bluuebunny/crossref_metadata_2025 huggingface dataset:
Activated protein C improves intestinal microcirculation in experimental endotoxaemia in the rat
Authors: Lehmann Christian , Meissner Konrad , Knöck Andreas , Diedrich Stephan , Pavlovic Dragan , Gründling Matthias , Usichenko Taras , Wendt Michael , Birnbaum Jürgen
Published: November 2006

Introduction

Successful treatment of severe sepsis and septic shock remains a major challenge in critical care medicine. The recently introduced recombinant human activated protein C (APC) remarkably improved the outcome of septic patients. The influence of APC on intestinal circulation is still poorly understood. Therefore, the present study aimed to investigate the effects of APC on intestinal microcirculation during experimental endotoxaemia in rats by using intravital microscopy.

Methods

A total of 44 male Lewis rats were randomly assigned to receive intravenous injections of 15 mg/kg lipopolysaccharide alone (LPS) (n = 11) or LPS followed by subsequent injection of 2 mg/kg recombinant human APC (LPS + APC) (n = 11), whereas control animals received either APC (n = 11) or saline (n = 11). Animals underwent observations of functional capillary density and leucocyte adherence on venular endothelium in the microcirculation of the intestinal wall by means of intravital fluorescence microscopy. Indicators of macrocirculation as well as plasma levels of tumour necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-10 were measured.

Results

Although APC administration of both LPS-treated and control rats did not change macrocirculation or release of inflammatory cytokines, it increased mucosal and muscular functional capillary density (p < 0.001 and p < 0.05, respectively) and reduced the number of firmly adhering leucocytes in intestinal submucosal V1 and V3 venules (p < 0.01) in LPS + APC-treated compared with LPS-treated animals, which did not receive APC. No remarkable differences that could be attributed to APC treatment were observed between the two control groups.

Conclusion

APC administration during experimental endotoxaemia improved intestinal microcirculation by protecting functional capillary density as a measure of microvascular perfusion and exerted anti-inflammatory effects by reducing leucocyte adherence to the endothelium in submucosal venules. Therefore, beneficial effects of APC in septic patients might be due, in part, to improved intestinal microcirculation.
Analysis of the Saccharomyces cerevisiae proteome with PeptideAtlas
Authors: King Nichole L , Deutsch Eric W , Ranish Jeffrey A , Nesvizhskii Alexey I , Eddes James S , Mallick Parag , Eng Jimmy , Desiere Frank , Flory Mark , Martin Daniel B , Kim Bong , Lee Hookeun , Raught Brian , Aebersold Ruedi
Published: November 2006

We present the Saccharomyces cerevisiae PeptideAtlas composed from 47 diverse experiments and 4.9 million tandem mass spectra. The observed peptides align to 61% of Saccharomyces Genome Database (SGD) open reading frames (ORFs), 49% of the uncharacterized SGD ORFs, 54% of S. cerevisiae ORFs with a Gene Ontology annotation of 'molecular function unknown', and 76% of ORFs with Gene names. We highlight the use of this resource for data mining, construction of high quality lists for targeted proteomics, validation of proteins, and software development.
ST2, an IL-1R family member, attenuates inflammation and lethality after intestinal ischemia and reperfusion
Authors: Fagundes Caio T , Amaral Flávio A , Souza Adriano L S , Vieira Angélica T , Xu Damo , Liew Foo Y , Souza Danielle G , Teixeira Mauro M
Published: November 2006

Ischemia reperfusion injury is characterized by local and systemic inflammation leading to considerable mortality. Previously, we have reported that soluble T1/ST2 (sST2), a member of the IL-1 receptor gene family, inhibits LPS-induced macrophage proinflammatory cytokine production. Here, we report the therapeutic effect of sST2-Fc in a murine model of intestinal ischemia reperfusion-induced injury. Administration of sST2-Fc fusion protein i.v., 10 min before reperfusion, reduced the production of TNF-α dose-dependently in the intestine and in the lungs. The sST2-Fc treatment with the highest dose (100 μg) resulted in inhibited vascular permeability, neutrophilia, and hemorrhage in the intestine and the lungs compared with controls treated with normal IgG. This was associated with down-regulated tissue levels of proinflammatory cytokines, markedly reduced serum TNF-α levels, and increased survival of mice from the sST2-Fc-treated group after ischemia and reperfusion injury. The beneficial effect of sST2-Fc treatment was associated with elevated IL-10 production in intestine and lung. sST2-Fc was not able to prevent the inflammatory response associated with intestinal ischemia and reperfusion in IL-10-deficient mice, suggesting that sST2 exerts its anti-inflammatory effect in a IL-10-dependent manner. These results also demonstrate that sST2-Fc may provide a novel, complementary approach in treating ischemic reperfusion injury.
Seismic attenuation of Atlantic margin basalts: Observations and modeling
Authors: Maresh Jennifer , White Robert S. , Hobbs Richard W. , Smallwood John R.
Published: November 2006

Paleogene basalts are present over much of the northeastern Atlantic European margin. In regions containing significant thicknesses of layered basalt flows, conducting seismic imaging within and beneath the volcanic section has proven difficult, largely because the basalts severely attenuate and scatter seismic energy. We use data from a vertical seismic profile (VSP) from well 164/07-1 that penetrated [Formula: see text] of basalt in the northern Rockall Trough west of Britain to measure the seismic attenuation caused by the in-situ basalts. The effective quality factor [Formula: see text] of the basalt layer is found from the VSP to be 15–35, which is considerably lower (more attenuative) than the intrinsic attenuation measured on basalt samples in the laboratory. We then run synthetic seismogram models to investigate the likely cause of the attenuation. Full waveform 1D modeling of stacked sequences of lava flows based on rock properties from the same well indicates that much of the seismic attenuation observed from the VSP can be accounted for by the scattering effects of multiple thin layers with high impedance contrasts. Phase-screen seismic modeling of the rugose basalt surface at the top-of-basalt sediment interface, with the magnitude and wavelength of the relief constrained by a 3D seismic survey around the well, suggests that surface scattering from this interface plays a much smaller role than internal scattering in attenuating the seismic signal as it passes through the basalt sequence.
Amplitude and frequency anomalies in regional 3D seismic data surrounding the Mallik 5L-38 research site, Mackenzie Delta, Northwest Territories, Canada
Authors: Riedel M. , Bellefleur G. , Dallimore S. R. , Taylor A. , Wright J. F.
Published: November 2006

Amplitude and frequency anomalies associated with lakes and drainage systems were observed in a 3D seismic data set acquired in the Mallik area, Mackenzie Delta, Northwest Territories, Canada. The site is characterized by large gas hydrate deposits inferred from well-log analyses and coring. Regional interpretation of the gas hydrate occurrences is mainly based on seismic amplitude anomalies, such as brightening or blanking of seismic energy. Thus, the scope of this research is to understand the nature of the amplitude behavior in the seismic data. We have therefore analyzed the 3D seismic data to define areas with amplitude reduction due to contamination from lakes and channels and to distinguish them from areas where amplitude blanking may be a geologic signal. We have used the spectral ratio method to define attenuation (Q) over different areas in the 3D volume and subsequently applied Q-compensation to attenuate lateral variations ofdispersive absorption. Underneath larger lakes, seismic amplitude is reduced and the frequency content is reduced to [Formula: see text], which is half the original bandwidth. Traces with source-receiver pairs located inside of lakes show an attenuation factor Q of [Formula: see text], approximately half of that obtained for source-receiver pairs situated on deep, continuous permafrost outside of lakes. Deeper reflections occasionally identified underneath lakes show low-velocity-related pull-down. The vertical extent of the washout zones is enhanced by acquisition with limited offsets and from processing parameters such as harsh mute functions to reduce noise from surface waves. The strong attenuation and seismic pull-down may indicate the presence of unfrozen water in deeper lakes and unfrozen pore water within the sediments underlying the lakes. Thus, the blanking underneath lakes is not necessarily related to gas migration or other in situ changes in physical properties potentially associated with the presence of gas hydrate.
Recursive prestack depth migration using CFP gathers
Authors: Thorbecke Jan , Berkhout A. J.
Published: November 2006

The common-focus-point technology (CFP) describes prestack migration by focusing in two steps: emission and detection. The output of the first focusing step represents a CFP gather. This gather defines a shot record that represents the subsurface response resulting from a focused source wavefield. We propose applying the recursive shot-record, depth-migration algorithm to the CFP gathers of a seismic data volume and refer to this process as CFP-gather migration. In the situation of complex geology and/or low signal-to-noise ratio, CFP-based image gathers are easier to interpret for nonalignment than the conventional image gathers. This makes the CFP-based image gathers better suited for velocity analysis. This important property is illustrated by examples on the Marmousi model.
Traveltime-based true-amplitude migration
Authors: Vanelle Claudia , Spinner Miriam , Hertweck Thomas , Jäger Christoph , Gajewski Dirk
Published: November 2006

True-amplitude Kirchhoff migration (TAKM) is an important tool in seismic-reflection imaging. In addition to a structural image, it leads to reflectivity maps of the subsurface. TAKM is carried out in terms of a weighted diffraction stack where the weight functions are computed with dynamic ray tracing (DRT) in addition to the diffraction traveltimes. DRT, however, is time-consuming and imposes restrictions on the velocity models, which are not always acceptable. An alternative approach to TAKM is proposed in which the weight functions are directly determined from the diffraction traveltimes. Because other methods exist for the generation of traveltimes, this approach is not limited by the requirements for DRT. Applications to a complex synthetic model and real data demonstrate that the image quality and accuracy of the reconstructed amplitudes are equivalent to those obtained from TAKM with DRT-generated weight functions.
A holistic approach to inversion of frequency-domain airborne EM data
Authors: Brodie Ross , Sambridge Malcolm
Published: November 2006

We have developed a holistic method for simultaneously calibrating, processing, and inverting frequency-domain airborne electromagnetic data. A spline-based, 3D, layered conductivity model covering the complete survey area was recovered through inversion of the entire raw airborne data set and available independent conductivity and interface-depth data. The holistic inversion formulation includes a mathematical model to account for systematic calibration errors such as incorrect gain and zero-level drift. By taking these elements into account in the inversion, the need to preprocess the airborne data prior to inversion is eliminated. Conventional processing schemes involve the sequential application of a number of calibration corrections, with data from each frequency treated separately. This is followed by inversion of each multifrequency sample in isolation from other samples.By simultaneously considering all of the available information in a holistic inversion, we are able to exploit interfrequency and spatial-coherency characteristics of the data. The formulation ensures that the conductivity and calibration models are optimal with respect to the airborne data and prior information. Introduction of interfrequency inconsistency and multistage error propagation stemming from the sequential nature of conventional processing schemes is also avoided. We confirm that accurate conductivity and calibration parameter values are recovered from holistic inversion of synthetic data sets. We demonstrate that the results from holistic inversion of raw survey data are superior to the output of conventional 1D inversion of final processed data. In addition to the technical benefits, we expect that holistic inversion will reduce costs by avoiding the expensive calibration-processing-recalibration paradigm. Furthermore, savings may also be made because specific high-altitude zero-level observations, needed for conventional processing, may not be required.
Comparison of source-independent methods of elastic waveform inversion
Authors: Xu Kun , Greenhalgh Stewart A. , Wang MiaoYue
Published: November 2006

In this paper, we investigate several source-independent methods of nonlinear full-waveform inversion of multicomponent elastic-wave data. This includes iterative estimation of source signature (IES), standard trace normalization (STN), and average trace normalization (ATN) inversion methods. All are based on the finite-element method in the frequency domain. One synthetic elastic crosshole model is used to compare the recovered images with all these methods as well as the known source signature (KSS) inversion method. The numerical experiments show that the IES method is superior to both STN and ATN methods in two-component, elastic-wave inversion in the frequency domain when the source signature is unknown. The STN and ATN methods have limitations associated with near-zero amplitudes (or polarity reversals) in traces from one of the components, which destroy the energy balance in the normalized traces and cause a loss of frequency information. But the ATN method is somewhat superior to the STN method in suppressing random noise and improving stability, as the developed formulas and the numerical experiments show. We suggest the IES method as a practical procedure for multicomponent seismic inversion.
Integrated wellbore-quality and risk-assessment study guides successful drilling in Amazon jungle
Authors: Tutuncu Azra N. , Geilikman Mikhail , Couzens Brent , van Duyvenboode Floris
Published: November 2006

Significant lost-circulation and wellbore-instability problems in the form of bit balling, stuck pipe, and adverse mud-shale interactions have been experienced in wells drilled prior to the study at three prospects in the Amazon jungle. An integrated borehole-stability and risk-assessment study has been carried out to enable successful drilling by optimizing borehole fluid pressures and predicting safe openhole times in various troublesome zones. The guidelines for hole-cleaning parameters and well-trajectory optimization have been obtained using improved fracture gradient and horizontal stress-anisotropy proprietary models based on special drill-cuttings data. Monopole and dipole sonic and imaging logs along with drilling data from the prospect wellshave been used to determine in-situ stresses, rock properties, andformation strength. These parameters have been utilized in borehole stability, hole cleaning, and open-hole time analyses for a comprehensive risk assessment and for selection of the optimum wellpath and drilling design. The wellbore pressures required for borehole stability turned out to be the highest for vertical wells and lowest for the horizontal ones, making drilling of highly deviated and horizontal wells attractive for the prospects. As a result, a wellpath with high deviation in the direction of maximum horizontal stress has been recommended as the most stable choice. The recommendations have been incorporated in the well design and implemented in the field with real-time borehole stability monitoring to result in successful drilling and efficient project economics.
Focal transformation, an imaging concept for signal restoration and noise removal
Authors: Berkhout A. J. , Verschuur D. J.
Published: November 2006

Interpolation of data beyond aliasing limits and removal of noise that occurs within the seismic bandwidth are still important problems in seismic processing. The focal transform is introduced as a promising tool in data interpolation and noise removal, allowing the incorporation of macroinformation about the involved wavefields. From a physical point of view, the principal action of the forward focal operator is removing the spatial phase of the signal content from the input data, and the inverse focal operator restores what the forward operator has removed. The strength of the method is that in the transformed domain, the focused signals at the focal area can be separated from the dispersed noise away from the focal area. Applications of particular interest in preprocessing are interpolation of missing offsets and reconstruction of signal beyond aliasing. The latter can be seen as the removal of aliasing noise.
Layer-induced seismic anisotropy from full-wave sonic logs: Theory, application, and validation
Authors: Liner Christopher L. , Fei Tong W.
Published: November 2006

Thin isotropic elastic layering in the earth is one cause of seismic VTI anisotropy, along with intrinsic anisotropy and fractures. An important issue related to the routine use of VTI seismic data processing is the estimation of the necessary parameters. The full set of layer-induced VTI anisotropy parameters can be computed from full-wave sonic and density log data using Backus averaging. Intrinsic anisotropy can be incorporated if it is known from laboratory analysis. The isotropic layering method is applied to six wells in eastern Saudi Arabia, and the estimated anisotropy parameters are persistent across distances of many kilometers. This leads to the possibility of parameter estimation at sparse well locations for use in seismic data processing. Validation is demonstrated by direct numerical simulation of elastic wavefields in original and Backus-averaged earth models with various window lengths. We observe precise equivalence of the full wavefield when the averaging length is less than or equal to one-third of the minimum dominant wavelength. First arrival information, used in depth migration, is preserved with much longer averaging windows, up to twice the minimum dominant wavelength.
Linear feature analysis for aeromagnetic data
Authors: Hansen R. O. , deRidder Eduard
Published: November 2006

This paper presents a new approach to detecting and two approaches to displaying lineaments associated with high-angle magnetic contacts, based on analysis of the curvature of the total horizontal gradient of the total magnetic field reduced to the pole. The first display is a contour or color plot of minus the principal curvature of largest absolute value. The second is a point plot of the local maxima of minus the largest principal curvature in regions where this curvature is negative. The paper also develops a depth-estimation technique for magnetic contacts based on the ratio of the curvature of the total gradient to the total gradient itself. Tests on synthetic data yield excellent results in detecting and delineating magnetic contact edges, and reasonable performance in producing depth estimates for the magnetic contacts. Results obtained using aeromagnetic data from the Finger Lakes region of New York State show good correlation with known structural features.
Target interaction with stratigraphy beneath shallow, frozen lakes: Quarter-wave resonances within GPR profiles
Authors: Arcone Steven A. , Finnegan David C. , Liu Lanbo
Published: November 2006

Resonances within ground-penetrating radar (GPR) reflection profiles recorded over shallow, frozen lakes located on an artillery and bombing range in interior Alaska originate near ice/bottom and freeze/thaw interface horizons and are similar to those caused by shallow utilities. The transmitted pulse spectra were centered near [Formula: see text]. Low-pass filtering differentiates the resonances from background scattering. The transit times between their onset and that of the overlying interface reflections correspond with spectral peaks predicted for layers with thickness of one in-situ quarter-wavelength, which we call quarter-wave resonance. The peaks are below [Formula: see text], which is well below the transmitted pulse bandwidth and may occur as a modulation of a reflection sequence. Although the transit times cannot resolve both layer thickness and permittivity, reasonable values of permittivity give overburden layers above the targets on the order of [Formula: see text], which is consistent with the persistence of the resonances. Numerical models of metal objects beneath an interface between materials of strong permittivity contrast reveal that significant energy at the predicted frequencies requires cylinder diameters too large to be ordnance. However, strong resonances at the predicted frequencies result from flat metal sheets of 0.5–1 m dimension, and so we interpret the resonances to be caused by nonhazardous targets. Late winter is an ideal time to survey for targets in this area because the ice affords repeatable positioning for the antennas and thermal high-dielectric-contrast interfaces are then well developed. The bandwidth of the pulse we used appears ideally suited for both resolution of the shallow strata and detection of the resonances, thereby allowing the resonances to be checked against quarter-wave theory.
Electrical resistivity tomography applied to geologic, hydrogeologic, and engineering investigations at a former waste-disposal site
Authors: Chambers Jonathan E. , Kuras Oliver , Meldrum Philip I. , Ogilvy Richard D. , Hollands Jonathan
Published: November 2006

A former dolerite quarry and landfill site was investigated using 2D and 3D electrical resistivity tomography (ERT), with the aims of determining buried quarry geometry, mapping bedrock contamination arising from the landfill, and characterizing site geology. Resistivity data were collected from a network of intersecting survey lines using a Wenner-based array configuration. Inversion of the data was carried out using 2D and 3D regularized least-squares optimization methods with robust (L1-norm) model constraints. For this site, where high resistivity contrasts were present, robust model constraints produced a more accurate recovery of subsurface structures when compared to the use of smooth (L2-norm) constraints. Integrated 3D spatial analysis of the ERT and conventional site investigation data proved in this case a highly effective means of characterizing the landfill and its environs. The 3D resistivity model was successfully used to confirm the position of the landfill boundaries, which appeared as electrically well-defined features that corresponded extremely closely to both historic maps and intrusive site investigation data. A potential zone of leachate migration from the landfill was identified from the electrical models; the location of this zone was consistent with the predicted direction of groundwater flow across the site. Unquarried areas of a dolerite sill were imaged as a resistive sheet-like feature, while the fault zone appeared in the 2D resistivity model as a dipping structure defined by contrasting bedrock resistivities.
Characteristics of Pheochromocytoma in a 4‐ to 20‐Year‐Old Population
Authors: BARONTINI MARTA , LEVIN GLORIA , SANSO GABRIELA
Published: November 2006

Abstract:  Hypertension in children and adolescents has become a major health problem recently recognized, and in a significant number of patients it is due to an endocrine tumor. The aim of this study was to establish the characteristics of pheochromocytoma in a population of 58 patients between 4 and 20 years of age studied at our Center. They represented a 23% of the total population of 255 pheochromocytoma patients studied.
In the younger group (under 20 years of age), there was a marked predominance of severe sustained hypertension (93%), only 7% presented paroxysmal hypertension and none of them was normotensive. The youngsters studied showed a higher incidence of bilateral adrenal pheochromocytoma (34%) and extra‐adrenal pheochromocytoma (22%). Malignancy was found in 12% of these patients. In addition, the incidence of familial pheochromocytoma was elevated in these patients (39%). Surprisingly, in contrast with the adult population where the most frequent familial pheochromocytomas were multiple endocrine neoplasia (MEN) type 2A (15%), the younger population showed a higher predominance of von Hippel–Lindau (VHL) (28%) and lower incidence of MEN 2A, MEN 2B, neurofibromatosis (NF), and succinate dehydrogenase subunit B (SDHB).
In the VHL group, only two patients belonging to one family, showed the R167W mutation, while the others showed novel mutations in conserved amino acids.
It may be speculated that the high incidence of VHL in youngsters may account for the biochemical and clinical features they usually present.
Lack of Symptoms in Patients with Histologic Evidence of Pheochromocytoma
Authors: COHEN DEBBIE L. , FRAKER DOUGLAS , TOWNSEND RAYMOND R.
Published: November 2006

Abstract:  Pheochromocytoma (Pheo) is a rare cause of hypertension (HTN). Classically, a triad of symptoms includes sweating, palpitations, and headache. HTN is often present and labile. Although a triad of symptoms is cited as the most frequent presenting complaints, our clinical experience leads us to question how often these are present. Thirty‐two patients with histologically proven pheo or paraganglionoma were evaluated. Around 84.4% patients had adrenal pheos and 15.6% had extra‐adrenal pheos. Two patients had bilateral adrenal tumors, two had a history of prior pheos, and four had a family history of pheo. There were 19 (59.4%) female and 13 (40.6%) male patients. Six (18.7%) patients were black and 26 (81.3%) were white. The mean age at presentation was 43.2 ± 13.9 years. Two patients were known to have neurofibromatosis type 1, two had von Hippel–Lindau disease, one had multiple endocrine neoplasia 2A, and one PGL/SDHD genetic mutation. Twenty‐six patients had sporadic tumors or had not had genetic testing. Biochemical diagnosis was confirmed with 24‐h urine measurements. Urine catecholamine measurements were elevated at least 2 to 4 times above normal levels. Mean SBP readings at presentation were 128 ± 19 mmHg. Mean DBP readings were 81 ± 13 mmHg. Around 65.6% patients were hypertensive at presentation. Fifty percent of the patients had palpitations, 40.6% had tachycardia, 34.4% had sweating, and 31.3% had headaches. Initial presenting symptoms were diverse. Pheo is a rare clinical entity and remains a huge diagnostic challenge for all clinicians.
Catecholamine Excretion and Circadian Blood Pressure Profile in Patients with Pheochromocytoma
Authors: DABROWSKA ELZBIETA , LEWANDOWSKI JACEK , JEDRUSIK PIOTR , SYMONIDES BARTOSZ , WOCIAL BOZENA , LAPINSKI MARIUSZ , GACIONG ZBIGNIEW
Published: November 2006

Abstract:  Circadian blood pressure (BP) rhythm is often disturbed in patients with secondary forms of hypertension. The aim of the present article was to investigate changes in circadian BP profile parameters using two‐step statistical approach by Fourier analysis in relation to day and night urinary catecholamine excretion in 35 patients with pheochromocytoma (mean age 42 ± 19 years). Twenty‐four‐hour ambulatory BP measurements (ABPM) were obtained using the SpaceLabs 90,207 monitor. Daytime and night‐time urine collection was obtained in all patients to determine circadian catecholamine excretion. Fourier analysis was applied to estimate measures of BP circadian rhythm in ABPM, including the highest (Max) and lowest (Min) systolic (SBP) and diastolic (DBP) BP values, norad (ampSBP, ampDBP), and early acrophase (APSBP, APDBP). The Fourier indices of circadian BP rhythm were: MaxSBP 153 ± 28 mm Hg, MaxDBP 99 ± 16 mm Hg, MinSBP 117 ± 17 mm Hg, MinDBP 69 ± 11 mm Hg, ampSBP 18 ± 8 mm Hg, ampDBP 14 ± 5 mm Hg, APSBP 10 ± 5 (h), and APDBP 11 ± 3 (h). Urine noradrenaline (NA), adrenaline (A), and dopamine (DA) excretion during the day (d) and night (n) were: dNA 103.5 ± 89.8 μg/14 h, nNA 52 ± 70.8 μg/10 h, dA 13.2 ± 17.9 μg/14 h; nA 6.13 ± 9.6 μg/10 h, dD 181.8 ± 87.3 μg/14 h, and nD 89.3 ± 59.8 μg/10 h. A positive correlation was observed between urine dNa excretion and MaxDBP (r= 0.37, P < 0.05), and urine nNA and urine dA excretion were correlated with APDBP (r= 0.47, r= 0.35, respectively, both P < 0.05). Thus, in addition to the effect on mean 24‐h BP values, catecholamines released by tumor may also disturb circadian BP rhythm in patients with pheochromocytoma.
Characteristics of Blood Pressure in Pheochromocytoma
Authors: ZELINKA TOMÁŠ , PACAK KAREL , WIDIMSKÝ JIŘÍ
Published: November 2006

Abstract: Pheochromocytomas are catecholamine‐producing tumors arising from chromaffin cells. One of the most typical symptoms of the catecholamine‐excess state is hypertension either in the sustained or paroxysmal form, and its severity does not depend on the level of circulating catecholamines. On the other hand, hypertension in pheochromocytoma is very often characterized by the amelioration or even inversion of the circadian blood pressure rhythm. In some subjects, high circulating levels of catecholamines lead to the enhanced blood pressure variability. One possible explanation for such blood pressure variability is the desensitization of the catecholamine receptors due to high levels of circulating catecholamines.
Genetic Mutation Screening in an Italian Cohort of Nonsyndromic Pheochromocytoma/Paraganglioma Patients
Authors: CASTELLANO M. , MORI L. , GIACCHÈ M. , AGLIOZZO E. , TOSINI R. , PANAROTTO A. , CAPPELLI C. , MULATERO P. , CUMETTI D. , VEGLIO F. , AGABITI‐ROSEI E.
Published: November 2006

Abstract:  To assess the prevalence of genetic mutations in nonsyndromic pheochromocytoma/paraganglioma (PHEO/PGL) patients we have performed a systematic search for mutations in the succinate dehydrogenase (SDH) B, C, and D subunits, von Hippel–Lindau (VHL), and RET genes by direct bidirectional sequencing. Patients were selected from the medical records of hypertension centers. After exclusion of syndromic patients, 45 patients with familial (F+, n= 3) and sporadic (F−, n= 42) cases of isolated PHEO/PGL were considered. They included 35 patients with PHEO, 7 with PGL, and 3 with head/neck PGL (hnPGL). Three patients with PHEO (2F−, 1F+) presented VHL mutations (P86A, G93C, and R167W), six with PGL (4F−, 2F+) were positive for SDH or VHL mutations (SDHB R230G in two patients, SDHB S8F, R46Q, R90Q, and VHL P81L in one subject each), and one with hnPGL carried the SDHD 348–351delGACT mutation. We have also detected missense (SDHB S163P, SDHD H50R and G12S), synonymous (SDHB A6A, SDHD S68S), and intronic mutations that have been considered nonpathological polymorphic variants. No mutation was found in SDHC or RET genes. Our data indicate that germline mutations of VHL and SDH subunits are not infrequent in familial as well as in sporadic cases of nonsyndromic PHEO/PGL (overall, 12 of 45 probands, 22%). Accordingly, screening for such mutations seems to be justified. However, a more precise characterization of the functional relevance of any observed sequence variant and of other genetic and environmental determinants of neoplastic transformation is essential in order to plan appropriate protocols for family screening and follow‐up.
Paraganglioma Syndrome
Authors: SCHIAVI FRANCESCA , SAVVOUKIDIS THEODOROS , TRABALZINI FRANCO , GREGO FRANCO , PIAZZA MICHELE , AMISTÀ PIETRO , DEMATTÈ SERENA , PIANO ANTONELLA DEL , CECCHINI MARIA ENRICA , ERLIC ZORAN , DE LAZZARI PAOLA , MANTERO FRANCO , OPOCHER GIUSEPPE
Published: November 2006

Abstract:  Paraganglioma syndrome includes head and neck paraganglioma and pheochromocytoma, and is classified according to the three susceptibility genes involved, SDHB, SDHC, and SDHD. This study assessed the prevalence of germline mutations in SDHB, SDHC, and SDHD genes in a consecutive population admitted to Padova Hospital consisting of 20 patients with head and neck paraganglioma (HNP). Mutations were identified in the three genes in four affected individuals, three sporadic cases and one with family history of HNP. The novel SDHB p.R242C mutation was identified in a sporadic monolateral carotid body tumor. The SDHC p.Q147X mutation, the first to be described in Italy, was detected in a sporadic monolateral jugulotympanic paraganglioma. The SDHD p.Y114C mutation was identified in two unrelated patients, one familial case of bilateral carotid body tumor and one multiple paraganglioma. SDHB, SDHC, and SDHD molecular screening is important in all HNPs, with or without primary indicators of paraganglioma syndrome, to orient mutation‐driven clinical screening for additional HNPs and pheochromocytoma.
Transcriptional Regulation of Phenylethanolamine N‐Methyltransferase in Pheochromocytomas from Patients with von Hippel–Lindau Syndrome and Multiple Endocrine Neoplasia Type 2
Authors: HUYNH THANH‐TRUC , PACAK KAREL , WONG DONA L. , LINEHAN W. MARSTON , GOLDSTEIN DAVID S. , ELKAHLOUN ABDEL G. , MUNSON PETER J. , EISENHOFER GRAEME
Published: November 2006

Abstract:  Pheochromocytomas in multiple endocrine neoplasia type 2 (MEN‐2) express phenylethanolamine N‐methyltransferase (PNMT), the enzyme that catalyzes conversion of norepinephrine to epinephrine, whereas those in von Hippel–Lindau (VHL) syndrome do not. Consequently, pheochromocytomas in MEN‐2 produce epinephrine, whereas those in VHL syndrome produce mainly norepinephrine. This study examined whether transcription factors known to regulate expression of PNMT explain the different tumor phenotypes in these syndromes. Quantitative polymerase chain reaction (PCR) and Western blotting were used to assess levels of mRNA and protein for the glucocorticoid receptor, early growth response 1 (Egr‐1), the Sp1 transcription factor (Sp1), and MYC‐associated zinc finger protein (MAZ) in 6 MEN‐2 and 13 VHL tumors. Results were cross‐checked with data obtained using microarray gene expression profiling in a further set of 10 MEN‐2 and 12 VHL tumors. Pheochromocytomas in MEN‐2 and VHL syndrome did not differ in expression of the glucocorticoid receptor, Egr‐1, Sp1, or MAZ as assessed by quantitative PCR and Western blotting. Microarray data also indicated no relevant differences in expression of the glucocorticoid receptor, Egr‐1, MAZ, and the AP2 transcription factor. Thus, our results do not support a role for the above transcription factors in determining differences in expression of PNMT in pheochromocytomas from patients with VHL syndrome and MEN‐2. Microarray analysis, however, did indicate differences in expression of genes involved in neural crest cell lineage and chromaffin cell development, consistent with differential survival of PNMT‐expressing cells in the two syndromes.
Animal Models of Pheochromocytoma Including NIH Initial Experience
Authors: OHTA SHOICHIRO , LAI EDWIN W. , TANIGUCHI SHUN'ICHIRO , TISCHLER ARTHUR S. , ALESCI SALVATORE , PACAK KAREL
Published: November 2006

Abstract:  Mouse models have been used to study the mechanisms underlying the carcinogenesis of a wide variety of human cancer. A considerable number of mouse and rat models, used for the study of elementary tumorgenic mechanisms, were found to develop pheochromocytomas. Some of these models resemble hereditary syndrome‐related pheochromocytoma in humans and some may serve as a new starting point for human pheochromocytoma research. Recently, we generated a model of catecholamine‐producing metastatic pheochromocytoma in athymic nude mice using tail‐vein injection of mouse pheochromocytoma cells (MPCs). This and alternative animal models of metastatic pheochromocytoma are promising avenues in preclinical studies to evaluate new therapeutic approaches for malignant pheochromocytoma.
Anatomical and Functional Imaging of Tumors in Animal Models
Authors: MARTINIOVA LUCIA , OHTA SHOICHIRO , GUION PETER , SCHIMEL DANIEL , LAI EDWIN W. , KLAUNBERG BRENDA , JAGODA ELAINE , PACAK KAREL
Published: November 2006

Abstract:  This review focuses on anatomical (computed tomography, magnetic resonance imaging) and functional (positron emission tomography) imaging methods for tumor localization and identification of experimentally induced tumors in animal models, especially pheochromocytoma. Although anatomical imaging can precisely locate primary and metastatic tumors, functional imaging has high specificity for some tumors, especially those of endocrine origin. This is due to the fact that endocrine tumor cells take up hormone precursors, express hormone receptors and transporters, and synthesize, store, and release hormones. These characteristic properties of endocrine tumors enable investigators to create highly specific radiopharmaceuticals, particularly for positron emission tomography. For example, localization of pheochromocytoma involves [18F]‐6F‐dopamine. It is a highly specific radiopharmaceutical since it uses the norepinephrine transporter system expressed in most pheochromocytoma cells. Here we review both anatomical and functional imaging methods that are used conjointly in order to localize and identify specific characteristics of tumors.
Does the Expression of c‐kit (CD117) in Neuroendocrine Tumors Represent a Target for Therapy?
Authors: KOCH CHRISTIAN A. , GIMM OLIVER , VORTMEYER ALEXANDER O. , AL‐ALI HAIFA K. , LAMESCH PETER , OTT RUDOLF , KLUGE REGINE , BIERBACH UTA , TANNAPFEL ANDREA
Published: November 2006

Abstract:  Neuroendocrine tumors are very heterogeneous, develop from a variety of tissues, and can be difficult to diagnose. Without the clinical manifestation of metastases, it is often difficult to characterize them as malignant. Even so‐called completely (R0) resected tumors can spread clinically visible metastases within a few months after initial surgery. Treatment options for neuroendocrine tumors including pheochromocytoma are limited. Molecular targeted therapies using tyrosine kinase inhibitors might prove to be helpful in patients with these tumors. In an immunohistochemical study, we examined KIT in 26 pheochromocytomas, 8 of which were malignant (3 adrenal pheochromocytomas, 5 paragangliomas). KIT expression was found in one of these 8 malignant tumors. This 2.5‐cm‐large adrenal pheochromocytoma originated from a woman with neurofibromatosis type 1 and spread into spine, skull, and lung. KIT expression could be demonstrated in 5% of tumor cells. On the basis of KIT expression immunohistochemically, we treated patients with neuroendocrine (i.e., medullary thyroid cancer) and other tumors with imatinib 400 mg per day, but without efficacy after 2 months of therapy. Similar results were shown by other investigators. Therefore, monotherapy with imatinib may not be efficacious in patients with neuroendocrine tumors that express KIT. Tyrosine kinase inhibitors such as sorafenib that targets several receptors in addition to KIT may be more efficacious in treating patients with neuroendocrine tumors.
Expression and Processing of the Neuroendocrine Protein Secretogranin II in Benign and Malignant Pheochromocytomas
Authors: GUILLEMOT JOHANN , BARBIER LAURE , THOUENNON ERWAN , VALLET‐ERDTMANN VIRGINIE , MONTERO‐HADJADJE MAITE , LEFEBVRE HERVE , KLEIN MARC , MURESAN MIHAELA , PLOUIN PIERRE‐FRANÇOIS , SEIDAH NABIL , VAUDRY HUBERT , ANOUAR YOUSSEF , YON LAURENT
Published: November 2006

Abstract:  The aim of the present study was to compare the expression levels of secretogranin II (SgII), prohormone convertases (PC)1 and PC2, and the proteolytic processing of SgII in benign versus malignant pheochromocytomas. Quantitative (Q)‐PCR experiments indicated that SgII, PC1, and PC2 mRNAs were overexpressed in pheochromocytoma compared to non‐tumoral chromaffin cells (P < 0.001) and in benign compared to malignant tumors (P < 0.01). Western blot analysis using a human SgII antiserum revealed the occurrence of a 97‐kDa band corresponding to the expected size of SgII, with significantly higher quantities in benign than in malignant tumors (P < 0.05). Using antisera directed against sequential regions of SgII (N‐terminal, secretoneurin [SN], EM66, internal, and C‐terminal sequences), we observed distinct processing profiles between benign and malignant pheochromocytomas. In contrast, using PC1 and PC2 antisera no differences between the two types of tumors were found. RIA measurement showed that EM66 median values between benign and malignant chromaffin cell tumors were significantly different (128.5 vs. 6.3 ng/mg protein, respectively; P < 0.001). Taken together, these results indicate that, in pheochromocytoma, malignancy is associated with reduced PC1, PC2, and SgII mRNA expression and decreased levels of processing products of SgII, in line with the low concentrations of EM66 that occur in malignant tumors. These data support the notion that SgII‐processing products, such as EM66, could represent prognostic markers of pheochromocytomas.
Attitudinal Balance and Cause‐Related Marketing: An Empirical Application of Balance Theory
Authors: Basil Debra Z. , Herr Paul M.
Published: November 2006

We examine the effects of pre‐existing organizational attitudes on consumer response to cause‐related marketing (CRM) alliances, using a Balance Theory framework. Two experiments demonstrate that balanced attitudes (either both positive or both negative) resulted in perceptions of appropriateness, but did not necessarily lead to positive affect. The positive balance scenario led to a synergistic attitudinal boost when both pre‐existing attitudes were positive. Attitudinal contamination was evident when either pre‐existing attitude was negative. Fit operated within the balance scenario to enhance perceptions of the strength of the CRM alliance, leading to more positive responses.
To Be or Not Be? The Influence of Dissociative Reference Groups on Consumer Preferences
Authors: White Katherine , Dahl Darren W.
Published: November 2006

The current research explores the effects of dissociative reference groups on consumer preferences. Males had more negative evaluations of, and were less inclined to choose, a product associated with a dissociative (i.e., female) reference group than a neutral product (Study 1). This finding was moderated by whether the product was consumed in public or private (Study 2) and public self‐consciousness (Study 3). We suggest the mechanism underlying our effects is a desire to present a positive self‐image to others. The role of dissociative reference groups in marketing communications is discussed.
The Horizontal/Vertical Distinction in Cross‐Cultural Consumer Research
Authors: Shavitt Sharon , Lalwani Ashok K. , Zhang Jing , Torelli Carlos J.
Published: November 2006

We argue for the importance of a relatively new cultural distinction in thehorizontal(valuing equality) orvertical(emphasizing hierarchy) nature of cultures and cultural orientations. A review of the existing cross‐cultural literature is presented suggesting that, although the contribution of the horizontal/vertical distinction is sometimes obscured by methods that conflate it with other dimensions, its impact is distinct from that associated with individualism–collectivism. We present studies that highlight several sources of value for the horizontal/vertical distinction—as a predictor of new consumer psychology phenomena and as a basis for refining the understanding of known phenomena. Results support the utility of examining this distinction for the understanding of personal values, advertising and consumer persuasion, self‐presentational patterns, and gender differences. Methodological issues in studying the horizontal/vertical distinction are also discussed.
Using the Horizontal/Vertical Distinction to Advance Insights Into Consumer Psychology
Authors: Meyers‐Levy Joan
Published: November 2006

This commentary aims to build on Shavitt, Lalwani, Zhang, and Torelli's (2006) target article and extant work that demonstrates the value added by considering people's vertical or horizontal orientation. I suggest several ways by which one might attempt to advance literature concerning the horizontal/vertical distinction as well as our understanding of consumer psychology. In particular, I offer ideas about how pertinent methodological concerns might be addressed, how this stream of work may help predict certain consumer activities or interests, and some ways by which this body of literature can be applied to other domains of inquiry. Hopefully, such ideas and suggestions will prompt further inquiry into this fertile area of research.
Reflections on the Meaning and Structure of the Horizontal/Vertical Distinction
Authors: Shavitt Sharon , Zhang Jing , Torelli Carlos J. , Lalwani Ashok K.
Published: November 2006

The commentaries by Aaker (2006), Meyers‐Levy (2006), and Oyserman (2006) extend the implications of the horizontal/vertical distinction described in our article (Shavitt, Lalwani, Zhang, & Torelli, 2006) in a number of interesting directions. We join these authors in calling for further research on horizontal and vertical individualism and collectivism constructs. We also highlight conceptual and structural issues that remain to be resolved and evaluate priming and other operational approaches to the study of horizontal and vertical individualism and collectivism.
The Effect of Corporate Social Responsibility (CSR) Activities on Companies With Bad Reputations
Authors: Yoon Yeosun , Gürhan‐Canli Zeynep , Schwarz Norbert
Published: November 2006

Based on theories of attribution and suspicion, three experiments highlight the mediating role of perceived sincerity of motives in determining the effectiveness of CSR activities. CSR activities improve a company's image when consumers attribute sincere motives, are ineffective when sincerity of motives is ambiguous, and hurt the company's image when motives are perceived as insincere. Variables affecting perceived sincerity include the benefit salience of the cause, the source through which consumers learn about CSR, and the ratio of CSR contributions and CSR‐related advertising. High benefit salience of the cause hurts the company, in particular when consumers learn about it from a company source. This backfire effect can be overcome by spending more on CSR activities than on advertising that features CSR.
Harmony in Linguistic Cognition
Authors: Smolensky Paul
Published: November 2006

In this article, I survey the integrated connectionist/symbolic (ICS) cognitive architecture in which higher cognition must be formally characterized on two levels of description. At the microlevel, parallel distributed processing (PDP) characterizes mental processing; this PDP system has special organization in virtue of which it can be characterized at the macrolevel as a kind of symbolic computational system. The symbolic system inherits certain properties from its PDP substrate; the symbolic functions computed constitute optimization of a well‐formedness measure called Harmony. The most important outgrowth of the ICS research program is optimality theory (Prince & Smolensky, 1993/2004), an optimization‐based grammatical theory that provides a formal theory of cross‐linguistic typology. Linguistically, Harmony maximization corresponds to minimization of markedness or structural ill‐formedness. Cognitive explanation in ICS requires the collaboration of symbolic and connectionist principles. ICS is developed in detail in Smolensky and Legendre (2006a); this article is a précis of and guide to those volumes.