregulation of ROS-producing extracellular superoxide dismutase (SOD3) in thyroid cancer cell lines although according to recent data, the expression of SOD3 at physiological levels stimulates normal and cancer cell proliferation. Therefore, to analyze the expression of SOD3 in tumor stroma, we characterized stromal cells from the thyroid. We report mutually exclusive desmoplasia and inflammation in papillary and follicular thyroid cancers and the presence of multipotent mesenchymal stem/stromal cells (MSCs) in non-carcinogenic thyroids and papillary thyroid cancer (PTC). The phenotypic and differentiation characteristics of Thyroid MSCs and PTC MSCs were comparable with bone marrow MSCs. A molecular level analysis showed increased FIBROBLAST ACTIVATING PROTEIN, COLLAGEN 1 TYPE A1, TENASCIN, and SOD3 expression in PTC MSCs compared to Thyroid MSCs, suggesting the presence of MSCs with a fibrotic fingerprint in papillary thyroid cancer tumors and the autocrine-paracrine conversion of SOD3 expression, which was enhanced by cancer cells. Stromal SOD3 had a stimulatory effect on cancer cell growth and an inhibitory effect on cancer cell migration, thus indicating that SOD3 might be a novel player in thyroid tumor stroma.
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Carcinoma Papilar/enzimología , Carcinoma Papilar/patología , Movimiento Celular , Espacio Extracelular/enzimología , Células Madre Mesenquimatosas/patología , Superóxido Dismutasa/metabolismo , Neoplasias de la Tiroides/enzimología , Neoplasias de la Tiroides/patología , Adenocarcinoma Folicular/enzimología , Adenocarcinoma Folicular/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma Papilar/genética , Proliferación Celular , Células Epiteliales/metabolismo , Células Epiteliales/patología , Fibrosis , Regulación Neoplásica de la Expresión Génica , Humanos , Comunicación Paracrina , Fenotipo , Cáncer Papilar Tiroideo , Glándula Tiroides/patología , Neoplasias de la Tiroides/genéticaRESUMEN
BACKGROUND: Spectra Optia (Terumo BCT, Lakewood, CO) was FDA approved for red blood cell exchange (RBCx) procedures in January 2014 and is expected to replace COBE spectra (Terumo BCT) very soon in the USA. The performance characteristics of these devices for Isovolemic Hemodilution (IHD-RBCx) procedure were compared in this study. METHODS: A total of 114 IHD-RBCx procedures from 19 patients were analyzed. For every patient, three procedures on each device with similar pre-procedure hematocrits were compared. Pre and post procedure laboratory parameters compared were hemoglobin S (HbS), hematocrits (Hct), platelet counts and fraction of cells remaining (FCR). Statistical analysis was performed using t-test adjusted by the Holm-Bonferroni method to reduce family-wise error rate. RESULTS: There were no significant differences between these two devices in regards to HbS, Hct, FCR and platelet counts (p = > 0.05). However, rinseback volume (124.2 ± 8.9 ml) and normal saline replacement volume during IHD phase (296.1 ± 97.2 ml) were lower in Spectra Optia as compared to COBE Spectra (337 ± 33.8 ml and 326.6 ± 105.2 ml, p value <0.001 and 0.030 respectively). Spectra Optia had a longer run time (107.1 ± 15.9 min vs 123.8 ± 19.6 min, p value <0.001) overall. CONCLUSIONS: Performance characteristics of Spectra Optia for HbS, Hct and FCR were similar to COBE Spectra for IHD-RBCx. IHD-RBCx procedure on Optia required less normal saline replacement volume and rinse back volume but with overall longer procedure run time.
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Eliminación de Componentes Sanguíneos/métodos , Eritrocitos/citología , Análisis Espectral/métodos , Adulto , Eliminación de Componentes Sanguíneos/efectos adversos , Femenino , Hemodilución , Humanos , Masculino , Adulto JovenRESUMEN
BACKGROUND/AIMS: Human mesenchymal stromal/stem cells (MSCs), derived from many different tissues, are characterized by a fibroblast-like morphology, the expression of certain cell surface markers and their ability to differentiate into adipocytes, chondrocytes and osteoblasts. A number of studies have shown that MSCs share many characteristics with fibroblasts; however, there is no well-defined set of phenotypic characteristics that could distinguish between these 2 types of cells. METHODS: We used 4 well-established human fibroblast strains from 3 different tissue sources and several human MSC strains from 2 different tissue sources to compare the phenotypic and immunological characteristics of these cells. RESULTS: Fibroblast strains had a similar morphology to MSCs, expressed the same cell surface markers as MSCs and could also differentiate into adipocytes, chondrocytes and osteoblasts. Also, similar to MSCs, these fibroblasts were capable of suppressing T cell proliferation and modulating the immunophenotype of macrophages. We also show that MSCs deposit extracellular matrices of collagen type I and fibronectin, and express FSP1 in patterns similar to fibroblasts. CONCLUSIONS: Based on currently accepted definitions for cultured human MSCs and fibroblasts, we could not find any immunophenotypic property that could make a characteristic distinction between MSCs and fibroblasts.
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Diferenciación Celular , Células Cultivadas , Proliferación Celular , Fibroblastos/citología , Humanos , Células Madre Mesenquimatosas/citología , Osteoblastos/citologíaRESUMEN
BACKGROUND AIMS: In the field of cellular therapy, potential cell entrapment in the lungs following intravenous administration in a compromised or injured pulmonary system is an important concern that requires further investigation. We developed a rat model of inflammatory and fibrotic lung disease to mimic the human clinical condition of obliterative bronchiolitis (OB) and evaluate the safety of intravenous infusion of mesenchymal stromal cells (MSCs). This model was used to obtain appropriate safety information and functional characterization to support the translation of an ex vivo-generated cellular product into human clinical trials. To overcome spontaneous recovery and size limitations associated with current animal models, we used a novel multiple dose bleomycin strategy to induce lasting lung injury in rats. METHODS: Intratracheal instillation of bleomycin was administered to rats on multiple days. MSCs were intravenously infused 7 days apart. Detailed pulmonary function tests including forced expiratory volume, total lung capacity, and invasive hemodynamic measurements were conducted to define the representative disease model and monitor cardiopulmonary hemodynamic consequences of the cell infusion. Post-euthanasia assessments included a thorough evaluation of lung morphology and histopathology. RESULTS: The double dose bleomycin instillation regimen resulted in severe and irreversible lung injury and fibrosis. Cardiopulmonary physiological monitoring reveled that no adverse events could be attributed to the cell infusion process. DISCUSSION: Although our study did not show the infusion of MSCs to result in an improvement in lung function or rescue of damaged tissue this study does confirm the safety of MSC infusion into damaged lungs.
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Lesión Pulmonar Aguda/patología , Lesión Pulmonar Aguda/terapia , Pulmón/patología , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Miocardio/patología , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/fisiopatología , Animales , Bleomicina , Modelos Animales de Enfermedad , Frecuencia Cardíaca , Humanos , Infusiones Intravenosas , Masculino , Trasplante de Células Madre Mesenquimatosas/efectos adversos , Trasplante de Células Madre Mesenquimatosas/métodos , Ratas , Ratas Sprague-Dawley , Pruebas de Función RespiratoriaRESUMEN
BACKGROUND: This study aims to assess the clinical utility of CK-MB measurement in patients suspected of acute coronary syndrome (ACS). METHODS: All CK-MB and troponin T measurements performed <1h apart during the study period were obtained and analyzed for concordance. A total of 1214 cases with discordant biomarkers results were found. Retrospective review of electronic health records (EHRs) was performed to assess the clinical impact, if any, of the discordant biomarkers results. RESULTS: In 401 cases, CK-MB concentrations were increased whereas troponin T concentrations were negative at <0.01 ng/ml. In this group, clinical interpretations included, rhabdomyolysis, demand ischemia, and drug intoxication. No additional investigations for ACS were conducted in this group. Among the remaining 813 cases, troponin T concentrations were increased in the presence of a normal CK-MB result. In this group, the discordant normal CK-MB lowered suspicion for ACS in only 22 cases (2.7%). Most common interpretations for isolated positive troponin were demand ischemia and impaired renal function. In most cases, discordant CK-MB results were not considered a significant finding. CONCLUSIONS: In the setting of suspected ACS, CK-MB has limited clinical impact when contemporary troponin assay results are available.
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Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/metabolismo , Forma MB de la Creatina-Quinasa/metabolismo , Inmunoensayo , Femenino , Humanos , Masculino , Estudios Retrospectivos , Troponina T/metabolismoRESUMEN
Inhibitory leukocyte immunoglobulin-like receptors (LILRBs 1-5) transduce signals via intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that recruit protein tyrosine phosphatase non-receptor type 6 (PTPN6 or SHP-1), protein tyrosine phosphatase non-receptor type 11 (PTPN11 or SHP-2), or Src homology 2 domain-containing inositol phosphatase (SHIP), leading to negative regulation of immune cell activation. Certain of these receptors also play regulatory roles in neuronal activity and osteoclast development. The activation of LILRBs on immune cells by their ligands may contribute to immune evasion by tumors. Recent studies found that several members of LILRB family are expressed by tumor cells, notably hematopoietic cancer cells, and may directly regulate cancer development and relapse as well as the activity of cancer stem cells. LILRBs thus have dual concordant roles in tumor biology - as immune checkpoint molecules and as tumor-sustaining factors. Importantly, the study of knockout mice indicated that LILRBs do not affect hematopoiesis and normal development. Therefore LILRBs may represent ideal targets for tumor treatment. This review aims to summarize current knowledge on expression patterns, ligands, signaling, and functions of LILRB family members in the context of cancer development.
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Genes cdc/inmunología , Neoplasias/inmunología , Receptores Inmunológicos/inmunología , Animales , Antígenos CD/inmunología , Antígenos CD/metabolismo , Humanos , Receptor Leucocitario Tipo Inmunoglobulina B1 , Neoplasias/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 6/inmunología , Proteína Tirosina Fosfatasa no Receptora Tipo 6/metabolismo , Receptores Inmunológicos/metabolismo , Transducción de Señal/fisiologíaRESUMEN
Inhibitory leukocyte immunoglobulin-like receptors (LILRB1-5) signal through immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in their intracellular domains and recruit phosphatases protein tyrosine phosphatase, non-receptor type 6 (PTPN6, SHP-1), protein tyrosine phosphatase, non-receptor type 6 (PTPN6, SHP-2), or Src homology 2 domain containing inositol phosphatase (SHIP) to negatively regulate immune cell activation. These receptors are known to play important regulatory roles in immune and neuronal functions. Recent studies demonstrated that several of these receptors are expressed by cancer cells. Importantly, they may directly regulate development, drug resistance, and relapse of cancer, and the activity of cancer stem cells. Although counterintuitive, these findings are consistent with the generally immune-suppressive and thus tumor-promoting roles of the inhibitory receptors in the immune system. This review focuses on the ligands, expression pattern, signaling, and function of LILRB family in the context of cancer development. Because inhibition of the signaling of certain LILRBs directly blocks cancer growth and stimulates immunity that may suppress tumorigenesis, but does not disturb normal development, LILRB signaling pathways may represent ideal targets for treating hematological malignancies and perhaps other tumors.
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Antígenos CD/metabolismo , Neoplasias/metabolismo , Receptores Inmunológicos/metabolismo , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Humanos , Modelos Biológicos , Neoplasias/patología , Unión Proteica , Isoformas de Proteínas/metabolismo , Proteínas Tirosina Fosfatasas no Receptoras/metabolismoRESUMEN
The aim of this study is to determine the effects of early intravenous (IV) infusion later followed by transendocardial (TE) injection of allogeneic mesenchymal stem cells (MSCs) following myocardial infarction (MI). Twenty-four swine underwent balloon occlusion reperfusion MI and were randomized into 4 groups: IV MSC (or placebo) infusion (post-MI day 2) and TE MSC (or placebo) injection targeting the infarct border with 2D X-ray fluoroscopy fused to 3D magnetic resonance (XFM) co-registration (post-MI day 14). Continuous ECG recording, MRI, and invasive pressure-volume analyses were performed. IV MSC plus TE MSC treated group was superior to other groups for contractility reserve (p = 0.02) and freedom from VT (p = 0.03) but had more lymphocytic foci localized to the peri-infarct region (p = 0.002). No differences were observed in post-MI remodeling parameters. IV followed by XFM targeted TE MSC therapy improves contractility reserve and suppresses VT but does not affect post-MI remodeling and may cause an immune response.