RESUMEN
X-ray grating interferometry is a powerful emerging tool in biomedical imaging, providing access to three complementary image modalities. In addition to the conventional attenuation modality, interferometry provides a phase modality, which visualizes soft tissue structures, and a dark-field modality, which relates to the number and size of sub-resolution scattering objects. A particularly strong dark-field signal originates from the alveoli or air sacs in the lung. Dark-field lung radiographs in animal models have already shown increased sensitivity in diagnosing lung diseases, such as lung cancer or emphysema, compared to conventional X-ray chest radiography. However, to date, X-ray dark-field lung imaging has either averaged information over several breaths or has been captured during a breath hold. In this paper, we demonstrate the first time-resolved dark-field imaging of a breath cycle in a mechanically ventilated mouse, in vivo, which was obtained using a grating interferometer. We achieved a time resolution of 0.1 s, visualizing the changes in the dark-field, phase, and attenuation images during inhalation and exhalation. These measurements show that the dark-field signal depends on the air volume and, hence, the alveolar dimensions of the lung. Conducting this type of scan with animal disease models would help to locate the optimum breath point for single-image diagnostic dark-field imaging and could indicate if the changes in the dark-field signal during breath provide a diagnostically useful complementary measure.
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Interferometría/métodos , Pulmón/diagnóstico por imagen , Radiografía Torácica/métodos , Animales , Femenino , Procesamiento de Imagen Asistido por Computador , Enfermedades Pulmonares/diagnóstico por imagen , Ratones , Ratones Endogámicos C57BL , Respiración ArtificialRESUMEN
For hares (Lepus spp., Leporidae, Lagomorpha, Mammalia) from Ethiopia no conclusive molecular phylogenetic data are available. To provide a first molecular phylogenetic model for the Abyssinian Hare (Lepus habessinicus), the Ethiopian Hare (L. fagani), and the Ethiopian Highland Hare (L. starcki) and their evolutionary relationships to hares from Africa, Eurasia, and North America, we phylogenetically analysed mitochondrial ATPase subunit 6 (ATP6; n = 153 / 416bp) and nuclear transferrin (TF; n = 155 / 434bp) sequences of phenotypically determined individuals. For the hares from Ethiopia, genotype composition at twelve microsatellite loci (n = 107) was used to explore both interspecific gene pool separation and levels of current hybridization, as has been observed in some other Lepus species. For phylogenetic analyses ATP6 and TF sequences of Lepus species from South and North Africa (L. capensis, L. saxatilis), the Anatolian peninsula and Europe (L. europaeus, L. timidus) were also produced and additional TF sequences of 18 Lepus species retrieved from GenBank were included as well. Median joining networks, neighbour joining, maximum likelihood analyses, as well as Bayesian inference resulted in similar models of evolution of the three species from Ethiopia for the ATP6 and TF sequences, respectively. The Ethiopian species are, however, not monophyletic, with signatures of contemporary uni- and bidirectional mitochondrial introgression and/ or shared ancestral polymorphism. Lepus habessinicus carries mtDNA distinct from South African L. capensis and North African L. capensis sensu lato; that finding is not in line with earlier suggestions of its conspecificity with L. capensis. Lepus starcki has mtDNA distinct from L. capensis and L. europaeus, which is not in line with earlier suggestions to include it either in L. capensis or L. europaeus. Lepus fagani shares mitochondrial haplotypes with the other two species from Ethiopia, despite its distinct phenotypic and microsatellite differences; moreover, it is not represented by a species-specific mitochondrial haplogroup, suggesting considerable mitochondrial capture by the other species from Ethiopia or species from other parts of Africa. Both mitochondrial and nuclear sequences indicate close phylogenetic relationships among all three Lepus species from Ethiopia, with L. fagani being surprisingly tightly connected to L. habessinicus. TF sequences suggest close evolutionary relationships between the three Ethiopian species and Cape hares from South and North Africa; they further suggest that hares from Ethiopia hold a position ancestral to many Eurasian and North American species.
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Evolución Biológica , ADN/genética , Liebres/clasificación , Liebres/genética , Animales , Teorema de Bayes , ADN/química , ADN Mitocondrial/química , ADN Mitocondrial/genética , ADN Mitocondrial/aislamiento & purificación , ADN Mitocondrial/metabolismo , Etiopía , Variación Genética , Genotipo , Haplotipos , Hibridación Genética , Repeticiones de Microsatélite/genética , ATPasas de Translocación de Protón Mitocondriales/genética , Fenotipo , Filogenia , Polimorfismo Genético , Densidad de Población , Análisis de Secuencia de ADN , Transferrina/genéticaRESUMEN
UNLABELLED: Treatment effects over 2 years of teriparatide vs. ibandronate in postmenopausal women with osteoporosis were compared using lumbar spine bone mineral density (BMD) and trabecular bone score (TBS). Teriparatide induced larger increases in BMD and TBS compared to ibandronate, suggesting a more pronounced effect on bone microarchitecture of the bone anabolic drug. INTRODUCTION: The trabecular bone score (TBS) is an index of bone microarchitecture, independent of bone mineral density (BMD), calculated from anteroposterior spine dual X-ray absorptiometry (DXA) scans. The potential role of TBS for monitoring treatment response with bone-active substances is not established. The aim of this study was to compare the effects of recombinant human 1-34 parathyroid hormone (teriparatide) and the bisphosphonate ibandronate (IBN), on lumbar spine (LS) BMD and TBS in postmenopausal women with osteoporosis. METHODS: Two patient groups with matched age, body mass index (BMI), and baseline LS BMD, treated with either daily subcutaneous teriparatide (N = 65) or quarterly intravenous IBN (N = 122) during 2 years and with available LS BMD measurements at baseline and 2 years after treatment initiation were compared. RESULTS: Baseline characteristics (overall mean ± SD) were similar between groups in terms of age 67.9 ± 7.4 years, body mass index 23.8 ± 3.8 kg/m(2), BMD L1-L4 0.741 ± 0.100 g/cm(2), and TBS 1.208 ± 0.100. Over 24 months, teriparatide induced a significantly larger increase in LS BMD and TBS than IBN (+7.6 % ± 6.3 vs. +2.9 % ± 3.3 and +4.3 % ± 6.6 vs. +0.3 % ± 4.1, respectively; P < 0.0001 for both). LS BMD and TBS were only weakly correlated at baseline (r (2) = 0.04) with no correlation between the changes in BMD and TBS over 24 months. CONCLUSIONS: In postmenopausal women with osteoporosis, a 2-year treatment with teriparatide led to a significantly larger increase in LS BMD and TBS than IBN, suggesting that teriparatide had more pronounced effects on bone microarchitecture than IBN.
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Conservadores de la Densidad Ósea/uso terapéutico , Densidad Ósea/efectos de los fármacos , Difosfonatos/uso terapéutico , Osteoporosis Posmenopáusica/tratamiento farmacológico , Teriparatido/uso terapéutico , Absorciometría de Fotón/métodos , Anciano , Conservadores de la Densidad Ósea/farmacología , Difosfonatos/farmacología , Evaluación de Medicamentos/métodos , Femenino , Humanos , Ácido Ibandrónico , Inyecciones Intravenosas , Inyecciones Subcutáneas , Vértebras Lumbares/fisiopatología , Persona de Mediana Edad , Osteoporosis Posmenopáusica/fisiopatología , Estudios Retrospectivos , Teriparatido/farmacología , Resultado del TratamientoRESUMEN
AIM: In this explorative study it should be evaluated how the introduction of non invasive first trimester diagnosis (nuchal translucency measurement, Combined Test, first trimester ultrasound screening) has influenced the indications and cytogenetic results of chorion villi samplings. MATERIALS AND METHODS: Between 1989 and 2008 3337 pregnancies with CVS between 11 and 14 weeks of gestation were examined retrospectively. They were divided in two groups: CVS 1989 - 2001 before introduction of non invasive first trimester diagnosis (n = 1698) and CVS 2002 - 2008 after introducing non invasive testing at the end of 2001 (n = 1639). In both groups the indications for CVS (maternal age, sonographic findings, past history, maternal anxiety, and abnormal results of the Combined Test only in the second group) and the cytogenetic results were evaluated. RESULTS: In the first group (1989 - 2001, n = 1698) 85,6% (n = 1454) of all CVS were performed because of maternal age and only 3% (n = 51) due to sonographic findings. In the second group (2002 - 2008, n = 1639) there was a distinct increase of sonographic findings leading to CVS (33,9%, n = 555) with a clear decrease of maternal age to 37,9% (n = 621). Abnormal cytogenetic results were found in 10,5% (n = 172) in the second group, in the first group only in 4,5% (n = 76), respectively. The parameter with the highest rate of chromosomal disorders was fetal hydrops (66,1%), follwed by hygroma colli (48,2%), malformations (12,9%) and increased nuchal translucency (11,2%). Regarding maternal age alone the rate of abnormal chromosomes was 3,1%. CONCLUSIONS: It could be shown that non invasive first trimester diagnosis has lead to a more specific indication for invasive fetal testing (sonographic findings 33,9 vs. 3%, maternal age 37,9 vs. 85,6%) with a higher rate of chromosomal disorder in this group (10,5 vs. 4,5%).
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Muestra de la Vellosidad Coriónica , Anomalías Congénitas/diagnóstico por imagen , Medida de Translucencia Nucal , Primer Trimestre del Embarazo , Ultrasonografía Prenatal , Adulto , Aberraciones Cromosómicas , Anomalías Congénitas/genética , Anomalías Congénitas/prevención & control , Femenino , Humanos , Recién Nacido , Linfangioma Quístico/diagnóstico por imagen , Edad Materna , Embarazo , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
European red deer are known to show a conspicuous phylogeographic pattern with three distinct mtDNA lineages (western, eastern and North-African/Sardinian). The western lineage, believed to be indicative of a southwestern glacial refuge in Iberia and southern France, nowadays covers large areas of the continent including the British Isles, Scandinavia and parts of central Europe, while the eastern lineage is primarily found in southeast-central Europe, the Carpathians and the Balkans. However, large parts of central Europe and the whole northeast of the continent were not covered by previous analyses. To close this gap, we produced mtDNA control region sequences from more than 500 red deer from Denmark, Germany, Poland, Lithuania, Belarus, Ukraine and western Russia and combined our data with sequences available from earlier studies to an overall sample size of almost 1,100. Our results show that the western lineage extends far into the European east and is prominent in all eastern countries except for the Polish Carpathians, Ukraine and Russia where only eastern haplotypes occurred. While the latter may actually reflect the natural northward expansion of the eastern lineage after the last ice age, the present distribution of the western lineage in eastern Europe may in large parts be artificial and a result of translocations and reintroduction of red deer into areas where the species became extinct in historical times.
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The Jena Institute of Pathology has been serving as a consultation and reference center for soft tissue tumors in Germany since 1978. The present study provides an overview of the clinicopathological data from a two-year period and an update on diagnostics and research. Retrospectively, 7043 cases sent to the institute in the years 2006 and 2007 were analyzed. The majority of cases (>77.7%) were soft tissue tumors, of which 49% were categorized as malignant, 11.4% as intermediate, 35% as benign and 4.6% as tumors of uncertain biological potential. Neoplasms with fibroblastic differentiation were the most frequent. The mean age of patients with a sarcoma was 63 years. The molecular pathological analysis of soft tissue tumors has attained a major role in diagnosis. This is further advanced at the Jena institute in the context of a German Federal Ministry of Education and Research (BMBF) project for molecular sarcoma diagnosis with the aim of developing and validating DNA probes for in situ hybridization detection of translocations and their associated chromosomal breaks on the one hand, and DNA chips for the detection of fusion transcripts on the other. Research projects relate to the analysis of specific biomarkers in large tumor collectives and the pathomechanisms in several sarcoma entities.
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Sistema de Registros , Sarcoma/patología , Neoplasias de los Tejidos Blandos/patología , Adulto , Anciano , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Aberraciones Cromosómicas , Estudios Transversales , Sondas de ADN , Femenino , Predisposición Genética a la Enfermedad/genética , Alemania , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Técnicas de Diagnóstico Molecular , Análisis de Secuencia por Matrices de Oligonucleótidos , Investigación , Estudios Retrospectivos , Sarcoma/clasificación , Sarcoma/epidemiología , Sarcoma/genética , Neoplasias de los Tejidos Blandos/clasificación , Neoplasias de los Tejidos Blandos/epidemiología , Neoplasias de los Tejidos Blandos/genética , Translocación Genética/genéticaRESUMEN
Agglomerates of nanosized metal particles can be deposited onto a variety of substrates using a custom-built, microgravity-compatible evaporation/condensation device. A metal aerosol with high solid loading is produced by rf-induction coil heating of a metal melt in a laminar inert gas flow. Valves and flow controllers operating in hypergravity and microgravity conditions allow powder samples to be prepared from such aerosols suppressing buoyancy and sedimentation effects. We present here the technical details for such a parabolic flight compatible metal aerosol source together with some initial results of nanoscale Ni agglomerates synthesized and deposited under microgravity conditions.
RESUMEN
We analyzed 121 golden jackals (Canis aureus) from six sample sites in Serbia with regard to genetic variability and differentiation as revealed by mitochondrial control region sequences and eight nuclear microsatellite loci. There was no variation at all in the mtDNA sequences, and nuclear variability was very low (average observed and expected heterozygosity of 0.29 and 0.34, respectively). This is in line with the considerable recent range expansion of this species in the Balkans and indicates a strong founder effect in the recently established Serbian population. We did not find evidence of differentiation between the northeastern jackals and those from the plain of Srem or those in between. F-statistics and Bayesian Structure analyses, however, were indicative of a low degree of overall differentiation in the Serbian population. A vagrant Austrian jackal that was also analyzed was genetically indistinguishable from its Serbian conspecifics.
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ADN Mitocondrial/genética , Efecto Fundador , Chacales/genética , Repeticiones de Microsatélite/genética , Animales , Teorema de Bayes , Variación Genética , Geografía , SerbiaRESUMEN
A population genetic analysis based on sequences of the mitochondrial control region in 110 red foxes from five sampling localities in northern Serbia was carried out. The analysis yielded nine different haplotypes. Neither haplotype phylogeny nor their distribution was in accordance with the geographic location of the populations. In particular, the data failed to detect an unequivocal influence of the two big rivers, the Danube and the Tisza, separating the populations studied. Population differentiation was altogether low, without any relationship to the rivers as possible migration barriers. Although the possibility of foxes crossing the rivers over bridges or by swimming, thus keeping up gene flow, cannot be ruled out, it is most probable that the control region sequences are not sensitive enough to resolve small-scale population relationships but rather show patterns determined by stochastic processes such as genetic drift or lineage sorting.
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ADN Mitocondrial/genética , Zorros/genética , Genética de Población , Mitocondrias/genética , Animales , Flujo Genético , Variación Genética , Haplotipos , Yugoslavia/epidemiologíaRESUMEN
PURPOSE: To pre p a re and explore new solutions of semifluorinated alkane in silicone oil, which have a specific gravity slightly higher than silicone oil and vitreous fluid (referred to in the following as heavier-than-water silicone oils (HWSs), and to investigate, in vitro, whether HWSs can be used to plug retina holes, while allowing dehydration of the subretinal space. METHODS: HWS solutions were pre p a red with silicone oil 5000 and perfluorohexyloctane (F6H8). The stability was investigated under different conditions. The viscosity was determined by means of a capillary viscometer. The surface and interface tension were measured using the ring method. RESULTS: HWSs are insoluble in an aqueous medium. Densiron(R)68 (HWS 1.06) is a transparent homogeneous liquid which is slightly heavier (1.06 g/cm3) than water and has a refractive index close to that of vitreous liquid. Densiron68 (HWS 1.06) has a low viscosity (1480 mPas) and interface tension (40.82 mN/m), making it an effective tamponade in the surgical treatment of an inferior detached retina. In addition, the interfaces between Densiron68 and other perfluorocarbon liquids are clearly visible. However, the interface layer between Densiron68 and water is not clear. Finally, all HWSs are stable over the long term at ambient temperatures, as well as physically and thermally resistant. CONCLUSIONS. Due to its physiochemical properties, Densiron68 could meet the requirements for a heavier-than-water tamponade.
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Dimetilpolisiloxanos/química , Fluorocarburos/química , Aceites de Silicona/química , Siliconas/química , Adulto , Animales , Dimetilpolisiloxanos/toxicidad , Drenaje , Combinación de Medicamentos , Estabilidad de Medicamentos , Fluorocarburos/toxicidad , Humanos , Células L/efectos de los fármacos , Ratones , Soluciones Oftálmicas/química , Soluciones Oftálmicas/toxicidad , Epitelio Pigmentado Ocular/efectos de los fármacos , Refractometría , Aceites de Silicona/toxicidad , Siliconas/toxicidad , Gravedad Específica , Tensión Superficial , ViscosidadRESUMEN
AIMS: To investigate the role of hospital volume and individual hospitals on long term outcomes (local recurrence and survival) of rectal cancer patients. METHODS: One thousand thirty-eight patients with rectal cancer were diagnosed between 1996 and 1998. From these, we analysed 884 patients with a resected invasive primary rectal cancer. Median follow-up was 5.7 years. The impact of hospital volume (<10, 10-30 and >30 rectal cancer patients annually) on local recurrence and survival was examined in a Cox model. Differences between the four largest clinics in the high volume group were also investigated. RESULTS: In the multivariate model predicting survival the following variables were significant: UICC stage, grade, age, local recurrence, and (neo-) adjuvant therapy treatment. In the multivariate model predicting local recurrence UICC stage, tumour localisation, and neoadjuvant therapy treatment were significant variables. Hospital volume was not a significant factor for survival or local recurrence. Within the high volume category one hospital showed significantly worse local recurrence rates than all other hospitals, but no survival difference could be seen between the four largest hospitals of the high volume group. CONCLUSIONS: This analysis of a rectal cancer population found that hospital volume did not determine survival or local recurrence. Detailed clinical data with long term follow-up from cancer registries are vital to demonstrate the quality of routine care.
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Procedimientos Quirúrgicos del Sistema Digestivo/estadística & datos numéricos , Procedimientos Quirúrgicos del Sistema Digestivo/normas , Hospitales/estadística & datos numéricos , Evaluación de Resultado en la Atención de Salud , Neoplasias del Recto/cirugía , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Pronóstico , Modelos de Riesgos Proporcionales , Análisis de SupervivenciaRESUMEN
The azo dye trypan blue and the cyanine dye indocyanine green have been used in ophthalmology since the 1980 s to dye the anterior capsule in cataract operations and to stain epiretinal membranes in order to remove the membrana limitans interna (ILM). By means of a standardized in vitro test in accordance with DIN EN ISO 10993, it has now been shown that both dyes and the theoretically possible alternatives - the anthrachinone alizarincyanine green and the trityl dyes fast green and lissamine green - are cytotoxic in the normal concentrations of maximum 1.5 g/l. On the other hand, the new product Blueron(R) with the trityl dye patent blue, which has been developed to dye the anterior capsule, is completely biocompatible, even at a high dosage of up to 2.8 g/l.
Asunto(s)
Extracción de Catarata , Colorantes/toxicidad , Verde de Indocianina/toxicidad , Azul de Tripano/toxicidad , Antraquinonas/administración & dosificación , Antraquinonas/toxicidad , Supervivencia Celular/efectos de los fármacos , Colorantes/administración & dosificación , Relación Dosis-Respuesta a Droga , Membrana Epirretinal/patología , Membrana Epirretinal/cirugía , Humanos , Técnicas In Vitro , Verde de Indocianina/administración & dosificación , Colorantes Verde de Lisamina/administración & dosificación , Colorantes Verde de Lisamina/toxicidad , Ensayo de Materiales , Desprendimiento de Retina/patología , Desprendimiento de Retina/cirugía , Colorantes de Rosanilina/administración & dosificación , Colorantes de Rosanilina/toxicidad , Azul de Tripano/administración & dosificación , Vitreorretinopatía Proliferativa/patología , Vitreorretinopatía Proliferativa/cirugíaRESUMEN
PURPOSE: To pre p a re and explore new solutions of semifluorinated alkane in silicone oil, which have a specific gravity slightly higher than silicone oil and vitreous fluid (referred to in the following as heavier-than-water silicone oils (HWSs), and to investigate, in vitro, whether HWSs can be used to plug retina holes, while allowing dehydration of the subretinal space. METHODS: HWS solutions were pre p a red with silicone oil 5000 and perfluorohexyloctane (F6H8). The stabiliy was investigated under different conditions. The viscosity was determined by means of a capillary viscometer. The surface and interface tension were measured using the ring method. RESULTS: HWSs are insoluble in an aqueous medium. Densiron68 (HWS 1.06) is a transparent homogeneous liquid which is slightly heavier (1.06 g/cm3) than water and has a refractive index close to that of vitreous liquid. Densiron68 (HWS 1.06) has a low viscosity (1480 mPas) and interface tension (40.82 mN/m), making it an effective tamponade in the surgical treatment of an inferior detached retina. In addition, the interfaces between Densiron68 and other perfluorocarbon liquids are clearly visible. However, the interface layer between Densiron68 and water is not clear. Finally, all HWSs are stable over the long term at ambient temperatures, as well as physically and thermally resistant. CONCLUSIONS: Due to its physiochemical properties, Densiron68 could meet the requirements for a heavier-than-water tamponade. (Eur J Ophthalmol 2005; 15: 627-37).
RESUMEN
Allozyme, microsatellite and mtDNA (RFLP and sequence) data of European red deer populations were examined as to their capability of indicating anthropogenic influences such as the keeping of animals in enclosures, selective hunting for trophies translocation of specimens to improve trophy quality and habitat fragmentation. Deer in enclosures revealed considerable deviations of allele frequencies from isolation-by-distance expectations but no remarkable loss of genetic diversity. Particular allozyme genotypes were associated with antler morphology, and selective hunting was shown to alter allele frequencies in the expected direction. Habitat fragmentation is reflected by various kinds of genetic markers but due to the lack of information on population histories no unequivocal evidence on particular human activities could be obtained.
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ADN Mitocondrial/genética , Ciervos/genética , Ambiente , Variación Genética , Crianza de Animales Domésticos , Animales , ADN Mitocondrial/química , Europa (Continente) , Humanos , Isoenzimas/genética , Italia , Conducta PredatoriaRESUMEN
The catalytic CVD synthesis, using propyne as carbon precursor and Fe(NO3)3 as catalyst precursor inside porous alumina, gives carbon nanotube (CNT) bags in a well-arranged two-dimensional order. The tubes have the morphology of bags or fibers, since they are completely filled with smaller helicoidal CNTs. This morphology has so far not been reported for CNTs. Owing to the dense filling of the outer mother CNTs with small helicoidal CNTs, the resulting CNT fibers appear to be stiff and show no sign of inflation, as sometimes observed with hollow CNTs. The fiber morphology was observed by raster electron microscopy (REM), transmission electron microscopy (TEM), and atomic force microscopy (AFM). The carbon material is graphitic as deduced from spectroscopic studies (X-ray diffraction, Raman and electron energy-loss spectroscopy (EELS)). From Mössbauer studies, the presence of two different oxidation states (Fe0 and FeIII) of the catalyst is proven. Geometric structuring of the template by two different methods has been studied. Inkjet catalyst printing shows that the tubes can be arranged in defined areas by a simple and easily applied technique. Laser-structuring creates grooves of nanotube fibers embedded in the alumina host. This allows the formation of defined architectures in the microm range. Results on hydrogen absorption and field emission properties of the CNT fibers are reported.
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A clinical evaluation and Cx26 mutation analysis was performed in 92 consecutive patients with sensorineural hearing loss in order to delineate the spectrum of genetically caused hearing loss. Among patients of Austrian origin, 53% were classified with hereditary hearing loss. Cx26 mutations were found in 26% of NSHL patients (40% of familial vs 18% of sporadic cases). The mutation 35delG accounted for 52.8% of all presumed GJB2 disease alleles. The second most frequent mutation was L90P (16.7%) having been reported with a prevalence of 0.7-3.5% in other populations. Three novel mutations were found. The novel mutation, R143Q, was associated with dominant high-frequency hearing loss. Pseudodominant transmission of NSHL was seen in four families with Cx26 mutations. A mutation 35delG carrier rate of 0.9% was observed among 672 controls from West-Austria. Cx26 mutations were found associated with mild to profound, and with asymmetric hearing impairment.
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Conexinas/genética , Pérdida Auditiva Sensorineural/genética , Mutación , Austria , Conexina 26 , Femenino , Humanos , Masculino , LinajeRESUMEN
Male "viable motheaten" (me(v)) mice, with a naturally occurring mutation in the gene of the SH2 domain protein tyrosine phosphatase SHP-1, are sterile. Known defects in sperm maturation in these mice correlate with an impaired differentiation of the epididymis, which has similarities to the phenotype of mice with a targeted inactivation of the Ros receptor tyrosine kinase. Ros and SHP-1 are coexpressed in epididymal epithelium, and elevated phosphorylation of Ros in the epididymis of me(v) mice suggests that Ros signaling is under control of SHP-1 in vivo. Phosphorylated Ros strongly and directly associates with SHP-1 in yeast two-hybrid, glutathione S-transferase pull-down, and coimmunoprecipitation experiments. Strong binding of SHP-1 to Ros is selective compared to six other receptor tyrosine kinases. The interaction is mediated by the SHP-1 NH(2)-terminal SH2 domain and Ros phosphotyrosine 2267. Overexpression of SHP-1 results in Ros dephosphorylation and effectively downregulates Ros-dependent proliferation and transformation. We propose that SHP-1 is an important downstream regulator of Ros signaling.
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Células Epiteliales/fisiología , Proteínas Tirosina Fosfatasas/genética , Proteínas Tirosina Fosfatasas/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Tirosina Quinasas Receptoras , Receptor trkA/fisiología , Transducción de Señal/fisiología , Células 3T3 , Animales , Línea Celular , Epidídimo/citología , Células Epiteliales/citología , Humanos , Péptidos y Proteínas de Señalización Intracelular , Masculino , Ratones , Ratones Noqueados , Ratones Mutantes , Proteína Tirosina Fosfatasa no Receptora Tipo 6 , Proteínas Tirosina Fosfatasas/química , Proteínas Proto-Oncogénicas/deficiencia , Proteínas Proto-Oncogénicas/genética , Receptor trkA/genética , Proteínas Recombinantes de Fusión/metabolismo , Transfección , Dominios Homologos srcRESUMEN
Human interdigestive intestinal motility follows a circadian rhythm with reduced nocturnal activity, but circadian pancreatic exocrine secretion is unknown. To determine whether circadian changes in interdigestive pancreatic secretion occur and are associated with motor events, pancreatic enzyme outputs, proximal jejunal motility, and plasma pancreatic polypeptide concentrations were measured during consecutive daytime and nighttime periods (12 h each) in seven healthy volunteers using orojejunal multilumen intubation. Studies were randomly started in the morning or evening. Nocturnally, motility decreased (motor quiescence: 67 +/- 22 vs. 146 +/- 37 min; motility index: 3.59 +/- 0.33 vs. 2.78 +/- 0.40 mmHg/min; both P < 0.05) but amylase output increased (273 +/- 78 vs. 384 +/- 100 U/min; P < 0.05) and protease output remained unchanged (P > 0.05); consequently, enzyme/motility ratio increased. Amylase outputs were always lowest during phase I. Motor but not pancreatic circadian activities were associated with sleep. Pancreatic polypeptide plasma concentrations were unchanged. Consequently, intestinal motor and pancreatic exocrine functions may have different circadian rhythms, i.e., decreased motor and stable secretory activity during the night. However, the association between individual phases of interdigestive motor and secretory activity is preserved. The nocturnal increase in enzyme/motility ratio is probably not caused by increased cholinergic tone.
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Ritmo Circadiano , Motilidad Gastrointestinal/fisiología , Páncreas/metabolismo , Amilasas/metabolismo , Ayuno/sangre , Humanos , Polipéptido Pancreático/sangre , Sueño/fisiología , Factores de TiempoRESUMEN
The purpose of this preliminary study was to investigate the advantages of the time-frequency analysis through the Continuous Wavelet Transform (CWT) compared to classical Fourier analysis using the Fast Fourier Transform (FFT) in arterial pressure signals from anesthetized mongrel dogs before and during standardized hemorrhages. Systemic arterial pressure pulsations were recorded using catheter-tip manometers. CWT and FFT were applied to arterial pressure pulsations to obtain module coefficients of this transformation and its associated contours during the evolution of progressive hemorrhages, in amounts of 15, 34, and 66% of the estimated total blood volume. This mathematical analysis enabled us to identify the evolution of the frequency components of aortic valve functions, heart dynamics, respiratory influences, and vasomotor activities. Furthermore, we isolated the modulating signal of amplitude modulation phenomenon present in the arterial pressure records, as described in previous papers, being the heart rate carrier frequency. The CWT is a very sensitive and reliable procedure to analyze (time-frequency) the oscillatory phenomena in two dimensions, and to provide more information than the FFT. This new analytical procedure may provide new insights in the study of shock pathophysiology.
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Determinación de la Presión Sanguínea/métodos , Hemorragia/fisiopatología , Procesamiento de Imagen Asistido por Computador/métodos , Animales , Perros , Femenino , Análisis de Fourier , MasculinoRESUMEN
Acute toxicity of heavy metals and organic pollutants was examined using Rhabditis oxycerca (Nematoda) and Paramecium spec. (Protozoa, Ciliata) as indicator organisms. The substances tested were based on the composition found in the river Odra. They were used in graduated dilution series (1000-fold, 500-, 250-, 167-, 125-, 100-, and 83-fold of the Odra concentration). In a special apparatus with an electric field the animals were induced to migrate from the anode to the cathode. Their migration activity (distance) and the number of migrating animals were influenced by the substances tested. To assess the extent of damage, results were compared with controls (tap water) and reference substances (aldicarb and chloracetamide). The investigations showed that heavy metal concentrations > 100-fold of the Odra concentration led to behavioural changes of both test organisms. The organic pollutants, in contrast, did not cause detectable changes in ciliates and only led to slight reductions in the migration activity of nematodes, without concentration-dependent gradations.