bluuebunny/crossref_metadata_2025 huggingface dataset:
Perforated Duodenal Diverticulitis: A Report of Three Cases
Authors: Miller George , Mueller Claudia , Yim Duke , Macari Michael , Liang Howard , Marcus Stuart , Shamamian Peter
Published: September 2005

Background: Duodenal diverticuli are present in up to 22% of the population. However, perforation of a duodenal diverticulum with spillage of enteric contents into the retroperitoneum is rare. Methods: We report three cases of perforated duodenal diverticulitis. Results: Clinical presentations varied widely from patients with acute abdominal findings and generalized sepsis to a patient with mild symptoms of abdominal discomfort. CT scanning was the imaging modality used to make an accurate diagnosis. Treatment approaches for the most stable patient included nonoperative management with antibiotics, bowel rest and parenteral alimentation, while the less stable patients underwent definitive surgery with complete diversion of gastric contents and biliary flow from the affected area of duodenum. Conclusions: This report highlights the salient issues in the presentation, diagnosis and modern management of patients with this potentially catastrophic disease.
TP53 Gene Mutation, an Unfavorable Prognostic Factor for Malignant Lymphomas in Autoimmune Diseases
Authors: Hoshida Yoshihiko , Hongyo Tadashi , Xu Jing-Xian , Sasaki Toru , Tomita Yasuhiko , Nomura Taisei , Aozasa Katsuyuki
Published: September 2005

Objectives: To investigate whether mutations of the TP53 tumor suppressor gene are associated with a poor prognosis in lymphoproliferative disorders (LPD) developing in patients with a history of autoimmune disease (AID). Methods: Fifty patients, 15 males and 35 females ranging in age from 23 to 83 (median, 61) years, were examined. Rheumatoid arthritis (21 cases) is the commonest type of AID followed by systemic lupus erythematosus (10), dermatomyositis (9), progressive systemic sclerosis (4), and autoimmune hemolytic anemia (6). The interval between the diagnosis of AID and LPD ranged from 1 to 660 months (mean 42 months). Histological, immunohistological, and in situ hybridization studies revealed that 37 tumors were B cell lymphomas and 13 were T cell lymphomas with the Epstein-Barr virus genome present in the tumor cells in 24% of cases. Stage of disease was I in 15 cases, II in 5, III in 9, and IV in 21. Results: Polymerase chain reaction-single strand conformation polymorphism followed by direct sequencing revealed TP53 mutations in 45.9% of B cell and 53.8% of T cell lymphomas. The follow-up study revealed an unfavorable prognosis in cases with mutations compared with those without: the 1-year survival rate was 43.5 and 73.0% in B cell and 16.7 and 50% in T cell lymphoma, respectively. Conclusions: The occurrence of a TP53 mutation is an unfavorable prognostic factor not only in B cell but also in T cell LPD in AID.
Common and Distinct Brain Activation to Threat and Safety Signals in Social Phobia
Authors: Straube Thomas , Mentzel Hans-Joachim , Miltner Wolfgang H.R.
Published: September 2005

Background: Little is known about the functional neuroanatomy underlying the processing of emotional stimuli in social phobia. Objectives: To investigate specific brain activation that is associated with the processing of threat and safety signals in social phobics. Methods: Using functional magnetic resonance imaging, brain activation was measured in social phobic and nonphobic subjects during the presentation of angry, happy and neutral facial expressions under free viewing conditions. Results: Compared to controls, phobics showed increased activation of extrastriate visual cortex regardless of facial expression. Angry, but not neutral or happy, faces elicited greater insula responses in phobics. In contrast, both angry and happy faces led to increased amygdala activation in phobics. Conclusions: The results support the hypothesis that the amygdala is involved in the processing of negative and positive stimuli. Furthermore, social phobics respond sensitively not only to threatening but also to accepting faces and common and distinct neural mechanisms appear to be associated with the processing of threat versus safety signals.
Platelet-Mimicry of Cancer Cells: Epiphenomenon with Clinical Significance
Authors: Tímár József , Tóvári József , Rásó Erzsébet , Mészáros Livia , Bereczky Bíborka , Lapis Károly
Published: September 2005

Stem cell mimicry of cancer cells has been known for a long time and is considered to be responsible for ectopic gene expressions. The stem cell characteristics of tumor cells are shown to be involved in epithelial-mesenchymal transition and in the phenomenon of vascular mimicry. Certain cancer types acquire a geno-phenotype closely resembling the platelets and express several megakaryocytic genes (adhesion receptors αIIbβ3, thrombin receptor and PECAM/CD31 and/or platelet-type 12-LOX) able to activate the coagulation cascade or the platelets themselves. Here we define these potentials as platelet mimicry of cancer cells typical of pancreatic, breast, prostate, colorectal and urogenital cancers and melanoma. Data all support that platelet mimicry of certain cancer types is an important factor in their hematogenous dissemination and provides an attractive therapeutic target. Besides the long-available preclinical data, clinical trials have only recently provided evidence that targeting platelet mimicry of cancers is an efficient way to prevent tumor progression. The systematic discovery of the markers of platelet mimicry in various cancer types and their molecular targeting may provide new supportive therapeutic modalities for the management of the progressing disease.
Interferon-α Promotes the Anti-Proliferative Effect of Gefitinib (ZD1839) on Human Colon Cancer Cell Lines
Authors: Yang Jia-Lin , Qu Xian-Jun , Russell Pamela J. , Goldstein David
Published: September 2005

Objective: Interferon-α (IFNα) treatment is associated with up-regulation of epidermal growth factor receptor (HER1/EGFR) expression and marked growth inhibition of colon cancer cell lines in vitro.We aimed to determine the effect of combining IFNα and gefitinib on colon cancer cell line growth. Methods: A panel of nine colon cancer cell lines were characterised for expression of HER1/EGFR and then treated with gefitinib alone, or IFNα alone, or IFNα plus gefitinib, following a pre-treatment using vehicle or IFNα. Crystal violet staining and flow cytometry were used to assess cell proliferation and expression of HER1/EGFR. The indexes and statistical assays were used to evaluate significant differences between treatment groups against vehicle control. Results: All cell lines except SW620 were HER1/EGFR positive. IFNα treatment was associated with significant up-regulation of cell surface HER1/EGFR expression in all HER1/EGFR-positive cell lines except KM12SM. Concurrent treatment with IFNα and gefitinib, or IFNα pre-treatment followed by gefitinib, or IFNα pre-treatment followed by a combination of IFNα plus gefitinib, additively or supra-additively/synergistically enhanced the sensitivity of the seven HER1/EGFR-up-regulated cell lines. Conclusion: IFNα improves the anti-proliferative effect of EGFR inhibition in colorectal cancer cell lines. This approach may have clinical implications for improving treatment based on targeting of HER1/EGFR.
Do Mothers’ Opinions Matter in Teens’ Sexual Activity?
Authors: Fingerson Laura
Published: September 2005

Using the Add Health data ( N = 9,530 dyads), this study explores sexual socialization in the family using the theory of reasoned action by assessing how mothers’ opinions are associated with their children’s sexual behavior. Findings suggest that the more sexually liberal teens think their mothers are, the more likely the teens are to have higher numbers of sex partners. Talking about sex and having a strong connection between mothers and teens contribute to sexual norm transmission. The more talk about sex there is within the dyad, the more likely the teen is to have had sex. The stronger the connection between mothers and teens, the less likely the teen is to have had sex. Finally, for boys, verbal communication with their mothers is more important in sexual norm transmission; and for girls, having a good connection in the dyad is more important.
Contributions to Family and Household Activities by the Husbands of Midlife Professional Women
Authors: Gordon Judith R. , Whelan-Berry Karen S.
Published: September 2005

This article presents an exploratory study that furthers our understanding of the functioning of two-career couples at midlife and, in particular, our understanding of the husband’s contributions to family and household activities. More specifically, it addresses the following questions regarding dual-career couples: (a) Whose career has precedence? (b) What is the nature of the husband’s contributions to the family and household? and (c) What types of support result? This study is part of a larger research project that focuses on the professional and personal lives of a group of midlife professional women who were married, had children, and had enduring careers. The results presented here describe the women’s perceptions of support (or lack of support) provided by their spouses in their family and household. It discusses the implications of such support for family functioning and for the ability of midlife women to pursue full-time careers.
African American Fathers
Authors: Smith Carolyn A. , Krohn Marvin D. , Chu Rebekah , Best Oscar
Published: September 2005

Much of the literature on African American fathers has tended to perpetuate a stereotype of absent and unsupportive parenting. This study employs a life course perspective to investigate the extent and predictors of involvement by young fathers. Data come from the Rochester Youth Development Study, a longitudinal study that has followed a representative sample of urban youth since they were in the seventh or eighth grade. Analysis is based on the young men in the sample who became fathers by age 22, of whom 67% are African American. Results suggest that African American fathers do not differ significantly from other young fathers in their contact with and support provided to their eldest biological child. For African American fathers, fulfilling a father role is, as hypothesized, related to the success of transition to adult roles and relationships and to prosocial behavior and problem behavior.
The Gendered Rice Bowl
Authors: Hanser Amy
Published: September 2005

This article examines new conceptions of gender and sexuality in China, asking how and why they have become so integral to the organization of service work regimes there. Drawing on ethnographic data collected in three urban Chinese retail settings, this article demonstrates how essentialized conceptions of gender and sexuality powerfully communicate class distinctions in service settings through associations with the imagery of China’s shift from socialism to a marketized society. A shift from the socialist “iron rice bowl” to the “rice bowl of youth” infuses youthful, feminine, urban bodies with value while simultaneously devaluing middle-aged and rural women. This article argues that an essentializing discourse of gender legitimates new inequalities in urban China by masking the class distinctions simultaneously produced.
Make Room for Daddy
Authors: Stein Arlene
Published: September 2005

What are the sources of continuing antipathy toward homosexuality, and what might they tell us about changing forms of American masculinity? This article documents some emergent homophobias circulating among conservative activists in relation to campaigns against gay rights in the early 1990s and against gay marriage in 2004. As feminist critiques of traditional masculinity make their way into conservative rhetoric and as men struggle to define a role that maintains male authority without sounding overly authoritarian, new forms of homophobia have emerged that are compatible with conservatives’ quest to be seen as compassionate protectors of the family.
Engendering Trauma
Authors: McGuffey C. Shawn
Published: September 2005

Using extra familial child sexual abuse (CSA) as an example of family trauma, the author interviewed 60 parents of sexually abused boys on multiple occasions to analyze the organization of gender, race, and class in parental coping processes. Despite access to alternative interpretations of CSA that challenge conventional notions of gender, parents in this study typically rely on traditional themes to make meaning of the CSA experience. The author organized the data analytically around gender strategies and found that parents used race- and class-specific gender strategies in the aftermath of trauma. Most important, mother-blame is theorized as a form of gender reaffirmation. The author uses the term gender reaffirmation to illustrate the way social actors recuperate after a situation has been interpreted as detrimental, challenging, or stressful to heteronormative gender relations. Mother-blaming accounts encouraged race and class enactments of gender that had negative consequences for women and helped maintain men’s cultural power.
Stratified Reproduction and Poor Women’s Resistance
Authors: McCormack Karen
Published: September 2005

The welfare mother is a powerful symbol of the supposed irresponsible, sexually promiscuous, and immoral behavior of the poor. Resting on dominant ideologies of race, class, and gender, the welfare mother suggests not a poor mother but a bad mother. Based on interviews with 34 mothers receiving public assistance, this article explores how women receiving assistance claim for themselves an identity as good mothers by defining the appropriate responsibilities of mothers to prioritize, protect, discipline, provide for, and spend time with their children. The material realities of poverty combined with work requirements now attached to public assistance exacerbate contradictions between these roles and create difficulties for these mothers. This article explores these contradictions and examines the possibilities for and limits of their use as resistance strategies.
Divorce Culture and Marital Gender Equality
Authors: Yodanis Carrie
Published: September 2005

This article examines the cross-national relationship between a divorce culture on a national level and gender equality in intact marriages. Based on multilevel analysis of data from 22 countries in the International Social Survey Programme, the results indicate that a divorce culture on the national level is associated with greater marital equality. In other words, in countries where divorce is accepted and practiced, the distribution of work between women and men in marriage is more equal. These findings support the enhanced equality hypothesis that the possibility of divorce provides women with leverage to gain more equal status within marriage.
Postcolonial Feminism, The Politics of Identification, and the Liberal Bargain
Authors: Sa’ar Amalia
Published: September 2005

The article focuses on the complex positioning of people from disempowered backgrounds with respect to liberalism and liberal dividends. The author offers the term liberal bargain, paraphrasing Deniz Kandiyoti’s “patriarchal bargain” and Cynthia Cockburn’s “ethnic bargain,” and dwells on the interconnections between the three. The liberal bargain indicates the particular consciousness and symbolic whitening that “colorized” (i.e., excluded/oppressed) people tend to adopt when they attempt to cash in on the liberal promise. Within the discourse of postcolonial feminism, the concept is intended to promote the discussion of power differentials among women, through refining the analytically dissatisfactory color metaphors habitually used to address issues of hegemony and ethnocentrism.
A proof-of-principle pharmacokinetic, pharmacodynamic, and clinical study with purine nucleoside phosphorylase inhibitor immucillin-H (BCX-1777, forodesine)
Authors: Gandhi Varsha , Kilpatrick John M. , Plunkett William , Ayres Mary , Harman Leigh , Du Min , Bantia Shanta , Davisson Jan , Wierda William G. , Faderl Stefan , Kantarjian Hagop , Thomas Deborah
Published: September 2005

The discovery of purine nucleoside phosphorylase (PNP) deficiency and T lymphocytopenia suggested that inhibition of this enzyme could serve as a therapeutic target. Inhibitors of PNP failed until structure-based synthesis of immucillin-H (BCX-1777, forodesine), a transition-state analog of PNP. The picomolar potency for PNP, T cell-selective cytotoxicity, and animal studies provided the rationale for use of forodesine in T-cell malignancies. Five patients were treated with an intravenous infusion of forodesine (40 mg/m2) on day 1; treatment continued on day 2; forodesine was administered every 12 hours for an additional 8 doses. Plasma and cellular pharmacokinetics and pharmaco-dynamics were investigated. Median peak level of forodesine (5.4 μM) was achieved at the end of infusion. This level was sufficient to increase plasma 2′-deoxyguanosine (dGuo) concentrations in all patients. Intracellular deoxyguanosine triphosphate (dGTP) increased by 2- to 40-fold in 4 of 5 patients (8 of 9 courses) and correlated with antileukemia activity in 4 patients. However, objective responses were not observed. This was the first clinical study in humans to demonstrate the plasma pharmacokinetics and the pharmacodynamic effectiveness of the PNP inhibitor, forodesine; however, regrowth of leukemia cells in the blood and marrow after course 1 suggested that a different therapeutic schedule should be considered for future studies.
KIR reconstitution is altered by T cells in the graft and correlates with clinical outcomes after unrelated donor transplantation
Authors: Cooley Sarah , McCullar Valarie , Wangen Rosanna , Bergemann Tracy L. , Spellman Stephen , Weisdorf Daniel J. , Miller Jeffrey S.
Published: September 2005

Although unrelated hematopoietic cell transplantation (HCT) is curative for many hematologic malignancies, complications and relapse remain challenging obstacles. Natural killer (NK) cells, which recover quickly after transplantation, produce cytokines and express killer immunoglobulin-like receptors (KIRs) that regulate their cytotoxicity. Some clinical trials based on a KIR ligand mismatch strategy are associated with less relapse and increased survival, but results are mixed. We hypothesized that T cells in the graft may affect NK cell function and KIR expression after unrelated transplantation and that these differences correlate with clinical outcomes. NK cell function was evaluated using 77 paired samples from the National Marrow Donor Program Research Repository. Recipient NK cells at 100 days after both unmanipulated bone marrow (UBM) and T-cell depleted (TCD) transplants were compared with NK cells from their healthy donors. NK cells expressed fewer KIRs and produced more interferon γ (IFN-γ) after UBM compared to TCD transplants. Multivariate models showed that increased NK cell IFN-γ production correlated with more acute graft-versus-host disease (GVHD), and decreased KIR expression correlated with inferior survival. These results support the notion that T cells in the graft affect NK cell reconstitution in vivo. Understanding these mechanisms may result in strategies to improve clinical outcomes from unrelated HCT.
TGF-β type II receptor–deficient thymocytes develop normally but demonstrate increased CD8+ proliferation in vivo
Authors: Levéen Per , Carlsén Maria , Makowska Anna , Oddsson Saemundur , Larsson Jonas , Goumans Marie-José , Cilio Corrado M. , Karlsson Stefan
Published: September 2005

We have taken advantage of the Cre/lox system to generate a mouse model with inducible deficiency of transforming growth factor β receptor II (TβRII). Using this approach, transforming growth factor β (TGF-β) signaling deficiency can be restricted to the hematopoietic system by bone marrow transplantation. Mice that received transplants with TβRII-/- bone marrow develop a lethal inflammatory disorder closely resembling that of TGF-β1-null mice. Previous in vitro studies have suggested multiple roles for TGF-β in T-cell development, including proliferation, apoptosis, and differentiation. We used our transplantation model to ask whether T-cell development is normal in the absence of TGF-β signaling. The findings show for the first time in vivo and in fetal thymus organ culture (FTOC) that TGF-β is not required for thymocytes to differentiate along the entire pathway of thymic T-cell development, as defined by the expression patterns of CD4, CD8, CD25, and CD44. In contrast to previous investigations, no increase of thymocyte apoptosis was observed. However, TβRII-deficient CD8+ thymocytes displayed a 2-fold increase in proliferation rate, as determined by bromodeoxyuridine (BrdU) incorporation in vivo. These results reinforce the importance of TGF-β as an immune regulator critical for T-cell function.
Interferon-γ-induced gene expression in CD34 cells: identification of pathologic cytokine-specific signature profiles
Authors: Zeng Weihua , Miyazato Akira , Chen Guibin , Kajigaya Sachiko , Young Neal S. , Maciejewski Jaroslaw P.
Published: September 2005

Hematopoietic effects of interferon-γ (IFN-γ) may be responsible for certain aspects of the pathology seen in bone marrow failure syndromes, including aplastic anemia (AA), paroxysmal nocturnal hemoglobinuria (PNH), and some forms of myelodysplasia (MDS). Overexpression of and hematopoietic inhibition by IFN-γ has been observed in all of these conditions. In vitro, IFN-γ exhibits strong inhibitory effects on hematopoietic progenitor and stem cells. Previously, we have studied the transcriptome of CD34 cells derived from patients with bone marrow failure syndromes and identified characteristic molecular signatures common to some of these conditions. In this report, we have investigated genome-wide expression patterns after exposure of CD34 and bone marrow stroma cells derived from normal bone marrow to IFN-γ in vitro and have detected profound changes in the transcription profile. Some of these changes were concordant in both stroma and CD34 cells, whereas others were specific to CD34 cells. In general, our results were in agreement with the previously described function of IFN-γ in CD34 cells involving activation of apoptotic pathways and immune response genes. Comparison between the IFN-γ transcriptome in normal CD34 cells and changes previously detected in CD34 cells from AA and PNH patients reveals the presence of many similarities that may reflect molecular signature of in vivo IFN-γ exposure.
Factors associated with early molecular remission after T cell-depleted allogeneic stem cell transplantation for chronic myelogenous leukemia
Authors: Savani Bipin N. , Rezvani Katayoun , Mielke Stephan , Montero Aldemar , Kurlander Roger , Carter Charles S. , Leitman Susan , Read Elizabeth J. , Childs Richard , Barrett A. John
Published: September 2005

Eighty patients with chronic myeloid leukemia (CML) underwent T cell-depleted stem cell transplantation from an HLA-identical sibling, with add-back of donor T cells on days 30 to 45 and days 60 to 100 in patients in whom grade 2 or greater acute graft-versus-host disease (GVHD) developed. The outcomes for 54 patients with chronic-phase (CP) and 26 with advanced-phase (AP) disease were as follows: overall survival, 85% ± 5% versus 36% ± 10%; transplantation-related mortality (TRM), 13% ± 5% versus 43% ± 11%; and current leukemia-free survival, 76% ± 6% versus 34% ± 9%. The day-30 lymphocyte count (LC30) was strongly associated with outcome. For patients in CP with counts greater than the median of 0.30 × 109/L, survival was 100% versus 70% ± 9% (P = .003); current LFS 100% versus 56% ± 9% (P = .002); and TRM 0% versus 26% ± 8% (P = .006). Higher-than-median LC30 correlated significantly with molecular remission (MR) at 3, 6, and 12 months and with higher CD34 doses. Lymphocyte subset analysis performed in 20 patients available for phenotyping showed that LC30 was highly correlated with absolute CD56+CD3- natural killer cell numbers (NK30), which also predicted for survival and MR. CD34 cell dose, LC30, and NK30, but not day-30 CD3+ cell count, were highly correlated and were significant predictors of transplantation outcome. These results suggest that transplanted CD34 cell doses greater than 5 × 106/kg may improve outcomes by increasing the early recovery of NK cells.
Hemolytic uremic syndrome–associated Shiga toxins promote endothelial-cell secretion and impair ADAMTS13 cleavage of unusually large von Willebrand factor multimers
Authors: Nolasco Leticia H. , Turner Nancy A. , Bernardo Aubrey , Tao Zhenyin , Cleary Thomas G. , Dong Jing-fei , Moake Joel L.
Published: September 2005

Shiga toxin 1 (Stx-1) and Stx-2 produced by enterohemorrhagic Escherichia coli cause the diarrhea-associated hemolytic uremic syndrome (HUS). This type of HUS is characterized by obstruction of the glomeruli and renal microvasculature by platelet-fibrin thrombi, acute renal failure, thrombocytopenia, microvascular hemolytic anemia, and plasma levels of von Willebrand factor (VWF)-cleaving protease (ADAMTS13) activity that are within a broad normal range. We investigated the mechanism of initial platelet accumulation on Stx-stimulated endothelial cells. Stx-1 or Stx-2 (1-10 nM) stimulated the rapid secretion of unusually large (UL) VWF multimeric strings from human umbilical vein endothelial cells (HUVECs) or human glomerular microvascular endothelial cells (GMVECs). Perfused normal human platelets immediately adhered to the secreted ULVWF multimeric strings. Nanomolar concentrations (1-10 nM) of the Shiga toxins were as effective in inducing the formation of ULVWF-platelet strings as millimolar concentrations (0.1-20 mM) of histamine. The rate of ULVWF-platelet string cleavage by plasma or recombinant ADAMTS13 was delayed by 3 to 10 minutes (or longer) in the presence of 10 nM Stx-1 or Stx-2 compared with 20 mM histamine. Stx-induced formation of ULVWF strings, and impairment of ULVWF-platelet string cleavage by ADAMTS13, may promote initial platelet adhesion above glomerular endothelial cells. These processes may contribute to the evolution of glomerular occlusion by platelet and fibrin thrombi in diarrhea-associated HUS.
Transformation of BCR-deficient germinal-center B cells by EBV supports a major role of the virus in the pathogenesis of Hodgkin and posttransplantation lymphomas
Authors: Bechtel Dörte , Kurth Julia , Unkel Claus , Küppers Ralf
Published: September 2005

In classic Hodgkin lymphoma (HL) and posttransplantation lymphoproliferative disease (PTLD), 2 malignancies frequently associated with Epstein-Barr virus (EBV), the tumor cells often appear to derive from B-cell receptor (BCR)–deficient and therefore preapoptotic germinal center (GC) B cells. To test whether EBV can rescue BCR-less GC B cells, we infected human tonsillar CD77+ GC B cells in vitro with EBV. More than 60 monoclonal lymphoblastoid cell lines (LCLs) were established. Among these, 28 cell lines did not express surface immunoglobulin (sIg). Two of the sIg-negative cell lines carry obviously destructive mutations that have been introduced into originally functional VH gene rearrangements during the process of somatic hypermutation. Quantitative reverse transcriptase–polymerase chain reaction (RT-PCR) showed that in most other lines the sIg deficiency was not simply the result of transcriptional down-regulation, but it was rather due to posttranscriptional defects. These findings strongly support the idea that EBV plays a central role in the pathogenesis of classic HL and PTLD by rescuing BCR-deficient, preapoptotic GC B cells from apoptosis, and that EBV infection renders the cells independent from survival signals normally supplied by a BCR. The monoclonal LCLs represent valuable models for early stages of lymphoma development in classic HL and PTLD.
TmaDB: a repository for tissue microarray data
Authors: Sharma-Oates Archana , Quirke Philip , Westhead David R
Published: September 2005

Background

Tissue microarray (TMA) technology has been developed to facilitate large, genome-scale molecular pathology studies. This technique provides a high-throughput method for analyzing a large cohort of clinical specimens in a single experiment thereby permitting the parallel analysis of molecular alterations (at the DNA, RNA, or protein level) in thousands of tissue specimens. As a vast quantity of data can be generated in a single TMA experiment a systematic approach is required for the storage and analysis of such data.

Description

To analyse TMA output a relational database (known as TmaDB) has been developed to collate all aspects of information relating to TMAs. These data include the TMA construction protocol, experimental protocol and results from the various immunocytological and histochemical staining experiments including the scanned images for each of the TMA cores. Furthermore the database contains pathological information associated with each of the specimens on the TMA slide, the location of the various TMAs and the individual specimen blocks (from which cores were taken) in the laboratory and their current status i.e. if they can be sectioned into further slides or if they are exhausted. TmaDB has been designed to incorporate and extend many of the published common data elements and the XML format for TMA experiments and is therefore compatible with the TMA data exchange specifications developed by the Association for Pathology Informatics community. Finally the design of the database is made flexible such that TMA experiments from several types of cancer can be stored in a single database, which incorporates the national minimum data set required for pathology reports supported by the Royal College of Pathologists (UK).

Conclusion

TmaDB will provide a comprehensive repository for TMA data such that a large number of results from the numerous immunostaining experiments can be efficiently compared for each of the TMA cores. This will allow a systematic, large-scale comparison of tumour samples to facilitate the identification of gene products of clinical importance such as therapeutic or prognostic markers. In addition this work will contribute to the establishment of a standard for reporting TMA data analogous to MIAME in the description of microarray data.
Expression capable library for studies of Neisseria gonorrhoeae, version 1.0
Authors: Brettin Thomas , Altherr Michael R , Du Ying , Mason Roxie M , Friedrich Alexandra , Potter Laura , Langford Chris , Keller Thomas J , Jens Jason , Howie Heather , Weyand Nathan J , Clary Susan , Prichard Kimberly , Wachocki Susi , Sodergren Erica , Dillard Joseph P , Weinstock George , So Magdalene , Arvidson Cindy Grove
Published: September 2005

Background

The sexually transmitted disease, gonorrhea, is a serious health problem in developed as well as in developing countries, for which treatment continues to be a challenge. The recent completion of the genome sequence of the causative agent, Neisseria gonorrhoeae, opens up an entirely new set of approaches for studying this organism and the diseases it causes. Here, we describe the initial phases of the construction of an expression-capable clone set representing the protein-coding ORFs of the gonococcal genome using a recombination-based cloning system.

Results

The clone set thus far includes 1672 of the 2250 predicted ORFs of the N. gonorrhoeae genome, of which 1393 (83%) are sequence-validated. Included in this set are 48 of the 61 ORFs of the gonococcal genetic island of strain MS11, not present in the sequenced genome of strain FA1090. L-arabinose-inducible glutathione-S-transferase (GST)-fusions were constructed from random clones and each was shown to express a fusion protein of the predicted size following induction, demonstrating the use of the recombination cloning system. PCR amplicons of each ORF used in the cloning reactions were spotted onto glass slides to produce DNA microarrays representing 2035 genes of the gonococcal genome. Pilot experiments indicate that these arrays are suitable for the analysis of global gene expression in gonococci.

Conclusion

This archived set of Gateway® entry clones will facilitate high-throughput genomic and proteomic studies of gonococcal genes using a variety of expression and analysis systems. In addition, the DNA arrays produced will allow us to generate gene expression profiles of gonococci grown in a wide variety of conditions. Together, the resources produced in this work will facilitate experiments to dissect the molecular mechanisms of gonococcal pathogenesis on a global scale, and ultimately lead to the determination of the functions of unknown genes in the genome.
Evidence for proteolytic cleavage of brevican by the ADAMTSs in the dentate gyrus after excitotoxic lesion of the mouse entorhinal cortex
Authors: Mayer Joanne , Hamel Michelle G , Gottschall Paul E
Published: August 2005

Background

Brevican is a member of the lectican family of aggregating extracellular matrix (ECM) proteoglycans that bear chondroitin sulfate (CS) chains. It is highly expressed in the central nervous system (CNS) and is thought to stabilize synapses and inhibit neural plasticity and as such, neuritic or synaptic remodeling would be less likely to occur in regions with intact and abundant, lectican-containing, ECM complexes. Neural plasticity may occur more readily when these ECM complexes are broken down by endogenous proteases, the ADAMTSs (a
disintegrin and metalloproteinase with thrombospondin motifs), that selectively cleave the lecticans. The purpose of these experiments was to determine whether the production of brevican or the ADAMTS-cleaved fragments of brevican were altered after deafferentation and reinnervation of the dentate gyrus via entorhinal cortex lesion (ECL).

Results

In the C57Bl6J mouse, synaptic density in the molecular layer of the dentate gyrus, as measured by synaptophysin levels in ELISA, was significantly attenuated 2 days (nearly 50% of contralateral) and 7 days after lesion and returned to levels not different from the contralateral region at 30 days. Immunoreactive brevican in immunoblot was elevated 2 days after lesion, whereas there was a significant increase in the proteolytic product at 7, but not 30 days post-lesion. ADAMTS activity, estimated using the ratio of the specific ADAMTS-derived brevican fragment and intact brevican levels was increased at 7 days, but was not different from the contralateral side at 2 or 30 days after deafferentation.

Conclusion

These findings indicate that ADAMTS activity in the dentate outer molecular layer (OML) is elevated during the initial synaptic reinnervation period (7 days after lesion). Therefore, proteolytic processing of brevican appears to be a significant extracellular event in the remodeling of the dentate after EC lesion, and may modulate the process of sprouting and/or synaptogenesis.
Soy isoflavone glycitein protects against beta amyloid-induced toxicity and oxidative stress in transgenic Caenorhabditis elegans
Authors: Gutierrez-Zepeda Astrid , Santell Ross , Wu Zhixin , Brown Marishka , Wu YanJue , Khan Ikhlas , Link Christopher D , Zhao Baolu , Luo Yuan
Published: August 2005

Background

Epidemiological studies have associated estrogen replacement therapy with a lower risk of developing Alzheimer's disease, but a higher risk of developing breast cancer and certain cardiovascular disorders. The neuroprotective effect of estrogen prompted us to determine potential therapeutic impact of soy-derived estrogenic compounds. TransgenicC. elegans, that express human beta amyloid (Aβ), were fed with soy derived isoflavones genistein, daidzein and glycitein (100 μg/ml) and then examined for Aβ-induced paralysis and the levels of reactive oxygen species.

Results

Among the three compounds tested, only glycitein alleviated Aβ expression-induced paralysis in the transgenicC. elegans. This activity of glycitein correlated with a reduced level of hydrogen peroxide in the transgenicC. elegans.In vitroscavenging effects of glycitein on three types of reactive oxygen species confirmed its antioxidant properties. Furthermore, the transgenicC. elegansfed with glycitein exhibited reduced formation of β amyloid.

Conclusion

These findings suggest that a specific soy isoflavone glycitein may suppress Aβ toxicity through combined antioxidative activity and inhibition of Aβ deposition, thus may have therapeutic potential for prevention of Aβ associated neurodegenerative disorders.
Signs and symptoms in children with a serious infection: a qualitative study
Authors: Van den Bruel Ann , Bruyninckx Rudi , Vermeire Etienne , Aerssens Peter , Aertgeerts Bert , Buntinx Frank
Published: August 2005

Background

Early diagnosis of serious infections in children is difficult in general practice, as incidence is low, patients present themselves at an early stage of the disease and diagnostic tools are limited to signs and symptoms from observation, clinical history and physical examination. Little is known which signs and symptoms are important in general practice. With this qualitative study, we aimed to identify possible new important diagnostic variables.

Methods

Semi-structured interviews with parents and physicians of children with a serious infection. We investigated all signs and symptoms that were related to or preceded the diagnosis. The analysis was done according to the grounded theory approach. Participants were recruited in general practice and at the hospital.

Results

18 children who were hospitalised because of a serious infection were included. On average, parents and paediatricians were interviewed 3 days after admittance of the child to hospital, general practitioners between 5 and 8 days after the initial contact.

The most prominent diagnostic signs in seriously ill children were changed behaviour, crying characteristics and the parents' opinion. Children either behaved drowsy or irritable and cried differently, either moaning or an inconsolable, loud crying. The parents found this illness different from previous illnesses, because of the seriousness or duration of the symptoms, or the occurrence of a critical incident. Classical signs, like high fever, petechiae or abnormalities at auscultation were helpful for the diagnosis when they were present, but not helpful when they were absent.

Conclusion

behavioural signs and symptoms were very prominent in children with a serious infection. They will be further assessed for diagnostic accuracy in a subsequent, quantitative diagnostic study.
Health status in older hospitalized patients with cancer or non-neoplastic chronic diseases
Authors: Corsonello Andrea , Pedone Claudio , Carosella Luciana , Corica Francesco , Mazzei Bruno , Antonelli Incalzi Raffaele ,   the Gruppo Italiano di Farmacovigilanza nell'Anziano (GIFA) investigators
Published: August 2005

Background

Whether cancer is more disabling than other highly prevalent chronic diseases in the elderly is not well understood, and represents the objective of the present study.

Methods

We used data from the Gruppo Italiano di Farmacovigilanza nell'Anziano (GIFA) study, a large collaborative observational study based in community and university hospitals located throughout Italy. Our series consisted of three groups of patients with non-neoplastic chronic disease (congestive heart failure, CHF, N = 832; diabetes mellitus, N = 939; chronic obstructive pulmonary disease, COPD, N = 399), and three groups of patients with cancer (solid tumors without metastasis, N = 813; solid tumors with metastasis, N = 259; leukemia/lymphoma, N = 326). Functional capabilities were ascertained using the activities of daily living (ADL) scale, and categorical variables for dependency in at least 1 ADL or dependency in 3 or more ADLs were considered in the analysis. Cognitive status was evaluated by the 10-items Hodgkinson Abbreviated Mental Test (AMT).

Results

Cognitive impairment was more prevalent in patients with CHF (28.0%) or COPD (25.8%) than in those with cancer (solid tumors = 22.9%; leukemia/lymphoma = 19.6%; metastatic cancer = 22.8%). Dependency in at least 1 ADL was highly prevalent in patients with metastatic cancer (31.3% vs. 24% for patients with CHF and 22.4% for those with non-metastatic solid tumors, p < 0.001). In people aged 80 years or more, metastatic cancer was not associated with increased prevalence of physical disability. In multivariable analysis, metastatic cancer was associated with a greater prevalence of physical (OR 2.09, 95%CI 1.51–2.90) but not cognitive impairment (OR 1.34, 95%CI 0.94–1.91) with respect to CHF patients. Finally, diabetes was significantly associated with cognitive impairment (OR 1.40, 95%CI 1.11–1.78).

Conclusion

Cancer should not be considered as an ineluctable cause of severe cognitive and physical impairment, at least not more than other chronic conditions highly prevalent in older people, such as CHF and diabetes mellitus.
The relationship between risk factors for falling and the quality of life in older adults
Authors: Ozcan Ayse , Donat Hulya , Gelecek Nihal , Ozdirenc Mehtap , Karadibak Didem
Published: August 2005

Background

Falls are one of the major health problems that effect the quality of life among older adults. The aim of this study was to explore the relationship between quality of life (Short Form-12) and the risk factors of falls (balance, functional mobility, proprioception, muscle strength, flexibility and fear of falling) in older adults.

Methods

One hundred sixteen people aged 65 or older and living in the T.C. Emekli Sandigi Narlidere nursing home participated in the study. Balance (Berg Balance test), functional mobility (Timed Up and Go), proprioception (joint position sense), muscle strength (back/leg dynamometer), flexibility (sit and reach) and fear of falling (Visual Analogue Scale) were assessed as risk factors for falls. The quality of life was measured by Short Form-12 (SF-12).

Results

A strong positive correlation was observed between Physical Health Component Summary of SF-12, General Health Perception and balance, muscle strength. Proprioception and flexibility did not correlated with SF-12 (p > 0.05). There was negative correlation between Physical Health Component Summary of SF-12, General Health Perception and fear of falling, functional mobility (p < 0.05).

Conclusion

We concluded that the risk factors for falls (balance, functional mobility, muscle strength, fear of falling) in older adults are associated with quality of life while flexibility and proprioception are not.
The impact of partial smokefree legislation on health inequalities: Evidence from a survey of 1150 pubs in North West England
Authors: Tocque Karen , Edwards Richard , Fullard Brenda
Published: September 2005

Background

The UK government claims that between 10 and 30% of pubs and bars will be exempt from proposed legislation to achieve smokefree enclosed public places across England. This arises from the contentious inclusion that pubs and bars that do not prepare and serve food and private members clubs, will be able to allow smoking. We aimed to survey pubs and bars across the North West of England to assess smoking policies and the proportion and variations by deprivation level of venues preparing and serving food.

Methods

We carried out a telephone survey of 1150 pubs and bars in 14 local authorities across the North West of England. The main data items were current smoking policy, food preparation and serving status, and intention to change food serving and smoking status in the event of implementation of the proposed English partial smokefree legislation.

Results

29 pubs and bars (2.5%) were totally smoke-free, 500 (44%) had partial smoking restrictions, and 615 (54%) allowed smoking throughout. Venues situated in the most deprived quintiles (4 and 5) of deprivation were more likely to allow unrestricted smoking (62% vs 33% for venues in quintiles 1 and 2). The proportion of pubs and bars not preparing and serving food on the premises was 44% (95% CI 42 to 46%), and ranged from 21% in pubs and bars in deprivation quintile 1 to 63% in quintile 5.

Conclusion

The proportion of pubs and bars which do not serve food was far higher than the 10–30% suggested by the UK government. The proportion of pubs allowing unrestricted smoking and of non-food venues was higher in more disadvantaged areas, suggesting that the proposed UK government policy of exempting pubs in England which do not serve food from smokefree legislation will exacerbate inequalities in smoking and health.
Pride and confidence at work: potential predictors of occupational health in a hospital setting
Authors: Nilsson Kerstin , Hertting Anna , Petterson Inga-Lill , Theorell Töres
Published: September 2005

Background

This study focuses on determinants of a healthy work environment in two departments in a Swedish university hospital. The study is based on previously conducted longitudinal studies at the hospital (1994–2001), concerning working conditions and health outcomes among health care personnel in conjunction with downsizing processes. Overall, there was a general negative trend in relation to mental health, as well as long-term sick leave during the study period. The two departments chosen for the current study differed from the general hospital trend in that they showed stable health development. The aim of the study was to identify and analyse experiential determinants of healthy working conditions.

Methods

Thematic open-ended interviews were carried out with seventeen managers and key informants, representing different groups of co-workers in the two departments. The interviews were transcribed verbatim and an inductive content analysis was made.

Results

In the two studied departments the respondents perceived that it was advantageous to belong to a small department, and to work in cooperation-oriented care. The management approaches described by both managers and co-workers could be interpreted as transformational, due to a strain of visionary, delegating, motivating, confirmative, supportive attitudes and a strongly expressed solution-oriented attitude. The daily work included integrated learning activities. The existing organisational conditions, approaches and attitudes promoted tendencies towards a work climate characterised by trust, team spirit and professionalism. In the description of the themes organisational conditions, approaches and climate, two core determinants, work-pride and confidence, for healthy working conditions were interpreted. Our core determinants augment the well-established concepts: manageability, comprehensiveness and meaningfulness. These favourable conditions seem to function as a buffer against the general negative effects of downsizing observed elsewhere in the hospital, and in the literature.

Conclusion

Research illuminating health-promoting aspects is rather unusual. This study could be seen as explorative. The themes and core dimensions we found could be used as a basis for further intervention studies in similar health-care settings. The result could also be used in future health promotion studies in larger populations. One of the first steps in such a strategy is to formulate relevant questions, and we consider that this study contributes to this.
Influence of condensation temperature on selected exhaled breath parameters
Authors: Goldoni Matteo , Caglieri Andrea , Andreoli Roberta , Poli Diana , Manini Paola , Vettori Maria Vittoria , Corradi Massimo , Mutti Antonio
Published: September 2005

Background

The effects of changes in cooling temperature on biomarker levels in exhaled breath condensate have been little investigated. The aim of the study was to test the effect of condensation temperature on the parameters of exhaled breath condensate and the levels of selected biomarkers.

Methods

Exhaled breath condensate was collected from 24 healthy subjects at temperatures of -10, -5, 0 and +5 C degrees. Selected parameters (condensed volume and conductivity) and biomarkers (hydrogen peroxide, malondialdehyde) were measured.

Results

There was a progressive increase in hydrogen peroxide and malondialdehyde concentrations, and condensate conductivity as the cooling temperature increased; total condensate volume increased as the cooling temperature decreased.

Conclusion

The cooling temperature of exhaled breath condensate collection influenced selected biomarkers and potential normalizing factors (particularly conductivity) in different ways ex vivo. The temperature of exhaled breath condensate collection should be controlled and reported.