bluuebunny/crossref_metadata_2025 huggingface dataset:
MODELING THE SCHISTOSOMIASIS ON THE ISLETS IN NANJING
Authors: QI LONGXING , CUI JING-AN , GAO YUAN , ZHU HUAIPING
Published: July 2011

A compartmental model is established for schistosomiasis infection in Qianzhou and Zimuzhou, two islets in the center of Yangtzi River near Nanjing, P. R. China. The model consists of five differential equations about the susceptible and infected subpopulations of mammalian Rattus norvegicus and Oncomelania snails. We calculate the basic reproductive number R0 and discuss the global stability of the disease free equilibrium and the unique endemic equilibrium when it exists. The dynamics of the model can be characterized in terms of the basic reproductive number. The parameters in the model are estimated based on the data from the field study of the Nanjing Institute of Parasitic Diseases. Our analysis shows that in a natural isolated area where schistosomiasis is endemic, killing snails is more effective than killing Rattus norvegicus for the control of schistosomiasis.
MODELING THE SPREAD OF HIV IN A STAGE STRUCTURED POPULATION: EFFECT OF AWARENESS
Authors: KAUR NAVJOT , GHOSH MINI , BHATIA S. S.
Published: July 2011

Human immunodeficiency virus (HIV) is a lenti-virus (a member of the retrovirus family) that causes acquired immunodeficiency syndrome (AIDS), a critical condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections. Over the past few years HIV has been spreading rapidly in the population. Almost, everyday there are thousands of new human cases of HIV infection being recorded in the world and these occur in almost every country of the world. However, the spread of HIV is relatively faster in the developing countries as compared to developed countries because developing countries have limited resources. Worldwide, 70% of HIV infections in the adults have been transmitted through heterosexual contact and vertical transmission accounts for more than 90% of global infection in infants and children. In this paper, we propose a nonlinear mathematical model to study the spread of HIV by considering transmission of disease by heterosexual contact and vertical transmission. A stage structured model is proposed and analyzed by considering the total population variable and dividing the whole population under consideration into three stages: children, adults and old. Also, in this paper it is assumed that the rates of recruitment are different in different groups of population. Equilibria of the model and their stability are also discussed. Using the stability theory of differential equations and computer simulation, it is shown that due to the increase in the awareness of the disease in the adult class the total infective population decreases in the region under consideration.
A Retrospective Study of Treatment Complexity and Efficiency in a Brazilian Undergraduate Comprehensive Dental Care Program
Authors: Reis Sandra Cristina Guimarães Bahia , Santos Laura Barbosa , Leles Cláudio Rodrigues
Published: July 2011

The aim of the study was to explore treatment efficiency in an undergraduate comprehensive dental care program (CDCP). The study sample consisted of the records of 652 patients from the CDCP of the School of Dentistry, Federal University of Goias, Brazil, who were treated in the period from 2004 through 2009. A total of 45 clinical procedures performed by the students was listed and a panel of 19 judges, graded the perceived complexity of each procedure on a 11-point scale using an adaptation of the Thurstone method. Spearman's correlation, one-way Anova, Kaplan-Meier, and Cox regression were used to build a predictive model for time-to-event data—completion of treatment (CT). Treatment time for CT was correlated with complexity scores (; ). The average estimated median months for CT was 23.0 (95%CI = 19.6–26.3) and was significantly different () among complexity levels (low 13.0, intermediary 19.0, high 47.0). When low complexity was the reference category, estimated changes in risk for incomplete treatment were greater for intermediary (; 95%CI = 0.40–0.75) and high complexity cases (; 95%CI = 0.23–0.45). The results indicated that treatment complexity has a large influence on undergraduate CDCP efficiency and should be considered when planning organizational strategies for the clinical environment.
An IgG4-Related Salivary Gland Disorder: A Case Series Presenting with a Different Clinical Setting
Authors: Ishida Masayuki , Fushiki Hiroaki , Watanabe Yukio
Published: July 2011

Küttner tumor is a chronic inflammatory disease that presents with a firm swelling of the submandibular gland and often mimics a neoplasm. Recently evidence suggests that Küttner tumor may be a type of disorder characterized by IgG4-related inflammations. Herein, we report 3 cases of submandibular gland swellings with severe fibrosis, inflammation with marked lymphoplasmacytic infiltration; this pathology mimics clinical manifestation of a malignant tumor in 18-fluorodeoxyglucose positron emission tomography (FDG-PET) findings.
Cementitious Spray Dryer Ash-Tire Fiber Material for Maximizing Waste Diversion
Authors: Riley Charles E. , Atadero Rebecca A. , van de Lindt John W. , Heyliger Paul R.
Published: July 2011

Spray dryer absorber (SDA) material, also known as spray dryer ash, is a byproduct of coal combustion and flue gas scrubbing processes that has self-cementing properties similar to those of class C fly ash. SDA material does not usually meet the existing standards for use as a pozzolan in Portland cement concrete due to its characteristically high sulfur content, and thus unlike fly ash, it is rarely put to beneficial use. This paper presents the results of a study with the objective of developing beneficial uses for SDA material in building materials when combined with tire fiber reinforcement originating from a recycling process. Specifically, spray dryer ash was investigated for use as the primary or even the sole binding component in a mortar or concrete. This study differs from previous research in that it focuses on very high contents of spray dryer ash (80 to 100 percent) in a hardened product. The overarching objective is to divert products that are normally sent to landfills and provide benefit to society in beneficial applications.
Entamoeba gingivalisin Acute Osteomyelitis of the Mandible
Authors: Bhaijee Feriyl , Bell Diana
Published: July 2011

An 86-year-old woman presented with osteonecrosis of the mandible following bisphosphonate therapy for multiple myeloma, and underwent surgical debridement and multiple dental extractions. Histopathologic examination of the necrotic bone fragments revealed acute osteomyelitis with mixed flora and organisms morphologically consistent withEntamoeba gingivalis. In addition to oral scrapings and sputum,E. gingivalishas been identified in specimens obtained from the uterus, cervix, neck lymph nodes, and lung. It is rarely found in lesions of the head and neck. We present an unusual case ofE. gingivalisin acute osteomyelitis of the mandible, following bisphosphonate therapy for multiple myeloma. To our knowledge, this is the first reported case ofE. gingivalisin association with osteomyelitis.
Doxorubicin Induced Nephrotoxicity: Protective Effect of Nicotinamide
Authors: Ayla Sule , Seckin Ismail , Tanriverdi Gamze , Cengiz Mujgan , Eser Mediha , Soner B. C. , Oktem Gulperi
Published: July 2011

Introduction. Nephrotoxicity is one of the important side effects of anthracycline antibiotics. The aim of this study was to investigate the effects of nicotinamide (NAD), an antioxidant agent, against nephrotoxicity induced by doxorubicin (DXR).Methods. The rats were divided into control, NAD alone, doxorubicin (20 mg/kg, i.p.) and DXR plus NAD (200 mg/kg, i.p.) groups. At the end of the 10th day, kidney tissues were removed for light microscopy and analysis. The level of tissues' catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), inducible nitric oxide (iNOS) and endothelial nitric oxide (eNOS) activities were determined.Results. The activities of CAT, GPx, and GSH were decreased, and Po was increased in renal tissue of doxorubicin group compared with other groups. The tissue of the doxorubicin group showed some histopathological changes such as glomerular vacuolization and degeneration, adhesion to Bowman's capsule and thickening and untidiness of tubular and glomerular capillary basement membranes. Histopathological examination showed that NAD prevented partly DXR-induced tubular and glomerular damage.Conclusions. Pretreatment with NAD protected renal tissues against DXR-induced nephrotoxicity. Preventive effects of NAD on these renal lesions may be via its antioxidant and anti-inflammatory action.
Poorly Differentiated Uterine or Cervical Sarcoma in a Young Dog
Authors: Cora Michelle C. , Neel Jennifer A.
Published: July 2011

A 1.5 year old, female, spayed, Labrador retriever with a history of three abdominal surgeries within the previous two months presented to the North Carolina State University Veterinary Teaching Hospital for evaluation of a pelvic inlet mass causing fecal tenesmus, obstipation, and dysuria. Abdominal ultrasound revealed a caudal abdominal mass extending into the pelvic cavity. Cytologic evaluation of the mass showed a pleomorphic round to fusiform cell population with histiocytic and suppurative inflammation. The primary differential was neoplasia, but inflammation with cellular pleomorphism could not be excluded. Via histopathology and immunohistochemistry, a diagnosis of poorly differentiated sarcoma originating from the uterus or cervix with widespread intra-abdominal dissemination and metastasis was made. Sarcomas of any type are rare in young dogs with only sporadic cases of poorly or undifferentiated sarcomas reported. This case is a unique presentation of an aggressive, poorly differentiated sarcoma arising from the cervix or uterus in a young dog and illustrates the importance of histologic evaluation of surgically resected tissues that are abnormal in appearance.
Cannabis, Collaterals, and Coronary Occlusion
Authors: De Silva Kalpa , Perera Divaka
Published: July 2011

A 51-year-old gentleman, who regularly smoked cannabis, presented with chest pain and diaphoresis. He was haemodynamically stable. ECG showed ST depression, inferiorly, and 1 mm ST elevation in lead aVR. Emergent coronary angiography showed thrombotic occlusion of the left main coronary artery (LMCA), the dominant RCA provided Rentrop grade II collaterals to the LAD. The LMCA was successfully reopened by deployment of a bare-metal stent. Animal heart models suggest that endogenous cannibinoids may cause ischaemic preconditioning. This case suggests that the severity of ischaemia, and hence ECG changes and haemodynamic consequences following an acute occlusion of the LMCA, can be ameliorated by coronary collateralisation and possibly by preconditioning of the myocardium.
Characterization of the Pore Filling of Solid State Dye Sensitized Solar Cells with Photoinduced Absorption Spectroscopy
Authors: Olson Carol , Veldman Dirk , Bakker Klaas , Lenzmann Frank
Published: July 2011

Near steady-state photoinduced absorption (PIA) and UV-Vis absorption spectroscopy are used to characterize the pore filling of spiro-MeOTAD (2,2′,7,7′-tetrakis-(N,N-di-p-methoxyphenylamine)9,9′-spirobifluorene) into the nanoparticulate TiO2electrode of a solid-state dye-sensitized solar cell (ssDSC). The volumetric ratio of filled to unfilled pore volumes, as well as the optical signature of interacting chemical species, that is, the hole-transfer yield (HTY), are investigated. PIA spectroscopy is used to measure the HTY, relative to the amount of spiro-MeOTAD present, without needing to determine the extinction coefficients of the dye and spiro-MeOTAD cation species. The Beer-Lambert law is used to relate the relative PIA signal to the penetration length of the hole-conductor in the TiO2film. For the sample thickness range of1.4–5 μm investigated here, the optimum characteristic penetration length is determined to be3.1+0.46 μm, which is compared to 1.4 μm for the 200 mgmL−1concentration of spiro-MeOTAD conventionally used. Therefore, doubling the effective penetration of spiro-MeOTAD is necessary to functionalize all the dye molecules in a ssDSC.
T Cell Recognition of Autoantigens in Human Type 1 Diabetes: Clinical Perspectives
Authors: Mallone Roberto , Brezar Vedran , Boitard Christian
Published: July 2011

Type 1 diabetes (T1D) is an autoimmune disease driven by the activation of lymphocytes against pancreaticβ-cells. Amongβ-cell autoantigens, preproinsulin has been ascribed a key role in the T1D process. The successive steps that control the activation of autoreactive lymphocytes have been extensively studied in animal models of T1D, but remains ill defined in man. In man, T lymphocytes, especially CD8+T cells, are predominant within insulitis. Developing T-cell assays in diabetes autoimmunity is, thus, a major challenge. It is expected to help defining autoantigens and epitopes that drive the disease process, to pinpoint key functional features of epitope-specific T lymphocytes along the natural history of diabetes and to pave the way towards therapeutic strategies to induce immune tolerance toβ-cells. New T-cell technologies will allow defining autoreactive T-cell differentiation programs and characterizing autoimmune responses in comparison with physiologically appropriate immune responses. This may prove instrumental in the discovery of immune correlates of efficacy in clinical trials.
Stabilization Using a Discrete Fuzzy PDC Control with PID Controllers and Pole Placement: Application to an Experimental Greenhouse
Authors: Chouchaine Amine , Feki Elyes , Mami Abdelkader
Published: July 2011

This paper proposes a control strategy for complex and nonlinear systems, based on a parallel distributed compensation (PDC) controller. A solution is presented to solve a stability problem that arises when dealing with a Takagi‐Sugeno discrete system with great numbers of rules. The PDC controller will use a classical controller like a PI, PID, or RST in each rule with a pole placement strategy to avoid causing instability. The fuzzy controller presented combines the multicontrol approach and the performance of the classical controllers to obtain a robust nonlinear control action that can also deal with time‐variant systems. The presented method was applied to a small greenhouse to control its inside temperature by variation in ventilation rate inside the process. The results obtained will show the efficiency of the adopted method to control the nonlinear and complex systems.
Lenalidomide-Associated ITP
Authors: Herold Christina I. , Gasparetto Cristina , Arepally Gowthami M.
Published: July 2011

Lenalidomide is a potent immunomodulatory agent being used increasingly for treatment of hematologic malignancies including multiple myeloma and myelodysplasia. The common toxicities of lenalidomide, including dose-limiting myelosuppression, are well described. However, the immunomodulatory properties of lenalidomide may give rise to unexpected autoimmune complications. Herein, we describe a case of immune thrombocytopenic purpura (ITP) associated with use of lenalidomide.
Multiple‐Parameter Hamiltonian Approach for Higher Accurate Approximations of a Nonlinear Oscillator with Discontinuity
Authors: Khan Najeeb Alam , Jamil Muhammad , Ara Asmat
Published: July 2011

We applied a new approach to obtain natural frequency of the nonlinear oscillator with discontinuity. He′s Hamiltonian approach is modified for nonlinear oscillator with discontinuity for which the elastic force term is proportional to sgn(u). We employed this method for higher‐order approximate solution of the nonlinear oscillator equation. This property is used to obtain approximate frequency‐amplitude relationship of a nonlinear oscillator with high accuracy. Many numerical results are given to prove the efficiency of the suggested technique.
Prevalence and Risk Factors of HIV Infection among Clients Attending ICTCs in Six Districts of Tamilnadu, South India
Authors: Ramachandran Rajeswari , Chandrasekaran V. , Muniyandi M. , Jaggarajamma K. , Bagchi Anasua , Sahu Supriya
Published: July 2011

Objective. To assess the HIV serostatus of clients attending integrated counseling and testing centres (ICTCs) in Tamilnadu, south India (excluding antenatal women and children), and to study its association with demographic, socioeconomic, and behavioral risk factors.Design. In a prospective observational study, we interviewed clients attending 170 ICTCs from six districts of Tamilnadu during 2007 utilizing a standard pretest assessment questionnaire. All the clients were tested for HIV with rapid test kits. Multiple logistic regression analysis was used to identify determinants of HIV infection.Results. Of 18329 clients counseled, 17958 (98%) were tested for HIV and 732 (4.1%; range 2.6 to 6.2%) were tested positive for HIV. Median age of clients was 30 years; 89% had never used condoms in their lives and 2% gave history of having received blood transfusion. In multivariate analysis HIV seropositivity was associated with HIV in the family (adjusted odds ratio) (AOR 11.6), history of having sex with sex workers (AOR 2.9), age ≥31 years (AOR 2.8); being married (AOR 2.5), previously tested for HIV (AOR 1.9), illiteracy (AOR 1.7), unemployment (AOR 1.5), and alcoholism (AOR 1.5).Conclusion. HIV seroprevalence being high in ICTC clients (varied from 2.6 to 6.2%), this group should also be included in routine programme monitoring of sero-positivity and risk factors for better understanding of the impact of the National AIDS Control Programme. This would help in evolving appropriate policies and strategies to reduce the spread of HIV infection.
Eye Movement Sequences during Simple versus Complex Information Processing of Scenes in Autism Spectrum Disorder
Authors: Au-Yeung Sheena K. , Benson Valerie , Castelhano Monica , Rayner Keith
Published: July 2011

Minshew and Goldstein (1998) postulated that autism spectrum disorder (ASD) is a disorder of complex information processing. The current study was designed to investigate this hypothesis. Participants with and without ASD completed two scene perception tasks: a simple “spot the difference” task, where they had to say which one of a pair of pictures had a detail missing, and a complex “which one's weird” task, where they had to decide which one of a pair of pictures looks “weird”. Participants with ASD did not differ from TD participants in their ability to accurately identify the target picture in both tasks. However, analysis of the eye movement sequences showed that participants with ASD viewed scenes differently from normal controls exclusively for the complex task. This difference in eye movement patterns, and the method used to examine different patterns, adds to the knowledge base regarding eye movements and ASD. Our results are in accordance with Minshew and Goldstein's theory that complex, but not simple, information processing is impaired in ASD.
Aspects of Prophylactic Vaccination against Cervical Cancer and Other Human Papillomavirus-Related Cancers in Developing Countries
Authors: Natunen Kari , Lehtinen Johannes , Namujju Proscovia , Sellors John , Lehtinen Matti
Published: July 2011

Cervical cancer and other human papillomavirus- (HPV-) related cancers are preventable, but preventive measures implemented in developing countries and especially in low-income rural regions have not been effective. Cervical cancer burden derived from sexually transmitted HPV infections is the heaviest in developing countries, and a dramatic increase in the number of cervical cancer cases is predicted, if no intervention is implemented in the near future. HPV vaccines offer an efficient way to prevent related cancers. Recently implemented school-based HPV vaccination demonstration programmes can help tackle the challenges linked with vaccine coverage, and access to vaccination and health services, but prevention strategies need to be modified according to regional characteristics. In urban regions WHO-recommended vaccination strategies might be enough to significantly reduce HPV-related disease burden, but in the rural regions additional vaccination strategies, vaccinating both sexes rather than only females when school attendance is the highest and applying a two-dose regime, need to be considered. From the point of view of both public health and ethics identification of the most effective prevention strategies is pivotal, especially when access to health services is limited. Considering cost-effectiveness versus justice further research on optional vaccination strategies is warranted.
Diffusion Tensor Imaging, Structural Connectivity, and Schizophrenia
Authors: Whitford Thomas J. , Kubicki Marek , Shenton Martha E.
Published: July 2011

A fundamental tenet of the “disconnectivity” theories of schizophrenia is that the disorder is ultimately caused by abnormal communication between spatially disparate brain structures. Given that the white matter fasciculi represent the primary infrastructure for long distance communication in the brain, abnormalities in these fiber bundles have been implicated in the etiology of schizophrenia. Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique that enables the visualization of white matter macrostructurein vivo, and which has provided unprecedented insight into the existence and nature of white matter abnormalities in schizophrenia. The paper begins with an overview of DTI and more commonly used diffusion metrics and moves on to a brief review of the schizophrenia literature. The functional implications of white matter abnormalities are considered, particularly with respect to myelin's role in modulating the transmission velocity of neural discharges. The paper concludes with a speculative hypothesis about the relationship between gray and white matter abnormalities associated with schizophrenia.
A Comparative Study on Performance Measurement of Decision-Making Units: A Case Study in Iranian Tejarat Banks
Authors: Hasannezhad M. , Hosseini S. E.
Published: July 2011

Nowadays, vicissitude in administrative systems through Performance Measurement (PM) is one of the necessary and inevitable subjects, on which the improvement of efficiency and effectiveness in banking systems depend greatly. In this paper, we focused on efficiency analysis of Tejarat bank branches in order to propose the corrective actions on utilizing resources. Hence, we compute the efficiencies of units based on input-oriented CCR model with three approaches which differ on combination method of inputs and outputs and then rank them by Anderson & Peterson (AP) model. The results represent that the CCR model based on confined fuzzy weights presents the high level of accuracy in identifying efficient units as well as giving useful information on improving the inefficient branches.
Hydroxyl Radical and Its Scavengers in Health and Disease
Authors: Lipinski Boguslaw
Published: July 2011

It is generally believed that diseases caused by oxidative stress should be treated with antioxidants. However, clinical trials with such antioxidants as ascorbic acid and vitamin E, failed to produce the expected beneficial results. On the other hand, important biomolecules can be modified by the introduction of oxygen atoms by means of non-oxidative hydroxyl radicals. In addition, hydroxyl radicals can reduce disulfide bonds in proteins, specifically fibrinogen, resulting in their unfolding and scrambled refolding into abnormal spatial configurations. Consequences of this reaction are observed in many diseases such as atherosclerosis, cancer and neurological disorders, and can be prevented by the action of non-reducing substances. Moreover, many therapeutic substances, traditionally classified as antioxidants, accept electrons and thus are effective oxidants. It is described in this paper that hydroxyl radicals can be generated by ferric ions without any oxidizing agent. In view of the well-known damaging effect of poorly chelated iron in the human body, numerous natural products containing iron binding agents can be essential in the maintenance of human health. However, beneficial effects of the great number of phytochemicals that are endowed with hydroxyl radical scavenging and/or iron chelating activities should not be considered as a proof for oxidative stress.
H∞ Estimation for a Class of Lipschitz Nonlinear Discrete‐Time Systems with Time Delay
Authors: Zhao Huihong , Zhang Chenghui , Wang Guangchen , Xing Guojing
Published: July 2011

The issue of H∞ estimation for a class of Lipschitz nonlinear discrete‐time systems with time delay and disturbance input is addressed. First, through integrating the H∞ filtering performance index with the Lipschitz conditions of the nonlinearity, the design of robust estimator is formulated as a positive minimum problem of indefinite quadratic form. Then, by introducing the Krein space model and applying innovation analysis approach, the minimum of the indefinite quadratic form is obtained in terms of innovation sequence. Finally, through guaranteeing the positivity of the minimum, a sufficient condition for the existence of the H∞ estimator is proposed and the estimator is derived in terms of Riccati‐like difference equations. The proposed algorithm is proved to be effective by a numerical example.
Automatic Segmentation of Dermoscopic Images by Iterative Classification
Authors: Zortea Maciel , Skrøvseth Stein Olav , Schopf Thomas R. , Kirchesch Herbert M. , Godtliebsen Fred
Published: July 2011

Accurate detection of the borders of skin lesions is a vital first step for computer aided diagnostic systems. This paper presents a novel automatic approach to segmentation of skin lesions that is particularly suitable for analysis of dermoscopic images. Assumptions about the image acquisition, in particular, the approximate location and color, are used to derive an automatic rule to select small seed regions, likely to correspond to samples of skin and the lesion of interest. The seed regions are used as initial training samples, and the lesion segmentation problem is treated as binary classification problem. An iterative hybrid classification strategy, based on a weighted combination of estimated posteriors of a linear and quadratic classifier, is used to update both the automatically selected training samples and the segmentation, increasing reliability and final accuracy, especially for those challenging images, where the contrast between the background skin and lesion is low.
A Predator's Perspective of the Accuracy of Ant Mimicry in Spiders
Authors: Nelson Ximena J.
Published: July 2011

Among spiders, resemblance of ants (myrmecomorphy) usually involves the Batesian mimicry, in which the spider coopts the morphological and behavioural characteristics of ants to deceive ant-averse predators. Nevertheless, the degree of resemblance between mimics and ants varies considerably. I usedPortia fimbriata,a jumping spider (Salticidae) with exceptional eyesight that specialises on preying on salticids, to test predator perception of the accuracy of ant mimicry.Portia fimbriata’s response to ants (Oecophylla smaragdina), accurate ant-like salticids (Synageles occidentalis), and inaccurate ant-like salticids (females ofMyrmarachne bakeriand sexually dimorphic males ofM. bakeri, which have enlarged chelicerae) was assessed.Portia fimbriataexhibited graded aversion in accordance with the accuracy of resemblance to ants (O. smaragdina>S. occidentalis> femaleM. bakeri> maleM. bakeri). These results support the hypothesis that ant resemblance confers protection from visual predators, but to varying degrees depending on signal accuracy.
Interaction between Mitochondria and the Endoplasmic Reticulum: Implications for the Pathogenesis of Type 2 Diabetes Mellitus
Authors: Leem Jaechan , Koh Eun Hee
Published: July 2011

Mitochondrial dysfunction and endoplasmic reticulum (ER) stress are closely associated withβ-cell dysfunction and peripheral insulin resistance. Thus, each of these factors contributes to the development of type 2 diabetes mellitus (DM). The accumulated evidence reveals structural and functional communications between mitochondria and the ER. It is now well established that ER stress causes apoptotic cell death by disturbing mitochondrial Ca2+homeostasis. In addition, recent studies have shown that mitochondrial dysfunction causes ER stress. In this paper, we summarize the roles that mitochondrial dysfunction and ER stress play in the pathogenesis of type 2 DM. Structural and functional communications between mitochondria and the ER are also discussed. Finally, we focus on recent findings supporting the hypothesis that mitochondrial dysfunction and the subsequent induction of ER stress play important roles in the pathogenesis of type 2 DM.
Induction of Specific Immunotherapy with Hymenoptera Venoms Using Ultrarush Regimen in Children: Safety and Tolerance
Authors: Köhli-Wiesner Alice , Stahlberger Lisbeth , Bieli Christian , Stricker Tamar , Lauener Roger
Published: July 2011

Background & Objective. Ultrarush induction for specific venom immunotherapy has been shown to be reliable and efficacious in adults. In this study its safety and tolerance in children was evaluated.
Methods. Retrospective analysis of 102 ultrarush desensitizations carried out between 1997 and 2005 in 94 children, aged 4 to 15 years. Diagnosis and selection for immunotherapy were according to recommendations of the European Academy of Allergy and Clinical Immunology. Systemic adverse reactions (SARs) were described using the classification of H. L. Mueller.
Results. All patients reached the cumulative dose of 111.1 μg hymenoptera venom within 210 minutes. Six patients (6%) had allergic reactions grade I; 2 patients (2%) grade II and 5 patients (5%) grade III. Three patients (3%) showed unclassified reactions. SARs did not occur in the 15 patients aged 4 to 8 years and they were significantly more frequent in girls (29%) compared with boys (12%) (, multivariant analysis) and in bee venom extract treated patients (20%) compared to those treated with wasp venom extract (8%) (OR 0.33, 95% Cl 0.07–1.25).
Conclusion. Initiation of specific immunotherapy by ultrarush regimen is safe and well tolerated in children and should be considered for treating children with allergy to hymenoptera venom.
Prioritizing Candidate Disease miRNAs by Topological Features in the miRNA Target–Dysregulated Network: Case Study of Prostate Cancer
Authors: Xu Juan , Li Chuan-Xing , Lv Jun-Ying , Li Yong-Sheng , Xiao Yun , Shao Ting-Ting , Huo Xiao , Li Xiang , Zou Yan , Han Qing-Lian , Li Xia , Wang Li-Hua , Ren Huan
Published: July 2011

Recently, microRNAs (miRNA), small noncoding RNAs, have taken center stage in the field of human molecular oncology. However, their roles in tumor biology remain largely unknown. According to the assumption that miRNAs implicated in a specific tumor phenotype will show aberrant regulation of their target genes, we introduce an approach based on the miRNA target–dysregulated network (MTDN) to prioritize novel disease miRNAs. Target genes have predicted binding sites for any miRNA. The MTDN is constructed by combining computational target prediction with miRNA and mRNA expression profiles in tumor and nontumor tissues. Application of the proposed method to prostate cancer reveals that known prostate cancer miRNAs are characterized by a greater number of dysregulations and coregulators and the tendency to coregulate with each other and that they share a higher proportion of targets with other prostate cancer miRNAs. Support vector machine classifier, based on these features and changes in miRNA expression, is constructed and gives an average overall prediction accuracy of 0.8872 in cross-validation tests. The classifier is then applied to miRNAs in the MTDN. Functions enriched by dysregulated targets of novel predicted miRNAs are closely associated with oncogenesis. In addition, predicted cancer miRNAs within families or from different families show combinatorial dysregulation of target genes, as revealed by analysis of the MTDN modular organization. Finally, 3 miRNA target regulations are verified to hold in prostate cancer cells by transfection assays. These results show that the network-centric method could prioritize novel disease miRNAs and model how oncogenic lesions are mediated by miRNAs, providing important insights into tumorigenesis. Mol Cancer Ther; 10(10); 1857–66. ©2011 AACR.
An Integrated Chemical Biology Approach Identifies Specific Vulnerability of Ewing's Sarcoma to Combined Inhibition of Aurora Kinases A and B
Authors: Winter Georg E. , Rix Uwe , Lissat Andrej , Stukalov Alexey , Müllner Markus K. , Bennett Keiryn L. , Colinge Jacques , Nijman Sebastian M. , Kubicek Stefan , Kovar Heinrich , Kontny Udo , Superti-Furga Giulio
Published: July 2011

Ewing's sarcoma is a pediatric cancer of the bone that is characterized by the expression of the chimeric transcription factor EWS-FLI1 that confers a highly malignant phenotype and results from the chromosomal translocation t(11;22)(q24;q12). Poor overall survival and pronounced long-term side effects associated with traditional chemotherapy necessitate the development of novel, targeted, therapeutic strategies. We therefore conducted a focused viability screen with 200 small molecule kinase inhibitors in 2 different Ewing's sarcoma cell lines. This resulted in the identification of several potential molecular intervention points. Most notably, tozasertib (VX-680, MK-0457) displayed unique nanomolar efficacy, which extended to other cell lines, but was specific for Ewing's sarcoma. Furthermore, tozasertib showed strong synergies with the chemotherapeutic drugs etoposide and doxorubicin, the current standard agents for Ewing's sarcoma. To identify the relevant targets underlying the specific vulnerability toward tozasertib, we determined its cellular target profile by chemical proteomics. We identified 20 known and unknown serine/threonine and tyrosine protein kinase targets. Additional target deconvolution and functional validation by RNAi showed simultaneous inhibition of Aurora kinases A and B to be responsible for the observed tozasertib sensitivity, thereby revealing a new mechanism for targeting Ewing's sarcoma. We further corroborated our cellular observations with xenograft mouse models. In summary, the multilayered chemical biology approach presented here identified a specific vulnerability of Ewing's sarcoma to concomitant inhibition of Aurora kinases A and B by tozasertib and danusertib, which has the potential to become a new therapeutic option. Mol Cancer Ther; 10(10); 1846–56. ©2011 AACR.
P53 Codon 72 (Arg72Pro) Polymorphism and Prostate Cancer Risk: Association between Disease Onset and Proline Genotype
Authors: Rogler Anja , Rogenhofer Michael , Borchardt Albert , Lunz Jens-Claudio , Knoell Antje , Hofstaedter Ferdinand , Tannapfel Andrea , Wieland Wolf , Hartmann Arndt , Stoehr Robert
Published: July 2011

The tumor suppressor gene p53 plays an important role in the stress response of the cell and is mutated in 50% of all human tumors. The p53 Arg72Pro single-nucleotide polymorphism (SNP) was found to be associated with an increased risk of various malignancies. Biochemical and biological differences between the 2 polymorphic variants of wild-type P53 might lead to distinct susceptibility to HPV- and non-HPV-induced tumors. For prostate cancer, only limited data are available, especially in the Caucasian pop-ulation. Therefore, we determined the distribution of the Arg72Pro SNP in a Caucasian case-control study including 118 prostate cancer patients and 194 male controls without any malignancy using restriction fragment length polymorphism analysis. A subset of 33 tumors was tested for HPV infection, and no HPV DNA was found. Cases and controls showed similar distributions of alleles in the SNP (p = 0.720). Regarding the onset of the disease, patients diagnosed at ≤60 years of age and older patients (>60 years of age) showed a significant difference in genotype distribution (p = 0.035); there was also an increased occurrence of risk allele Pro72 in cases aged ≤60 years (p = 0.045). A subset of 64 prostate tumors was stained immunohistochemically for P53. 5 of 64 prostate tumors (7.8%) were positive for P53 expression, indicating integrity of the protein in the majority of cases. Genotype distribution showed no association with the Gleason score or additional histopathological characteristics. This study shows that the overall risk of prostate cancer was not associated with Arg72Pro SNP and HPV infection in our cohort. However, disease onset might be modulated by the p53 Pro72 allele, suggesting an important role of apoptosis regulation in prostate carcinogenesis.
Lim1, an Embryonal Transcription Factor, Is Absent in Multicystic Renal Dysplasia, but Reactivated in Nephroblastomas
Authors: Guertl Barbara , Senanayake Upeka , Nusshold Elisa , Leuschner Ivo , Mannweiler Sebastian , Ebner Birgit , Hoefler Gerald
Published: July 2011

Objective:Lim1 (Lim homeobox 1) plays an important role during rodent renal development; however, its rolein human kidney development and disease is still unclear. Methods: We investigated LIM1 expression during human renal development, in dysplastic kidneys and in renal neoplasms using immunohistochemistry. RNA levels in renal carcinomas were determined by quantitative RT-PCR, and the potential roles of LIM1 in mesenchymal-epithelial transition and cell cycle were investigated in a cell culture model. Results: LIM1 was detected in pretubular aggregates, S-shaped and comma-shaped bodies as well as immature glomeruli between 10 and 30 weeks of gestation. Eleven dysplastic kidneys showed no expression of LIM1. In contrast, 12 of 32 nephroblastomas showed nuclear positivity. One regressive nephroblastoma had diffuse expression of LIM1 in tubular structures, all others showed focal positivity in mesenchymal, blastemal and epithelial structures. Renal cell carcinomas revealed no expression of LIM1. Overexpression of LIM1 in a cell culture model led to an increase in KERATIN7 expression but no change in the cell cycle. Conclusion: Our study supports the concept of a causative role of LIM1 deficiency in the development of multicystic kidney. In a small subset of nephroblastomas with a more diffuse expression pattern LIM1 might also contribute to the pathogenesis of these lesions.
Assembly of the Inner Perivitelline Layer, a Homolog of the Mammalian Zona Pellucida: An Immunohistochemical and Ultrastructural Study
Authors: Rodler Daniela , Sasanami Tomohiro , Sinowatz Fred
Published: July 2011

The avian inner perivitelline layer (IPVL), a homologous structure to the mammalian zona pellucida, is deposited between the granulosa cells and the oocyte cell membrane during folliculogenesis. The glycoprotein meshwork of the IPVL forms a 3-dimensional matrix and possesses important functions in the fertilization process: it contributes to the binding of avian spermatozoa to the oocyte and induces acrosomal exocytosis. In contrast to the zona pellucida of mammals, the IPVL does not prevent the physiological polyspermy found in birds. Previous studies have shown that in the Japanese quail (Coturnix japonica) at least 5 glycoproteins are constituents of the IPVL (ZP1, ZP2, ZP3, ZP4, and ZPD). In this study, we investigated the spatiotemporal assembly pattern of the IPVL during folliculogenesis using immunohistochemical and ultrastructural methods. The obtained results clearly show that these glycoproteins are incorporated into the IPVL at distinct points during follicular development, supporting the hypothesis that ZP2 and ZP4 form a type of prematrix into which ZP1, ZP3, and ZPD are integrated at a later stage of development.
Comparison of Plasma Cell Type of Castleman’s Disease and IgG4-Related Sclerosing Disease: A Histopathological and Immunohistochemical Study
Authors: Jo Jeong-Hyeon , Park Young-Soo , Jeon Yoon Kyung , Nam Soo Jeong , Huh Jooryung
Published: July 2011

Objectives: Castleman’s disease (CD) is a group of rare atypical lymphoproliferative disorders classified as hyaline vascular (HV) and plasma cell (PC) types. CD may be closely mimicked by IgG4-related sclerosing disease (IgG4-SD) involving the lymph nodes. We retrospectively analyzed findings in patients with CD to elucidate the relationship between CD and IgG4-SD. Methods: Clinicopathological and immunophenotypical characteristics, including IgG+ and IgG4 expression by plasma cells, were analyzed in 87 consecutive patients diagnosed with CD from 1999 to 2010 at two major Korean hospitals. Results: The numbers of IgG+ (p < 0.001) and IgG4+ (p < 0.001) cells and the IgG4:IgG ratio (p = 0.003) were significantly higher in the PC than in the HV group. The mean IgG4+:IgG+ plasma cell ratio in the PC group was 25.1%, with 10 patients having a ratio >40%, the threshold IgG4:IgG ratio in patients with IgG4-SD. Conclusions: Patients with the PC form of CD and IgG4-related lymphadenopathy share some features, including the pattern of plasma cell distribution and high-level infiltration of IgG4+ cells. Some patients thought to have the PC form of CD could be reclassified as showing IgG4-related lymphadenopathy.
Tributyltin Alters Osteocalcin, Matrix Metalloproteinase 20 and Dentin Sialophosphoprotein Gene Expression in Mineralizing Mouse Embryonic Tooth in vitro
Authors: Salmela Eija , Alaluusua Satu , Sahlberg Carin , Lukinmaa Pirjo-Liisa
Published: July 2011

We showed in a previous in vitro study that tributyltin (TBT) arrests dentin mineralization and enamel formation in developing mouse tooth. The present aim was to investigate the effect of TBT on the expression of genes associated with mineralization of dental hard tissues. Embryonic day 18 mouse mandibular first molars were cultured for 3, 5 or 7 days and exposed to 1.0 µM TBT and studied by real-time quantitative polymerase chain reaction (RT-QPCR) for the expressions of osteocalcin (Ocn), alkaline phosphatase (Alpl), dentin matrix protein 1 (Dmp1), dentin sialophosphoprotein (Dspp) and matrix metalloproteinase 20 (Mmp-20).Ocn, Mmp-20 and Dspp, whose expressions showed changes in RT- QPCR, were further analyzed by in situ hybridization of tissue sections. In situ hybridization showed that TBT decreased Ocn expression in odontoblasts but increased the expression in the epithelial tooth compartment. In QPCR assays, the net effect in the whole tooth was increased expression. TBT also reduced Mmp-20 expression in ameloblasts and odontoblasts. Dspp expression varied but both QPCR assays and in situ hybridization showed a decreasing trend. TBT exposure had no clear effect on Alpl and Dmp1 expressions. Increased Ocn expression by epithelial enamel organ may inhibit dentin mineralization and enamel formation. Decreased Ocn, Mmp-20 and Dspp expressions in odontoblasts may indicate delayed cell differentiation, or TBT may specifically decrease the expression of genes involved in dentin mineralization. While decreased Mmp-20 expression by TBT in ameloblasts may impair enamel mineralization, the coincident reduction in Mmp-20 and Dspp expressions in odontoblasts may potentiate the delay of dentin mineralization.
Changes in Cerebral Perfusion around the Time of Delayed Cerebral Ischemia in Subarachnoid Hemorrhage Patients
Authors: Dankbaar J.W. , de Rooij N.K. , Smit E.J. , Velthuis B.K. , Frijns C.J.M. , Rinkel G.J.E. , van der Schaaf I.C.
Published: July 2011

Background: Because the pathogenesis of delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) is unclear, we studied cerebral perfusion at different time points around the occurrence of DCI. Methods: We prospectively enrolled 53 patients admitted to the University Medical Center Utrecht who underwent CT perfusion (CTP) scans on admission, and within 2 weeks after hemorrhage on 2 scheduled time points or during clinical deterioration. The occurrence of DCI was assessed according to predefined criteria by 2 neurological observers blinded to perfusion results. Clinically stable patients (no-DCI) served as reference, and patients with other causes of deterioration (n = 11) were excluded. In DCI patients, the day of DCI onset and in no-DCI patients the median day of DCI onset was taken as t = 0. Scans made before and after DCI were clustered into 5 additional time points. At each time point, cerebral blood volume (CBV) and flow (CBF), and mean transit time (MTT) were measured, and absolute and relative (interhemispheric asymmetry) values were compared between DCI and no-DCI patients. Results: Absolute CBF was lower and MTT was higher in the 18 DCI patients than in the 24 no-DCI patients before, during and after DCI. MTT asymmetry increased during DCI and partially recovered afterwards in DCI patients while it remained constant in no-DCI patients. Absolute and relative CBV remained constant in both groups. Conclusions: Our findings suggest that DCI patients already have diffusely worse perfusion (absolute values) than no-DCI patients before focal worsening (increased asymmetry) occurs and becomes symptomatic. The partial recovery in the measured areas suggests that DCI can be partly reversible.
Natural Pollen Exposure Increases the Response Plateau to Adenosine 5'-Monophosphate and Bronchial but Not Alveolar Nitric Oxide in Sensitized Subjects
Authors: Lopez V. , Prieto L. , Perez-Frances C. , Barato D. , Marin J.
Published: July 2011

Background: The effect of allergen exposure on airway responsiveness and exhaled nitric oxide (NO) has been well documented, but no information is available on allergen-induced changes in the response plateau to adenosine 5′-monophosphate (AMP) and in bronchial NO flux (J'awNO) and alveolar NO (CANO). Objectives: To determine the effect of natural allergen exposure, a proinflammatory stimulus, on the shape of the concentration-response curve to AMP and NO production in airway and alveolar sites. Methods: Airway responsiveness to high concentrations of methacholine and AMP, J'awNO and CANO values were obtained in 31 subjects with pollen allergy and in 11 healthy controls. Subjects with pollen allergy were studied before and at the height of the pollen season whereas healthy controls were tested on one occasion only. Results: In the group with pollen allergy, natural pollen exposure increased J'awNO (p = 0.03), but had no effect on CANO (p = 0.12). In the 18 subjects with pollen allergy who showed a response plateau to AMP in at least one period, the response plateau to AMP increased from a mean of 13.4% (95% CI: 8.2-18.5) out of season to 22.5% (95% CI: 15.5-29.4, p = 0.004) during the pollen season. Similar results were obtained with methacholine. Compared with healthy controls, subjects with pollen allergy had a higher response plateau and higher J'awNO values. Conclusions: These findings suggest that inflammatory changes induced by natural allergen exposure in sensitized subjects are predominantly located in the airways and associated with modifications in the shape of the concentration-response curve to direct and indirect agonists.