RESUMEN
BACKGROUND: The finding of new biomarkers is needed to have a better sub-classification of primary renal tumors (RCC) as well as more reliable predictors of outcome and therapy response. In this study, we evaluated the role of circulating FGF21, an endocrine factor, as a diagnostic and prognostic biomarker for ccRCC. MATERIALS AND METHODS: Serum samples from healthy controls (HC), clear cell and chromophobe RCC cancer patients were obtained from the serum biobank "Biobanco Público de Muestras Séricas Oncológicas" (BPMSO) of the "Instituto de Oncología "Ángel H. Roffo". Serum FGF21 and leptin were measured by ELISA while other metabolic markers were measured following routinely clinical procedures. RESULTS: One of our major findings was that FGF21 levels were significantly increased in ccRCC patients compared with HC. Moreover, we showed an association between the increased serum FGF21 levels and the shorter disease free survival in a cohort of 98 ccRCC patients, after adjustment for other predictors of outcome. CONCLUSION: Our results suggest that higher FGF21 serum level is an independent prognostic biomarker, associated with worse free-disease survival.
RESUMEN
Primary cutaneous T-cell lymphomas (CTCL) mycosis fungoides (Mf) and Sézary syndrome (SS) belong to the group of non-Hodgkin lymphomas which are characterized by clonally proliferating CD4+ cells localized in the skin. SS is a leukemic variant of CTCL and is characterized by erythroderma, generalized lymphadenopathy, and circulating atypical T-cells with cerebriform nuclei, so-called Sézary cells. Palmoplantar hyperkeratosis, generalized alopecia, and severe pruritus are additional symptoms that are associated with SS. Patients have a poor prognosis with an estimated five year survival of 12.5 to 27 percent and estimated median survival of 14.5 to 18 months. The incidence of MF and also SS has increased with time and may be in part due to improved clinical awareness and especially advances in diagnostic testing.
Asunto(s)
Síndrome de Sézary/patología , Neoplasias Cutáneas/patología , Reordenamiento Génico de Linfocito T , Humanos , Síndrome de Sézary/genética , Neoplasias Cutáneas/genéticaRESUMEN
Expulsion of adult Nippostrongylus brasiliensis worms from the small intestine is profoundly impaired in signal transducer and activator of transcription (STAT)6-deficient mice. IL-5 transgenic (Tg) mice with constitutive eosinophilia show profound early resistance in the skin and/or later pre-lung phase of primary infections with N. brasiliensis. This study was designed to assess the importance of the eosinophil chemokine eotaxin and the STAT6/interleukin (IL)-4/IL-13 signalling pathway in early resistance to N. brasiliensis. Eosinophil recruitment into the skin following injection of N. brasiliensis larvae was reduced in STAT6- or eotaxin-deficient/IL-5 Tg double mutant mice. While ablation of eotaxin did not impair resistance in the pre-lung phase of N. brasiliensis infections in IL-5 Tg mice, elimination of STAT6 caused a modest reduction in resistance in both primary and secondary infections on this genetic background. STAT6(-/-)-, IL-13(-/-)- and IL-4Ralpha(-/-)-deficient single mutant and IL-13(-/-)/IL-4Ralpha(-/-) double mutant mice were more susceptible than WT mice during the pre-lung phase of secondary N. brasiliensis infections. In contrast, primary or secondary resistance were unaffected at either the pre-lung or gut stages of infection in eotaxin(-/-) single mutant mice. STAT6(-/-) and eotaxin(-/-) mice with or without the IL-5 transgene, were no more susceptible than WT or IL-5 Tg mice to protracted primary infections with Heligmosomoides bakeri, a parasitic nematode that is restricted to the gut. Our data suggest that parasitic nematodes that transit through the skin and lungs en route to the gut may be susceptible to early (pre-lung) innate and adaptive immune mechanisms that are dependent on the STAT6/IL-4/IL-13 signalling pathway, and this may be important for the development of effective therapies and vaccines.
Asunto(s)
Quimiocina CCL11/fisiología , Eosinófilos/metabolismo , Heligmosomatoidea/fisiología , Nippostrongylus/fisiología , Factor de Transcripción STAT6/fisiología , Transducción de Señal/fisiología , Animales , Quimiocina CCL11/deficiencia , Quimiocina CCL11/genética , Eosinófilos/citología , Eosinófilos/parasitología , Heces/parasitología , Femenino , Interacciones Huésped-Parásitos , Inmunidad Innata , Interleucina-5/genética , Interleucina-5/metabolismo , Interleucina-5/fisiología , Mucosa Intestinal/metabolismo , Intestinos/parasitología , Larva/fisiología , Pulmón/metabolismo , Pulmón/parasitología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos CBA , Ratones Noqueados , Ratones Transgénicos , Recuento de Huevos de Parásitos , Receptores de Superficie Celular/deficiencia , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/fisiología , Factor de Transcripción STAT6/deficiencia , Factor de Transcripción STAT6/genética , Piel/metabolismo , Piel/parasitologíaRESUMEN
Nippostrongylus brasiliensis larvae are particularly susceptible to immunological attack during the pre-lung stage of primary and secondary infections in mice. Whilst most of the common laboratory strains of mice are permissive hosts for the parasite, in this study we report for the first time, the strong resistance of naive FVB/N mice to N. brasiliensis. Damage to larvae is evident within the first 24 h of infection and this may be critical to later larval development and reproductive success. Inflammatory responses in the skin, and larval escape from this tissue were comparable in susceptible CBA/Ca and resistant FVB/N mice, with most larvae exiting within 4 h of a primary infection. Lung larval burdens were also similar between strains, but larvae recovered from FVB/N mice were smaller and less motile. In FVB/N mice, larval colonization of the gut was impaired and worms produced very few eggs. However FVB/N mice did not show enhanced resistance to Heligmosomoides bakeri (also known as Heligmosomoides polygyrus), a nematode largely restricted to the gut. Damage done in the pre-lung or lung stages of infection with N. brasiliensis is likely to contribute to ongoing developmental and functional abnormalities, which are profoundly evident in the gut phase of infection.
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Inmunidad Innata/genética , Nippostrongylus/fisiología , Infecciones por Strongylida/genética , Infecciones por Strongylida/inmunología , Animales , Proteínas de Unión a Ácidos Grasos/genética , Femenino , Inmunidad Celular , Inmunidad Innata/inmunología , Intestinos/parasitología , Larva/fisiología , Leucocitos/inmunología , Pulmón/parasitología , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos CBA , Ratones Endogámicos , Ratones Transgénicos , Nematospiroides/fisiología , Recuento de Huevos de ParásitosRESUMEN
Experimental tanks were used to observe predatory effects in three different size classes of Mozambique tilapia Oreochromis mossambicus (one of the world's most widespread exotic species and generally regarded to be a herbivore or both herbivore and detritivore) when tested against 10 juvenile Australian freshwater fish species, and significant levels of predation against all were recorded. There was a general trend for larger O. mossambicus to kill more prey and this was also reflected in a separate series of experiments using juvenile barramundi Lates calcarifer over a range of size classes. Predatory effects by O. mossambicus broadly reflected the accepted models of predator-prey interactions, being that mortality (and survival) was closely related to relative body size and mouth gape limitation. Experimental evidence for piscivory in O. mossambicus was supported by field sampling that detected prey fish remains in 16% of all fish surveyed (n = 176). The recognition of active piscivory by O. mossambicus in laboratory and field situations is the first such evidence, and suggests a need to re-evaluate the nature of their effects in introduced environments.
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Peces/fisiología , Agua Dulce , Especies Introducidas , Conducta Predatoria , Tilapia/fisiología , Animales , Australia , Tamaño Corporal/fisiología , Conservación de los Recursos NaturalesRESUMEN
This paper focuses on the two-parameter latent trait model for binary data. Although the prior distribution of the latent variable is usually assumed to be a standard normal distribution, that prior distribution can be estimated from the data as a discrete distribution using a combination of EM algorithms and other optimization methods. We assess with what precision we can estimate the prior from the data, using simulations and bootstrapping. A novel calibration method is given to check that near optimality is achieved for the bootstrap estimates. We find that there is sufficient information on the prior distribution to be informative, and that the bootstrap method is reliable. We illustrate the bootstrap method for two sets of real data.
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Interpretación Estadística de Datos , Modelos Estadísticos , Distribución Normal , Pruebas Psicológicas/estadística & datos numéricos , Psicometría/estadística & datos numéricos , Algoritmos , Análisis de Varianza , Aptitud , Actitud , Niño , Comparación Transcultural , Emociones , Femenino , Humanos , Funciones de Verosimilitud , Masculino , Método de Montecarlo , Probabilidad , Estadísticas no ParamétricasRESUMEN
beta thalassemia is one of the most common genetic diseases worldwide resulting from aberrant beta-globin chain production. It is highly prevalent in regions with endemic malaria, but it is also present at low frequency in the indigenous populations of non-tropical areas such as Britain. Screening beta thalassemia trait individuals from Northern Ireland has detected 2 Mediterranean mutations, 39 (C --> T) and IVS-I-110 (G --> A); the previously reported IVS-II-850 (G --> A) mutation originally described in individuals of Scottish/English ancestry; and 2 novel mutations, initiation codon A --> C and 109 delG. Haplotype analysis indicates that the Mediterranean mutations are present on previously described haplotypes, suggesting that they have arisen due to migration. It remains to be established whether the novel mutations have arisen de novo in Northern Ireland.
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Mutación , Talasemia beta/genética , Adolescente , Adulto , Anciano , Niño , Análisis Mutacional de ADN , Femenino , Mutación del Sistema de Lectura , Globinas/genética , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Irlanda del Norte , Mutación Puntual , Grupos de PoblaciónRESUMEN
We solve the linearized Poisson-Boltzmann equation analytically, subject to justifiable approximations, for a suspension containing a large number of identical spherical macroions under conditions of constant surface charge and zero added salt, in order to investigate the phase behavior of charge-stabilized colloidal suspensions. Our results for the electrostatic part of the Helmholtz free energy lead to an interaction which resembles the intermolecular interaction in the theory of molecular fluids. When combined with the ideal gas free energy of the counterions, this produces a van der Waals loop in the pV diagram, indicating coexistence between phases with different densities, for certain values of the macroion radius and charge. We also derive an expression for the surface potential of the macroions, and clarify the interpretation of the Poisson-Boltzmann equation.
RESUMEN
Although there have been studies of clients' perceptions of health visiting, the views of single, unsupported mothers about the health visiting service have been under-researched. Therefore, this study investigated their views using semi-structured interviews with 12 single, unsupported mothers identified by health visitors within one National Health Service Community Trust. The data were analysed using Burnard's (1991) thematic content analysis, which enabled a number of identifiable themes to emerge. Findings showed that the participants perceived the health visiting service as being concerned almost exclusively with babies and there was a general lack of understanding about the broader role of the health visitor. Clinics were seen as places to visit to weigh the baby but not as a contact point with a health visitor. Some health visitors were perceived as being judgemental in attitude and not necessarily interested in the clients as individuals. Participants considered that health visitors should be friendly, interested, able to promote their confidence and offer individualized advice. Overall the study suggests that health visitors may not be utilizing all dimensions of their role with single, unsupported mothers and may not be communicating effectively with them about this. The study also shows that single, unsupported mothers wish to be treated in the same way as other mothers but at present some feel that they are stigmatized and treated differently. The paper concludes with an outline of the implications of the findings and recommendations for practice and future research.
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Actitud Frente a la Salud , Enfermería en Salud Comunitaria , Madres/psicología , Padres Solteros/psicología , Adolescente , Adulto , Inglaterra , Femenino , Humanos , Lactante , Entrevistas como Asunto/métodos , Relaciones Enfermero-PacienteRESUMEN
Five female adult Macaca nemestrina monkeys, given a unilateral intracarotid (ic) infusion of 2.3-3.5 mg of MPTP-HCl, were studied for 6-8 years. Two to 3 days after MPTP, the animals developed hemiparkinsonism characterized by rigidity and flexed posture of the arm contralateral to the side of infusion with episodes of tremor, circling ipsilateral to the lesioned side, a slight balance disturbance, and stooped posture. Rating of parkinsonian features 4 months after ic infusion, and yearly thereafter, did not show any statistically significant changes. The animals maintained their usual appetite and body weight increased normally. Each animal responded to l-DOPA methyl ester with decreased parkinsonian signs and symptoms and increased contralateral turning. In contrast, after control vehicle administration, the animals continued to have the same parkinsonian signs and predominant ipsilateral turns. In three of the five monkeys, contralateral turns after vehicle significantly increased after 6-8 years. Unilateral intracarotid MPTP induced asymmetric motor behavior that remained stable after 6-8 years. Animals that showed an increased frequency of contralateral circling after control vehicle showed a decrease in contralateral turns after l-DOPA methyl ester, suggesting neuroplastic changes over the years.
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Dopaminérgicos/toxicidad , Intoxicación por MPTP , Enfermedad de Parkinson Secundaria/inducido químicamente , Animales , Antiparkinsonianos/farmacología , Arterias Carótidas , Esquema de Medicación , Femenino , Estudios de Seguimiento , Infusiones Intraarteriales , Levodopa/análogos & derivados , Levodopa/farmacología , Macaca nemestrina , Actividad Motora/efectos de los fármacos , RotaciónRESUMEN
Nitrate-nitrite toxicosis causes numerous cattle deaths every year in western Nebraska. Its role in fetal abortions is complex and still speculative. This paper reports composite fetal nitrate diagnostic levels, fetal abattoir nitrate levels and observations of bovine perinates from cow-calf livestock units.
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Líquidos Corporales/metabolismo , Bovinos/metabolismo , Nitratos/metabolismo , Preñez/metabolismo , Aborto Inducido , Alimentación Animal/envenenamiento , Animales , Enfermedades de los Bovinos/inducido químicamente , Desarrollo Embrionario y Fetal/efectos de los fármacos , Femenino , Riñón/efectos de los fármacos , Metahemoglobina/metabolismo , Nebraska , Nitratos/sangre , Nitratos/envenenamiento , Nitritos/metabolismo , Nitritos/envenenamiento , Plantas Comestibles/metabolismo , Embarazo , Efectos Tardíos de la Exposición PrenatalRESUMEN
Measurement of diamine oxidase (DAO) activity in vaginal fluid as an aid to diagnosis of premature rupture of the fetal membranes was studied. In 76 patients following artificial rupture of the membranes and in 70 patients with known intact membranes, the accuracy was 100%. One hundred and forty-nine patients were admitted to hospital with suspected ruptured membranes; using the criteria outlined in this paper, 51 had ruptured membranes and in 98 the membranes were intact. The overall accuracy was 96%.
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Amina Oxidasa (conteniendo Cobre)/análisis , Líquidos Corporales/enzimología , Pruebas Enzimáticas Clínicas , Rotura Prematura de Membranas Fetales/diagnóstico , Vagina/metabolismo , Amina Oxidasa (conteniendo Cobre)/metabolismo , Errores Diagnósticos , Femenino , Humanos , EmbarazoRESUMEN
Pulmonary function was studied in six divers living in a hyperbaric chamber at a pressure nearly fifty times normal (49.5 atmospheres absolute (ATA), equivalent to 488 m or 1600 ft seawater (fsw)). As expected, ventilatory function was reduced. At 49.5 ATA, maximum voluntary ventilation (MVV) was 45% less than the control value. Instantaneous rates of gas flow during forced expiration were similarly reduced, especially those flow rates measured high in the lung volume. These reductions occurred despite an apparent increase in functional residual capacity (FRC) and the use of transpulmonary pressures considerably greater than those exerted during the same maneuvers at normal (sea-level) pressure. During underwater work at 49.5 ATA, the divers rapidly became exhausted at moderate levels of oxygen consumption (1.9 liters/min), showing severe dyspnea and impending syncope. These symptoms were not due to retention of carbon dioxide, nor to hemodynamic or metabolic causes. Thus, dense gas breathing, like asthma, exemplifies a state in which severe dyspnea may occur with normal or low arterial carbon dioxide and normal oxygen transport. The physiological adjustments the divers employed were similar to those seen in acute asthma, imposing an elastic load in addition to the flow-resistive work of breathing a gas mixture eight times as dense as air. Although men can do moderate work under conditions similar to those of this experiment, they will have only a limited physiological reserve available to meet the possibilities of emergencies or respiratory infections.