bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding sustained behavior change: the role of life crises and the process of reinvention
Authors: Ogden Jane , Hills Louisa
Published: September 2008

Much research has addressed behavior change but has tended to focus on short term changes. This study aimed to explore the mechanisms behind sustained changes in behavior and involved qualitative interviews with 34 `success stories' who had either lost weight through changes in diet and exercise ( n = 24) or stopped smoking ( n = 10) and had maintained this change for at least 3 years. The results showed that the majority described how their sustained behavior change had been triggered by a significant life crisis relating to their health, relationships or salient milestones. This initial change was then translated into sustained change if three sustaining conditions were met: the function of the unhealthy behavior was disrupted, the individual perceived that their choice over carrying out the unhealthy behavior had been reduced and they adhered to a behavioral model of their problem. Further, these conditions functioned by enabling a process of reinvention with participants showing a shift in identity toward a new healthier self. The results are discussed in terms of self-regulation and the establishment of a new post-crisis healthier equilibrium.
Negotiating the diagnostic uncertainty of contested illnesses: physician practices and paradigms
Authors: Swoboda Debra A.
Published: September 2008

In the absence of scientific consensus about contested illnesses such as Chronic Fatigue Syndrome (CFS), Multiple Chemical Sensitivities (MCS), and Gulf War Syndrome (GWS), physicians must make sense of competing accounts and develop practices for patient evaluation. A survey of 800 United States physicians examined physician propensity to diagnose CFS, MCS, and GWS, and the factors shaping clinical decision making. Results indicate that a substantial portion of physicians, including nonexperts, are diagnosing CFS, MCS, and GWS. Diagnosing physicians manage the uncertainty associated with these illnesses by using strategies that enhance bounded rationality and aid in thinking beyond current disease models. Strategies include consulting ancillary information sources, conducting analytically informed testing, and considering physiological explanations of causation. By relying on these practices and paradigms, physicians fit CFS, MCS, and GWS into an explanatory system that makes them credible and understandable to them, their patients, and the medical community. Findings suggest that physicians employ rational decision making for diagnosing contested illnesses, creating a blueprint of how illnesses lacking conclusive pathogenic and etiological explanations can be diagnosed. Findings also suggest that patients with contested illnesses might benefit from working with physicians who use these diagnostic strategies, since they help manage the complexity and ambiguity of the contested illness diagnostic process and aid in diagnosis. In addition, findings provide a window into how emerging illnesses get diagnosed in the absence of medical and scientific consensus, and suggest that diagnosing physicians advance the legitimacy of controversial illnesses by constructing the means for their diagnosis.
Discourse of `transformational leadership' in infection control
Authors: Koteyko Nelya , Carter Ronald
Published: September 2008

The article explores the impact of the `transformational leadership' style in the role of modern matron with regards to infection control practices. Policy and guidance on the modern matron role suggest that it is distinctive in its combination of management and clinical components, and in its reliance on transformational leadership. Senior nurses are therefore expected to motivate staff by creating high expectations, modelling appropriate behaviour, and providing personal attention to followers by giving respect and responsibility. In this article, we draw on policy documents and interview data to explore the potential impact of this new management style on infection control practices. Combining the techniques of discourse analysis and corpus linguistics, we identify examples where matrons appear to disassociate themselves from the role of `an empowered manager' who has control over human and financial resources to resolve problems in infection control efficiently.
The artist as surgical ethnographer: participant observers outside the social sciences
Authors: Harris Anna
Published: September 2008

Artists and novelists have rarely been considered as ethnographers in the medical social sciences. This article pursues the idea that ethnographically informed artistic works can be viewed as critical cultural texts alongside sociological and anthropological studies of surgery. It is proposed that art provides fresh perspectives on topics of interest in health sociology and medical anthropology while simultaneously expanding our engagement with ethnographic representation. Discussion revolves around a video installation incorporating images of heart surgery by contemporary artist Bill Viola and a recent novel by Ian McEwan detailing the day-in-the-life of a neurosurgeon. Considering an emerging re-engagement, particularly in contemporary art that artists are having with medical themes, and a concurrent `ethnographic turn' in art practice, it seems timely to recognize the potentially critical contribution of non-social scientist ethnographers to our understanding of a rapidly changing medical culture.
Constructions of the self in interaction with the Beck Depression Inventory
Authors: Galasiński Dariusz
Published: September 2008

In this article, I am interested in discourses of people completing the Polish version of the Beck Depression Inventory (BDI). I focus upon the negotiation of the spaces for constructing the self opened by the BDI. My corpus consists of transcripts of 50 sessions in which self-reportedly healthy people were asked to `think aloud' while completing the BDI. I shall demonstrate that in interactions with the `depression scale', the informants mostly rejected the spaces offered by it. Three strategies of such rejection are discussed: reformulation, recontextualization and an explicit challenge to the categories offered by the BDI. I shall argue that the concerns of lived experience in a particular context, when not subdued by the relationship of power in the situation of medical examination, overrule the frame imposed by the a-contextual questionnaire of sadness. Insight into depression or its intensity offered by `context-free' psychological or psychiatric instrument, set outside lived experience, is extremely problematic.
High Levels of Plasma Malondialdehyde, Protein Carbonyl, and Fibrinogen Have Prognostic Potential to Predict Poor Outcomes in Patients With Diabetic Foot Wounds: A Preliminary Communication
Authors: Rattan Roma , Nayak Debashish
Published: September 2008

Diabetic foot ulcer (DFU) is the leading cause of lower extremity amputation and is generally known to have poor prognosis. Oxidative stress is considered important in the pathogenesis of chronic wounds. Fibrinogen is a recognized marker in peripheral vascular disease; increasing levels predict an increased mortality and risk of amputation. The aim of this study was to evaluate if plasma malondialdehyde (MDA), protein carbonyl (PC) and fibrinogen levels can be used as prognostic markers in patients with DFU. The study design was prospective, nonrandomized, and controlled. A total of 41 DFU grade 1 and 20 DFU grade 2 patients were studied in this case—control study. Diabetic controls without foot ulcers and healthy controls were also studied. Plasma MDA, PC, and fibrinogen levels were significantly higher in patients with DFU compared with those without ulcers ( P < .05) and nondiabetic controls ( P < .001). These parameters increased in association with DFU grade ( P < .01). Increased levels of plasma fibrinogen, MDA, and PC correlated with worsened outcomes. An augmented oxidative stress and plasma fibrinogen level >300.4 mg% (95% confidence interval, 100% sensitivity, 99.2% specificity) was correlated with a high risk of amputation in DFU.
Leg Wound Infections Following Greater Saphenous Vein Harvesting: Minimally Invasive Vein Harvesting Versus Conventional Vein Harvesting
Authors: Reed James F.
Published: September 2008

Wound complications associated with long incisions used to harvest the greater saphenous vein are common and well documented. We compared leg wound infection rates, wound healing disturbances (WHDs), length of vein harvested, vein harvest time, and total surgical time between minimally invasive saphenous vein harvesting (MIVH) and conventional vein harvesting (CVH) techniques. This meta-analysis showed a significant reduction in wound infections in favor of the MIVH group (odds ratio = 0.19; 95% confidence interval = 0.14-0.25) and a significant reduction in WHDs in favor of the MIVH group (odds ratio = 0.26; 95% confidence interval = 0.20-0.34). The MIVH and CVH techniques are equivalent with respect to saphenous vein harvest time, saphenous vein harvest length, and total surgical time. A visual inspection of “funnel” plots suggests a mild to moderate publication bias. This meta-analysis suggests that leg wound infections and wound healing disturbances are reduced using MIVH techniques.
Inherited and acquired variations in the hyaluronan synthase 1 (HAS1) gene may contribute to disease progression in multiple myeloma and Waldenstrom macroglobulinemia
Authors: Adamia Sophia , Reichert Amanda A. , Kuppusamy Hemalatha , Kriangkum Jitra , Ghosh Anirban , Hodges Jennifer J. , Pilarski Patrick M. , Treon Steven P. , Mant Michael J. , Reiman Tony , Belch Andrew R. , Pilarski Linda M.
Published: September 2008

To characterize genetic contributions toward aberrant splicing of the hyaluronan synthase 1 (HAS1) gene in multiple myeloma (MM) and Waldenstrom macroglobulinemia (WM), we sequenced 3616 bp in HAS1 exons and introns involved in aberrant splicing, from 17 patients. We identified a total of 197 HAS1 genetic variations (GVs), a range of 3 to 24 GVs/patient, including 87 somatic GVs acquired in splicing regions of HAS1. Nearly all newly identified inherited and somatic GVs in MM and/or WM were absent from B chronic lymphocytic leukemia, nonmalignant disease, and healthy donors. Somatic HAS1 GVs recurred in all hematopoietic cells tested, including normal CD34+ hematopoietic progenitor cells and T cells, or as tumor-specific GVs restricted to malignant B and plasma cells. An in vitro splicing assay confirmed that HAS1 GVs direct aberrant HAS1 intronic splicing. Recurrent somatic GVs may be enriched by strong mutational selection leading to MM and/or WM.
Rapidly proliferating CD44hi peripheral T cells undergo apoptosis and delay posttransplantation T-cell reconstitution after allogeneic bone marrow transplantation
Authors: Alpdogan S. Önder , Lu Sydney X. , Patel Neel , McGoldrick Suzanne , Suh David , Budak-Alpdogan Tulin , Smith Odette M. , Grubin Jeremy , King Christopher , Goldberg Gabrielle L. , Hubbard Vanessa M. , Kochman Adam A. , van den Brink Marcel R. M.
Published: September 2008

Delayed T-cell recovery is an important complication of allogeneic bone marrow transplantation (BMT). We demonstrate in murine models that donor BM-derived T cells display increased apoptosis in recipients of allogeneic BMT with or without GVHD. Although this apoptosis was associated with a loss of Bcl-2 and Bcl-XL expression, allogeneic recipients of donor BM deficient in Fas-, tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)- or Bax-, or BM-overexpressing Bcl-2 or Akt showed no decrease in apoptosis of peripheral donor-derived T cells. CD44 expression was associated with an increased percentage of BM-derived apoptotic CD4+ and CD8+ T cells. Transplantation of RAG-2-eGFP–transgenic BM revealed that proliferating eGFPloCD44hi donor BM-derived mature T cells were more likely to undergo to apoptosis than nondivided eGFPhiCD44lo recent thymic emigrants in the periphery. Finally, experiments using carboxyfluorescein succinimidyl ester–labeled T cells adoptively transferred into irradiated syngeneic hosts revealed that rapid spontaneous proliferation (as opposed to slow homeostatic proliferation) and acquisition of a CD44hi phenotype was associated with increased apoptosis in T cells. We conclude that apoptosis of newly generated donor-derived peripheral T cells after an allogeneic BMT contributes to delayed T-cell reconstitution and is associated with CD44 expression and rapid spontaneous proliferation by donor BM-derived T cells.
Adhesive activity of Lu glycoproteins is regulated by interaction with spectrin
Authors: An Xiuli , Gauthier Emilie , Zhang Xihui , Guo Xinhua , Anstee David J. , Mohandas Narla , Chasis Joel Anne
Published: September 2008

The Lutheran (Lu) and Lu(v13) blood group glycoproteins function as receptors for extracellular matrix laminins. Lu and Lu(v13) are linked to the erythrocyte cytoskeleton through a direct interaction with spectrin. However, neither the molecular basis of the interaction nor its functional consequences have previously been delineated. In the present study, we defined the binding motifs of Lu and Lu(v13) on spectrin and identified a functional role for this interaction. We found that the cytoplasmic domains of both Lu and Lu(v13) bound to repeat 4 of the α spectrin chain. The interaction of full-length spectrin dimer to Lu and Lu(v13) was inhibited by repeat 4 of α-spectrin. Further, resealing of this repeat peptide into erythrocytes led to weakened Lu-cytoskeleton interaction as demonstrated by increased detergent extractability of Lu. Importantly, disruption of the Lu-spectrin linkage was accompanied by enhanced cell adhesion to laminin. We conclude that the interaction of the Lu cytoplasmic tail with the cytoskeleton regulates its adhesive receptor function.
Characteristics and outcome of chronic myeloid leukemia patients with F317L BCR-ABL kinase domain mutation after therapy with tyrosine kinase inhibitors
Authors: Jabbour Elias , Kantarjian Hagop M. , Jones Dan , Reddy Neeli , O'Brien Susan , Garcia-Manero Guillermo , Burger Jan , Cortes Jorge
Published: September 2008

Mutations in codon 317 after treatment with imatinib and dasatinib have been reported. We reviewed patients with chronic myeloid leukemia and mutations after tyrosine kinase inhibitor (TKI) therapy. F317L was detected in 20, including 12/99 (12%) with mutation after imatinib failure, and 8/16 (50%) after dasatinib (P = .001). Median follow-up from mutation detection was 25 months. At the time of F317L, 8 patients were in chronic phase (CP), 6 in accelerated phase, and 6 in blast phase. There was no difference in characteristics between patients with or without F317L mutations, or with no mutations. A complete cytogenetic response was acheived in 3 of 6 patients treated with nilotinib, 2 of 2 with imatinib, and 0 of 3 with dasatinib. Survival of patients with F317L was similar to those with other mutations (P = .45). Patients in CP had better outcome, with a 2-year survival of 75%. F317L mutation is resistant to dasatinib but sensitive to other TKIs. The prognosis is dependent mostly on the disease stage.
CD44-specific antibody treatment and CD44 deficiency exert distinct effects on leukocyte recruitment in experimental arthritis
Authors: Hutás Gábor , Bajnok Éva , Gál István , Finnegan Alison , Glant Tibor T. , Mikecz Katalin
Published: September 2008

CD44, the leukocyte adhesion receptor for hyaluronan, has been considered a therapeutic target on the basis of the robust anti-inflammatory effect of CD44-specific antibodies in animal models of immune-mediated diseases. However, CD44 deficiency does not provide substantial protection against inflammation. Using intravital video microscopy in a murine model of rheumatoid arthritis, we show that CD44 deficiency and anti-CD44 antibody treatment exert disparate effects on leukocyte recruitment in inflamed joints. Leukocyte rolling, which is increased in CD44-deficient mice, is promptly abrogated in anti–CD44-treated wild-type mice. CD44-specific antibodies also trigger platelet deposition on granulocytes and subsequent depletion of this leukocyte subset in the circulation. These in vivo effects require CD44 cross-linking and are reproducible with an antibody against Gr-1, a molecule that, like CD44, is highly expressed on granulocytes. Anticoagulant pretreatment, which prevents platelet deposition, mitigates both granulocyte depletion and the suppressive effect of CD44-specific antibody on joint swelling. Our observations suggest that cross-linking of prominent cell surface molecules, such as CD44 or Gr-1, can initiate a rapid self-elimination program in granulocytes through engagement of the coagulation system. We conclude that the robust anti-inflammatory effect of CD44-specific antibodies in arthritis is primarily the result of their ability to trigger granulocyte depletion.
Defective synthesis or association of T-cell receptor chains underlies loss of surface T-cell receptor–CD3 expression in enteropathy-associated T-cell lymphoma
Authors: Tjon Jennifer M. L. , Verbeek Wieke H. M. , Kooy-Winkelaar Yvonne M. C. , Nguyen Binh H. , van der Slik Arno R. , Thompson Allan , Heemskerk Mirjam H. M. , Schreurs Marco W. J. , Dekking Liesbeth H. A. , Mulder Chris J. , van Bergen Jeroen , Koning Frits
Published: September 2008

Enteropathy-associated T-cell lymphoma, an often fatal complication of celiac disease, can result from expansion of aberrant intraepithelial lymphocytes in refractory celiac disease type II (RCD II). Aberrant intraepithelial lymphocytes and lymphoma cells are intracellularly CD3ϵ+ but lack expression of the T-cell receptor (TCR)–CD3 complex on the cell surface. It is unknown what causes the loss of TCR-CD3 expression. We report the isolation of a cell line from an RCD II patient with the characteristic phenotype of enteropathy-associated T-cell lymphoma. We demonstrate that in this cell line the TCR-α and -β chains as well as the CD3γ, CD3δ, CD3ϵ, and ζ-chains are present intracellularly and that assembly of the CD3γϵ, CD3δϵ, and ζζ-dimers is normal. However, dimerization of the TCR chains and proper assembly of the TCR-CD3 complex are defective. On introduction of exogenous TCR-β chains, but not of TCR-α chains, assembly and functional cell surface expression of the TCR-CD3 complex were restored. Defective synthesis of both TCR chains was found to underlie loss of TCR expression in similar cell lines isolated from 2 additional patients. (Pre)malignant transformation in RCD II thus correlates with defective synthesis or defective association of the TCR chains, resulting in loss of surface TCR-CD3 expression.
Anti-CD3 prevents factor VIII inhibitor development in hemophilia A mice by a regulatory CD4+CD25+-dependent mechanism and by shifting cytokine production to favor a Th1 response
Authors: Waters Braden , Qadura Mohammad , Burnett Erin , Chegeni Rouzbeh , Labelle Andrea , Thompson Patrick , Hough Christine , Lillicrap David
Published: September 2008

Non–Fc-receptor binding anti-CD3 Ab therapy, in the setting of several different autoimmune disorders, can induce antigen-specific and long-lasting immunologic tolerance. Because factor VIII (FVIII) inhibitor formation is the most serious treatment-related complication for hemophilia A patients, we tested the efficacy of anti-CD3 to prevent FVIII inhibitor formation in hemophilia A BALB/c and C57BL/6 mice. A short course of low-dose anti-CD3 significantly increased expression of CD25 and the proportion of CD4+CD25+ regulatory T cells in the spleen and potently prevented the production of inhibitory and non-neutralizing anti-FVIII antibodies in both strains of mouse. Depleting the CD4+CD25+ cells during anti-CD3 therapy completely ablated tolerance to FVIII. Further phenotypic characterization of regulatory cells in tolerant mice showed a consistently higher number of CD4+GITR+ and CD4+FoxP3+ cells in both strains of mice. In addition, in tolerant C57BL/6 mice we observed an increase in CD4+CD25+CTLA-4+ and CD4+CD25+mTGF-β1+ cells. Finally, in vitro cytokine profiling demonstrated that splenocytes from tolerant BALB/c and C57BL/6 were polarized toward a Th1-immune response. Taken together, these findings indicate that anti-CD3 induces tolerance to FVIII and that the mechanism(s) regulating this response almost certainly occurs through the generation of several distinct regulatory T-cell lineages and by influencing cytokine production and profile.
Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator
Authors: Jiao Yan , Wilkinson John , Di Xiumin , Wang Wei , Hatcher Heather , Kock Nancy D. , D'Agostino Ralph , Knovich Mary Ann , Torti Frank M. , Torti Suzy V.
Published: September 2008

Curcumin is a natural product currently in human clinical trials for a variety of neoplastic, preneoplastic, and inflammatory conditions. We previously observed that, in cultured cells, curcumin exhibits properties of an iron chelator. To test whether the chelator activity of curcumin is sufficient to induce iron deficiency in vivo, mice were placed on diets containing graded concentrations of both iron and curcumin for 26 weeks. Mice receiving the lowest level of dietary iron exhibited borderline iron deficiency, with reductions in spleen and liver iron, but little effect on hemoglobin, hematocrit, transferrin saturation, or plasma iron. Against this backdrop of subclinical iron deficiency, curcumin exerted profound 2 effects on systemic iron, inducing a dose-dependent decline in hematocrit, hemoglobin, serum iron, and transferrin saturation, the appearance of microcytic anisocytotic red blood cells, and decreases in spleen and liver iron content. Curcumin repressed synthesis of hepcidin, a peptide that plays a central role in regulation of systemic iron balance. These results demonstrate that curcumin has the potential to affect systemic iron metabolism, particularly in a setting of subclinical iron deficiency. This may affect the use of curcumin in patients with marginal iron stores or those exhibiting the anemia of cancer and chronic disease.
Modifying the DPClus algorithm for identifying protein complexes based on new topological structures
Authors: Li Min , Chen Jian-er , Wang Jian-xin , Hu Bin , Chen Gang
Published: September 2008

Background

Identification of protein complexes is crucial for understanding principles of cellular organization and functions. As the size of protein-protein interaction set increases, a general trend is to represent the interactions as a network and to develop effective algorithms to detect significant complexes in such networks.

Results

Based on the study of known complexes in protein networks, this paper proposes a new topological structure for protein complexes, which is a combination of subgraph diameter (or average vertex distance) and subgraph density. Following the approach of that of the previously proposed clustering algorithm DPClus which expands clusters starting from seeded vertices, we present a clustering algorithm IPCA based on the new topological structure for identifying complexes in large protein interaction networks. The algorithm IPCA is applied to the protein interaction network of Sacchromyces cerevisiae and identifies many well known complexes. Experimental results show that the algorithm IPCA recalls more known complexes than previously proposed clustering algorithms, including DPClus, CFinder, LCMA, MCODE, RNSC and STM.

Conclusion

The proposed algorithm based on the new topological structure makes it possible to identify dense subgraphs in protein interaction networks, many of which correspond to known protein complexes. The algorithm is robust to the known high rate of false positives and false negatives in data from high-throughout interaction techniques. The program is available at http://netlab.csu.edu.cn/bioinformatics/limin/IPCA.
An ontology for Xenopus anatomy and development
Authors: Segerdell Erik , Bowes Jeff B , Pollet Nicolas , Vize Peter D
Published: September 2008

Background

The frogs Xenopus laevis and Xenopus (Silurana) tropicalis are model systems that have produced a wealth of genetic, genomic, and developmental information. Xenbase is a model organism database that provides centralized access to this information, including gene function data from high-throughput screens and the scientific literature. A controlled, structured vocabulary for Xenopus anatomy and development is essential for organizing these data.

Results

We have constructed a Xenopus anatomical ontology that represents the lineage of tissues and the timing of their development. We have classified many anatomical features in a common framework that has been adopted by several model organism database communities. The ontology is available for download at the Open Biomedical Ontologies Foundry http://obofoundry.org.

Conclusion

The Xenopus Anatomical Ontology will be used to annotate Xenopus gene expression patterns and mutant and morphant phenotypes. Its robust developmental map will enable powerful database searches and data analyses. We encourage community recommendations for updates and improvements to the ontology.
Gene expression profiling of liver from dairy cows treated intra-mammary with lipopolysaccharide
Authors: Jiang Li , Sørensen Peter , Røntved Christine , Vels Lotte , Ingvartsen Klaus L
Published: September 2008

Background

Liver plays a profound role in the acute phase response (APR) observed in the early phase of acute bovine mastitis caused byEscherichia coli(E. coli). To gain an insight into the genes and pathways involved in hepatic APR of dairy cows we performed a global gene expression analysis of liver tissue sampled at different time points before and after intra-mammary (IM) exposure toE. colilipopolysaccharide (LPS) treatment.

Results

Approximately 20% target transcripts were differentially expressed and eight co-expression clusters were identified. Each cluster had a unique time-dependent expression profile and consisted of genes involved in different biological processes. Our findings suggest that APR in the liver is triggered by the activation of signaling pathways that are involved with common and hepatic-specific transcription factors and pro-inflammatory cytokines. These mediators in turn stimulated or repressed the expression of genes encoding acute phase proteins (APP), collectins, complement components, chemokines, cell adhesion molecules and key metabolic enzymes during the APR. Hormones, anti-inflammatory and other hypothalamus-pituitary-adrenal axis (HPAA) linked mediators also seemed to participate in APR.

Conclusion

Performing global gene expression analysis on liver tissue from IM LPS treated cows verified that the liver plays a major role in the APR ofE. colimastitis, and that the bovine hepatic APR follows the same pattern as other mammals when they are challenged with LPS. Our work presents the first insight into the dynamic changes in gene expression in the liver that influences the induction, kinetics and clinical outcome of the APR in dairy cows.
Upregulation of CD94 on CD8+T Cells in Anterior Chamber-Associated Immune Deviation
Authors: He Hao , Yang Peizeng , Jiang Liqiong , Zhang Junfeng , Zhao Changlin , Chen Lina , Lin Xiaomin , Zhou Hongyan , Kijlstra Aize
Published: September 2008

Background

CD8+regulatory T cells (Treg) have been considered to be involved in a model of ocular-induced tolerance, known as anterior chamber-associated immune deviation (ACAID). The phenotype and characteristics of CD8+Treg in ACAID remain only poorly understood. Recent studies have reported that the CD94-Qa-1 system is implicated in the induction of ACAID CD8+Treg, but the functions and characteristics of CD8+CD94+T cells remain unclear.

Results

Both mRNA and protein of CD94 and NKG2A were markedly up-regulated on splenic CD8+T cells of ACAID mice compared with controls. Flow cytometric analysis showed that very few CD8+CD94+T cells express granzyme B, perforin and Foxp3. CD8+CD94+T cells, but not CD8+CD94-T cells, magnetically isolated from the spleens of ACAID mice, produced large amounts of TGF-beta1 and exhibited suppressive activity in vitro. Neutralization of TGF-beta1 caused reversal of suppression mediated by CD8+CD94+T cells.

Conclusion

CD8+CD94+T cells from ACAID mice exhibited suppressive activity in association with enhanced expression of TGF-beta1, suggesting that CD8+Treg are mainly distributed in CD94+T cell subpopulations.
Outcome of HIV-associated Pneumocystis pneumonia in hospitalized patients from 2000 through 2003
Authors: Radhi Saba , Alexander Travis , Ukwu Michelle , Saleh Samer , Morris Alison
Published: September 2008

Background

Pneumocystis pneumonia (PCP) remains a leading cause of morbidity and mortality in HIV-infected persons. Epidemiology of PCP in the recent era of highly active antiretroviral therapy (HAART) is not well known and the impact of HAART on outcome of PCP has been debated.

Aim

To determine the epidemiology of PCP in HIV-infected patients and examine the impact of HAART on PCP outcome.

Methods

We performed a retrospective cohort study of 262 patients diagnosed with PCP between January 2000 and December 2003 at a county hospital at an academic medical center. Death while in the hospital was the main outcome measure. Multivariate modeling was performed to determine predictors of mortality.

Results

Overall hospital mortality was 11.6%. Mortality in patients requiring intensive care was 29.0%. The need for mechanical ventilation, development of a pneumothorax, and low serum albumin were independent predictors of increased mortality. One hundred and seven patients received HAART before hospitalization and 16 patients were started on HAART while in the hospital. HAART use either before or during hospitalization was not associated with mortality.

Conclusion

Overall hospital mortality and mortality predictors are similar to those reported earlier in the HAART era. PCP diagnoses in HAART users likely represented failing HAART regimens or non-compliance with HAART.
Co-up-regulation of three P450 genes in response to permethrin exposure in permethrin resistant house flies, Musca domestica
Authors: Zhu Fang , Li Ting , Zhang Lee , Liu Nannan
Published: September 2008

Background

Insects may use various biochemical pathways to enable them to tolerate the lethal action of insecticides. For example, increased cytochrome P450 detoxification is known to play an important role in many insect species. Both constitutively increased expression (overexpression) and induction of P450s are thought to be responsible for increased levels of detoxification of insecticides. However, unlike constitutively overexpressed P450 genes, whose expression association with insecticide resistance has been extensively studied, the induction of P450s is less well characterized in insecticide resistance. The current study focuses on the characterization of individual P450 genes that are induced in response to permethrin treatment in permethrin resistant house flies.

Results

The expression of 3 P450 genes, CYP4D4v2, CYP4G2, and CYP6A38, was co-up-regulated by permethrin treatment in permethrin resistant ALHF house flies in a time and dose-dependent manner. Comparison of the deduced protein sequences of these three P450s from resistant ALHF and susceptible aabys and CS house flies revealed identical protein sequences. Genetic linkage analysis located CYP4D4v2 and CYP6A38 on autosome 5, corresponding to the linkage of P450-mediated resistance in ALHF, whereas CYP4G2 was located on autosome 3, where the major insecticide resistance factor(s) for ALHF had been mapped but no P450 genes reported prior to this study.

Conclusion

Our study provides the first direct evidence that multiple P450 genes are co-up-regulated in permethrin resistant house flies through the induction mechanism, which increases overall expression levels of P450 genes in resistant house flies. Taken together with the significant induction of CYP4D4v2, CYP4G2, and CYP6A38 expression by permethrin only in permethrin resistant house flies and the correlation of the linkage of the genes with resistance and/or P450-mediated resistance in resistant ALHF house flies, this study sheds new light on the functional importance of P450 genes in response to insecticide treatment, detoxification of insecticides, the adaptation of insects to their environment, and the evolution of insecticide resistance.
Application of a haematopoetic progenitor cell-targeted adeno-associated viral (AAV) vector established by selection of an AAV random peptide library on a leukaemia cell line
Authors: Stiefelhagen Marius , Sellner Leopold , Kleinschmidt Jürgen A , Jauch Anna , Laufs Stephanie , Wenz Frederik , Zeller W Jens , Fruehauf Stefan , Veldwijk Marlon R
Published: September 2008

Background

For many promising target cells (e.g.: haematopoeitic progenitors), the susceptibility to standard adeno-associated viral (AAV) vectors is low. Advancements in vector development now allows the generation of target cell-selected AAV capsid mutants.

Methods

To determine its suitability, the method was applied on a chronic myelogenous leukaemia (CML) cell line (K562) to obtain a CML-targeted vector and the resulting vectors tested on leukaemia, non-leukaemia, primary human CML and CD34+ peripheral blood progenitor cells (PBPC); standard AAV2 and a random capsid mutant vector served as controls.

Results

Transduction of CML (BV173, EM3, K562 and Lama84) and AML (HL60 and KG1a) cell lines with the capsid mutants resulted in an up to 36-fold increase in CML transduction efficiency (K562: 2-fold, 60% ± 2% green fluorescent protein (GFP)+ cells; BV173: 9-fold, 37% ± 2% GFP+ cells; Lama84: 36-fold, 29% ± 2% GFP+ cells) compared to controls. For AML (KG1a, HL60) and one CML cell line (EM3), no significant transduction (<1% GFP+ cells) was observed for any vector. Although the capsid mutant clone was established on a cell line, proof-of-principle experiments using primary human cells were performed. For CML (3.2-fold, mutant: 1.75% ± 0.45% GFP+ cells, p = 0.03) and PBPC (3.5-fold, mutant: 4.21% ± 3.40% GFP+ cells) a moderate increase in gene transfer of the capsid mutant compared to control vectors was observed.

Conclusion

Using an AAV random peptide library on a CML cell line, we were able to generate a capsid mutant, which transduced CML cell lines and primary human haematopoietic progenitor cells with higher efficiency than standard recombinant AAV vectors.
Expressed sequence tags (ESTs) from immune tissues of turbot (Scophthalmus maximus) challenged with pathogens
Authors: Pardo Belén G , Fernández Carlos , Millán Adrián , Bouza Carmen , Vázquez-López Araceli , Vera Manuel , Alvarez-Dios José A , Calaza Manuel , Gómez-Tato Antonio , Vázquez María , Cabaleiro Santiago , Magariños Beatriz , Lemos Manuel L , Leiro José M , Martínez Paulino
Published: September 2008

Background

The turbot (Scophthalmus maximus; Scophthalmidae; Pleuronectiformes) is a flatfish species of great relevance for marine aquaculture in Europe. In contrast to other cultured flatfish, very few genomic resources are available in this species.Aeromonas salmonicidaandPhilasterides dicentrarchiare two pathogens that affect turbot culture causing serious economic losses to the turbot industry. Little is known about the molecular mechanisms for disease resistance and host-pathogen interactions in this species. In this work, thousands of ESTs for functional genomic studies and potential markers linked to ESTs for mapping (microsatellites and single nucleotide polymorphisms (SNPs)) are provided. This information enabled us to obtain a preliminary view of regulated genes in response to these pathogens and it constitutes the basis for subsequent and more accurate microarray analysis.

Results

A total of 12584 cDNAs partially sequenced from three different cDNA libraries of turbot (Scophthalmus maximus) infected withAeromonas salmonicida,Philasterides dicentrarchiand from healthy fish were analyzed. Three immune-relevant tissues (liver, spleen and head kidney) were sampled at several time points in the infection process for library construction. The sequences were processed into 9256 high-quality sequences, which constituted the source for the turbot EST database. Clustering and assembly of these sequences, revealed 3482 different putative transcripts, 1073 contigs and 2409 singletons. BLAST searches with public databases detected significant similarity (e-value ≤ 1e-5) in 1766 (50.7%) sequences and 816 of them (23.4%) could be functionally annotated. Two hundred three of these genes (24.9%), encoding for defence/immune-related proteins, were mostly identified for the first time in turbot. Some ESTs showed significant differences in the number of transcripts when comparing the three libraries, suggesting regulation in response to these pathogens. A total of 191 microsatellites, with 104 having sufficient flanking sequences for primer design, and 1158 putative SNPs were identified from these EST resources in turbot.

Conclusion

A collection of 9256 high-quality ESTs was generated representing 3482 unique turbot sequences. A large proportion of defence/immune-related genes were identified, many of them regulated in response to specific pathogens. Putative microsatellites and SNPs were identified. These genome resources constitute the basis to develop a microarray for functional genomics studies and marker validation for genetic linkage and QTL analysis in turbot.
A synaptic nidogen: Developmental regulation and role of nidogen-2 at the neuromuscular junction
Authors: Fox Michael A , Ho Matthew SP , Smyth Neil , Sanes Joshua R
Published: September 2008

Background

The skeletal neuromuscular junction is a useful model for elucidating mechanisms that regulate synaptogenesis. Developmentally important intercellular interactions at the neuromuscular junction are mediated by the synaptic portion of a basal lamina that completely ensheaths each muscle fiber. Basal laminas in general are composed of four main types of glycosylated proteins: laminins, collagens IV, heparan sulfate proteoglycans and nidogens (entactins). The portion of the muscle fiber basal lamina that passes between the motor nerve terminal and postsynaptic membrane has been shown to bear distinct isoforms of the first three of these. For laminins and collagens IV, the proteins are deposited by the muscle; a synaptic proteoglycan, z-agrin, is deposited by the nerve. In each case, the synaptic isoform plays key roles in organizing the neuromuscular junction. Here, we analyze the fourth family, composed of nidogen-1 and -2.

Results

In adult muscle, nidogen-1 is present throughout muscle fiber basal lamina, while nidogen-2 is concentrated at synapses. Nidogen-2 is initially present throughout muscle basal lamina, but is lost from extrasynaptic regions during the first three postnatal weeks. Neuromuscular junctions in mutant mice lacking nidogen-2 appear normal at birth, but become topologically abnormal as they mature. Synaptic laminins, collagens IV and heparan sulfate proteoglycans persist in the absence of nidogen-2, suggesting the phenotype is not secondary to a general defect in the integrity of synaptic basal lamina. Further genetic studies suggest that synaptic localization of each of the four families of synaptic basal lamina components is independent of the other three.

Conclusion

All four core components of the basal lamina have synaptically enriched isoforms. Together, they form a highly specialized synaptic cleft material. Individually, they play distinct roles in the formation, maturation and maintenance of the neuromuscular junction.
The BHU bicentric bipolar prosthesis in fracture neck femur in active elderly
Authors: Rai Anil K , Agarwal Rakesh , Singh Saurabh , Ratan Ratnav
Published: September 2008

Background

55 BHU bicentric bipolar hemiarthroplasties were reviewed after a mean follow up of 4 years (range 1–5 years). Patients with displaced subcapital fractures were selected for operation on the basis of good mobility before the fracture. Object of the study was to see the efficacy of BHU bipolar prostheses and functional outcome.

Results

There were no incidences of dislocation. Modified Harris hip scoring system scoring system was used which included sitting crosslegged and squatting in view of the sociocultural needs of the patients of Indian subcontinent. Modified Harris hip scoring system 89% had a good or excellent result and 94% had no or only occasional pain. Majority of the patients returned to their prefracture activity.

Conclusion

Thus at follow up of 4 year the BHU bicentric bipolar prosthesis has been shown to be a good option for intracapsular fractures of neck femur with encouraging results.
Effect of arginase II on L-arginine depletion and cell growth in murine cell lines of renal cell carcinoma
Authors: Tate David J , Vonderhaar Derek J , Caldas Yupanqui A , Metoyer Toye , Patterson John R , Aviles Diego H , Zea Arnold H
Published: September 2008

Background

L-arginine is the common substrate for the two isoforms of arginase. Arginase I, highly expressed in the liver and arginase II mainly expressed in the kidney. Arginase I-producing myeloid derived suppressor cells have been shown to inhibit T-cell function by the depletion of L-arginine. On the other hand, arginase II has been detected in patients with cancer and is thought to metabolize L-arginine to L-ornithine needed to sustain rapid tumor growth; however its role in L-arginine depletion is unclear. Thus, in tumor biology, L-arginine metabolism may play a dual role in tumor growth and in the induction of T cell dysfunction. Therefore, we studied in murine renal cell carcinoma (RCC) cell lines, the effect of arginase II on tumor cell proliferation and L-arginine depletion. The effect of arginase inhibitors on cell proliferation was also tested.

Methods

Three murine renal cell carcinoma (mRCC) cell lines were tested for the presence of arginase. nor-NOHA, an arginase inhibitor was used to substantiate the effect of arginase on cell growth and L-arginine depletion. Amino acid levels were tested by HPLC.

Results

Our results show that mRCC cell lines express only arginase II and were able to deplete L-arginine from the medium. Cell growth was independent of the amount of arginase activity expressed by the cells. nor-NOHA significantly (P = 0.01) reduced arginase II activity and suppressed cell growth in cells exhibiting high arginase activity.

The depletion of L-arginine by mRCC induced the decrease expression of CD3ζ a key element for T-cell function.

Conclusion

The results of this study show for the first time that arginase II produced by RCC cell lines depletes L-arginine resulting in decreased expression of CD3ζ. These results indicate that RCC cell lines expressing arginase II can modulate the L-arginine metabolic pathway to regulate both cell growth and T-cell function. Blocking arginase may lead to a decrease in RCC cell growth and aid in restoring immune function by increasing L-arginine availability for T-cell use. Understanding the interplay between arginase II and its interaction with the immune system may provide future therapeutic benefits to treat patients with RCC.
Efficient inhibition of murine breast cancer growth and metastasis by gene transferred mouse survivin Thr34→Ala mutant
Authors: Peng Xing-Chen , Yang Li , Yang Li-Ping , Mao Yong-Qiu , Yang Han-Shuo , Liu Ji-Yan , Zhang Dong-Mei , Chen li-Juan , Wei Yu-Quan
Published: September 2008

Background

Metastasis in breast cancer is a vital concern in treatment because most women with primary breast cancer have micrometastases to distant sites at diagnosis. As a member of the inhibitor of apoptosis protein (IAP) family, survivin has been proposed as an attractive target for new anticancer interventions. In this study, we investigated the role of the plasmid encoding the phosphorylation-defective mouse survivin threonine 34→alanine mutant (Msurvivin T34A plasmid) in suppressing both murine primary breast carcinomas and pulmonary metastases.

Methods

In vitro study, induction of apoptosis by Msurvivin T34A plasmid complexed with cationic liposome (DOTAP/Chol) was examined by PI staining fluorescence microscopy and flow cytometric analysis. The anti-tumor and anti-metastases activity of Msurvivin T34A plasmid complexed with cationic liposome (DOTAP/Chol) was evaluated in female BALB/c mice bearing 4T1 s.c. tumors. Mice were treated twice weekly with i.v. administration of Msurvivin T34A plasmid complexed with cationic liposome (DOTAP/Chol), PORF-9 null plasmid complexed with cationic liposome (DOTAP/Chol), 0.9% NaCl solution for 4 weeks. Tumor volume was observed. After sacrificed, tumor net weight was measured and Lung metastatic nodules of each group were counted. Assessment of apoptotic cells by TUNEL assay was conducted in tumor tissue. Microvessel density within tumor tissue was determined by CD31 immunohistochemistry. Alginate-encapsulated tumor cells test was conducted to evaluate the effect on angiogenesis. By experiment of cytotoxicity T lymphocytes, we test whether Msurvivin T34A plasmid complexed with cationic liposome (DOTAP/Chol) can induce specific cell immune response.

Results

Administration of Msurvivin T34A plasmid complexed with cationic liposome (DOTAP/Chol) resulted in significant inhibition in the growth and metastases of 4T1 tumor model. These anti-tumor and anti-metastases responses were associated with triggering the apoptosis of tumor cells directly, inhibiting angiogenesis and inducing specific cellular immune response.

Conclusion

The present findings suggest that the Msurvivin T34A plasmid complexed with cationic liposome may provide an effective approach to inhibit the growth and metastases of a highly metastatic mouse breast cancer model with minimal side effects.
Gene expression regulation in the context of mouse interspecific mosaic genomes
Authors: L'Hôte David , Serres Catherine , Veitia Reiner A , Montagutelli Xavier , Oulmouden Ahmad , Vaiman Daniel
Published: September 2008

Background

Accumulating evidence points to the mosaic nature of the mouse genome. However, little is known about the way the introgressed segments are regulated within the context of the recipient genetic background. To address this question, we have screened the testis transcriptome of interspecific recombinant congenic mouse strains (IRCSs) containing segments of Mus spretus origin at a homozygous state in a Mus musculus background.

Results

Most genes (75%) were not transcriptionally modified either in the IRCSs or in the parent M. spretus mice, compared to M. musculus. The expression levels of most of the remaining transcripts were 'dictated' by either M. musculus transcription factors ('trans-driven'; 20%), or M. spretus cis-acting elements ('cis-driven'; 4%). Finally, 1% of transcripts were dysregulated following a cis-trans mismatch. We observed a higher sequence divergence between M. spretus and M. musculus promoters of strongly dysregulated genes than in promoters of similarly expressed genes.

Conclusion

Our study indicates that it is possible to classify the molecular events leading to expressional alterations when a homozygous graft of foreign genome segments is made in an interspecific host genome. The inadequacy of transcription factors of this host genome to recognize the foreign targets was clearly the major path leading to dysregulation.