bluuebunny/crossref_metadata_2025 huggingface dataset:
The Swiss IMRT dosimetry intercomparison using a thorax phantom
Authors: Schiefer H. , Fogliata A. , Nicolini G. , Cozzi L. , Seelentag W. W. , Born E. , Hasenbalg F. , Roth J. , Schnekenburger B. , Münch‐Berndl K. , Vallet V. , Pachoud M. , Reiner B. , Dipasquale G. , Krusche B. , Fix M. K.
Published: July 2010

Purpose:

In 2008, a national intensity modulated radiation therapy (IMRT) dosimetry intercomparison was carried out for all 23 radiation oncology institutions in Switzerland. It was the aim to check the treatment chain focused on the planning, dose calculation, and irradiation process.

Methods:

A thorax phantom with inhomogeneities was used, in which thermoluminescence dosimeter (TLD) and ionization chamber measurements were performed. Additionally, absolute dosimetry of the applied beams has been checked. Altogether, 30 plan‐measurement combinations have been used in the comparison study. The results have been grouped according to dose calculation algorithms, classified as “type a” or “type b,” as proposed by Knöös et al. [“Comparison of dose calculation algorithms for treatment planning in external photon beam therapy for clinical situations,” Phys. Med. Biol. 51, 5785–5807 (2006)].

Results:

Absolute dosimetry check under standard conditions: The mean ratio between the dose derived from the single field measurement and the stated dose, calculated with the treatment planning system, was for the ionization chamber and ( deviation) for the TLD measurements. IMRT Plan Check: In the lung tissue of the planning target volume, a significantly better agreement between measurements (TLD, ionization chamber) and calculations is shown for type b algorithms than for type a . In regions outside the lungs, the absolute differences between TLD measured and stated dose values, relative to the prescribed dose, , are and , respectively. These data show the same degree of accuracy between the two algorithm types if low‐density medium is not present.

Conclusions:

The results demonstrate that the performed intercomparison is feasible and confirm the calculation accuracies of type a and type b algorithms in a water equivalent and low‐density environment. It is now planned to offer the intercomparison on a regular basis to all Swiss institutions using IMRT techniques.
Collimator angle influence on dose distribution optimization for vertebral metastases using volumetric modulated arc therapya)
Authors: Mancosu Pietro , Cozzi Luca , Fogliata Antonella , Lattuada Paola , Reggiori Giacomo , Cantone Marie Claire , Navarria Pierina , Scorsetti Marta
Published: July 2010

Purpose:

The cylindrical symmetry of vertebrae favors the use of volumetric modulated arc therapy in generating a dose “hole” on the center of the vertebrae limiting the dose to the spinal cord. The authors have evaluated if collimator angle is a significant parameter for dose distribution optimization in vertebral metastases.

Methods:

Three patients with one‐three vertebrae involved were considered. Twenty‐one differently optimized plans (nine single‐arc and 12 double‐arc plans) were performed, testing various collimator angle positions. Clinical target volume was defined as the whole vertebrae, excluding the spinal cord canal. The planning target volume (PTV) was defined as. Dose prescription was with normalization to PTV mean dose. The dose at of spinal cord was limited to 11.5Gy.

Results:

The best plans in terms of target coverage and spinal cord sparing were achieved by two arcs and Arc1–80° and Arc2–280° collimator angles for all the cases considered (i.e., leaf travel parallel to the spinal cord primary orientation). If one arc is used, only 80° reached the objectives.

Conclusions:

This study demonstrated the role of collimation rotation for the vertebrae metastasis irradiation, with the leaf travel parallel to the spinal cord primary orientation to be better than other solutions. Thus, optimal choice of collimator angle increases the optimization freedom to shape a desired dose distribution.
Extraction of depth‐dependent perturbation factors for parallel‐plate chambers in electron beams using a plastic scintillation detector
Authors: Lacroix Frédéric , Guillot Mathieu , McEwen Malcolm , Cojocaru Claudiu , Gingras Luc , Beddar A. Sam , Beaulieu Luc
Published: July 2010

Purpose: This work presents the experimental extraction of the overall perturbation factor in megavoltage electron beams for NACP‐02 and Roos parallel‐plate ionization chambers using a plastic scintillation detector (PSD).

Methods: The authors used a single scanning PSD mounted on a high‐precision scanning tank to measure depth‐dose curves in 6, 12, and 18 MeV clinical electron beams. The authors also measured depth‐dose curves using the NACP‐02 and PTW Roos chambers.

Results: The authors found that the perturbation factors for the NACP‐02 and Roos chambers increased substantially with depth, especially for low‐energy electron beams. The experimental results were in good agreement with the results of Monte Carlo simulations reported by other investigators. The authors also found that using an effective point of measurement (EPOM) placed inside the air cavity reduced the variation of perturbation factors with depth and that the optimal EPOM appears to be energy dependent.

Conclusions: A PSD can be used to experimentally extract perturbation factors for ionization chambers. The dosimetry protocol recommendations indicating that the point of measurement be placed on the inside face of the front window appear to be incorrect for parallel‐plate chambers and result in errors in the of approximately 0.4 mm at 6 MeV, 1.0 mm at 12 MeV, and 1.2 mm at 18 MeV.
Radiation dose evaluation in tomosynthesis and C‐arm cone‐beam CT examinations with an anthropomorphic phantom
Authors: Koyama Shuji , Aoyama Takahiko , Oda Nobuhiro , Yamauchi‐Kawaura Chiyo
Published: July 2010

Purpose:

The objective of this study was to evaluate organ dose and the effective dose to patients undergoing tomosynthesis (TS) and C‐arm cone‐beam computed tomography (CBCT) examinations and to compare the doses to those in multidetector CT (MDCT) scans.

Methods:

Patient doses were measured with small sized silicon‐photodiode dosimeters, 48 in number, which were implanted at various tissue and organ positions within an anthropomorphic phantom. Output signals from photodiode dosimeters were read out on a personal computer, from which organ and effective doses were computed. The doses in head, chest, abdomen, and hip‐joint TS, and in head and abdomen C‐arm CBCT were evaluated for routine protocols on Shimadzu TS and C‐arm CBCT systems, and the doses in MDCT with the same scan regions as in TS and CBCT were on Toshiba 64‐detector‐row CT scanners.

Results:

In TS examination of the head, chest, abdomen, and hip‐joint, organ doses for organs within scan ranges were 1–4 mGy, and effective doses were 0.07 mSv for the head scan and around 1 mSv for other scans. In C‐arm CBCT examinations of the head and abdomen, organ doses within scan range were 2–37 mGy, and effective doses were 1.2 mSv for the head scan and 4–5 mSv for abdominal scans. Effective doses in TS examinations were approximately a factor of 10 lower, while the doses in CBCT examinations were nearly the same level, compared to the doses in the corresponding MDCT examinations.

Conclusions:

TS examinations with low doses and excellent resolutions in coronal images compared to recent MDCT would widely be used in tomographic examinations of the chest, abdomen, pelvis, skeletal‐joints, and knee instead of MDCT examinations with significantly high doses. Since patient dose in C‐arm CBCT was nearly the same level as that in recent MDCT, the same consideration for high radiation dose would be required for the use of CBCT.
Validation of a treatment plan‐based calibration method for 2D detectors used for treatment delivery quality assurance
Authors: Olch Arthur J. , Whitaker Matthew L.
Published: July 2010

Purpose:

Dosimetry using film, CR, electronic portal imaging, or other 2D detectors requires calibration of the raw image data to obtain dose. Typically, a series of known doses are given to the detector, the raw signal for each dose is obtained, and a calibration curve is created. This calibration curve is then applied to the measured raw signals to convert them to dose. With the advent of IMRT, film dosimetry for quality assurance has become a routine and labor intensive part of the physicist's day. The process of calibrating the film or other 2D detector takes time and additional film or images for performing the calibration, and comes with its own source of errors. This article studies a new methodology for the relative dose calibration of 2D imaging detectors especially useful for IMRT QA, which relies on the treatment plan dose image to provide the dose information which is paired with the raw QA image data after registration of the two images (plan‐based calibration).

Methods:

Validation of the accuracy and robustness of the method is performed on ten IMRT cases performed using EDR2 film with conventional and plan‐based calibration. Also, for each of the ten cases, a 5 mm registration error was introduced and the Gamma analysis was reevaluated. In addition, synthetic image tests were performed to test the limits of the method. The Gamma analysis is used as a measure of dosimetric agreement between plan and film for the clinical cases and a dose difference metric for the synthetic cases.

Results:

The QA image calibrated by the plan‐based method was found to more accurately match the treatment plan doses than the conventionally calibrated films and also to reveal dose errors more effectively when a registration error was introduced. When synthetic acquired images were systematically studied, localized and randomly placed dose errors were correctly identified without excessive falsely passing or falsely failing pixels, unless the errors were concentrated in a majority of pixels in a contiguous narrow dose band. Irregularities seen in the calibration curve expose these errors.

Conclusions:

The plan‐based calibration method was found to be an accurate, efficient procedure, capable of detecting IMRT QA relative dosimetry errors as well as, or better than conventional calibration methods.
High‐resolution x‐ray guided three‐dimensional diffuse optical tomography of joint tissues in hand osteoarthritis: Morphological and functional assessments
Authors: Yuan Zhen , Zhang Qizhi , Sobel Eric S. , Jiang Huabei
Published: July 2010

Purpose:

The aim of this study was to investigate the potential use of multimodality functional imaging techniques to identify the quantitative optical findings that can be used to distinguish between osteoarthritic and normal finger joints.

Methods:

Between 2006 and 2009, the distal interphalangeal finger joints from 40 female subjects including 22 patients and 18 healthy controls were examined clinically and scanned by a hybrid imaging system. This system integrated x‐ray tomosynthetic setup with a diffuse optical imaging system. Optical absorption and scattering images were recovered based on a regularization‐based hybrid reconstruction algorithm. A receiver operating characteristic curve was used to calculate the statistical significance of specific optical features obtained from osteoarthritic and healthy joints groups.

Results:

The three‐dimensional optical and x‐ray images captured made it possible to quantify optical properties and joint space width of finger joints. Based on the recovered optical absorption and scattering parameters, the authors observed statistically significant differences between healthy and osteoarthritis finger joints.

Conclusions:

The statistical results revealed that sensitivity and specificity values up to 92% and 100%, respectively, can be achieved when optical properties of joint tissues were used as classifiers. This suggests that these optical imaging parameters are possible indicators for diagnosing osteoarthritis and monitoring its progression.
FAN1 Acts with FANCI-FANCD2 to Promote DNA Interstrand Cross-Link Repair
Authors: Liu Ting , Ghosal Gargi , Yuan Jingsong , Chen Junjie , Huang Jun
Published: July 2010

Fanconi Anemia Protein in DNA Binding

Fanconi anemia patients suffer a number of symptoms, including increased sensitivity to chemicals that cross-link DNA strands of the double helix together. Such aberrations can lead to genome instability. Mutations in 13 different genes implicated in repairing damaged DNA are known to be involved in the disease.

Liu
et al.

(p.
693
, published online 29 July) have identified a new factor, FAN1 (Fanconi anemia–associated nuclease 1), which they find to be associated with a complex of two of the FANC proteins, FANCI and FANCD2 (the ID complex). The mono-ubiquitylated ID complex locates to sites of DNA damage to which it recruits FAN1, a mono-ubiquitin–binding protein. FAN1 has a DNA branch–specific nuclease activity that is required for the removal and subsequent repair of the interstrand DNA cross-links.
The poor man's cell block: Figure 1
Authors: Mayall Frederick , Darlington Ann
Published: July 2010

The authors describe a simple method for making formalin or isopropyl alcohol vapour fixed cell blocks from fine needle aspiration cytology specimens that we refer to as ‘The Poor Man's Cell Block.’
Methylation of TET2, CBL and CEBPA in Ph-negative myeloproliferative neoplasms
Authors: Chim C S , Wan T S , Fung T K , Wong K F
Published: July 2010

A loss-of-function mutation of TET2, CBL and CEBPA has been implicated in the pathogenesis or leukaemic transformation of myeloproliferative neoplasm. As tumour suppressor genes may potentially be inactivated by promoter hypermethylation, the authors studied the methylation status of these genes in three cell lines and diagnostic marrow samples from 45 patients with myeloproliferative neoplasm (MPN) (essential thrombocythaemia, N=34; polycythaemia vera, N=7 and primary myelofibrosis, N=4) by methylation-specific PCR. TET2 was heterozygously methylated in MEG-01 and K562 but completely unmethylated in HEL. On the other hand, both CBL and CEBPA were completely unmethylated in all three cell lines. In the primary marrow samples, methylation of TET2 occurred in two (5.9%) patients with essential thrombocythaemia (4.4% of all patients), both without JAK2 V617 mutation, but not in polycythaemia vera or primary myelofibrosis. There was no association between TET2 methylation with the type of MPN (p=0.713). Hypermethylation of CBL or CEBPA was not detected in any patients. In summary, methylation of TET2, CBL and CEBPA is infrequent in MPN at diagnosis. The role of methylation of these genes at the time of leukaemic transformation warrants further study.
VISCOUS DARK ENERGY AND GENERALIZED SECOND LAW OF THERMODYNAMICS
Authors: SETARE M. R. , SHEYKHI A.
Published: July 2010

We examine the validity of the generalized second law of thermodynamics in a non-flat universe in the presence of viscous dark energy. First we assume that the universe is filled only with viscous dark energy. Then, we extend our study to the case where there is an interaction between viscous dark energy and pressureless dark matter. We examine the time evolution of the total entropy, including the entropy associated with the apparent horizon and the entropy of the viscous dark energy inside the apparent horizon. Our study shows that the generalized second law of thermodynamics is always protected in a universe filled with interacting viscous dark energy and dark matter in a region enclosed by the apparent horizon. Finally, we show that the the generalized second law of thermodynamics is fulfilled for a universe filled with interacting viscous dark energy and dark matter by taking into account the Casimir effect.
ON M-THEORY EMBEDDING OF TOPOLOGICALLY MASSIVE GRAVITY
Authors: LÜ H. , WANG ZHAO-LONG
Published: July 2010

We show that topologically massive gravity can be obtained by the consistent Kaluza–Klein reduction from recently constructed seven-dimensional gravity with topological terms. The internal four-manifold should be Einstein with the Pontryagin four-form constantly proportional to the volume form. We also discuss the possible lift of the system to D = 11. This enables us to connect the mass parameter [Formula: see text] in D = 3 to the M5-brane charge. The dimensionless quantity [Formula: see text] is discrete and proportional to N, where N is the number of M5-branes.
CYCLIC OXIDATION OF Ti-48%Al-2%Cr-2%Nb-(0~1%)W ALLOYS BETWEEN 800 AND 1000°C IN AIR
Authors: BAK SANG-HWAN , SEO DONG YI , KIM SEON-JIN , LEE JAE CHUN , LEE DONG BOK
Published: July 2010

Ti-48%Al-2%Cr-2%Nb-(0, 0.5, 1) at.%W alloys were synthesized via the powder metallurgical route, and cyclically oxidized at 800, 900, or 1000°C in air for up to 100 h in order to find the effects of W on their oxidation characteristics. At 800°C, they oxidized relatively slowly, and the scales were thin and adherent. At 900°C, the scales began to spall locally. At 1000°C, they spalled repetitively during oxidation. Cr , Nb , and W improved the cyclic oxidation resistance of TiAl alloys. The oxides formed were TiO2 and Al2O3 , which contained the alloying elements of Cr , Nb , and W . Nitrides formed were TiN and Ti2AlN .
THE STUDY ON GRANTING BIOACTIVITY OF Ti ALLOY BY SURFACE TREATMENT
Authors: HA N. R. , YANG Z. X. , KIM G. C. , HWANG K. H. , SEO D. S. , LEE J. K.
Published: July 2010

Titanium alloys are superior of biocompatibility, mechanical properties and chemical stability. The biocompatibility of Ti alloy is related to the surface effect between human tissue and implant. Therefore, the purpose of this study is to investigate the bioactivity of Ti alloy by alkali and acid chemical surface treatment; and the biocompatibility of Ti alloy was evaluated by in vitro test. Higher bone-bonding ability and bioactivity of the substrate were obtained by the formation of apatite layers on the Ti alloy in simulated body fluid. The microstructures of apatite layer were investigated by scanning electron microscope (SEM) and the formed phases were analyzed with X-ray diffraction (XRD).
CHARACTERIZATIONS OF THE CORE-SHELL STRUCTURED MgB2/CARBON FIBER SYNTHESIS BY RF-SPUTTERING AND THERMAL EVAPORATION
Authors: PARK SUNG CHANG , LIM YEONG JIN , LEE TAE-KEUN , KIM CHEOL JIN
Published: July 2010

MgB2 /carbon fibers have been synthesized by the combination of RF-sputtering of B and thermal evaporation of Mg , followed by co-evaporation. First, boron layer was deposited by RF-sputtering on the carbon fiber with average diameter of 7.1 μm. Later this coated layer of B was reacted with Mg vapor to transform into MgB2 . Since the MgB2 reaction proceed with Mg diffusion into the boron layer, Mg vapor pressure and the diffusion time had to be controlled precisely to secure the complete reaction. Also the deposition rate of each element was controlled separately to obtain stoichiometric MgB2 , since Mg was evaporated by thermal heating and B by sputtering system. The sintered B target was magnetron sputtered at the RF-power of ~200 W, which corresponded to the deposition rate of ~3.6 Å/s. With the deposition rate of B fixed, the vapor pressure of Mg was controlled by varying the temperature of tungsten boat with heating element control unit between 100 and 900°C. The MgB2 layers with the thickness of 200–950 nm could be obtained and occasionally MgO appeared as a second phase. Superconducting transition temperatures were measured around ~38 K depending on the deposition condition.
DEPOSITION OF Al2O3 POWDERS USING NANO-PARTICLE DEPOSITION SYSTEM
Authors: SONG WOOJIN , JUNG KYUBONG , CHUN DOO-MAN , AHN SUNG-HOON , LEE CAROLINE SUNYONG
Published: July 2010

In this paper, alumina film was deposited using supersonic micronozzle in nano-particle deposition System (NPDS). Powder deposition at room temperature is important in the field of film deposition since high processing temperature can be a serious limitation for the deposition on flexible substrate. Previously, many studies have been reported on particle deposition, such as aerosol deposition method (ADM) or cold spray method. However, these deposition methods cannot be applied to various types of powders. Recently, NPDS using aluminum nozzle was designed to resolve these problems but it cannot deposit precise patterns less than 1 mm. In this study, alumina particles were deposited using Silicon-based micronozzle in NPDS. Three-dimensional silicon micronozzle was fabricated using semiconductor processing method, specifically deep reactive ion etching (DRIE) method. The silicon micronozzle fabricated by Bosch process is advantageous over the conventionally used nozzle, since the hardness of silicon is higher than that of aluminum and the lifetime can be increased. In this study, alumina nano-particles were accelerated to supersonic level at the neck of micronozzle and deposited on the substrate in a low vacuum condition. The film characteristics were evaluated using field-emission scanning electronic microscope (FE-SEM) and alpha step to measure its thickness of the deposited layer. The deposition result showed that alumina powders were successfully deposited using the fabricated micronozzle by means of NPDS.
SELECTIVE SYNTHESIS OF ZnO ARRAYS
Authors: LU PAI , XUE DONGFENG
Published: July 2010

ZnO nanosheet and nanorod arrays were selectively synthesized on zinc substrate through the reaction of zinc foil with dilute alkaline solution at 120–180°C for 12–24 h. The microscopic morphology and crystal phase of these products were characterized by scanning electron microscopy (SEM), and X-ray powder diffraction (XRD). The growth mechanism and morphology evolution of the nanostructured ZnO arrays were investigated. Due to their uniform morphologies and large surface areas, the as-prepared ZnO nanosheet and nanorod arrays may be used as photovoltaic films and gas sensors for future applications.
A THEORETICAL INVESTIGATION OF THE INTERACTIONS BETWEEN CELLULOSE AND 1-BUTYL-3-METHYLIMIDAZOLIUM CHLORIDE
Authors: GUO JINXIN , ZHANG DONGJU , LIU CHENGBU
Published: July 2010

To better understand the interactions between cellulose and imidazolium-based ionic liquids (ILs), quantum chemistry calculations have been performed on the systems composed of one cellulose unit with the anion, cation, and the ion pair of 1-butyl-3-methylimidazolium chloride ( [bmim]Cl ) by the density functional method. The relevant geometries, energies, electronic properties and IR characteristics have been systematically discussed. It is found that H-bond interaction is essential for the systems under consideration. The hydroxyls in cellulose bind to chloride anions strongly through H -bonds, which could be predominant to cellulose dissolution in ILs. Chloride anion prefers to occur between two adjacent hydroxyls in cellulose to form bridging OH⋯Cl⋯HO hydrogen bonds. In contrast, weak hydrogen bonds exist between the hydrogen atoms on the imidazolium cation and hydroxyl oxygen atoms of cellulose, which are too much weaker than the hydrogen bonds between the cellulose hydroxyls and chloride anions to be detected by the experiments. The phenomena of cellulose dissolution in ILs should be a result of the joint interactions of chloride anions and [bmim]+ cations with hydroxyls in cellulose.
Transcriptional inhibition of intestinal NHE8 expression by glucocorticoids involves Pax5
Authors: Xu Hua , Zhang Bo , Li Jing , Chen Huacong , Wang Chunhui , Ghishan Fayez K.
Published: July 2010

Sodium/hydrogen exchangers (NHEs) are a family of proteins that transport sodium ions into the cells by moving protons out of the cells. They play a major role in sodium absorption, cell volume regulation, and intracellular pH regulation. Three out of nine identified NHEs (NHE2, NHE3, and NHE8) are expressed on the apical membrane of intestinal epithelial cells. Glucocorticoids have been found to regulate NHE3 function in the intestine, but it is unknown if they have a similar function on NHE8 expression. Interestingly, high glucocorticoid levels in the intestine coincide chronologically with the change from high expression of NHE8 to high expression of NHE3. Studies were performed to explore the role of glucocorticoids on NHE8 expression during intestinal maturation. Brush-border membrane vesicles were isolated from intestinal epithelia, and Western blotting was performed to determine NHE8 protein expression of suckling male rats treated with methylpredisolone. Real-time PCR was used to quantitate NHE8 mRNA expression in rats and Caco-2 cells. Human NHE8 promoter activity was characterized through transfection of Caco-2 cells. Gel mobility shift assays (GMSAs) were used to identify the promoter sequences and the transcription factors involved in glucocorticoid-mediated regulation. Our results showed that the expression of NHE8 mRNA and protein was decreased in glucocorticoid-treated rats and human intestinal epithelial cells (Caco-2). The activity of the human NHE8 gene promoter transfected in Caco-2 cells was also reduced by glucocorticoid treatment. GMSAs suggested that the reduction in promoter activity in the presence of glucocorticoids was due to enhanced transcription factor Pax5 binding on the NHE8 proximal promoter region. In conclusion, this study showed that glucocorticoids inhibit NHE8 gene expression by increasing Pax5 binding on NHE8 gene promoter, suggesting an important role for Pax5 during intestinal maturation.
CFTR and calcium-activated chloride channels in primary cultures of human airway gland cells of serous or mucous phenotype
Authors: Fischer Horst , Illek Beate , Sachs Lorne , Finkbeiner Walter E. , Widdicombe Jonathan H.
Published: July 2010

Using cell culture models, we have investigated the relative importance of cystic fibrosis transmembrane conductance regulator (CFTR) and calcium-activated chloride channels (CaCC) in Cl secretion by mucous and serous cells of human airway glands. In transepithelial recordings in Ussing chambers, the CFTR inhibitor CFTRinh-172 abolished 60% of baseline Cl secretion in serous cells and 70% in mucous. Flufenamic acid (FFA), an inhibitor of CaCC, reduced baseline Cl secretion by ∼20% in both cell types. Methacholine and ATP stimulated Cl secretion in both cell types, which was largely blocked by treatment with 1,2-bis(2-aminophenoxy)ethane- N, N, N′, N′-tetraacetic acid (BAPTA) and partially by mucosal FFA or CFTRinh-172 with the exception of methacholine responses in mucous cells, which were not blocked by FFA and partially (∼60%) by CFTRinh-172. The effects of ionomycin on short-circuit current ( Isc) were less than those of ATP or methacholine. Forskolin stimulated Cl secretion only if Cl in the mucosal medium was replaced by gluconate. In whole cell patch-clamp studies of single isolated cells, cAMP-induced Cl currents were ∼3-fold greater in serous than mucous cells. Ionomycin-induced Cl currents were 13 times (serous) or 26 times (mucous) greater than those generated by cAMP and were blocked by FFA. In serous cells, mRNA for transmembrane protein 16A (TMEM16A) was ∼10 times more abundant than mRNA for CFTR. In mucous cells it was ∼100 times more abundant. We conclude: 1) serous and mucous cells both make significant contributions to gland fluid secretion; 2) baseline Cl secretion in both cell types is mediated predominantly by CFTR, but CaCC becomes increasingly important after mediator-induced elevations of intracellular Ca; and 3) the high CaCC currents seen in patch-clamp studies and the high TMEM16A expression in intact polarized cells sheets are not reflected in transepithelial current recordings.
Thermoregulation in multiple sclerosis
Authors: Davis Scott L. , Wilson Thad E. , White Andrea T. , Frohman Elliot M.
Published: July 2010

Multiple sclerosis (MS) is a progressive neurological disorder that disrupts axonal myelin in the central nervous system. Demyelination produces alterations in saltatory conduction, slowed conduction velocity, and a predisposition to conduction block. An estimated 60–80% of MS patients experience temporary worsening of clinical signs and neurological symptoms with heat exposure. Additionally, MS may produce impaired neural control of autonomic and endocrine functions. This review focuses on five main themes regarding the current understanding of thermoregulatory dysfunction in MS: 1) heat sensitivity; 2) central regulation of body temperature; 3) thermoregulatory effector responses; 4) heat-induced fatigue; and 5) countermeasures to improve or maintain function during thermal stress. Heat sensitivity in MS is related to the detrimental effects of increased temperature on action potential propagation in demyelinated axons, resulting in conduction slowing and/or block, which can be quantitatively characterized using precise measurements of ocular movements. MS lesions can also occur in areas of the brain responsible for the control and regulation of body temperature and thermoregulatory effector responses, resulting in impaired neural control of sudomotor pathways or neural-induced changes in eccrine sweat glands, as evidenced by observations of reduced sweating responses in MS patients. Fatigue during thermal stress is common in MS and results in decreased motor function and increased symptomatology likely due to impairments in central conduction. Although not comprehensive, some evidence exists concerning treatments (cooling, precooling, and pharmacological) for the MS patient to preserve function and decrease symptom worsening during heat stress.
Xrcc2 Modulates Spontaneous and Radiation-Induced Tumorigenesis in Apcmin/+ Mice
Authors: Haines Jackie W. , Coster Margaret R. , Adam Julie , Cheeseman Michael , Ainsbury Elizabeth A. , Thacker John , Bouffler Simon D.
Published: July 2010

XRCC2 has an important role in repair of DNA damage by homologous recombination. Adult Apcmin/+ (min, multiple intestinal neoplasia) mice, wild-type or heterozygous for Xrcc2 deficiency, were sham-irradiated or 2-Gy X-irradiated. Spontaneous mammary and intestinal tumor incidences are lower in Apcmin/+ Xrcc2+/− mice than in Apcmin/+ Xrcc2+/+ mice (mammary tumors: 14% and 38%, respectively, χ2 P = 0.03; intestinal adenomas in mice reaching full life span: 108.6 and 130.1, respectively, t-test P = 0.005). Following irradiation, the increase in mammary tumors was greatest in female mice heterozygous for Xrcc2 (7.25 ± 0.50-fold in Apcmin/+ Xrcc2+/− mice compared with 2.57 ± 0.35-fold in Apcmin/+ Xrcc2+/+ mice; t-test P < 0.001). The increase in intestinal tumor multiplicity following irradiation was significantly greater in Apcmin/+ Xrcc2+/− mice (Apcmin/+ Xrcc2+/−, 4.14 ± 0.05-fold, versus Apcmin/+ Xrcc2+/+, 3.30 ± 0.05-fold; t-test P < 0.001). Loss of heterozygosity of all chromosome 18 markers was greater in intestinal tumors from Apcmin/+ Xrcc2+/− mice than in tumors from Apcmin/+ Xrcc2+/+ mice. These findings indicate that Xrcc2 haploinsufficiency reduces spontaneous tumor incidence on an Apcmin/+ background but increases the tumorigenic response to radiation. Mol Cancer Res; 8(9); 1227–33. ©2010 AACR.
Myocardial Calcification and Hypertension following Chronic Renal Failure and Ameliorative Effects of Furosemide and Captopril
Authors: Rahman Mizanur , Kim Shang-Jin , Kim Jin-Shang , Kim Sung-Zoo , Lee Young-Up , Kang Hyung-Sub
Published: July 2010

Objectives: The aim of this study was to prevent metastatic myocardial calcification and hypertension following chronic renal failure (CRF). Methods: A total of 50 male Sprague-Dawley rats were allocated to one of five groups: the control group (sham), the NxNT group (nephrectomized rats receiving no treatment), the NxFuro group (nephrectomized rats treated with furosemide), the NxCap group (nephrectomized rats treated with captopril) and the NxFuroCap group (nephrectomized rats treated with furosemide and captopril). Surgery (5/6 nephrectomy) was performed to induce CRF. Oral treatment with furosemide (20 mg/kg) and/or captopril (0.05 mg/kg) was given twice daily for 5 weeks. Parameters were studied after 5 weeks. Results: In the NxNT group, arterial blood pressure was significantly increased compared with the controls. Monotherapy with furosemide or captopril and both in combination maintained blood pressure to near or below control. Myocardial and remnant-kidney calcification was detected in NxNT rats, but calcification was absent in the NxFuroCap rats. Cardiac hypertrophy and fibrosis was observed in the NxNT group but not in treatment groups. Both plasma inorganic phosphate and Ca2+ significantly increased in the NxNT group, but the difference was not significant in the treatment groups. Conclusion: Furosemide, either alone or in combination with captopril, is capable to prevent myocardial calcification, cardiac hypertrophy and hypertension, maintaining blood Ca2+ and phosphate levels by slowing CRF.
Ecthyma-Gangrenosum-Like Bullous Pemphigoid
Authors: Geiss Steiner Jana , Trüeb Ralph M. , Kerl Katrin , Mühleisen Beda , French Lars E. , Hofbauer Günther F.L.
Published: July 2010

Bullous pemphigoid (BP) is a chronic, autoimmune, subepidermal blistering skin disease with varied clinical presentations. Diagnosis is based on the clinical picture, histopathological findings, and direct and indirect immunofluorescence studies. In unclear cases, ELISA or Western blot analysis helps to establish a definite diagnosis by the detection of immunoglobulin G autoantibodies specific for the hemidesmosomal BP antigens BP230 and BP180. We report 3 cases of BP with an as yet not characterized, distinctive ecthyma-gangrenosum-like presentation. Patients were female, above 80 years of age, physically immobile, and skin lesions showed truncal localization and bacterial colonization. Factors contributing to physical immobility were a high body mass index, psychiatric disease, sedative medication and rheumatic disease. The clinical picture resembled ecthyma gangrenosum but lacked systemic infection with Pseudomonas aeruginosa. Lesional bacteriological studies revealed Staphylococcusaureus and/or P. aeruginosa. Diagnosis proved challenging in all cases. Suspicion has to be high, and repeated diagnostic procedures and additional laboratory studies may be necessary to establish a definitive diagnosis of BP. In summary, we propose this combination of truncal ecthyma-gangrenosum-like lesions with bacterial colonization in the context of older age and immobility as a clinically distinct presentation or variant of BP.
Ets-1 and Ets-2 Regulate the Expression of MicroRNA-126 in Endothelial Cells
Authors: Harris Tamia A. , Yamakuchi Munekazu , Kondo Maiko , Oettgen Peter , Lowenstein Charles J.
Published: July 2010

Objective—

MicroRNA plays important roles in vascular biology, but the regulation of endothelial-specific microRNA is not well characterized. MicroRNA-126 (miR-126) is highly expressed in endothelial cells, and it regulates angiogenesis and vascular inflammation. Here we show that the transcription factors Ets-1 and Ets-2 regulate miR-126 expression.

Methods and Results—

A genomic region between −71 and −100 bp upstream of the miR-126 transcriptional start site is critical for transactivation of the gene containing miR-126. This genomic region contains a potential Ets binding site. Mutations within the Ets binding site block transactivation, and Ets-1 and Ets-2 interact with this critical genomic region. Knockdown of endogenous Ets-1 and Ets-2 decreases miR-126 expression. Finally, knockdown of miR-126 alters regulation of an Ets-1 target gene.

Conclusion—

Taken together, these data show that the transcription factors Ets-1 and Ets-2 play a key role in controlling the expression of miR-126 and suggest that miR-126 may mediate some of their vascular effects.
Genetic
Ace2
Deficiency Accentuates Vascular Inflammation and Atherosclerosis in the
ApoE
Knockout Mouse
Authors: Thomas Merlin C. , Pickering Raelene J. , Tsorotes Despina , Koitka Audrey , Sheehy Karen , Bernardi Stella , Toffoli Barbara , Nguyen-Huu Thu-Phuc , Head Geoffrey A. , Fu Yi , Chin-Dusting Jaye , Cooper Mark E. , Tikellis Chris
Published: July 2010

Rationale:

Angiotensin-converting enzyme (ACE)2 opposes the actions of angiotensin (Ang) II by degrading it to Ang 1-7.

Objective:

Given the important role of Ang II/Ang 1-7 in atherogenesis, we investigated the impact of ACE2 deficiency on the development of atherosclerosis.

Methods and Results:

C57Bl6
,
Ace2
knockout (KO), apolipoprotein E (
ApoE
) KO and
ApoE/Ace2 double
KO
mice were followed until 30 weeks of age. Plaque accumulation was increased in
ApoE/Ace2
double KO mice when compared to
ApoE
KO
mice. This was associated with increased expression of adhesion molecules and inflammatory cytokines, including interleukin-6, monocyte chemoattractant protein-1, and vascular cell adhesion molecule-1, and an early increase in white cell adhesion across the whole aortae on dynamic flow assay. In the absence of a proatherosclerotic (
ApoE
KO
) genotype,
ACE2
deficiency was also associated with increased expression of these markers, suggesting that these differences were not an epiphenomenon.
ACE
inhibition prevented increases of these markers and atherogenesis in
ApoE/ACE2
double
KO
mice. Bone marrow macrophages isolated from
Ace2
KO
mice showed increased proinflammatory responsiveness to lipopolysaccharide and Ang II when compared to macrophages isolated from C57Bl6 mice. Endothelial cells isolated from
Ace2
KO
mice also showed increased basal activation and elevated inflammatory responsiveness to TNF-α. Similarly, selective inhibition of ACE2 with MLN-4760 also resulted in a proinflammatory phenotype with a physiological response similar to that observed with exogenous Ang II (10
−7
mol/L).

Conclusions:

Genetic
Ace2
deficiency is associated with upregulation of putative mediators of atherogenesis and enhances responsiveness to proinflammatory stimuli. In atherosclerosis-prone
ApoE
KO
mice, these changes potentially contribute to increased plaque accumulation. These findings emphasize the potential utility of ACE2 repletion as a strategy to reduce atherosclerosis.
Bone Marrow Mesenchymal Stem Cells Stimulate Cardiac Stem Cell Proliferation and Differentiation
Authors: Hatzistergos Konstantinos E. , Quevedo Henry , Oskouei Behzad N. , Hu Qinghua , Feigenbaum Gary S. , Margitich Irene S. , Mazhari Ramesh , Boyle Andrew J. , Zambrano Juan P. , Rodriguez Jose E. , Dulce Raul , Pattany Pradip M. , Valdes David , Revilla Concepcion , Heldman Alan W. , McNiece Ian , Hare Joshua M.
Published: July 2010

Rationale:

The regenerative potential of the heart is insufficient to fully restore functioning myocardium after injury, motivating the quest for a cell-based replacement strategy. Bone marrow–derived mesenchymal stem cells (MSCs) have the capacity for cardiac repair that appears to exceed their capacity for differentiation into cardiac myocytes.

Objective:

Here, we test the hypothesis that bone marrow derived MSCs stimulate the proliferation and differentiation of endogenous cardiac stem cells (CSCs) as part of their regenerative repertoire.

Methods And Results:

Female Yorkshire pigs (n=31) underwent experimental myocardial infarction (MI), and 3 days later, received transendocardial injections of allogeneic male bone marrow–derived MSCs, MSC concentrated conditioned medium (CCM), or placebo (Plasmalyte). A no-injection control group was also studied. MSCs engrafted and differentiated into cardiomyocytes and vascular structures. In addition, endogenous c-kit
+
CSCs increased 20-fold in MSC-treated animals versus controls (
P
<0.001), there was a 6-fold increase in GATA-4
+
CSCs in MSC versus control (
P
<0.001), and mitotic myocytes increased 4-fold (
P
=0.005). Porcine endomyocardial biopsies were harvested and plated as organotypic cultures in the presence or absence of MSC feeder layers. In vitro, MSCs stimulated c-kit
+
CSCs proliferation into enriched populations of adult cardioblasts that expressed Nkx2–5 and troponin I.

Conclusions:

MSCs stimulate host CSCs, a new mechanism of action underlying successful cell-based therapeutics.
Sphingosine-1-Phosphate–Dependent Activation of p38 MAPK Maintains Elevated Peripheral Resistance in Heart Failure Through Increased Myogenic Vasoconstriction
Authors: Hoefer Judith , Azam M. Ali , Kroetsch Jeffrey T.E. , Leong-Poi Howard , Momen M. Abdul , Voigtlaender-Bolz Julia , Scherer Elias Q. , Meissner Anja , Bolz Steffen-Sebastian , Husain Mansoor
Published: July 2010

Rationale:

Mechanisms underlying vasomotor abnormalities and increased peripheral resistance exacerbating heart failure (HF) are poorly understood.

Objective:

To explore the role and molecular basis of myogenic responses in HF.

Methods and Results:

10 weeks old C57Bl6 mice underwent experimental myocardial infarction (MI) or sham surgery. At 1 to 12 weeks postoperative, mice underwent hemodynamic studies, mesenteric, cerebral, and cremaster artery perfusion myography and Western blot. Organ weights and hemodynamics confirmed HF and increased peripheral resistance after MI. Myogenic responses, ie, pressure-induced vasoconstriction, were increased as early as 1 week after MI and remained elevated. Vasoconstrictor responses to phenylephrine were decreased 1 week after MI, but not at 2 to 6 weeks after MI, whereas those to endothelin (ET)-1 and sphingosine-1-phosphate (S1P) were increased at all time points after MI. An antagonist (JTE-013) for the most abundant S1P receptor detected in mesenteric arteries (S1P
2
R) abolished the enhanced myogenic responses of HF, with significantly less effect on controls. Mice with genetic absence of sphingosine-kinases or S1P
2
R (

Sphk1
−/−
; Sphk1
−/−
/Sphk2
+/−
; S1P
2
R
−/−

) did not manifest enhanced myogenic responses after MI. Mesenteric arteries from HF mice exhibited increased phosphorylation of myosin light chain, with deactivation of its phosphatase (MLCP). Among known S1P-responsive regulators of MLCP, GTP-Rho levels were unexpectedly reduced in HF, whereas levels of activated p38 MAPK and ERK1/2 (extracellular signal-regulated kinase 1/2) were increased. Inhibiting p38 MAPK abolished the myogenic responses of animals with HF, with little effect on controls.

Conclusions:

Rho-independent p38 MAPK-mediated deactivation of MLCP underlies S1P/S1P
2
R-regulated increases in myogenic vasoconstriction observed in HF. Therapeutic targeting of these findings in HF models deserves study.
High Myeloid-Related Protein
Authors: Ionita Mihaela G. , Catanzariti Louise M. , Bots Michiel L. , de Vries Jean-Paul P.M. , Moll Frans L. , Sze Siu Kwan , Pasterkamp Gerard , de Kleijn Dominique P.V.
Published: July 2010

Background and Purpose—

Myeloid-related protein (Mrp) 8/14 complex is the functional relevant form of Mrp-8 and Mrp-14. Mrp-8/14 complex is actively formed in the cytoplasm of circulating neutrophils and monocytes and then secreted. Plasma Mrp-8/14 complex is emerging as a new biomarker that may discriminate between patients with an acute coronary syndrome and those with stable coronary heart disease. Little is known about the predictive value of Mrp-8/14 plaque and plasma levels for cardiovascular events after atherectomy.

Methods and Results—

Plasma and plaque Mrp-8/14 levels were determined by ELISA in 230 consecutive patients (mean age 73) who underwent carotid endarterectomy. Patients were followed for 3 years for recurrent cardiovascular events (vascular death, nonfatal vascular event, and peripheral intervention). During follow-up, 62 patients experienced an event. Baseline Mrp-8/14 levels were higher in patients who experienced an event than in event-free patients (plasma 0.78±0.63 versus 0.57±0.67 mg/L;
P
=0.030 and plaque 0.54±1.23 versus 0.08±1.51 mg/kg;
P
=0.027). In a Cox model, a 1 U increase in log Mrp-8/14 was associated with an increased risk of recurrent events (plasma, hazard ratio [HR], 1.51; 95% CI, 1.02 to 2.23,
P
=0.040; and plaque, HR, 1.23, 95% CI, 1.04 to 1.46,
P
=0.018). After multivariate adjustment for risk factors (both plasma and plaque Mrp-8/14) and plaque characteristics (only plaque Mrp-8/14), the HR remained the same for both plasma (HR, 1.50, 95% CI, 1.01 to 2.30;
P
=0.046) and plaque (HR, 1.20, 95% CI, 1.01 to 1.44;
P
=0.042).

Conclusion—

High Mrp-8/14 plasma and plaque levels are related to an increased risk of adverse cardiovascular events after a carotid endarterectomy, independent of traditional cardiovascular risk factors.
The Association of the 4q25 Susceptibility Variant for Atrial Fibrillation With Stroke Is Limited to Stroke of Cardioembolic Etiology
Authors: Lemmens Robin , Buysschaert Ian , Geelen Veerle , Fernandez-Cadenas Israel , Montaner Joan , Schmidt Helena , Schmidt Reinhold , Attia John , Maguire Jane , Levi Christopher , Jood Katarina , Blomstrand Christian , Jern Christina , Wnuk Marcin , Slowik Agniezska , Lambrechts Diether , Thijs Vincent ,   International Stroke Genetics Consortium
Published: July 2010

Background and Purpose—

Genome-wide association studies recently identified 2 variants on chromosome 4q25 as susceptibility factors for atrial fibrillation. Interestingly, these variants were subsequently also shown to be associated with stroke. However, it remains unclear whether 4q25 associates with all the stroke subtypes or with cardioembolic stroke in particular, which is often attributable to atrial fibrillation.

Methods—

We performed a large case-control association study in 4199 ischemic stroke patients, all subtyped according to Trial of Org 10172 in Acute Stroke Treatment criteria, and 3750 controls derived from 6 studies conducted in Australia, Austria, Belgium, Poland, Spain, and Sweden. Two variants on chromosome 4q25, rs1906591 and rs10033464, were genotyped.

Results—

Within cases, the A-allele of rs1906591 was associated with atrial fibrillation (odds ratio, 1.64 [95% CI, 1.43 to 1.90];
P
=9.2 · 10
−12
), whereas rs10033464 was only marginally associated. There was an association between overall ischemic stroke and rs1906591 (odds ratio, 1.20 [95% CI, 1.09 to 1.32];
P
=1.2 · 10
−4
). However, this was probably caused by the large effect of stroke of cardioembolic etiology because no relation was obtained in any other subgroup of stroke. The rs10033464 variant failed to show any relationship with ischemic stroke.

Conclusions—

We replicated the association of the rs1906591 variant on chromosome 4q25 with atrial fibrillation and ischemic stroke of cardioembolic etiology. The 4q25 locus failed to associate with noncardiac subtypes of ischemic stroke.