bluuebunny/crossref_metadata_2025 huggingface dataset:
The Multilevel Crossed Random Effects Growth Model for Estimating Teacher and School Effects: Issues and Extensions
Authors: Palardy Gregory J.
Published: December 2009

This article examines the multilevel linear crossed random effects growth model for estimating teacher and school effects from repeated measurements of student achievement. Results suggest that even a small degree of unmodeled nonlinearity can result in a substantial upward bias in the magnitude of the teacher effect, which raises concerns about its appropriateness for estimating teacher effects. To address this issue, a piecewise linear crossed random effect growth model is proposed. A comparison with the linear growth form shows that the piecewise specification provides more accurate estimates of teacher effects when achievement growth departs from linear growth across grade levels or over summer, which are prevalent conditions. Fitted examples using nationally representative data and Bayesian estimation methods are provided.
The Concerns-Based Adoption Model: A Framework for Examining Implementation of a Character Education Program
Authors: Hollingshead Barbara
Published: December 2009

Hall and Hord’s (2005) concerns-based adoption model (CBAM) served as the framework to study a districtwide implementation of Rachel’s Challenge in Rockwall, Texas. This article describes CBAM principles and strategies that were used to increase awareness of the change process during the first year of implementing the character education program. In particular, the article presents data collected through CBAM and the analysis that identified and interpreted both the concerns and extent of program adoption by teachers. Finally, the article discusses the ways CBAM provided administrators and campus facilitators with information necessary to develop strategies that would support teachers’ advancement in the program to higher levels of implementation.
Intergenerational Conflicts Among Latinos in Early Adulthood: Separating Values Conflicts With Parents From Acculturation Conflicts
Authors: Dennis Jessica , Basañez Tatiana , Farahmand Anahita
Published: December 2009

An investigation of Latino and non-Latino college students sought to examine the ways in which perceived intergenerational conflicts with parents are related to acculturation, family dynamics, and psychosocial functioning. Participants reported the extent to which they experienced two types of intergenerational conflicts with parents: values/expectations conflicts and acculturation conflicts such as their parents’ perception that they are “too American”. First- and second-generation Latinos reported experiencing more acculturation conflicts than third-generation Latinos and European Americans or African Americans. Regression analyses within the Latino sample indicated that both types of conflicts with parents were predicted by acculturation variables, lower family cohesion, and increased family control. Both types of conflicts were significant predictors of depression and lower self-esteem, even after controlling for generation status and family variables.
Measuring the Psychosocial Characteristics of Teacher Candidates Through the Academic Self-Identity: Self-Observation Yearly (ASI SOY) Inventory
Authors: Bustos Flores Belinda , Riojas Clark Ellen , Guerra Norma S. , Casebeer Cindy M. , Sánchez Serafin V. , Mayall Hayley J.
Published: December 2009

This study contends that multiple psychosocial factors mediate students’ pursuit of the teaching profession, including beliefs, ethnic identity, acculturation, efficacy, and motivation. Despite the myriad literature addressing teacher characteristics, less is known about how these factors influence the academic or personal development of teacher candidates preparing to teach in diverse classrooms. The authors examined the psychometric properties of the Academic Self-Identity: Self-Observation Yearly (ASI SOY), specifically developed to measure teacher candidates’ psychosocial characteristics. A total of 670 ASI SOY inventories were collected from teacher candidates attending a Hispanic-serving institution. It was found that the ASI SOY is reliable and valid for measuring four out of five proposed constructs. ASI SOY may be useful in identifying the academic, personal, and professional development characteristics of teacher candidates.
Metachromatic Leukodystrophy: A Case of Triplets With the Late Infantile Variant and a Systematic Review of the Literature
Authors: Mahmood Asif , Berry Jay , Wenger David A. , Escolar Maria , Sobeih Magdi , Raymond Gerald , Eichler Florian S.
Published: December 2009

Metachromatic leukodystrophy is a rare disorder with great clinical variability. We report the first case of triplets with the late infantile form of the disease and their systematic progression of symptoms. We reviewed the literature and identified all human studies that reported new cases since 1921. We analyzed survival by decade to assess the impact of historical changes in the management of care. Mean age at death and the 5-year survival from onset of symptoms for late infantile, juvenile, and adult phenotypes were 4.2 years and 24.9%, 17.4 years and 70.3%, and 43.1 years and 88.6%, respectively. The 5-year survival of cases reported after 1990 was significantly better than cases reported before 1970 in all subtypes of metachromatic leukodystrophy (late infantile: 52% vs 14%, juvenile: 100% vs 46%, adult: 95% vs 67%). Survival in the late infantile subtype was worse than that in other subtypes. Survival significantly improved over time in all subtypes.
Exploring the Apparel Needs and Preferences of Tween Girls and Their Mothers
Authors: Brock Mary Katherine , Ulrich Pamela V. , Connell Lenda Jo
Published: December 2009

During their tween years, most girls go through puberty and their bodies change at a rapid pace. Like adults, increasing numbers of this group are now characterized as overweight or obese (Centers for Disease Control (CDC), 1999). Thus, given this period of rapid change, compounded by problems with obesity, it was theorized that there are many subgroups, particularly related to age and size, that affect these consumers’ apparel relationships. The purpose of this research was thus, to characterize subgroups based on age and size of female tween consumers. Mothers were included in this study in order to understand how mother/daughter relationships affect the tweens’ apparel relationships. This exploratory study used content analysis of segmented focus groups and an emergent theme methodology, to show that tween girls have complex apparel relationships. Subjects in all groups indicated that they were unable to find clothing that was stylish, age appropriate, and fit their bodies. These identified gaps show the potential for niche markets within the tween consumer group and establishes a conceptual framework for further research.
Neo-Charismatic Leadership and the Fate of Mergers and Acquisitions: An Institutional Model of CEO Leadership
Authors: Tikhomirov Aleksey A. , Spangler William D.
Published: December 2009

CEOs face complex situational demands at each phase of the merger process. We offer an institutional perspective on how pre-merger and post-merger objectives and demands translate into CEO leadership role requirements. By illustrating how these role requirements are well-served by CEO neo-charismatic leadership, we answer why the rise of CEO neo-charismatic leadership is relevant to the merger context. Our model contributes to the institutional understanding of the merger process and its demands, and specifies forms of executive leadership needed for mergers to be successful.
Methylene Blue: A Simple Marker for Intraoperative Detection of Gastroduodenal Perforations During Laparoscopic Pyloromyotomy
Authors: Vegunta Ravindra K. , Rawlings Arthur L. , Jeziorczak Paul M.
Published: December 2009

Introduction. We studied the feasibility of using methylene blue (MB) as a marker to detect mucosal perforations during laparoscopic pyloromyotomy using in vitro and in vivo animal models. Materials and methods. MB was initially tested in pig stomachs in vitro. Information gathered from these experiments was then used to test the marker during experimental live piglet laparoscopic surgery. Results. MB stained the gastric mucosa blue; this tint could be seen through the intact mucosal layer exposed via myotomy. Dye extravasation was seen during laparoscopic surgery with mucosal perforations of 1.2 mm and greater with or without air insufflation of the stomach. Air extravasation was seen with perforations of 2.0 mm and greater. Conclusion. Full strength 1% MB dye instilled into the gastric lumen can potentially be used as a marker for detection of mucosal perforations of 1.2 mm or greater during laparoscopic pyloromyotomy.
Masculinity in Nontraditional Occupations: Ecological Constructions
Authors: Shen-Miller David S. , Olson Deborah , Boling Timothy
Published: December 2009

The authors present Bronfenbrenner’s ecological model as a conceptual framework to explore interlocking systemic and interpersonal influences on the development and perpetuation of men’s gender role—related distress. To demonstrate the utility of this model, the authors present results from an exploratory qualitative study of men in nontraditional occupations. Using the constant comparison method, the authors’ analysis of multiple interviews with elementary educators and medical support staff unearthed interwoven themes among the effects of cultural notions of masculinity on relationships, job tasks, and perceptions of themselves as men. Expectations about men (e.g., that men confront danger, remain calm in chaotic situations, and/or are predators) affected hiring decisions and interactions with colleagues, limited the scope of the men’s work, and provided opportunities to reinforce traditional notions of masculinity and affirm the value of masculinity in their occupations. These different experiences all interacted to inform participants’ senses of themselves as men.
The Maturation of Synthetic Scaffolds for Osteochondral Donor Sites of the Knee
Authors: Bedi Asheesh , Foo Li Foong , Williams Riley J. , Potter Hollis G. ,   the Cartilage Study Group
Published: December 2009

Objective:

The purpose of this study was to analyze the morphological imaging characteristics and incorporation of TruFit bone graft substitute (BGS) plugs using cartilage-sensitive magnetic resonance imaging (MRI) and quantitative T2 mapping.

Design:

Twenty-six patients (mean age, 28.72 years; range, 11-56 years) underwent osteochondral autologous transplantation (OATS) for chondral defects with filling of the knee joint donor sites using Trufit BGS plugs. The mean follow-up interval between implantation and MRI analysis was 21.3 months (range, 6-39 months). During this period, 43 cartilage-sensitive and 25 quantitative T2-mapping MRI studies were performed. The donor sites were assessed for plug and interface morphology, displacement, hypertrophy, subchondral edema, presence of bony overgrowth, percentage fill, and degree of incorporation. T2 relaxation times were measured for the superficial and deep layers of the repair tissue. A linear regression and correlational analysis was performed with Bonferroni correction, and P < 0.05 was defined as significant.

Results:

Longitudinal analysis revealed favorable plug appearance at early follow-up (≤6 months), with 75% of plugs demonstrating flush morphology and 78% demonstrating near complete to complete fill. Plug appearance deteriorated at intermediate follow-up (~12 months), with only 26% of plugs demonstrating flush morphology and 52% with near complete or complete fill. Plug appearance substantially improved with longer follow-up (≥16 months), with 70% of plugs demonstrating flush morphology and 90% demonstrating near complete or complete fill. Interface resorption was common at ~12 months ( P < 0.0001) and was associated with older age ( P = 0.01) or a single-plug configuration ( P = 0.04). T2 values for the repair cartilage approached that of normal cartilage with increasing duration after surgery ( P < 0.004), more so for single- compared with multiple-plug configurations ( P = 0.03).

Conclusions:

The Trufit BGS plug demonstrates a predictable pattern of postoperative maturation on MRI images that parallels its biological incorporation. An intermediate postoperative interval can be associated with unfavorable MRI findings. However, the plug appearance significantly improves with greater postoperative duration and has mean T2 relaxation times that approach those of normal articular cartilage.
Idiopathic CD4+ T-cell lymphocytopenia is associated with impaired membrane expression of the chemokine receptor CXCR4
Authors: Scott-Algara Daniel , Balabanian Karl , Chakrabarti Lisa A. , Mouthon Luc , Dromer Françoise , Didier Céline , Arenzana-Seisdedos Fernando , Lortholary Olivier
Published: December 2009

Idiopathic CD4+ T-cell lymphocytopenia (ICL) is a rare acquired T-cell immunodeficiency of unknown pathogenic basis. Six adults with ICL who developed opportunistic infections were investigated using extensive immunophenotyping analysis and functional evaluation of the chemokine receptor CXCR4. For all 6 patients studied, a profound defect in CXCR4 expression was detected at the surface of CD4+ T lymphocytes, in association with an abnormal intracellular accumulation of CXCR4 and of its natural ligand, the chemokine CXCL12. For all patients studied, CD4+ T-cell chemotactic response toward CXCL12 was decreased, whereas sensitivity to CXCL8 was preserved. CXCR4 recovery after ligand-induced endocytosis was impaired in ICL CD4+ T cells. Upon in vitro addition of interleukin-2 (IL-2), membrane expression of CXCR4 returned to normal levels in 5 of 6 patients, whereas intracellular accumulation of CXCR4 and CXCL12 disappeared. Upon therapeutic administration of IL-2, CD4+ T-cell count and membrane CXCR4 expression and function improved over time in 3 of 4 patients treated. Therefore, our data indicate that ICL is associated with defective surface expression of CXCR4, which may be reversed by IL-2.
Placenta growth factor in sickle cell disease: association with hemolysis and inflammation
Authors: Brittain Julia E. , Hulkower Ben , Jones Susan K. , Strayhorn Dell , De Castro Laura , Telen Marilyn J. , Orringer Eugene P. , Hinderliter Alan , Ataga Kenneth I.
Published: December 2009

Placenta growth factor (PlGF) is released by immature erythrocytes and is elevated in sickle cell disease (SCD). Previous data generated in vitro suggest that PlGF may play a role in the pathophysiology of SCD-associated pulmonary hypertension (PHT) by inducing the release of the vasoconstrictor, endothelin-1. In this cross-sectional study of 74 patients with SCD, we confirm that PlGF is significantly elevated in SCD compared with healthy control subjects. We found significantly higher levels of PlGF in SCD patients with PHT but observed no association of PlGF with the frequency of acute pain episodes or history of acute chest syndrome. The observed correlation between PlGF and various measures of red cell destruction suggests that hemolysis, and the resultant erythropoietic response, results in the up-regulation of PlGF. Although relatively specific, PlGF, as well as N-terminal pro-brain natriuretic peptide and soluble vascular cell adhesion molecule, has low predictive accuracy for the presence of PHT. Prospective studies are required to conclusively define the contribution of PlGF to the pathogenesis of PHT and other hemolytic complications in SCD.
CC chemokine receptor 7 and 9 double-deficient hematopoietic progenitors are severely impaired in seeding the adult thymus
Authors: Krueger Andreas , Willenzon Stefanie , Łyszkiewicz Marcin , Kremmer Elisabeth , Förster Reinhold
Published: December 2009

T-cell development depends on recruitment of bone marrow–derived precursor cells to the thymus via a multistep adhesion cascade involving the chemokine receptor CCR9. However, CCR9 deficiency does not result in complete abrogation of progenitor entry into the adult thymus. Therefore, we tested the hypothesis that additional chemokine/chemokine receptor systems might play a role in this process. To this end, we generated mice deficient in both CCR9 and CCR7. Deficiency in both chemokine receptors resulted in severely reduced numbers of early T-cell progenitors and in near-complete abrogation of thymus reconstitution. Progenitors in bone marrow and peripheral blood remained largely unaffected in CCR7−/−CCR9−/− mice, and direct intrathymic transfer of precursors from CCR7−/−CCR9−/− mice as well as single-mutant mice showed that intrathymic differentiation of these precursors remained functional. Thus, our data reveal a previously unrecognized role of CCR7 in progenitor seeding of the adult thymus, which is largely masked by compensatory effects of CCR9 signals. In turn, CCR7 signals can partially compensate for CCR9 signals, thus explaining the rather mild phenotype of CCR9−/− mice with respect to progenitor seeding.
Membrane remodeling during reticulocyte maturation
Authors: Liu Jing , Guo Xinhua , Mohandas Narla , Chasis Joel A. , An Xiuli
Published: December 2009

The transition of reticulocytes into erythrocytes is accompanied by extensive changes in the structure and properties of the plasma membrane. These changes include an increase in shear resistance, loss of surface area, and acquisition of a biconcave shape. The processes by which these changes are effected have remained largely undefined. Here we examine how the expression of 30 distinct membrane proteins and their interactions change during murine reticulocyte maturation. We show that tubulin and cytosolic actin are lost, whereas the membrane content of myosin, tropomyosin, intercellular adhesion molecule-4, glucose transporter-4, Na-K-ATPase, sodium/hydrogen exchanger 1, glycophorin A, CD47, Duffy, and Kell is reduced. The degradation of tubulin and actin is, at least in part, through the ubiquitin-proteasome degradation pathway. In regard to the protein-protein interactions, the formation of membrane-associated spectrin tetramers from dimers is unperturbed, whereas the interactions responsible for the formation of the membrane-skeletal junctions are weaker in reticulocytes, as is the attachment of transmembrane proteins to these structures. This weakness, in part, results from the elevated phosphorylation of 4.1R in reticulocytes, which leads to a decrease in shear resistance by reducing its interaction with spectrin and actin. These observations begin to unravel the mechanistic basis of crucial changes accompanying reticulocyte maturation.
Acute erythroid leukemia: a reassessment using criteria refined in the 2008 WHO classification
Authors: Hasserjian Robert P. , Zuo Zhuang , Garcia Christine , Tang Guilin , Kasyan Armen , Luthra Rajyalakshmi , Abruzzo Lynne V. , Kantarjian Hagop M. , Medeiros L. Jeffrey , Wang Sa A.
Published: December 2009

Acute erythroid leukemia (AEL) is a rare type of acute myeloid leukemia (AML) for which diagnostic criteria have been refined in the 2008 World Health Organization (WHO) classification of AML. The relationship of AEL to myelodysplastic syndromes (MDSs) and to AML with myelodysplasia-related changes (AML-MRC) is not clearly defined. We conducted a retrospective, multi-institutional study of patients with AEL and compared them with patients with MDS or AML-MRC with erythroid hyperplasia (≥ 50% erythroid cells). Among a total of 124 patients with AEL, 32% had a history of MDS or chronic cytopenia, 32% had therapy-related disease, and 35% had de novo disease. Sixty-four percent of patients had unfavorable AML risk-group karyotypes. FLT3 and RAS mutations were infrequent, occurring in 6% and 2%, respectively. The median overall survival (OS) of all AEL patients was 8 months, comparable with that of patients with MDS or AML-MRC with erythroid hyperplasia. The OS was related to cytogenetic risk group, but not blast count or morphologic dysplasia. Our findings suggest that AEL is in the continuum of MDS and AML with erythroid hyperplasia, where karyotype rather than an arbitrary blast cutoff represents the most important prognostic factor.
Perforin activates clathrin- and dynamin-dependent endocytosis, which is required for plasma membrane repair and delivery of granzyme B for granzyme-mediated apoptosis
Authors: Thiery Jerome , Keefe Dennis , Saffarian Saviz , Martinvalet Denis , Walch Michael , Boucrot Emmanuel , Kirchhausen Tomas , Lieberman Judy
Published: December 2009

Cytotoxic T lymphocytes and natural killer cells destroy target cells via the polarized exocytosis of lytic effector proteins, perforin and granzymes, into the immunologic synapse. How these molecules enter target cells is not fully understood. It is debated whether granzymes enter via perforin pores formed at the plasma membrane or whether perforin and granzymes are first endocytosed and granzymes are then released from endosomes into the cytoplasm. We previously showed that perforin disruption of the plasma membrane induces a transient Ca2+ flux into the target cell that triggers a wounded membrane repair response in which lysosomes and endosomes donate their membranes to reseal the damaged membrane. Here we show that perforin activates clathrin- and dynamin-dependent endocytosis, which removes perforin and granzymes from the plasma membrane to early endosomes, preserving outer membrane integrity. Inhibiting clathrin- or dynamin-dependent endocytosis shifts death by perforin and granzyme B from apoptosis to necrosis. Thus by activating endocytosis to preserve membrane integrity, perforin facilitates granzyme uptake and avoids the proinflammatory necrotic death of a membrane-damaged cell.
Reconstructing nonlinear dynamic models of gene regulation using stochastic sampling
Authors: Mazur Johanna , Ritter Daniel , Reinelt Gerhard , Kaderali Lars
Published: December 2009

Background

The reconstruction of gene regulatory networks from time series gene expression data is one of the most difficult problems in systems biology. This is due to several reasons, among them the combinatorial explosion of possible network topologies, limited information content of the experimental data with high levels of noise, and the complexity of gene regulation at the transcriptional, translational and post-translational levels. At the same time, quantitative, dynamic models, ideally with probability distributions over model topologies and parameters, are highly desirable.

Results

We present a novel approach to infer such models from data, based on nonlinear differential equations, which we embed into a stochastic Bayesian framework. We thus address both the stochasticity of experimental data and the need for quantitative dynamic models. Furthermore, the Bayesian framework allows it to easily integrate prior knowledge into the inference process. Using stochastic sampling from the Bayes' posterior distribution, our approach can infer different likely network topologies and model parameters along with their respective probabilities from given data. We evaluate our approach on simulated data and the challenge #3 data from the DREAM 2 initiative. On the simulated data, we study effects of different levels of noise and dataset sizes. Results on real data show that the dynamics and main regulatory interactions are correctly reconstructed.

Conclusions

Our approach combines dynamic modeling using differential equations with a stochastic learning framework, thus bridging the gap between biophysical modeling and stochastic inference approaches. Results show that the method can reap the advantages of both worlds, and allows the reconstruction of biophysically accurate dynamic models from noisy data. In addition, the stochastic learning framework used permits the computation of probability distributions over models and model parameters, which holds interesting prospects for experimental design purposes.
A white-box approach to microarray probe response characterization: the BaFL pipeline
Authors: Thompson Kevin J , Deshmukh Hrishikesh , Solka Jeffrey L , Weller Jennifer W
Published: December 2009

Background

Microarrays depend on appropriate probe design to deliver the promise of accurate genome-wide measurement. Probe design, ideally, produces a unique probe-target match with homogeneous duplex stability over the complete set of probes. Much of microarray pre-processing is concerned with adjusting for non-ideal probes that do not report target concentration accurately. Cross-hybridizing probes (non-unique), probe composition and structure, as well as platform effects such as instrument limitations, have been shown to affect the interpretation of signal. Data cleansing pipelines seldom filter specifically for these constraints, relying instead on general statistical tests to remove the most variable probes from the samples in a study. This adjusts probes contributing to ProbeSet (gene) values in a study-specific manner. We refer to the complete set of factors as biologically applied filter levels (BaFL) and have assembled an analysis pipeline for managing them consistently. The pipeline and associated experiments reported here examine the outcome of comprehensively excluding probes affected by known factors on inter-experiment target behavior consistency.

Results

We present here a 'white box' probe filtering and intensity transformation protocol that incorporates currently understood factors affecting probe and target interactions; the method has been tested on data from the Affymetrix human GeneChip HG-U95Av2, using two independent datasets from studies of a complex lung adenocarcinoma phenotype. The protocol incorporates probe-specific effects from SNPs, cross-hybridization and low heteroduplex affinity, as well as effects from scanner sensitivity, sample batches, and includes simple statistical tests for identifying unresolved biological factors leading to sample variability. Subsequent to filtering for these factors, the consistency and reliability of the remaining measurements is shown to be markedly improved.

Conclusions

The data cleansing protocol yields reproducible estimates of a given probe or ProbeSet's (gene's) relative expression that translates across datasets, allowing for credible cross-experiment comparisons. We provide supporting evidence for the validity of removing several large classes of probes, and for our approaches for removing outlying samples. The resulting expression profiles demonstrate consistency across the two independent datasets. Finally, we demonstrate that, given an appropriate sampling pool, the method enhances the t-test's statistical power to discriminate significantly different means over sample classes.
Keratin 18 attenuates estrogen receptor α-mediated signaling by sequestering LRP16 in cytoplasm
Authors: Meng Yuanguang , Wu Zhiqiang , Yin Xiaoyun , Zhao Yali , Chen Meixia , Si Yiling , Yang Jie , Fu Xiaobing , Han Weidong
Published: December 2009

Background

Oncogenesis in breast cancer is often associated with excess estrogen receptor α(ERα) activation and overexpression of its coactivators. LRP16 is both an ERα target gene and an ERα coactivator, and plays a crucial role in ERα activation and proliferation of MCF-7 breast cancer cells. However, the regulation of the functional availability of this coactivator protein is not yet clear.

Results

Yeast two-hybrid screening, GST pulldown and coimmunoprecipitation (CoIP) identified the cytoplasmic intermediate filament protein keratin 18 (K18) as a novel LRP16-interacting protein. Fluorescence analysis revealed that GFP-tagged LRP16 was primarily localized in the nuclei of mock-transfected MCF-7 cells but was predominantly present in the cytoplasm of K18-transfected cells. Immunoblotting analysis demonstrated that the amount of cytoplasmic LRP16 was markedly increased in cells overexpressing K18 whereas nuclear levels were depressed. Conversely, knockdown of endogenous K18 expression in MCF-7 cells significantly decreased the cytoplasmic levels of LRP16 and increased levels in the nucleus. CoIP failed to detect any interaction between K18 and ERα, but ectopic expression of K18 in MCF-7 cells significantly blunted the association of LRP16 with ERα, attenuated ERα-activated reporter gene activity, and decreased estrogen-stimulated target gene expression by inhibiting ERα recruitment to DNA. Furthermore, BrdU incorporation assays revealed that K18 overexpression blunted the estrogen-stimulated increase of S-phase entry of MCF-7 cells. By contrast, knockdown of K18 in MCF-7 cells significantly increased ERα-mediated signaling and promoted cell cycle progression.

Conclusions

K18 can effectively associate with and sequester LRP16 in the cytoplasm, thus attenuating the final output of ERα-mediated signaling and estrogen-stimulated cell cycle progression of MCF-7 breast cancer cells. Loss of K18 increases the functional availability of LRP16 to ERα and promotes the proliferation of ERα-positive breast tumor cells. K18 plays an important functional role in regulating the ERα signaling pathway.
Production and characterization of recombinant pertactin, fimbriae 2 and fimbriae 3 from Bordetella pertussis
Authors: Xu Yinghua , Wang Yaying , Tan Yajun , Zhang Huajie , Wu Lijie , Wang Lichan , Hou Qiming , Zhang Shumin
Published: December 2009

Background

Bordetella pertussisis a causative agent of pertussis or whooping cough in humans. Pertactin (Prn), fimbriae 2 (Fim2) and fimbriae 3 (Fim3) ofB. pertussisare important virulence factors and immunogens which have been included in some acellular pertussis vaccines. In this present study, we cloned, expressed and purified Prn, Fim2 and Fim3, respectively. The immunogenicity and protective efficacy of the three recombinant proteins (rPrn, rFim2 and rFim3) were investigated in mouse model.

Results

Three recombinant proteins with amount of 12 to 25 mg/L were produced. Compared to the control mice only immunized with adjuvant, serum IgG antibody responses were significantly induced in the mice immunized with rPrn, rFim2 or rFim3 (P< 0.001 for all three proteins). Furthermore, T cell responses characteristic of increased production of IL-2 and TNF-α (only for rPrn) were elicited in the mice immunized with the three proteins (P< 0.05 for all three proteins). Immunization with rPrn, but not with rFim2 or rFim3, significantly enhanced clearance of bacteria in the lungs of mice after intranasal challenge withB. pertussis(P< 0.05). When tested in a lethal intracerebral infection model, certain protection was observed in mice immunized with rPrn.

Conclusions

We have developed an efficient method to produce large amounts of rPrn, rFim2, and rFim3 fromB. pertussis. The three recombinant proteins induced both humoral and cellular immune responses in mice. Immunization with rPrn also conferred protection against pertussis in mouse infection models. Our results indicated that the recombinant proteins still retain their immunological properties and highlighted the potential of the recombinant proteins for the future development of theB. pertussisvaccines.
Restoration of contact inhibition in human glioblastoma cell lines after MIF knockdown
Authors: Schrader Jörg , Deuster Oliver , Rinn Birgit , Schulz Martina , Kautz Andreas , Dodel Richard , Meyer Bernhard , Al-Abed Yousef , Balakrishnan Karthikeyan , Reese Jens P , Bacher Michael
Published: December 2009

Background

Studies of the role of the cytokine macrophage-migration-inhibitory-factor (MIF) in malignant tumors have revealed its stimulating influence on cell-cycle progression, angiogenesis and anti-apoptosis.

Results

Here we show that in vitro targeting MIF in cultures of human malignant glioblastoma cells by either antisense plasmid introduction or anti-MIF antibody treatment reduced the growth rates of tumor cells. Of note is the marked decrease of proliferation under confluent and over-confluent conditions, implying a role of MIF in overcoming contact inhibition. Several proteins involved in contact inhibition including p27, p21, p53 and CEBPalpha are upregulated in the MIF antisense clones indicating a restoration of contact inhibition in the tumor cells. Correspondingly, we observed a marked increase in MIF mRNA and protein content under higher cell densities in LN18 cells. Furthermore, we showed the relevance of the enzymatic active site of MIF for the proliferation of glioblastoma cells by using the MIF-tautomerase inhibitor ISO-1.

Conclusion

Our study adds another puzzle stone to the role of MIF in tumor growth and progression by showing the importance of MIF for overcoming contact inhibition.
Management of gastro-bronchial fistula complicating a subtotal esophagectomy: a case report
Authors: Martin-Smith James D , Larkin John O , O'Connell Finbar , Ravi Narayanasamy , Reynolds John Vincent
Published: December 2009

Background

The development of a fistula between the tracheobronchial tree and the gastric conduit post esophagectomy is a rare and often fatal complication.

Case presentation

A 68 year old man underwent radical esophagectomy for esophageal adenocarcinoma. On postoperative day 14 the nasogastric drainage bag dramatically filled with air, without deterioration in respiratory function or progressive sepsis. A fiberoptic bronchoscopy was performed which demonstrated a gastro-bronchial fistula in the posterior aspect of the left main bronchus. He was managed conservatively with antibiotics, enteral nutrition via jejunostomy, and non-invasive respiratory support. A follow- up bronchoscopy 60 days after the diagnostic bronchoscopy, confirmed spontaneous closure of the fistula

Conclusions

This is the first such case where a conservative approach with no surgery or endoprosthesis resulted in a successful outcome, with fistula closure confirmed at subsequent bronchoscopy. Our experience would suggest that in very carefully selected cases where bronchopulmonary contamination from the fistula is minimal or absent, there is no associated inflammation of the tracheobronchial tree and the patient is stable from a respiratory point of view without evidence of sepsis, there may be a role for a trial of conservative management.
Prediction of breast self-examination in a sample of Iranian women: an application of the Health Belief Model
Authors: Tavafian Sedigheh Sadat , Hasani Laleh , Aghamolaei Teamur , Zare Shahram , Gregory David
Published: December 2009

Background

Iranian women, many of whom live in small cities, have limited access to mammography and clinical breast examinations. Thus, breast self examination (BSE) becomes an important and necessary approach to detecting this disease in its early stages in order to limit its resultant morbidity and mortality. This study examined constructs arising from the Health Belief Model as predictors of breast self examination behavior in a sample of women living in Bandar Abbas, Iran.

Methods

This study was conducted in eight health centers located in Bandar Abbas, Iran. The sample consisted of 240 eligible women who were selected from referrals to the centers. The inclusion criteria were as follows: aged 30 years and over; and able to read and write Farsi. Women with breast cancer, who were pregnant, or breast feeding, were excluded from the study. Data were collected by using a self administered questionnaire which included demographic characteristics and Champion's Health Belief Model Scale. This instrument measures the concepts of disease susceptibility (3 items), seriousness (6 items), benefits (4 items), barriers (8 items) and self-efficacy (10 items).

Results

The subjects' mean age was 37.2 (SD = 6.1) years. Just under a third of the subjects (31.7%) had performed BSE in the past and 7.1% of them performed it at least monthly. Perceived benefits and perceived self-efficacy of the women who performed BSE were significantly higher compared with women who did not practice BSE (p < 0.03). Furthermore, perceived barriers were lower among those who had performed BSE (p < 0.001). Logistic regression analysis indicated that women who perceived fewer barriers (OR: 0.70, 95% CI: 0.63-0.77, p < 0.001) and had higher self-efficacy (OR: 1.08, 95% CI: 1.02-1.13, p = 0.003) were more likely to perform BSE (R2 = 0.52).

Conclusion

Findings from this study indicated that perceived barriers and perceived self-efficacy could be predictors of BSE behavior among the sample of women. Therefore, BSE training programs that emphasize self-efficacy and address perceived barriers are recommended.
Rapid spread of complex change: a case study in inpatient palliative care
Authors: Penna Richard Della , Martel Helene , Neuwirth Esther B , Rice Jennifer , Filipski Marta I , Green Jennifer , Bellows Jim
Published: December 2009

Background

Based on positive findings from a randomized controlled trial, Kaiser Permanente's national executive leadership group set an expectation that all Kaiser Permanente and partner hospitals would implement a consultative model of interdisciplinary, inpatient-based palliative care (IPC). Within one year, the number of IPC consultations program-wide increased almost tenfold from baseline, and the number of teams nearly doubled. We report here results from a qualitative evaluation of the IPC initiative after a year of implementation; our purpose was to understand factors supporting or impeding the rapid and consistent spread of a complex program.

Methods

Quality improvement study using a case study design and qualitative analysis of in-depth semi-structured interviews with 36 national, regional, and local leaders.

Results

Compelling evidence of impacts on patient satisfaction and quality of care generated 'pull' among adopters, expressed as a remarkably high degree of conviction about the value of the model. Broad leadership agreement gave rise to sponsorship and support that permeated the organization. A robust social network promoted knowledge exchange and built on an existing network with a strong interest in palliative care. Resource constraints, pre-existing programs of a different model, and ambiguous accountability for implementation impeded spread.

Conclusions

A complex, hospital-based, interdisciplinary intervention in a large health care organization spread rapidly due to a synergy between organizational 'push' strategies and grassroots-level pull. The combination of push and pull may be especially important when the organizational context or the practice to be spread is complex.
Differential expression of apoptotic genes PDIA3 and MAP3K5 distinguishes between low- and high-risk prostate cancer
Authors: Pressinotti Nicole Chui , Klocker Helmut , Schäfer Georg , Luu Van-Duc , Ruschhaupt Markus , Kuner Ruprecht , Steiner Eberhard , Poustka Annemarie , Bartsch Georg , Sültmann Holger
Published: December 2009

Background

Despite recent progress in the identification of genetic and molecular alterations in prostate cancer, markers associated with tumor progression are scarce. Therefore precise diagnosis of patients and prognosis of the disease remain difficult. This study investigated novel molecular markers discriminating between low and highly aggressive types of prostate cancer.

Results

Using 52 microdissected cell populations of low- and high-risk prostate tumors, we identified via global cDNA microarrays analysis almost 1200 genes being differentially expressed among these groups. These genes were analyzed by statistical, pathway and gene enrichment methods. Twenty selected candidate genes were verified by quantitative real time PCR and immunohistochemistry. In concordance with the mRNA levels, two genes MAP3K5 and PDIA3 exposed differential protein expression. Functional characterization of PDIA3 revealed a pro-apoptotic role of this gene in PC3 prostate cancer cells.

Conclusions

Our analyses provide deeper insights into the molecular changes occurring during prostate cancer progression. The genes MAP3K5 and PDIA3 are associated with malignant stages of prostate cancer and therefore provide novel potential biomarkers.
The GYMSSA trial: a prospective randomized trial comparing gastrectomy, metastasectomy plus systemic therapy versus systemic therapy alone
Authors: Kerkar Sid P , Kemp Clinton D , Duffy Austin , Kammula Udai S , Schrump David S , Kwong King F , Quezado Martha , Goldspiel Barry R , Venkatesan Aradhana , Berger Ann , Walker Melissa , Toomey Mary Ann , Steinberg Seth M , Giaccone Guiseppe , Rosenberg Steven A , Avital Itzhak
Published: December 2009

Background

The standard of care for metastatic gastric cancer (MGC) is systemic chemotherapy which leads to a median survival of 6-15 months. Survival beyond 3 years is rare. For selected groups of patients with limited MGC, retrospective studies have shown improved overall survival following gastrectomy and metastasectomies including peritoneal stripping with continuous hyperthermic peritoneal perfusion (CHPP), liver resection, and pulmonary resection. Median survival after liver resection for MGC is up to 34 months, with a five year survival rate of 24.5%. Similarly, reported median survival after pulmonary resection of MGC is 21 months with long term survival of greater than 5 years a possibility. Several case reports and small studies have documented evidence of long-term survival in select individuals who undergo CHPP for MGC.

Design

The GYMSSA trial is a prospective randomized trial for patients with MGC. It is designed to compare two therapeutic approaches: gastrectomy with metastasectomy plus systemic chemotherapy (GYMS) versus systemic chemotherapy alone (SA). Systemic therapy will be composed of the FOLFOXIRI regimen. The aim of the study is to evaluate overall survival and potential selection criteria to determine those patients who may benefit from surgery plus systemic therapy. The study will be conducted by the Surgery Branch at the National Cancer Institute (NCI), National Institutes of Health (NIH) in Bethesda, Maryland. Surgeries and followup will be done at the NCI, and chemotherapy will be given by either the local oncologist or the medical oncology branch at NCI.

Trial Registration

ClinicalTrials.gov ID. NCT00941655
Improved quality monitoring of multi-center acupuncture clinical trials in China
Authors: Zhao Ling , Liang Fan-rong , Li Ying , Zhang Fu-wen , Zheng Hui , Wu Xi
Published: December 2009

Background

In 2007, the Chinese Science Division of the State Administration of Traditional Chinese Medicine(TCM) convened a special conference to discuss quality control for TCM clinical research. Control and assurance standards were established to guarantee the quality of clinical research. This paper provides practical guidelines for implementing strict and reproducible quality control for acupuncture randomized controlled trials (RCTs).

Methods

A standard quality control program (QCP) was established to monitor the quality of acupuncture trials. Case report forms were designed; qualified investigators, study personnel and data management personnel were trained. Monitors, who were directly appointed by the project leader, completed the quality control programs. They guaranteed data accuracy and prevented or detected protocol violations. Clinical centers and clinicians were audited, the randomization system of the centers was inspected, and the treatment processes were audited as well. In addition, the case report forms were reviewed for completeness and internal consistency, the eligibility and validity of the patients in the study was verified, and data was monitored for compliance and accuracy.

Results and discussion

The monitors complete their reports and submit it to quality assurance and the sponsors. Recommendations and suggestions are made for improving performance. By holding regular meetings to discuss improvements in monitoring standards, the monitors can improve quality and efficiency.

Conclusions

Supplementing and improving the existed guidelines for quality monitoring will ensure that large multi-centre acupuncture clinical trials will be considered as valid and scientifically stringent as pharmaceutical clinical trials. It will also develop academic excellence and further promote the international recognition of acupuncture.
Toxic epidermal necrolysis following treatment of pseudotumour cerebri: a case report
Authors: El Ghonemi Mohamed , Omar Hesham R , Rashad Rania , Kolla Jaya , Mangar Devanand , Camporesi Enrico
Published: December 2009

Toxic Epidermal Necrolysis and Steven-Johnson syndrome are entities on a spectrum of cutaneous reactions that usually occur as an idiosyncratic reaction to certain drugs. The distinction between TEN and SJS is based on the percentage of skin involved with SJS being less than 10% and TEN being more than 30%. They exhibit severe skin blistering and sloughing with mucosal involvement and can be fatal in many cases. Discontinuation of the offending agent is mandatory together with reduction of skin manipulation and avoiding infection. Plasmapharesis, intravenous immunoglobulins and immunosuppressants have been used with conflicting results. In this manuscript we are describing a 22 year old female patient from Egypt who presented with severe skin sloughing with mucosal involvement following carbamazepine therapy. The incriminated drug was discontinued and urgent life saving therapy in the form of broad spectrum antibiotic, immunosuppression with cyclophosphamide, Intensive Care Unit admission and nursing care was started followed by dramatic response. The clinical presentation, pathogenesis and modalities of treatment will be described in details.
The Systemic Inflammatory Response Syndrome (SIRS) in acutely hospitalised medical patients: a cohort study
Authors: Comstedt Pål , Storgaard Merete , Lassen Annmarie T
Published: December 2009

Background

Sepsis is an infection which has evoked a systemic inflammatory response. Clinically, the Systemic Inflammatory Response Syndrome (SIRS) is identified by two or more symptoms including fever or hypothermia, tachycardia, tachypnoea and change in blood leucocyte count. The relationship between SIRS symptoms and morbidity and mortality in medical emergency ward patients is unknown.

Methods

We conducted a prospective cohort study of the frequency of SIRS and its relationship to sepsis and death among acutely hospitalised medical patients. In 437 consecutive patients, SIRS status, blood pressure, infection and comorbidity on admission was registered together with 28-day mortality.

Results

A hundred and fifty-four patients (35%) had SIRS on admission, 211 patients (48%) had no SIRS, and 72 patients (16%) had insufficient data to evaluate their SIRS status. SIRS patients were 2.2 times more frequently infected, with 66/154 SIRS patients versus 41/211 non-SIRS patients: p < 0.001, relative risk (RR) 2.2 (95% confidence interval (CI) 1.6-3.1), and they had a 6.9 times higher 28-day mortality than non-SIRS patients with 15/154 SIRS patients versus 3/211 non-SIRS patients: p = 0.001, RR 6.9 (95% CI 2.0-23.3). Most of the deaths among patients with SIRS occurred among patients with malignant conditions. Septic shock developed in 4/154 (3%) of the patients with SIRS, whereas this occurred in only one of the 211 patients (0.5%) without SIRS on arrival: p = 0.08, RR 5.5 (95% CI 0.6-48.6).

Conclusion

We found SIRS status on admission to be moderately associated with infection and strongly related to 28-day mortality.