bluuebunny/crossref_metadata_2025 huggingface dataset:
Chain Entanglements and Mechanical Behavior of High Density Polyethylene
Authors: Cheng Joy J. , Alvarado-Contreras José A. , Polak Maria A. , Penlidis Alexander
Published: December 2009

It has long been suspected that physical chain entanglements in the amorphous phase affect the strain hardening behavior of polyethylene. The precise number of chain entanglements in solid polyethylene cannot be measured using any current techniques. Since entanglements in the melt state are known to be preserved in the polymer upon solidification, determination of the molecular weight between entanglements (Me) is used as a measure of chain entanglements for polyethylene. A decrease in molecular weight between entanglements means an increase in the number of entanglements in the polymer. As the Me value decreases, increasing tensile strain hardening of polyethylene is observed. In addition to experimental work, parallel micromechanical modeling was carried out to study the entanglement effect in uniaxial tensile deformation. The model was able to shed more light over the earlier empirical speculations. By combining experimental observations and modeling results, the presence of physical chain entanglements in the amorphous phase was demonstrated to be the controlling factor in strain hardening behavior of polyethylene.
Infrared Radiative Properties of Thin Polyethylene Coating Pigmented With Titanium Dioxide Particles
Authors: Baneshi Mehdi , Maruyama Shigenao , Komiya Atsuki
Published: December 2009

The infrared (IR) radiative properties of TiO2 pigment particles must be known to perform thermal analysis of a TiO2 pigmented coating. Resins generally used in making pigmented coatings are absorbing at IR wavelengths, which means that the conventional Mie solution (MS) may not be adequate in this domain. There are two approaches to evaluating radiative properties in an absorbing medium: far field approximation (FFA) and near field approximation (NFA). In this study, after reviewing these two approaches, we evaluated the radiative properties of TiO2 particles in polyethylene resin as an absorbing matrix in the wavelength range of 1.7–15 μm based on the MS, FFA, and NFA. We then calculated the effective scattering and absorption coefficients for different models. To investigate the effect of the particle size and volume concentration on the transmittance of IR wavelengths, we made a nongray radiative heat transfer in an anisotropic scattering monodisperse pigmented layer, with independent scattering using the radiation element method by the ray emission model. The results showed that all three approaches predicted similar results in the particle size domain and volume fraction range utilized in pigmented coatings.
Multi-Objective Optimization for the Force System of Orthodontic Retraction Spring Using Genetic Algorithms
Authors: Kazem Bahaa I.
Published: December 2009

In this study, Castigliano’s second theorem is applied to predict the force and moment system produced by orthodontics T-spring. The developed analytical formulas include all spring design parameters (material, geometrical shape and wire cross section, type and position of spring end mounting system, and direction and magnitude of the activation forces). The analytical results are compared with those obtained by nonlinear finite element formulation with nonlinear capabilities as a large deflection and showed an acceptable agreement for the current application. The reliability of the proposed model is successfully tested to predict the effect of some design parameters on spring stiffness. The developed analytic force system formulas are used as an objective function for solving a multi-objective optimization problem to produce the required force and moment at spring ends. A new genetic algorithm scheme is developed to obtain optimal spring design parameters according to design objectives and constraints. The results show that depending on the above methodology we can make a good estimation of the required design parameters of the T-spring for a specific application.
Sustainable Floodplains Through Large-Scale Reconnection to Rivers
Authors: Opperman Jeffrey J. , Galloway Gerald E. , Fargione Joseph , Mount Jeffrey F. , Richter Brian D. , Secchi Silvia
Published: December 2009

If riverside levees are strategically removed or repositioned, the result can be reduced flood risk and increased goods and services.
Channeling Your Fear
Authors: Ray L. Bryan
Published: December 2009

An acid-sensitive channel in the brain promotes fear responses to CO
2
.
Those Irritating Acellular Mitochondria
Authors: Gough Nancy R.
Published: December 2009

Particular causes of cellular necrosis trigger an innate inflammatory response that involves the mitochondria of the necrotic cell.
RANKLed About Fevers?
Authors: Adler Elizabeth M.
Published: December 2009

RANKL-RANK signaling mediates the central fever response to inflammatory cytokines and plays a role in female thermoregulation.
An Ancient Association
Authors: VanHook Annalisa M.
Published: December 2009

Homologs of noncore components of vertebrate hedgehog signaling are required for cilia function in planarians, suggesting an ancestral association between Hh signaling components and cilia.
Metamorphosis Signal Reception
Authors: VanHook Annalisa M.
Published: December 2009

The neuropeptide PTTH initiates metamorphosis in the fruit fly through the receptor tyrosine kinase Torso.
Parallel Paths to Predictive Biomarkers in Oncology: Uncoupling of Emergent Biomarker Development and Phase III Trial Execution
Authors: Sikorski Robert , Yao Bin
Published: December 2009

Predictive biomarkers can be integrated into phase III clinical trials by several approaches, including one that anticipates that a new biomarker will emerge during the course of the trial.
Outbreak of Skin Infections in College Football Team Members Due to an Unusual Strain of Community-Acquired Methicillin-Susceptible
Staphylococcus aureus
Authors: Fontanilla Jose-Mario , Kirkland Kathryn B. , Talbot Elizabeth A. , Powell Kenton E. , Schwartzman Joseph D. , Goering Richard V. , Parsonnet Jeffrey
Published: December 2009

We report a skin and soft-tissue infection outbreak among football team members due to a USA300 methicillin-susceptible
Staphylococcus aureus
(MRSA) strain with genes coding for Panton-Valentine leukocidin and the arginine catabolic mobile element. We postulate that the strain is a community-associated USA300 MRSA strain that lost methicillin resistance but retained important virulence factors.
Current concepts: scapular dyskinesis
Authors: Kibler W Ben , Sciascia Aaron
Published: December 2009

The scapula serves many roles in order for proper shoulder function to occur. These roles include providing synchronous scapular rotation during humeral motion, serving as a stable base for rotator cuff activation and functioning as a link in the kinetic chain. Each role is vital to proper arm function and can only occur when the anatomy around the shoulder is uncompromised. The presence of bony and soft tissue injury as well as muscle weakness and inflexibility can alter the roles of the scapula and alter scapular resting position and/or dynamic motion. This altered scapular position/movement has been termed ‘scapular dyskinesis’. Although it occurs in a large number of shoulder injuries, it appears that scapular dyskinesis is a non-specific response to a painful condition in the shoulder rather than a specific response to certain glenohumeral pathology. The presence or absence of scapular dyskinesis needs to be determined during the clinical examination. An examination consisting of visual inspection of the scapular position at rest and during dynamic humeral movements, along with the performance of objective posture measurements and scapular corrective maneuvers, will help the clinician ascertain the extent to which the scapula is involved in the shoulder injury. Treatment of scapular dyskinesis should begin with optimised anatomy and then progress to the restoration of dynamic scapular stability by strengthening of the scapular stabilisers utilising kinetic chain-based rehabilitation protocols.
A Conversation with John B. Fenn
Authors: Fenn John B. , El-Shall M. Samy
Published: December 2009

Editor's Note Every year, the Editorial Committee of each Annual Reviews series asks an internationally distinguished researcher to prepare a prefatory article for the volume being planned. It was an easy choice for us to seek a contribution from John B. Fenn (b. 1917), who since 1994 has been a professor of analytical chemistry at Virginia Commonwealth University in Richmond, Virginia. Few people have achieved the originality and the impact that John Fenn has shown in his development of new instruments for chemical analysis. Anyone using supersonic jet expansions or electrospray ionization owes a huge debt to this special individual, who was awarded the Nobel Prize in Chemistry in 2002. A full account of the development of electrospray ionization may be found in Fenn's 2002 article in the Journal of Biomolecular Techniques (see Related Resources at the end of the interview).

What follows is a transcript of an interview that Fenn's colleague Professor Samy El-Shall kindly conducted on our behalf. This interview captures the spirit and the imagination of this singular individual. It also shows that the path to discovery is seldom straight and narrow.

-Richard N. Zare
Endothelial cells isolated from caveolin-2 knockout mice display higher proliferation rate and cell cycle progression relative to their wild-type counterparts
Authors: Xie Leike , Frank Philippe G. , Lisanti Michael P. , Sowa Grzegorz
Published: December 2009

The goal of this study was to determine whether caveolin-2 (Cav-2) is capable of controlling endothelial cell (EC) proliferation in vitro. To realize this goal, we have directly compared proliferation rates and cell cycle-associated signaling proteins between lung ECs isolated from wild-type (WT) and Cav-2 knockout (KO) mice. Using three independent proliferation assays, we have determined that Cav-2 KO ECs proliferate by ca. 2-fold faster than their WT counterparts. Cell cycle analysis by flow cytometry of propidium iodide-stained cells showed a relatively higher percentage of Cav-2 KO ECs in S and G2/M and lower percentage in Go/G1 phases of cell cycle relative to their WT counterparts. Furthermore, an over 2-fold increase in the percentage of S phase-associated Cav-2 KO relative to WT ECs was independently determined with bromodeoxyuridine incorporation assay. Mechanistically, the increase in proliferation/cell cycle progression of Cav-2 KO ECs correlated well with elevated expression levels of predominantly S phase- and G2/M phase-associated cyclin A and B1, respectively. Further mechanistic analysis of molecular events controlling cell cycle progression revealed increased level of hyperphosphorylated (inactive) form of G1 to S phase transition inhibitor, the retinoblastoma protein in hyperproliferating Cav-2 KO ECs. Conversely, the expression level of the two cyclin-dependent kinase inhibitors p16INK4 and p27Kip1 was reduced in Cav-2 KO ECs. Finally, increased phosphorylation (activation) of proproliferative extracellular signal-regulated kinase 1/2 was observed in hyperproliferating Cav-2 KO ECs. Overall, our data suggest that Cav-2 negatively regulates lung EC proliferation and cell cycle progression.
MammalianTribbleshomolog 3 impairs insulin action in skeletal muscle: role in glucose-induced insulin resistance
Authors: Liu Jiarong , Wu Xuxia , Franklin John L. , Messina Joseph L. , Hill Helliner S. , Moellering Douglas R. , Walton R. Grace , Martin Mitchell , Garvey W. Timothy
Published: December 2009

Tribbles homolog 3 (TRIB3) was found to inhibit insulin-stimulated Akt phosphorylation and modulate gluconeogenesis in rodent liver. Currently, we examined a role for TRIB3 in skeletal muscle insulin resistance. Ten insulin-sensitive, ten insulin-resistant, and ten untreated type 2 diabetic (T2DM) patients were metabolically characterized by hyperinsulinemic euglycemic glucose clamps, and biopsies of vastus lateralis were obtained. Skeletal muscle samples were also collected from rodent models including streptozotocin (STZ)-induced diabetic rats, db/db mice, and Zucker fatty rats. Finally, L6 muscle cells were used to examine regulation of TRIB3 by glucose, and stable cell lines hyperexpressing TRIB3 were generated to identify mechanisms underlying TRIB3-induced insulin resistance. We found that 1) skeletal muscle TRIB3 protein levels are significantly elevated in T2DM patients; 2) muscle TRIB3 protein content is inversely correlated with glucose disposal rates and positively correlated with fasting glucose; 3) skeletal muscle TRIB3 protein levels are increased in STZ-diabetic rats, db/db mice, and Zucker fatty rats; 4) stable TRIB3 hyperexpression in muscle cells blocks insulin-stimulated glucose transport and glucose transporter 4 (GLUT4) translocation and impairs phosphorylation of Akt, ERK, and insulin receptor substrate-1 in insulin signal transduction; and 5) TRIB3 mRNA and protein levels are increased by high glucose concentrations, as well as by glucose deprivation in muscle cells. These data identify TRIB3 induction as a novel molecular mechanism in human insulin resistance and diabetes. TRIB3 acts as a nutrient sensor and could mediate the component of insulin resistance attributable to hyperglycemia (i.e., glucose toxicity) in diabetes.
Muscle blood flow responses to dynamic exercise in young obese humans
Authors: Limberg Jacqueline K , De Vita Michael D. , Blain Gregory M. , Schrage William G.
Published: December 2009

Exercise is a common nonpharmacological way to combat obesity; however, no studies have systematically tested whether obese humans exhibit reduced skeletal muscle blood flow during dynamic exercise. We hypothesized that exercise-induced blood flow to skeletal muscle would be lower in young healthy obese subjects (body mass index of >30 kg/m2) compared with lean subjects (body mass index of <25 kg/m2). We measured blood flow (Doppler Ultrasound of the brachial and femoral arteries), blood pressure (auscultation, Finapress), and heart rate (ECG) during rest and two forms of single-limb, steady-state dynamic exercise: forearm exercise (20 contractions/min at 4, 8, and 12 kg) and leg exercise (40 kicks/min at 7 and 14 W). Forearm exercise increased forearm blood flow (FBF) similarly in both groups ( P > 0.05; obese subjects n = 9, lean subjects n = 9). When FBF was normalized for perfusion pressure, forearm vascular conductance was not different between groups at increasing workloads ( P > 0.05). Leg exercise increased leg blood flow (LBF) similarly in both groups ( P > 0.05; obese subjects n = 10, lean subjects n = 12). When LBF was normalized for perfusion pressure, leg vascular conductance was not different between groups at increasing workloads ( P > 0.05). These results were confirmed when relative blood flow was expressed at average relative workloads. In conclusion, our results show that obese subjects exhibited preserved FBF and LBF during dynamic exercise.
Merging of Healthy Motor Modules Predicts Reduced Locomotor Performance and Muscle Coordination Complexity Post-Stroke
Authors: Clark David J. , Ting Lena H. , Zajac Felix E. , Neptune Richard R. , Kautz Steven A.
Published: December 2009

Evidence suggests that the nervous system controls motor tasks using a low-dimensional modular organization of muscle activation. However, it is not clear if such an organization applies to coordination of human walking, nor how nervous system injury may alter the organization of motor modules and their biomechanical outputs. We first tested the hypothesis that muscle activation patterns during walking are produced through the variable activation of a small set of motor modules. In 20 healthy control subjects, EMG signals from eight leg muscles were measured across a range of walking speeds. Four motor modules identified through nonnegative matrix factorization were sufficient to account for variability of muscle activation from step to step and across speeds. Next, consistent with the clinical notion of abnormal limb flexion-extension synergies post-stroke, we tested the hypothesis that subjects with post-stroke hemiparesis would have altered motor modules, leading to impaired walking performance. In post-stroke subjects ( n = 55), a less complex coordination pattern was shown. Fewer modules were needed to account for muscle activation during walking at preferred speed compared with controls. Fewer modules resulted from merging of the modules observed in healthy controls, suggesting reduced independence of neural control signals. The number of modules was correlated to preferred walking speed, speed modulation, step length asymmetry, and propulsive asymmetry. Our results suggest a common modular organization of muscle coordination underlying walking in both healthy and post-stroke subjects. Identification of motor modules may lead to new insight into impaired locomotor coordination and the underlying neural systems.
Generation of Myocardial Wall Surface Meshes from Segmented MRI
Authors: Škrinjar Oskar , Bistoquet Arnaud
Published: December 2009

This paper presents a novel method for the generation of myocardial wall surface meshes from segmented 3D MR images, which typically have strongly anisotropic voxels. The method maps a premeshed sphere to the surface
of the segmented object. The mapping is defined by the gradient field of the solution of the Laplace equation between
the sphere and the surface of the object. The same algorithm is independently used to generate the surface meshes of
the epicardium and endocardium of the four cardiac chambers. The generated meshes are smooth despite the strong
voxel anisotropy, which is not the case for the marching cubes and related methods. While the proposed method
generates more regular mesh triangles than the marching cubes and allows for a complete control of the number of
triangles, the generated meshes are still close to the ones obtained by the marching cubes. The method was tested
on 3D short‐axis cardiac MR images with strongly anisotropic voxels in the long‐axis direction. For the five tested
subjects, the average in‐slice distance between the meshes generated by the proposed method and by the marching
cubes was 0.4 mm.
Significance of Circulating Tumor Cells Detected by the CellSearch System in Patients with Metastatic Breast Colorectal and Prostate Cancer
Authors: Miller M. Craig , Doyle Gerald V. , Terstappen Leon W. M. M.
Published: December 2009

The increasing number of treatment options for patients with metastatic carcinomas has created a concomitant need for new methods to monitor their use. Ideally, these modalities would be noninvasive, be independent of treatment, and provide quantitative real-time analysis of tumor activity in a variety of carcinomas. Assessment of circulating tumor cells (CTCs) shed into the blood during metastasis may satisfy this need. We developed the CellSearch System to enumerate CTC from 7.5 mL of venous blood. In this review we compare the outcomes from three prospective multicenter studies investigating the use of CTC to monitor patients undergoing treatment for metastatic breast (MBC), colorectal (MCRC), or prostate cancer (MPC) and review the CTC definition used in these studies. Evaluation of CTC at anytime during the course of disease allows assessment of patient prognosis and is predictive of overall survival.
Reprogramming T Lymphocytes for Melanoma Adoptive Immunotherapy by T-Cell Receptor Gene Transfer with Lentiviral Vectors
Authors: Bobisse Sara , Rondina Maria , Merlo Anna , Tisato Veronica , Mandruzzato Susanna , Amendola Mario , Naldini Luigi , Willemsen Ralph A. , Debets Reno , Zanovello Paola , Rosato Antonio
Published: December 2009

T-cell receptor (TCR) gene transfer for cancer immunotherapy is limited by the availability of large numbers of tumor-specific T cells. TCR α and β chains were isolated from a highly lytic HLA-A2–restricted cytotoxic T lymphocyte (CTL) clone recognizing the melanoma-associated Melan-A/MART-1 antigen and inserted into a lentiviral vector carrying a bidirectional promoter capable of robust and coordinated expression of the two transgenes. Lentiviral vector–based gene delivery systems have shown increased transfer efficiency and transgene expression compared with the widely used γ-retroviral vectors. This vector performed more efficiently than a γ-retrovirus–based vector containing the same expression cassette, resulting in a T-cell population with 60% to 80% of transgenic TCR expression with mainly CD8+ intermediate effector phenotype. Transgenic T cells specifically produced cytokine in response to and killed antigen-expressing melanoma cells, retained an overlapping functional avidity in comparison with the TCR donor CTL clone, and exerted significant therapeutic effects in vivo upon adoptive transfer in melanoma-bearing severe combined immunodeficient mice. Optical imaging showed their accumulation in the tumor site. Overall, our results indicate that lentiviral vectors represent a valid tool for stable and high-intensity expression of transgenic TCR and support clinical exploitation of this approach for therapeutic application. [Cancer Res 2009;69(24):9385–94]
Gene Networks and microRNAs Implicated in Aggressive Prostate Cancer
Authors: Wang Liang , Tang Hui , Thayanithy Venugopal , Subramanian Subbaya , Oberg Ann L. , Cunningham Julie M. , Cerhan James R. , Steer Clifford J. , Thibodeau Stephen N.
Published: December 2009

Prostate cancer, a complex disease, can be relatively harmless or extremely aggressive. To identify candidate genes involved in causal pathways of aggressive prostate cancer, we implemented a systems biology approach by combining differential expression analysis and coexpression network analysis to evaluate transcriptional profiles using lymphoblastoid cell lines from 62 prostate cancer patients with aggressive phenotype (Gleason grade ≥ 8) and 63 prostate cancer patients with nonaggressive phenotype (Gleason grade ≤ 5). From 13,935 mRNA genes and 273 microRNAs (miRNA) tested, we identified significant differences in 1,100 mRNAs and 7 miRNAs with a false discovery rate (FDR) of <0.01. We also identified a coexpression module demonstrating significant association with the aggressive phenotype of prostate cancer (P = 3.67 × 10−11). The module of interest was characterized by overrepresentation of cell cycle–related genes (FDR = 3.50 × 10−50). From this module, we further defined 20 hub genes that were highly connected to other genes. Interestingly, 5 of the 7 differentially expressed miRNAs have been implicated in cell cycle regulation and 2 (miR-145 and miR-331-3p) are predicted to target 3 of the 20 hub genes. Ectopic expression of these two miRNAs reduced expression of target hub genes and subsequently resulted in cell growth inhibition and apoptosis. These results suggest that cell cycle is likely to be a molecular pathway causing aggressive phenotype of prostate cancer. Further characterization of cell cycle–related genes (particularly, the hub genes) and miRNAs that regulate these hub genes could facilitate identification of candidate genes responsible for the aggressive phenotype and lead to a better understanding of prostate cancer etiology and progression. [Cancer Res 2009;69(24):9490–7]
Autocrine Bone Morphogenetic Protein-9 Signals through Activin Receptor-like Kinase-2/Smad1/Smad4 to Promote Ovarian Cancer Cell Proliferation
Authors: Herrera Blanca , van Dinther Maarten , ten Dijke Peter , Inman Gareth J.
Published: December 2009

Bone morphogenetic proteins (BMPs) act as central regulators of ovarian physiology and may be involved in ovarian cancer development. In an effort to understand these processes, we characterized transforming growth factor β/BMP receptor and Smad expression in immortalized ovarian surface epithelial cells and a panel of ovarian cancer cell lines. These studies prompted us to evaluate the potential role of BMP9 signaling in ovarian cancer. Using small interfering RNA, ligand trap, inhibitor, and ligand stimulation approaches, we show that BMP9 acts as a proliferative factor for immortalized ovarian surface epithelial cells and ovarian cancer cell lines, signaling predominantly through an ALK2/Smad1/Smad4 pathway rather than through ALK1, the major BMP9 receptor in endothelial cells. Importantly, we find that some ovarian cancer cell lines have gained autocrine BMP9 signaling that is required for proliferation. Furthermore, immunohistochemistry analysis of an ovarian cancer tissue microarray reveals that ∼25% of epithelial ovarian cancers express BMP9, whereas normal human ovarian surface epithelial specimens do not. Our data indicate that BMP9 signaling through ALK2 may be a novel therapeutic target in ovarian cancer. [Cancer Res 2009;69(24):9254–62]
Differential Thymidylate Synthase Expression in Different Variants of Large-Cell Carcinoma of the Lung
Authors: Monica Valentina , Scagliotti Giorgio V. , Ceppi Paolo , Righi Luisella , Cambieri Alberto , Lo Iacono Marco , Saviozzi Silvia , Volante Marco , Novello Silvia , Papotti Mauro
Published: December 2009

Purpose: In non–small cell lung cancer, higher thymidylate synthase (TS) levels have been reported in squamous cell carcinoma (SCC) compared with adenocarcinoma (ADC). Data on TS expression in large-cell carcinoma (LCC) are scanty.

Experimental Design: TS mRNA and protein levels were analyzed in 42 surgical cases of pulmonary LCC, including 8 large-cell neuroendocrine carcinomas, and were compared with controls represented by ADC (n = 41), SCC (n = 30), and small-cell lung carcinoma (SCLC; n = 33). TS levels were also correlated with the expression of Ki67 and E2F1. Moreover, the reliability of TS expression analysis was assessed in 22 matched cytologic and surgical specimens of non–small cell lung cancer.

Results: TS mRNA levels of LCC were comparable with those of control SCC, but significantly higher than those of ADC (P < 0.001) and lower than SCLC (P < 0.001). A correlation between TS mRNA and protein levels was observed in control ADC and SCC, but not in LCC. Large-cell neuroendocrine carcinomas had the highest TS expression, whereas in non-neuroendocrine LCCs, TS protein levels were significantly higher (P = 0.02) in LCC immunoreactive for p63 and desmocollin3 (markers of squamous differentiation) than those expressing TTF-1 (a marker of ADC). Both E2F1 and Ki67 levels were not correlated with TS in LCCs. Finally, a linear correlation in TS protein levels was observed between matched cytologic and surgical specimens.

Conclusion: The pulmonary LCC immunoprofile may resemble that of SCCs or ADCs. This immunoprofile is associated with differential TS expression levels, which may support a more appropriate therapeutic strategy decision. (Clin Cancer Res 2009;15(24):7547–52)
Barriers to Integrating Gene Profiling for Stage II Colon Cancer
Authors: Kopetz Scott , Abbruzzese James L.
Published: December 2009

The identification of high-risk subsets of colon cancers has undergone extensive study over the years, and multidimensional gene signatures have shown promise for colon cancer. However, several hurdles need to be overcome in order to show the benefit of this approach and successfully apply them to the clinic. (Clin Cancer Res 2009;15(24):7451–2)
Severe Micrognathia: Indications for EXIT-to-Airway
Authors: Morris Lee M. , Lim Foong-Yen , Elluru Ravindhra G. , Hopkin Robert J. , Jaekle Ronald K. , Polzin William J. , Crombleholme Timothy M.
Published: December 2009

The ex utero intrapartum treatment (EXIT) procedure has become an important management option in cases of fetal airway obstruction. Select cases of severe micrognathia may be candidates for EXIT-to-Airway due to high-risk of airway obstruction at birth. Here we present three successful EXIT-to-Airway procedures for the management of congenital micrognathia in its most severe manifestations. Case 1: A 23-year-old G3P1011 with a pregnancy complicated by severe micorgnathia, jaw index <5th percentile, as well as polyhydramnios. At 36 weeks EXIT-to-Airway was performed utilizing a bronchoscopically positioned laryngeal mask airway (LMA) during 23 min of uteroplacental support followed by tracheostomy. Case 2: A 26-year-old G4P0120 with a pregnancy complicated by severe micrognathia, jaw index <5th percentile, and an obstructed oropharynx associated with polyhydramnios. At 37 weeks EXIT-to-Airway was performed with placement of tracheostomy. Case 3: A 36-year-old G6P3023 with fetal magnetic resonance imaging (MRI) revealing esophageal atresia, polyhydramnios, and severe micrognathia with a jaw index <5th percentile. At 35 weeks the patient underwent EXIT-to-Airway with formal tracheostomy during 35 min of uteroplacental bypass. In the most severe cases of fetal micrognathia, EXIT-to-Airway provides time to evaluate and secure the fetal airway prior to delivery. We propose indications for EXIT-to-Airway in micrognathia to include a jaw index <5%, with indirect evidence of aerodigestive tract obstruction such as polyhydramnios, glossoptosis or an absent stomach bubble.
Comparative Genomics of 3 Farm Canids in Relation to the Dog
Authors: Switonski M. , Szczerbal I. , Nowacka-Woszuk J.
Published: December 2009

There are 3 canids besides the dog (Canis familiaris): the red fox (Vulpes vulpes), arctic fox (Alopex lagopus) and Chinese raccoon dog (Nyctereutes procyonoides procyonoides), which have been extensively studied with the use of cytogenetic and molecular genetics techniques. These 3 species are considered as farm fur-bearing animals. In addition, they are also useful models in comparative genomic studies of the canids. In this review genome organization, karyotype evolution, comparative marker maps, DNA polymorphism and similarity of selected gene sequences of the 3 farm species are discussed in relation to the dog. Also the nature and variability of the B chromosomes, present in the red fox and the Chinese raccoon dog, were considered. These comparative analyses showed that among the studied canids the Chinese raccoon dog is phylogenetically the closest species to the dog. On the other hand, the most advanced linkage and cytogenetic marker maps of the red fox genome facilitate genome scanning studies with the aim to search for chromosome locations of QTL regions for behavior and production traits.
Comparative RH Maps of the River Buffalo and Bovine Y Chromosomes
Authors: Stafuzza N.B. , Abbassi H. , Grant J.R. , Rodrigues-Filho E.A. , Ianella P. , Kadri S.M. , Amarante M.V. , Stohard P. , Womack J.E. , Ponce de León F.A. , Amaral M.E.J.
Published: December 2009

Radiation hybrid maps were constructed for river buffalo and cattle Y chromosomes. A total of 41 cattle-derived Y-chromosome molecular markers were selected and tested with 2 previously described 5,000-rad whole-genome radiation hybrid (RH) panels (river buffalo – BBURH5000 and cattle – BTARH5000) for generation of maps. Among the initial 41 selected markers, a subset of 26 markers generated PCR products suitable for scoring with the BBURH5000 panel. Of these, 19 markers (73%) were distributed in 1 linkage group spanning 341.3 cR. Retention frequencies (RF) for individual markers ranged from 17.8% for SMCY to 56.7% for BTY1, with an average RF of 37.6%. From the selected markers, 37 generated reliable scores using the BTARH5000 panel. The newly constructed BTAY RH map contains 28 markers distributed within 1 linkage group. Twenty-four of these markers had been previously mapped on BTAY using a 7,000-rad cattle-hamster WG-RH panel and 4 markers were mapped for the first time (ZFY, SeqRep, RepSeqS4 and BTY1). The length of the BTAY RH map was estimated to be 602.4 cR. Retention frequencies for individual mapped markers ranged from 10% (INRA126) to 63.3% (SeqRep), with an average RF of 35.3%. RH marker positions along the Y chromosome were compared between BBUY and BTAY, which revealed differences in the order of some of the markers. The BBUY pseudoautosomal region (PAR) is delineated by 3 BTAY PAR markers (MAF45, TGLA325 and UMN2008). These markers are telomeric in both species but are not found in the same order. Here we have demonstrated the effective use of bovine Y chromosome markers for the development of the first BBUY RH map. Likewise, these set of markers can be used for comparative assessment of Y chromosomes in other members of the Bovidae family.
Comparative Mapping and Genomic Annotation of the Bovine Oncosuppressor Gene WWOX
Authors: Manera S. , Bonfiglio S. , Malusà A. , Denis C. , Boussaha M. , Russo V. , Roperto F. , Perucatti A. , Di Meo G.P. , Eggen A. , Ferretti L.
Published: December 2009

WWOX (WW domain-containing oxidoreductase) is the gene mapping at FRA16D HSA16q23.1, the second most active common fragile site in the human genome. In this study we characterized at a detailed molecular level WWOX in the bovine genome. First, we sequenced cDNA from various tissues and obtained evidence in support of a 9-exon structure for the gene, similar to the human gene. Then, we recovered BACs using exon tags and annotated the gene to a >1-Mb genomic region of BTA18 using the Btau 4.0 genome assembly as a reference, thus resolving an issue related to exon 9, which is not included in the genomic annotation of the gene in the Entrez database. Finally, BACs spanning WWOX were used as FISH probes to obtain comparative mapping of the gene in Bos taurus, Bubalus bubalis, Ovis aries and Capra hircus to BTA18q12.1, BBU18q13, OAR14q12.1 and CHI18q12.1, respectively. Our data show that the chromosomal location of WWOX is conserved between man and 4 major domesticated species. Moreover, the annotation of the bovine gene also suggests a highly conserved genomic arrangement, including number and size of introns.
Laparoscopic Pyeloplasty: A Versatile Alternative to Open Pyeloplasty
Authors: Srivastava Aneesh , Singh Pratipal , Maheshwari Ruchir , Ansari Mohd S. , Dubey Deepak , Kapoor Rakesh , Kumar Anant , Mandhani Anil
Published: December 2009

Objective: To report the safety, efficacy and versatility of laparoscopic pyeloplasty (LPP) in treatment of pelviureteric junction obstruction (PUJO). Patients and Methods: From January 2002 to November 2006, 185 patients (186 units; 182 with primary and 4 with secondary PUJO) underwent LPP (transperitoneal approach in 184; retroperitoneal approach in 2). A double J stent was placed antegradely in 121 (68.4%) units, cystoscopically in 50 units (28.2%), and 6 units (3.4%) were stentless. Patients were followed up clinically, with additional diuretic renogram. Results: Surgery was completed laparoscopically in 177 units, and conversion was required in 9 (4.8%) units. Pyeloplasty was dismembered in 143 units, Foley YV plasty in 26 units, and Fenger pyeloplasty in 8 units. The median estimated blood loss, operative time and hospital stay were 50 ml, 180 min and 4 days, respectively. Overall, 18 (9.6%) patients had complications. Improvements in drainage patterns of 167 out of 177 units (94.3%) were shown on a renal scan at a median follow-up of 39 months (range: 3–63 months). Conclusion: LPP is a safe, effective and versatile method for treatment of PUJO, which is applicable to all age groups, even in the presence of secondary stones, crossing vessels and secondary PUJO.
Oral Chemotherapy in Hormone-Refractory Prostate Carcinoma Patients Unwilling to Be Admitted to Hospital
Authors: Serretta Vincenzo , Altieri Vincenzo , Morgia Giuseppe , Siragusa Alfredo , De Grande Gaetano , Napoli Matteo , Falsaperla Mario , Melloni Darvinio , Allegro Rosalinda
Published: December 2009

Objectives: To investigate the safety and efficacy in terms of PSA response of a low-dose oral combination of estramustine phosphate (EMP) and etoposide (VP16) in hormone- refractory prostate cancer (HRPC) patients. Well-tolerated outpatient chemotherapy regimens for patients unfit and/or unwilling to be admitted to hospital are needed. Methods: Fifty-six HRPC patients with metastatic disease (median age 75 years) were randomized between arm A (daily oral EMP 10 mg/kg, in 3 doses) and arm B (28-day cycle with low-dose EMP 3 mg/kg once daily plus VP16 25 mg/m2 once daily on days 1 through 14). Baseline characteristics between the two groups were similar. LHRH therapy was maintained. Anti- androgen was stopped 1 month before entry. Results: The low-dose combination was better tolerated, with a significant advantage in terms of time to treatment interruption for any reason (p = 0.01) or toxicity (6 vs. 12 months, p = 0.02). A trend in favour of arm B was evident in terms of PSA reduction (41.4 vs. 15%), performance status and pain improvement. Hospital admission due to toxicity was never required for arm B patients and there were no treatment-related deaths. Conclusions: Low-dose oral combination of EMP and VP16 might represent a treatment option for patients unfit for i.v. chemotherapy. This regimen requires minimal toxicity monitoring when administered at home for prolonged periods.
An in vitro Study Comparing the Coagulation and Cautery Effects of Bipolar and Unipolar Cutting Modalities on Prostatic Tissue
Authors: Akgül Turgay , Nuhoğlu Barış , Polat Osman , Ayyıldız Ali , Astarcı Müzeyyen , Germiyanoğlu Cankon , Üstün Hüseyin
Published: December 2009

Introduction: We aimed to compare plasmakinetic prostate resection (PKRP), plasmakinetic prostate vaporization (PKVP) and transurethral prostate resection (TURP) procedures according to cautery artifacts in tissue specimens and to compare the coagulation depths of these procedures. Materials and Methods: The prostate specimens of 10 patients that underwent open transvesical prostatectomy were used. TURP, PKVP and PKRP procedures were performed immediately. Artifactual pathological patterns that were identified in the specimens included: abnormal cellular orientation and spindling, artifactual cellular detachment from the underlying basement membrane, atypical cytological changes and stromal coagulative artifacts. The severity of cautery artifact was graded as absent, mild, moderate or severe according to the sum of points in each specimen. Results: When the groups were compared according to moderate and severe artifacts, it was observed that PKRP caused more moderate artifacts and TURP caused more severe artifacts than the other two groups (p < 0.05). The depth of the tissue affected by coagulation was 1.52 ± 1.29 mm with the TURP procedure. There were significant differences between TURP and the other two methods (p < 0.05). Conclusions: Three transurethral procedures cause cautery artifacts of varying grades. The application of TURP seems to cause more severe artifacts and PKRP and PKVP procedures seem to result in a deeper coagulation zone in the residual prostatic tissue.
Multifocal Brain Metastases in Clear Cell Renal Cell Carcinoma with Complete Response to Sunitinib
Authors: Zeng Hao , Li Xiang , Yao Jin , Zhu Yuchun , Liu Jiyan , Yang Yuru , Qiang Wei
Published: December 2009

We report the case of a 70-year-old man who received sunitinib treatment for brain metastatic clear cell renal cell carcinoma. After 6 months of treatment, brain MRI showed complete disappearance of two brain metastases. To the best of our knowledge, this is the first reported case of multifocal brain metastases in renal cell carcinoma with complete response to sunitinib.
Prenatal Diagnosis of Androgen Insensitivity Syndrome
Authors: Bianca S. , Cataliotti A. , Bartoloni G. , Torrente I. , Barrano B. , Boemi G. , Lo Presti M. , Indaco L. , Barone C. , Ettore G.
Published: December 2009

Androgen insensitivity syndrome (AIS) (OMIM 300068) is an X-linked recessive genetic disorder with an XY karyotype that is caused by androgen receptor (AR) defects. We report a prenatal diagnosis case with clinical and molecular findings. The fetal phenotype was female, moreover the autopsy revealed the presence of abdominal testes confirmed by histopathological examination. The AR gene molecular analysis performed on the fetal DNA showed the presence of a c.2493C>T change in exon 4. The single nucleotide change resulted in a Q711X amino acid substitution within the AR ligand-binding domain of the protein that has never been described before in the literature. AIS is an important consideration in pregnancies that show sex discordance in ultrasonography and karyotype results with the opportunity to perform molecular analysis of the AR gene in order to confirm the diagnosis.
Anticoagulation for Cerebral Venous Thrombosis with Subarachnoid Hemorrhage: A Case Report
Authors: Hegazi Mohamed Osama , Ahmed Sherif , Sakr Mohamed Gaber , Hassanien Omar Ahmed
Published: December 2009

Objectives: To report the success of anticoagulation (AC) treatment in a case of cerebral venous thrombosis (CVT) with subarachnoid hemorrhage (SAH) in view of the limited evidence seen in the literature supporting such a treatment option. Clinical Presentation and Intervention: A 38-year-old lady with CVT and SAH presented 12 h after the onset of symptoms. AC with low-molecular-weight heparin was started 4 days later, when the repeated brain CT showed regression of the SAH. Heparin was changed to warfarin, and she was asymptomatic over a 12-month follow-up period. Discussion: In a limited number of small studies, AC has been found to be beneficial for cases of CVT with hemorrhagic complications. The proper time to start AC in such cases was not clearly defined, and a delay of 4–33 days was observed after the onset of symptoms. In cases of spontaneous intracranial hemorrhage (ICH) in general, active bleeding is usually confined to the first 6 h, and chances of hematoma enlargement are higher in the first 24 h. On the other hand, it has been advised to rule out a coincidental vascular malformation and to radiologically confirm regression (or at least non-progression) of the ICH before starting AC. Conclusion: AC for cases of CVT may remain beneficial in the presence of SAH. The time to start AC for CVT with hemorrhagic complications is unclear; however, AC was successful when given 4 days after the onset of symptoms in our case. It may be wise to repeat CT after at least 24 h from the onset of symptoms (to confirm regression or at least non-progression of the ICH) before starting AC. It may also be prudent to perform magnetic resonance angiography, or digital subtraction angiography to rule out a coincidental intracranial aneurysm before AC.
Prostatic Ductal Adenocarcinoma: A Mini Review
Authors: Epstein Jonathan I.
Published: December 2009

Prostatic ductal adenocarcinomas may arise either in large primary periurethral prostatic ducts or in the peripheral prostatic ducts. Ductal adenocarcinomas are composed of tall columnar cells arranged in cribriform, papillary, solid, single glands, and PIN-like patterns. Other than the prostatic intraepithelial neoplasia (PIN)-like ductal pattern, which behaves like Gleason pattern 3, ductal adenocarcinoma is comparable to Gleason pattern 4 prostate cancer. Ductal adenocarcinoma can have a patchy basal cell layer and typically expresses prostate-specific antigen (PSA) immunohistochemically. Mimickers of ductal adenocarcinoma include prostatic urethral polyps, hyperplastic benign prostate glands, high-grade PIN, colorectal adenocarcinoma, and papillary urothelial carcinoma.
Perinatal Outcome of Monochorionic Twins with Selective Intrauterine Growth Restriction and Different Types of Umbilical Artery Doppler under Expectant Management
Authors: Ishii Keisuke , Murakoshi Takeshi , Takahashi Yuichiro , Shinno Takashi , Matsushita Mitsuru , Naruse Hiroo , Torii Yuichi , Sumie Masahiro , Nakata Masahiko
Published: December 2009

Objectives: To evaluate the prognosis of monochorionic twins with selective intrauterine growth restriction (sIUGR), classified according to the type of umbilical artery Doppler, under expectant management. Methods: The outcome of 81 cases with isolated sIUGR was evaluated according to a classification based on umbilical artery (UA) Doppler diastolic flow in the IUGR twin (I: present, II: constantly absent/reverse, III: intermittently absent/reverse). Selective feticide was not considered due to legal constraints. Perinatal outcomes included perinatal death and neurological outcome at 6 months of age. Results: From 81 cases with the diagnosis of sIUGR, twin-twin transfusion was diagnosed in 18 cases. This left 63 cases, of which 23 were classified as type I (36.5%), 27 as type II (42.9%) and 13 as type III (20.6%). Intrauterine death occurred in 4.3% (1), 29.6% (8) and 15.4% (2) among IUGR twins, and 4.3% (1), 22.2% (6) and 0.0% (0) among larger twins. Neonatal death occurred in 0.0% (0), 18.5% (5) and 0.0% (0) among IUGR twins, and 0.0% (0), 11.1% (3) and 23.0% (3) among larger twins. Neurological abnormalities at 6 months were found in 4.3% (1), 14.8% (4) and 23.1% (3) in smaller twins and 0.0% (0), 11.1% (3) and 38.5% (5) in larger twins, respectively. Intact survival at 6 months was recorded in 91% (21), 37% (10) and 61% (8) in smaller twins and 95% (22), 55% (15) and 38% (5) in larger twins, respectively. Conclusion: The outcome in monochorionic twins with sIUGR and abnormal umbilical artery Doppler is poor under expectant management. Normal Doppler seems to be associated with a good prognosis.
Lung Tissue Blood Perfusion Changes Induced by in utero Tracheal Occlusion in a Rabbit Model of Congenital Diaphragmatic Hernia
Authors: Cruz-Martinez Rogelio , Moreno-Alvarez Oscar , Prat Jordi , Krauel Lucas , Tarrado Xavier , Castañón Montserrat , Hernandez-Andrade Edgar , Albert Asteria , Gratacós Eduard
Published: December 2009

Objective: To analyze the impact of in utero tracheal occlusion (TO) on lung tissue blood perfusion, as measured by fractional moving blood volume (FMBV) and conventional spectral Doppler, in a rabbit model of congenital diaphragmatic hernia (CDH). Methods: In 50 fetal rabbits, a left CDH was surgically created at 23 days of gestational age (GA). At 28 days of GA, the surviving CDH fetuses were randomly assigned to undergo either TO (CDH+TO group) or a sham operation (CDH group). Twenty littermates, which were not operated on, served as internal normal controls. At 30 days of GA, lung perfusion estimated by FMBV and spectral Doppler of the proximal intrapulmonary artery were evaluated in the right lung during cesarean section. Doppler waveform analysis included the pulsatility index (PI), peak early diastolic reverse flow and peak systolic velocity. Results: Eleven CDH fetuses, 9 CDH+TO and 20 controls were suitable for the study. CDH fetuses showed a significantly higher PI [8.0 (SD 1.8) vs. 5.22 (SD 1.1), p < 0.001] and lower FMBV [13.5% (SD 4.6) vs. 23.0% (SD 2.1), p < 0.001] than the controls. In contrast, CDH+TO fetuses had a significantly lower PI [5.8 (SD 2.3) vs. 8.0 (SD 1.8), p = 0.015] and higher FMBV [27.6% (SD 7.1) vs. 13.5% (SD 4.6), p < 0.001] than CDH fetuses, with values similar to the controls. Peak early diastolic reverse flow and peak systolic velocity showed nonsignificant differences among the study groups. The lung to body weight ratio at necropsy correlated positively with lung FMBV (r = 0.60, p < 0.001) and negatively with the pulmonary artery PI (r = –0.48, p < 0.01). Conclusion: Tracheal occlusion is consistently associated with increased lung tissue perfusion and decreased intrapulmonary impedance in a rabbit model of CDH.