bluuebunny/crossref_metadata_2025 huggingface dataset:
Polyploidization Facilitates BiotechnologicalIn VitroTechniques in the GenusCucumis
Authors: Skálová Dagmar , Ondřej Vladan , Doležalová Ivana , Navrátilová Božena , Lebeda Aleš
Published: December 2010

Prezygotic interspecific crossability barrier in the genusCucumisis related to the ploidy level of the species (cucumber (C. sativus), ; muskmelon (C. melo) and wildCucumisspecies, ). Polyploidization of maternal plants helps hybridization among otherCucumisspecies by overcoming prezygotic genetic barriers. The main objective of this paper is to compare the results of several methods supporting interspecific crosses in cucumber without and with polyploidization (comparison between diploid (2x) and mixoploid (2x/4x) cucumber maternal plants). Mixoploid plants were obtained afterin vivoandin vitropolyploidization by colchicine and oryzalin. Ploidy level was estimated by flow cytometry. Embryo rescue,in vitropollination, and isolation of mesophyll protoplast were tested and compared. Positive effect of polyploidization was observed during all experiments presented by higher regeneration capacity of cultivated mixoploid cucumber embryos, ovules, and protoplasts. Nevertheless, the hybrid character of putative hybrid accessions obtained after crossin vivoandin vitropollination was not confirmed.
Colour Mixing Modelling and Simulation: Optimization of Colour Recipe for Carded Fibres
Authors: Furferi Rocco , Carfagni Monica
Published: December 2010

Colour matching between carded and finished fibres is an important
challenge for textile industry. The straightforward approach for
mixing together some differently coloured fibres in order to
obtain a blend of a desired colour is to perform a trial and error
approach starting from a given colour recipe and optimizing it
with several attempts. Unfortunately, dyeing process so as the
carding procedure may result in a carded fibre whose colour is
different from the desired one. As a consequence textile companies
have to modify the original recipe in order to reduce the gap
between the colour of the final product and the desired one. The
present work describes a model able to simulate the colour mixing
of fibres in order to assess the best recipe. The model consists
in two modules: a “prediction module” predicts the colour of a
blend obtained by mixing together several fibres; an “optimization
module” is used to optimize the final recipe. The devised system
has been tested for optimizing the recipe of a set of 200 blends.
The mean error in predicting the blend colour is about 15% with a
variance of 0.165. The time for optimizing the recipe is reduced
by 92%.
Very Wideband, Compact Microstrip Bandstop Filter Covering S-Band to Ku-Band
Authors: Singh Kamaljeet , Nagachenchaiah K.
Published: December 2010

This paper reports a wide bandwidth planar bandstop filter with improved RF characteristics. The proposed filter on alumina is realized incorporating tapped open stub along with spurline topology. Further, stepped impedance resonator (SIR) approach has been introduced in the tapped stubs to achieve wider band performance with improved selectivity. The proposed topology effectively controls the transmission poles. Fabrication of this BSF has been carried out on glass substrate showing minimal effect of permittivity variation on bandwidth performance. This validates the applied approach with achievable bandwidth of more than 100% ranging from S- to Ku-band. Close agreement with simulation and practical results have been demonstrated with measured insertion loss of less than 1 dB and attenuation loss better than 30 dB at C-band.
An Overview of the Topological Gradient Approach in Image Processing: Advantages and Inconveniences
Authors: Jaafar Belaid Lamia
Published: December 2010

Image analysis by topological gradient approach is a technique based upon the historic application of the topological asymptotic expansion to crack localization problem from boundary
measurements. This paper aims at reviewing this methodology through various applications in image
processing; in particular image restoration with edge detection, classification and segmentation problems for both grey level and color images is presented in this work. The numerical experiments show
the efficiency of the topological gradient approach for modelling and solving different image analysis
problems. However, the topological gradient approach presents a major drawback: the identified
edges are not connected and then the results obtained particularly for the segmentation problem can
be degraded. To overcome this inconvenience, we propose an alternative solution by combining the
topological gradient approach with the watershed technique. The numerical results obtained using
the coupled method are very interesting.
Fourteen-Year Long-Term Results after Gastric Banding
Authors: Stroh Christine , Hohmann Ulrich , Schramm Harald , Meyer Frank , Manger Thomas
Published: December 2010

Background. Gastric banding (GB) is a common bariatric procedure that is performed worldwide. Weight loss can be substantial after this procedure, but it is not sufficient in a significant portion of patients. Long-term rates for associated complications increase with every year of follow up, and only a few long-term studies have been published that examine these rates. We present our results after 14 years of postoperative follow up.Methods. Two hundred patients were operated upon form 01.02.1995 to 31.01.2009. Data collection was performed prospectively. In retrospective analysis, we analyzed weight loss, short- and long-term complications, amelioration of comorbidities and long-term outcome.Results. The mean postoperative follow up time was 94.4 months (range 2–144). The follow up rate was 83.5%. The incidence of postoperative complications for slippage was 2.5%, for pouch dilatation was 9.5%, for band migration was 5.5% and 12.0% for overall band removal. After 14 years, the reoperation rate was 30.5% with a reoperation rate of 2.2% for every year of follow up. Excess weight loss was 40.2% after 1 year, 46.3% after 2 years, 45.9% after 3 years, 41.9% after five years, 33.3% after 8 years, 30.8% after 10 years, 33.3% after 12 years and 15.6% after 14 years of follow up.Conclusion. The complication and reoperation rate after GB is high. Nevertheless, GB is still a therapeutic option in morbid obese patients, but the criteria for patient selection should be carefully evaluated.
Prognostication and Risk-Adapted Therapy of Hodgkin's Lymphoma Using Positron Emission Tomography
Authors: Kasamon Yvette L.
Published: December 2010

The use of18F-fluorodeoxyglucose positron emission tomography (FDG-PET) for response assessment in lymphoma is now widespread. Prognostic information obtained from PET performed after two to three cycles of chemotherapy may guide more individualized, risk-adapted therapeutic strategies. Progress in the risk stratification of Hodgkin's lymphoma through midtreatment PET is reviewed, with a focus on management implications in newly diagnosed and relapsed disease. How to tailor treatment on the basis of the interim PET result is not yet defined but is the subject of ongoing trials.
FPGA Implementation for GMM-Based Speaker Identification
Authors: EhKan Phaklen , Allen Timothy , Quigley Steven F.
Published: December 2010

In today's society, highly accurate personal identification systems are required. Passwords or pin numbers can be forgotten or forged and are no longer considered to offer a high level of security. The use of biological features, biometrics, is becoming widely accepted as the next level for security systems. Biometric-based speaker identification is a method of identifying persons from their voice. Speaker-specific characteristics exist in speech signals due to different speakers having different resonances of the vocal tract. These differences can be exploited by extracting feature vectors such as Mel-Frequency Cepstral Coefficients (MFCCs) from the speech signal. A well-known statistical modelling process, the Gaussian Mixture Model (GMM), then models the distribution of each speaker's MFCCs in a multidimensional acoustic space. The GMM-based speaker identification system has features that make it promising for hardware acceleration. This paper describes the hardware implementation for classification of a text-independent GMM-based speaker identification system. The aim was to produce a system that can perform simultaneous identification of large numbers of voice streams in real time. This has important potential applications in security and in automated call centre applications. A speedup factor of ninety was achieved compared to a software implementation on a standard PC.
Automated Analysis of Crackles in Patients with Interstitial Pulmonary Fibrosis
Authors: Flietstra B. , Markuzon N. , Vyshedskiy A. , Murphy R.
Published: December 2010

Background. The crackles in patients with interstitial pulmonary fibrosis (IPF) can be difficult to distinguish from those heard in patients with congestive heart failure (CHF) and pneumonia (PN). Misinterpretation of these crackles can lead to inappropriate therapy. The purpose of this study was to determine whether the crackles in patients with IPF differ from those in patients with CHF and PN.Methods. We studied 39 patients with IPF, 95 with CHF and 123 with PN using a 16-channel lung sound analyzer. Crackle features were analyzed using machine learning methods including neural networks and support vector machines.Results. The IPF crackles had distinctive features that allowed them to be separated from those in patients with PN with a sensitivity of 0.82, a specificity of 0.88 and an accuracy of 0.86. They were separated from those of CHF patients with a sensitivity of 0.77, a specificity of 0.85 and an accuracy of 0.82.Conclusion. Distinctive features are present in the crackles of IPF that help separate them from the crackles of CHF and PN. Computer analysis of crackles at the bedside has the potential of aiding clinicians in diagnosing IPF more easily and thus helping to avoid medication errors.
Treatment of Disseminated Mycobacterial Infection with High-Dose IFN-γin a Patient with IL-12Rβ1 Deficiency
Authors: Alangari Abdullah A. , Al-Zamil Fahad , Al-Mazrou Abdulrahman , Al-Muhsen Saleh , Boisson-Dupuis Stéphanie , Awadallah Sitalbanat , Kambal Abdelmageed , Casanova Jean-Laurent
Published: December 2010

IFN-γhas been used in the treatment of IL-12Rβ1 deficiency patients with disseminated BCG infection (BCGosis), but the optimal dose to reach efficacy is not clear. We used IFN-γin the treatment of a 2.7-year-old patient with IL-12Rβ1 deficiency and refractory BCG-osis. IFNγwas started at a dose of 50 μg/m23 times per week. The dose was upgraded to 100 mcg/m2after 3 months, then to 200 mcg/m26 months afterwards. Serum mycobactericidal activity and lymphocytes number and function were evaluated throughout the study. There was no clinical response to IFN-γwith 50 or 100 μg/m2doses. However, there was some response to the 200 μg/m2dose with no additional adverse effects. The serum mycobactericidal activity was not significantly different during the whole treatment period. Lymphocytes proliferation in response to PHA was significantly higher after 3 months of using the highest dose as compared to the lowest dose. The tuberculin skin test reaction remained persistently negative. We conclude that in a patient with IL-12Rβ1 deficiency, IFN-γat a dose of 200 μg/m2, but not at lower dosages, was found to have a noticeable clinical effect with no additional adverse effects.
Long Memory from Sauerbrey Equation: A Case in Coated Quartz Crystal Microbalance in terms of Ammonia
Authors: Wang Xiaohua , Li Ming , Chen Shengyong
Published: December 2010

The Sauerbrey equation is a useful empirical model in material science to represent the dynamics of frequency change denoted by Δf
in an area, denoted by A, of the electrode in terms of the increment of the mass, which is denoted by Δm, loaded on the surface of the crystal under a certain resonant frequency f0. For the purpose of studying Δf from the point of view of time series, we first propose two types of the modified representations of the Sauerbrey equation by taking time as an argument to represent Δf as a function expressed by x(t, f0, A, Δm), where t is time. Usually, Δf is studied experimentally for the performance evaluation of the tested quartz used in ammonia sensors. Its properties in time series, however, are rarely reported. This paper presents the fractal properties of Δf. We will show that Δf is long range dependent (LRD). Consequently, it is heavy tailed according to the Taqqu′s theorem. The Hurst parameter (H) of Δf approaches one, implying its strong long memory, providing a new explanation of the repeatability of the experiments and novel point of view of the dynamics of Δf relating to the Sauerbrey equation in material science.
Asymptotic Behavior of Solutions to Half‐Linear q‐Difference Equations
Authors: Řehák Pavel
Published: December 2010

We derive necessary and sufficient conditions for (some or all) positive solutions of the half‐linear
q‐difference equation
Dq(Φ(Dqy(t))) + p(t)Φ(y(qt)) = 0, t ∈ {qk : k ∈ ℕ0} with q > 1, Φ(u) = |u|α−1sgn u with α > 1, to behave like
q‐regularly varying or
q‐rapidly varying or
q‐regularly bounded functions (that is, the functions
y, for which a special limit behavior of
y(qt)/y(t) as t → ∞ is prescribed). A thorough discussion on such an asymptotic behavior of solutions is provided. Related Kneser type criteria are presented.
Select Heterozygous Keap1 Mutations Have a Dominant-Negative Effect on Wild-Type Keap1 In Vivo
Authors: Suzuki Takafumi , Maher Jonathan , Yamamoto Masayuki
Published: December 2010

Under homeostatic conditions, Keap1 constitutively mediates the proteasomal degradation Nrf2. However, tertiary changes in Keap1 in response to the cellular environment allow for liberation of Nrf2 to transcriptionally regulate downstream cytoprotective genes that aid in cell survival. KEAP1/NRF2 somatic mutations causing constitutive NRF2 activation have been estimated to occur in approximately 25% of human lung tumors, with similar rates believed to exist in other tissue subtypes. As the stoichiometry between Keap1 and Nrf2 is 2:1, we hypothesized that heterozygous Keap1 mutations could suppress wild-type Keap1 (Keap1WT) activity by functioning as a dominant-negative protein through heterodimerization of mutant Keap1 (Keap1mutant) with Keap1WT. When Keap1G430C or Keap1G364C mutants were expressed in lieu of Keap1WT, premature juvenile mortality was observed. To test the hypothesis of a dominant-negative effect, Keap1-null mice were engineered to coexpress both Keap1WT and Keap1G430C transgenes, a phenotype analogous to that previously observed from a human lung tumor. These mice were viable, but phenotypically displayed hyperactivation of downstream Nrf2 target genes and moderate esophageal hyperkeratosis. Similar to the transgenic mouse Keap1G430C mutant, Keap1C273&288A substitutions also diminished Keap1WT activity in vivo. To further delineate involvement of the dominant-negative heterodimer, transgenic mice with a deletion or strategic mutation in Broad-complex, Tramtrack and Bric-a-Brac (BTB) domain that disallowed Keap1 dimerization were generated in the presence of Keap1WT, and failed to induce the dominant-negative effect in vivo. These results thus demonstrate that sequestration of Keap1WT into a Keap1mutant–Keap1WT heterodimer leads to a dominant-negative effect in vivo and gives rise to Nrf2 activation. Cancer Res; 71(5); 1700–9. ©2010 AACR.
Frequency of Circulating Tregs with Demethylated FOXP3 Intron 1 in Melanoma Patients Receiving Tumor Vaccines and Potentially Treg-Depleting Agents
Authors: de Vries I. Jolanda M. , Castelli Chiara , Huygens Caroline , Jacobs Joannes F.M. , Stockis Julie , Schuler-Thurner Beatrice , Adema Gosse J. , Punt Cornelis J.A. , Rivoltini Licia , Schuler Gerold , Coulie Pierre G. , Lucas Sophie
Published: December 2010

Purpose: Regulatory T cells (Tregs) are thought to inhibit antitumor immune responses, and their depletion could therefore have a synergistic effect with therapeutic cancer vaccines. We investigated the impact of three medications on blood Treg frequency in vaccinated cancer patients.

Experimental Design: To date, the most specific marker for human Tregs is demethylation in the DNA that encodes the transcription factor FOXP3. Thus, we used a FOXP3 methylation-specific quantitative PCR assay (MS-qPCR) to measure Treg frequencies in the peripheral blood mononuclear cells (PBMCs) of melanoma patients. The patients participated in three clinical trials that combined tumor vaccines with potential Treg-depleting agents: low-dose cyclophosphamide, anti-CD25 monoclonal antibody daclizumab, and the IL-2/diphtheria toxin fusion protein denileukin diftitox.

Results: In the nine control patients, blood Treg frequencies varied over time; there was a 46% reduction in one patient. In treated patients, a more than 2-fold decrease in Tregs was observed in one out of 11 patients receiving cyclophosphamide and in four out of 13 receiving daclizumab, but there was no such Treg decrease in any of the six patients who received denileukin diftitox. As a positive control, a more than 2-fold increase in blood Tregs was detected in four out of nine patients who were treated with interleukin-2.

Conclusions: We used a MS-qPCR method that detects Tregs but not other activated T lymphocytes; however, none of the Treg-depleting strategies that we tested led, in the majority of patients, to a conservative 50% reduction in blood Tregs. Clin Cancer Res; 17(4); 1–8. ©2010 AACR.
Unfavorable Polysomnographic Sleep Patterns Predict Poor Sleep and Poor Psychological Functioning 3 Years Later in Patients with Restless Legs Syndrome
Authors: Brand Serge , Beck Johannes , Hatzinger Martin , Savic Mirjana , Holsboer-Trachsler Edith
Published: December 2010

Background: Amongst the variety of disorders affecting sleep, restless legs syndrome (RLS) merits particular attention. Little is known about long-term outcomes for sleep or psychological functioning following a diagnosis of RLS. The aim of the present study was thus to evaluate sleep and psychological functioning at a 3-year follow-up and based on polysomnographic measurements. Method: Thirty-eight patients (18 female and 20 male patients; mean age: 56.06, SD = 12.07) with RLS and sleep electroencephalographic recordings were followed-up 33 months later. Participants completed a series of self-rating questionnaires related to sleep and psychological functioning. Additionally, they completed a sleep log for 7 consecutive days. Results: Age, male gender, increased light sleep (S1, S2) and sleep onset latency, along with low sleep efficiency, predicted psychological functioning and sleep 33 months later. Specifically, sleep fragmentation predicted poor psychological functioning, and both sleep fragmentation and light sleep predicted poor sleep. Conclusions: In patients with RLS, irrespective of medication or duration of treatment, poor objective sleep patterns at diagnosis predicted both poor psychological functioning and poor sleep about 3 years after diagnosis. The pattern of results suggests the need for more thorough medical and psychotherapeutic treatment and monitoring of patients with RLS.
Non-Proteolytic Aeroallergens from Mites, Cat and Dog Exert Adjuvant-Like Activation of Bronchial Epithelial Cells
Authors: Österlund Camilla , Grönlund Hans , Gafvelin Guro , Bucht Anders
Published: December 2010

Background: Exposure to seasonal or indoor allergens may cause sensitisation and development of allergic airway diseases. We have previously demonstrated that the non-proteolytic major house dust mite (HDM) allergen Der p 2 stimulates pro-inflammatory responses in bronchial epithelial cells. We aimed to determine if other clinically relevant non-proteolytic aeroallergens originating from HDMs, storage mites, cat, dog, birch and timothy also activate respiratory epithelial cells. Methods: Cultures of human bronchial epithelial cell line BEAS-2B, normal human bronchial epithelial cells and alveolar epithelial cell line A549 were exposed to recombinant (r)Der p 2, natural (n)Der f 2, rEur m 2, rLep d 2, rFel d 1, nFel d 1, rCan f 2, rBet v 1 or rPhl p 5a. A panel of secreted mediators and expression of cell adhesion receptors involved in recruitment, survival and adhesion of inflammatory cells in asthmatic airways was assessed. Results: The mite allergens rDer p 2, nDer f 2, rEur m 2 and rLep d 2 as well as the cat and dog allergens rFel d 1, nFel d 1 and rCan f 2 induced granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interleukin (IL)-6, IL-8, monocyte-chemotactic protein-1 and macrophage inflammatory protein-3α secretion from bronchial epithelial cells as well as surface expression of intracellular adhesion molecule-1. The pollen allergens rBet v 1 and rPhl p 5a from birch and timothy did not activate the cells. None of the studied allergens affected the alveolar epithelial cells. Conclusion: These results show that both mite and structurally unrelated cat and dog allergens can activate respiratory epithelial cells by adjuvant-like protease-independent mechanisms.
The Efficacy and Safety of a Chinese Herbal Product (Xiao-Feng-San) for the Treatment of Refractory Atopic Dermatitis: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Cheng Hui-Man , Chiang Leih-Chin , Jan Ya-Min , Chen Guang-Wei , Li Tsai-Chung
Published: December 2010

Background: Severe and widespread atopic dermatitis often fails to respond adequately to topical steroids and oral antihistamines and requires immunomodulatory drugs which, although effective, have undesirable toxic effects. Methods: In this prospective, randomized, double-blind, placebo-controlled trial, 71 patients with severe intractable atopic dermatitis were given an 8-week treatment with oral Xiao-Feng-San (XFS; 47 patients) or placebo (24 patients). Total lesion score, erythema score, surface damage score, pruritus score and sleep score were measured at 4-week intervals. Results: Fifty-six patients completed both the treatment and follow-up periods. The decrease in the total lesion score in the treatment group at 8 weeks was significantly greater than that of the placebo group (79.7 ± 5.8% vs. 13.5 ± 7.64%; p < 0.001). There was also a statistically significant difference between the treatment and placebo groups with regard to erythema, surface damage, pruritus and sleep scores. The difference between the 2 groups was still significant for all outcome measures except the erythema score at the 12-week follow-up, 4 weeks after the 8-week treatment had ended. Patients reported no side effects from treatment, although some commented on the unpalatability of the medication. Conclusion: Our study results suggest that the traditional Chinese herbal medicine XFS may be an alternative choice of therapy for severe, refractory, extensive and nonexudative atopic dermatitis.
Protective Effect of Thymoquinone in Experimental Testicular Torsion
Authors: Gökçe Ahmet , Oktar Suleyman , Koc Ahmet , Gonenci Ramazan , Yalcinkaya Fatih , Yonden Zafer , Duru Mehmet
Published: December 2010

Objectives: To investigate the protective role of thymoquinone (TQ) on unilateral testicular ischemia-reperfusion (I/R) injury in mice. Materials and Methods: Experiments were performed on male C57BL/6 mice (8 weeks old, 20–25 g). The animals were divided into 3 groups including 6 mice in each group: control (sham), torsion/detorsion (TD) and TD+TQ. Mice, except the sham-operated group, were subjected to left unilateral torsion (720° rotation in the clockwise direction). The experiments were finished after sham operation time for controls, 120 min torsion and 240 min detorsion for the other groups. In the TD+TQ group 10 mg TQ was injected intraperitoneally 30 min before detorsion. Results: In the TD group total oxidative stress (TOS), oxidative stress index (OSI) and malondialdehyde (MDA) levels were higher than in the controls. TQ treatment decreased MDA, TOS and OSI values, but did not affect the total antioxidant capacity and myeloperoxidase activity in the TD+TQ group. Upon histological examination, mice in the TD group displayed moderate-to-severe disruption of the seminiferous epithelium. Treatment with TQ resulted in significantly reduced histological damage associated with I/R injury. Conclusion: Our results suggested that TQ treatment may have a protective effect on testicular I/R injury.
Bladder Diverticulum Robotic Surgery: Systematic Review of Case Reports
Authors: Moreno Sierra Jesus , Galante-Romo Isabel , Ortiz-Oshiro Elena , Castillon-Vela Ignacio T. , Fernandez-Perez Cristina , Silmi-Moyano Angel
Published: December 2010

Introduction: We report one case of robot-assisted transperitoneal bladder diverticulectomy and perform a systematic review of published experience. Patient and Methods: Our patient was a 64-year-old male with a history of lower urinary tract symptoms secondary to benign prostatic enlargement for 6 years with recurrent urinary tract infection. Ultrasound and voiding cystourethrogram showed a 7-cm diverticulum in the posterior bladder wall. After bibliographic search in PubMed/Medline, 17 articles on laparoscopic diverticulectomy and 8 on robotic diverticulectomy were selected. Results: Transperitoneal robot-assisted diverticulectomy was performed with the Da Vinci 4-arm system (Intuitive Surgical Inc., Sunnyvale, Calif., USA) without perioperative complications. Operative time was 80 min and blood loss less than 100 ml. Transurethral prostatic resection combined with Greenlight laser vaporization was performed in a second step. Conclusions: Robot-assisted bladder diverticulectomy is safe, effective, reproducible and minimally invasive. Cost is higher than for laparoscopic surgery and access to this technology is limited.
The Role of the House Dust Mite-Induced Innate Immunity in Development of Allergic Response
Authors: Jacquet Alain
Published: December 2010

House dust mite (HDM) represents one of the most common sources of aeroallergens worldwide and more than 50% of allergic patients are sensitized to these allergenic molecules. HDM allergy research in the past has been mainly focused on adaptive, mite allergen-dependent immune responses. In recent years it has become clear that, although the allergen-specific CD4+ Th2 cellsorchestrate HDM allergic response,the innate immune system also plays a critical role in HDM-induced allergy pathogenesis. This review will summarize insights into diverse determinants that contribute to the HDM allergenicity through the activation of innate immunity. In addition to the capacity of mite allergens to directly activate mainly skin keratinocytes and airway epithelial cells, innate pattern recognition receptor ligands derived from HDM carriers are also involved in the development of allergic response by HDM.
A Balanced Translocation t(6;14)(q25.3;q13.2) Leading to Reciprocal Fusion Transcripts in a Patient with Intellectual Disability and Agenesis of Corpus Callosum
Authors: Backx L. , Seuntjens E. , Devriendt K. , Vermeesch J. , Van Esch H.
Published: December 2010

We identified a male patient presenting with intellectual disability and agenesis of the corpus callosum, carrying an apparently balanced, reciprocal, de novo translocation t(6;14)(q25.3;q13.2). Breakpoint mapping, using array painting, identified 2 interesting candidate genes, ARID1B and MRPP3, disrupted in the patient. Unexpectedly, the rearrangement produced 3 in-frame reciprocal fusion transcripts that were further characterized. Formation of fusion transcripts is mainly reported in acquired malignancies and is very rarely observed in patients with intellectual disability (ID) and/or multiple congenital malformations (MCA). Additional experimental results suggest that ARID1B, a gene involved in chromatin remodeling, constitutes a good candidate for the central nervous system phenotype present in the patient.
High-Resolution Mapping of Interstitial Telomeric Repeats in Syrian Hamster Metaphase Chromosomes
Authors: Demin S. , Pleskach N. , Svetlova M. , Solovjeva L.
Published: December 2010

Karyotype analysis of the Syrian hamster (Mesocricetus auratus) was performed after DAPI-banding of metaphase chromosomes obtained from cultivated skin fibroblasts of a newborn animal. Fluorescence in situ hybridization with telomeric FITC-conjugated peptide nucleic acid probe was applied to map interstitial blocks of (TTAGGG)n repeats. Strong fluorescence in situ hybridization signals corresponded to interstitial telomeric repeats in pericentromeric chromatin bands of chromosomes 2, 4, 14, 20, and X. High-resolution DAPI-banding allowed specifying the arrangement of bands in the pericentromeric regions of these chromosomes.
Advances in Neuroprotective Strategies: Potential Therapies for Intracerebral Hemorrhage
Authors: Hwang Brian Y. , Appelboom Geoffrey , Ayer Amit , Kellner Christopher P. , Kotchetkov Ivan S. , Gigante Paul R. , Haque Raqeeb , Kellner Michael , Connolly E. Sander
Published: December 2010

Intracerebral hemorrhage (ICH) is associated with higher mortality and morbidity than any other form of stroke. However, there currently are no treatments proven to improve outcomes after ICH, and therefore, new effective therapies are urgently needed. Growing insight into ICH pathophysiology has led to the development of neuroprotective strategies that aim to improve the outcome through reduction of secondary pathologic processes. Many neuroprotectants target molecules or pathways involved in hematoma degradation, inflammation or apoptosis, and have demonstrated potential clinical benefits in experimental settings. We extensively reviewed the current understanding of ICH pathophysiology as well as promising experimental neuroprotective agents with particular focus on their mechanisms of action. Continued advances in ICH knowledge, increased understanding of neuroprotective mechanisms, and improvement in the ability to modulate molecular and pathologic events with multitargeting agents will lead to successful clinical trials and bench-to-bedside translation of neuroprotective strategies.
Identification of Bacterial DNA in Noninfectious Pleural Fluid with a Highly Sensitive PCR Method
Authors: Cremades Rosa , Galiana Antonio , Rodriguez Juan Carlos , Santos Ana , Lopez Pilar , Ruiz Montserrat , Garcia-Pachon Eduardo , Royo Gloria
Published: December 2010

Background: Bacterial DNA due to bacterial translocation has been identified in noninfectious ascitic fluid samples. Objective: This study investigated the possible presence of bacterial DNA in the pleural fluid of patients with pleural effusions of noninfectious origin, using a highly sensitive PCR-based method. Methods: Pleural fluid samples from 175 patients (average age ± SD: 69 ± 14 years) with noninfectious pleural effusion (62 transudates, 113 exudates) were analyzed. Bacterial DNA was detected using nested PCR with amplification of a fragment of the gene r16S, with 2 amplification protocols, i.e. low sensitivity (10 and 40 cycles) and high sensitivity (40 and 40 cycles). Results: With the less sensitive amplification process, only 1 sample was positive (Haemophilus parainfluenzae in a patient with hepatic hydrothorax). With the highly sensitive nested PCR method, bacterial DNA was identified in the pleural fluid, of both transudative and exudative origin, of 75 of the 175 patients (43%). In cases of isolation of a single bacterium, the more frequent were Escherichia coli, Salmonella enterica and Streptococcus pneumoniae.Conclusions: Regardless of its origin, bacterial DNA can be identified in almost half of noninfectious pleural effusions by using a highly sensitive PCR-based method. The possible clinical significance or prognostic value of these findings deserves to be evaluated.
Left Ventricular Diverticulum Associated with Neovascularization in an Adult
Authors: Huang Chung-Li , Yang Wen-Yi , Shi Shing-Hong , Lee Andrew Ying-Siu
Published: December 2010

We present a case of congenital left ventricular diverticulum, associated with neovascularization involving the distal segments of all the coronary arteries. There were no other thoraco-abdominal or cardiac anomalies. To our knowledge, this is the first reported case of ventricular diverticulum associated with neovascularization in an adult.
Ectopic Intrathyroidal Thymus in Children: A Long-Term Follow-Up Study
Authors: Segni Maria , di Nardo Raffaela , Pucarelli Ida , Biffoni Marco
Published: December 2010

Background: Ectopic intrathyroidal thymus has recently been reported in children as a cause of surgery and/or invasive diagnostic procedures when mistaken for a thyroid nodule. Thymus has a unique appearance at ultrasound (US). Methods: We report a follow-up study (mean 34 months, range 6–84) performed by US on 9 children (5 females) with a mean age of 6.3 ± 3.2 years with intrathyroidal thymic inclusions diagnosed by US as ‘incidentalomas’. None has palpable nodules. Results: Intrathyroidal thymic inclusions appeared on US as a hypoechoic area, with regular linear or punctuate internal hyperechoic echoes. The 2 oldest patients (13 and 17 years) showed a regression in both size and hypoechogenicity of thymic inclusions over time – reflecting the normal thymic involution with advancing age. Conclusions: Indeed, the lack of progression seen in our 9 patients over a mean time of 34 months confirmed the substantially benign and self-limited nature of this process. The increasing use of thyroid ultrasonography in children may result in an increased detection of intrathyroidal thymic inclusions – an embryologic anomaly that should be considered in the differential diagnosis of thyroid nodules in children and adolescents.
Human Liver-Specific Nanocarrier in a Novel Mouse Xenograft Model Bearing Noncancerous Human Liver Tissue
Authors: Matsuura Yoshifumi , Yagi Hiroshi , Matsuda Sachiko , Itano Osamu , Aiura Koichi , Kuroda Shun’ichi , Ueda Masakazu , Kitagawa Yuko
Published: December 2010

For the targeted delivery of genes and drugs to the human liver, hepatitis B virus (HBV) envelope L particles, which form hollow nanoparticles and display a peptide that is indispensable for liver-specific infection by HBV in humans, should be a useful tool. To test the efficacy of these particles in vivo, in the present study we generated a small animal model harboring a functional human liver tissue xenograft. An anti-asialo GM1 antibody was administered to SCID mice to induce the depletion of natural-killer-cell-dependent immune responsibility and then the mice underwent transplantation of a noncancerous liver tissue originating in humans into the kidney capsule. Interestingly, human liver tissues were engrafted in 58% of the animals at least for 14 days shown by a human hepatocyte-specific antibody. The engineered HBV nanoparticles which contained fluorescent chemicals could selectively bind to the xenograft in these immune-deficient mice when they were administered systemically. These results suggested that the model animal was usable to demonstrate the efficacy of the nanoparticles that could deliver chemicals specific to the normal human liver tissue by systemic administration, which will facilitate the study of human liver cell biology, drug metabolism and infections with hepatotropic viruses.
Distribution of Dexamethasone and Preservation of Inner Ear Function following Intratympanic Delivery of a Gel-Based Formulation
Authors: Salt Alec N. , Hartsock Jared , Plontke Stefan , LeBel Carl , Piu Fabrice
Published: December 2010

Intratympanic (IT) delivery of drugs to the ear is increasingly used for both clinical and research purposes. One limitation of IT delivery is that drugs are rapidly lost from the middle ear by a number of processes, so that prolonged delivery of drug is technically difficult. In the present study, the delivery characteristics of a poloxamer hydrogel formulation containing dexamethasone (dex) were evaluated. The gel is liquid at room temperature, allowing IT injection, but transitions to a gel at body temperature, providing a prolonged residence time in the middle ear. A 50-µl volume of control or dex-containing gel (dex-gel) was injected through the tympanic membrane of guinea pigs. Cochlear function was assessed with cochlear action potential and acoustic emission thresholds measured immediately, 6 or 24 h after IT gel injection. After 6- or 24-hour treatment with dex-gel, perilymph drug gradients along the cochlea were assessed by taking samples sequentially from the apex, and endolymph was sampled from the basal turn. Control gel injections caused small changes in sound field calibrations and functional measures for low-frequency stimuli, consistent with an induced conductive loss. Within 24 h, responses returned to normal. Twenty-four hours after dex-gel injection, low-frequency changes remained as the dex-gel was retained better in the middle ear, but there was no indication of high-frequency loss. While perilymph sample data showed that dex gradients were substantially lower than after single injections of dex solution, quantitative analysis of this result suggests that some dex may have entered the perilymph through the thin bone in the apical region of the cochlea. Endolymph levels of dex remained lower than those in the perilymph. This study confirms that a poloxamer hydrogel-based dex formulation provides an effective method for a prolonged delivery, providing a more uniform distribution of drug in the inner ear.
Progesterone Rapidly Attenuates ATP-Evoked Transient Currents in Cultured Rat Dorsal Root Ganglion Neurons
Authors: Fan Juan , Lu Yi , Yu Li-hua , Zhang Yanmin , Ni Xin , Burnstock Geoffrey , Ma Bei
Published: December 2010

Background: Progesterone has been shown to play a role in pain perception. However, the effects of progesterone on P2X3 receptors, the nociception-related receptors in primary sensory neurons, remain unclear. Methods: We investigated the effects of progesterone on P2X3-receptor-mediated responses of rat dorsal root ganglion neurons by using whole-cell patch clamp techniques. Results: Progesterone (10 pmol/l to 1 µmol/l) inhibited ATP (100 µmol/l)-induced transient currents and the transient component of biphasic currents in a dose-dependent manner, but had no effect on the sustained currents. The effect of progesterone could be blocked by its receptor inhibitor, RU38486. Actidione, an inhibitor of protein synthesis, did not change the rapid effect. Investigations of the signaling pathways of progesterone showed that a nonselective antagonist of protein kinase, H-9, totally blocked the depressive effect of progesterone on ATP currents in a dose-dependent manner. Blocking protein kinase A with H-89 or KT5720 also affected progesterone-induced depression. The protein kinase A activator, forskolin, mimicked the effect of progesterone on ATP currents. Conclusion: These results suggest that progesterone may modulate pain signal transmission on dorsal root ganglia via regulating P2X3 receptor function. The cAMP-PKA signaling pathway is involved in the downregulating effect of progesterone on P2X3 receptors.
Relationship between the Three-Dimensional Structure of the Human Plantar Epidermis and the Dermoscopic Patterns Seen in Melanocytic Nevi
Authors: Nagashima Yoko , Akita Masumi , Tsuchida Tetsuya
Published: December 2010

Objective: Our aim was to investigate the relationship between the distribution of the dermoscopic patterns seen in plantar melanocytic nevi and the 3-dimensional structures of the epidermis. Methods: The precise locations of 69 melanocytic nevi on the sole and the border areas were investigated, with attention paid to each dermoscopic pattern. In addition, the basal surfaces of the plantar epidermis from 14 anatomical areas were observed by scanning electron microscopy (SEM). Results: In the weight-bearing area, melanocytic nevi with a fibrillar pattern were preferentially observed. Those with a lattice-like pattern were observed in the arch area, whereas those with a crista reticulated pattern were seen in the border area. On SEM observations, transverse ridges formed a couple of parallel lamellae on the crista profunda limitans (limiting ridges). Between the limiting ridges and the crista profunda intermedia (intermediate ridges), the transverse ridges had different shapes according to the anatomical location of the sole. Conclusion: These results suggest that the characteristic dermoscopic patterns seen in plantar melanocytic nevi simulate the arrangement of transverse ridges.
Rapid Neurological Recovery after Intravenous Tissue Plasminogen Activator in Stroke: Prognostic Factors and Outcome
Authors: Machumpurath Bejoy , Davis Stephen M. , Yan Bernard
Published: December 2010

Background: Treatment with tissue plasminogen activator (tPA) is associated with improved outcome in acute ischemic stroke. Of note, a proportion of patients demonstrate rapid and significant neurological recovery within 24 h. This has previously not been systematically studied. We aimed to examine its incidence, predictive factors and correlation with clinical outcomes. Methods: We included 161 patients with acute ischemic stroke who received intravenous tPA within 4.5 h. Patient demographics and clinical data were collected. Rapid neurological recovery was defined as an improvement of at least 50% within 24 h as measured by the National Institute of Health Stroke Scale (NIHSS) score, and long-term outcomes were assessed by 3-month modified Rankin Scale. The incidence of rapid neurological recovery and its correlation with outcomes were studied. The predictors of the phenomenon were examined by univariate analysis. Results: Rapid neurological recovery was present in 44 of the 161 patients (27.3%). This correlated with favorable outcomes at 3 months (p < 0.0005). Lower baseline NIHSS score (p = 0.006), mild (NIHSS score <12) versus severe stroke (NIHSS score ≧12; p = 0.002), normal serum glucose levels on admission (3.3–7.7 mmol/l; p = 0.009) and younger age (p = 0.043) predicted rapid neurological recovery. However, there was no association with time to treatment (p = 0.3). Conclusion: Rapid neurological recovery defines a rapid responder population and was demonstrated in a quarter of patients treated with intravenous tPA. It strongly predicts a good clinical outcome.
Growth Pattern of Untreated Boys with Simple Virilizing Congenital Adrenal Hyperplasia Indicates Relative Androgen Insensitivity during the First Six Months of Life
Authors: Bonfig W. , Schwarz H.P.
Published: December 2010

Context: Mild forms of simple virilizing congenital adrenal hyperplasia (CAH) may be missed in newborn screening. In the pre-newborn-screening era, missed diagnosis of simple virilizing CAH was not infrequent in boys. Elevated adrenal androgens lead to accelerated growth and bone maturation. Traditional treatment of CAH consists of the suppression of ACTH through glucocorticoid replacement, in an attempt to reduce excessive androgen production. Objective: To retrospectively analyze early growth pattern and bone maturation in untreated boys with simple virilizing CAH. Patients: In the pre-newborn screening era, 13 boys had a late diagnosis of simple virilizing classical CAH. Diagnosis of 21-hydroxylase deficiency was confirmed by mutation analysis of the CYP21A2 gene in all patients. Growth data were retrospectively collected from standarized preventive medical checkups at the regular pediatrician until the time of diagnosis of CAH. Results: Length was 0.1 ± 0.8 SDS (mean ± SD) at birth, 0.2 ± 1 SDS at 3 months, 0.2 ± 0.9 SDS at 6 months, 0.7 ± 1 SDS at 1 year, +1.1 ± 0.9 SDS at 2 years and +1.8 ± 1.2 SDS at 4 years. At diagnosis, mean chronological age was 4.4 ± 1.6 years and height SDS was 2 ± 1.7. Bone age was accelerated (9.4 ± 4 years) at diagnosis. Signs that had led to diagnosis were pubic hair (n = 11), accelerated growth rate (n = 6) and birth of an affected sister (n = 3). Despite late start of hydrocortisone treatment, mean final height was –1 ± 0.9 SDS. Seven of 18 patients had a final height within 1 SD of target height. Conclusion: Height velocity is not markedly increased in untreated boys with simple virilizing CAH in the first 6 months of life, indicating that infants are relatively androgen insensitive during that period. After the first 6 months of life, growth velocity increases significantly and elevated androgens lead to advanced skeletal maturation. This observation has implications for lower hydrocortisone doses to be used in CAH children during the first 6 months of life. In addition, staying alert for clinical symptoms and signs of simple virilizing CAH is still warranted, since mild forms may be missed in newborn screening.
Hospital Admissions for Ischemic Stroke: Does Long-Term Exposure to Air Pollution Interact with Major Risk Factors?
Authors: Oudin Anna , Strömberg Ulf , Jakobsson Kristina , Stroh Emilie , Lindgren Arne G. , Norrving Bo , Pessah-Rasmussen Hélène , Engström Gunnar , Björk Jonas
Published: December 2010

Background: The aim was to investigate whether the effects of major risk factors for ischemic stroke were modified by long-term exposure to air pollution in Scania, southern Sweden. Methods: Cases were defined as first-ever ischemic strokes in patients born between 1923 and 1965 during 2001–2006 (n = 7,244). Data were collected from The Swedish National Stroke Register (Riks-stroke) and the Malmö and Lund Stroke Registers. Population controls were matched on age and sex. Modeled outdoor annual mean NOx concentrations were used as proxy for long-term exposure to air pollution. Heterogeneity across NOx categories was tested for smoking, hypertension, diabetes mellitus, atrial fibrillation and physical inactivity. Data were analyzed as case-control data and to some extent as case-only data, with logistic regression analysis. Results: The case-control odds ratios for ischemic stroke in association with diabetes were 1.3 [95% confidence interval (CI): 1.1–1.6] and 2.0 (95% CI: 1.2–3.4) in the lowest and highest NOx category, respectively (p value for testing heterogeneity across the categories = 0.056). The case-only approach gave further support for the risk associated with diabetes to increase with NOx (p for trend = 0.033). We observed no main effect of mean NOx or any conclusive effect modifications between NOx and smoking, hypertension, atrial fibrillation or physical inactivity. Conclusions: In a low-level air pollution area, the risk for ischemic stroke associated with diabetes seemed to increase with long-term exposure to air pollution.
The CD6 Scavenger Receptor Is Differentially Expressed on a CD56dim Natural Killer Cell Subpopulation and Contributes to Natural Killer-Derived Cytokine and Chemokine Secretion
Authors: Braun Monika , Müller Bernadette , ter Meer Dominik , Raffegerst Silke , Simm Barbara , Wilde Susanne , Spranger Stefani , Ellwart Joachim , Mosetter Barbara , Umansky Ludmila , Lerchl Tina , Schendel Dolores J. , Falk Christine S.
Published: December 2010

The CD6 scavenger receptor is known to be expressed on virtually all T cells and is supposed to be involved in costimulation, synapse formation, thymic selection and leukocyte migration. Here, we demonstrate that CD6 is differentially expressed by a subpopulation of peripheral CD56dim natu- ral killer (NK) cells and absent on CD56bright NK cells. CD56dimCD16+ cells represent the major NK subset in the periphery, and most cells within this group are positive for CD6. Most killer immunoglobulin-like receptor- and immunoglobulin-like transcript-positive cells also belong to the CD6+ subpopulation, as expected from their restricted expression on CD56dim NK cells. In addition, CD6+ NK cells are similar to the newly identified CD94lowCD56dim NK subpopulation and most distant from the recently defined CD27+ NK subpopulation based on the reverse correlation of expression between CD6 and CD27, a marker associated primarily with CD56bright NK cells. With respect to CD6 function on NK cells, direct CD6 triggering did not result in degranulation but induced secretion of cytokines (interferon-γ and tumor necrosis factor-α) and chemokines [CXCL10 (IP-10), CXCL1 (GRO-α)]. Thus, CD6 expression on peripheral NK cells marks a novel CD56dim subpopulation associated with distinct patterns of cytokine and chemokine secretion.