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AIM: The purpose of this paper is to report on the evaluation of the online Global Leadership Mentoring Community, a programme designed to build relationships across seven global regions and promote leadership development for emerging nurse leaders. BACKGROUND: There is a pressing need and opportunity for sustainable global leadership mentoring programmes. This programme of Sigma Theta Tau International (Sigma) brought mentors and mentees together from across the world to build leadership capacity, understand global leadership issues and build networks. Community coordinators purposively selected mentors from each of Sigma's seven Global Regions, and mentees were chosen through a process of snowball sampling. Mentors and mentees met monthly with quarterly group calls. METHODS: The study followed a programme evaluation, outcomes-focused approach. All eleven pairs of mentors-mentees were invited to complete online surveys at the outset and end of programme capturing both quantitative and qualitative data. Quantitative data were analysed using descriptive statistics and for qualitative data, a thematic analysis. FINDINGS: Quantitative data confirmed that all 22 participants gained from the experience. From qualitative analysis, themes emerged illustrating the scope of achievements: 1. facilitation of successful outcomes for both mentors and mentees, 2. challenges of global mentoring and 3. strategies for successful global mentoring. DISCUSSION/CONCLUSION: Participants reported that creating global leadership is a longitudinal process that needs sustained attention to effect change. This evaluation identified many strengths of the programme and recommended its continuation to help further development of global leaders, particularly through focusing more purposefully on policy issues. IMPLICATIONS FOR NURSING POLICY: Empowerment of nurses globally through a Global Leadership Mentoring Community can improve leadership at all levels, thus emboldening their voices to influence nursing and health policy and ultimately improve patient care.
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Tutoría , Creación de Capacidad , Humanos , Liderazgo , Mentores , Evaluación de Programas y Proyectos de SaludRESUMEN
AIM: To compare the safety and efficacy of percutaneous computed tomography (CT)-guided core-needle biopsy (CNB) of pancreatic masses traversing the gastrointestinal tract or solid viscera versus trans-mesenteric and retroperitoneal approaches. MATERIALS AND METHODS: CT-guided CNB of pancreatic lesions performed between May 2004 and December 2014 were retrospectively analysed at a single centre. Biopsies were performed using 18- or 20-G needles with a coaxial system. CT images, histopathology reports, medical records, and procedural details for all patients were reviewed to evaluate the biopsy route, complications, and diagnostic accuracy. According to the routes, biopsies were divided into trans-mesenteric, retroperitoneal and trans-organ approaches for comparison. RESULTS: A total of 85 patients, who had undergone 89 CNBs for pancreatic masses were reviewed. The overall sensitivity, specificity, and accuracy of CNB for detecting malignancy via various routes were 88.8%, 100%, and 89.9%, respectively, with a complication rate of 20.2%. Trans-organ biopsies of pancreatic masses (n=22) were performed safely via a direct pathway traversing the stomach (n=14), colon (n=3), small bowel (n=2), liver (n=2), and spleen (n=1). The sensitivity, specificity, and accuracy were 90.5%, 100%, and 90.9%, respectively. In the trans-organ biopsy group, three biopsies (13.6%) resulted in minor haematomas, but no major complications occurred. There were no statistically significant differences in the diagnostic efficacy or complication rate among the different biopsy routes. CONCLUSION: Percutaneous CT-guided CNB using a trans-organ approach is a feasible technique for diagnosing pancreatic malignancy; however, as this series was small, more data is required.
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Biopsia con Aguja Gruesa/métodos , Biopsia Guiada por Imagen/métodos , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/patología , Radiografía Intervencional/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Anciano de 80 o más Años , Biopsia con Aguja Gruesa/efectos adversos , Humanos , Biopsia Guiada por Imagen/efectos adversos , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto JovenRESUMEN
AIM: To evaluate the safety and efficacy of computed tomography (CT)-guided percutaneous fine-needle aspiration biopsy (FNAB) of pancreatic masses that traverses the gastrointestinal tract or solid viscera. MATERIALS AND METHODS: From January 2002 to December 2012, 144 patients underwent 165 CT-guided biopsies of pancreatic masses. Biopsies were performed using a 21 or 22 G needle. Cytology reports, medical records, and procedure details for all patients were retrospectively reviewed to evaluate the biopsy route, complications, and diagnostic accuracy. RESULTS: Trans-organ biopsies of pancreatic masses were safely performed via a direct pathway traversing the stomach (n = 45), colon (n = 14), jejunum (n = 4), or liver (n = 5). There were five self-limiting mesenteric haematomas along the biopsy route on immediate post-procedure CT and all patients remained asymptomatic. All haematomas occurred after a trans-mesenteric approach rather than passage through abdominal organs. Three patients had acute pancreatitis. There was no significant difference in complications and diagnostic yields between the groups. The sensitivity, specificity, positive predictive value, and negative predictive value of final FNAB cytology for malignancy were 98.3%, 100%, 100% and 71.4%, respectively. The overall accuracy was 98.4%. CONCLUSION: Percutaneous FNAB using the trans-organ approach is a safe and effective technique to diagnose pancreatic malignancy.
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Biopsia Guiada por Imagen/métodos , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/patología , Radiografía Intervencional/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Anciano de 80 o más Años , Biopsia con Aguja Fina , Estudios de Cohortes , Estudios de Factibilidad , Femenino , Humanos , Masculino , Mesenterio , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
AIM: To present our experience of the clinical management of spontaneous isolated dissection of superior mesenteric artery (SIDSMA) and analyse the clinical features, imaging findings, and treatment outcomes. MATERIALS AND METHODS: In this retrospective study, eight consecutive patients with symptomatic SIDSMA were treated in Chang Gung Memorial Hospital between April 2007 and April 2010; among these patients, six underwent endovascular stent placement. The clinical manifestations, imaging findings, endovascular stent placement outcome, and follow-up results of the patients were retrospectively analysed. RESULTS: Eight patients were diagnosed with SIDSMA by contrast-enhanced computer tomography. One patient died due to comorbidity before angiography. Six patients underwent percutaneous endovascular stent placement in the superior mesenteric artery (SMA): four patients with bare stents and two with stent grafts. Because it was not appropriate to perform stent implantation in the remaining patient, he received only conservative treatment. All seven patients had an uneventful recovery and the follow-up period was 16 month, ranging from 1 to 35 months. CONCLUSION: For patients with symptomatic SIDSMA, endovascular repair is a feasible treatment choice with a high success rate and good clinical outcome.
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Procedimientos Endovasculares , Arteria Mesentérica Superior/cirugía , Enfermedades Vasculares/cirugía , Anciano , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Enfermedades Vasculares/diagnósticoRESUMEN
BACKGROUND: CRIPTO-1 (CR-1) is involved in the pathogenesis and progression of human carcinoma of different histological origin. In this study we addressed the expression and the functional role of CR-1 in cutaneous melanoma. METHODS: Expression of CR-1 protein in melanomas and melanoma cell lines was assessed by immunohistochemistry, western blotting and/or flow cytometry. Levels of mRNA were evaluated by real-time PCR. Invasion assays were performed in Matrigel-coated modified Boyden chambers. RESULTS: Expression of CR-1 protein and/or mRNA was found in 16 out of 37 primary human cutaneous melanomas and in 12 out of 21 melanoma cell lines. Recombinant CR-1 protein activated in melanoma cells c-Src and, at lesser extent, Smad signalling. In addition, CR-1 significantly increased the invasive ability of melanoma cells that was prevented by treatment with either the ALK4 inhibitor SB-431542 or the c-Src inhibitor saracatinib (AZD0530). Anti-CR-1 siRNAs produced a significant inhibition of the growth and the invasive ability of melanoma cells. Finally, a close correlation was found in melanoma cells between the levels of expression of CR-1 and the effects of saracatinib on cell growth. CONCLUSION: These data indicate that a significant fraction of cutaneous melanoma expresses CR-1 and that this growth factor is involved in the invasion and proliferation of melanoma cells.
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Proteínas Ligadas a GPI/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Melanoma/metabolismo , Melanoma/patología , Proteínas de Neoplasias/metabolismo , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Receptores de Activinas Tipo I/antagonistas & inhibidores , Receptores de Activinas Tipo I/metabolismo , Benzamidas/farmacología , Benzodioxoles/farmacología , Western Blotting , Proteína Tirosina Quinasa CSK , Adhesión Celular , Movimiento Celular , Proliferación Celular/efectos de los fármacos , Dioxoles/farmacología , Citometría de Flujo , Proteínas Ligadas a GPI/antagonistas & inhibidores , Proteínas Ligadas a GPI/genética , Humanos , Técnicas para Inmunoenzimas , Péptidos y Proteínas de Señalización Intercelular/genética , Melanoma/genética , Invasividad Neoplásica , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/genética , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Proteínas Tirosina Quinasas/metabolismo , Quinazolinas/farmacología , ARN Mensajero/genética , ARN Interferente Pequeño/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias Cutáneas/genética , Proteínas Smad/metabolismo , Células Tumorales Cultivadas , Familia-src QuinasasRESUMEN
AIM: To document the computed tomography (CT) and magnetic resonance imaging (MRI) features of acinar cell carcinoma of the pancreas and to correlate them with pathological findings to determine the unique imaging manifestations of this rare subtype tumour of the pancreas. MATERIALS AND METHODS: From January 1986 to August 2008, six patients (five men and one woman, mean age 61.3 years) with histologically proven acinar cell carcinoma of the pancreas underwent CT (n=6) and MRI (n=4) examinations. The imaging features of each tumour were documented and compared with pathological findings. RESULTS: The tumours were distributed in the head (n=4), body (n=1), and tail (n=1) of the pancreas. Four masses (67%) were uniformly or partially well-defined with thin, enhancing capsules. Central cystic components were found in five tumours (83%). Two tumours (33%) exhibited intratumoural haemorrhage, and one tumour (17%) had amorphous intratumoural calcification. In both CT and MRI, the tumours enhanced less than the adjacent normal pancreatic parenchyma. The signal intensity on MRI was predominantly T1 hypointense and T2 iso- to hyperintense. CONCLUSION: Acinar cell carcinoma of the pancreas has distinct imaging features, and both CT and MRI are useful and complementary imaging methods.
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Carcinoma de Células Acinares , Imagen por Resonancia Magnética , Neoplasias Pancreáticas , Tomografía Computarizada por Rayos X , Adulto , Anciano , Carcinoma de Células Acinares/diagnóstico por imagen , Carcinoma de Células Acinares/patología , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Páncreas Exocrino , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/patología , Estudios Retrospectivos , Distribución por Sexo , alfa-Fetoproteínas/metabolismoRESUMEN
Branched RNA-linked multicopy single-stranded DNA (msDNA) originally detected in myxobacteria has now been found in a clinical isolate of Escherichia coli. Although lacking homology in the primary structure, the E. coli msDNA is similar in secondary structure to the myxobacterial msDNA's, including the 2',5'-phosphodiester linkage between RNA and DNA. A chromosomal DNA fragment responsible for the production of msDNA was cloned in an E. coli K12 strain; its DNA sequence revealed an open reading frame (ORF) of 586 amino acid residues. The ORF shows sequence similarity with retroviral reverse transcriptases and ribonuclease H. Disruption of the ORF blocked msDNA production, indicating that this gene is essential for msDNA synthesis.
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ADN de Cadena Simple/genética , Escherichia coli/genética , ARN Bacteriano/genética , ADN Polimerasa Dirigida por ARN/genética , Retroviridae/enzimología , Secuencia de Aminoácidos , Secuencia de Bases , Clonación Molecular , Sondas de ADN , Enzimas de Restricción del ADN , ADN Bacteriano/genética , ADN de Cadena Simple/análisis , ADN de Cadena Simple/biosíntesis , Endorribonucleasas/genética , Escherichia coli/enzimología , Genes Bacterianos , VIH/enzimología , VIH/genética , Virus Linfotrópico T Tipo 1 Humano/enzimología , Virus Linfotrópico T Tipo 1 Humano/genética , Datos de Secuencia Molecular , Myxococcales/genética , Hibridación de Ácido Nucleico , ARN Bacteriano/análisis , ARN Bacteriano/biosíntesis , Retroviridae/genética , Ribonucleasa H , Homología de Secuencia de Ácido Nucleico , Transformación BacterianaRESUMEN
CONTEXT AND OBJECTIVES: Conveying empathy is a multi-phase process involving an inner resonation phase, communication phase, and reception phase. Previous investigations on physician empathy have focused on a physician's inner resonation phase or communication phase and not on the patient's reception phase. The purpose of this study was to investigate the differences in the perception of physicians' empathy between emergency physicians (EPs) and their patients. The answer to this question will allow us to more fully understand all phases of empathy and will help guide the teaching of how to effectively communicate empathy in the clinical setting. METHODS: From 2004 to 2005, we conducted in-depth, semi-structured interviews with 7 each of EPs, patients, patients' family members and nurses. A phenomenological approach was used to analyze the data. RESULTS: Four themes emerged from the analysis: (1) When patients expressed their feelings, EPs usually did not resonate with their concerns; (2) Patients needed EPs to provide psychological comfort, but EPs focused only on patients' physical discomfort; (3) Patients needed appropriate feedback from EPs, but EPs did not reflect on whether their patients had received empathy from them; (4) EPs' ability to empathize was affected by environmental factors, which EPs found difficult to overcome. CONCLUSION: EPs and their patients perceive the physicians' empathy differently. These findings provide insights into patients' perceptions of their physicians' empathic expressions and provide a framework for teaching physicians how to convey empathy in the emergency department setting.
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Medicina de Emergencia , Empatía , Satisfacción del Paciente , Relaciones Médico-Paciente , Adulto , Anciano , Actitud del Personal de Salud , Actitud Frente a la Salud , Educación Médica/organización & administración , Educación Médica/normas , Enfermería de Urgencia , Servicio de Urgencia en Hospital , Femenino , Humanos , Masculino , Persona de Mediana Edad , Relaciones Profesional-Familia , Investigación Cualitativa , TaiwánRESUMEN
Full healing was achieved within eight weeks in a malignant fungating wound using the principles of the TIME paradigm. This concept appears to provide a structured and systematic approach for managing such non-healing wounds.
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Neoplasias de la Mama/patología , Cuidados de la Piel/métodos , Neoplasias Cutáneas/prevención & control , Cicatrización de Heridas , Infección de Heridas/prevención & control , Adulto , Vendas Hidrocoloidales , Carboximetilcelulosa de Sodio/uso terapéutico , Protocolos Clínicos , Combinación de Medicamentos , Exudados y Transudados , Femenino , Gelatina/uso terapéutico , Humanos , Humedad , Control de Infecciones , Inflamación , Metronidazol/uso terapéutico , Evaluación en Enfermería , Odorantes , Cuidados Paliativos/métodos , Selección de Paciente , Pectinas/uso terapéutico , Polienos/uso terapéutico , Derivación y Consulta , Cuidados de la Piel/instrumentación , Cuidados de la Piel/enfermería , Neoplasias Cutáneas/secundario , Infección de Heridas/etiologíaRESUMEN
BACKGROUND/OBJECTIVE: Thrombin-activatable fibrinolysis inhibitor (TAFI) is a plasma carboxypeptidase that renders a fibrin-containing thrombus less sensitive to lysis. In the present study, we describe the development of a murine model of vena cava thrombosis and its use to characterize the antithrombotic activity of potato carboxypeptidase inhibitor (PCI) of TAFIa (activated TAFI) in mice. METHODS/RESULTS: Vena cava thrombosis was induced by various concentrations of FeCl(3) in C57BL/6 mice. A relatively mild stimulus (3.5% FeCl(3)) induced thrombosis that was consistent and sensitive to reference antithrombotic agents such as clopidogrel and heparin. Dose-response studies identified a PCI dose (5 mg kg(-1) bolus plus 5 mg kg(-1) h(-1), i.v.) that produced a maximum 45% decrease in vena cava thrombus mass as assessed by protein content (n = 8, P < 0.01 compared to vehicle) in the 3.5% FeCl(3)-induced model without exogenous tissue plasminogen activator administration. In contrast, PCI had no effect on 3.5% FeCl(3)-induced carotid artery thrombosis in mice. In a tail transection bleeding model, the 5 mg kg(-1) bolus plus 5 mg kg(-1) h(-1) dose of PCI increased tail-bleeding time up to 3.5 times control (n = 8, P < 0.05). The ex vivo activity of antithrombotic doses of PCI was also demonstrated by the enhanced lysis of whole blood clots formed in a thrombelastograph with the addition of a sub-threshold concentration of tPA. CONCLUSION: These studies provide evidence for a role of TAFIa in venous thrombosis in mice, and describe an optimized vena cava injury model appropriate for the evaluation of antithrombotic drugs and the characterization of novel therapeutic targets.
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Trombosis de la Vena/tratamiento farmacológico , Animales , Carboxipeptidasa B2/sangre , Carboxipeptidasas/antagonistas & inhibidores , Trombosis de las Arterias Carótidas/sangre , Trombosis de las Arterias Carótidas/inducido químicamente , Trombosis de las Arterias Carótidas/tratamiento farmacológico , Cloruros , Modelos Animales de Enfermedad , Compuestos Férricos/toxicidad , Fibrinolíticos/administración & dosificación , Fibrinolíticos/farmacología , Técnicas In Vitro , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas de Plantas/administración & dosificación , Proteínas de Plantas/farmacología , Inhibidores de Proteasas/administración & dosificación , Inhibidores de Proteasas/farmacología , Solanum tuberosum , Terapia Trombolítica , Venas Cavas , Trombosis de la Vena/sangre , Trombosis de la Vena/inducido químicamenteRESUMEN
BACKGROUND: Increased plasma levels of coagulation factor (F) XI are a risk factor for venous thrombosis. OBJECTIVE: To further explore the relationship between FXI and venous thrombosis, we evaluated FXI-deficient and wild-type mice in a ferric chloride (FeCl(3))-induced vena cava thrombosis model. METHODS AND RESULTS: Thrombosis was induced by 3-min topical application of filter papers containing increasing concentrations of FeCl(3) and the thrombus was measured at 30 min. In contrast to wild-type mice, FXI-deficient mice failed to form a thrombus with 5% FeCl(3,) and were partially protected against 7.5% and 10% FeCl(3,) respectively. The protective effect was substantially stronger than a high dose of heparin (1,000 units kg(-1), i.v.), clopidogrel (30 mg kg(-1), p.o.) or argatroban (30 mg kg(-1), i.p.). These antithrombotic agents resulted in off-scale bleeding in a tail bleeding time assay, whereas the bleeding time of FXI-deficient mice was unchanged compared to wild-type mice. In addition to its known effect on the coagulation cascade, enhanced clot lysis was demonstrated in FXI-deficient mouse and human plasma compared to those supplemented with FXIa. CONCLUSION: Given the strong antithrombotic efficacy (possibly contributed by strong anticoagulant activity associated with increased fibrinolytic activity) and mild bleeding diathesis associated with FXI deficiency, therapeutic inhibition of FXI may be a reasonable therapeutic strategy to treat or prevent venous thrombosis.
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Deficiencia del Factor XI/complicaciones , Compuestos Férricos/farmacología , Venas Cavas/patología , Trombosis de la Vena/prevención & control , Animales , Cloruros , Modelos Animales de Enfermedad , Fibrinólisis , Fibrinolíticos/farmacología , Ratones , Trombosis de la Vena/inducido químicamenteRESUMEN
Mel-cell adhesion molecule (CAM), also known as MUC18 and CD146, is a novel member of the immunoglobulin supergene family. Mel-CAM was first identified as an integral membrane glycoprotein in human melanoma and is also abundantly expressed by endothelial cells of various origins. In a previous study (I. M. Shih et al., Cancer Res., 54: 2514-2520, 1994), we showed that Mel-CAM is a cell-cell adhesion molecule with a possible role in melanoma invasion and metastasis. Here, we define the molecular mechanism responsible for cell-cell adhesion of Mel-CAM and demonstrate its role in melanoma-endothelial cell interactions. Most of human melanoma cells, including Mel-CAM-negative SBcl-2 cells, adhered to nitrocellulose-immobilized Mel-CAM produced by baculovirus recombinants. This adhesion can be blocked by full-length Mel-CAM or polyclonal antiserum against Mel-CAM. Adhesion is not affected by the presence of EDTA, truncated Mel-CAM extracellular domain, or heparan sulfate proteoglycan. In cell aggregation assays, Mel-CAM-negative SBcl-2 cells cluster with U937TM cells (U937 transfected with Mel-CAM cDNA) but not with control nontransfectants, suggesting that SBcl-2 cells express the ligand for Mel-CAM. SBcl-2 cells also form heterotypic aggregates with Mel-CAM-positive human endothelial cells but not with Mel-CAM-negative but ligand-positive smooth muscle cells. Taken together, our results show that Mel-CAM mediates cell-cell adhesion through heterophilic adhesion to an as yet unidentified ligand present on melanoma but not on endothelial cells. Thus, melanoma-endothelial interactions during metastasis may occur through this novel mechanism.
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Antígenos CD , Moléculas de Adhesión Celular/fisiología , Comunicación Celular/fisiología , Melanoma/fisiopatología , Glicoproteínas de Membrana/fisiología , Proteínas de Neoplasias/fisiología , Moléculas de Adhesión de Célula Nerviosa , Antígeno CD146 , Moléculas de Adhesión Celular/metabolismo , Agregación Celular/efectos de los fármacos , Proteoglicanos de Heparán Sulfato , Heparitina Sulfato/metabolismo , Humanos , Melanoma/metabolismo , Melanoma/patología , Glicoproteínas de Membrana/metabolismo , Proteínas de Neoplasias/metabolismo , Proteoglicanos/metabolismo , Proteínas Recombinantes , Células Tumorales CultivadasRESUMEN
Basic fibroblast growth factor (bFGF or FGF-2) is produced by nearly all melanomas in vitro and in vivo but not by normal melanocytes, which require exogenous bFGF for growth. In this study, we transduced normal human melanocytes to overexpress two forms of bFGF: (bFGF-Long and bFGF-Short) using replication-deficient adenovirus 5 vectors. bFGF-Long induced the 17.8, 22.5, 23.1 and 24.2 kDa forms of bFGF, whereas bFGF-Short induced only the 17.8 kDa mature form. Growth of cultured melanocytes transduced with either vector was similar to that of nevus and melanoma cells and was independent of exogenous bFGF and of insulin/insulin-like growth factor 1, and cyclic AMP enhancers, requiring only phorbol ester as an exogenous mitogen. Like primary melanoma cells, transduced normal melanocytes grew anchorage independently in soft agar. When injected into the dermis of human skin grafted to mice, bFGF-transduced melanocytes proliferated for at least 20 days, whereas cells from control cultures showed poor survival and no proliferation. These results demonstrate that bFGF upregulation is a critical component in melanoma progression.
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Factor 2 de Crecimiento de Fibroblastos/fisiología , Melanocitos/citología , Adenoviridae/genética , División Celular/fisiología , Línea Celular Transformada , Células Cultivadas , Factor 2 de Crecimiento de Fibroblastos/biosíntesis , Vectores Genéticos , Humanos , FenotipoRESUMEN
Factor XI (FXI) and factor IX (FIX) are zymogens of plasma serine proteases required for normal hemostasis. The purpose of this work was to evaluate FXI and FIX as potential therapeutic targets by means of a refined ferric chloride (FeCl(3))-induced arterial injury model in factor-deficient mice. Various concentrations of FeCl(3) were used to establish the arterial thrombosis model in C57BL/6 mice. Carotid artery blood flow was completely blocked within 10 min in C57BL/6 mice by application of 3.5% FeCl(3). In contrast, FXI- and FIX-deficient mice were fully protected from occlusion induced by 5% FeCl(3), and were partially protected against the effect of 7.5% FeCl(3). The protective effect was comparable to very high doses of heparin (1000 units kg(-1)) and substantially more effective than aspirin. While FXI and FIX deficiencies were indistinguishable in the carotid artery injury model, there was a marked difference in a tail-bleeding-time assay. FXI-deficient and wild-type mice have similar bleeding times, while FIX deficiency was associated with severely prolonged bleeding times (>5.8-fold increase, P < 0.01). Given the relatively mild bleeding diathesis associated with FXI deficiency, therapeutic inhibition of FXI may be a reasonable strategy for treating or preventing thrombus formation.
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Arterias Carótidas/efectos de los fármacos , Factor IX/fisiología , Deficiencia del Factor XI/patología , Factor XI/fisiología , Compuestos Férricos/farmacología , Hemofilia B/patología , Animales , Arterias/efectos de los fármacos , Arterias/lesiones , Aspirina/farmacología , Tiempo de Sangría , Velocidad del Flujo Sanguíneo , Enfermedades de las Arterias Carótidas/patología , Cloruros , Relación Dosis-Respuesta a Droga , Genotipo , Heparina/química , Heparina/farmacología , Homocigoto , Ratones , Ratones Endogámicos C57BL , Agregación Plaquetaria , Flujo Sanguíneo Regional/efectos de los fármacos , Trombosis/patología , Trombosis/terapia , Factores de TiempoRESUMEN
Based on clinical and histopathological features, five steps of melanoma progression have been proposed: common acquired and congenital nevi with structurally normal melanocytes, dysplastic nevus with structural and architectural atypia, early radial growth phase (RGP) primary melanoma, advanced vertical growth phase primary melanoma (VGP) with competence for metastasis, and metastatic melanoma. Despite a wealth of research resources (tissues, cell lines, and antibodies), the genetic alterations responsible for the development and stepwise progression of melanoma are still unclear. Cytogenetic analyses have failed to identify consistent gene deletions, mutations, translocations, or amplifications in sporadic cases. However, in vitro characterization of melanoma cells has revealed fundamental differences from normal melanocytes. Earlier work using monoclonal antibodies has defined a variety of melanoma-associated antigens that mediate cell-cell or cell-substratum adhesion, growth regulation, proteolysis, and modulation of immune responses. Functional studies of these individual candidate molecules will lead to a better understanding of the pathogenesis of melanoma and of potential targets for rational therapy.
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Antígenos de Neoplasias/metabolismo , Melanoma , Moléculas de Adhesión Celular/metabolismo , Citocinas/metabolismo , Progresión de la Enfermedad , Proteínas de la Matriz Extracelular/metabolismo , Humanos , Melanoma/genética , Melanoma/metabolismo , Melanoma/patología , Receptores de Factores de Crecimiento/metabolismoRESUMEN
In our previous work, two-dimensional gel electrophoretic analysis of the translational products from mRNA of lens from rats maintained on 50% galactose up to 45 days has suggested that synthesis of mRNA was not arrested by the disease process, but it decreased significantly relative to the control. The loss in mRNA number was due mainly to loss in cell population. Specifically, the gamma-crystallin mRNA product decreased to very low levels at onset of the disease. However, this mRNA was resynthesized in the surviving cells as the cataracts matured. Therefore, it became of interest to explore whether reversal or inhibition of cataracts would lead to some measurable changes in mRNA population in the experimental lens. The results show that the percentage (relative to the total mRNA population) of the in vitro [35S]-labeled translational products from alpha-, beta- and gamma-crystallin mRNAs combined, remained unchanged irrespective of the state of the lens. The severity of the cataracts was examined by indirect immunofluorescence with polyclonal MP26 antibody. Reversal of cataracts led to partial recovery of normal fiber cell morphology. Treatment with sorbinil in combination with galactose led to inhibition of cataracts with indication of appearance of vacuoles at longer periods of exposure to the drug. The translational products profile reflected the expected variation in non-crystallin and crystallin mRNA synthesis. It is concluded that there appears to be a combined fixed level of synthesis for the crystallins, such that inhibition in synthesis of gamma-crystallin mRNAs appears to lead to an increase in synthesis of alpha-crystallin mRNAs, while synthesis of beta-crystallin mRNAs showed insignificant fluctuation. A similar conclusion may also be drawn relative to the combined synthesis for the non-crystallin mRNAs.
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Catarata/metabolismo , Galactosemias/metabolismo , Cristalino/análisis , Cristalino/metabolismo , ARN Mensajero/análisis , HumanosRESUMEN
Bone marrow examinations were performed on 20 patients with acquired immune deficiency syndrome (AIDS) and 39 with AIDS-related complex (ARC). Fever of unknown origin and thrombocytopenia were common in ARC, but anemia and leukopenia were most frequent in AIDS. Changes in stromal cells and perivascular cuffing of plasma cells were found significantly more often in patients with AIDS than in those with ARC. Malignancies were common in both groups. Human immunodeficiency virus (HIV) nucleic acids were detected with the use of a 3H-labeled cDNA probe with an in situ hybridization method in 11 bone marrow samples (three ARC and eight AIDS). Most commonly positive cells were mononucleated, resembling lymphocytes and histiocytes. Endothelial cells, interdigitating reticulum cells, nucleated red blood cells, and immature myeloid cells also had positive results in some instances. The number of HIV-positive cells was not related to the size of the bone biopsies or the clinical diagnoses. The authors postulate that changes in the peripheral blood and bone marrow of these patients may be related to latent persistent infection with HIV.
Asunto(s)
Complejo Relacionado con el SIDA/patología , Síndrome de Inmunodeficiencia Adquirida/patología , Médula Ósea/patología , Complejo Relacionado con el SIDA/microbiología , Síndrome de Inmunodeficiencia Adquirida/microbiología , Tejido Adiposo/patología , Adulto , Médula Ósea/microbiología , Sondas de ADN , Eritropoyesis , Femenino , VIH/genética , VIH/aislamiento & purificación , Hematopoyesis , Células Madre Hematopoyéticas/patología , Histiocitos/patología , Humanos , Masculino , Persona de Mediana Edad , Hibridación de Ácido Nucleico , Ácidos Nucleicos/análisis , Fagocitosis , Células Plasmáticas/patología , Estudios RetrospectivosRESUMEN
Brugia malayi and B. Pahangi microfilariae from gerbil intraperitoneal infections were inoculated into the thorax of male and female Toxorhynchites amboinesis and developed into third-stage larvae as early as 11 days. In a comparative study with Aedes togoi fed on microfilaremic gerbils, third-stage larvae were found at 10 days. Some third-stage larvae of B. malayi inoculated into gerbils developed to advanced stages. Third-stage larvae of Wuchereria bancrofti were recovered in low numbers from Tx. amboinesis and Tx. aurifluus inoculated with microfilariae recovered from human blood by membrane filtration. Development of all filarial species was similar in both male and female mosquitoes. Toxorhynchites species are plant feeders and therefore reduce the hazards of laboratory transmission of pathogenic agents. Because of their large size, manipulations with this mosquito species are easy and the size allows for a larger inoculum to be used. This group of mosquitoes should develop into useful laboratory vectors for the transmission of arthropod-borne diseases.
Asunto(s)
Brugia/crecimiento & desarrollo , Culicidae/parasitología , Filarioidea/crecimiento & desarrollo , Wuchereria bancrofti/crecimiento & desarrollo , Wuchereria/crecimiento & desarrollo , Animales , Femenino , Masculino , Microfilarias/crecimiento & desarrollo , Especificidad de la EspecieRESUMEN
Infective larvae of Wuchereria bancrofti from laboratory-raised Culex pipiens fatigans and Aedes togoi mosquitoes fed on human volunteers in Jakarta, Indonesia (J strain) and Kinmen Island, China (K strain) were introduced into Taiwan monkeys (Macaca cyclopis) by subcutaneous inoculation, by foot puncture, or by permitting infected mosquitoes to feed weekly on the monkeys. Some animals were splenectomized and others were treated with varying regimens of immunosuppressants. Necropsy was done on monkeys that died or were killed and the entire bodies were examined for worms. A total of 78 monkeys (43 males and 35 females) were exposed to infection and parasites were found in 29% of the females and 63% of males. In infections of 38 days or less worms were recovered from the testes of males and the pelt, carcass and lymph nodes of both sexes, but after 42 days of infection most worms were in the testes of males, and a few were recovered from lymph nodes and carcasses of females. Worms recovered at 8-11 days were third-stage, those found between 14 and 38 days fourth-stage, and ones found between 42 and 103 days were young adults. After 148 days most were adults and microfilariae were seen in the uteri of female worms at 160 days and later. The parasites continued to grow in size with time. Microfilariae were detected in the blood of nine monkeys between 8 and 18 months and the patent period varied from 5-21 months. Microfilarial densities were low and erratic, and periodicity could not be determined. The effectiveness of methods of administering infections and the value of various treatment regimens seem uncertain; monkey antilymphocytic sera, however, appeared to have some influence. Parasites were found in 36% of the Taiwan monkeys given the J strain and 54% of those given the K strain. A limited number of M. mulatta (3), M.irus (fascicularis) (3) and Aotus trivirgatus (4) were also given infective larvae and adult W. bancrofti were recovered from the testes of one male M. mulatta and one male M. irus; uterine microfilariae were found in one female worm from the latter monkey. A. trivirgatus were negative. Low numbers of infective larvae recovered from mosquitoes fed on patent monkeys were introduced intermittently into seven clean monkeys and one became microfilaremic between 11 and 17 months postinoculation.
Asunto(s)
Modelos Animales de Enfermedad , Filariasis/transmisión , Enfermedades de los Monos , Aedes/parasitología , Animales , Aotus trivirgatus , Culex , Femenino , Filariasis/parasitología , Filariasis/patología , Haplorrinos , Humanos , Terapia de Inmunosupresión , Ganglios Linfáticos/parasitología , Ganglios Linfáticos/patología , Macaca , Macaca fascicularis , Macaca mulatta , Masculino , Microfilarias/crecimiento & desarrollo , Taiwán , Testículo/parasitología , Testículo/patología , Wuchereria bancrofti/crecimiento & desarrolloRESUMEN
An important approach in studies of normal, diseased, and malignant cells is their growth in culture. The isolation and subsequent culture of human eplderma1 melanocytes has been attempted since 1957 (1-5), but only since 1982 have pure normal human melanocyte cultures been reproducibly established to yield cells in sufficient quantity for biological, biochemical, and molecular analyses (6). Selective growth of melanocytes, which comprise only 3-7% of epldermal cells in normal human skin, was achieved by suppressing the growth of keratinocytes and fibroblasts in epidermal cell suspensions with the tumor promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA) and the intracellular cyclic adenosine 3', 5' monophosphate (cAMP) enhancer cholera toxin, respectively, which both also act as melanocyte growth promoters. Recent progress in basic cell-culture technology, along with an improved understanding of culture requirements, has led to an effective and standardized isolation method, and special culture media for selective growth and long-term maintenance of human melanocytes. The detailed description of this method is aimed at encouraging its use in basic and applied biological research.