bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating exotic predator control programs using non-invasive genetic tagging
Authors: Piggott Maxine P. , Wilson Rebecca , Banks Sam C. , Marks Clive A. , Gigliotti Frank , Taylor Andrea C.
Published: November 2008

Carnivorous predators are difficult to detect using conventional survey methods, especially at low levels of abundance. The introduced red fox (Vulpes vulpes) in Australia is monitored to determine the effectiveness of control programs, but assessing population parameters such as abundance and recruitment is difficult. We carried out a feasibility study to determine the effectiveness of using faecal DNA analysis methods to identify individual foxes and to assess abundance before and after lethal control. Fox faeces were collected in two sampling periods over four separate transects, and genotyped at five microsatellite loci. Two transects were subject to lethal control between collection periods. DNA was extracted from 170 fox faeces and, in total, 54 unique genotypes were identified. Fifteen biopsy genotypes from 30 foxes killed during lethal control were detected among the faecal genotypes. Overall, a similar number of genotypes were detected in both sampling periods. The number of individuals sampled in both periods was low (n = 6) and new individuals (n = 24) were detected in the second collection period. We were also able to detect animals that avoided lethal control, and movement of individuals between transects. The ability to identify individual foxes using these DNA techniques highlighted the shortcomings of the sample design, in particular the spatial scale and distances between transects. This study shows that non-invasive DNA sampling can provide valuable insight into pre and post fox abundance in relation to lethal control, individual behaviour and movement, as well as sample design. The information gained from this study will contribute to the design of future studies and, ultimately, control strategies.
Diets of native and introduced mammalian herbivores in shrub-encroached grassy woodland, south-eastern Australia
Authors: Davis Naomi E. , Coulson Graeme , Forsyth David M.
Published: November 2008

Effective management of sympatric mammalian herbivore populations requires an understanding of interspecific interactions. At Wilsons Promontory National Park, Victoria, sympatric native and introduced mammalian herbivores are thought to be contributing to modification of shrub-encroached Coastal Grassy Woodland. We estimated the diets of the five terrestrial mammalian herbivore species present using microhistological techniques. The diets of introduced hog deer (Axis porcinus) and native swamp wallabies (Wallabia bicolor) consisted mainly of dicots. The diet of introduced European rabbits (Oryctolagus cuniculus) contained similar proportions of monocots and dicots. The diets of native eastern grey kangaroos (Macropus giganteus) and native common wombats (Vombatus ursinus) consisted mainly of monocots but kangaroos also consumed moderate amounts of dicots. Deer and wallabies consumed more native plants than did the other species and rabbits consumed more exotic plants than did all other species except kangaroos. Diet breadth was narrowest for kangaroos and broadest for swamp wallabies and hog deer. Overlap in food use by the five herbivores was high, particularly between deer and wallabies, and between kangaroos and both rabbits and wombats. Our results suggest that the potential impacts of native and introduced species on the vegetation of Coastal Grassy Woodland are similar, and that the entire herbivore assemblage will need to be managed to increase fine fuel loads if fire is used as a restoration tool.
Riparian corridors enhance movement of a forest specialist bird in fragmented tropical forest
Authors: Gillies Cameron S. , St. Clair Colleen Cassady
Published: November 2008

Riparian corridors and fencerows are hypothesized to increase the persistence of forest animals in fragmented landscapes by facilitating movement among suitable habitat patches. This function may be critically important for forest birds, which have declined dramatically in fragmented habitats. Unfortunately, direct evidence of corridor use has been difficult to collect at landscape scales and this limits support for corridors in conservation planning. Using telemetry and handheld GPS units, we examined the movement of forest birds by translocating territorial individuals of barred antshrikes (Thamnophilus doliatus; a forest specialist) and rufous-naped wrens (Campylorhynchus rufinucha; a forest generalist) 0.7–1.9 km from their territories in the highly fragmented tropical dry forest of Costa Rica. In each translocation, the directly intervening habitat comprised 1 of 3 treatments: forested riparian corridor, linear living fencerow, or open pasture. Antshrikes returned faster and with greater success in riparian corridors relative to pasture treatments. This species also traveled more directly in riparian corridor treatments, detoured to use forested routes in the other 2 treatments, and did not use fencerows even when they led directly to their home territories. By contrast, wrens were more likely to use fencerows when returning, and return time and success were equivalent among the 3 treatments. Both species crossed fewer gaps in tree cover during riparian corridor treatments than in fencerow or pasture treatments. We conclude that antshrikes, which may be representative of other forest specialists, use forested corridors for movement in this landscape and that fencerows are avoided as movement conduits.
A functional proteomics approach links the ubiquitin-related modifier Urm1 to a tRNA modification pathway
Authors: Schlieker Christian D. , Van der Veen Annemarthe G. , Damon Jadyn R. , Spooner Eric , Ploegh Hidde L.
Published: November 2008

Urm1 is a highly conserved ubiquitin-related modifier of unknown function. A reduction of cellular Urm1 levels causes severe cytokinesis defects in HeLa cells, resulting in the accumulation of enlarged multinucleated cells. To understand the underlying mechanism, we applied a functional proteomics approach and discovered an enzymatic activity that links Urm1 to a tRNA modification pathway. Unlike ubiquitin (Ub) and many Ub-like modifiers, which are commonly conjugated to proteinaceous targets, Urm1 is activated by an unusual mechanism to yield a thiocarboxylate intermediate that serves as sulfur donor in tRNA thiolation reactions. This mechanism is reminiscent of that used by prokaryotic sulfur carriers and thus defines the evolutionary link between ancient Ub progenitors and the eukaryotic Ub/Ub-like modification systems.
IRF7 activation by Epstein–Barr virus latent membrane protein 1 requires localization at activation sites and TRAF6, but not TRAF2 or TRAF3
Authors: Song Yoon-Jae , Izumi Kenneth M. , Shinners Nicholas P. , Gewurz Benjamin E. , Kieff Elliott
Published: November 2008

Epstein–Barr virus (EBV) latent infection membrane protein 1 (LMP1), a constitutively aggregated and activated pseudoreceptor, activates IFN regulatory factor 7 (IRF7) through RIP1. We now report that the LMP1 cytoplasmic carboxyl terminal amino acids 379–386 bound IRF7 and activated IRF7. IRF7 activation required TRAF6 and RIP1, but not TRAF2 or TRAF3. LMP1 Y
384
YD
386
, which are required for TRADD and RIP1 binding and for NF-κB activation, were not required for IRF7 binding, but were required for IRF7 activation, implicating signaling through TRADD and RIP1 in IRF7 activation. Association with active LMP1 signaling complexes was also critical for IRF7 activation because (
i
) a dominant-negative IRF7 bound to LMP1, blocked IRF7 association and activation, but did not inhibit LMP1 induced NF-κB or TBK1 or Sendai virus-mediated IFN stimulated response element activation; and (
ii
) two different LMP1 transmembrane domain mutants, which fail to aggregate, each bound IRF7 and prevented LMP1 from binding and activating IRF7 in the same cell, but did not prevent NF-κB activation. Thus, efficient IRF7 activation required association with LMP1 CTAR2 in proximity to LMP1 CTAR2 mediated kinase activation sites.
Psychological interventions for infertile patients: a review of existing research and A new comprehensive approach
Authors: Haemmerli Katja , Znoj Hansjoerg , Burri Salome , Graf Patricia , Wunder Dorothea , Perrig-Chiello Pasqualina
Published: November 2008

The usefulness of psychological support for infertile patients has been highlighted in the literature over the past number of years. This article provides a review of existing research on psychological interventions for infertile patients, and presents the Fertility Group Intervention as an example of the application of existing research. There is clear empirical evidence of high levels of depressive symptoms, anxiety, and distress among infertile patients undergoing assisted reproductive treatment (ART). Infertile patients need and require increased psychological support. Various studies indicate the efficacy of psychological interventions for infertile patients with respect to their mental health and, in part, pregnancy rates. However, many such studies exhibit methodological problems. Therefore, in future research, additional studies of high‐quality design are needed to achieve more definitive answers on the efficacy and indication of psychological interventions for infertile patients. Currently, the Fertility Group Intervention represents a comprehensive therapeutic approach integrating established empirical and theoretical approaches with the aim of helping infertile patients – particularly those undergoing ART – cope with distress related to their infertility and medical treatment. This article further outlines the therapeutic background and structures, treatment goals, practical implications, and feasibility of the Fertility Group Intervention.
Induction of cell retraction by the combined actions of Abl–CrkII and Rho–ROCK1 signaling
Authors: Huang XiaoDong , Wu Diana , Jin Hua , Stupack Dwayne , Wang Jean Y.J.
Published: November 2008

Dynamic modulation of cell adhesion is integral to a wide range of biological processes. The small guanosine triphosphatase (GTPase) Rap1 is an important regulator of cell–cell and cell–matrix adhesions. We show here that induced expression of activated Abl tyrosine kinase reduces Rap1-GTP levels through phosphorylation of Tyr221 of CrkII, which disrupts interaction of CrkII with C3G, a guanine nucleotide exchange factor for Rap1. Abl-dependent down-regulation of Rap1-GTP causes cell rounding and detachment only when the Rho–ROCK1 pathway is also activated, for example, by lysophosphatidic acid (LPA). During ephrin-A1–induced retraction of PC3 prostate cancer cells, we show that endogenous Abl is activated and disrupts the CrkII–C3G complex to reduce Rap1-GTP. Interestingly, ephrin-A1–induced PC3 cell retraction also requires LPA, which stimulates Rho to a much higher level than that is activated by ephrin-A1. Our results establish Rap1 as another downstream target of the Abl–CrkII signaling module and show that Abl–CrkII collaborates with Rho–ROCK1 to stimulate cell retraction.
p120 catenin induces opposing effects on tumor cell growth depending on E-cadherin expression
Authors: Soto Edwin , Yanagisawa Masahiro , Marlow Laura A. , Copland John A. , Perez Edith A. , Anastasiadis Panos Z.
Published: November 2008

p120 catenin regulates the activity of the Rho family guanosine triphosphatases (including RhoA and Rac1) in an adhesion-dependent manner. Through this action, p120 promotes a sessile cellular phenotype when associated with epithelial cadherin (E-cadherin) or a motile phenotype when associated with mesenchymal cadherins. In this study, we show that p120 also exerts significant and diametrically opposing effects on tumor cell growth depending on E-cadherin expression. Endogenous p120 acts to stabilize E-cadherin complexes and to actively promote the tumor-suppressive function of E-cadherin, potently inhibiting Ras activation. Upon E-cadherin loss during tumor progression, the negative regulation of Ras is relieved; under these conditions, endogenous p120 promotes transformed cell growth both in vitro and in vivo by activating a Rac1–mitogen-activated protein kinase signaling pathway normally activated by the adhesion of cells to the extracellular matrix. These data indicate that both E-cadherin and p120 are important regulators of tumor cell growth and imply roles for both proteins in chemoresistance and targeted therapeutics.
AnkyrinG is required for maintenance of the axon initial segment and neuronal polarity
Authors: Hedstrom Kristian L. , Ogawa Yasuhiro , Rasband Matthew N.
Published: November 2008

The axon initial segment (AIS) functions as both a physiological and physical bridge between somatodendritic and axonal domains. Given its unique molecular composition, location, and physiology, the AIS is thought to maintain neuronal polarity. To identify the molecular basis of this AIS property, we used adenovirus-mediated RNA interference to silence AIS protein expression in polarized neurons. Some AIS proteins are remarkably stable with half-lives of at least 2 wk. However, silencing the expression of the cytoskeletal scaffold ankyrinG (ankG) dismantles the AIS and causes axons to acquire the molecular characteristics of dendrites. Both cytoplasmic- and membrane-associated proteins, which are normally restricted to somatodendritic domains, redistribute into the former axon. Furthermore, spines and postsynaptic densities of excitatory synapses assemble on former axons. Our results demonstrate that the loss of ankG causes axons to acquire the molecular characteristics of dendrites; thus, ankG is required for the maintenance of neuronal polarity and molecular organization of the AIS.
MotifMap: a human genome-wide map of candidate regulatory motif sites
Authors: Xie Xiaohui , Rigor Paul , Baldi Pierre
Published: November 2008

Motivation: Achieving a comprehensive map of all the regulatory elements encoded in the human genome is a fundamental challenge of biomedical research. So far, only a small fraction of the regulatory elements have been characterized, and there is great interest in applying computational techniques to systematically discover these elements. Such efforts, however, have been significantly hindered by the overwhelming size of non-coding DNA regions and the statistical variability and complex spatial organizations of mammalian regulatory elements.

Results: Here we combine information from multiple mammalian genomes to derive the first fairly comprehensive map of regulatory elements in the human genome. We develop a procedure for identifying regulatory sites, with high levels of conservation across different species, using a new scoring scheme, the Bayesian branch length score (BBLS). Using BBLS, we predict 1.5 million regulatory sites, corresponding to 380 known regulatory motifs, with an estimated false discovery rate (FDR) of <50%. We demonstrate that the method is particularly effective for 155 motifs, for which 121 056 sites can be mapped with an estimated FDR of <10%. Over 28K SNPs are located in regions overlapping the 1.5 million predicted motif sites, suggesting potential functional implications for these SNPs. We have deposited these elements in a database and created a user-friendly web server for the retrieval, analysis and visualization of these elements. The initial map provides a systematic view of gene regulation in the genome, which will be refined as additional motifs become available.

Availability:  http://motifmap.ics.uci.edu

Contact:  xhx@ics.uci.edu; pfbaldi@ics.uci.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Pediatric Neck Abscesses—Changing Organisms and Empiric Therapies
Authors: Inman Jared C. , Rowe Mark , Ghostine Michelle , Fleck Terry
Published: November 2008

Objective: To examine the causative organisms in pediatric neck infections, delineate risk factors in methicillin‐resistant Staphylococcus aureus (MRSA) pediatric neck infections, and define patient populations that should be empirically treated with MRSA sensitive antibiotics.

Study Design: Retrospective chart review.

Methods: Two hundred twenty‐eight consecutive patients were reviewed, ages 0 to 17, presenting at a tertiary care center between 1999 and 2007 with computed tomography proven neck abscesses. Characteristics of patients with differing causative organisms were compared.

Results: Forty‐eight percent of all pediatric patients' with head and neck abscesses had S. aureus as the causative organism, 29% of which were community‐acquired MRSA—recent years showed that up to 66% of pediatric neck abscesses were MRSA culture positive. When comparing MRSA infections vs. other causative organisms multiple clinical characteristics were found which did not help to differentiate those patients at a higher risk for MRSA. Characteristics which did trend to predict an MRSA infection were few. For example, the average age of patients with MRSA was 32.5 months compared with only 16 months for the methicillin‐sensitive S. aureus patients. MRSA sensitivities and resistances were also examined.

Conclusions: This study presents a large cohort of pediatric neck abscess patients, in which the emergence and characteristics of MRSA are shown. As community‐acquired MRSA infections become more prevalent, empiric antibiotic therapy must be considered. The results of this study show that the incidence of MRSA has greatly increased and clinical risk factors are not helpful in choosing those patients which may be at higher risk for an MRSA infection.
Carotid Artery Resection and Reconstruction With Expanded Polytetrafluoroethylene for Head and Neck Cancer
Authors: Miao Beiping , Lu Yongtian , Pan Xinliang , Liu Dayu
Published: November 2008

Objective:There are controversies on management of carotid artery invasion in advanced head and neck cancer. En bloc resection has been considered a curative modality. In this study, we evaluated the feasibility of using expanded polytetrafluoroethylene (ePTFE) in reconstructing the common carotid artery in patients with carotid artery invasion requiring resection.

Method:A retrospective study including 13 patients managed from 2002 to 2005. All patients underwent en bloc resection of the tumor and internal carotid artery then reconstructed with ePTFE.

Results:All patients had en bloc resection of the tumor together with internal carotid artery and reconstruction with ePTFE. Some patients required wound coverage with myocutaneous flaps in eight patients and local flaps in five patients. Intraoperative shunting was used in all patients. Intraoperative heparin infusion and postoperative low dose aspirin were used to prevent thrombosis. One patient developed graft blowout and he was treated with ligation without hemiplegia. One patient had minor stroke. The follow‐up period was 18.4 ± 8.6 months. No patient suffered from neurological deficit or graft occlusion. Disease survival was 61.5% in 1 year and 38.5% in 2 years. Overall survival was 18.3 months.

Conclusion:En bloc resection and tumor together with carotid artery and ePTFE reconstruction is shown to be a feasible modality in treatment of advanced head and neck cancer with carotid artery invasion.
Analysis of Recurrent Angiotensin Converting Enzyme Inhibitor‐Induced Angioedema
Authors: Roberts Daniel S. , Mahoney Elizabeth J. , Hutchinson Christoph T. , Aliphas Avner , Grundfast Kenneth M.
Published: November 2008

Objective/Hypothesis: A known risk for patients taking angiotensin converting enzyme‐inhibitors (ACE‐Is) is angioedema that can involve the face, lips, oral cavity, and larynx. Such upper airway obstruction may be severe enough to require an emergency department visit or even necessitate prompt airway intervention. Once a patient has had an episode of ACE‐inhibitor induced angioedema (AIIA), certainly a thrust of continuing case management would be to avoid the occurrence of subsequent episodes of AIIA that potentially can be life‐threatening. Nevertheless, recurrent episodes of AIIA do occur. This study aims to characterize a patient's risk for recurrent AIIA, determine the cause for repeat episodes of AIIA and recommend steps to be taken to minimize the recurrence of AIIA.

Study Design: Retrospective study.

Methods: A retrospective chart review of all patient encounters at our medical center between January 1, 1991 and December 30, 2005 with a diagnosis of angioedema was performed. The documented etiology of the angioedema, comorbidities, and documentation of an “allergy” to ACE‐I were noted. Observations regarding risk factors for recurrent AIIA were made.

Results: Recurrent AIIA occurred in 23 patients with a recurrence rate of 6.2%. Risk factors for recurrence were categorized as patient factors, physician factors, or systems factors. Physician error with failure to document in the medical record, the suspicion of AIIA, and failure to consider risk in prescribing ACE‐I after an episode of angioedema had occurred were the most common causes of recurrent AIIA.

Conclusions: Angioedema can cause life‐threatening airway compromise yet patients with a history of one episode of AIIA are at risk for a subsequent episode. Physicians can modify clinical practices to avert the potentially life‐threatening side effects of ACE‐inhibitors in patients with a prior episode of AIIA.
End‐to‐Side Venous Anastomosis With an Anastomotic Coupling Device for Microvascular Free‐Tissue Transfer in Head and Neck Reconstruction
Authors: Chernichenko Natalya , Ross Douglas A. , Shin Joseph , Sasaki Clarence T. , Ariyan Stephen
Published: November 2008

Objective: The purpose of this study is to demonstrate the success rate of using a coupling device for end‐to‐side venous anastomosis in patients undergoing free‐tissue transfer (FTT) in head and neck reconstruction.

Methods and Measures: Retrospective data were collected in consecutive series of 134 patients undergoing surgical resection of head and neck tumors followed by FTT. All microvascular FTTs were performed at Yale‐New Haven Hospital between November 2001 and August 2007. The Unilink coupling device was used to perform arterial and venous anastomosis in this case series. Flap survival and thrombosis of the venous anastomoses were determined.

Results: One hundred thirty‐four consecutive patients underwent a total of 137 microvascular FTTs using a coupling device. In our series, a total of 173 end‐to‐side anastomoses were completed in 96 patients. Of these, 77 patients had both venous anastomoses, 17 underwent one end‐to‐side and one end‐to‐end anastomoses, and two patients had one venous anastomosis per patient performed in end‐to‐side fashion. Reconstruction included 76 radial forearm, 17 fibula, and three rectus abdominis free flaps. There were three vascular insufficiency related complications of which two were salvageable. There was one case of flap failure (1%), resulting in a free flap survival rate of 99%.

Conclusion: This largest reported series of end‐to‐side venous anastomoses with an anastomotic coupling device demonstrates feasibility and efficacy of this technique in head and neck reconstruction.
Laryngeal Transplantation in the Setting of Cancer: A Rat Model
Authors: Shipchandler Taha Z. , Lorenz Robert R. , Lee Walter T. , Teker Aysenur Meric , Dan Olivia , Strome Marshall
Published: November 2008

Objective: Traditional immunosuppressive regimens make laryngeal transplantation in cancer patients prohibitive because of the increased risk of recurrence. Everolimus, a recently developed immunosuppressant, has demonstrated significant antitumor properties. The purpose of this study was to examine the effects of everolimus alone and in combination with other immunosuppressants on tumor growth in a combined laryngeal transplantation and tumor model.

Study Design: Animal, prospective, randomized, controlled, and blinded.

Methods: One million squamous cell carcinoma cells (SCC‐158) were injected intravenously into a total of 40 rats 1 day before laryngeal transplantation. Rats were divided into four groups differing by immunosuppressive regimens. Lung surface metastases were counted 21 days after inoculation, and numerical transplantation rejection scores were recorded. A separate experiment for comparison was performed with no transplant on 24 rats, but with the same immunosuppressive treatment groups.

Results: The median number of lung surface metastases were: a) control (i.e., no immunosuppression): 85; b) everolimus 1.0 mg/kg: 25; c) tacrolimus 1.2 mg/kg: 1650; d) everolimus 1.0 mg/kg + tacrolimus 0.05 mg/kg: 1300. Rats receiving everolimus alone showed a statistically significant decrease in pulmonary surface metastases compared with the other groups. Transplanted rats had no difference in their outcomes when compared with nontransplanted rats.

Conclusion: Everolimus significantly decreases SCC‐158 growth in our combined transplantation and tumor model compared with controls and other immunosuppressants.
Modeling Flow in a Compromised Pediatric Airway Breathing Air and Heliox
Authors: Mihaescu Mihai , Gutmark Ephraim , Murugappan Shanmugam , Elluru Ravindhra , Cohen Aliza , Willging J Paul
Published: November 2008

Objectives/Hypothesis: The aim of this study was to perform computer simulations of flow within an accurate model of a pediatric airway with subglottic stenosis. It is believed that the airflow characteristics in a stenotic airway are strongly related to the sensation of dyspnea.

Methodology: Computed tomography images through the respiratory tract of an infant with subglottic stenosis, were used to construct the three‐dimensional geometry of the airway. By using computational fluid dynamics (CFD) modeling to capture airway flow patterns during inspiration and expiration, we obtained information pertaining to flow velocity, static airway wall pressure, pressure drop across the stenosis, and wall shear stress. These simulations were performed with both air and heliox.

Results: Unlike air, heliox maintained laminar flow through the stenosis. The calculated pressure drop over stenosis was lower for the heliox flow, in contrast to the airflow case. This lead to an approximately 40% decrease in airway resistance when using heliox, and presumably causes a decrease in the level of effort required for breathing.

Conclusions: CFD simulations offer a quantitative method of evaluating airway flow dynamics in patients with airway abnormalities. CFD modeling illustrated the flow features and quantified flow parameters within a pediatric airway with subglottic stenosis. Simulations with air and heliox conditions mirrored the known clinical benefits of heliox as compared with air. We anticipate that computer simulation models will ultimately allow a better understanding of changes in flow caused by specific medical and surgical interventions in patients with conditions associated with dyspnea.
Role of Surgery in Limited (T1‐2, N0‐1) Cancers of the Oropharynx
Authors: Walvekar Rohan R. , Li Ryan J. , Gooding William E. , Gibson Michael K. , Heron Dwight , Johnson Jonas T. , Ferris Robert L.
Published: November 2008

Hypothesis: To define the role of surgical staging in limited (T1‐2, N0‐1) oropharyngeal squamous cell cancers.

Study Design: Retrospective.

Methods: Forty‐nine limited oropharyngeal squamous cell cancers of the tonsil, tongue base, or posterior pharyngeal wall‐treated surgically were identified.

Results: Thirty‐five percent were cT1 and 65% were cT2 tumors although 58% were cN0 and 42% were cN1. Forty‐six patients underwent neck dissections. Surgical staging altered T‐stage in 26% (13/49), nodal status in 23% (11/46), and clinical staging in 40% (20/49) of patients. Among 35 disease‐free patients, 28% (4/20) of stage I/II patients received postoperative radiation and chemotherapy was avoided in 80% (12/15) of stage III patients. T1 tumors seemed to have better outcomes (P = .06). The 3 year disease‐free survival and 5 year overall survival was 85% and 83%, respectively.

Conclusions: Surgical staging identifies patients in whom intensification of treatment with chemotherapy can be most appropriately applied, and enables de‐intensification of therapy in pathology confirmed stage I/II disease.
Vascular Pattern and Spectral Parameters of Power Doppler Ultrasound as Predictors of Malignancy Risk in Thyroid Nodules
Authors: Bakhshaee Mehdi , Davoudi Yasamin , Mehrabi Mostafa , Layegh Parvin , Mirsadaee Saadat , Rad Masoud Pezeshki , Leyegh Parvaneh
Published: November 2008

Introduction: Determination whether spectral Doppler ultrasound parameters, including resistance index (RI) and pulsatility index (PI), or vascular pattern can be used to distinguish malignant from benign thyroid nodules.

Materials and Methods: We prospectively examined 85 thyroid nodules in patients undergoing surgery. The flow pattern seen via power Doppler examination was ranked for each nodule on a scale of 0 to 4 as follows: absent, perinodular alone, mixed with perinodular prominency, mixed with intranodular prominency, and exclusively intranodular, respectively. For each nodule, the RI and PI values were recorded as the average of the recordings obtained. Pathological examination were used as a proof of final diagnosis to categorize all nodules as benign or malignant.

Results: The malignant nodules had a mean RI of 0.72 ± 0.13. These values were significantly higher than those associated with benign nodules (0.60 ± 0.08) (P = .000). Malignant nodules had a mean PI of 1.15 ± 0.33 that were also significantly different from those associated with benign nodules (0.91 ± 0.19) (P = .000). Shifting to intranodular vascularization had a significant correlation with malignancy (P = .001).

Conclusion: Spectral parameter and vascular pattern are useful to distinguish malignant from benign thyroid nodules, especially for those with suspicious or undetermined fine‐needle aspiration biopsy.
Real-time PCR for detecting circulating dengue virus in the Guangdong Province of China in 2006
Authors: Bai Zhijun , Liu Licheng , Tu Zeng , Yao Lisi , Liu Jianwei , Xu Bing , Tang Boheng , Liu Jinhua , Wan Yongji , Fang Meiyu , Chen Weijun
Published: November 2008

Dengue virus (DENV) causes a wide range of diseases in humans, from the acute febrile illness dengue fever (DF) to life-threatening dengue haemorrhagic fever/dengue shock syndrome. We developed four real-time quantitative PCR assays for each serotype of DENV based on computational analysis. These assays had high sensitivity and specificity without cross-reactivity for the four serotypes. To evaluate the performance of these assays in detecting and typing the virus in clinical samples, we analysed 64 serum samples from Guangdong during 2006. The results showed that 71 % of those samples were positive by the DEN-1 assay. The DENV assay results, in agreement with the serological tests and sequencing analysis, showed that the pathogen resulting in the DF explosion in Guangdong in 2006 belonged to DEN-1. Compared to the serological assays, the real-time PCR assays that we developed were much more sensitive in the 1–3 days after onset of the symptoms.
l‐type amino acid transporter 1 and CD98 expression in primary and metastatic sites of human neoplasms
Authors: Kaira Kyoichi , Oriuchi Noboru , Imai Hisao , Shimizu Kimihiro , Yanagitani Noriko , Sunaga Noriaki , Hisada Takeshi , Tanaka Shigebumi , Ishizuka Tamotsu , Kanai Yoshikatsu , Endou Hitoshi , Nakajima Takashi , Mori Masatomo
Published: November 2008

The significance of l‐type amino acid transporter (LAT) 1 expression remains unclear in the metastatic process of human neoplasms, whereas experimental studies have demonstrated that LAT1 is associated with the metastatic process of cancer cells. We compared the immunohistochemical expression of LAT1 and CD98 between the primary site and a concordant pulmonary metastatic site in 93 cancer patients, all of whom had undergone thoracotomy. LAT1, CD98, Ki‐67 labeling index, vascular endothelial growth factor (VEGF), CD31, and CD34 were analyzed by immunohistochemical staining in the resected tumors of 93 cancer patients: 45 colon cancers; nine breast cancers; eight head and neck cancers; 11 genital cancers; 14 soft‐tissue sarcomas; and six other cancers. The expression of these markers was significantly higher in the metastatic sites than in the primary sites. In total, the positive rates of LAT1, CD98, Ki‐67, VEGF, CD31, and CD34 were 40, 24, 56, 41, 45, and 39%, respectively, in the primary sites and 65, 45, 84, 67, 73, and 61%, respectively, in the metastatic sites. LAT1 expression was closely correlated with CD98 expression, angiogenesis, and cell proliferation. The association between LAT1 and CD98 expression was strongest in the primary and metastatic sites. The present study suggests that overexpression of LAT1 and CD98 has an important role to play in the metastatic process of variable human neoplasms. Moreover, LAT1 expression was significantly correlated with cell proliferation and angiogenesis. (Cancer Sci 2008; 99: 2380–2386)
Desmopressin responsiveness in children with Ehlers‐Danlos syndrome associated bleeding symptoms
Authors: Mast Kelley J. , Nunes Mark E. , Ruymann Frederick B. , Kerlin Bryce A.
Published: November 2008

Ehlers‐Danlos Syndrome (EDS) is caused by heritable collagen defects and may be associated with bleeding symptoms. Desmopressin has been described in case reports to decrease bleeding times in these patients. This study sought to assess bleeding time responsiveness to desmopressin therapy in a cohort of children with EDS‐associated bleeding manifestations. A retrospective chart review of children with EDS referred for bleeding symptoms was utilized. Twenty‐six children were included; 19 (73%) had a desmopressin challenge. The mean bleeding time was 11·26 (±4·39) min, decreasing to 5·95 (±2·41) min with treatment (P < 0·01). Desmopressin normalizes bleeding times in children with EDS.
Efficacy of a combination of human recombinant erythropoietin + 13‐cis‐retinoic acid and dihydroxylated vitamin D3 to improve moderate to severe anaemia in low/intermediate risk myelodysplastic syndromes
Authors: Ferrero Dario , Darbesio Antonella , Giai Valentina , Genuardi Mariella , Dellacasa Chiara Maria , Sorasio Roberto , Bertini Marilena , Boccadoro Mario
Published: November 2008

The efficacy of human recombinant erythropoietin (rEPO) in myelodysplastic syndromes (MDS) has generally been best in untransfused patients with ‘refractory anaemia’ according to the World Health Organization (WHO). We treated 63 MDS patients [excluding refractory anaemia with excess blasts, type 2 (RAEB2)] with a previously tested combination of 13‐cis‐retinoic acid and dihydroxylated vitamin D3 ± 6‐thioguanine in addition to rEPO. Most patients were categorized as refractory cytopenia with multilineage dysplasia and RAEB1, with intermediate 1 International Prognostic Scoring System (IPSS) score; all had Hb <95 g/l, and 70% required regular erythrocyte transfusions. Treatment was well tolerated, and erythroid response rate according to new International Working Group criteria was 60%: 50% in RAEB1 and 64% in non‐RAEB patients (P = 0·383). Response rate was not affected by transfusion requirement (63%; 58% in untransfused), IPSS and WHO Prognostic Scoring System scores, and weekly rEPO dosage (30–50 000 U vs. 80 000 U). Median response duration was 16 months. Median survival reached 14 months for RAEB1 and 55 months for non‐RAEB patients, with a significant difference in the latter between responders and non‐responders (median 82 months vs. 44 months; P = 0·036). Our combined therapy, independent of rEPO dosage, achieved in patients with unfavourable response predictors, a rate of anaemia improvement comparable to the best obtained in lower risk patients by high‐dose rEPO.
Dysregulated repair in asthmatic paediatric airway epithelial cells: the role of plasminogen activator inhibitor‐1
Authors: Stevens P. T. , Kicic A. , Sutanto E. N. , Knight D. A. , Stick S. M.
Published: November 2008

Background
Asthma is associated with structural changes to airways such as extracellular matrix deposition and epithelial damage. Evidence suggests that asthmatic airway epithelial repair is abnormal and that elevated plasminogen activator inhibitor‐1 levels observed in asthma may be involved in the epithelial repair process and in excessive matrix accumulation.

Objective
To assess the ability of asthmatic airway epithelial cells (AECs) to repair mechanically induced wounds and to investigate the role that plasminogen activator inhibitor‐1 plays in the repair process.

Methods
AECs were isolated from atopic asthmatic and healthy non‐atopic children by bronchial brushing, subcultured and wound repair experiments were performed. Plasminogen activator inhibitor‐1 gene expression was assessed using real‐time PCR while protein activity was measured in cell lysates as well as plasma. The role of plasminogen activator inhibitor‐1 in epithelial proliferation and wound repair was investigated using siRNA.

Results
Cells from asthmatic children have a significantly longer repair time in comparison with cells from otherwise healthy donors. Plasminogen activator inhibitor‐1 mRNA expression was up‐regulated 68‐fold in freshly isolated asthmatic cells compared with normal cells, and protein levels were also significantly elevated in the asthmatic cell lysates, but plasma levels were similar in both groups. Plasminogen activator inhibitor‐1 cells expression increased in both cohorts during culture. Gene silencing substantially reduced the rate of proliferation in asthmatic and healthy cells. Mechanical wounding of epithelial monolayers induced plasminogen activator inhibitor‐1 expression in asthmatic and non‐asthmatic cohorts, while gene silencing delayed wound repair of healthy cell, with minimal effect on those from asthmatics.

Conclusion
Asthmatic AECs are inherently dysfunctional in their ability to repair wounds; plasminogen activator inhibitor‐1 mRNA and protein activity are constitutively up‐regulated in asthmatic epithelium and play functional roles in both proliferation and repair of healthy cells. In asthmatic cells, elevated plasminogen activator inhibitors‐1 levels fail to stimulate epithelial repair.
Immunomodulatory therapy of eosinophil‐associated gastrointestinal diseases
Authors: Stone K. D. , Prussin C.
Published: November 2008

Eosinophil‐associated gastrointestinal disorders (EGIDs), including eosinophilic esophagitis (EE) and eosinophilic gastroenteritis (EG), are a spectrum of increasingly recognized inflammatory diseases characterized by gastrointestinal symptoms and eosinophilic infiltration of the gastrointestinal tract. Significant morbidity is associated with the development of esophageal strictures in some patients. Immune‐mediated reactions to food allergens appear to drive the inflammation in a subset of patients, especially those with solitary EE, but dietary interventions remain difficult in EE and are less effective in EG. Despite the increasing incidence of these disorders and their increased recognition by physicians, there are currently no medications that either United States or European Union regulatory agencies have specifically approved for use in EGIDs. This lack of safe and effective therapies for EGIDs is a major obstacle in the care of these patients and underscores the need for new therapeutic approaches. This review briefly discusses the currently available ‘off label’ drug treatments for EGIDs, most notably topical and systemic corticosteroids. Pathogenesis studies of EGIDs suggest possible therapeutic targets, and conversely, clinical trials of mechanistically‐targeted therapeutics give insight into disease pathogenesis. Thus, EGID pathogenesis is discussed as an introduction to mechanistically‐targeted immunotherapeutics. The two biologic categories that have been used in EGIDs, anti‐IgE (omalizumab) and anti‐IL‐5 (SCH55700/reslizumab and mepolizumab), are discussed. Because there are similarities in the pathogenesis of EGIDs with asthma and atopic dermatitis, biologic therapeutics currently in early trials for asthma management are also briefly discussed as potential therapeutic agents for EGIDs. Given the deficiencies of current therapeutics and the rapidly advancing knowledge of the pathogenesis of these disorders, EGIDs are an ideal model for translating recent advances in understanding immunopathogenesis into mechanistically‐based therapeutics. Further understanding of the early events in pathogenesis is also needed to develop preventive and disease‐modifying treatments.
Clinical Immunology Review Series: An approach to the patient with angio-oedema
Authors: Grigoriadou S , Longhurst H J
Published: November 2008

ARTICLES PUBLISHED IN THIS CLINICAL IMMUNOLOGY REVIEW SERIES

allergy in childhood, allergy diagnosis by use of the clinical immunology laboratory, anaphylaxis, angioedema, management of pulmonary disease in primary antibody deficiency, recurrent infections in childhood, recurrent infections in adulthood, recurrent oro-genital ulceration, recurrent superficial abscesses, SLE and Sjögren's syndrome, urticaria, vasculitis/CTD

Angio-oedema is a common reason for attendance at the accident and emergency department and for referral to immunology/allergy clinics. Causative factors should always be sought, but a large proportion of patients have the idiopathic form of the disease. A minority of patients represent a diagnostic and treatment challenge. Failure to identify the more unusual causes of angio-oedema may result in life-threatening situations. Common and rare causes of angio-oedema will be discussed in this article, as well as the diagnostic and treatment pathways for the management of these patients. A comprehensive history and close monitoring of response to treatment are the most cost-effective diagnostic and treatment tools.
Short-term anti-CD25 monoclonal antibody administration down-regulated CD25 expression without eliminating the neogenetic functional regulatory T cells in kidney transplantation
Authors: Wang Z , Shi B-Y , Qian Y-Y , Cai M , Wang Q
Published: November 2008

CD4+CD25+ forkhead box P3 (FoxP3)+regulatory T (Treg) cells are generated and play a key role in the induction and maintenance of transplant tolerance in organ recipients. It has been proposed that interleukin (IL)-2/IL-2 receptor (IL-2R) signalling was essential for the development and proliferation of antigen-activated T cells that included both effector T cells and Treg cells. Basiliximab (Simulect™), a chimeric monoclonal antibody directed against the α-chain of the IL-2R (CD25), can be expected to not only affect alloreactive effector T cells, but also reduce the number and function of Treg cells. We therefore examined the effect of basiliximab induction therapy on the number and function of the Treg cells in renal recipients. Basiliximab decreased the percentage of CD4+CD25+T cells, but failed to influence the percentage of CD4+FoxP3+ Treg cells. The cellular CD25 expression was decreased significantly by basiliximab injection, but CD4+CD25+ T cells was not depleted from the circulating pool through monoclonal antibody activation-associated apoptosis. Functional analysis revealed that inhibitory function of Treg cells from recipients with basiliximab injection was not significantly different from recipients without injection. These data indicate that the functional Treg population may not be influenced by short-term basiliximab treatment.
Myocardial perfusion defects in Bartter and Gitelman syndromes
Authors: Scognamiglio R. , Calò L. A. , Negut C. , Coccato M. , Mormino P. , Pessina A. C.
Published: November 2008

Background  Normotensive hypokalaemic tubulopathies (Bartter and Gitelman syndromes (BS/GS)) are genetic diseases that are considered benign. However, QT prolongation, left ventricular dysfunction and reduction of cardiac index upon exercise leading to arrhythmias and sudden cardiac death have been reported in these patients. Hence, we aimed to verifying whether an isometric exercise could represent a useful tool for the identification of patients at risk for future cardiac events.

Patients and methods  Myocardial function (MF) and perfusion, evaluated as myocardial blood flow (MBF) of 10 BS/GS patients and 10 healthy controls, were investigated at rest and during isometric exercise. MF and MBF were evaluated using quantitative two‐dimensional and myocardial contrast echocardiography.

Results  BS/GS patients had normal baseline MF and MBF. During exercise in BS/GS patients, corrected QT (QTc) was prolonged to peak value of 494 ± 9·1 ms (P < 0·001). In controls, MF increased from resting to peak exercise (left ventricular ejection fraction: 65 ± 4% to 78 ± 5%, P < 0·003) while in seven BS/GS patients (Group 1) it declined (64 ± 5% to 43 ± 9%, P < 0·001). Myocardial perfusion increased upon exercise in controls as shown by changes of its markers: β (a measure of myocardial flow velocity; 0·89 ± 0·12 vs. 0·99 ± 0·12, P < 0·001) and myocardial blood volume (14·4 ± 2 vs. 20·2 ± 0·25, P < 0·001), while in Group 1 BS/GS it decreased (0·87 ± 0·15 vs. 0·67 ± 0·15, P < 0·001; and 14·5 ± 1·9 vs. 8·3 ± 0·22, P < 0·001, respectively).

Conclusions  Our results document for the first time that exercise induce coronary microvascular and myocardial defects in BS/GS patients. Therefore, this may challenge the idea that BS/GS are benign diseases. In addition, the diagnostic approach to these syndromes should include an in‐depth cardiac assessment in order to identify patients at higher risk.
The prognostic relevance of preoperative transcatheter arterial chemoembolization (TACE) and PCNA/VEGF expression in patients with Wilms’ tumour
Authors: Liu W.‐G. , Gu W.‐Z. , Zhou Y.‐B. , Tang H.‐F. , Li M.‐J. , Ma W.‐X.
Published: November 2008

Background  Wilms’ tumour is the most frequent renal tumour in children. Based on the SIOP strategy, children with Wilms’ tumour may benefit from preoperative chemotherapy, but few publications address the effect of preoperative transcatheter arterial chemoembolization (TACE) on patients with Wilms’ tumours. The aims of this study were to investigate the prognostic relevance of preoperative TACE followed by tumour resection, proliferating cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF) expression in patients with Wilms’ tumours.

Materials and methods  Two therapeutic strategies including tumour resection only and TACE, followed by tumour resection were conducted in a cohort of 44 patients with Wilms’ tumours. Clinical and follow‐up data was analysed. Immunohistochemistry staining was used to explore PCNA and VEGF expression in the Wilms’ tumour.

Results  Two years tumour‐free survival of the patients in the TACE group was significantly higher than that of the patients in the control group (P < 0·001) and recurrence and cases of death within one year in the TACE group was markedly lower than that in the control group (P < 0·001). Fifty‐five percent of patients in the control group were PCNA‐positive vs. 4·17% of patients in the TACE group (P < 0·001). Fifty percent of patients in the control group were VEGF‐positive vs. 29·17% of patients in the TACE group (P > 0·05).

Conclusions  Patients with Wilms’ tumours benefited from preoperative TACE treatment. PCNA expression was significantly lower in patients in the TACE group than those in the control group. There was no significant difference on VEGF expression between the patients in TACE and control groups.
Delayed complete remission in a patient with multiple myeloma
Authors: Ria R. , Vacca A. , Mangialardi G. , Dammacco F.
Published: November 2008

We report a strikingly positive, late response to bortezomib in conjunction with pegylated liposomal doxorubicin in a 79‐year old woman with multiple myeloma (MM). The patient obtained a partial remission after eight courses of therapy and a complete remission about 10 months after the end of therapy.

This delayed complete remission may be similar to the spontaneous regression reported for other malignancies such as melanoma or lymphoma. We postulate that the immune response and a persistent anti‐angiogenic effect of bortezomib could well explain the delayed complete remission in our patient.