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The time-evolution operator obtained from the fractional-time Schrödinger equation (FTSE) is said to be nonunitary since it does not preserve the norm of the vector state in time. As done in the time-dependent non-Hermitian quantum formalism, for a traceless non-Hermitian two-level quantum system, we demonstrate that it is possible to map the nonunitary time-evolution operator in a unitary one. It is done by considering a dynamical Hilbert space with a time-dependent metric operator, constructed from a Hermitian time-dependent Dyson map, in respect to which the system evolves in a unitary way, and the standard quantum mechanics interpretation can be made properly. To elucidate our approach, we consider three examples of Hamiltonian operators and their corresponding unitary dynamics obtained from the solutions of FTSE, and the respective Dyson maps.
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We address the problem of random search for a target in an environment with a space-dependent diffusion coefficient D(x). Considering a general form of the diffusion differential operator that includes Itô, Stratonovich, and Hänggi-Klimontovich interpretations of the associated stochastic process, we obtain and analyze the first-passage-time distribution and use it to compute the search efficiency E=ã1/tã. For the paradigmatic power-law diffusion coefficient D(x)=D_{0}|x|^{α}, where x is the distance from the target and α<2, we show the impact of the different interpretations. For the Stratonovich framework, we obtain a closed-form expression for E, valid for arbitrary diffusion coefficient D(x). This result depends only on the distribution of diffusivity values and not on its spatial organization. Furthermore, the analytical expression predicts that a heterogeneous diffusivity profile leads to a lower efficiency than the homogeneous one with the same average level within the space between the target and the searcher initial position, but this efficiency can be exceeded for other interpretations.
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Population survival depends on a large set of factors and on how they are distributed in space. Due to landscape heterogeneity, species can occupy particular regions that provide the ideal scenario for development, working as a refuge from harmful environmental conditions. Survival occurs if population growth overcomes the losses caused by adventurous individuals that cross the patch edge. In this work, we consider a single species dynamics in a patch with a space-dependent diffusion coefficient. We show analytically, within the Stratonovich framework, that heterogeneous diffusion reduces the minimal patch size for population survival when contrasted with the homogeneous case with the same average diffusivity. Furthermore, this result is robust regardless of the particular choice of the diffusion coefficient profile. We also discuss how this picture changes beyond the Stratonovich framework. Particularly, the Itô case, which is nonanticipative, can promote the opposite effect, while Hänggi-Klimontovich interpretation reinforces the reduction effect.
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We investigate by molecular dynamics simulations the mobility of the water located at the DNA minor and major grooves. We employ the TIP3P water model, and our system is analyzed for a range of temperatures 190-300 K. For high temperatures, the water at the grooves shows an Arrhenius behavior similar to that observed in the bulk water. At lower temperatures, a departure from the bulk behavior is observed. This slowing down in the dynamics is compared with the dynamics of the hydrogen of the DNA at the grooves and with the autocorrelation functions of the water hydrogen bonds. Our results indicate that the hydrogen bonds of the water at the minor grooves are highly correlated, which suggests that this is the mechanism for the slow dynamics at this high confinement.
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Frío , ADN/química , Modelos Moleculares , Agua/química , Difusión , Enlace de Hidrógeno , Simulación de Dinámica MolecularRESUMEN
Children change their body size, shape, and gross motor coordination (GMC) as they grow. Further, GMC is expected to link to changes in children's body size, physical activity (PA), and physical fitness (PF). The objective was to model GMC changes in children followed longitudinally and to investigate associations between these changes and PA and PF levels. A total of 245 children (122 girls) were observed at 6 years of age and followed annually until 9 years. A sequence of allometric models was fitted, that is, 1. body mass, stature, and PA; 2. addition of four PF tests; 3. addition of four more PF tests. In Model 1, changes in GMC are nonlinear, and body mass (-0.60 ± 0.07, P < .001) and stature (2.91 ± 0.35, P < .001) parameter estimates were significant suggesting children with a more linear body size/shape showed higher GMC performances. Girls tend to outperform boys across time, and PA was not associated with GMC changes. Model 2 fitted the data better, and the PF tests (handgrip, standing long jump, 50-yard dash, and shuttle run) were significantly linked to GMC change. In Model 3, adding the remaining PF tests did not change the order of any factors importance. The greatest GMC changes were achieved by children whose body size/shape has an ectomorphic dominance across the years. Considering that leaner and physically fitter children tended to be more coordinated, physical education should also focus on PF development in components related to muscular strength, speed, agility, and aerobic capacity, along with nutritional education to reduce fat mass.
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Desarrollo Infantil , Ejercicio Físico , Destreza Motora , Aptitud Física , Estatura , Tamaño Corporal , Niño , Femenino , Fuerza de la Mano , Humanos , Estudios Longitudinales , Masculino , Modelos Teóricos , SomatotiposRESUMEN
WHAT IS KNOWN ON THE SUBJECT?: Self-confident health professionals with positive and understanding attitudes can take better care of people with suicidal behaviour, but the factors associated with these attitudes are not known. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: The majority of nursing professionals had no experience or training in mental health or suicide. They were less self-confident and had more negative attitudes. Nurses and nursing assistants who worked before in mental health services were more understanding with people with suicidal behaviour. Nurses and nursing assistants who were working in prehospital services were less self-confident to taking care of people with suicidal behaviour. Some members of the nursing team had already seriously considered committing suicide. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: The practicing, support and training in mental health may improve the nurses' attitudes and emotional competencies. It is important to know why few nurses had suicide-related training, despite the relevance of this issue. Training in mental health or suicide need to include attitudinal and emotional competencies. It is important to offer emotional support to emergency nursing professionals. ABSTRACT: Background The attitudes towards suicide of emergency nurses may affect the care provided. However, the factors associated with these attitudes remain unclear. Objective To investigate attitudes towards suicidal behaviour and associated factors among nursing professionals working in emergency settings. Methods A cross-sectional observational study including 28 nurses and 118 who were nursing assistants employed at two emergency services in Brazil was conducted. Data were collected in 2015 using a self-administered sociodemographic questionnaire and the Suicide Behavior Attitude Questionnaire (SBAQ). Results The majority of participants reported having no experience or training in mental health or suicide. They reported more negative feelings towards the patient and a lower self-perception of professional competence regarding suicidal behaviours, and these attitudes seemed to reinforce each other. Nurses who worked in mental health services reported less moralistic/judgemental attitudes. Working in prehospital services was associated with having a lower self-perception of professional competence. There were professionals who reported thinking seriously about committing suicide. Conclusion When combined with support and training, practicing mental health nursing may serve as an opportunity to develop favourable attitudes and emotional competences, and these issues need to be addressed in suicide education strategies.
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Actitud del Personal de Salud , Competencia Clínica , Conocimientos, Actitudes y Práctica en Salud , Enfermeras y Enfermeros/psicología , Asistentes de Enfermería/psicología , Suicidio/psicología , Adulto , Actitud del Personal de Salud/etnología , Brasil/etnología , Femenino , Conocimientos, Actitudes y Práctica en Salud/etnología , Humanos , Masculino , Persona de Mediana Edad , Suicidio/etnologíaRESUMEN
We use the H theorem to establish the entropy and the entropic additivity law for a system composed of subsystems, with the dynamics governed by the Klein-Kramers equations, by considering relations among the dynamics of these subsystems and their entropies. We start considering the subsystems governed by linear Klein-Kramers equations and verify that the Boltzmann-Gibbs entropy is appropriated to this dynamics, leading us to the standard entropic additivity, S_{BG}^{(1âª2)}=S_{BG}^{1}+S_{BG}^{2}, consistent with the fact that the distributions of the subsystem are independent. We then extend the dynamics of these subsystems to independent nonlinear Klein-Kramers equations. For this case, the results show that the H theorem is verified for a generalized entropy, which does not preserve the standard entropic additivity for independent distributions. In this scenario, consistent results are obtained when a suitable coupling among the nonlinear Klein-Kramers equations is considered, in which each subsystem modifies the other until an equilibrium state is reached. This dynamics, for the subsystems, results in the Tsallis entropy for the system and, consequently, verifies the relation S_{q}^{(1âª2)}=S_{q}^{1}+S_{q}^{2}+(1-q)S_{q}^{1}S_{q}^{2}/k, which is a nonadditive entropic relation.
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A investigação química da espécie Pilocarpus spicatus, popularmente conhecida como jaborandi e usada na medicina tradicional para doenças como estomatite, febre, bronquite e psoríase, teve por objetivo o isolamento e/ou identificação de substâncias ativas e a avaliação da atividade antiparasitária dos extratos frente às formas epimastigotas de Trypanosoma cruzi. O estudo resultou na identificação de nove substâncias, tais como: tridecanona, 2-heptadecanona, espatulenol, aromadendreno, β-cariofileno, ácido 3α-hidroxitirucala-7,24-dien-21-óico, (+)-isoangenomalina, episesamina e sesamina. As estr uturas dos compostos foram elucidadas por análises espectroscópicas e comparação com dados da literatura. Os extratos hexânico e metanólico de folhas e raízes foram testados in vitro contra o Trypanosoma cruzi cepa Y e apresentaram atividade tripanomicida.
The chemical investigation of the species Pilocarpus spicatus - popularly known as jaborandi and used in traditional medicine for diseases, such as stomatitis, fever, bronchitis and psoriasis - aimed to isolate and / or identify the active substances and evaluate the antiparasitic activity of the extracts against the Trypanosoma cruzi epimastigote forms. The study resulted in the identification of nine substances, such as tridecanone, 2-heptadecanone, spathulenol, aromadendrene, β-caryophyllene, 3α-hydroxytirucalla-7,24-dien-21-oic acid, (+)-isoangenomaline, episesamin and sesamin. The structures were elucidated by spectroscopic analysis and comparison with literature data. The hexane and methanol extracts from leaves and roots were tested in vitro against Trypanosoma cruzi Y strain and showed trypanocidal activity.
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Trypanosoma cruzi/aislamiento & purificación , Jaborandi/farmacología , Pilocarpus/química , Extractos Vegetales/síntesis química , Rutaceae/clasificación , Antiparasitarios/farmacologíaRESUMEN
OBJECTIVE: The purpose of this study was to examine the efficacy and toxicity of treating small arteriovenous malformations (AVMs) (≤3 cm in diameter) with a median marginal applied dose of 14 Gy. METHODS: Two hundred and thirteen patients diagnosed with AVMs were treated between January 1991 and December 2005. Seventy-three percent of the patients had hemorrhaged prior to treatment, 13% had had previous surgery and 19.2% had had previous embolization. The median follow-up duration was 48.1 months. RESULTS: The Kaplan-Meier analysis estimated that the 36-month obliteration rate was 65.5% for patients undergoing their first stereotactic radiosurgery (SRS) and 68.3% for those undergoing repeated SRS. The Kaplan-Meier analysis estimated the 60-month AVMs obliteration rate for the entire cohort to be 82.4%. The median time to AVM obliteration was 40 ± 2.8 months. We found a statistically significant relationship between the time of obliteration and the following factors: site of the AVMs (sites other than brainstem), a higher prescribed dose and a positive history of previous hemorrhage. Thirteen patients (7.6%) experienced toxicities. CONCLUSIONS: SRS was an effective and safe treatment for AVMs ≤3 cm in diameter, with acceptable toxicity.
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Malformaciones Arteriovenosas Intracraneales/cirugía , Radiocirugia/métodos , Adulto , Estudios de Seguimiento , Humanos , Dosificación Radioterapéutica , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Field collections of the most common urban mosquito vectors Anopheles gambiae and Culex quinquefasciatus were carried out in June 2003, March 2004 and November 2005 to gather preliminary data on the insecticide susceptibility in mosquitoes from Lobito (Angola) using the WHO standard bioassays. Bioassays were performed on F0 adults emerging from the field larval collections and on unfed adults from landing catches on volunteers. Batches of mosquitoes from three selected locations (Alto Liro, San Jao and Bela Vista) were exposed for 1 hour to several insecticides such as DDT 4%, carbosulfan 0.4%, permethrin 1%, deltamethrin 0.05% and cyfluthrin 0.15%, in order to estimate the immediate knockdown times (kdT50 and kdT95) and the mortality rate after exposure. The results revealed that mosquito susceptibility to insecticides varied depending on the insecticide, the site and the period of collection. The main local malaria vector A. gambiae (both M and S forms) was basically resistant to DDT and susceptible to all pyrethoids, regardless of the period and the site of collections. The overall mortality rate due to DDT was 73% in Alto Liro, 89% in San Jao and varied depending on the period in Bela Vista between 95% in March 2004 and 100% in November 2005. The mortality due to pyrethoids was 100% at all locations, with the kdT50 and KdT95 times ranging between 9 and 16 minutes and between 18 and 29 minutes, respectively. Concerning the C. quinquefasciatus, populations from Yard and Caponte were resistant to all insecticides tested; the mortality rate was 40% with deltamethrin and 70% with permethrin, while no lethal effect was observed with DDT or carbosulfan. In conclusion, despite its probable high resistance to DDT, the main local malaria vector A. gambiae remained fully susceptible to pyrethroids. This could forecast a good biological efficacy of the scheduled vector control interventions in Angola, based on a large-scale distribution of long-lasting, insecticide-treated nets and on the implementation of indoor residual spraying. The local vector control programme must include well-adapted IEC campaigns and full participation of the community for better management of the insecticide resistance in targeted mosquitoes and for better control of malaria vector populations.
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Anopheles , Culex , Insecticidas , Angola , Animales , DDT , Femenino , Insectos Vectores , Resistencia a los Insecticidas , Control de Mosquitos/métodos , PiretrinasRESUMEN
In the megaesophagus of Chagas' disease, chronic esophagitis is caused by stasis of swallowed food and saliva. In this environment, the overgrowth of aerobic and anaerobic bacteria, including nitrate-reducing bacteria, is observed. The reduction of nitrate into nitrite by the action of these bacteria has been associated with the formation of volatile nitrosamines in different situations of gastric bacterial overgrowth. We have hypothesized that this phenomenon could occur in the esophageal lumen of patients with megaesophagus. To evaluate the concentration of nitrite, the presence of volatile nitrosamines and the concentration of nitrate-reducing bacteria in the esophageal lumen of patients with non-advanced megaesophagus of Chagas' disease and in a group of patients without esophageal disease. Fifteen patients with non-advanced megaesophagus [megaesophagus group (MG)] and 15 patients without any esophageal disease [control group (CG)] were studied. Saliva samples were taken for nitrate and nitrite quantitative determination and esophageal stasis liquid samples were taken for nitrate and nitrite quantitative determination, volatile nitrosamines qualitative determination and reductive bacteria quantitative determination. MG and CG were equivalent in nitrate and nitrite saliva concentration and in nitrate esophageal concentration. Significant difference was found in nitrite (p = 0.003) and reductive bacteria concentration (p < 0.0001), both higher in MG. Volatile nitrosamines were identified in three MG patients and in none of the CG patients, but this was not significant (p = 0.113). There is a higher concentration of reductive bacteria in MG, responsible for the rise in nitrite concentration at the esophageal lumen and, eventually, for the formation of volatile nitrosamines.
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Bacterias/aislamiento & purificación , Enfermedad de Chagas/microbiología , Acalasia del Esófago/microbiología , Esófago/microbiología , Nitratos/metabolismo , Nitritos/metabolismo , Adulto , Anciano , Bacterias/metabolismo , Enfermedad de Chagas/complicaciones , Acalasia del Esófago/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nitrosaminas/metabolismo , Saliva/químicaRESUMEN
BACKGROUND: The site and distribution of inflammation in the airways of asthmatic patients has been largely investigated. Inflammatory cells are distributed in both large and small airways in asthma. It has been demonstrated that distal lung inflammation in asthma may significantly contribute to the pathophysiology of the disease. The upper airways have also been implicated in the overall asthmatic inflammation. Although it is now accepted that lung inflammation is not restricted to the intrapulmonary airways in asthma, little is known about cell distribution in the other lung compartments and their relation to the intrapulmonary airways. OBJECTIVE: We aimed to map the inflammatory process in fatal asthma (FA), from the upper airways to the lung parenchyma. METHODS: Eosinophil, neutrophil, mast cell and lymphocyte content were determined in nasal mucosa, the trachea, intrapulmonary airways and parenchyma (peribronchiolar and distal) of 20 patients with FA and 10 controls. RESULTS: Eosinophil content was higher in all studied areas in FA compared with controls (P<0.02). Mast cell content was higher in the outer area of larger airways, small membranous bronchioles and in peribronchiolar parenchyma of FA compared with controls (P<0.04). CD3+, CD4+and CD20+cells showed increased content in FA intrapulmonary airways compared with controls (P<0.05). There was a positive correlation between CD4+cell content in nasal mucosa and larger airways in asthmatics. Increased neutrophil content was observed only in peribronchiolar parenchyma of FA (P=0.028). CONCLUSION: Eosinophils present a widespread distribution within the respiratory tract in FA, from the nasal mucosa to the distal lung. The outer wall of small membranous bronchioles is the main site of inflammatory changes in FA. There is a localized distribution of alveolar inflammation at the peribronchiolar region for mast cells and neutrophils. Our findings provide further evidence of the importance of the lung periphery in the pathophysiology of FA.
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Inflamación/patología , Sistema Respiratorio/patología , Estado Asmático/patología , Adolescente , Adulto , Anciano , Antígenos CD/inmunología , Bronquios/química , Bronquios/inmunología , Bronquios/patología , Recuento de Células , Niño , Eosinófilos/química , Eosinófilos/inmunología , Femenino , Humanos , Inmunohistoquímica/métodos , Inflamación/inmunología , Pulmón/química , Pulmón/inmunología , Pulmón/patología , Linfocitos/química , Linfocitos/inmunología , Masculino , Mastocitos/química , Mastocitos/inmunología , Persona de Mediana Edad , Mucosa Nasal/química , Mucosa Nasal/inmunología , Mucosa Nasal/patología , Neutrófilos/química , Neutrófilos/inmunología , Sistema Respiratorio/inmunología , Estado Asmático/inmunología , Estado Asmático/mortalidad , Tráquea/química , Tráquea/inmunología , Tráquea/patologíaRESUMEN
Two polymerase chain reaction (PCR) protocols showed low sensitivity (36% and 53% for TB AMPLICOR and MPB64 nested PCR, respectively), when compared with classic microbiological methods (73% and 54% for Ziehl-Neelsen staining and culture, respectively), in the diagnosis of tuberculous meningitis in 91 patients in southeastern Brazil. Only three PCR-positive, microbiologically negative patients were found. Analysis of sequential cerebrospinal fluid samples by nested PCR detected Mycobacterium tuberculosis DNA up to 29 days after the introduction of antituberculosis chemotherapy.
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Reacción en Cadena de la Polimerasa , Tuberculosis Meníngea/diagnóstico , Brasil , Humanos , Estudios Prospectivos , Sensibilidad y EspecificidadRESUMEN
A case of asthma due to menthol is reported in a 40-year-old woman with no history of asthma or any other allergy. During the last two years, the patient had presented dyspnea, wheezing and nasal symptoms when exposed to mentholated products such as toothpaste and candies. The etiology was suggested by the history of exposure and diagnosis was established by skin tests and bronchial challenge with menthol. The patient achieved control of symptoms by avoiding menthol and its derivatives.
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Antipruriginosos/efectos adversos , Asma/inducido químicamente , Mentol/efectos adversos , Adulto , Asma/diagnóstico , Pruebas de Provocación Bronquial , Femenino , Humanos , Pruebas CutáneasRESUMEN
BACKGROUND: Among other factors, control of jejunal microflora depends on intestinal emptiness, and it can be impaired by Chagas disease. This study was developed to identify the microecology of the proximal jejunum in chagasic megacolon. Our objective was to characterize both the jejunal microbial stasis before surgery and the microflora after surgical treatment in patients with chagasic megacolon. METHODS: The intestinal fluids were collected, and the proximal jejunum microflora was analyzed. RESULTS: Preoperative microflora had shown an increase in bacteria compatible with bacterial overgrowth syndrome, mainly facultative and strict anaerobes microorganisms and fungi. The microflora had changed in the postoperative period in 83% of these patients, with significant decrease in the number of transient microorganisms. CONCLUSIONS: Chagasic megacolon was related to an increase in jejunal microflora. By removing the impairment of the colon there was a transient decrease in the proximal jejunum microflora.
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Enfermedad de Chagas/complicaciones , Yeyuno/microbiología , Megacolon/microbiología , Adulto , Fenómenos Fisiológicos Bacterianos , Técnicas Bacteriológicas , Enfermedad de Chagas/cirugía , Recuento de Colonia Microbiana , Femenino , Hongos/aislamiento & purificación , Mucosa Gástrica/metabolismo , Humanos , Masculino , Periodo Posoperatorio , Cuidados Preoperatorios , Sensibilidad y EspecificidadRESUMEN
AIMS: The aim of the study was to evaluate some clinicopathologic characteristics and the outcome of patients with ovarian germ cell cancer (OGCC) treated with cisplatin-based chemotherapy. METHODS: It was a clinical retrospective study. The clinical charts of 31 patients with OGCC assisted at the Department of Obstetrics and Gynecology of the State University of Campinas, Brazil, from January 1986 to June 1997 were reviewed. RESULTS: Ten patients had dysgerminoma and 21 patients nondysgerminomatous tumors. Women with dysgerminoma and nondysgerminomatous tumors did not present differences regarding surgical staging, age, ascites or residual tumor after the initial surgery. Frozen section, performed in 16 patients, showed some discrepancy with paraffin histology diagnosis in 8 patients. Platinum-based chemotherapy was used in 5/10 patients with dysgerminoma and in 17/21 patients with nondysgerminomatous tumors, with a 5-year survival of 100% for the dysgerminoma and 53% for the nondysgerminomatous group. CONCLUSIONS: Women with dysgerminoma and nondysgerminomatous tumors did not present differences regarding clinicopathologic characteristics. The prognosis for patients with dysgerminoma was better than for those with nondysgerminomatous tumors. Frozen section had a high error rate in diagnosing OGCC intraoperatively.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Disgerminoma/diagnóstico , Disgerminoma/terapia , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/terapia , Adolescente , Adulto , Biopsia , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Disgerminoma/tratamiento farmacológico , Disgerminoma/patología , Disgerminoma/cirugía , Femenino , Estudios de Seguimiento , Secciones por Congelación , Humanos , Neoplasia Residual , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Pronóstico , Reoperación , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
The activity of important glycolytic enzymes (hexokinase, phosphofructokinase, aldolase, phosphohexoseisomerase, pyruvate kinase and lactate dehydrogenase) and glutaminolytic enzymes (phosphate-dependent glutaminase) was determined in the thymus and mesenteric lymph nodes of Wistar rats submitted to protein malnutrition (6% protein in the diet rather than 20%) from conception to 12 weeks after birth. The wet weight (g) of the thymus and mesenteric lymph nodes decreased due to protein malnutrition by 87% (from 0.30 +/- 0.05 to 0.04 +/- 0.01) and 75% (0.40 +/- 0.04 to 0.10 +/- 0.02), respectively. The protein content was reduced only in the thymus from 102.3 +/- 4.4 (control rats) to 72.6 +/- 6.6 (malnourished rats). The glycolytic enzymes were not affected by protein malnutrition, but the glutaminase activity of the thymus and lymph nodes was reduced by half in protein-malnourished rats as compared to controls. This fact may lead to a decrease in the cellularity of the organ and thus in its size, weight and protein content.
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Glucosa/metabolismo , Glutamina/metabolismo , Glucólisis/fisiología , Ganglios Linfáticos/enzimología , Desnutrición Proteico-Calórica/enzimología , Timo/enzimología , Animales , Proteínas en la Dieta/metabolismo , Fructosa-Bifosfato Aldolasa/metabolismo , Glucosa-6-Fosfato Isomerasa/metabolismo , Glutaminasa/metabolismo , Hexoquinasa/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Masculino , Fosfofructoquinasa-1/metabolismo , Piruvato Quinasa/metabolismo , Ratas , Ratas WistarRESUMEN
We describe herein the expression of the VLA6 complex by murine thymic epithelial cells (TEC). The immunohistochemical distribution revealed that VLA6 is found in both thymic medullary and subcapsullary areas. Moreover, studies by immunoelectron microscopy revealed a membrane labeling of the VLA6 molecule, including at desmosomal sites. By means of immunoblotting, immunoprecipitation, and affinity chromatography of extracts from a mouse TEC line, we further demonstrated that VLA6 is a laminin (LN) receptor in these cells. In keeping with this finding, we showed that TEC adhesion, spreading, and proliferation were enhanced in vitro by LN. The fact that VLA6 is also expressed by the large majority of thymocytes raised the hypothesis that it might be involved in LN-mediated TEC-thymocyte interactions. Interestingly, in vitro experiments showed that there is an increase in the TEC-thymocyte adhesion upon glucocorticoid hormone treatment, a situation in which the expression of VLA6 as well as LN is enhanced. Most importantly, this adhesion can be reversed by pre-treating TEC with an anti-alpha 6 integrin mAb. Additionally, spontaneous in vitro thymocyte release by thymic nurse cell complexes was enhanced by LN and partially blocked by anti-alpha 6 or anti-beta 1 antibodies. Our results suggest that VLA6 is involved in LN-mediated TEC-thymocyte interactions that can be relevant for thymic microenvironmental cell physiology and intrathymic T cell differentiation events.
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Desmosomas/ultraestructura , Laminina/fisiología , Receptores de Antígeno muy Tardío/inmunología , Linfocitos T/inmunología , Timo/inmunología , Animales , Anticuerpos Monoclonales , Adhesión Celular , División Celular , Línea Celular , Cromatografía de Afinidad , Células Epiteliales , Femenino , Citometría de Flujo , Integrinas/análisis , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Microscopía Inmunoelectrónica , Pruebas de Precipitina , Timo/citologíaRESUMEN
Thymic epithelial cell physiology is known to be under neuroendocrine control. In particular, thyroid hormones modulate thymic hormone secretion by thymic epithelial cells in vivo and in vitro, thus suggesting the existence of specific receptors for those hormones in this component of the thymic microenvironment. Yet, thyroid hormone-binding sites have previously been detected only in crude thymus fractions and lymphocytes. We, thus, decided to search for T3 receptors in the thymic epithelium, by using an antinuclear T3 receptor monoclonal antibody. In situ immunohistochemical analysis of thymic frozen sections showed nuclear labeling of both lymphoid and nonlymphoid cells in the cortex and medulla. Moreover, in vitro studies using thymic epithelial cell lines and the so-called thymic nurse cells revealed a positive reaction in the chromatin, with nucleoli remaining negative. Immunoblot data clearly showed a single protein band of 57K reactive with the antinuclear T3 receptor antibody in murine thymus extracts as well as in the thymic epithelial cell lines. Lastly, in vitro treatment of these cells with T3 resulted in a transient, yet profound, down-modulation of the receptor. In conclusion, our findings provide molecular evidence that the action of thyroid hormones on thymic epithelium occurs via the typical 57K nuclear T3 receptors.