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1.
J R Soc Interface ; 16(153): 20190035, 2019 04 26.
Artículo en Inglés | MEDLINE | ID: mdl-31014202

RESUMEN

The halteres of flies are mechanosensory organs that serve a crucial role in the control of agile flight, providing sensory input for rapid course corrections to perturbations. Derived from hind wings, halteres are actively flapped and are thus subject to a variety of inertial forces as the fly undergoes complex flight trajectories. Previous analyses of halteres modelled them as a point mass, showing that Coriolis forces lead to subtle deflections orthogonal to the plane of flapping. By design, these models could not consider the effects of force gradients associated with a mass distribution, nor could they reveal three-dimensional spatio-temporal patterns of strain that result from those forces. In addition, diversity in the geometry of halteres, such as shape and asymmetries, could not be simply modelled with a point mass on a massless rod. To study the effects of mass distributions and asymmetries, we examine the haltere subject to both flapping and body rotations using three-dimensional finite-element simulations. We focus on a set of simplified geometries, in which we vary the stalk and bulb shape. We find that haltere mass distribution gives rise to two unreported deformation modes: (i) halteres twist with a magnitude that strongly depends on stalk and bulb geometry and (ii) halteres with an asymmetric mass distribution experience out-of-plane bending due to centrifugal forces, independent of body rotation. Since local strains at the base of the haltere drive deformations of mechanosensory neurons, we combined measured neural encoding mechanisms with our structural analyses to predict the spatial and temporal patterns of neural activity. This activity depends on both the flapping and rotation dynamics, and we show how the timing of neural activity is a viable mechanism for rotation-rate encoding. Our results provide new insights in haltere dynamics and show the viability for timing-based encoding of fly body rotations by halteres.


Asunto(s)
Dípteros/anatomía & histología , Vuelo Animal/fisiología , Mecanorreceptores , Alas de Animales/fisiología , Animales , Fenómenos Biomecánicos , Modelos Biológicos
2.
Br J Dermatol ; 174(4): 778-85, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26676514

RESUMEN

BACKGROUND: Nonmelanoma skin cancer (NMSC) is the most common cancer in Germany, but detailed information on survival is lacking. OBJECTIVES: To provide survival estimates for female and male patients with basal cell carcinoma (BCC), squamous cell carcinoma (SCC), sarcoma, adenocarcinoma and Merkel cell carcinoma. Further subgroup analyses were carried out by age, tumour stage and body site. METHODS: In total 459 640 patients diagnosed with NMSC in 1997-2011 were included from population-based cancer registers, covering a population of 33 million inhabitants. Age-standardized absolute and relative 5-year and 10-year survival were calculated using period analysis. RESULTS: The absolute and relative 5-year survival were 87·1% and 102·9% for BCC, 77·6% and 93·6% for SCC, 82·1% and 96·0% for sarcoma, 71·4% and 85·7% for adenocarcinoma and 60·0% and 70·7% for Merkel cell carcinoma, respectively. Higher age, female sex and advanced stage were associated with lower survival. CONCLUSIONS: A comprehensive overview of NMSC survival in Germany is provided. The differences between the NMSC subtypes require a more differentiated consideration of patient survival. The survival advantage of patients with BCC may be related to health-promoting factors related to the BCC diagnosis, such as changes to a healthier lifestyle.


Asunto(s)
Neoplasias Cutáneas/mortalidad , Adenocarcinoma/mortalidad , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Carcinoma Basocelular/mortalidad , Carcinoma de Células de Merkel/mortalidad , Femenino , Alemania/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Sarcoma/mortalidad , Distribución por Sexo , Análisis de Supervivencia , Adulto Joven
3.
J R Soc Interface ; 12(104): 20141088, 2015 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-25631565

RESUMEN

Insects perform fast rotational manoeuvres during flight. While two insect orders use flapping halteres (specialized organs evolved from wings) to detect body dynamics, it is unknown how other insects detect rotational motions. Like halteres, insect wings experience gyroscopic forces when they are flapped and rotated and recent evidence suggests that wings might indeed mediate reflexes to body rotations. But, can gyroscopic forces be detected using only changes in the structural dynamics of a flapping, flexing insect wing? We built computational and robotic models to rotate a flapping wing about an axis orthogonal to flapping. We recorded high-speed video of the model wing, which had a flexural stiffness similar to the wing of the Manduca sexta hawkmoth, while flapping it at the wingbeat frequency of Manduca (25 Hz). We compared the three-dimensional structural dynamics of the wing with and without a 3 Hz, 10° rotation about the yaw axis. Our computational model revealed that body rotation induces a new dynamic mode: torsion. We verified our result by measuring wing tip displacement, shear strain and normal strain of the robotic wing. The strains we observed could stimulate an insect's mechanoreceptors and trigger reflexive responses to body rotations.


Asunto(s)
Alas de Animales/fisiología , Animales , Fenómenos Biomecánicos , Simulación por Computador , Vuelo Animal/fisiología , Insectos/fisiología , Manduca , Modelos Biológicos , Movimiento , Oscilometría , Rango del Movimiento Articular , Robótica , Rotación , Resistencia al Corte , Estrés Mecánico
4.
J Microsc ; 259(2): 114-120, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25627873

RESUMEN

Electron-electron interactions and detector bandwidth limit the maximal imaging speed of single-beam scanning electron microscopes. We use multiple electron beams in a single column and detect secondary electrons in parallel to increase the imaging speed by close to two orders of magnitude and demonstrate imaging for a variety of samples ranging from biological brain tissue to semiconductor wafers.


Asunto(s)
Microscopía Electrónica de Rastreo/instrumentación , Microscopía Electrónica de Rastreo/métodos , Animales , Encéfalo/ultraestructura , Electrones , Ratones , Semiconductores
5.
Bioinspir Biomim ; 9(2): 025005, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24855064

RESUMEN

Insect wings deform significantly during flight. As a result, wings act as aeroelastic structures wherein both the driving motion of the structure and the aerodynamic loading of the surrounding fluid potentially interact to modify wing shape. We explore two key issues associated with the design of compliant wings: over a range of driving frequencies and phases of pitch-heave actuation, how does wing stiffness influence (1) the lift and thrust generated and (2) the relative importance of fluid loading on the shape of the wing? In order to examine a wide range of parameters relevant to insect flight, we develop a computationally efficient, two-dimensional model that couples point vortex methods for fluid force computations with structural finite element methods to model the fluid-structure interaction of a wing in air. We vary the actuation frequency, phase of actuation, and flexural stiffness over a range that encompasses values measured for a number of insect taxa (10-90 Hz; 0-π rad; 10(-7)-10(-5) N m(2)). We show that the coefficients of lift and thrust are maximized at the first and second structural resonant frequencies of the system. We also show that even in regions of structural resonance, fluid loading never contributes more than 20% to the development of flight forces.


Asunto(s)
Biomimética/métodos , Vuelo Animal/fisiología , Insectos/fisiología , Modelos Biológicos , Reología/métodos , Alas de Animales/fisiología , Animales , Simulación por Computador , Módulo de Elasticidad/fisiología , Retroalimentación Fisiológica/fisiología , Fricción , Estrés Mecánico
6.
Cancer Epidemiol ; 37(4): 492-7, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23623488

RESUMEN

INTRODUCTION: The aim of this study was to provide detailed age-specific (5-year age groups) and histology-specific (histologic subtypes of seminoma and nonseminoma) relative survival estimates of testicular germ cell cancer patients in Germany and the United States (U.S.) for the years 2002-2006 and to compare these estimates between countries. METHODS: We pooled data from 11 cancer registries of Germany and used data from the U.S. (SEER-13 database) including 11,508 and 10,774 newly diagnosed cases (1997-2006) in Germany and the U.S., respectively. We estimated 5-year relative survival (5-year-RS) by histology and age based on period analysis. RESULTS: 5-year-RS for testicular germ cell tumors was 96.7% and 96.3% in Germany and the U.S., respectively. 5-Year-RS for spermatocytic seminoma was close to 100% in both countries. 5-Year-RS for nonseminoma was lower than for classical seminoma in Germany (93.3% versus 97.6%) and the U.S. (91.0% versus 98.2%). Among nonseminomas, choriocarcinomas provided the lowest 5-year-RS in both countries (Germany 80.1%, U.S. 79.6%). Age-specific 5-year-RS for seminoma showed only little variation by age. 5-Year-RS for nonseminomas tended to be lower at higher ages, especially for malignant teratoma. DISCUSSION: This is the first study that provides up-to-date survival estimates for testicular cancer by histology and age in Germany and the U.S. Survival after a diagnosis of testicular cancer is very comparable between Germany and the U.S. 5-Year-RS for spermatocytic seminoma was close to 100% and the lowest 5-year-RS occurred among choriocarcinoma. Higher age at diagnosis is associated with a poorer prognosis among nonseminoma patients.


Asunto(s)
Neoplasias de Células Germinales y Embrionarias/epidemiología , Seminoma/epidemiología , Neoplasias Testiculares/epidemiología , Adolescente , Adulto , Factores de Edad , Coriocarcinoma/epidemiología , Coriocarcinoma/patología , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de Células Germinales y Embrionarias/patología , Pronóstico , Sistema de Registros , Programa de VERF , Seminoma/patología , Espermatocitos/patología , Tasa de Supervivencia , Teratoma/epidemiología , Teratoma/patología , Neoplasias Testiculares/patología , Estados Unidos/epidemiología , Adulto Joven
7.
Gesundheitswesen ; 75(2): 94-8, 2013 Feb.
Artículo en Alemán | MEDLINE | ID: mdl-22581626

RESUMEN

BACKGROUND: The results of population-based cancer survival analyses are essential criteria with regard to the evaluation of oncological care. Their use and their interpretation as such require knowledge and transparency with regard to the data basis in order to avoid inadequate conclusions. METHOD: The working group 'survival analysis' of the Association of Population-Based Cancer Registries in Germany (GEKID) has identified factors within cancer registration and data evaluation which may distort population-based cancer survival analyses to a relevant degree. Recommendations in terms of standards of reporting were developed by mutual consent following empirical studies and discussions within GEKID. RESULTS: We provide a list of 17 indicators to be taken into account and to be presented within the scope of population-based survival analyses. CONCLUSIONS: Referring to the "standards of reporting concerning population-based cancer survival analyses" introduced by GEKID there is a proposal on data transparency on hand, which might contribute substantially to the assessability of outcome quality in oncological care.


Asunto(s)
Adhesión a Directriz/estadística & datos numéricos , Notificación Obligatoria , Neoplasias/mortalidad , Neoplasias/terapia , Guías de Práctica Clínica como Asunto , Sistema de Registros/normas , Análisis de Supervivencia , Interpretación Estadística de Datos , Alemania/epidemiología , Humanos , Prevalencia , Sistema de Registros/estadística & datos numéricos , Tasa de Supervivencia , Resultado del Tratamiento
8.
Cancer Epidemiol ; 36(5): 417-20, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22677151

RESUMEN

BACKGROUND: In 2002, colonoscopy was introduced as a tool for colorectal cancer screening in Germany. The long-term objective was to reduce the incidence in colorectal cancer (CRC) by detection and removal of advanced adenomas. Currently, the effect of colonoscopy screening on the population-based incidence of CRC in Germany is unknown. METHODS: We provide data on stage-specific (age-standardized) incidence rates in three federal states in Germany, 6 years after the implementation of colonoscopy. RESULTS: Between 2002 and 2008 a statistically significant decrease in CRC incidence could be observed (annually 3.0%, 95% confidence interval [CI]: -3.8; -2.2). The decline could be observed in all advanced tumor categories (T2, T3, and T4), whereas the incidence of in situ carcinomas (Tis) increased annually by 51.6% (95% CI: 28.0; 79.4) until 2004, and remained stable until 2008. CONCLUSION: The observed changes cannot be attributed definitively to the screening activities, but the presented data support a possible causal association.


Asunto(s)
Colonoscopía/estadística & datos numéricos , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/prevención & control , Implementación de Plan de Salud/estadística & datos numéricos , Tamizaje Masivo/organización & administración , Tamizaje Masivo/estadística & datos numéricos , Distribución por Edad , Anciano , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/epidemiología , Carcinoma in Situ/patología , Carcinoma in Situ/prevención & control , Neoplasias Colorrectales/diagnóstico , Detección Precoz del Cáncer/estadística & datos numéricos , Femenino , Alemania/epidemiología , Humanos , Incidencia , Masculino , Estadificación de Neoplasias , Distribución por Sexo
9.
Anal Biochem ; 426(2): 147-52, 2012 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-22543092

RESUMEN

Chromatin immunoprecipitation (ChIP) is an analytical method used to investigate the interactions between proteins and DNA in vivo. ChIP is often used as a quantitative tool, and proper quantification relies on the use of adequate references for data normalization. However, many ChIP experiments involve analyses of samples that have been submitted to experimental treatments with unknown effects, and this precludes the choice of suitable internal references. We have developed a normalization method based on the use of a synthetic DNA-antibody complex that can be used as an external reference instead. A fixed amount of this synthetic DNA-antibody complex is spiked into the chromatin extract at the beginning of the ChIP experiment. The DNA-antibody complex is isolated together with the sample of interest, and the amounts of synthetic DNA recovered in each tube are measured at the end of the process. The yield of synthetic DNA recovery in each sample is then used to normalize the results obtained with the antibodies of interest. Using this approach, we could compensate for losses of material, reduce the variability between ChIP replicates, and increase the accuracy and statistical resolution of the data.


Asunto(s)
Anticuerpos/química , Inmunoprecipitación de Cromatina , Cromatina/metabolismo , ADN/química , Animales , Anticuerpos/inmunología , Cromatina/inmunología , Inmunoprecipitación de Cromatina/normas , Digoxigenina/química , Drosophila/metabolismo , Células HeLa , Histonas/inmunología , Histonas/metabolismo , Humanos , Estándares de Referencia
10.
Br J Cancer ; 106(11): 1875-80, 2012 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-22555397

RESUMEN

BACKGROUND: Colorectal cancer is the most common cancer in Germany and the second most common cause of cancer-related deaths in both men and women. The aim of this study is to provide detailed analysis of recent developments in survival of colorectal cancer patients using newly available data on a national basis. METHODS: We included data from 11 German cancer registries covering a population of 33 million inhabitants. Period analysis and modelled period analysis were used to provide most up-to-date estimates of 5-year relative survival in 2002-2006. RESULTS: The analysis was based on records of 164 996 colorectal cancer patients. Five-year relative survival was 63.0% overall, decreased with age and was significantly higher among women than among men in patients under 75 years. Overall age-adjusted 5-year relative survival increased from 60.6 to 65.0% over the period 2002-2006. Significant increase in survival was only observed in patients with localised or regional disease. Highest subsite-specific survival was observed in patients with cancer in descending (67.7%) and ascending (66.5%) colon. CONCLUSION: Survival of patients with colorectal cancer continued to increase in the early 21st century in Germany, with 5-year relative survival reaching 65% in 2006. However, lack of progress still persisted in patients with advanced disease.


Asunto(s)
Carcinoma/mortalidad , Carcinoma/patología , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Adolescente , Adulto , Distribución por Edad , Anciano , Femenino , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros , Análisis de Supervivencia , Adulto Joven
11.
Z Gastroenterol ; 48(12): 1358-66, 2010 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-21125511

RESUMEN

BACKGROUND: A quality assured colonoscopy screening was implemented in Germany in the year 2002. Persons aged 55 years or older with a health insurance are eligible. The primary aim of colonoscopy screening is the early detection of cancer. Furthermore, an incidence decrease is expected due to systematic adenomectomy. Up to date, neither a systematic monitoring of epidemiological data nor a mortality evaluation has been contracted by law. MATERIALS AND METHODS: Four population-based cancer registries of the federal states Bremen, Hamburg, Saarland, and Schleswig-Holstein in Germany provided incidence data on colorectal cancers during 2000 - 2006. Age-standardised and stage-specific incidence rates and time trends (Joinpoint analysis and APC method) are reported. RESULTS: Overall 34,100 colorectal cancers were registered, of which 91 % were within the screening-eligible age group. The incidence rise of in situ-cancers of the colon and rectum was significant. Changes in tumours of the T 3- and T 4-categories were not consistent. DISCUSSION: There seems to be a temporal linkage between the implementation of a quality assured colonoscopy screening and the epidemiology of colorectal cancers in Germany. The observed changes cannot be attributed definitively to the screening activities, because required data are not available on the population level. A linkage of screenees and cancer data from registered tumour patients, which allows an individual follow-up and a mortality evaluation, would be desirable.


Asunto(s)
Colonoscopía/estadística & datos numéricos , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/prevención & control , Tamizaje Masivo/estadística & datos numéricos , Adulto , Anciano , Carcinoma in Situ/epidemiología , Carcinoma in Situ/mortalidad , Carcinoma in Situ/patología , Carcinoma in Situ/prevención & control , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Estudios Transversales , Diagnóstico Precoz , Femenino , Alemania , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Vigilancia de la Población , Sistema de Registros , Tasa de Supervivencia , Revisión de Utilización de Recursos/tendencias
12.
Gesundheitswesen ; 72(10): 692-9, 2010 Oct.
Artículo en Alemán | MEDLINE | ID: mdl-20049680

RESUMEN

Cancer is an important issue within the German health care system with an estimated annual number of 435 000 incident cases and almost 210 000 deaths. Data of population-based cancer registries enable us to identify improvements of survival in oncological patients due to progress in therapeutic care and secondary prevention, as well as to investigate regional and international differences of this outcome. Comparing cancer survival rates, however, requires considering the impact of both methodical approaches and data quality. Potential factors of influence like algorithms, reference population, completeness of case ascertainment and quality of follow-up are discussed. For the first time harmonized proceedings are recommended in order to achieve comparability of population-based cancer survival rates in Germany.


Asunto(s)
Neoplasias/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Causas de Muerte , Comparación Transcultural , Recolección de Datos/estadística & datos numéricos , Femenino , Humanos , Incidencia , Masculino , Cómputos Matemáticos , Persona de Mediana Edad , Programas Nacionales de Salud/estadística & datos numéricos , Sistema de Registros , Programas Informáticos , Análisis de Supervivencia , Adulto Joven
13.
Gesundheitswesen ; 67(10): 729-35, 2005 Oct.
Artículo en Alemán | MEDLINE | ID: mdl-16235142

RESUMEN

PURPOSE: To exclude bias of registration evidenced by relevant differences among German cancer registries in the incidence of malignant melanoma (melanocarcinoma). METHODS: Cancer registries in the Federal German states of Hamburg, Schleswig-Holstein, Bremen, Rhineland-Palatinate, Saarland, the Munich District and the County of Münster featured registration data of malignant melanoma diagnosed in 2000 A. D. Figures and incidence rates, distribution of T-stage of the primary tumour were analysed as well as the distribution of sources reporting melanoma to the registries. Details of outpatient treatment of cutaneous melanoma by dermatologists in private practice were investigated. RESULTS: Data of 2,471 malignant melanoma cases were analysed. The highest age standardised incidence rates were 15.7 per 100,000 women and 19 per 100,000 men while the lowest rates were reported as 7.8 and 6.6 per 100,000, respectively (European standard). The proportion of stage T1 tumours varied between 21.5 and 59.2 %. We observed remarkable variations in the structure of reporting sources among the registries. The proportion of reports from dermatologists in private practice varied between 2.2 and 62 %, with higher proportions associated with more T1-T2 tumours but also lower completeness of stage reports. No clear association was identified between incidence of melanoma and reporting sources. CONCLUSION: Malignant melanomas of smaller size (T1-T2) are reported more frequently in an outpatient setting but very often without data. Hospital departments of dermatology contribute high-quality data with better completeness especially for later stage melanomas. Desirable inclusion of notifications from nationwide operating dermatopathology laboratories is complicated by the Federal German structure of cancer registration. Especially in case of malignant melanoma of the skin notification reports from all sectors of the health care system are imperative for valid epidemiological results.


Asunto(s)
Melanoma/epidemiología , Sistema de Registros , Neoplasias Cutáneas/epidemiología , Estudios de Cohortes , Femenino , Alemania/epidemiología , Humanos , Masculino , Melanoma/mortalidad , Factores Sexuales , Neoplasias Cutáneas/mortalidad
14.
J Recept Signal Transduct Res ; 21(1): 25-45, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11693171

RESUMEN

Antagonist and agonist activities of chemically synthetized mouse agouti protein fragment (91-131) (AP91-131) at the melanocortin type-1 receptor (MC1-R) were assessed using B 16-F1 mouse melanoma cells in vitro and the following assay systems: (i) receptor binding, (ii) adenylate cyclase, (iii) tyrosinase, (iv) melanin production, and (v) cell proliferation. In competition binding studies AP91-131 was about 3-fold less potent than the natural agonist alpha-melanocyte-stimulating hormone (alpha-MSH) in displacing the radioligand [125I]-[Nle4, D-Phe7]-alpha-MSH (Ki 6.5 +/- 0.8 nmol/l). Alpha-MSH-induced tyrosinase activation and melanin production were completely inhibited by a 100-fold higher concentration of AP9 l -131; the IC50 values for AP91-131 in thetwo assay systems were 91 +/- 22 nM and 95 +/- 15 nM respectively. Basal melanin production and adenylate cyclase activity in the absence of agonist were decreased by AP91-131 with IC50 values of 9.6+/-1.8 nM and 5.0+/-2.4 nM, respectively. This indicates inverse agonist activity of AP91-131 similar to that of native AP. The presence of 10 nM melanin-concentrating hormone (MCH) slightly potentiated the inhibitory activity of AP91-131 in the adenylate cyclase and melanin assays. On the other hand, AP91-131 inhibited cell growth similar to alpha-MSH (IC50 11.0 +/- 2.1 nM; maximal inhibition 1.8-fold higher than that of alpha-MSH). Furthermore, MC1-R was down-regulated by AP91-131 with about the same potency and time-course as with alpha-MSH. These results demonstrate that AP91-131 displays both agonist and antagonist activities at the MC1-R and hence that it is the cysteine-rich region of agouti protein which inhibits and mimics the different alpha-MSH functions, most likely by simultaneous modulation of different intracellular signalling pathways.


Asunto(s)
Péptidos y Proteínas de Señalización Intercelular , Fragmentos de Péptidos/farmacología , Proteínas/farmacología , Receptores de Corticotropina/agonistas , Receptores de Corticotropina/antagonistas & inhibidores , Adenilil Ciclasas/metabolismo , Proteína de Señalización Agouti , Secuencia de Aminoácidos , Animales , Unión Competitiva , División Celular/efectos de los fármacos , Cinética , Ligandos , Melaninas/biosíntesis , Melanoma Experimental/metabolismo , Melanoma Experimental/patología , Ratones , Datos de Secuencia Molecular , Monofenol Monooxigenasa/metabolismo , Fragmentos de Péptidos/síntesis química , Fragmentos de Péptidos/metabolismo , Proteínas/síntesis química , Proteínas/metabolismo , Receptores de Corticotropina/metabolismo , Receptores de Melanocortina , Células Tumorales Cultivadas , alfa-MSH/agonistas , alfa-MSH/antagonistas & inhibidores , alfa-MSH/metabolismo
15.
J Recept Signal Transduct Res ; 21(1): 93-116, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11693176

RESUMEN

Melanin-concentrating hormone (MCH) and alpha-melanocyte-stimulating hormone (alpha-MSH) are known to exhibit mostly functionally antagonistic, but in some cases agonistic activities, e.g., in pigment cells and in the brain. Neuropeptide E-I (NEI) displays functional MCH-antagonist and MSH-agonist activity in different behavioral paradigms; the role of neuropeptide G-E (NGE) is not known. This study addressed the question of possible molecular interactions between alpha-MSH, MCH and the MCH-precursor-derived peptides NEI and NGE at the level of the pigment cell MCH receptor subtype (MCH-Rpc) and the different melanocortin (MC) receptors. Radioreceptor assays using [125I]MCH, [125l]alpha-MSH and [125I]NEI as radioligands and bioassays were performed with MCI-R-positive and MC1-R-negative mouse B16 melanoma cells and with COS cells expressing the different MC receptors. The IC50s of alpha-MSH and NEI or NGE for [125I]MCH displacement from mouse MCH-Rpc were 80-fold and, respectively, >300-fold higher than that of MCH, and the IC50s for MCH and NEI or NGE for [125I]alpha-MSH displacement from mouse MC1-R were 50,000-fold and >200,000-fold higher than that of alpha-MSH. No high-affinity binding sites for NEI were detected on B16 melanoma cells and there was no significant displacement of [1251]alpha-MSH by MCH, NEI or NGE with MC3-R, MC4-R and MC5-R expressed in COS cells. At concentrations of 100 nM to 10 microM, however, MCH, NEI and NGE induced cAMP formation and melanin synthesis which could be blocked by agouti protein or inhibitors of adenylate cyclase or protein kinase A. This shows that mammalian MCH-precursor-derived peptides may mimic MSH signalling via MC1-R activation at relatively high, but physiologically still relevant concentrations, as e.g. found in autocrine/paracrine signalling mechanisms.


Asunto(s)
Hormonas Hipotalámicas/metabolismo , Melaninas/metabolismo , Oligopéptidos/metabolismo , Fragmentos de Péptidos/metabolismo , Hormonas Hipofisarias/metabolismo , Receptor de Melanocortina Tipo 3 , Receptores de Corticotropina/metabolismo , Receptores de la Hormona Hipofisaria/metabolismo , alfa-MSH/metabolismo , Animales , Unión Competitiva , Células COS , Expresión Génica , Humanos , Cinética , Melaninas/biosíntesis , Melanoma Experimental/metabolismo , Ratones , Ensayo de Unión Radioligante , Receptores de Corticotropina/clasificación , Receptores de Corticotropina/genética , Receptores de Melanocortina , Receptores de la Hormona Hipofisaria/clasificación , Receptores de la Hormona Hipofisaria/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transducción de Señal , Células Tumorales Cultivadas
16.
Epilepsia ; 42(3): 295-304, 2001 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11442143

RESUMEN

Recent studies by Isojärvi et al. have raised the issue of an increased incidence of polycystic ovary syndrome (PCOS) in women with epilepsy treated with valproate (VPA) and have proposed replacement with lamotrigine (LTG). Polycystic ovaries (PCO) are a common finding, with a prevalence >20% in the general population, and are easily detected by pelvic or vaginal ultrasonography, whereas PCOS is comparatively rare: few women with PCO have fully developed PCOS, which includes hirsutism, acne, obesity, hypofertility. hyperandrogenemia, and menstrual disorders. From an extensive review of the current literature, it appears that there are no reliable data on the actual prevalence of PCOS in normal women and in women with epilepsy. The pathogenesis of PCO is multifactorial, including genetic predisposition and the intervention of environmental factors, among which weight gain and hyperinsulinism with insulin resistance may play a part. The roles of central (hypothalamic/pituitary), peripheral, and local ovarian factors are still debated. PCO and PCOS appear to be more frequent in women with epilepsy, but there are no reliable data showing a greater prevalence after VPA. The recent studies by Isojärvi et al. may have been biased by the retrospective selection of patients. To date, there is no reason to contraindicate the use of VPA in women with epilepsy. However, patients should be informed about the risk of weight gain and its consequences.


Asunto(s)
Anticonvulsivantes/efectos adversos , Epilepsia/tratamiento farmacológico , Síndrome del Ovario Poliquístico/inducido químicamente , Ácido Valproico/efectos adversos , Adolescente , Adulto , Anticonvulsivantes/uso terapéutico , Comorbilidad , Epilepsia/epidemiología , Femenino , Humanos , Hiperinsulinismo/epidemiología , Resistencia a la Insulina , Persona de Mediana Edad , Síndrome del Ovario Poliquístico/epidemiología , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina , Prevalencia , Ácido Valproico/uso terapéutico
17.
Klin Monbl Augenheilkd ; 218(5): 363-5, 2001 May.
Artículo en Inglés | MEDLINE | ID: mdl-11417337

RESUMEN

PURPOSE: The present study investigates whether beta-adrenoreceptor agents such as isoproterenol and propranolol can regulate Na(+)-K(+)-ATPase activity in cultured human non-pigmented ciliary epithelial cells. METHODS: Human non-pigmented ciliary epithelial cells (ODM2) were grown to confluence. The active ion transport mediated by the Na(+)-K(+)-ATPase was evaluated by measuring ouabain-sensitive rubidium (Rb+) uptake. In a first set of experiments, cells were exposed to the beta-adrenoreceptor agonist isoproterenol (0.01-10 microM). In a second set of experiments, cells were exposed to isoproterenol (1 microM) in the presence of different concentrations of the beta-adrenoreceptor antagonist propranolol (0.01, 0.1, 1 microM). RESULTS: In a concentration-dependent manner, isoproterenol induced an increase in Na(+)-K(+)-ATPase activity. The maximal Na(+)-K(+)-ATPase activity was observed at a concentration of 1 microM of isoproterenol (283 +/- 58%, P < 0.001). The increase in Na(+)-K(+)-ATPase activity evoked by isoproterenol (1 microM) was inhibited. In a concentration dependent manner, by propranolol (maximum: 659 +/- 39 vs. 141 +/- 42 pM/mg protein/min, P < 0.01). CONCLUSION: The beta-adrenoreceptor agents isoproterenol and propranolol are apparently able to modulate Na(+)-K(+)-ATPase activity in cultured human non-pigmented ciliary epithelial cells.


Asunto(s)
Agonistas Adrenérgicos beta/farmacología , Antagonistas Adrenérgicos beta/farmacología , Cuerpo Ciliar/enzimología , Isoproterenol/farmacología , Epitelio Pigmentado Ocular/enzimología , Propranolol/farmacología , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Línea Celular Transformada , Células Cultivadas , Relación Dosis-Respuesta a Droga , Humanos
18.
Anticancer Res ; 21(1A): 71-5, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11299792

RESUMEN

BACKGROUND: TT-232, a somatostatin analogue, induces apoptosis in various tumours. The aim of our study was to characterise its effect on human melanoma cells and tumours. MATERIALS AND METHODS: Proliferation of seven melanoma cell lines was tested in vitro with the methylene blue test. D10 and 205 cells were also implanted into CB17-scid mice which received 30-150-750 micrograms/kg/day of TT-232 or saline. Animals with 205 cells received twice-daily subcutaneous injections whereas animals with D10 cells were treated with osmotic mini-pumps. In addition, TT-232 metabolites were generated with tissue homogenates and tested in vitro. RESULTS: TT-232 strongly inhibited proliferation of all cell lines in vitro and tumour growth in vivo. Two out of 8 animals (30-150 micrograms/kg) in the 205 model and one out of 8(150 micrograms/kg) in the D10 model became completely tumour-free at the 11th and 9th day of treatment, respectively. TT-232 was degraded only by liver homogenate whilst its metabolite had no antiproliferative effect in vitro. CONCLUSIONS: TT-232 is a promising drug candidate for melanoma.


Asunto(s)
Antineoplásicos/uso terapéutico , Melanoma/tratamiento farmacológico , Melanoma/patología , Péptidos Cíclicos/uso terapéutico , Somatostatina/análogos & derivados , Animales , Antineoplásicos/farmacocinética , Antineoplásicos/farmacología , División Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Ratones , Ratones SCID , Péptidos Cíclicos/farmacocinética , Péptidos Cíclicos/farmacología , Células Tumorales Cultivadas
19.
Invest Ophthalmol Vis Sci ; 42(1): 206-9, 2001 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11133869

RESUMEN

PURPOSE: To evaluate whether the receptors for melanin-concentrating hormone (MCH) and its functional antagonist alpha-melanocyte-stimulating hormone (alpha-MSH) are expressed in the ciliary epithelium. Furthermore, to examine whether MCH, a neuropeptide involved in fluid and electrolyte homeostasis, may influence ion flux mediated by Na,K (adenosine triphosphatase)-ATPase in a ciliary epithelial cell line. METHODS: Expression of MCH receptors (MCH-R) and alpha-MSH receptors (MSH-R) on primary porcine ciliary pigmented epithelial (PE) cells and on a human nonpigmented ciliary epithelial (NPE) cell line, ODM-2 was investigated by radioligand binding studies and reverse transcription-polymerase chain reaction (RT-PCR). The MCH-R was further characterized by photocrosslinking. Influence of MCH on Na, K-ATPase activity was evaluated by an Rb(+) transport assay. RESULTS: MCH-R expression was observed at both the mRNA and protein levels in PE and NPE cells. In contrast, MSH-Rs were not detectable. At the mRNA level, expression of slc-1 was shown and with crosslinking, a 44-kDa protein was labeled. MCH showed no effect on Na,K-ATPase activity of NPE cells. CONCLUSIONS: The presence of MCH-R in ciliary epithelial cells of both human and porcine origin but the absence of MSH-Rs indicates that in these cells, MCH and alpha-MSH do not form a functionally antagonistic hormonal pair as they do in several other systems. Although effects of MCH on intestinal water and ion transport have been documented, a direct control of Na,K-ATPase activity was not detected in human NPE cells in vitro.


Asunto(s)
Cuerpo Ciliar/metabolismo , Proteínas del Ojo/genética , Epitelio Pigmentado Ocular/metabolismo , ARN Mensajero/biosíntesis , Receptores de la Hormona Hipofisaria/genética , Animales , Unión Competitiva , Línea Celular , Cartilla de ADN/química , Proteínas del Ojo/biosíntesis , Expresión Génica , Proteínas de Unión al GTP Heterotriméricas/metabolismo , Humanos , Ensayo de Unión Radioligante , Receptores de la Hormona Hipofisaria/biosíntesis , Receptores de Somatostatina/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Porcinos , alfa-MSH/biosíntesis , alfa-MSH/genética
20.
Ann Epidemiol ; 10(7): 481, 2000 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-11018431

RESUMEN

PURPOSE: To determine the role of occupational and personal risk factors of carpal tunnel syndrome (CTS) separately in men and women.METHODS: Men (n = 404) and women (n = 404) younger than 65 years with first surgery for CTS in 1995/96 were sampled at random from the Bremen population (0.65 million) and matched to controls by age and gender sampled from the population registry. A self-administered questionnaire with 77 questions inquired about personal factors and activities during work and private environment (response: 60% of eligible cases and 52% in controls, respectively).RESULTS: CTS risk increased with body mass index (BMI): odds ratio for each unit of BMI [kg/m(2)] OR(men) = 1.13; (95%-confidence-limits CL(men) 1.06, 1.20), OR(women) = 1.09 (CL(women) 1.04, 1.14). Multivariate analysis adjusting for BMI showed more pronounced risks in men compared with women for repetitive movements of the hand: OR(m) = 2.89 (CL 1.82, 4.58); OR(w) = 2.10 (CL 1.37, 3.22), for forceful grip: OR(m) = 2.69 (CL 1.70, 4.27); OR(w) = 2.29 (CL 1.43, 3.66), but not for household chores: OR(m) = 0.64 (CL 0.40, 1.03); OR(w) = 0.88 (CL 0.34, 2.29). Women worked less hours per week than men but manual exposures remained more relevant in men after adjustment. Exposure-response-relationships could be demonstrated for all work related exposures. Women were at higher risk for CTS if they had had more than two births or a history of hysterectomy. Adding these factors to the logistic model still showed an association between manual work and CTS. Blinded expert rating (manual vs. non-manual) of jobs held by respondents and non-respondents and by cases and controls did not reveal relevant selection effects or recall-bias.CONCLUSIONS: CTS is a work related disease in both men and women, the fraction attributable to work in the Bremen population under age 65 is estimated to be 33% in men and 15% in women. Funding: German Federal Ministry for Education & Research: 01 EG 9512.

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