bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimation of treatment effect adjusting for dependent censoring using the IPCW method: an application to a large primary prevention study for coronary events (MEGA study)
Authors: Yoshida Mizuki , Matsuyama Yutaka , Ohashi Yasuo
Published: September 2007

Background The MEGA study is a randomized controlled trial conducted in Japan to evaluate the primary preventive effect of pravastatin against coronary heart disease (CHD), in which 8214 subjects are randomized to diet or diet plus pravastatin. Pravastatin reduces the incidence of CHD (hazard ratio = 0.67; 95%CI: 0.49—0.91). In the MEGA study, in addition to the usual loss to follow-up cases, there is another problem of drop-outs due to the refusal of further follow-up at 5 years.

Purpose To estimate the treatment effect adjusting for some types of dependent censorings observed in the MEGA study and to assess the sensitivity of standard analysis results for these censoring cases.

Methods The proposed method is a straightforward extension of the inverse probability of censoring weighted (IPCW) method for settings with more than one reason for censoring, where the propensities for drop-outs are modeled separately for each reason. Simulation studies are also conducted to compare the properties of the IPCW estimate with the standard analysis assuming independent censorings.

Results Simulation studies show that the IPCW estimate can correct for selection bias due to dependent censoring that can be explained by measured factors, while the standard analysis is biased. Applying the proposed method to the MEGA study data, several prognostic factors are associated with the censoring processes, and after adjusting for these dependent censorings, slightly larger treatment effects for pravastatin are observed for both CHD (primary endpoint) and stroke (secondary endpoint) events.

Limitations The method developed is based on the fundamental assumption of sequentially ignorable censoring.

Conclusions Our proposed method provides a valuable approach for estimating treatment effect adjusting for several types of dependent censorings. Dependent censorings observed in the MEGA study did not cause a severe selection bias attributable to the covariates and the results from the standard analysis were robust in relation to the censorings. Clinical Trials 2007; 4: 318—328. http:// ctj.sagepub.com
Witness, Democracy and Civil Society: Reflections on John Howard Yoder's Exilic Ecclesiology
Authors: Bourne Richard
Published: September 2007

This article examines the compatibility between an ecclesial focus in contemporary theological ethics and an account of democratic citizenship. It focuses on the work of the Mennonite theologian John Howard Yoder. It explores the use of a motif that appeared with increasing frequency in Yoder's later writings, and has yet to receive much substantial academic attention — that of exilic citizenship. It then notes parallels between this exilic ecclesiology and contemporary understandings of civil society. It concludes that an exilic reading of Christian witness provides a fruitful basis for a theology of democratic participation.
Emerging Powers of Influence
Authors: Pugsley Peter C. , Jia Gao
Published: September 2007

/ The focus of this study is the perceived influence of TV `anchors' (presenters) on Chinese television in the past 10 years or so, including the approaches and/or various institutional guidelines and disciplinary measures imposed by government departments and media institutions. Through the case of China Central Television (CCTV) and based on a theoretical framework that draws on the discourse of `news culture', the study explores the different types of `anchored' media presented in the genres of news and current affairs, and tracks the rise of four of China's most popular anchors in these genres. Using a combination of discourse, visual and policy analysis, this article illustrates how the popularity of high-profile anchor people in China since the mid-1990s has created a new type of influence, one not without its limitations but which may also contribute to a `public sphere' with Chinese characteristics.
CD74 induces TAp63 expression leading to B-cell survival
Authors: Lantner Frida , Starlets Diana , Gore Yael , Flaishon Liat , Yamit-Hezi Ayala , Dikstein Rivka , Leng Lin , Bucala Richard , Machluf Yossy , Oren Moshe , Shachar Idit
Published: September 2007

Most mature follicular B cells circulate within the periphery in a quiescent state, without actively contributing to an acute immune response. Lasting B-cell persistence in the periphery is dependent on survival signals that are transduced by cell surface receptors. We recently demonstrated that cell surface CD74 controls mature B-cell survival. Stimulation of cell surface CD74 leads to NF-κB activation, which enables entry of the stimulated B cells into the S phase, induction of DNA synthesis, and cell division, and augments the expression of survival genes. In the present study, we investigated CD74 target genes to determine the identities of the molecules whose expression is modulated by CD74, thereby regulating B-cell survival. We report that CD74 activates the p65 member of the NF-κB family, which in turn up-regulates the expression of p53-related TAp63 proteins. TAp63 then binds and transactivates the Bcl-2gene and induces the production of Bcl-2 protein, thereby providing the cells with increased survival capacity. Thus, the CD74/NF-κB/TAp63 axis defines a novel antiapoptotic pathway in mature B cells, resulting in the shaping of both the B-cell repertoire and the immune response.
Phase 2 study of pegylated liposomal doxorubicin in combination with interleukin-12 for AIDS-related Kaposi sarcoma
Authors: Little Richard F. , Aleman Karen , Kumar Pallavi , Wyvill Kathleen M. , Pluda James M. , Read-Connole Elizabeth , Wang Victoria , Pittaluga Stefania , Catanzaro Andrew T. , Steinberg Seth M. , Yarchoan Robert
Published: September 2007

Thirty-six patients with AIDS-associated Kaposi sarcoma (KS) requiring chemotherapy were treated for six 3-week cycles of pegylated liposomal doxorubicin (20 mg/m2) plus interleukin-12 (IL-12; 300 ng/kg subcutaneously twice weekly), followed by 500 ng/kg subcutaneous IL-12 twice weekly for up to 3 years. All received highly active antiretroviral therapy (HAART). Twenty-two had poor-prognosis KS (T1S1). Thirty patients had a major response, including 9 with complete response, yielding an 83.3% major response rate (95% confidence interval: 67.2%-93.6%). Median time to first response was 2 cycles. Median progression was not reached at median potential follow-up of 46.9 months. Of 27 patients with residual disease when starting maintenance IL-12, 15 had a new major response compared with this new baseline. The regimen was overall well tolerated; principal toxicities were neutropenia, anemia, transaminitis, and neuropsychiatric toxicity. Patients had increases in serum IL-12, interferon gamma, and inducible protein-10 (IP-10), and these remained increased at weeks 18 and 34. The regimen of IL-12 plus liposomal doxorubicin yielded rapid tumor responses and a high response rate in patients with AIDS-KS receiving HAART, and responses were sustained on IL-12 maintenance therapy. A randomized trial of IL-12 in this setting may be warranted. This study is registered at http://www.clinicaltrials.gov as no. NCT00020449.
Dynamic expression of ancient and novel molluscan shell genes during ecological transitions
Authors: Jackson Daniel J , Wörheide Gert , Degnan Bernard M
Published: September 2007

Background

The Mollusca constitute one of the most morphologically and ecologically diverse metazoan phyla, occupying a wide range of marine, terrestrial and freshwater habitats. The evolutionary success of the molluscs can in part be attributed to the evolvability of the external shell. Typically, the shell first forms during embryonic and larval development, changing dramatically in shape, colour and mineralogical composition as development and maturation proceeds. Major developmental transitions in shell morphology often correlate with ecological transitions (e.g. from a planktonic to benthic existence at metamorphosis). While the genes involved in molluscan biomineralisation are beginning to be identified, there is little understanding of how these are developmentally regulated, or if the same genes are operational at different stages of the mollusc's life.

Results

Here we relate the developmental expression of nine genes in the tissue responsible for shell production – the mantle – to ecological transitions that occur during the lifetime of the tropical abalone Haliotis asinina (Vetigastropoda). Four of these genes encode evolutionarily ancient proteins, while four others encode secreted proteins with little or no identity to known proteins. Another gene has been previously described from the mantle of another haliotid vetigastropod. All nine genes display dynamic spatial and temporal expression profiles within the larval shell field and juvenile mantle.

Conclusion

These expression data reflect the regulatory complexity that underlies molluscan shell construction from larval stages to adulthood, and serves to highlight the different ecological demands placed on each stage. The use of both ancient and novel genes in all stages of shell construction also suggest that a core set of shell-making genes was provided by a shared metazoan ancestor, which has been elaborated upon to produce the range of molluscan shell types we see today.
Comparative phylogenomic analyses of teleost fish Hox gene clusters: lessons from the cichlid fish Astatotilapia burtoni
Authors: Hoegg Simone , Boore Jeffrey L , Kuehl Jennifer V , Meyer Axel
Published: September 2007

Background

Teleost fish have seven paralogous clusters of Hox genes stemming from two complete genome duplications early in vertebrate evolution, and an additional genome duplication during the evolution of ray-finned fish, followed by the secondary loss of one cluster. Gene duplications on the one hand, and the evolution of regulatory sequences on the other, are thought to be among the most important mechanisms for the evolution of new gene functions. Cichlid fish, the largest family of vertebrates with about 2500 species, are famous examples of speciation and morphological diversity. Since this diversity could be based on regulatory changes, we chose to study the coding as well as putative regulatory regions of their Hox clusters within a comparative genomic framework.

Results

We sequenced and characterized all seven Hox clusters of Astatotilapia burtoni, a haplochromine cichlid fish. Comparative analyses with data from other teleost fish such as zebrafish, two species of pufferfish, stickleback and medaka were performed. We traced losses of genes and microRNAs of Hox clusters, the medaka lineage seems to have lost more microRNAs than the other fish lineages. We found that each teleost genome studied so far has a unique set of Hox genes. The hoxb7a gene was lost independently several times during teleost evolution, the most recent event being within the radiation of East African cichlid fish. The conserved non-coding sequences (CNS) encompass a surprisingly large part of the clusters, especially in the HoxAa, HoxCa, and HoxDa clusters. Across all clusters, we observe a trend towards an increased content of CNS towards the anterior end.

Conclusion

The gene content of Hox clusters in teleost fishes is more variable than expected, with each species studied so far having a different set. Although the highest loss rate of Hox genes occurred immediately after whole genome duplications, our analyses showed that gene loss continued and is still ongoing in all teleost lineages. Along with the gene content, the CNS content also varies across clusters. The excess of CNS at the anterior end of clusters could imply a stronger conservation of anterior expression patters than those towards more posterior areas of the embryo.
The Fangshan/Family-based Ischemic Stroke Study In China (FISSIC) protocol
Authors: Tang Xun , Hu Yonghua , Chen Dafang , Zhan Siyan , Zhang Zongxin , Dou Huidong
Published: September 2007

Background

The exact etiology of ischemic stroke remains unclear, because multiple genetic predispositions and environmental risk factors may be involved, and their interactions dictate the complexity. Family-based studies provide unique features in design, while they are currently underrepresented for studies of ischemic stroke in developing countries. The Fangshan/Family-based Ischemic Stroke Study In China (FISSIC) program aims to conduct a genetic pedigree study of ischemic stroke in rural communities of China.

Methods/Design

The pedigrees of ischemic stroke with clear documentation are recruited by using the proband-initiated contact method, based on the stroke registry in hospital and communities. Blood samples and detailed information of pedigrees are collected through the health care network in the rural area, and prospective follow-up of the pedigrees cohort is scheduled. Complementary strategies of both family-based design and matched case-spousal control design are used, and comprehensive statistical methods will be implemented to ascertain potential complex genetic and environmental factors and their interactions as well.

Discussion

This study is complementary to other genetic pedigree studies of ischemic stroke, such as the Siblings With Ischemic Stroke Study (SWISS), which are established in developed countries. We describe the protocol of this family-based genetic epidemiological study that may be used as a new practical guideline and research paradigm in developing countries and facilitate initiatives of stroke study for international collaborations.
New active site oriented glyoxyl-agarose derivatives of Escherichia colipenicillin G acylase
Authors: Cecchini Davide A , Serra Immacolata , Ubiali Daniela , Terreni Marco , Albertini Alessandra M
Published: September 2007

Background

Immobilized Penicillin G Acylase (PGA) derivatives are biocatalysts that are industrially used for the hydrolysis of Penicillin G by fermentation and for the kinetically controlled synthesis of semi-synthetic β-lactam antibiotics. One of the most used supports for immobilization is glyoxyl-activated agarose, which binds the protein by reacting through its superficial Lys residues. Since in E. coli PGA Lys are also present near the active site, an immobilization that occurs through these residues may negatively affect the performance of the biocatalyst due to the difficult diffusion of the substrate into the active site. A preferential orientation of the enzyme with the active site far from the support surface would be desirable to avoid this problem.

Results

Here we report how it is possible to induce a preferential orientation of the protein during the binding process on aldehyde activated supports. A superficial region of PGA, which is located on the opposite side of the active site, is enriched in its Lys content. The binding of the enzyme onto the support is consequently forced through the Lys rich region, thus leaving the active site fully accessible to the substrate. Different mutants with an increasing number of Lys have been designed and, when active, immobilized onto glyoxyl agarose. The synthetic performances of these new catalysts were compared with those of the immobilized wild-type (wt) PGA. Our results show that, while the synthetic performance of the wt PGA sensitively decreases after immobilization, the Lys enriched mutants have similar performances to the free enzyme even after immobilization.

We also report the observations made with other mutants which were unable to undergo a successful maturation process for the production of active enzymes or which resulted toxic for the host cell.

Conclusion

The desired orientation of immobilized PGA with the active site freely accessible can be obtained by increasing the density of Lys residues on a predetermined region of the enzyme. The newly designed biocatalysts display improved synthetic performances and are able to maintain a similar activity to the free enzymes. Finally, we found that the activity of the immobilized enzyme proportionally improves with the number of introduced Lys.
Modulation by decitabine of gene expression and growth of osteosarcoma U2OS cells in vitro and in xenografts: Identification of apoptotic genes as targets for demethylation
Authors: Al-Romaih Khaldoun , Somers Gino R , Bayani Jane , Hughes Simon , Prasad Mona , Cutz Jean-Claude , Xue Hui , Zielenska Maria , Wang Yuzhuo , Squire Jeremy A
Published: September 2007

Background

Methylation-mediated silencing of genes is one epigenetic mechanism implicated in cancer. Studies regarding the role of modulation of gene expression utilizing inhibitors of DNA methylation, such as decitabine, in osteosarcoma (OS) have been limited. A biological understanding of the overall effects of decitabine in OS is important because this particular agent is currently undergoing clinical trials. The objective of this study was to measure the response of the OS cell line, U2OS, to decitabine treatment both in vitro and in vivo.

Results

Microarray expression profiling was used to distinguish decitabine-dependent changes in gene expression in U2OS cells, and to identify responsive loci with demethylated CpG promoter regions. U2OS xenografts were established under the sub-renal capsule of immune-deficient mice to study the effect of decitabine in vivo on tumor growth and differentiation. Reduced nuclear methylation levels could be detected in xenografts derived from treated mice by immunohistochemistry utilizing a 5-methylcytidine antibody. Decitabine treatment reduced tumor xenograft size significantly (p < 0.05). Histological analysis of treated U2OS xenograft sections revealed a lower mitotic activity (p < 0.0001), increased bone matrix production (p < 0.0001), and a higher number of apoptotic cells (p = 0.0329). Microarray expression profiling of U2OS cultured cells showed that decitabine treatment caused a significant induction (p < 0.0025) in the expression of 88 genes. Thirteen had a ≥2-fold change, 11 of which had CpG-island-associated promoters. Interestingly, 6 of these 11 were pro-apoptotic genes and decitabine resulted in a significant induction of cell death in U2OS cells in vitro (p < 0.05). The 6 pro-apoptotic genes (GADD45A, HSPA9B, PAWR, PDCD5, NFKBIA, and TNFAIP3) were also induced to ≥2-fold in vivo. Quantitative methylation pyrosequencing confirmed that the tested pro-apoptotic genes had CpG-island DNA demethylationas a result of U2OS decitabine treatment both in vitro and in xenografts

Conclusion

These data provide new insights regarding the use of epigenetic modifiers in OS, and have important implications for therapeutic trials involving demethylation drugs. Collectively, these data have provided biological evidence that one mode of action of decitabine may be the induction of apoptosis utilizing promoter-CpG demethylation of specific effectors in cell death pathways in OS.
Neuroimaging Revolutionizes Therapeutic Approaches to Chronic Pain
Authors: Borsook David , Moulton Eric A , Schmidt Karl F , Becerra Lino R
Published: September 2007

An understanding of how the brain changes in chronic pain or responds to pharmacological or other therapeutic interventions has been significantly changed as a result of developments in neuroimaging of the CNS. These developments have occurred in 3 domains: (1) Anatomical Imaging which has demonstrated changes in brain volume in chronic pain; (2) Functional Imaging (fMRI) that has demonstrated an altered state in the brain in chronic pain conditions including back pain, neuropathic pain, and complex regional pain syndromes. In addition the response of the brain to drugs has provided new insights into how these may modify normal and abnormal circuits (phMRI or pharmacological MRI); (3) Chemical Imaging (Magnetic Resonance Spectroscopy or MRS) has helped our understanding of measures of chemical changes in chronic pain. Taken together these three domains have already changed the way in which we think of pain – it should now be considered an altered brain state in which there may be altered functional connections or systems and a state that has components of degenerative aspects of the CNS.
Spectrocolorimetric assessment of cartilage plugs after autologous osteochondral grafting: correlations between color indices and histological findings in a rabbit model
Authors: Hattori Koji , Uematsu Kota , Tanikake Yohei , Habata Takashi , Tanaka Yasuhito , Yajima Hiroshi , Takakura Yoshinori
Published: September 2007

We investigated the use of a commercial spectrocolorimeter and the application of two color models (L* a* b* colorimetric system and spectral reflectance distribution) to describe and quantify cartilage plugs in a rabbit model of osteochondral autografting. Osteochondral plugs were removed and then replaced in their original positions in Japanese white rabbits. The rabbits were sacrificed at 4 or 12 weeks after the operation and cartilage samples were assessed using a spectrocolorimeter. The samples were retrospectively divided into two groups on the basis of the histological findings (group H: hyaline cartilage, successful; group F: fibrous tissue or fibrocartilage, failure) and investigated for possible significant differences in the spectrocolorimetric analyses between the two groups. Moreover, the relationships between the spectrocolorimetric indices and the Mankin histological score were examined. In the L* a* b* colorimetric system, the L* values were significantly lower in group H than in group F (P = 0.02), whereas the a* values were significantly higher in group H than in group F (P = 0.006). Regarding the spectral reflectance distribution, the spectral reflectance percentage 470 (SRP470) values, as a coincidence index for the spectral reflectance distribution (400 to 470 nm in wavelength) of the cartilage plugs with respect to intact cartilage, were 99.8 ± 6.7% in group H and 119.8 ± 10.6% in group F, and the difference between these values was significant (P = 0.005). Furthermore, the a* values were significantly correlated with the histological score (P = 0.004, r = -0.76). The SRP470 values were also significantly correlated with the histological score (P = 0.01, r = 0.67). Our findings demonstrate the ability of spectrocolorimetric measurements to predict the histological findings of cartilage plugs after autologous osteochondral grafting. In particular, the a* values and SRP470 values can be used to judge the surface condition of an osteochondral plug on the basis of objective data. Therefore, spectrocolorimetry may contribute to orthopedics, rheumatology and related research in arthritis, and arthroscopic use of this method may potentially be preferable for in vivo assessment.
Association of the microsatellite in the 3' untranslated region of the CD154 gene with rheumatoid arthritis in females from a Spanish cohort: a case-control study
Authors: Martin-Donaire Trinidad , Losada-Fernandez Ignacio , Perez-Chacon Gema , Rua-Figueroa Iñigo , Erausquin Celia , Naranjo-Hernandez Antonio , Rosado Silvia , Sanchez Florentino , Garcia-Saavedra Ayoze , Citores Maria Jesus , Vargas Juan A , Perez-Aciego Paloma
Published: September 2007

CD40–CD154 interaction is an important mediator of inflammation and has been implicated in T helper type 1-mediated autoimmune diseases including rheumatoid arthritis (RA). Linkage studies have shown association of markers in the proximity of the CD154 gene. In the present work we investigated whether specific allele variants of the microsatellite in the 3' UTR of the CD154 gene might modulate the risk of RA. The study, in a case-control setting, included 189 patients and 150 healthy controls from the Canary Islands, Spain. The 24CAs allele was less represented in female patients than in controls (0.444 in controls versus 0.307 in patients, P = 0.006, odds ratio (OR) 0.556, 95% confidence interval (CI) 0.372 to 0.831) but not in males (0.414 versus 0.408), and only when homozygous (P = 0.012; OR 0.35, 95% CI 0.16 to 0.77). We also verified that CD154 association with RA was independent of human leukocyte antigen (HLA) phenotype. A further functional study showed that after stimulation anti-CD3, CD154 mRNA was more stable in CD4+ T lymphocytes from patients with RA bearing the 24CAs allele (mRNA half-life 208 minutes) than in patients without the 24CAs allele (109 minutes, P = 0.009). However, a lower percentage of CD154+CD4+ T lymphocytes was seen in freshly isolated peripheral blood mononuclear cells from patients carrying 24CAs alleles (mean 4.28 versus 8.12; P = 0.033), and also in CD4+ T lymphocytes stimulated with anti-CD3 (median 29.40 versus 47.60; P = 0.025). These results were concordant with the smaller amounts of CD154 mRNA isolated from stimulated T lymphocytes with 24CAs alleles. The CD154 microsatellite therefore seems to affect the expression of the gene in a complex manner that implies not only mRNA stability. These data suggest that the CD154 microsatellite contributes to the regulation of mRNA and protein expression, although further studies will be necessary to elucidate its role in disease predisposition.
Interrelated modulation of endothelial function in Behcet's disease by clinical activity and corticosteroid treatment
Authors: Protogerou Athanase D , Sfikakis Petros P , Stamatelopoulos Kimon S , Papamichael Christos , Aznaouridis Kostas , Karatzis Emmanuil , Papaioannou Theodore G , Ikonomidis Ignatios , Kaklamanis Phedon , Mavrikakis Myron , Lekakis John
Published: September 2007

Corticosteroids are commonly used in empirical treatment of Behçet's disease (BD), a systemic inflammatory condition associated with reversible endothelial dysfunction. In the present study we aimed to dissect the effects of clinical disease activity and chronic or short-term corticosteroid treatment on endothelial function in patients with BD. In a case-control, cross-sectional study, we assessed endothelial function by endothelium dependent flow mediated dilatation (FMD) at the brachial artery of 87 patients, who either were or were not receiving chronic corticosteroid treatment, and exhibiting variable clinical disease activity. Healthy individuals matched for age and sex served as controls. Endothelial function was also assessed in a prospective study of 11 patients before and after 7 days of treatment with prednisolone given at disease relapse (20 mg/day). In the cross-sectional component of the study, FMD was lower in patients than in control individuals (mean ± standard error: 4.1 ± 0.4% versus 5.7 ± 0.2%, P = 0.003), whereas there was a significant interaction between the effects of corticosteroids and disease activity on endothelial function (P = 0.014, two-factor analysis of variance). Among patients with inactive BD, those who were not treated with corticosteroids (n = 33) had FMD comparable to that in healthy control individuals, whereas those treated with corticosteroids (n = 15) had impaired endothelial function (P = 0.023 versus the respective control subgroup). In contrast, among patients with active BD, those who were not treated with corticosteroids (n = 20) had lower FMD than control individuals (P = 0.007), but in those who were receiving corticosteroids (n = 19) the FMD values were comparable to those in control individuals. Moreover, FMD was significantly improved after 7 days of prednisolone administration (3.7 ± 0.9% versus 7.6 ± 1.4%, P = 0.027). Taken together, these results imply that although corticosteroid treatment may impair endothelial function per se during the remission phase of the inflammatory process, it restores endothelial dysfunction during active BD by counteracting the harmful effects of relapsing inflammation.
Quantitative gait analysis as a method to assess mechanical hyperalgesia modulated by disease-modifying antirheumatoid drugs in the adjuvant-induced arthritic rat
Authors: Simjee Shabana Usman , Jawed Huma , Quadri Javeria , Saeed Sheikh Arshad
Published: September 2007

In the present study, azothioprine, chloroquine, D-penicillamine, methotrexate and sodium aurothiomalate (gold salt) were evaluated for possible disease-modifying effects in the adjuvant-induced arthritis model of human rheumatoid arthritis in rats. Gait analysis was used to examine the role of disease-modifying antirheumatic drugs in the development of pain. Body weights were also measured to monitor the progression of disease and the systemic antiarthritic effects of the test compounds used in this study, as well as their systemic toxicity. Our results showed that azothioprine (5 mg/kg/day), chloroquine (12.5 mg/kg/day), sodium aurothiomalate (2.5 mg/kg/day) and methotrexate (1 mg/kg/week) not only inhibited the macroscopic changes such as erythema and swelling of limbs, but also exhibited significant reversal of gait deficits seen in the untreated or saline-treated arthritic rats. No reduction in the body weights were observed in the arthritic rats treated with azothioprine, chloroquine, sodium aurothiomalate and methotrexate. D-Penicillamine (12.5 mg/kg/day), however, showed a significant reduction (P < 0.03) in the body weights of the arthritic rats over a period of 22 days; furthermore, it was unable to show any reduction in arthritic score (P < 0.1). In earlier experiments, chloroquine and methotrexate failed to suppress carageenan-induced edema, suggesting that the mode of antiarthritic action may be different from those of nonsteroidal anti-inflammatory agents. Since these disease-modifying antirheumatic drugs are reported to have an immunomodulatory role, especially the gold salt, which influences the monocyte–macrophage system, it is suggested that the observed antiarthritic effects of disease-modifying antirheumatic drugs may be partly attributed to their immunomodulatory activity.
Role of human HGFIN/nmbin breast cancer
Authors: Metz Rebecca L , Patel Prem S , Hameed Meera , Bryan Margaret , Rameshwar Pranela
Published: September 2007

Introduction

HGFIN, previously identified as nmb, and its homolog osteoactivin are single transmembrane proteins that are expressed in differentiated immune cells. These proteins exhibit properties that could potentiate tumorigenesis or decrease invasiveness. These seemingly opposing roles of HGFIN suggest that this protein might be central to malignancies and might also behave as a tumor suppressor. Consistent with the reported roles for HGFIN is the fact that this gene is regulated by p53 through multiple binding sites in the 5' flanking region, and is expressed in osteoblasts.

Methods

This study used siRNA to knock-out HGFIN in non-tumorigenic breast cells and ectopically expressed HGFIN in breast cancer cells. In addition, in situ hybridization studies analyzed primary breast tissues from archived breast surgeries. Reporter gene assays studied the untranslated exon 1 of HGFIN.

Results

HGFIN expression led to reduced cell growth of breast cancer cells and reduced migration. At the molecular level, reporter gene analyses determined the untranslated exon 1 to be a negative regulator of the upstream enhancing effect. Ectopic expression of wild-type p53 in breast cancer cells that expressed endogenous mutant p53 resulted in increased HGFIN reporter gene activities.

Conclusion

As the majority of cancer cells have mutations in p53, further studies on the relationship between p53 and HGFIN expression, and its role in tumor genesis and bone invasion, might uncover novel therapy targets for breast and other cancers. The results show a central role for p53 in HGFIN expression, which appears to determine the behavior of the cancer cells.
Coverage and error models of protein-protein interaction data by directed graph analysis
Authors: Chiang Tony , Scholtens Denise , Sarkar Deepayan , Gentleman Robert , Huber Wolfgang
Published: September 2007

Using a directed graph model for bait to prey systems and a multinomial error model, we assessed the error statistics in all published large-scale datasets for Saccharomyces cerevisiae and characterized them by three traits: the set of tested interactions, artifacts that lead to false-positive or false-negative observations, and estimates of the stochastic error rates that affect the data. These traits provide a prerequisite for the estimation of the protein interactome and its modules.
The LeFE algorithm: embracing the complexity of gene expression in the interpretation of microarray data
Authors: Eichler Gabriel S , Reimers Mark , Kane David , Weinstein John N
Published: September 2007

Interpretation of microarray data remains a challenge, and most methods fail to consider the complex, nonlinear regulation of gene expression. To address that limitation, we introduce Learner of Functional Enrichment (LeFE), a statistical/machine learning algorithm based on Random Forest, and demonstrate it on several diverse datasets: smoker/never smoker, breast cancer classification, and cancer drug sensitivity. We also compare it with previously published algorithms, including Gene Set Enrichment Analysis. LeFE regularly identifies statistically significant functional themes consistent with known biology.
Compulsive hoarding: A qualitative investigation of partner and carer perspectives
Authors: Wilbram Mark. , Kellett Stephen. , Beail Nigel.
Published: September 2007

Objective

This study explores the experiences of family members caring for a person who compulsively hoards.

Design

Ten participants, all ‘key carers’ for a hoarding family member, were interviewed using a semi‐structured interview schedule designed for the purpose of the study.

Methods

Transcribed interviews were analysed using interpretive phenomenological analysis.

Results

Five superordinate, discrete but interconnecting themes were identified: ‘loss of normal family life’; ‘the need for understanding’; ‘coping with the situation’; ‘impact on relationships’; and ‘marginalization’. Carers' accommodation of hoarding behaviours and role isolation were examined in drawing connections between themes. Outlying themes suggesting factors protective of relationships and facilitating coping were also identified.

Conclusion

Carers struggled to cope with both the environmental and interpersonal impacts of the hoarding. Lacking both formal and informal networks of support, carers are in need of information and treatment options for themselves and their families. Possible avenues for future clinical and theoretical research are suggested.
Expectancies, not aroma, explain impact of lavender aromatherapy on psychophysiological indices of relaxation in young healthy women
Authors: Howard Siobhán , Hughes Brian M.
Published: September 2007

Objectives In aromatherapy, lavender aroma is reputed to assist with relaxation. However, while there is much anecdotal evidence to that effect, the empirical literature is very inconsistent. Failure to employ adequate placebos, proper blinding, objective measures, or screening of prior beliefs about aromatherapy means that many previous findings could have been influenced by expectancy biases. The present study sought to establish whether lavender aroma and/or expectancies affect post‐stress relaxation.

Design A double‐blind, 3 (aroma)×3 (instruction)×10 (time in minutes) mixed‐factorial placebo‐controlled trial.

Method In a laboratory, 96 healthy undergraduate women were exposed to lavender, placebo, or no aroma during physiologically assessed relaxation after an arousing cognitive task. Where an aroma was presented, an instructional priming procedure was used to manipulate participants' expectancies about the aroma's likely impact on their ability to relax.

Results Results showed no effect of aroma on galvanic skin response during relaxation. However, the nature of instructional prime was associated with relaxation patterns: when expecting the aroma to inhibit them, participants relaxed more; when expecting facilitation, participants relaxed less. The effect was not seen with regard to self‐reported relaxation (as represented by changes in state anxiety) and was independent of ratings of attitudes towards aromatherapy.

Conclusions The findings imply that the previous associations of lavender aroma with assisted relaxation may have been influenced by expectancy biases, and that the relevant expectancies are easily manipulable.
Intra-nasal Inoculation of American Bison (Bison bison) with Ovine Herpesvirus-2 (OvHV-2) Reliably Reproduces Malignant Catarrhal Fever
Authors: O'Toole D. , Taus N. S. , Montgomery D. L. , Oaks J. L. , Crawford T. B. , Li H.
Published: September 2007

Sheep-associated malignant catarrhal fever (MCF) due to infection with ovine herpesvirus 2 (OvHV-2) is common in commercial herds of American bison ( Bison bison). Inability to propagate OvHV-2 in vitro has been a constraint on experimental studies of the disease. We sought to establish whether nasal secretions from sheep that shed OvHV-2 might induce the disease in bison and to define a minimum challenge dose. Fourteen bison were nebulized with sheep nasal sections containing 103–107 OvHV-2 deoxyribonucleic acid (DNA) copies. Most challenged bison (11/14, 78.6%) developed clinical signs at 29–52 days postnebulization (DPN). The mean incubation time was 42.18 (±7.33 SD) DPN. Using real-time polymerase chain reaction, we detected OvHV-2 DNA in peripheral blood leukocytes at 21–31 DPN. All bison that developed MCF had antibodies against the MCF group viruses. Gross and histologic lesions were typical of the acute disease. There was no morphologic evidence of a dose-related difference in the severity or distribution of lesions. This is the first successful reproduction of MCF in bison using a nasal route of exposure. Experimentally challenged bison are more susceptible to MCF, compared with experimentally challenged domestic cattle in a previous experiment. Bison are a pertinent ruminant species in which the pathogenesis of the disease can be investigated.
Immunohistochemical Characterization and Evaluation of Prognostic Factors in Canine Oral Melanomas with Osteocartilaginous Differentiation
Authors: Sánchez J. , Ramirez G. A. , Buendia A. J. , Vilafranca M. , Martinez C. M. , Altimira J. , Navarro J. A.
Published: September 2007

Melanomas are the most common malignant oral neoplasm in dogs. Osteocartilaginous differentiation in oral melanomas is a rare feature described both in veterinary and human medicine. Here, 10 cases of this type of neoplasm were used to study their immunohistochemical, biological, and clinical characteristics. Reactivity for S100 and melan A antigen was evaluated, and 4 prognosis factors (mitotic index, invasiveness of epithelium, nuclear atypia, and proliferation index) were analyzed and correlated with the clinical course of the neoplasms after diagnosis. Immunohistochemical analysis of the studied neoplasms, including the osteocartilaginous areas, showed positive immunoreaction for S100 and melan A, except in one dog, which was negative for melan A. Analysis of the results showed that oral melamonas with osteocartilaginous differentiation have a clinical course similar to that of other melanomas in the oral cavity. Analysis of the mitotic index and the expression of proliferation marker Ki-67 could be useful tools for predicting the biological behavior of these neoplasms.
Evaluation of the Effectiveness of Clear Water Repellent Coatings on Partially Grouted Single-Wythe Concrete Masonry Walls
Authors: Greenwald Jeffrey H. , Young Thomas C.
Published: September 2007

The use of architectural concrete masonry to construct commercial and institutional buildings is common in the northwestern United States. By combining different block sizes, shapes, colors, and surface treatments, architects have designed many striking structures. This test program focused on the evaluation of clear water repellent coatings because they are an important component of a water resistant wall system. The number of repellents produced has grown and their chemical composition has changed during recent years. The test results will provide guidance in updating the industry recommendation used by design professionals and building owners. A total of 14 walls were constructed and tested in accordance with ASTM E 514, “Standard Test Method for Water Penetration and Leakage Through Masonry.” The walls were all constructed with materials shipped from northwest block producers and represent construction techniques used in the Pacific Northwest. Each wall was initially tested uncoated to establish a baseline performance. Afterwards, a clear water repellent was applied and each wall was retested. The walls were then tested a third time after aging outside for approximately one year. The test results will establish comparative behavior between wall assemblies.
Eine Parametrierung reduzierter stabiler Modelle und stabilisierender Regler (A Parameterization of Reduced Stable Models and Controllers)
Authors: Yousefi Amirhossein , Lohmann Boris
Published: September 2007

Der Beitrag beschäftigt sich mit der Stabilitätserhaltung bei der Ordnungsreduktion linearer Modelle und linearer Regler. Es wird eine Parametrierung angegeben, die ausgehend von einem Modell (oder Regler) hoher Ordnung eine große Klasse stabiler reduzierter Modelle (oder regelkreisstabilisierender reduzierter Regler) beschreibt. Hiermit können verschiedene bestehende Reduktionsverfahren, die mittels Ähnlichkeitstransformationen oder singulärer Perturbation operieren und nicht zwingend stabilisieren, sinnvoll erweitert werden.

This note addresses the problem of instability in both model and controller reduction methods based on similarity transformations. For a given model (controller) a general framework is proposed that parameterizes a large set of reduced models (controllers) that preserve the stability of the original model (closed loop system). As an application of the main results, it is shown how different reduction methods can be modified, if they fail to maintain stability.
Black and Hispanic: The Racial Identification of Afro-Cuban Immigrants in the Southwest
Authors: Newby C. Alison , Dowling Julie A.
Published: September 2007

Although studies document the successful adaptation of Cuban exiles in Miami, little research has examined the settlement experiences of recent Afro-Cuban immigrants. Many of these Afro-Cubans have settled in relocation sites throughout the United States, including the Southwest. The adjustment of these immigrants in areas with mostly White and Mexican-origin populations, and a smaller African American group, creates identity conflicts as these immigrants struggle to find their place in this largely white/black/brown triracial system. Drawing on interviews with forty-five Afro-Cubans in Austin, Texas, and Albuquerque, New Mexico, this study employs a constructionist approach, exploring the ways in which racial and ethnic identities are formed in dialogue with both self-appraisal and external classification from others. Findings reveal the complicated identification processes involved as Afro-Cubans attempt to maintain identification as both “Cuban” and “Black” in the face of external classification as either “Black” or “Hispanic.”
Court Context and Discrimination: Exploring Biases across Juvenile and Criminal Courts
Authors: Kupchik Aaron , Harvey Angela
Published: September 2007

Prior research on juvenile and criminal courts argues that because of contextual differences between these two forums, court actors' perceptions of guilt and culpability may be more influenced by racial/ethnic or gender stereotypes in juvenile courts than in criminal courts, regarding the prosecution of adolescents. In this article, the authors explore this differential bias hypothesis, using both quantitative and qualitative data. After comparing the factors that shape sentencing outcomes across court types, the article turns to qualitative data to understand whether the contextual distinctions between these two types of courts create greater opportunity for discrimination in juvenile court. Neither the quantitative nor qualitative results support this differential bias hypothesis. The quantitative analyses do not find a significantly different effect of race/ethnicity or sex across court types. The qualitative analyses help explain this result; although juvenile courts may expose adolescents to greater risks of being judged according to stereotypes, two contextual features protect adolescents by mitigating the impact of these potential hazards: aggressive and well-organized public defenders in juvenile court and the similarity of case processing during the sentencing phases of juvenile and criminal court.
Free-Air Treatment for Mental Patients: The Deinstitutionalization Debate of the Nineteenth Century
Authors: Tuntiya Nana
Published: September 2007

The development of ideas on deinstitutionalization of mental patients has a much longer history in the United States than is commonly acknowledged in the sociological literature. The present analysis of publications in the American Journal of Insanity from 1844 to 1900 corrects this research gap by examining the nineteenth-century deinstitutionalization discourse within American psychiatry. The role of the oldest community care program originating in Gheel, Belgium, in promoting alternative modes of treatment in the United States is emphasized, and the relevance of these findings for community mental health care and existing sociological work on deinstitutionalization is discussed.
Efficacy of Highly Active Antiretroviral Therapy in HIV-1–Infected Children in Kenya
Authors: Song Rinn , Jelagat Justine , Dzombo Doris , Mwalimu Marietta , Mandaliya Kishorchandra , Shikely Khadija , Essajee Shaffiq
Published: September 2007

OBJECTIVE. Few studies have investigated the efficacy of antiretroviral therapy among HIV-infected children in resource-poor settings. This observational, retrospective analysis describes the clinical, immunologic, and virologic effects of highly active antiretroviral therapy in treatment-naive, HIV-infected children in Mombasa, Kenya. In keeping with a public health approach, all children were treated by using a simplified, nationally approved, triple-drug regimen.

METHODS. Clinical data and stored plasma samples from 29 children who were followed prospectively between April 2003 and October 2004 were analyzed. All children received generic formulations of nevirapine, zidovudine, and lamivudine and were evaluated at baseline and at 3, 6, 9, 12, and 15 months. At each visit, weight and CD4 lymphocyte counts were measured and plasma samples were stored for analysis. HIV RNA load was determined retrospectively at baseline and 9 months after initiation of therapy.

RESULTS. The mean age of the children was 8.5 years (range: 2–16 years). At baseline, the mean CD4 count (±SD) was 182.3 × 106 cells per μL (±145.6). On treatment, CD4 counts increased step-wise by a mean of 187 × 106 cells per μL at 3 months, 293 cells per μL at 6 months, 308 cells per μL at 9 months, 334 cells per μL at 12 months, and 363 cells per μL at 15 months. The mean plasma viral load decreased from a baseline level of 622 712 to 35369 copies per mL, and at 9 months was undetectable in 55% of the patients. Mean z scores for weight for age increased from a baseline of −1.61 to −1.12 at 12 months into therapy.

CONCLUSIONS. A public health approach using 1 treatment regimen in generic form showed excellent efficacy among treatment-naive, HIV-infected children in a resource-limited country. Clinical and immunologic improvement occurred in all patients, but 9 months after the start of therapy, only 55% of the children had an undetectable viral load.