Prevalencia y trascendencia de los hallazgos extracardíacos encontrados en resonancia magnética de corazón / Prevalence and significance of extracardiac findings in cardiac magnetic resonance imaging

Objetivos: Valorar el número de lesiones incidentales detectadas por resonancia magnética (RM) cardíaca, establecer el porcentaje de hallazgos incluidos en el informe y definir el porcentaje de lesiones extracardíacas con implicancia en el manejo del paciente. Materiales y métodos: Se revisaron retrospectivamente 918 RM de corazón, realizadas desde mayo de 2006 hasta marzo de 2015, en busca de hallazgos extracardíacos. Estos fueron clasificados en nada/poco relevantes o relevantes, y en relación causa-efecto con la sintomatología cardíaca. Resultados: Se encontraron 271 hallazgos extracardíacos. El 35,7% resultó relevante y el 18,8% tenía una relación de causa-efecto con la sintomatología cardíaca. Los hallazgos extracardíacos relevantes fueron informados en el 58,4% de los casos y los poco/nada relevantes en el 26,6%. Discusión: Diferentes muestras poblacionales y protocolos de RM cardíaca pueden condicionar los porcentajes de los hallazgos extracardíacos detectados. Además, el análisis de estas imágenes tiene peculiaridades que requieren conocimiento y entrenamiento para una correcta valoración. Conclusión: Se detectaron hallazgos extracardíacos de diversa relevancia en un 26,4% de los pacientes. Analizar estos hallazgos y establecer su valoración es parte fundamental del informe radiológico de la RM cardíaca.

Objectives: To assess the number of incidental lesions detected on cardiac magnetic resonance imaging (MRI), in order to establish the percentage of findings included in the report and evaluate the percentage of extracardiac lesions that have implications on patient management. Materials and methods: A retrospective review was conducted on 918 cardiac MRI (performed from May 2006 to March 2015) to search for extracardiac findings. These were classified in not relevant or relevant, and in relation with cause-effect cardiac symptoms. Results: A total of 271 extracardiac findings were observed, of which 35.7% were relevant, and 18.8% had a cause-effect relationship with the cardiac symptoms. Relevant extracardiac findings were reported in 58.4% of cases, and not relevant findings in 26.6% of cases. Discussion: Different sample populations and protocols (performing cardiac MRI) can determine differences when establishing percentage of extracardiac findings. Furthermore, analysis of cardiac MR images has peculiarities that require knowledge and training for proper assessment. Conclusión: Extracardiac findings of distinct relevance were detected in 26.4% of patients. To analyse and to assess the importance of these findings is a fundamental part of the cardiac MRI report.

Calcificaciones serpiginosas en la filariasis mamaria: un descriptor no incluido en el sistema BI-RADS / Serpiginous calcifications in breast filariasis: A descriptor not included in the BI-RADS classification system

La filariasis es una enfermedad parasitaria causada por nemátodos, de curso benigno, endémica en algunas regiones tropicales, aunque las corrientes migratorias hacen que cada vez se vean más pacientes en nuestros centros. La muerte de los parásitos puede originar calcificaciones visibles en las mamografías con características específicas que no hay que confundir con otras enfermedades. Sin embargo, su aspecto no se recoge en los sistemas de clasificación de calcificaciones mamográficas más habituales (BI-RADS), lo que puede generar confusión. En este artículo planteamos la necesidad de actualizar estos sistemas de descripción, así como advertir del aspecto de estas calcificaciones para poder diagnosticarlas y no confundirlas con otras enfermedades (AU)

Filariasis is a parasitic disease with a benign course caused by nematodes. Filariasis is endemic in some tropical regions, and immigration has made it increasingly common in some centers in Spain. The death of the parasites can lead to calcifications that are visible in mammograms; these calcifications have specific characteristics and should not be confused with those arising in other diseases. However, the appearance of calcifications due to filariasis is not included in the most common systems used for the classification of calcifications on mammograms (BI-RADS), and this can lead to confusion. In this article, we discuss the need to update classification systems and warn radiologists about the appearance of these calcifications to ensure their correct diagnosis and avoid confusion with other diseases (AU)

[Serpiginous calcifications in breast filariasis: A descriptor not included in the BI-RADS classification system]. / Calcificaciones serpiginosas en la filariasis mamaria: un descriptor no incluido en el sistema BI-RADS.

Filariasis is a parasitic disease with a benign course caused by nematodes. Filariasis is endemic in some tropical regions, and immigration has made it increasingly common in some centers in Spain. The death of the parasites can lead to calcifications that are visible in mammograms; these calcifications have specific characteristics and should not be confused with those arising in other diseases. However, the appearance of calcifications due to filariasis is not included in the most common systems used for the classification of calcifications on mammograms (BI-RADS), and this can lead to confusion. In this article, we discuss the need to update classification systems and warn radiologists about the appearance of these calcifications to ensure their correct diagnosis and avoid confusion with other diseases.

G protein-coupled receptor kinase 2 moderates recruitment of THP-1 cells to the endothelium by limiting histamine-invoked Weibel-Palade body exocytosis.

BACKGROUND: G protein-coupled receptors (GPCRs) are a major family of signaling molecules, central to the regulation of inflammatory responses. Their activation upon agonist binding is attenuated by GPCR kinases (GRKs), which desensitize the receptors through phosphorylation. G protein-coupled receptor kinase 2(GRK2) down-regulation in leukocytes has been closely linked to the progression of chronic inflammatory disorders such as rheumatoid arthritis and multiple sclerosis. Because leukocytes must interact with the endothelium to infiltrate inflamed tissues, we hypothesized that GRK2 down-regulation in endothelial cells would also be pro-inflammatory. OBJECTIVES: To determine whether GRK2 down-regulation in endothelial cells is pro-inflammatory. METHODS: siRNA-mediated ablation of GRK2 in human umbilical vein endothelial cells (HUVECs) was used in analyses of the role of this kinase. Microscopic and biochemical analyses of Weibel-Palade body (WPB) formation and functioning, live cell imaging of calcium concentrations and video analyses of adhesion of monocyte-like THP-1 cells provide clear evidence of GRK2 function in histamine activation of endothelial cells. RESULTS: G protein-coupled receptor kinase 2 depletion in HUVECs increases WPB exocytosis and P-selectin-dependent adhesion of THP-1 cells to the endothelial surface upon histamine stimulation, relative to controls. Further, live imaging of intracellular calcium concentrations reveals amplified histamine receptor signaling in GRK2-depleted cells, suggesting GRK2 moderates WPB exocytosis through receptor desensitization. CONCLUSIONS: G protein-coupled receptor kinase 2 deficiency in endothelial cells results in increased pro-inflammatory signaling and enhanced leukocyte recruitment to activated endothelial cells. The ability of GRK2 to modulate initiation of inflammatory responses in endothelial cells as well as leukocytes now places GRK2 at the apex of control of this finely balanced process.

G protein-coupled receptor kinase 2 moderates recruitment of THP-1 cells to the endothelium by limiting histamine-invoked Weibel-Palade body exocytosis.

BACKGROUND: G protein-coupled receptors (GP-CRs) are a major family of signaling molecules, central to the regulation of inflammatory responses. Their activation upon agonist binding is attenuated by GPCR kinases (GRKs), which desensitize the receptors through phosphorylation. G protein-coupled receptor kinase 2(GRK2) down-regulation in leukocytes has been closely linked to the progression of chronic inflammatory disorders such as rheumatoid arthritis and multiple sclerosis. Because leukocytes must interact with the endothelium to infiltrate inflamed tissues, we hypothesized that GRK2 down-regulation in endothelial cells would also be pro-inflammatory. OBJECTIVES: To determine whether GRK2 down-regulation in endothelial cells is pro-inflammatory. METHODS: siRNA-mediated ablation of GRK2 in human umbilical vein endothelial cells (HUVECs) was used in analyses of the role of this kinase. Microscopic and biochemical analyses of Weibel-Palade body (WPB) formation and functioning, live cell imaging of calcium concentrations and video analyses of adhesion of monocyte-like THP-1 cells provide clear evidence of GRK2 function in histamine activation of endothelial cells. RESULTS: G protein-coupled receptor kinase 2 depletion in HUVECs increases WPB exocytosis and P-selectin-dependent adhesion of THP-1 cells to the endothelial surface upon histamine stimulation, relative to controls. Further, live imaging of intracellular calcium concentrations reveals amplified histamine receptor signaling in GRK2-depleted cells, suggesting GRK2 moderates WPB exocytosis through receptor desensitization. CONCLUSIONS: G protein-coupled receptor kinase 2 deficiency in endothelial cells results in increased pro-inflammatory signaling and enhanced leukocyte recruitment to activated endothelial cells. The ability of GRK2 to modulate initiation of inflammatory responses in endothelial cells as well as leukocytes now places GRK2 at the apex of control of this finely balanced process.

[Extrahepatic vessels depending on the hepatic artery. Identification and management]. / Vasos extrahepáticos dependientes de la arteria hepática. Identificación y manejo.

Patients with malignant liver tumors, whether primary tumors or metastases, that are not candidates for surgical treatment can benefit from different endovascular treatments with proven efficacy in local control of the disease. Correct treatment requires a careful angiographic technique and precise knowledge about the vascular anatomy afferent to the lesion. Occasionally, lesions considered relapse are actually areas that were untreated because the afferent pedicle was not adequately detected. On the other hand, some of the complications of endovascular treatments are related with material passing into non-hepatic vessels. Knowing the hepatic vascular anatomy and correctly identifying all the extrahepatic vessels will make it possible to perform safer, more efficacious treatments. In this article, we present different representative examples of extrahepatic vessels that originate in the hepatic artery.

Vasos extrahepáticos dependientes de la arteria hepática. Identificación y manejo / Extrahepatic vessels depending on the hepatic artery. Identification and management

Los pacientes con tumores hepáticos malignos, tanto primarios como metastásicos no susceptibles de tratamiento quirúrgico, pueden beneficiarse de distintos tipos de tratamientos endovasculares que han demostrado ser eficaces en el control local de la enfermedad. Para realizar un correcto tratamiento, además de una técnica angiográfica cuidadosa, es necesario conocer con precisión la anatomía vascular aferente a la lesión. En ocasiones, las recidivas son realmente áreas no tratadas que se originan por no detectar adecuadamente el pedículo aferente. Por otro lado, algunas de las complicaciones de los tratamientos endovasculares están relacionadas con el paso de material a vasos no hepáticos. El conocimiento de la anatomía vascular hepática y una identificación correcta de todos los vasos extrahepáticos permitirá realizar tratamientos más seguros y eficaces. En este artículo se presentan diferentes ejemplos representativos de vasos extrahepáticos con origen en la arteria hepática(AU)

Patients with malignant liver tumors, whether primary tumors or metastases, that are not candidates for surgical treatment can benefit from different endovascular treatments with proven efficacy in local control of the disease. Correct treatment requires a careful angiographic technique and precise knowledge about the vascular anatomy afferent to the lesion. Occasionally, lesions considered relapse are actually areas that were untreated because the afferent pedicle was not adequately detected. On the other hand, some of the complications of endovascular treatments are related with material passing into non-hepatic vessels. Knowing the hepatic vascular anatomy and correctly identifying all the extrahepatic vessels will make it possible to perform safer, more efficacious treatments. In this article, we present different representative examples of extrahepatic vessels that originate in the hepatic artery(AU)

Involvement of SNAP-23 and syntaxin 6 in human neutrophil exocytosis.

To understand the molecular basis of exocytosis in human neutrophils, the role of syntaxin 6 and SNAP-23 in neutrophil degranulation was examined. Human syntaxin 6 was cloned and identified as a 255-amino acid protein with a carboxy-terminal transmembrane region and two coiled-coil domains. Syntaxin 6 was localized mainly in the plasma membrane of human resting neutrophils, whereas SNAP-23 was located primarily in the mobilizable tertiary and specific granules. SNAP-23 was translocated to the cell surface, colocalizing with syntaxin 6, on neutrophil activation. In vitro binding studies established that SNAP-23 binds to syntaxin 6. Coimmunoprecipitation assays indicated that SNAP-23 interacts with syntaxin 6 in vivo, and this interaction was dramatically increased on neutrophil activation. Antibodies against SNAP-23 inhibited Ca(++) and GTP-gamma-S-induced exocytosis of CD67-enriched specific granules, but they hardly affected exocytosis of the CD63-enriched azurophilic granules, when introduced into electropermeabilized neutrophils. Anti-syntaxin 6 antibodies prevented exocytosis of both CD67- and CD63-enriched granules in electropermeabilized neutrophils. These data show that syntaxin 6 and SNAP-23 are involved in human neutrophil exocytosis, demonstrating that vesicle SNAP receptor-target SNAP receptor (v-SNARE- t-SNARE) interactions modulate neutrophil secretion. Syntaxin 6 acts as a target for secretion of specific and azurophilic granules, whereas SNAP-23 mediates specific granule secretion.

Co-expression of several human syntaxin genes in neutrophils and differentiating HL-60 cells: variant isoforms and detection of syntaxin 1.

Syntaxins are major components of vesicle trafficking and their pattern of expression depends on the cell type. Using reverse transcriptase-polymerase chain reaction (RT-PCR), cloning, and sequencing techniques, we have found that human neutrophils and neutrophil-differentiated HL-60 cells co-express syntaxins 1A, 3, 4, 5, 6, 7, 9, 11, and 16. These genes are also expressed in human peripheral blood lymphocytes and SH-SY5Y neuroblastoma cells, which, unlike neutrophils, also expressed syntaxin 10. We have identified two isoforms of syntaxin 3. Syntaxin 3A, similar to the previously reported syntaxin 3, and the novel isoform syntaxin 3B, which is identical to syntaxin 3A but lacks 37 amino acid residues at the carboxy-terminal region. Syntaxin 1 was mainly located to neutrophil granule membranes by confocal microscopy and by immunoblotting of subcellular fractions. These data indicate that syntaxin 1 cannot be considered specific to neural tissues. The level of expression of syntaxins 3, 4, 6, and 11 was increased during neutrophil differentiation of HL-60 cells, whereas that of syntaxins 1A, 5, 9, and 16 was unchanged. Syntaxin 7 was not expressed in undifferentiated HL-60 cells, but its expression was induced on neutrophil differentiation. The expression of several syntaxin genes in human neutrophils could be related to the high secretory capacity of these cells as well as to the presence of different cytoplasmic granules with distinct exocytic capabilities.

Physiological activation of human neutrophils down-regulates CD53 cell surface antigen.

Tetraspanin transmembrane proteins have a metastasis suppressor effect by acting as cell motility brakes in tumor cells. CD53 is a panleukocyte antigen that belongs to the tetra-span superfamily. Human neutrophils express high levels of CD53. We tested the hypothesis that this antigen level changes when cells are activated. Treatment of human neutrophils with their physiological activators, tumor necrosis factor alpha or platelet-activating factor, resulted in down-regulation of this antigen from the cell surface, as assessed by immunofluorescence flow cytometry. Similar responses were observed when neutrophils were stimulated with chemotactic N-formyl-methionyl-leucyl-phenylalanine, phorbol ester, or the calcium ionophore ionomycin. The CD53 antigen down-regulation upon neutrophil stimulation was further confirmed by immunoblotting analysis and was not correlated with a change in the level of CD53 transcripts. This CD53 antigen down-regulation paralleled that of CD43 and CD44 antigens in these cells, despite their different protein structure. The down-regulation of the three antigens CD53, CD43, and CD44 could be inhibited by phenylmethylsulfonyl fluoride, suggesting that CD53 antigen down-regulation is the result of the activation of a proteolytic mechanism. Down-regulation of CD53 antigen level, as a result of cellular stimulation, might play a role in the different aspects of neutrophil biology, by modulating its interactions on the cell surface.

Selective induction of apoptosis in cancer cells by the ether lipid ET-18-OCH3 (Edelfosine): molecular structure requirements, cellular uptake, and protection by Bcl-2 and Bcl-X(L).

The ether lipid 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3; Edelfosine) has been shown to be a rapid inducer of apoptosis in human leukemic cells and has been considered as a promising drug in cancer treatment. Here we have found that ET-18-OCH3 induced apoptosis not only in human tumor cell lines but also in primary tumor cell cultures from cancer patients. Human leukemic cells were highly sensitive to ET-18-OCH3, whereas normal cells remained unaffected. Among the distinct modifications of the ET-18-OCH3 molecule assayed, we found that substitutions in positions sn-2 and sn-3 of the glycerol backbone resulted in a complete loss of its capacity to induce apoptosis, highlighting the importance of the molecular structure of ET-18-OCH3 in its apoptotic effect. Induction of apoptosis by ET-18-OCH3 was very well correlated with the uptake of this ether lipid. ET-18-OCH3-resistant 3T3 fibroblasts became sensitive and incorporated significant amounts of the ether lipid following transformation with the SV40 virus. ET-18-OCH3-induced apoptosis as well as ET-18-OCH3 uptake were not mediated through binding of the ether lipid to the platelet-activating factor receptor. Overexpression of bcl-2 or bcl-xL by gene transfer in the human erythroleukemic HEL cells abrogated apoptosis induced by ET-18-OCH3. ET-18-OCH3 did not affect the expression of bcl-2, bcl-xL, or bax in HEL and HL-60 human leukemic cells but induced expression of c-myc, an important effector of apoptosis in several systems. Thus, ET-18-OCH3 behaves as a potent and highly selective antitumor drug able to induce an apoptotic pathway of cell death in tumor cells but not in nonmalignant cells.