bluuebunny/crossref_metadata_2025 huggingface dataset:
DOPING: A NEW NON-PARAMETRIC DEPROJECTION SCHEME
Authors: CHAKRABARTY DALIA , FERRARESE LAURA
Published: March 2008

We present a new non-parametric deprojection algorithm, DOPING (Deprojection of Observed Photometry using an INverse Gambit), which is designed to extract the three-dimensional luminosity density distribution ρ, from the observed surface brightness profile of an astrophysical system such as a galaxy or a galaxy cluster, in a generalised geometry, while taking into account changes in the intrinsic shape of the system. The observable is the 2D surface brightness distribution of the system. While the deprojection schemes presented hitherto have always worked within the limits of an assumed intrinsic geometry, in DOPING, geometry and inclination can be provided as inputs. The ρ that is most likely to project to the observed brightness data is sought; the maximisation of the likelihood is performed with the Metropolis algorithm. Unless the likelihood function is maximised, ρ is tweaked in shape and amplitude, while maintaining positivity, but otherwise the luminosity distribution is allowed to be completely free-form. Tests and applications of the algorithm are discussed.
KALUZA–KLEIN SOLITONS RE-EXAMINED
Authors: PONCE DE LEON J.
Published: March 2008

In 4 + 1 gravity the assumption that the five-dimensional metric is independent of the fifth coordinate permits the extra dimension to be either spacelike or timelike. As a consequence of this, the time coordinate and the extra coordinate are interchangeable, which in turn allows the conception of different scenarios in 4D from a single solution in 5D. In this paper, we make a thorough investigation of all possible 4D scenarios, associated with this interchange, for the well-known Kramer–Gross–Perry–Davidson–Owen set of solutions. We show that there are three families of solutions with very distinct geometrical and physical properties. They correspond to different sets of values of the parameters which characterize the solutions in 5D. The solutions of physical interest are identified on the basis of physical requirements on the induced matter in 4D. We find that only one family satisfies these requirements; the other two violate the positivity of mass-energy density. The "physical" solutions possess a lightlike singularity which coincides with the horizon. The Schwarzschild black string solution as well as the zero moment dipole solution of Gross and Perry are obtained in different limits. These are analyzed in the context of Lake's geometrical approach. We demonstrate that the parameters of the solutions in 5D are not free, as previously considered. Instead, they are totally determined by measurements in 4D — namely, by the surface gravitational potential of the astrophysical phenomena, like the Sun or other stars, modeled in Kaluza–Klein theory. This is an important result which may help in observations for an experimental/observational test of the theory.
UNDERSTANDING THE DYNAMICS OF INDUSTRIAL NETWORKS USING KAUFFMAN BOOLEAN NETWORKS
Authors: EASTON GEOFF , BROOKS ROGER J. , GEORGIEVA KRISTINA , WILKINSON IAN
Published: March 2008

Industrial networks offer a prime example of the tension between system stability and change. Change is necessary as a response to environmental variation, whereas stability provides the underpinning for long-term investment and the exploitation of efficiencies. Whilst one of the key themes in industrial network research has been the dynamics of change, relatively little work, empirical or theoretical, has been devoted to the dynamics of stability. This paper presents a new approach to this problem by using Boolean networks, which were originally devised by Stuart Kauffman as an abstract model of genetic networks. The elements in the model are connected by rules of Boolean logic, and a novel aspect of this research is that the elements represent the industrial network exchanges rather than stock entities (the organizations). The model structure consists of interactions between the exchanges, and the results represent the pattern of exchange episodes. A total of 42 networks were modeled and the dynamics analyzed in detail, and five of these cases are presented in this paper. The models produced realistic behavior and provided some insights into the reasons for stability in industrial networks.
Detecting splogs via temporal dynamics using self-similarity analysis
Authors: Lin Yu-Ru , Sundaram Hari , Chi Yun , Tatemura Junichi , Tseng Belle L.
Published: March 2008

This article addresses the problem of spam blog (splog) detection using temporal and structural regularity of content, post time and links. Splogs are undesirable blogs meant to attract search engine traffic, used solely for promoting affiliate sites. Blogs represent popular online media, and splogs not only degrade the quality of search engine results, but also waste network resources. The splog detection problem is made difficult due to the lack of stable content descriptors.

We have developed a new technique for detecting splogs, based on the observation that a blog is a dynamic, growing sequence of entries (or posts) rather than a collection of individual pages. In our approach, splogs are recognized by their temporal characteristics and content. There are three key ideas in our splog detection framework. (a) We represent the blog temporal dynamics using self-similarity matrices defined on the histogram intersection similarity measure of the time, content, and link attributes of posts, to investigate the temporal changes of the post sequence. (b) We study the blog temporal characteristics using a visual representation derived from the self-similarity measures. The visual signature reveals correlation between attributes and posts, depending on the type of blogs (normal blogs and splogs). (c) We propose two types of novel temporal features to capture the splog temporal characteristics. In our splog detector, these novel features are combined with content based features. We extract a content based feature vector from blog home pages as well as from different parts of the blog. The dimensionality of the feature vector is reduced by Fisher linear discriminant analysis. We have tested an SVM-based splog detector using proposed features on real world datasets, with appreciable results (90% accuracy).
Not quite the average
Authors: Weinreich Harald , Obendorf Hartmut , Herder Eelco , Mayer Matthias
Published: March 2008

In the past decade, the World Wide Web has been subject to dramatic changes. Web sites have evolved from static information resources to dynamic and interactive applications that are used for a broad scope of activities on a daily basis. To examine the consequences of these changes on user behavior, we conducted a long-term client-side Web usage study with twenty-five participants. This report presents results of this study and compares the user behavior with previous long-term browser usage studies, which range in age from seven to thirteen years. Based on the empirical data and the interview results, various implications for the interface design of browsers and Web sites are discussed.

A major finding is the decreasing prominence of backtracking in Web navigation. This can largely be attributed to the increasing importance of dynamic, service-oriented Web sites. Users do not navigate on these sites searching for information, but rather interact with an online application to complete certain tasks. Furthermore, the usage of multiple windows and tabs has partly replaced back button usage, posing new challenges for user orientation and backtracking. We found that Web browsing is a rapid activity even for pages with substantial content, which calls for page designs that allow for cursory reading. Click maps provide additional information on how users interact with the Web on page level. Finally, substantial differences were observed between users, and characteristic usage patterns for different types of Web sites emphasize the need for more adaptive and customizable Web browsers.
Mobile ad hoc networking and the IETF
Authors: Chakeres Ian D. , Macker Joseph P.
Published: March 2008

This article is part of a continuing series to discuss ongoing activities within the mobile ad hoc networking (MANET) working group (WG) of the IETF. This article provides a brief overview of recent events.
Hand Position Affects Saccadic Reaction Times in Monkeys and Humans
Authors: Thura David , Boussaoud Driss , Meunier Martine
Published: March 2008

In daily life, activities requiring the hand and eye to work separately are as frequent as activities requiring tight eye–hand coordination, and we effortlessly switch from one type of activity to the other. Such flexibility is unlikely to be achieved without each effector “knowing” where the other one is at all times, even when it is static. Here, we provide behavioral evidence that the mere position of the static hand affects one eye movement parameter: saccadic reaction time. Two monkeys were trained and 11 humans instructed to perform nondelayed or delayed visually guided saccades to either a right or a left target while holding their hand at a location either near or far from the eye target. From trial to trial, target locations and hand positions varied pseudorandomly. Subjects were tested both when they could and when they could not see their hand. The main findings are 1) the presence of the static hand in the workspace did affect saccade initiation; 2) this interaction persisted when the hand was invisible; 3) it was strongly influenced by the delay duration: hand–target proximity retarded immediate saccades, whereas it could hasten delayed saccades; and 4) this held true both for humans and for each of the two monkeys. We propose that both visual and nonvisual hand position signals are used by the primates' oculomotor system for the planning and execution of saccades, and that this may result in a hand–eye competition for spatial attentional resources that explains the delay-dependent reversal observed.
Involvement of Fibroblast Growth Factor Receptor 2 Isoform Switching in Mammary Oncogenesis
Authors: Cha Jiyoung Y. , Lambert Que T. , Reuther Gary W. , Der Channing J.
Published: March 2008

We identified the IIIb C2 epithelial cell–specific splice variant of fibroblast growth factor receptor 2 (FGFR2 IIIb C2) receptor tyrosine kinase in a screen for activated oncogenes expressed in T-47D human breast carcinoma cells. We found FGFR2 IIIb C2 expression in breast carcinoma cell lines and, additionally, expression of the mesenchymal-specific FGFR2 IIIc splice variant in invasive breast carcinomas. FGFR2 IIIc expression was associated with loss of epithelial markers and gain of mesenchymal markers. Although FGFR2 IIIb is expressed in epithelial cells, previous studies on FGFR2 IIIb transformation have focused on NIH 3T3 fibroblasts. Therefore, we compared the transforming activities of FGFR2 IIIb C2 in RIE-1 intestinal cells and several mammary epithelial cells. FGFR2 IIIb C2 caused growth transformation of epithelial cells but morphologic transformation of only NIH 3T3 cells. FGFR2 IIIb C2–transformed NIH 3T3, but not RIE-1 cells, showed persistent activation of Ras and increased cyclin D1 protein expression. NIH 3T3 but not RIE-1 cells express keratinocyte growth factor, a ligand for FGFR2 IIIb C2. Ectopic treatment with keratinocyte growth factor caused FGFR2 IIIb C2–dependent morphologic transformation of RIE-1 cells, as well as cyclin D1 up-regulation, indicating that both ligand-independent and stromal cell–derived, ligand-dependent mechanisms contribute to RIE-1 cell transformation. Our results support cell context distinct mechanisms of FGFR2 IIIb C2 transformation. (Mol Cancer Res 2008;6(3):435–45)
Modulation of Endocrine Pancreas Development but not β-Cell Carcinogenesis by Sprouty4
Authors: Jäggi Fabienne , Cabrita Miguel A. , Perl Anne-Karina T. , Christofori Gerhard
Published: March 2008

Sprouty (Spry) proteins modulate signal transduction pathways elicited by receptor tyrosine kinases (RTK). Depending on cell type and the particular RTK, Spry proteins exert dual functions: They can either repress RTK-mediated signaling pathways, mainly by interfering with the Ras/Raf/mitogen-activated protein kinase pathway or sustaining RTK signal transduction, for example by sequestering the E3 ubiquitin-ligase c-Cbl and thus preventing ubiquitylation, internalization, and degradation of RTKs. Here, by the inducible expression of murine Spry4 in pancreatic β cells, we have assessed the functional role of Spry proteins in the development of pancreatic islets of Langerhans in normal mice and in the Rip1Tag2 transgenic mouse model of β-cell carcinogenesis. β cell–specific expression of mSpry4 provokes a significant reduction in islet size, an increased number of α cells per islet area, and impaired islet cell type segregation. Functional analysis of islet cell differentiation in cultured PANC-1 cells shows that mSpry4 represses adhesion and migration of differentiating pancreatic endocrine cells, most likely by affecting the subcellular localization of the protein tyrosine phosphatase PTP1B. In contrast, transgenic expression of mSpry4 during β-cell carcinogenesis does not significantly affect tumor outgrowth and progression to tumor malignancy. Rather, tumor cells seem to escape mSpry4 transgene expression. (Mol Cancer Res 2008;6(3):468–82)
Route of Administration of Illicit Drugs among Remand Prison Entrants
Authors: Niveau G. , Ritter C.
Published: March 2008

Aims: To describe the self-reported routes of administration of illicit drugs among subjects entering a remand prison and the different drugs used by this population. Methods: A cross-sectional study, with a sample of 770 subjects, was conducted in Geneva (Switzerland). Participants were assessed with the semi-structured interview from the Council of Europe Pompidou Group multi-city study. Results: 428 (55.6%) subjects admitted to having used illicit drugs during the 3 months prior to entry. Amongst these illicit drug users, 54.7% took several drugs. Injectable drugs (heroin, cocaine or illicit benzodiazepines) were taken by 75.7% of drug users but the majority (84.1%) declared that they had not injected drugs during the 3 months prior to entering prison. 68 subjects (8.8% of the total sample) declared that they had injected drugs during the 3 months prior to entering prison, either alone or in association with other methods. Conclusion: By extrapolation it is possible to suggest that about 200 intravenous drug users entered the remand prison in Geneva in 1 year. This confirms the need for prison health services to implement a policy of treatment, prevention and education adapted to patterns of drug use in the local context.
siRNA Targeting against EGFR, a Promising Candidate for a Novel Therapeutic Application to Lung Adenocarcinoma
Authors: Yamanaka Sumitaka , Gu Zhaodi , Sato Masami , Fujisaki Rumi , Inomata Kenichi , Sakurada Akira , Inoue Akira , Nukiwa Toshihiro , Kondo Takashi , Horii Akira
Published: March 2008

Objective: To understand the molecular pathogenesis of lung cancer and to establish a novel therapeutic application, we examined the genetic alterations in lung cancer, and studied the effects of gefitinib and siRNA-mediated knockdown of EGFR on lung cancer. Methods: We analyzed mutations in EGFR, KRAS, TP53, and ERBB2 in 198 surgically resected lung cancer specimens. We then analyzed the effects of gefitinib and siRNA treatment on lung adenocarcinoma cell lines. Results: Mutations in EGFR were found only in adenocarcinoma (35 of 106 adenocarcinoma), mainly in females (73%). Mutually exclusive mutations of EGFR and KRAS genes were observed.Mutations of EGFR were well associated with a positive response to gefitinib. Cells with EGFR mutations were very sensitive to gefitinib as well as siRNA-mediated knockdown of EGFR, those with KRAS mutations responded poorly, and those without mutations of KRAS and EGFR showed moderate responses to both treatments. Conclusions: Our present results imply that (1) mutation analyses of EGFR and KRAS provide valuable information about whether or not to apply treatments targeting against EGFR and the selection of dosage for such treatments, and (2) siRNA-mediated knockdown is effective in lung adenocarcinomas with EGFR mutation, probably in those with resistance to gefitinib by acquired mutation in EGFR.
Negative Regulators of Angiogenesis in Inflammatory Bowel Disease: Thrombospondin in the Spotlight
Authors: Danese Silvio
Published: March 2008

Angiogenesis is the growth of new blood vessels. In the two major forms of inflammatory bowel disease (IBD), Crohn’s disease and ulcerative colitis, robust angiogenesis exists, and its blockade may have therapeutic potential, as shown in animal models of experimental intestinal inflammation. While abundant literature is available on the positive regulators of intestinal pathological angiogenesis, e.g. VEGF, b-FGF, IL-8, CD40 and CD40L, almost no data exist on negative regulators. Thrombospondin-1 is a negative regulator of angiogenesis, and it plays a new role in IBD-associated angiogenesis. In addition, recombinant thrombospondin-1 may inhibit pathological angiogenesis and may offer a new therapeutic approach to intestinal inflammation.
Large-Scale Analysis of Cell Cycle Regulators in Urothelial Bladder Cancer Identifies p16 and p27 as Potentially Useful Prognostic Markers
Authors: Brunner Andrea , Verdorfer Irmgard , Prelog Martina , Mayerl Christina , Mikuz Gregor , Tzankov Alexandar
Published: March 2008

Aims: We investigated the value of multiple cell cycle markers for their prognostic impact on overall survival and recurrence-free survival in urothelial carcinoma (UC). Methods: A tissue microarray consisting of 99 UCs was evaluated for the expression of p53, p16, p21, p27, cyclin D1, cyclin E , Bcl-2, Ki-67 and PCNA. Statistical analysis was performed applying Kaplan-Meier and Cox regression models using receiver operator characteristic curves for determination of markers’ cutoffs. Results: Expression above the cutoffs of Ki-67, p53 and p27, particularly in high-grade and early-stage UC, was associated with worse overall survival, while expression of p16 indicated a better outcome in low-grade and low-stage tumors. Recurrence-free survival was better in patients with high-grade UC expressing PCNA, p16 and cyclin E, and low-grade UC expressing Bcl-2 above the cutoffs, but worse in all tumors with high Ki-67. Conclusion: Cell cycle deregulation in UC is complex and the prognostic value of the various involved proteins should be differentially regarded with respect to this complexity and other tumor characteristics such as grade and stage. Our results point towards the role of p16- and p27-associated pathways in tumor progression and indicate that, by using standardized approaches for tissue antigen expression, evaluation and cutoff determination, single potentially useful prognostic markers could be identified.
Spatial and Phenotypic Characterization of Vascular Remodeling in a Mouse Model of Asthma
Authors: Su Xinming , Taniuchi Namiko , Jin Enjing , Fujiwara Masakazu , Zhang Lei , Ghazizadeh Mohammad , Tashimo Hiroyuki , Yamashita Naomi , Ohta Ken , Kawanami Oichi
Published: March 2008

Asthma is a chronic inflammatory disease characterized by airway wall remodeling in which vascular remodeling is thought to be a main contributor. Vascular endothelial growth factor (VEGF) is known as a major regulator of angiogenesis and enhancer of vascular permeability. Here, we define the spatial nature of vascular remodeling and the role of VEGF and its receptors (Flt-1 and Flk-1) in the allergic response in mice (A/J) susceptible to the development of allergen-induced airway hyperresponsiveness using morphometric and quantitative approaches. Increased vascularity, vasodilatation, and endothelial cell proliferation were found in the tracheal and bronchial walls in the early and late phases of asthma. Vascular changes were observed not only in small vessels but also in larger vessels. In contrast to normal control, lung tissue from the asthma model showed dual expression for CD31 and von Willebrand factor in the endothelial cells and α-smooth muscle actin and desmin in the mural cells of the vessels, suggesting a phenotypic and functional transformation. The mRNA levels of VEGF isoforms, VEGF164 and VEGF188, were significantly increased in the tracheal and lung tissue, respectively. In addition, the mRNA level of VEGF receptor Flk-1 was significantly increased in the trachea. These results establish the existence of vascular remodeling in the airways in a mouse model of allergic asthma and support a key role for the expression of unique VEGF isoform genes as mediators of structural changes.
Successful Late Management of Esophageal Perforation with T-Tube Drainage
Authors: Nakabayashi Toshihiro , Kudo Michiaki , Hirasawa Toshiaki , Kuwano Hiroyuki
Published: March 2008

The late management of spontaneous esophageal perforation is the most challenging problem for the surgeon. In this paper, we present a case in whom a spontaneous esophageal perforation was successfully treated by T-tube drainage after unsuccessful conservative treatment. The patient, a 68-year-old male, was admitted to the hospital with sudden upper abdominal pain. After 2 days, esophageal perforation was diagnosed, and conservative management was begun. Thereafter, the subcutaneous emphysema disappeared, and the patient’s temperature decreased. However, on day 13, the patient’s temperature spiked above 38°C, and computed tomography showed a mediastinal abscess. An emergency left thoracotomy with laparotomy was performed. Since a 2-cm longitudinal perforation with severe inflammatory reactions was observed, the T-tube drainage method was performed. The patient was discharged without postoperative complications and has not experienced any gastrointestinal symptoms, such as gastroesophageal reflux or dysphagia. In conclusion, the T-tube drainage method appears to be a simple and effective method for the late management of esophageal perforation with severe inflammatory reaction.
Resection of Segments 4, 5 and 8 for a Cystic Liver Tumor Using the Double Liver Hanging Maneuver
Authors: Nanashima Atsushi , Sumida Yorihisa , Abo Takafumi , Nonaka Takashi , Sengyoku Hideyori , Sawai Terumitsu , Yasutake Toru , Nagayasu Takeshi
Published: March 2008

To achieve complete anatomic central hepatectomy for a large tumor compressing surrounding vessels, transection by an anterior approach is preferred but a skillful technique is necessary. We propose the modified technique of Belghiti’s liver hanging maneuver (LHM). The case was a 77-year-old female with a 6-cm liver cystic tumor in the central liver compressing hilar vessels and the right hepatic vein. At the hepatic hilum, the spaces between Glisson’s pedicle and hepatic parenchyma were dissected, which were (1) the space between the right anterior and posterior Glisson pedicles and (2) the space adjacent to the umbilical Glisson pedicle. Two tubes were repositioned in each space and ‘double LHM’ was possible at the two resected planes of segments 4, 5 and 8. Cut planes were easily and adequately obtained and the compressed vessels were secured. Double LHM is a useful surgical technique for hepatectomy for a large tumor located in the central liver.
Evaluating the Quality of Longitudinal Statistical Applications in Original Publications on Alzheimer’s Disease
Authors: Xiong Chengjie , Tang Yuxiao , van Belle Gerald , Miller J. Philip , Launer Lenore J. , Morris John C.
Published: March 2008

Background/Aims: To evaluate the quality of longitudinal statistical applications in published studies on Alzheimer’s disease (AD). Methods: A 21-item instrument, the Quality of Longitudinal AD Studies (QLADS), was developed by the research team (4 biostatisticians, 1 neuroepidemiologist, and 1 neurologist). All items were extensively discussed within the team for content validity. After pilot testing on 5 publications, the instrument was revised and tested for reliability with a sample of 40 published longitudinal AD studies randomly sampled from MEDLINE. Results: Item-specific test-retest reliability coefficients for QLADS ranged from 0.53 to 1.00 with the associated standard error (SE) ranging from 0.02 to 0.13. The test-retest reliability for the overall score over the 21 items was high (intraclass correlation coefficient (ICC) = 0.94, 95% CI 0.90, 0.97). Item-specific inter-rater reliability coefficients for QLADS ranged from 0.46 to 1.00 with the associated SE ranging from 0.07 to 0.18. The inter-rater reliability for the overall score was also high (ICC = 0.87, 95% CI 0.77, 0.93). Conclusions: This study indicates that the quality of longitudinal statistical applications in AD publications can be reliably assessed.
Pediatric Extradural Spinal Tumors
Authors: Kumar Raj , Giri Pramod J.
Published: March 2008

We have reviewed 16 children with extradural spinal tumors, both benign and malignant, treated from 1998 to 2006 in Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India. The duration of symptomatology, clinical signs, radiological investigations, surgical approach, outcome and histopathological variation from the Western world was noted and evaluated. The age of these children ranged from 3 to 20 years. There were 11 boys and 5 girls. The duration of symptoms was 2–18 months, relatively longer in benign (mean 9.5 months) than malignant (mean 4.2 months) tumors. The follow-up ranged from 3 to 72 months and patients were graded preoperatively and postoperatively with the McCormick Functional Grading System. There was significant improvement in grade III–V patients, i.e. 74% of patients were grade III–IV at presentation, and only 35% at the last follow-up. There was deterioration from grade III to grade IV in 2 patients (PNET + metastatic adenocarcinoma) and 2 patients (neuroblastoma + Ewing’s sarcoma) maintained their grades of IV and V, respectively. There was a wide range of histological variants seen in our series and the patients were treated primarily with a suitable surgical approach and adjuvant chemoradiotherapy, wherever indicated.
Setting Sun Eye in Normal Healthy Infants
Authors: Nejat Farideh , Yazdani Shahrooz , El Khashab Mostafa
Published: March 2008

Background: The setting sun eye is a common sign associated with severe disorders signifying intracranial hypertension. Rarely it can be observed in a healthy infant. We conducted this study to evaluate and follow setting sun eye in normal infants without any obvious intracranial diseases. Methods: A cross-sectional study was conducted in the Children’s Hospital Medical Center in Tehran from June 2001 to 2006. The study included 15 healthy infants who were referred to the neurosurgery clinic for setting sun eye. All were evaluated with brain imaging, and laboratory tests including at least thyroid function tests, and serum calcium and phosphorus. The cases were followed by regular outpatient visits until the age of 2 years. Results: They were 3–8 months old at the time of referring to the outpatient clinic. Setting sun eye was observed by the mother in all cases and confirmed during their visit to the clinic. All had normal brain imaging and normal laboratory tests (thyroid function and electrolytes). Setting sun eye disappeared gradually during the follow-up period with a range of 2–8 months after detection by the mother. Conclusion: Despite the fact that setting sun eye is a grave sign, most commonly accompanied by other neurological signs and symptoms suggesting serious diseases, it might be observed as a sole finding in a totally normal infant with inconclusive brain imaging and laboratory tests. We found that this type of setting sun eye has a benign course and will disappear without any intervention several months after its detection (commonly before the age of 2 years without any intervention).
Unusual Case of Leptomeningeal Dissemination of a Diffuse Pontine High-Grade Astrocytoma in a Child
Authors: Postovsky Sergey , Eran Ayelet , Weyl Ben Arush Myriam
Published: March 2008

A 12-year-old girl was seen in our hospital and diagnosed with diffuse pontine glioma. Treatment with radiotherapy was suggested, but the parents rejected this plan and took the child to another hospital where partial resection of the tumor was performed. The histological diagnosis was anaplastic astrocytoma. Returning to our hospital, the parents agreed to radiotherapy which was given in a total dose of 54 Gy. However, 3 months after completion of radiotherapy, the child developed widespread leptomeningeal dissemination of her disease and died 12 months after the initial diagnosis. Since no effective curative methods of treatment exist for patients with diffuse pontine gliomas and surgical intervention is obsolete in this situation and may facilitate leptomeningeal dissemination of the disease, further innovative methods of treatment are needed to improve the bleak prognosis of these patients.
Progressive Changes in Hepatoma Cells Stably Transfected with Hepatitis B Virus X Gene
Authors: Ye Lihong , Dong Nan , Wang Qi , Xu Zhili , Cai Na , Wang Honghui , Zhang Xiaodong
Published: March 2008

Objective: The aim of this study is to investigate the molecular mechanism of hepatocellular carcinoma (HCC) development induced by hepatitis B virus X protein (HBx). Methods: We previously established a H7402-X cell line that constitutively expresses HBx protein. In the present study, H7402-X gene expression profiles and proteins were examined using cDNA microarrays and Western blot analysis. Apoptosis was induced by adriamycin in H7402-X cells. The transcriptional activities of NF-ĸB and AP-1 were examined using a luciferase reporter gene. Results: The DNA expression profiles identified candidate genes showing aberrant expression in cells overexpressing HBx. Western blot analysis showed that cyclin D, cyclin E, survivin, Bcl-2, and PCNA were up-regulated, whereas p27 was down-regulated in H7402-X cells. Treatment with RNAi targeting HBx mRNA led to the down-regulation of these genes. H7402-X cells were resistant to adriamycin-induced apoptosis. Luciferase reporter gene analysis revealed that HBx induces the transcriptional activities of NF-ĸB and AP-1. Conclusion: Our data provide additional insight into cellular targets of HBx, which allows a better understanding of HBx function and the progressive changes during HBx-mediated hepatocarcinogenesis.
The Effectiveness of Voice Therapy for Teachers with Dysphonia
Authors: Niebudek-Bogusz E. , Sznurowska-Przygocka B. , Fiszer M. , Kotyło P. , Sinkiewicz A. , Modrzewska M. , Sliwinska-Kowalska M.
Published: March 2008

Objective: An incorrect voice emission is a risk factor for developing occupational voice disorders. The study aimed at assessing the effectiveness of voice therapy in female teachers with dysphonia. Methods: The study comprised 133 subjects with voice disorders, taking part in a vocal training programme. A reference group for the present study included 53 teachers with dysphonia. Questionnaire surveys, phoniatric examination and videostroboscopic evaluation were conducted at initial and control examination. Results: In the study group, an improvement after the vocal training was noted in most of the reported symptoms and also in some quantitative parameters of phoniatric examinations compared to the findings for the reference group. The number of patients who assessed their voice as normal increased significantly after the vocal training (2.3 vs. 46.6%). A significant increase in the mean maximum phonation time, from 13.3 to 16.6 s, was observed. The same applied to voice frequency range (increase from 171 to 226.8 Hz). Conclusions: The outcomes of vocal training, such as a subjective improvement of voice quality and an increase in the quantitative parameters (prolonged maximum phonation time, extended voice range) seem to be important parameters for monitoring the effectiveness of training in correct voice emission.
Review of the Treatment of Trigeminal Neuralgia with Gamma Knife Radiosurgery
Authors: Guo Susan , Chao Samuel T. , Reuther Alwyn M. , Barnett Gene H. , Suh John H.
Published: March 2008

Background: Trigeminal neuralgia is a debilitating condition caused by compression of the trigeminal nerve, ganglions, or divisions. Gamma knife radiosurgery has been increasingly used in the treatment of trigeminal neuralgia as a non-invasive alternative to microvascular decompression and rhizotomies. Methods: We reviewed the medical literature regarding outcomes, time course, and prognostic factors for successful pain control in gamma knife radiosurgery. The dosimetry, target, complications of treatment, as well as perceived quality of life in treatment were also reviewed. Results and Conclusion: The growing body of literature suggests that the low rates of complications of gamma knife radiosurgery, coupled with the high success rates and patient satisfaction, allow it to be increasingly used as primary intervention for trigeminal neuralgia for appropriate patients.
Comparison of Atlas- and Magnetic-Resonance-Imaging-Based Stereotactic Targeting of the Subthalamic Nucleus in the Surgical Treatment of Parkinson’s Disease
Authors: Patel Nikunj K. , Khan Sadaquate , Gill Steven S.
Published: March 2008

Aims: To assess the variability of the subthalamic nucleus (STN) size, orientation and target coordinates from direct visualization on high-resolution magnetic resonance (MR) images in patients undergoing surgical intervention for Parkinson’s disease. Methods: Sixty-six patients with Parkinson’s disease were included in this study. The STN was visualized directly on high-resolution MR images, the size and orientation in both coronal and axial planes were recorded, as were the coordinates of the dorsolateral STN target in relation to the anterior-posterior commissural (AC-PC) line. The same STN target was defined in the Schaltenbrand atlas and atlas-based coordinates in proportion to the patient’s AC-PC dimension were calculated. MR-imaging-based STN target coordinates were compared with the corresponding atlas-based coordinates. Results: Marked variation of STN size and orientation was observed. A significant difference was demonstrated on comparing left- and right-sided x and y coordinates. The comparison between MR-imaging-based and atlas-derived target coordinates demonstrated a significant difference in all directions except the left y coordinate. Conclusions: This study demonstrates the substantial individual variability of STN size, orientation and target coordinates and a significant difference between target coordinates obtained by direct visual targeting on MR images and those obtained by indirect targeting based on atlases.
Direct Localization of Subthalamic Nucleus Supplemented by Single-Track Electrophysiological Guidance in Deep Brain Stimulation Lead Implantation: Techniques and Clinical Results
Authors: Koike Yu , Shima Fumio , Nakamizo Akira , Miyagi Yasushi
Published: March 2008

Background/Aims: In subthalamic nucleus (STN) deep brain stimulation (DBS) lead implantation, it is still controversial whether it is more appropriate to employ indirect or direct methods in magnetic resonance imaging (MRI)-based tentative targeting and to select single- or multiple-track recording in electrophysiological definitive targeting. The efficacy of single-track electrophysiological recording through direct targeting was compared with the conventional indirect targeting methods in light of the identified STN thickness and clinical results. Methods: The identified mean STN thickness, pre- and 6-month postoperative Unified Parkinson’s Disease Rating Scale (UPDRS), dose change of L-dopa and dopaminergic agonists were compared in indirect (midcommissural point-based, 44 procedures) and direct (image-based, 44 procedures) targeting methods. Results: The identified mean STN thickness was significantly greater in the group employing direct methods. For evaluation of the UPDRS, a significant scale improvement was noted in part 2 OFF for both groups. Significant scale improvements occurred in parts 3 and 4 in the group employing the direct method. Both groups revealed significant L-dopa dose reduction with the tendency towards a greater reduction in the group employing the direct method. Conclusion: MRI-based direct targeting supplemented by single-track recording could be justified as a standard for DBS lead implantation to achieve better clinical results.
Sensitivity of Mesenchymal Stem Cells and Their Progeny to Medicines Used for the Treatment of Hematoproliferative Diseases
Authors: Nifontova Irina , Svinareva Daria , Petrova Tatiana , Drize Nina
Published: March 2008

Background/Aims: The influence of cytostatic medicines on mesenchymal stem cells (MSC) and their progeny, fibroblastic colony-forming units (CFU-F), was investigated. Methods: Mice were treated with busulfan, cyclophosphamide, cytarabine, methotrexate and bortezomib, as used in clinical practice. MSC and CFU-F were analyzed 3 days and 6 weeks after the treatment termination. To estimate MSC numbers, the ectopic foci formation method was used. Briefly, a donor bone marrow plug was transplanted under the renal capsule of a syngeneic animal, leading to ectopic foci formation. The systemic response of the hematopoietic microenvironment to these drugs was studied using the same method applied to recipients pretreated with the medicines. Results: CFU-F concentration was halved in the bone marrow of mice treated with busulfan, methotrexate and cyclophosphamide, and was not restored for the next 6 weeks. Proliferative potential and differentiation abilities of MSC were not affected by these medicines. The enlargement of foci size in mice treated with cytostatic agents was not conditioned by MSC, but by more mature stromal precursor cells. Conclusions: Cytostatic medicines affect stromal precursors in 2 ways: they decrease CFU-F concentration in the ‘steady-state’ bone marrow, while stimulating growth of the stromal microenvironment during its de novo formation. MSC are not sensitive to the cytostatic agents used.
A Randomized Phase II Trial of Pemetrexed plus Irinotecan (ALIRI) versus Leucovorin-Modulated 5-FU plus Irinotecan (FOLFIRI) in First-Line Treatment of Locally Advanced or Metastatic Colorectal Cancer
Authors: Underhill Craig , Goldstein David , Gorbounova Vera A. , Biakhov Mikhail Y. , Bazin Igor S. , Granov Dmitry A. , Hossain Anwar M. , Blatter Johannes , Kaiser Christopher , Ma Doreen
Published: March 2008

Background: This multicenter, randomized trial compared overall response rate between pemetrexed plus irinotecan (ALIRI) and leucovorin-modulated 5-fluorouracil plus irinotecan (FOLFIRI) in patients with advanced colorectal cancer. Secondary objectives included overall and progression-free survival, duration of response, toxicities, and biomarkers. Patients and Methods: ALIRI patients received pemetrexed 500 mg/m2 and irinotecan 350 mg/m2 with vitamin supplementation on day 1 of each 21-day cycle. FOLFIRI patients received irinotecan 180 mg/m2 on days 1, 15, 29; on days 1, 2, 15, 16, 29, 30, patients received leucovorin 200 mg/m2, bolus 5-fluorouracil 400 mg/m2, and 5-fluorouracil 600 mg/m2 as 22-hour infusion. Results: Of 132 patients randomly assigned, 130 patients (64 = ALIRI, 66 = FOLFIRI) received ≧1 dose of treatment. Response rates (ALIRI = 20.0%, FOLFIRI = 33.3%) were not significantly different between arms (p = 0.095). Progression-free survival was 5.7 months for ALIRI and 7.7 months for FOLFIRI (p < 0.001). Neutropenia, fatigue, diarrhea, nausea, and vomiting were the major toxicities. There were 5 drug-related deaths (ALIRI = 4, FOLFIRI = 1). Biomarker analysis failed to reveal that any of the 18 preselected genes were clearly associated with tumor response. Conclusions: Neither efficacy nor safety improved on the ALIRI arm compared to the FOLFIRI arm. Progression-free survival on FOLFIRI was significantly longer compared to ALIRI. Potential biomarkers capable of predicting response to either regimen in advanced or metastatic colorectal carcinoma need further characterization.
Phase II Study of a Combination of Irinotecan and S-1 in Patients with Advanced Gastric Cancer (OGSG0002)
Authors: Uedo Noriya , Narahara Hiroyuki , Ishihara Ryu , Takiuchi Hiroya , Goto Masahiro , Fujitani Kazumasa , Hirao Motohiro , Tsujinaka Toshimasa , Imano Motohiro , Furukawa Hiroshi , Tsukuma Hideaki , Taguchi Tetsuo
Published: March 2008

Background/Aims: To investigate the efficacy and safety of the combination therapy of irinotecan (CPT-11) plus S-1 in patients with advanced gastric cancer at the dose recommended by a previous phase I study. Methods: A total of 23 patients received 80 mg/m2 of CPT-11 on days 1 and 15, and S-1 at a dose level set on the basis of the body surface area (BSA): 40 (BSA <1.25 m2), 50 (BSA ≧1.25 to <1.5 m2) or 60 mg (BSA ≧1.5 m2) b.i.d. was given from days 1–21. Results: The overall response rate was 47.8% (11 of 23, 95% confidence interval, CI: 27.4–68.2%). The median time to progression (TTP) was 210 days (95% CI: 145–322 days) and the median survival time was 394 days (95% CI: 241–484 days). The incidence of grade 3 or 4 hematological and non-hematological toxicity was 17.4 and 8.7%. The most common hematological toxicity was anemia and the most common non-hematological toxicity was diarrhea. Conclusion: The combination therapy of CPT-11 and S-1 provided prolonged TTP with low toxicity, and the results warrant a further phase III study to define the efficacy in improvement of survival in patients with advanced gastric cancer.
Gene Expression of Fructosamine 3 Kinase in Patients with Colorectal Cancer
Authors: Caruso Maria Gabriella , Notarnicola Maria , Altomare Donato Francesco , Misciagna Giovanni
Published: March 2008

Objective: Spontaneous non-enzymatic reaction of protein amino groups with glucose and other reducing sugars, known as glycation or Maillard reaction, has long been considered irreversible and inevitably followed by slow conversion of fructosamines and advanced glycation end products. Instead, recent identification of fructosamine 3 kinase (FN3K) has unveiled that fructosamines can be physiologically repaired, so that the FN3K enzyme could be considered a new form of protein repair. Methods: Thirty-one consecutive patients with colorectal cancer were enrolled in the study. FN3K gene expression was determined using quantitative RT-PCR. Results: The mean level of FN3K gene expression was significantly lower in cancer tissue than in the corresponding normal colorectal mucosa, and FN3K gene was under-expressed most particularly in the tumours located on the left side of the colon. Conclusions: Low mRNA levels of this enzyme in colon cancer tissue with respect to normal surrounding mucosa suggests that neoplastic cells have lost a protective enzymatic system. Reduced FN3K gene expression may be important in the pathogenesis and progression of colorectal cancer.
Retinoid Receptor Alpha and Beta Expression in Serous Ovarian Tumors
Authors: Daponte A. , Kostopoulou E. , Chiotoglou I. , Vanakara P. , Minas M. , Nakou M. , Kallitsaris A. , Kollia P. , Koukoulis G. , Messinis I.E.
Published: March 2008

The expression of retinoid acid receptors α (RARα) and β (RARβ) and estrogen receptor α (ERα) was assessed by immunohistochemistry and Western blotting in normal ovaries, serous cystadenoma (n = 20), serous borderline (n = 14), and serous ovarian cancer (n = 47) and was correlated in cancer cases with stage, grade, progress-free survival (PFS), and survival. RARα was increasingly expressed in benign cystadenomas, borderline, and low-stage and advanced-stage neoplasms (p < 0.001). In stage III, G3 serous carcinoma, increased RARα expression was an independent prognostic factor associated with lower chemoresponse to first-line chemotherapy (taxol and carboplatin) and shorter PFS (p < 0.002).RARβ and ERα expression did not correlate with RARα tumor characteristics or PFS and survival.
Frequency of Dysphoria and Mixed States
Authors: Bertschy G. , Gervasoni N. , Favre S. , Liberek C. , Ragama-Pardos E. , Aubry J.-M. , Gex-Fabry M. , Dayer A.
Published: March 2008

Background: Mixed states are a complex entity in the field of mood disorders. Dysphoria has been advocated as an important clinical dimension of mixed states. The objective of this work is to study the frequency of dysphoria within a population of patients with DSM-IV major depressive and/or manic episodes and to determine if it may help establish diagnostic criteria for subthreshold cases of depressive or manic mixed states. Sampling and Methods: A total of 165 patients were assessed using the Mini International Neuropsychiatric Interview complemented by a section defining dysphoria as a constellation of 3 among 4 symptoms (inner tension, irritability, aggressive behavior and hostility). Results: When classifying patients according to the number of symptoms of the opposite polarity, changes in the frequency of dysphoria revealed a clear contrast between the 2 opposite manic and depressive poles and the full mixed state (DSM-IV definition). The frequency of dysphoria was 17.5% in pure depression, 22.7% in pure mania and 73.3% in full mixed state. Two threshold effects were identified: (1) the frequency of dysphoria increased from 17.5 to 61.1% (p = 0.002) when the number of manic symptoms in DSM-IV depressed patients increased from 0 to 1, and (2) dysphoria increased from 14.3 to 69.2% (p = 0.057) when the number of depressive symptoms increased from 2 to 3 in DSM-IV manic patients. Conclusion: Dysphoria is strongly but not necessarily associated with mixed states. When used as a clinical marker for mixed states, dysphoria confirms the modern delimitations of sub-threshold mixed states by specifying the required number of symptoms of the opposite polarity (which could be lower for depressive mixed states than for manic mixed states). The study has limitations related to the inclusion of patients who are not drug-free, to the definition of dysphoria and to the sample size.
Social and Communication Difficulties and Obsessive-Compulsive Disorder
Authors: Cullen Bernadette , Samuels Jack , Grados Marco , Landa Rebecca , Bienvenu O. Joseph , Liang Kung-Yee , Riddle Mark , Hoehn-Saric Rudolf , Nestadt Gerald
Published: March 2008

Background: The relationship between pervasive developmental disorder (PDD) and obsessive-compulsive disorder (OCD) has not been extensively studied despite having some phenomenological features in common. Abnormal social and communication behaviors (pragmatic behaviors) are key components of PDD and are also part of the broader autism phenotype (BAP). In this study we sought to establish if there is any association between the presence of abnormal pragmatic behaviors and OCD and whether this association delineates a familial subtype of OCD. Sampling and Methods: As part of the Johns Hopkins OCD Family Study, 80 OCD case probands were recruited and matched with 73 control probands. Probands and their first-degree relatives were interviewed using the Schedule for Affective Disorders and Schizophrenia-Lifetime Anxiety and other diagnostic instruments. A Pragmatic Rating Scale (PRS) to assess pragmatic behaviors was completed by the examiner. Results: The PRS was completed on 395 subjects, of which 3% (n = 11) achieved a score of greater than 6. The prevalence of high PRS scores was significantly greater amongst case probands and relatives (5%) compared to control probands and relatives (0.5%, p = 0.011). In case relatives the prevalence of OCD was significantly higher in those relatives who had a family member with a high PRS score (p < 0.001). Conclusions: The presence of social and communication difficulties in members of OCD case families appears to identify a familial subtype of OCD that may be related to PDD and/or BAP. This study was limited to using the PRS to identify pragmatic behaviors in subjects with OCD.