Evidence for accelerated colorectal adenoma--carcinoma progression in MUTYH-associated polyposis?

Background And Aim: MUTYH-associated polyposis (MAP) is an autosomal recessive inherited disorder characterised by the development of polyposis in the upper and lower gastrointestinal tract and a high risk of colorectal cancer (CRC). We evaluated the natural history of the disease and the outcome of colorectal surveillance and management.

Methods: A large Western European dataset of biallelic MUTYH mutation carriers comprising 254 patients was used.

Heat shock protein expression and change of cytochrome c oxidase activity: presence of two phylogenic old systems to protect tissues in ischemia and reperfusion.

Induction of heat shock proteins (hsp) has been shown to protect cells from ischemia by providing transient tolerance against myocardial injury and improving postischemic functional recovery. Attenuation of ATP depletion and earlier restoration of ATP content on reperfusion are thought to play a role in this scenario. Hsp induction is accompanied by altered enzyme activity of the respiratory chain, the major generator of ATP under physiological conditions.

The stringent response is essential for Pseudomonas aeruginosa virulence in the rat lung agar bead and Drosophila melanogaster feeding models of infection.

The stringent response is a regulatory system that allows bacteria to sense and adapt to nutrient-poor environments. The central mediator of the stringent response is the molecule guanosine 3',5'-bispyrophosphate (ppGpp), which is synthesized by the enzymes RelA and SpoT and which is also degraded by SpoT. Our laboratory previously demonstrated that a relA mutant of Pseudomonas aeruginosa, the principal cause of lung infections in cystic fibrosis patients, was attenuated in virulence in a Drosophila melanogaster feeding model of infection.

Regulation of mitochondrial respiration and apoptosis through cell signaling: cytochrome c oxidase and cytochrome c in ischemia/reperfusion injury and inflammation.

Cytochrome c (Cytc) and cytochrome c oxidase (COX) catalyze the terminal reaction of the mitochondrial electron transport chain (ETC), the reduction of oxygen to water. This irreversible step is highly regulated, as indicated by the presence of tissue-specific and developmentally expressed isoforms, allosteric regulation, and reversible phosphorylations, which are found in both Cytc and COX. The crucial role of the ETC in health and disease is obvious since it, together with ATP synthase, provides the vast majority of cellular energy, which drives all cellular processes.

Plutonium uptake and distribution in mammalian cells: molecular vs. polymeric plutonium.

Purpose: To study the cellular responses to molecular and polymeric forms of plutonium using PC12 cells derived from a rat pheochromocytoma.

Materials And Methods: Serum starved PC12 cells were exposed to polymeric and molecular forms of plutonium for 3 h. Cells were washed with 10 mM ethylene glycol tetraacetic acid (EGTA), 100 mM NaCl at pH 7.

Direct determination of the intracellular oxidation state of plutonium.

Microprobe X-ray absorption near edge structure (μ-XANES) measurements were used to determine directly, for the first time, the oxidation state of intracellular plutonium in individual 0.1-μm(2) areas within single rat pheochromocytoma cells (PC12). The living cells were incubated in vitro for 3 h in the presence of Pu added to the media in different oxidation states (Pu(III), Pu(IV), and Pu(VI)) and in different chemical forms.

A strategy to establish a gene-activated matrix on titanium using gene vectors protected in a polylactide coating.

Bioactive implants are promising tools in regenerative medicine. Here we describe a versatile procedure for preparing a gene-activated matrix on titanium. Lyophilized copolymer-protected gene vectors (COPROGs) suspended in poly(d,l-lactide) (PDLLA) solutions in ethyl acetate were used to varnish solid surfaces.

Iterative image reconstruction techniques: Applications for cardiac CT.

Background: Traditional limitations of cardiac CT are related to image noise, blooming artifacts from calcifications and stents, and radiation exposure. We evaluated whether these limitations can be ameliorated by the use of iterative reconstruction in image space (IRIS) instead of traditional filtered back projection (FBP) image reconstruction techniques.

Methods: We compared image reconstruction with the use of IRIS with traditional FBP for their effect on image quality, noise, volume of heavy coronary artery calcifications, and stents as a measure of "blooming" artifacts, and radiation dose at cardiac CT.

An iron-dependent and transferrin-mediated cellular uptake pathway for plutonium.

Plutonium is a toxic synthetic element with no natural biological function, but it is strongly retained by humans when ingested. Using small-angle X-ray scattering, receptor binding assays and synchrotron X-ray fluorescence microscopy, we find that rat adrenal gland (PC12) cells can acquire plutonium in vitro through the major iron acquisition pathway--receptor-mediated endocytosis of the iron transport protein serum transferrin; however, only one form of the plutonium-transferrin complex is active. Low-resolution solution models of plutonium-loaded transferrins derived from small-angle scattering show that only transferrin with plutonium bound in the protein's C-terminal lobe (C-lobe) and iron bound in the N-terminal lobe (N-lobe) (Pu(C)Fe(N)Tf) adopts the proper conformation for recognition by the transferrin receptor protein.

Microvascular tissue oxygenation and oxidative metabolism changes in the pedicled latissimus dorsi muscle during graded hypoxia: correlation between near infrared and 31P nuclear magnetic resonance spectroscopy.

Background: In this study, the microvascular tissue oxygenation and oxidative muscle metabolism during graded hypoxia and reoxygenation were examined in a rabbit model by near-infrared (NIR) spectroscopy and correlated with high-energy phosphates measured by (31)P nuclear magnetic resonance (NMR) spectroscopy.

Materials And Methods: Graded hypoxia was performed in a New Zealand rabbit model (n = 20, 2.0 ± 0.

The role of mitochondrial membrane potential in ischemic heart failure.

The molecular events occurring during myocardial infarction and cardioprotection are described with an emphasis on the changes of the mitochondrial membrane potential (ΔΨ(m)). The low ΔΨ(m) values of the normal beating heart (100-140 mV) are explained by the allosteric ATP-inhibition of cytochrome c oxidase (CcO) through feedback inhibition by ATP at high [ATP]/[ADP] ratios. During ischemia the mechanism is reversibly switched off by signaling through reactive oxygen species (ROS).

Elemental profiling of single bacterial cells as a function of copper exposure and growth phase.

The elemental composition of single cells of Nitrosomonas europaea 19718 was studied via synchrotron X-ray fluorescence microscopy (XFM) as a function of inhibition by divalent copper (Cu(II)) and batch growth phase. Based on XFM, the intracellular Cu concentrations in exponential phase cultures of N. europaea exposed to Cu(II) were statistically higher than in stationary phase cultures at the 95% confidence interval (α = 0.

Retinal pigment epithelial expression of complement regulator CD46 is altered early in the course of geographic atrophy.

In geographic atrophy (GA), the non-neovascular end stage of age-related macular degeneration (AMD), the macular retinal pigment epithelium (RPE) progressively degenerates. Membrane cofactor protein (MCP, CD46) is the only membrane-bound regulator of complement expressed on the human RPE basolateral surface. Based on evidence of the role of complement in AMD, we hypothesized that altered CD46 expression on the RPE would be associated with GA development and/or progression.

Sufficient release of antibiotic by a spacer 6 weeks after implantation in two-stage revision of infected hip prostheses.

Background: Although antibiotic-loaded spacers are commonly used to treat periprosthetic infections, it is unclear whether spacers continue to release bactericidal levels of antibiotic 6 weeks after implantation.

Questions/purposes: We asked whether an antibiotic can be detected in the tissue surrounding the spacer 6 weeks after implantation and whether the concentration is higher than the minimal inhibition concentration (MIC) previously determined for pathogens that are responsible for most periprosthetic infections.

Methods: We removed 14 spacers used in two-stage septic revisions of infected hip prostheses 6 weeks after the primary implantations and determined the concentration of the antibiotics in the membrane formed between the spacer and the neighboring bone on the acetabular and the femoral sides.

Coronary CT angiography: image quality, diagnostic accuracy, and potential for radiation dose reduction using a novel iterative image reconstruction technique-comparison with traditional filtered back projection.

Objectives: To compare image noise, image quality and diagnostic accuracy of coronary CT angiography (cCTA) using a novel iterative reconstruction algorithm versus traditional filtered back projection (FBP) and to estimate the potential for radiation dose savings.

Methods: Sixty five consecutive patients (48 men; 59.3 ± 7.

The dependence of autologous chondrocyte transplantation on varying cellular passage, yield and culture duration.

Matrix-assisted chondrocyte transplantation (m-ACI) still lacks any standardization in its execution in terms of cell passage (P), cell yield (C) and in vitro membrane-holding time (T). It was the goal of this study to analyze the effect of shifting cell culture parameters (P, C, T) on the in vitro as well as in vivo effort of a regulated animal m-ACI. Autologous rabbit knee articular chondrocytes were seeded within bilayer collagen I/III 3-D matrices in variation of P, C and T.

Zernike phase contrast in scanning microscopy with X-rays.

Scanning X-ray microscopy focuses radiation to a small spot and probes the sample by raster scanning. It allows information to be obtained from secondary signals such as X-ray fluorescence, which yields an elemental mapping of the sample not available in full-field imaging. The analysis and interpretation from these secondary signals can be considerably enhanced if these data are coupled with structural information from transmission imaging.

Quantitative comparison of preparation methodologies for X-ray fluorescence microscopy of brain tissue.

X-ray fluorescence microscopy (XFM) facilitates high-sensitivity quantitative imaging of trace metals at high spatial resolution over large sample areas and can be applied to a diverse range of biological samples. Accurate determination of elemental content from recorded spectra requires proper calibration of the XFM instrument under the relevant operating conditions. Here, we describe the manufacture, characterization, and utilization of multi-element thin-film reference foils for use in calibration of XFM measurements of biological and other specimens.

Zinc sparks are triggered by fertilization and facilitate cell cycle resumption in mammalian eggs.

In last few hours of maturation, the mouse oocyte takes up over twenty billion zinc atoms and arrests after the first meiotic division, until fertilization or pharmacological intervention stimulates cell cycle progression toward a new embryo. Using chemical and physical probes, we show that fertilization of the mature, zinc-enriched egg triggers the ejection of zinc into the extracellular milieu in a series of coordinated events termed zinc sparks. These events immediately follow the well-established series of calcium oscillations within the activated egg and are evolutionarily conserved in several mammalian species, including rodents and nonhuman primates.

Paradoxical embolization of brachiocephalic and pulmonary arteries in a case of persistent foramen ovale: a case report.

Paradoxical embolism is the result of systemic arterial embolism and pulmonary embolism. It indicates the presence of an intracardial defect in the area of the atrial or ventricular septum. The most frequent cause of an intracardiac defect associated with paradoxical embolism is a patent foramen ovale (PFO).

Calcium-dependent copper redistributions in neuronal cells revealed by a fluorescent copper sensor and X-ray fluorescence microscopy.

Dynamic fluxes of s-block metals like potassium, sodium, and calcium are of broad importance in cell signaling. In contrast, the concept of mobile transition metals triggered by cell activation remains insufficiently explored, in large part because metals like copper and iron are typically studied as static cellular nutrients and there are a lack of direct, selective methods for monitoring their distributions in living cells. To help meet this need, we now report Coppersensor-3 (CS3), a bright small-molecule fluorescent probe that offers the unique capability to image labile copper pools in living cells at endogenous, basal levels.

Radiation damage in protein crystals is reduced with a micron-sized X-ray beam.

Radiation damage is a major limitation in crystallography of biological macromolecules, even for cryocooled samples, and is particularly acute in microdiffraction. For the X-ray energies most commonly used for protein crystallography at synchrotron sources, photoelectrons are the predominant source of radiation damage. If the beam size is small relative to the photoelectron path length, then the photoelectron may escape the beam footprint, resulting in less damage in the illuminated volume.

Reduced utilization of selenium by naked mole rats due to a specific defect in GPx1 expression.

Naked mole rat (MR) Heterocephalus glaber is a rodent model of delayed aging because of its unusually long life span (>28 years). It is also not known to develop cancer. In the current work, tissue imaging by x-ray fluorescence microscopy and direct analyses of trace elements revealed low levels of selenium in the MR liver and kidney, whereas MR and mouse brains had similar selenium levels.