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1.
Radiologe ; 61(5): 426-432, 2021 May.
Artículo en Alemán | MEDLINE | ID: mdl-33852030

RESUMEN

BACKGROUND: Ligamentous lesions of the fingers are common everyday injuries and usually the result of distortion or overloading. Numerous examination methods are available for dedicated radiological diagnosis of sometimes complex injury patterns. OBJECTIVES: To review radiological diagnosis of the ligamentous structures of the finger joints including the presentation of anatomical, biomechanical and therapeutic aspects. MATERIALS AND METHODS: Presentation of the anatomy and biomechanics as well as the most common trauma mechanisms of the ligamentous structures. Review of the literature, discussion of recent work and diagnostic expert recommendations. RESULTS: The most relevant ligamentous structures are collateral ligaments, pulley ligaments, volar plates and tendons. The goal of radiologic diagnosis is to accurately define the injury pattern and to differentiate between simple and complicated ligamentous lesions. In unclear cases, magnetic resonance imaging (MRI) has become standard for further diagnostics, which may allow depiction of ligamentous structures in submillimetre resolution. CONCLUSIONS: Today, differential diagnosis includes all radiological modalities, which ensures the determination of an adequate therapy and prevention of sequel at a high standard.


Asunto(s)
Traumatismos de los Dedos , Traumatismos de los Dedos/diagnóstico por imagen , Humanos , Ligamentos/diagnóstico por imagen , Ligamentos/lesiones , Ligamentos Articulares/diagnóstico por imagen , Ligamentos Articulares/lesiones , Imagen por Resonancia Magnética , Radiografía , Tendones
2.
Neuropathol Appl Neurobiol ; 46(7): 673-685, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32497293

RESUMEN

AIMS: The deposition of amyloid-ß (Aß) peptides in the form of extracellular plaques in the brain represents one of the classical hallmarks of Alzheimer's disease (AD). In addition to 'full-length' Aß starting with aspartic acid (Asp-1), considerable amounts of various shorter, N-terminally truncated Aß peptides have been identified by mass spectrometry in autopsy samples from individuals with AD. METHODS: Selectivity of several antibodies detecting full-length, total or N-terminally truncated Aß species has been characterized with capillary isoelectric focusing assays using a set of synthetic Aß peptides comprising different N-termini. We further assessed the N-terminal heterogeneity of extracellular and vascular Aß peptide deposits in the human brain by performing immunohistochemical analyses using sporadic AD cases with antibodies targeting different N-terminal residues, including the biosimilar antibodies Bapineuzumab and Crenezumab. RESULTS: While antibodies selectively recognizing Aß1-x showed a much weaker staining of extracellular plaques and tended to accentuate cerebrovascular amyloid deposits, antibodies detecting Aß starting with phenylalanine at position 4 of the Aß sequence showed abundant amyloid plaque immunoreactivity in the brain parenchyma. The biosimilar antibody Bapineuzumab recognized Aß starting at Asp-1 and demonstrated abundant immunoreactivity in AD brains. DISCUSSION: In contrast to other studied Aß1-x -specific antibodies, Bapineuzumab displayed stronger immunoreactivity on fixed tissue samples than with sodium dodecyl sulfate-denatured samples on Western blots. This suggests conformational preferences of this antibody. The diverse composition of plaques and vascular deposits stresses the importance of understanding the roles of various Aß variants during disease development and progression in order to generate appropriate target-developed therapies.


Asunto(s)
Enfermedad de Alzheimer/metabolismo , Anticuerpos Monoclonales Humanizados/farmacología , Encéfalo/metabolismo , Placa Amiloide/metabolismo , Anciano , Anciano de 80 o más Años , Péptidos beta-Amiloides/metabolismo , Animales , Modelos Animales de Enfermedad , Humanos , Fragmentos de Péptidos/metabolismo
3.
Phys Rev Lett ; 118(5): 053003, 2017 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-28211728

RESUMEN

Multiphoton ionization of potassium atoms with a sequence of two counter-rotating circularly polarized femtosecond laser pulses produces vortex-shaped photoelectron momentum distributions in the polarization plane describing Archimedean spirals. The pulse sequences are produced by polarization shaping and the three-dimensional photoelectron distributions are tomographically reconstructed from velocity map imaging measurements. We show that perturbative ionization leads to electron vortices with c_{6} rotational symmetry. A change from c_{6} to c_{4} rotational symmetry of the vortices is demonstrated for nonperturbative interaction.

4.
Environ Sci Technol ; 51(9): 4897-4906, 2017 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-28402123

RESUMEN

In this study, we couple iron isotope analysis to microscopic and mineralogical investigation of iron speciation during circumneutral Fe(II) oxidation and Fe(III) precipitation with photosynthetically produced oxygen. In the presence of the cyanobacterium Synechococcus PCC 7002, aqueous Fe(II) (Fe(II)aq) is oxidized and precipitated as amorphous Fe(III) oxyhydroxide minerals (iron precipitates, Feppt), with distinct isotopic fractionation (ε56Fe) values determined from fitting the δ56Fe(II)aq (1.79‰ and 2.15‰) and the δ56Feppt (2.44‰ and 2.98‰) data trends from two replicate experiments. Additional Fe(II) and Fe(III) phases were detected using microscopy and chemical extractions and likely represent Fe(II) and Fe(III) sorbed to minerals and cells. The iron desorbed with sodium acetate (FeNaAc) yielded heavier δ56Fe compositions than Fe(II)aq. Modeling of the fractionation during Fe(III) sorption to cells and Fe(II) sorption to Feppt, combined with equilibration of sorbed iron and with Fe(II)aq using published fractionation factors, is consistent with our resulting δ56FeNaAc. The δ56Feppt data trend is inconsistent with complete equilibrium exchange with Fe(II)aq. Because of this and our detection of microbially excreted organics (e.g., exopolysaccharides) coating Feppt in our microscopic analysis, we suggest that electron and atom exchange is partially suppressed in this system by biologically produced organics. These results indicate that cyanobacteria influence the fate and composition of iron in sunlit environments via their role in Fe(II) oxidation through O2 production, the capacity of their cell surfaces to sorb iron, and the interaction of secreted organics with Fe(III) minerals.


Asunto(s)
Compuestos Ferrosos/química , Synechococcus/metabolismo , Compuestos Férricos/química , Hierro/química , Isótopos de Hierro/química , Oxidación-Reducción , Oxígeno
5.
Foot Ankle Surg ; 20(3): 192-4, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25103707

RESUMEN

BACKGROUND: There is inhomogeneous data about the hallucal extensor apparatus and the occurrence of accessory tendon slips and their function. We performed this study to clarify its anatomical features and make conclusions about its function. METHODS: Investigations were performed prospectively during operative correction of severe hallux valgus and interphalangeus in 60 consecutive cases. The occurrence, topographic location and size of accessory extensor tendons as well as the insertion patterns were recorded. After dissection traction of the accessory tendon was carried out to gain information about its function. RESULTS: In contradiction to previous studies reporting numerous variations in the distal attachments of the hallucal extensor apparatus with different accessory tendons described, our investigations showed constant anatomical features. In all but one case (98.3%) there was an accessory medial extensor hallucis longus tendon adjacent to the main tendon, always inserting on the dorsomedial aspect of the metatarsophalangeal joint capsule. We therefore chose the terminology extensor hallucis capsularis (EHC) used in previous studies. The intraoperative testing of the tendon showed it to exert a pretension of the metatarsophalangeal (MTP) joint capsule. CONCLUSION: Our study showed consistent anatomical features with an occurrence of the EHC tendon in 98.3%. We determined that its function is to pretension the MTP joint capsule, therefore avoiding capsular impingement during hallucal extension. The high incidence of the EHC tendon in our study may also postulate a correlation with MTP joint deformities and further cadaveric studies will be necessary to evaluate a possible predisposition for hallux valgus genesis.


Asunto(s)
Hallux Valgus/patología , Articulación Metatarsofalángica/patología , Articulación Metatarsofalángica/fisiopatología , Tendones/anomalías , Tendones/fisiopatología , Adulto , Anciano , Disección , Femenino , Hallux Valgus/fisiopatología , Hallux Valgus/cirugía , Humanos , Incidencia , Cápsula Articular/patología , Cápsula Articular/fisiopatología , Cápsula Articular/cirugía , Masculino , Articulación Metatarsofalángica/cirugía , Persona de Mediana Edad , Estudios Prospectivos , Rango del Movimiento Articular , Adulto Joven
6.
Rev Sci Instrum ; 95(9)2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39287480

RESUMEN

We introduce an extreme ultraviolet (XUV)-beamline designed for the time-resolved investigation and coherent control of attosecond (as) electron dynamics in atoms and molecules by polarization-shaped as-laser pulses. Shaped as-pulses are generated through high-harmonic generation (HHG) of tailored white-light supercontinua (WLS) in noble gases. The interaction of shaped as-pulses with the sample is studied using velocity map imaging (VMI) techniques to achieve the differential detection of photoelectron wave packets. The instrument consists of the WLS-beamline, which includes a hollow-core fiber compressor and a home-built 4f polarization pulse shaper, and the high-vacuum XUV-beamline, which combines an HHG-stage and a versatile multi-experiment vacuum chamber equipped with a home-built VMI spectrometer. The VMI spectrometer allows the detection of photoelectron wave packets from both the multiphoton ionization (MPI) of atomic or molecular samples by the tailored WLS-pulses and the single-photon ionization (SPI) by the shaped XUV-pulses. To characterize the VMI spectrometer, we studied the MPI of xenon atoms by linearly polarized WLS pulses. To validate the interplay of these components, we conducted experiments on the SPI of xenon atoms with linearly polarized XUV-pulses. Our results include the reconstruction of the 3D photoelectron momentum distribution (PMD) and initial findings on the coherent control of the PMD by tuning the spectrum of the XUV-pulses with the spectral phase of the WLS. Our results demonstrate the performance of the entire instrument for HHG-based photoelectron imaging spectroscopy with prototypical shaped pulses. Perspectively, we will employ polarization-tailored WLS-pulses to generate polarization-shaped as-pulses.

7.
Sci Adv ; 7(14)2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33789903

RESUMEN

Fundamental insight on predator-prey dynamics in the deep sea is hampered by a lack of combined data on hunting behavior and prey spectra. Deep-sea niche segregation may evolve when predators target specific prey communities, but this hypothesis remains untested. We combined environmental DNA (eDNA) metabarcoding with biologging to assess cephalopod community composition in the deep-sea foraging habitat of two top predator cetaceans. Risso's dolphin and Cuvier's beaked whale selectively targeted distinct epi/meso- and bathypelagic foraging zones, holding eDNA of 39 cephalopod taxa, including 22 known prey. Contrary to expectation, extensive taxonomic overlap in prey spectra between foraging zones indicated that predator niche segregation was not driven by prey community composition alone. Instead, intraspecific prey spectrum differences may drive differentiation for hunting fewer, more calorific, mature cephalopods in deeper waters. The novel combination of methods presented here holds great promise to disclose elusive deep-sea predator-prey systems, aiding in their protection.


Asunto(s)
Cefalópodos , ADN Ambiental , Animales , Cefalópodos/genética , Ecosistema , Conducta Predatoria , Ballenas
9.
Ann Med Surg (Lond) ; 54: 62-64, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32346473

RESUMEN

The disruption to healthcare provision as a result of the COVID-19 pandemic has compelled us to streamline healthcare delivery. This has given us an opportunity to implement healthcare technology, reform inter-disciplinary collaboration and ultimately enhance patient care. We discuss some of the advances made by the foot and ankle department at our hospital. These innovations have broad applicability and will hopefully ignite discussion amoung a number of healthcare teams about improving the future care of their patients.

10.
Hand Surg Rehabil ; 38(2): 121-124, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30708121

RESUMEN

Two men and one woman (age 31, 36 and 45 years) felt a painful pop in the left middle, right middle and right index finger during sport-related activities (2 sport climbing and 1 judo). Clinical examination found a painful flexor tendon in zone 2 but no function deficit specific to the flexor digitorum superficialis (FDS) tendon. MRI and ultrasonography revealed a complete disruption of the radial FDS tendon slip only, which was found retracted between the A2 and A3 pulleys. All flexor tendon pulleys remained intact. Conservative and functional treatment resulted in unrestricted normal function and return to sport. Disruption of one FDS tendon slip is a differential diagnosis for a popping incident in the finger, which is typically associated with a closed flexor tendon pulley injury.


Asunto(s)
Traumatismos en Atletas/terapia , Traumatismos de los Tendones/diagnóstico por imagen , Traumatismos de los Tendones/terapia , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Modalidades de Fisioterapia , Férulas (Fijadores) , Ultrasonografía
11.
Nat Commun ; 10(1): 658, 2019 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-30737394

RESUMEN

Polarization-tailored bichromatic femtosecond laser fields with cycloidal polarization profiles have emerged as a powerful tool for coherent control of quantum processes. We present an optical scheme to create and manipulate three-dimensional free electron wave packets with arbitrary rotational symmetry by combining advanced supercontinuum pulse shaping with high resolution photoelectron tomography. Here we use carrier-envelope phase-stable polarization-tailored bichromatic (3ω:4ω) counter- and corotating femtosecond laser pulses to generate 7-fold rotational symmetric and asymmetric photoelectron momentum distributions by multiphoton ionization of sodium atoms. To elucidate the physical mechanisms, we investigate the interplay between the symmetry properties of the driving field and the resulting electron wave packets by varying the optical field parameters. Our results show that the symmetry properties of electron wave packets are not fully determined by the field symmetry, but completely described by multipath quantum interference of states with different angular momenta.

12.
Clin Mass Spectrom ; 14 Pt B: 83-88, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34917764

RESUMEN

In the field of Alzheimer's disease, there is an urgent need for novel analytical tools to identify disease-specific biomarkers and to evaluate therapeutics. Preclinical trials commonly employ amyloid beta (Aß) peptide signatures as a read-out. In this paper, we report a simplified and detailed protocol for robust immunoprecipitation of Aß in brain tissue prior to mass spectrometric detection exemplified by a study using transgenic mice. The established method employed murine monoclonal and rabbit polyclonal antibodies and was capable of yielding well-reproducible peaks of high intensity with low background signal intensities corresponding to various Aß forms.

13.
Sci Rep ; 9(1): 16908, 2019 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-31729401

RESUMEN

Ocean acidification (OA), a direct consequence of increasing atmospheric CO2 concentration dissolving in ocean waters, is impacting many fish species. Little is known about the molecular mechanisms underlying the observed physiological impacts in fish. We used RNAseq to characterize the transcriptome of 3 different larval stages of Atlantic cod (Gadus morhua) exposed to simulated OA at levels (1179 µatm CO2) representing end-of-century predictions compared to controls (503 µatm CO2), which were shown to induce tissue damage and elevated mortality in G. morhua. Only few genes were differentially expressed in 6 and 13 days-post-hatching (dph) (3 and 16 genes, respectively), during a period when maximal mortality as a response to elevated pCO2 occurred. At 36 dph, 1413 genes were differentially expressed, most likely caused by developmental asynchrony between the treatment groups, with individuals under OA growing faster. A target gene analysis revealed only few genes of the universal and well-defined cellular stress response to be differentially expressed. We thus suggest that predicted ocean acidification levels constitute a "stealth stress" for early Atlantic cod larvae, with a rapid breakdown of cellular homeostasis leading to organismal death that was missed even with an 8-fold replication implemented in this study.


Asunto(s)
Gadus morhua/genética , Perfilación de la Expresión Génica , Concentración de Iones de Hidrógeno , Agua de Mar/análisis , Agua de Mar/química , Estrés Fisiológico , Transcriptoma , Animales , Biología Computacional/métodos , Ontología de Genes , Secuenciación de Nucleótidos de Alto Rendimiento , Larva , Osmorregulación
14.
Int J Surg Case Rep ; 39: 1-4, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28779701

RESUMEN

INTRODUCTION: Isolated cuboid dislocations are rare injuries Jacobson (1990). It is clinically significant and important in surgical education, as it is an injury and a source of lateral foot pain that can be misdiagnosed at the time of initial presentation and may be difficult to identify clinically or with imaging Drummond and Hastings (1969). PRESENTATION OF CASE: We present a case report in a 33year old rugby player, who was injured during a match after a tackle. The patient had ongoing concerns that he was not recovering following initial discharge, as he was unable to weight bear since his initial presentation to the Emergency Department (E.D.), and he had ongoing lateral foot pain. DISCUSSION: Important clinical findings include lateral foot pain, a palpable gap at the cuboid level and difficulty weight-bearing. Closed reduction is usually difficult as it can be blocked mechanically by the extensor digitorum brevis muscle or peroneus longus tendon Dobbs et al. (1969). Initial X-Rays may be inconclusive with this presentation. CT scanning is indicated if suspicion for pathology is high. Open reduction and internal fixation with Kirschner wires are usually necessary for isolated cuboid dislocations. CONCLUSION: Our take home message from this case report is that cuboid dislocations are rare injuries and are important to be aware of in reviewing X-rays in the E.D. Particularly in patients with inversion and plantar flexion type injuries to their foot and ankle joint, with an inability to weight bear and lateral midfoot pain following their injury.

15.
Neuroscience ; 139(4): 1343-54, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16581193

RESUMEN

Neuronal death is a pathological hallmark of Alzheimer's disease. We have shown previously that phosphorylated double-stranded RNA-dependent protein kinase is present in degenerating hippocampal neurons and in senile plaques of Alzheimer's disease brains and that genetically down-regulating double-stranded RNA-dependent protein kinase activity protects against in vitro beta-amyloid peptide neurotoxicity. In this report, we showed that two double-stranded RNA-dependent protein kinase blockers attenuate, in human neuroblastoma cells, beta-amyloid peptide toxicity evaluated by caspase 3 assessment. In addition, we have used the newly engineered APP(SL)/presenilin 1 knock-in transgenic mice, which display a severe neuronal loss in hippocampal regions, to analyze the activation of double-stranded RNA-dependent protein kinase. Western blots revealed the increased levels of activated double-stranded RNA-dependent protein kinase and the inhibition of eukaryotic initiation factor 2 alpha activity in the brains of these double transgenic mice. Phosphorylated RNA-dependent protein kinase-like endoplasmic reticulum-resident kinase was also increased in the brains of these mice. The levels of activated double-stranded RNA-dependent protein kinase were also increased in the brains of patients with Alzheimer's disease. At 3, 6 and 12 months, hippocampal neurons display double stranded RNA-dependent protein kinase labelings in both the nucleus and the cytoplasm. Confocal microscopy showed that almost constantly activated double-stranded RNA-dependent protein kinase co-localized with DNA strand breaks in apoptotic nuclei of CA1 hippocampal neurons. Taken together these results demonstrate that double-stranded RNA-dependent protein kinase is associated with neurodegeneration in APP(SL)/presenilin 1 knock-in mice and could represent a new therapeutic target for neuroprotection.


Asunto(s)
Enfermedad de Alzheimer/patología , Modelos Animales de Enfermedad , Neuronas/patología , eIF-2 Quinasa/metabolismo , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/tratamiento farmacológico , Secretasas de la Proteína Precursora del Amiloide , Péptidos beta-Amiloides/toxicidad , Animales , Ácido Aspártico Endopeptidasas , Western Blotting/métodos , Caspasa 3 , Caspasas/metabolismo , Muerte Celular/efectos de los fármacos , Muerte Celular/fisiología , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Endopeptidasas/genética , Activación Enzimática/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Humanos , Inmunohistoquímica/métodos , Etiquetado Corte-Fin in Situ/métodos , Indoles , Proteínas de la Membrana/genética , Ratones , Ratones Transgénicos , Neuroblastoma , Neuronas/efectos de los fármacos , Neuronas/enzimología , Fragmentos de Péptidos/toxicidad , Presenilina-1
16.
Neurosci Lett ; 403(1-2): 15-9, 2006 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-16701946

RESUMEN

During the last three to four decades, interest in the interaction of circulating and brain cholesterol has increased. As the CNS matures and cholesterol pools in the brain become constant, the rate of de novo synthesis of cholesterol in the brain is expected to decline. We measured cholesterol, its precursors and its brain specific metabolite 24S-hydroxycholesterol in hippocampus from 7 female and 13 male corpses by highly sensitive and specific gas chromatography-mass spectrometry. Two age groups (young, n=10; elderly, n=10) were formed with a cut-off at the median age of 38 years. The amount of cholesterol was comparable in young and elderly subjects. The concentrations of the cholesterol precursors lanosterol and lathosterol were significantly higher in young (P=0.036 and 0.005, respectively) than in elderly subjects. In accordance, there was a significantly negative correlation between age and lathosterol concentrations (r=-0.505; P=0.023). Absolute levels of 24S-hydroxycholesterol in the brain were slightly, but not significantly, lower in the hippocampal specimens from the elderly subjects. We conclude that during aging, cholesterol synthesis is decreased in the hippocampus, while absolute cholesterol content remains at a stable level.


Asunto(s)
Envejecimiento/metabolismo , Colesterol/biosíntesis , Hipocampo/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad
17.
Clin Neuropathol ; 25(4): 163-71, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16866297

RESUMEN

Recent evidence indicates that both intraneuronal Abeta and Cu are involved in the pathological processes in Alzheimer's disease (AD). This perspective shows a possible interrelation of these factors. AbetaPP, the precursor of Abeta which represents the main constituent of amyloid plaques, is involved in Cu homeostasis in mammals. In vitro observations and in vivo data obtained from AbetaPP mouse models provide strong evidence that AbetaPP and the resulting Abeta overproduction facilitate intracellular Cu to leave the cell. An increased Cu efflux seems to lead to Cu deficiency and, subsequently, reduced SOD-1 activity. The Cu-dependent SOD-1 activity is the main enzyme involved in detoxifying free radicals. Several reports have shown that oxidative stress is an invariable age-dependent feature in the brain of AD patients. Increased oxidative stress leads to an increase in intraneuronal Abeta accumulation, which has been shown to be the main trigger for neuronal loss in transgenic mouse models. Thus, we conclude that bioavailability of Cu is a crucial point for the pathogenesis of AD.


Asunto(s)
Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Cobre/metabolismo , Estrés Oxidativo/fisiología , Enfermedades por Prión/metabolismo , Animales , Cobre/deficiencia , Modelos Animales de Enfermedad , Humanos , Ratones , Ratones Transgénicos , Neuronas/metabolismo , Superóxido Dismutasa/metabolismo , Superóxido Dismutasa-1
18.
Cancer Res ; 59(8): 1980-6, 1999 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-10213510

RESUMEN

A model for medulloblastoma-like primitive neuroectodermal tumors was established in rat using retrovirally transduced SV40 large T antigen (LT) as an inducing agent (O. D. Wiestler et al., Brain Pathol., 2: 47-59, 1992). A cell line isolated from such a tumor and clonal derivatives thereof were biologically and molecularly characterized. In the parental tumor cell line, TZ870, which had been selected for G418 resistance, virtually all cells expressed LT and wild-type p53, which were complexed to each other. When plated in soft agar, these cells grew relatively slowly and formed disperse colonies. However, when grown without selection pressure, these cells reproducibly gave rise to LT-negative and G418-sensitive derivatives, LT-0 cells. Surprisingly, these latter cells exhibited a higher degree of malignancy both in vitro, growing readily to large colonies in soft agar, and in vivo, where they gave rise to a rapidly growing malignant tumor. Clonal selection from TZ870 cells revealed two types of clones: in one type, LT expression was stably maintained, even without selection pressure, whereas the other type lost the LT coding sequences. All LT-negative clones exhibited the same phenotype as the LT-0 cells. Reexpression of LT had no effect. However, LT no longer formed complexes with p53, and p53 was metabolically stable, suggesting that it had been mutated. Sequence analyses and diagnostic restriction digests of the p53 gene revealed that (a) both the parental LT-transformed cells and their derivatives contained only one complete p53 allele and (b) all LT-positive clones expressed wild-type p53, whereas all LT-negative clones expressed a mutant allele with a common mutation at Cys-174-->Tyr, indicating their clonal origin. We assume that the loss of LT coding sequences is the consequence of the p53 mutation, perhaps by inducing genomic instability, and that both the p53 mutation and additional genetic alterations that accompany the loss of LT coding sequences might contribute to enhanced malignancy.


Asunto(s)
Antígenos Virales de Tumores/genética , Tumores Neuroectodérmicos Periféricos Primitivos/genética , Proteína p53 Supresora de Tumor/genética , Animales , Antígenos Virales de Tumores/biosíntesis , Neoplasias Encefálicas/patología , Pruebas de Carcinogenicidad , Línea Celular , Transformación Celular Viral , Mutación , Tumores Neuroectodérmicos Periféricos Primitivos/inducido químicamente , Ratas , Reproducibilidad de los Resultados , Retroviridae/genética , Virus 40 de los Simios/genética , Células Tumorales Cultivadas , Integración Viral
19.
Cancer Res ; 47(22): 6126-33, 1987 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-3664512

RESUMEN

The value of estrogen and progesterone receptor (ER and PgR, respectively) determinations in predicting the recurrence-free survival (RFS) has been evaluated in a group of 807 node negative breast cancer patients. All of these patients are enrolled in the Danish Breast Cancer Cooperative Group (DBCG) 77-1a and 82-a protocols for low risk patients, and none of them have received systemic adjuvant therapy. At a median observation time of 50 months and in an evaluation of the total patient population as an entity, ER+ patients had only a marginally significant (P = 0.07) longer RFS than ER- patients while PgR+ patients experienced a significant advantage (P = 0.02). Among patients subgrouped according to menopausal status, both ER and PgR statuses were found to be significant prognostic factors for predicting RFS in the premenopausal women (less than 50 years) but not in peri- or postmenopausal women. Using Cox's multivariate analysis, nuclear pleomorphy was found to be the only significant prognostic variable, while the value of PgR status as a prognostic factor approached significance (P = 0.065). Although knowledge of ER status did not significantly improve distinction between patients with good and poor prognoses in the relatively small subgroup of premenopausal patients (n = 120) when PgR status was known, ER+PgR- patients have a lower risk of recurrence or death than ER-PgR- patients. Using a log-likelihood model, significant and distinct cut-off limits for the definition of receptor positivity were found for premenopausal patients: these were 5 fmol/mg cytosol protein for ER and 10 fmol/mg cytosol protein for PgR. These cut-off levels may reflect the ability of the ligand binding assay method used to discriminate between tissues with and without receptor proteins. Qualitative assessment of receptor status was as valuable as quantitative expression of receptor concentrations in predicting the RFS of the natural course of the disease among node negative premenopausal patients.


Asunto(s)
Neoplasias de la Mama/patología , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Adulto , Anciano , Análisis de Varianza , Femenino , Humanos , Metástasis Linfática , Menopausia , Persona de Mediana Edad , Pronóstico
20.
Mar Environ Res ; 119: 40-50, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27209121

RESUMEN

Climate change scenarios predict intensified terrestrial storm runoff, providing coastal ecosystems with large nutrient pulses and increased turbidity, with unknown consequences for the phytoplankton community. We conducted a 12-day mesocosm experiment in the Mediterranean Thau Lagoon (France), adding soil (simulated runoff) and fish (different food webs) in a 2 × 2 full factorial design and monitored phytoplankton composition, shade adaptation and stoichiometry. Diatoms (Chaetoceros) increased four-fold immediately after soil addition, prymnesiophytes and dinoflagellates peaked after six- and 12 days, respectively. Soil induced no phytoplankton shade adaptation. Fish reduced the positive soil effect on dinoflagellates (Scripsiella, Glenodinium), and diatom abundance in general. Phytoplankton community composition drove seston stoichiometry. In conclusion, pulsed terrestrial runoff can cause rapid, low quality (high carbon: nutrient) diatom blooms. However, bloom duration may be short and reduced in magnitude by fish. Thus, climate change may shift shallow coastal ecosystems towards famine or feast dynamics.


Asunto(s)
Ecosistema , Monitoreo del Ambiente , Eutrofización , Fitoplancton/crecimiento & desarrollo , Aguas Residuales/análisis , Contaminación del Agua/estadística & datos numéricos , Animales , Cambio Climático , Diatomeas , Dinoflagelados , Cadena Alimentaria , Francia , Modelos Estadísticos , Agua de Mar , Aguas Residuales/estadística & datos numéricos
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