bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro Paclitaxel and Radiation Effects on the Cell Types Responsible for Vascular Stenosis: A Preliminary Analysis
Authors: Zhang J. , Melhem M. , Kassing W. , Kelly B. , Wang Y. , Krishnamoorthy M. , Heffelfinger S. , Desai P. , Roy-Chaudhury P.
Published: December 2006

Hemodialysis vascular access dysfunction as a result of venous neointimal hyperplasia in dialysis access grafts and fistulae is currently a huge clinical problem. The aim of this study was to assess the effects of paclitaxel and radiation, both singly and in combination on the proliferation of cell types present within the lesion of venous neointimal hyperplasia (vascular smooth muscle cells, fibroblasts and endothelial cells within the neointimal microvessels). Vascular smooth muscle cells, fibroblasts and endothelial cells were plated onto 96-well plates and exposed to different concentrations and doses of paclitaxel and radiation, respectively (both individually and in combination). Growth inhibition was assessed with an MTT assay. Both paclitaxel and radiation resulted in significant growth inhibition of all three cell types. However, even small doses of paclitaxel appeared to attenuate the antiproliferative effect of radiation on these cell types. Further experiments to elucidate the mechanism behind these findings could result in a better understanding of combination antiproliferative therapies.
Fragmented Pictures Revisited: Long-Term Changes in Repetition Priming, Relation to Skill Learning, and the Role of Cognitive Resources
Authors: Kennedy Kristen M. , Rodrigue Karen M. , Raz Naftali
Published: December 2006

Background: Whereas age-related declines in declarative memory have been demonstrated in multiple cross-sectional and longitudinal studies, the effect of age on non-declarative manifestations of memory, such as repetition priming and perceptual skill learning, are less clear. The common assumption, based on cross-sectional studies, is that these processes are only mildly (if at all) affected by age. Objective: To investigate long-term changes in repetition priming and age-related differences in identification of fragmented pictures in a 5-year longitudinal design. Method: Healthy adults (age 28–82 years) viewed drawings of objects presented in descending order of fragmentation. The identification threshold (IT) was the highest fragmentation level at which the object was correctly named. After a short interval, old pictures were presented again along with a set of similar but novel pictures. Five years later the participants repeated the experiment. Results: At baseline and 5-year follow-up alike, one repeated exposure improved IT for old (priming) and new (skill acquisition) pictures. However, long-term retention of priming gains was observed only in young adults. Working memory explained a significant proportion of variance in within-occasion priming, long-term priming, and skill learning. Conclusion: Contrary to cross-sectional results, this longitudinal study suggests perceptual repetition priming is not an age-invariant phenomenon and advanced age and reduced availability of cognitive resources may contribute to its decline.
Donepezil in Alzheimer’s Disease: What to Expect after 3 Years of Treatment in a Routine Clinical Setting
Authors: Wallin Åsa K. , Andreasen Niels , Eriksson Sture , Båtsman Stellan , Näsman Birgitta , Ekdahl Anne , Kilander Lena , Grut Mikaela , Rydén Marie , Wallin Anders , Jonsson Mikael , Olofsson Hasse , Londos Elisabeth , Wattmo Carina , Eriksdotter Jönhagen Maria , Minthon Lennart
Published: December 2006

Background/Aims: Clinical short-term trails have shown positive effects of donepezil treatment in patients with Alzheimer’s disease. The outcome of continuous long-term treatment in the routine clinical settings remains to be investigated. Methods: The Swedish Alzheimer Treatment Study (SATS) is a descriptive, prospective, longitudinal, multicentre study. Four hundred and thirty-five outpatients with the clinical diagnosis of Alzheimer’s disease, received treatment with donepezil. Patients were assessed with Mini-Mental State Examination (MMSE), Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog), global rating (CIBIC) and Instrumental Activities of Daily Living (IADL) at baseline and every 6 months for a total period of 3 years. Results: The mean MMSE change from baseline was positive for more than 6 months and in subgroups of patients for 12 months. After 3 years of treatment the mean change from baseline in MMSE-score was 3.8 points (95% CI, 3.0–4.7) and the ADAS-cog rise was 8.2 points (95% CI, 6.4–10.1). This is better than expected in untreated historical cohorts, and better than the ADAS-cog rise calculated by the Stern equation (15.6 points; 95% CI, 14.5–16.6). After 3 years with 38% of the patients remaining, 30% of the them were unchanged or improved in the global assessment. Conclusion: Three-year donepezil treatment showed a positive global and cognitive outcome in the routine clinical setting.
Heterogeneity of Hepatitis B Virus Genotype D in Japan
Authors: Michitaka Kojiro , Horiike Norio , Duong Tran Nhu , Yagura Michiyasu , Harada Hideharu , Shibayama Takao , Inui Ayano , Fujisawa Tomoo , Matsuura Kana , Hiasa Yoichi , Onji Morikazu
Published: December 2006

Objective: Hepatitis B virus (HBV) genotypes B and C are predominant in Japan. Previously, we reported that approximately 9% of HBV carriers in the Ehime area of western Japan were infected with genotype D (HBV/D) and their sequences closely related. Recently, serum samples from 3 patients with chronic HBV/D infections living in Tokyo and the surrounding area became available for testing. The purpose of this study was to determine whether the HBV/D isolates from these different areas of Japan are closely related. Methods: Of the 3 Tokyo area patients infected with HBV/D, 2 had chronic hepatitis, and 1 had hemophilia with a history of frequent coagulation factor injections. The complete HBV/D genome sequences of each were determined, and compared with those of subjects from the Ehime area. Results: All 3 HBV/D sequences had a genomic length of 3,182 bases, and the hepatitis B surface antigen subtype was ayw3. Phylogenetic analysis revealed that the 1 of the HBV/D isolates was closely related to the isolates from Ehime Prefecture, while 1 was similar and 1 was clearly distinct. Conclusion: Our results indicate that HBV/D infections in Japan are heterogeneous.
Differential gene expression of bone anabolic factors and trabecular bone architectural changes in the proximal femoral shaft of primary hip osteoarthritis patients
Authors: Truong Le-Hoa , Kuliwaba Julia S , Tsangari Helen , Fazzalari Nicola L
Published: December 2006

Previous studies have shown a generalised increase in bone mass in patients with osteoarthritis (OA). Using molecular histomorphometry, this study examined the in vivo expression of mRNA encoding bone anabolic factors and collagen type I genes (COL1A1, COL1A2) in human OA and non-OA bone. Bone samples were obtained from the intertrochanteric (IT) region of the proximal femur, a skeletal site distal to the active site of disease, from individuals with hip OA at joint replacement surgery and from autopsy controls. Semi-quantitative reverse transcription-polymerase chain reaction analysis revealed elevated mRNA expression levels of alkaline phosphatase (p < 0.002), osteocalcin (OCN) (p < 0.0001), osteopontin (p < 0.05), COL1A1 (p < 0.0001), and COL1A2 (p < 0.002) in OA bone compared to control, suggesting possible increases in osteoblastic biosynthetic activity and/or bone turnover at the IT region in OA. Interestingly, the ratio of COL1A1/COL1A2 mRNA was almost twofold greater in OA bone compared to control (p < 0.001), suggesting the potential presence of collagen type I homotrimer at the distal site. Insulin-like growth factor (IGF)-I, IGF-II, and transforming growth factor-β1 mRNA levels were similar between OA and control bone. Bone histomorphometric analysis indicated that OA IT bone had increased surface density of bone (p < 0.0003), increased trabecular number (Tb.N) (p < 0.0003), and decreased trabecular separation (Tb.Sp) (p < 0.0001) compared to control bone. When the molecular and histomorphometric data were plotted, positive associations were observed in the controls for OCN/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) versus bone tissue volume (r = 0.82, p < 0.0007) and OCN/GAPDH versus Tb.N (r = 0.56, p < 0.05) and a negative association was observed for OCN/GAPDH versus Tb.Sp (r = -0.64, p < 0.02). These relationships were not evident in trabecular bone from patients with OA, suggesting that bone regulatory processes leading to particular trabecular structures may be altered in this disease. The finding of differential gene expression, as well as architectural changes and differences in molecular histomorphometric associations between OA and controls, at a skeletal site distal to the active site of joint degeneration supports the concept of generalised involvement of bone in the pathogenesis of OA.
Perspectives on Violence
Authors: KRAUSS HERBERT H.
Published: December 2006

Abstract:  The worldwide rise in violence, especially that directed against females of all ages, led the World Health Organization (WHO) to undertake steps to deal with that problem. To do so, WHO adopted a public health approach. This entailed (1) developing a definition of violence, (2) devising a typology of violent acts, (3) creating a uniform database for reporting violence, and (4) promulgating a model for understanding violence and its attendant phenomena. This essay reviews, analyzes, and critiques those efforts.
Transcriptional Profiling of Hematologic Malignancies with a Low-Density DNA Microarray
Authors: Álvarez Patricia , Sáenz Pilar , Arteta David , Martínez Antonio , Pocoví Miguel , Simón Laureano , Giraldo Pilar
Published: December 2006

Background: High-density microarrays are powerful tools for expression analysis of thousands of genes simultaneously; however, experience with low-density microarrays in gene expression studies has been limited.

Methods: We developed an optimized procedure for gene expression analysis based on a microarray containing 538 oligonucleotides and used this procedure to analyze neoplastic cell lines and whole-blood samples from healthy individuals and patients with different hematologic neoplasias. Hierarchical clustering and the Welch t-test with adjusted P values were used for data analysis.

Results: This procedure detects 0.2 fmol of mRNA and generates a linear response of 2 orders of magnitude, with CV values of <20% for hybridization and label replicates. We found statistically significant differences between Jurkat and U937 cell lines, between blood samples from 15 healthy donors and 59 chronic lymphocytic leukemia (CLL) samples, and between 6 acute myeloid leukemia patients and 4 myelodysplastic syndrome patients. A classification system constructed from the expression data predicted healthy or CLL status from a whole-blood sample with a 97% success rate.

Conclusion: Transcriptional profiling of whole-blood samples was carried out without any cellular or sample manipulation before RNA extraction. This gene expression analysis procedure uncovered statistically significant differences associated with different hematologic neoplasias and made possible the construction of a classification system that predicts the healthy or CLL status from a whole-blood sample.
Asymmetrical Dimethylarginine Independently Predicts Total and Cardiovascular Mortality in Individuals with Angiographic Coronary Artery Disease (The Ludwigshafen Risk and Cardiovascular Health Study)
Authors: Meinitzer Andreas , Seelhorst Ursula , Wellnitz Britta , Halwachs-Baumann Gabriele , Boehm Bernhard O , Winkelmann Bernhard R , März Winfried
Published: December 2006

Background: Asymmetrical dimethylarginine (ADMA) is increased in conditions associated with increased risk of atherosclerosis. We investigated the use of ADMA to predict total and cardiovascular mortality in patients scheduled for coronary angiography.

Methods: In 2543 persons with and 695 without coronary artery disease (CAD) identified by angiography we measured ADMA and recorded total and cardiovascular mortality during a median follow-up of 5.45 years.

Results: ADMA was correlated positively to age, female sex, diabetes mellitus, former and current smoking, and C-reactive protein and inversely to HDL cholesterol and triglycerides. ADMA was not associated with body mass index, hypertension, LDL cholesterol, or the presence or absence of angiographic CAD. Glomerular filtration rate and homocysteine were the strongest predictors of ADMA. At the 2nd, 3rd and 4th quartile of ADMA, hazard ratios for all-cause mortality adjusted for age, sex, and cardiovascular risk factors were 1.12 [95% confidence interval (CI) 0.83–1.52], 1.35 (95% CI 1.01–1.81), and 1.87 (95% CI 1.43–2.44), respectively, compared with the 1st quartile. Hazard ratios for cardiovascular death were 1.13 (95% CI 0.78–1.63), 1.42 (95% CI 1.00–2.02), and 1.81 (95% CI 1.31–2.51). ADMA in the highest quartile remained predictive of mortality after accounting for medication at baseline. The predictive value of ADMA was similar to that in the entire cohort in persons with CAD, stable or unstable, but was not statistically significant in persons without angiographic CAD.

Conclusions: ADMA concentration predicts all-cause and cardiovascular mortality in individuals with CAD independently of established and emerging cardiovascular risk factors.
Efficient Establishment of Mouse Embryonic Stem Cell Lines from Single Blastomeres and Polar Bodies
Authors: Wakayama Sayaka , Hikichi Takafusa , Suetsugu Rinako , Sakaide Yuko , Bui Hong-Thuy , Mizutani Eiji , Wakayama Teruhiko
Published: December 2006

Recently, ES cell lines were established from single blastomeres taken from eight-cell embryos in mice and humans with success rates of 4% and 2%, respectively, which suggests that the method could be used in regenerative medicine to reduce ethical concerns over harm to embryos. However, those studies used other ES cells as supporting cells. Here, we report a simple and highly efficient method of establishing mouse ES cell lines from single blastomeres, in which single blastomeres are simply plated onto a feeder layer of mouse embryonic fibroblasts with modified ES cell medium. A total of 112 ES cell lines were established from two-cell (establishment rate, 50%–69%), early four-cell (28%–40%), late four-cell (22%), and eight-cell (14%–16%) stage embryos. We also successfully established 18 parthenogenetic ES cell lines from first (36%–40%) and second polar bodies (33%), the nuclei of which were reconstructed to embryos by nuclear transfer. Most cell lines examined maintained normal karyotypes and expressed markers of pluripotency, including germline transmission in chimeric mice. Our results suggest that the single cells of all early-stage embryos or polar bodies have the potential to be converted into ES cells without any special treatment.

Disclosure of potential conflicts of interest is found at the end of this article.
Survival, synaptogenesis, and regeneration of adult mouse spiral ganglion neurons in vitro
Authors: Wei Dongguang , Jin Zhe , Järlebark Leif , Scarfone Eric , Ulfendahl Mats
Published: December 2006

The inner ear spiral ganglion is populated by bipolar neurons connecting the peripheral sensory receptors, the hair cells, with central neurons in auditory brain stem nuclei. Hearing impairment is often a consequence of hair cell death, e.g., from acoustic trauma. When deprived of their peripheral targets, the spiral ganglion neurons (SGNs) progressively degenerate. For effective clinical treatment using cochlear prostheses, it is essential to maintain the SGN population. To investigate their survival dependence, synaptogenesis, and regenerative capacity, adult mouse SGNs were separated from hair cells and studied in vitro in the presence of various neurotrophins and growth factors. Coadministration of fibroblast growth factor 2 (FGF‐2) and glial cell line‐derived neurotrophic factor (GDNF) provided support for long‐term survival, while FGF‐2 alone could strongly promote neurite regeneration. Fibroblast growth factor receptor FGFR‐3‐IIIc was found to upregulate and translocate to the nucleus in surviving SGNs. Surviving SGNs formed contacts with other SGNs after they were deprived of the signals from the hair cells. In coculture experiments, neurites extending from SGNs projected toward hair cells. Interestingly, adult mouse spiral ganglion cells could carry out both symmetric and asymmetric cell division and give rise to new neurons. The authors propose that a combination of FGF‐2 and GDNF could be an efficient route for clinical intervention of secondary degeneration of SGNs. The authors also demonstrate that the adult mammalian inner ear retains progenitor cells, which could commit neurogenesis. © 2006 Wiley Periodicals, Inc. J Neurobiol 67: 108–122, 2007
The association of alcohol dependency with employment probability: evidence from the population survey ‘Health 2000 in Finland’
Authors: Johansson Edvard , Alho Hannu , Kiiskinen Urpo , Poikolainen Kari
Published: December 2006

In this paper, we investigate to what extent alcohol‐dependent individuals fare worse in the Finnish labour market, using data from a large Finnish health survey. We used the DSM‐IV criteria for alcohol dependence assessed by a composite international diagnostic interview (CIDI). We find that there are substantial disadvantages for alcohol‐dependent men and women in the labour market, in the sense that they have lower employment probabilities. Treating alcohol dependence as an exogenous variable, we find that alcohol dependence is associated with decrease in the probability of full‐time or part‐time work of around 14 percentage points for men and 11 percentage points for women. However, accounting for endogeneity increases the negative effect to some 50 percentage points for men and to some 40 percentage points for women. Copyright © 2006 John Wiley & Sons, Ltd.
Tumor necrosis factor receptor superfamily member TROY is a novel melanoma biomarker and potential therapeutic target
Authors: Spanjaard Remco A. , Whren Kara M. , Graves Carole , Bhawan Jag
Published: December 2006

Incidence of melanoma continues to rise, and a better understanding of its genetics will be critical to improve diagnosis and develop new treatments. Here, we search for novel melanoma‐specific genes that may serve as biomarkers and therapeutic targets by using an in vitro genetic screen. One identified cDNA encoded TROY, a member of the tumor necrosis factor receptor superfamily (TNFRSF). TROY is widely expressed during embryogenesis, but in adults expression is restricted to hair follicles and brain. However, TROY had never been associated with melanoma, and it was selected for further study. First we show that expression in melanoma is specific by semiquantitative RT‐PCR analysis of a large panel of established tumor cell lines. Next, specificity of expression was evaluated by immunohistochemistry analysis of primary cell cultures and patient tissues. TROY is expressed in 2/2 primary melanoma cells and 45/45 melanoma tissue samples (p < 0.0001). With the exception of sebaceous glands, TROY is not expressed in normal skin biopsies (p < 0.0001) or primary skin cell cultures that contain keratinocytes and epidermal melanocytes, nor is it expressed in other skin tumor cells (p < 0.0001). Finally, we show that TROY regulates melanoma growth, because replication of melanoma cells with reduced TROY levels through treatment with short‐interfering RNA was significantly decreased relative to control cells (p < 0.004). In summary, TROY is the first TNFRSF member that is a biomarker for melanoma. TROY also presents a potentially novel cell surface signaling target for inhibitors, cell and/or antibody‐based immunotherapies. © 2006 Wiley‐Liss, Inc.
Variant alleles of TGFB1 and TGFBR2 are associated with a decreased risk of gastric cancer in a Chinese population
Authors: Jin Guangfu , Wang Lina , Chen Wensen , Hu Zhibin , Zhou Yan , Tan Yongfei , Wang Jianming , Hua Zhaolai , Ding Weiliang , Shen Jing , Zhang Zuofeng , Wang Xinru , Xu Yaochu , Shen Hongbing
Published: December 2006

Growing evidence suggests that the transforming growth factor β (TGF‐β) signaling pathway occupies a central position in the signaling networks that control cell growth and differentiation. TGF‐β1 and its receptor TGF‐βRII have been correlated with the development of certain forms of cancer, including gastric cancer. We hypothesized that functional genetic variants in TGFB1 and TGFBR2 are associated with gastric cancer risk. To test this hypothesis, we genotyped C‐509T and Leu10Pro polymorphisms in TGFB1 and G‐875A variant in TGFBR2, using the primer‐introduced restriction analysis (PIRA)‐PCR assay, in a case–control study of 675 gastric cancer cases and 704 healthy controls in a Chinese population. We found that the variant alleles of the promoter polymorphisms, TGFB1 C‐509T and TGFBR2 G‐875A, were associated with a significantly decreased risk of gastriccancer [adjusted odds ratio (OR) = 0.65, 95% confidence interval (CI) = 0.52–0.82 for −509CT/TT and adjusted OR = 0.67, 95% CI = 0.53–0.85 for −875GA/AA]. Furthermore, subjects with both variant genotypes of the TGFB1 C‐509T and TGFBR2 G‐875A were associated with a significantly (56%) decreased risk of gastric cancer (adjusted OR = 0.44, 95% CI = 0.32–0.62). These findings indicate, for the first‐time, that the functional variants in the promoter of TGFB1 and TGFBR2 might contribute to gastric cancer susceptibility. © 2006 Wiley‐Liss, Inc.
Fibrinolytic properties of lysine‐derivatized polyethylene in contact with flowing whole blood (Chandler loop model)
Authors: McClung W.G. , Babcock D.E. , Brash J.L.
Published: December 2006

This article reports on the concept of a fibrinolytic surface based on the preferential adsorption of endogenous plasminogen from blood. Data are presented indicating that such a surface, when pretreated with tissue‐type plasminogen activator (tPA), is able to dissolve nascent thrombus generated in contact with flowing whole blood. Polyethylene (PE) surfaces were modified by attaching a lysine‐containing polymer using photochemical methods as reported previously (McClung et al., J Biomed Mater Res 2000;49:409–414). The lysine residues were bound chemically to the polymer via the α‐amino groups leaving the ε‐amino groups free (ε‐Lys surface). Control surfaces were (a) unmodified PE, (b) PE modified with the coating polymer containing no lysine, and (c) PE modified with the polymer containing lysine bound via the ε‐amino group. The materials in tubing form were evaluated in contact with nonanticoagulated flowing human whole blood in a modified Chandler Loop experiment. They were first treated with tPA to allow activation of adsorbed plasminogen to plasmin. It was found that thrombus formation was initiated within 15–25 min (depending on donor blood) on all surfaces, as indicated by the formation of platelet aggregates. On the controls (including the lysine‐containing material in which the ε‐amino group was used in the binding reaction) thrombogenesis continued till the tubing was occluded and blood flow ceased. On the ε‐Lys surface, thrombogenesis was interrupted at various stages depending on the donor blood; in all cases any thrombus generated was dissolved within minutes. It was shown that thrombolysis was due to the fibrinolytic action of plasmin generated at the surface and not to plasmin formed by traces of tPA released into the blood. This work provides further evidence of the efficacy of this approach to the development of a fibrinolytic surface. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res 80A:, 2007
Thermo‐responsive poly(NiPAAm‐co‐DEGMA) substrates for gentle harvest of human corneal endothelial cell sheets
Authors: Nitschke Mirko , Gramm Stefan , Götze Thomas , Valtink Monika , Drichel Juliane , Voit Brigitte , Engelmann Katrin , Werner Carsten
Published: December 2006

Gentle harvesting of corneal endothelial cell sheets grown in culture is of interest for the development of cornea replacement strategies. Thin films of a fast responding copolymer of N‐isopropylacrylamide (NiPAAm) and diethyleneglycol methacrylate (DEGMA) with a phase transition temperature of 32°C were prepared and evaluated for that purpose. The polymer layers were immobilized onto fluorocarbon substrates using low pressure argon plasma treatment. Cell culture and detachment experiments were performed with L929 mouse fibroblasts and human corneal endothelial cells (HCEC) at standard conditions. The hydrogel‐coated supports were found to permit adhesion, spreading, and proliferation of both cell types. Harvesting of cell sheets was achieved upon lowering the temperature to about 30°C. The formation of a closed monolayer as a crucial prerequisite for maintaining ionic pump function in HCEC was proven by ZO‐1 immunostainung. Labeling of fibronectin indicated that the vast majority of the extracellular matrix is detached from the hydrogel coatings together with the cell layer. Inspired by this result, the reuse of the hydrogel‐coated culture carriers was investigated confirming the suitability of the substrates for repeated cell harvesting. Altogether, the introduced thermoresponsive coating was found advantageous for the efficient generation of HCEC sheets and will be further utilized in transplantation strategies. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res 80A:, 2007
Continuous requirement for pp60‐Src and phospho‐paxillin during fibronectin matrix assembly by transformed cells
Authors: Wierzbicka‐Patynowski Iwona , Mao Yong , Schwarzbauer Jean E.
Published: December 2006

Fibronectin (FN) matrix assembly is an integrin‐mediated process that is regulated by both the extracellular environment and intracellular signaling pathways. The activity of Src‐family kinases is important for initiation of FN assembly by normal fibroblasts. Here we report that in HT1080 fibrosarcoma cells, Src kinase activity is required not only for the assembly of FN matrix but also for the maintenance of FN matrix fibrils at the cell surface. Dexamethasone‐induced FN fibril formation by these cells was completely blocked for at least 24 h when Src‐family kinase activity was inhibited by either PP1 or SU6656. Inhibition of Src after significant matrix had already been assembled, resulted in an increased rate of loss of detergent‐insoluble FN. Binding of activation‐dependent integrin antibodies reveals a role for Src in maintaining integrin activity. The requirement for Src kinase activity appears to depend, in part, on phosphorylation of paxillin at tyrosine 118 (Y118). Phospho‐paxillin co‐localized with FN fibrils, and overexpression of GFP‐paxillin but not of GFP‐paxillinY118F enhanced cell‐mediated assembly of FN. Our results indicate that Src maintains FN matrix at the cell surface through its effect on integrin activity and paxillin phosphorylation. J. Cell. Physiol. 210: 750–756, 2007. © 2006 Wiley‐Liss, Inc.
Pathwidth of outerplanar graphs
Authors: Coudert David , Huc Florian , Sereni Jean‐Sébastien
Published: December 2006

We are interested in the relation between the pathwidth of a biconnected outerplanar graph and the pathwidth of its (geometric) dual. Bodlaender and Fomin [3], after having proved that the pathwidth of every biconnected outerplanar graph is always at most twice the pathwidth of its (geometric) dual plus two, conjectured that there exists a constant c such that the pathwidth of every biconnected outerplanar graph is at most c plus the pathwidth of its dual. They also conjectured that this was actually true with c being one for every biconnected planar graph. Fomin [10] proved that the second conjecture is true for all planar triangulations. First, we construct for each p ≥ 1, a biconnected outerplanar graph of pathwidth 2p + 1 whose (geometric) dual has pathwidth p + 1, thereby disproving both conjectures. Next, we also disprove two other conjectures (one of Bodlaender and Fomin [3], implied by one of Fomin [10]. Finally we prove, in an algorithmic way, that the pathwidth of every biconnected outerplanar graph is at most twice the pathwidth of its (geometric) dual minus one. A tight interval for the studied relation is therefore obtained, and we show that all cases in the interval happen. © 2006 Wiley Periodicals, Inc. J Graph Theory 55: 27–41, 2007
Progress toward remediation of the Sydney Tar Ponds: A major Canadian PCB/PAH “superfund” site
Authors: Lee G. Fred , Jones‐Lee Anne
Published: December 2006

The Muggah Creek estuary in Sydney, Nova Scotia, received liquid and solid wastes from a steel mill and its associated coke ovens for approximately 100 years. This resulted in pollution of soils and sediments with polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), heavy metals, and other pollutants, including those in untreated domestic wastewaters. The Canadian federal and Nova Scotia provincial governments organized the Sydney Tar Ponds Agency (STPA) to develop a remediation approach for the Coke Ovens site soils and Sydney Tar Ponds sediments. The STPA developed a remediation approach for the Sydney Tar Ponds sediments, involving solidification/stabilization (S/S) through mixing cement and other materials into the sediments, and then capping them as a waste pile. High‐density polyethylene (HDPE) plastic sheeting vertical barriers are proposed to be used to divert groundwater and surface water from entering into the S/S‐treated sediments and to collect any water and associated pollutants released from the S/S‐treated sediments. The Coke Ovens site soils are proposed to be landfarmed to reduce some of the PAHs and other pollutants and then capped with a layer of soil. This remediation program is estimated to cost on the order of $400 million (CAN). This article presents a review of the significant potential problems with the STPA proposed remediation strategy of the Sydney Tar Ponds sediments and Coke Ovens site soils. © 2006 Wiley Periodicals, Inc.
Ethanol prevents development of destructive arthritis
Authors: Jonsson Ing-Marie , Verdrengh Margareta , Brisslert Mikael , Lindblad Sofia , Bokarewa Maria , Islander Ulrika , Carlsten Hans , Ohlsson Claes , Nandakumar Kutty Selva , Holmdahl Rikard , Tarkowski Andrej
Published: December 2006

Environmental factors are thought to play a major role in the development of rheumatoid arthritis. Because the use of ethanol is widespread, we assessed the role of ethanol intake on the propensity to develop chronic arthritis. Collagen type II-immunized mice were given water or water containing 10% (vol/vol) ethanol or its metabolite acetaldehyde. Their development of arthritis was assessed, as well as the impact of ethanol on leukocyte migration and activation of intracellular transcription factors. Mice exposed daily to this dose of ethanol did not display any liver toxicity, and the development of erosive arthritis was almost totally abrogated. In contrast, the antibody-mediated effector phase of collagen-induced arthritis was not influenced by ethanol exposure. Also, the major ethanol metabolite, acetaldehyde, prevented the development of arthritis. This antiinflammatory and antidestructive property of ethanol was mediated by (
i
) down-regulation of leukocyte migration and (
ii
) up-regulation of testosterone secretion, with the latter leading to decreased NF-κB activation. We conclude that low but persistent ethanol consumption delays the onset and halts the progression of collagen-induced arthritis by interaction with innate immune responsiveness.
Laboratory handling and histology reporting of breast specimens from patients who have received neoadjuvant chemotherapy
Authors: Pinder S E , Provenzano E , Earl H , Ellis I O
Published: December 2006

Neoadjuvant chemotherapy is increasingly being offered to patients with invasive breast carcinoma but surgical excision specimens following such therapy may be difficult to interpret in the pathology laboratory, both macroscopically and histologically. We provide here some guidelines for handling such postneoadjuvant chemotherapy samples and describe the histopathological features which may be encountered in both the breast and lymph nodes received. We also present a brief review of the literature and suggest a simple method for quantifying the degree of response to neoadjuvant chemotherapy in both the primary breast carcinoma and the lymph nodes.
Patterns of nurse activity
Authors: Moores Brian , Moult Anne
Published: December 2006

A major study was undertaken In three acute hospitals of how nursing staff occupied their time on the medical, surgical and orthopaedic wards, the observation technique adopted being systematic activity sampling. In addition all the interactions patients received from nurses were recorded, the categorization scheme for both sets of data being identical. This paper presents the overall results which emerged from the computer analysis of this material. One of the less expected results is the amount of nursing performed which is categorized as Basic.
Nurses’views about cancer
Authors: Elkind Andrea Knopf
Published: December 2006

To examine the impression of cancer the nurse is likely to convey to the public, 785 female hospital nurses were asked by means of postal questionnaire to give their opinion of the curability and treatment of cancer and the extent to which they regard the disease as alarming. Seven out of ten nurses disagreed with the statement that a patient who had had cancer can never really be cured. Characteristics leading to a better appreciation of the curability of cancer included training, increasing age and length of service and accurate knowledge of survival rates. Positive, personal experience of cancer was more important than professional experience of cancer nursing, suggesting it is the nature of the experience that is important. Young learners had a very poor understanding of the curability of cancer. The majority of nurses considered it at least sometimes true that treatment could do more harm than good and this conclusion is reached very early on in the nurse's career. Trained nurses had a better appreciation of palliative treatment. Nurses, like women generally, tend to regard cancer as the most alarming condition, although this view is less prevalent among trained or experienced nurses. While characterizing nurses’views about cancer as optimistic or pessimistic is not necessarily helpful, it is clear that a minority of nurses would find it difficult to present anything other than a negative view of cancer to their social network.
Ritual and rational action in hospitals
Authors: Chapman G.E.
Published: December 2006

Menzies argues that nursing hierarchies and ritual practices protect nurses from the anxieties provoked by encountering human suffering. This proposition is examined with particular reference to ritual practices in nursing. It is argued that Menzies studied nurses in isolation from the societal and subcultural norms and values which direct hospital activity. Her psychodynamic model is contrasted with a sociological model of human conduct and action. The characteristics of ritual and rational action, and the difference between non‐rational and irrational rituals, is explored. The findings of three 5‐month periods of participant observation are presented as illustrative case material to support the authors view, that ritual procedures are not only defence mechanisms against anxiety, but social acts which generate and convey meaning. Ritual practices described in this analysis include rituals surrounding birth, death, status and power. It is concluded that if nurses wish to change or alter ritual nursing practices in hospital it is necessary to understand their social as well as their psychological meaning.
Role conflict and intention to leave nursing
Authors: Murray M.
Published: December 2006

To test the hypothesis that one of the reasons why nurses leave their job is that they find it difficult to meet the public expectations 246 student and qualified nurses answered a questionnaire to assess this form of role conflict. It emerged that role conflict was highest among second and third year students and that particular aspects of it were strongly related to an expressed intention to leave nursing. The implications of these findings are discussed.
Intraepidermal lymphocytes in psoriatic lesions are activated GMP‐17(TIA‐1)+CD8+CD3+ CTLs as determined by phenotypic analysis
Authors: Austin Lisa M. , Covens Todd R. , Bhardwaj Nina , Steinman Ralph , Krueger James G.
Published: December 2006

The onset and persistence of psoriatic lesions are linked to the presence of an inflammatory infiltrate of CD3+ lymphocytes that includes CD4+ and CD8+ subsets. Since a primary susceptibility factor for psoriasis is the Class I HLA‐Cw6 molecule, we set out to learn more about the features of the epidermal CD8+ lymphocytes. The markers tested were GMP‐17, a cytotoxic granule protein found in activated cytotoxic lymphocytes (CTLs), and the alpha chain of the IL‐2 receptor (CD25), a plasma membrane molecule found on activated T cells. Lymphocytes in lesional skin expressed the GMP‐17 protein, whereas lymphocytes in non‐lesional skin, resolving lesional skin and normal skin had little or no GMP‐17. By flow cytometry analysis, lesional epidermal GMP‐17+ cells were CD8+CD3+, with a subpopulation expressing the activation marker CD25+. Due to the abundance of activated GMP‐17+CD8+CD3+ lymphocytes (the phenotype of activated cytotoxic cells) in psoriatic lesions compared to non‐lesional and normal skin, we hypothesize that they are contributing directly to the psoriatic phenotype.
Staining of eccrine and apocrine neoplasms and metastatic adenocarcinoma with IKH‐4, a monoclonal antibody specific for the eccrine gland
Authors: Ishihara Masabiko , Mehregan Darius R. , Hashimoto Ken , Yotsumoto Shinichi , Toi Yoichiro , Pietruk Teresa , Mehregan Amir H. , Mehregan David A.
Published: December 2006

The histogenesis of apocrine and eccrine neoplasms has always interested dermatopathologists. In addition, the histologic differential diagnosis of eccrine carcinoma from metastatic adenocarcinoma is of practical importance. We describe a novel monoclonal antibody IKH‐4 which stains the eccrine secretory coil, but not the apocrine secretory segment. Positive staining was observed in eccrine hidradenoma, eccrine poroma, eccrine spiradenoma, papillary eccrine adenoma, eccrine hidrocystoma, syringoma, eccrine carcinoma, and in 1 case of syringocystadenoma papilliferum. Negative staining was observed in apocrine adenocarcinoma, hidradenoma papilliferum, erosive adenomatosis of the nipple, and primary and metastatic adenocarcinomas. IKH‐4 antibody was useful in differentiating eccrine from apocrine neoplasms and in differentiating eccrine carcinoma from metastatic adenocarcinomas.
Lichen planoporitis: keratosis lichenoides chronica revisited
Authors: Kossard Steven , Lee Stephen
Published: December 2006

We report a 70‐year‐old woman who over a 7‐year period developed a widespread violaceous, reticulate and striate eruption with a keratotic component in a clinical pattern previously described as keratosis lichenoides chronica. Multiple biopsies showed a lichenoid reaction centred over the acrosyringium and eccrine ducts entering the epidermis. The acrosyringeal ducts were surrounded by an epidermis that was associated with saw‐tooth acanthosis. The ducts displayed hypergranulosis and keratin plugs that extended into the stratum corneum. In the upper dermis the eccrine ducts showed squamous metaplasia with liquefaction of degeneration of their basal cells as well as apoptotic keratinocytes. The subepidermal acrosyringial zone and the eccrine ducts were associated with lymphocytic inflammation and fibrosis. These histopathological findings may represent the counterpart of lichen planopilaris targeting the eccrine ducts. The clinical features defining keratosis lichenoides chronica probably represents a heterogeneous group of conditions including this distinctive subset of lichen planus which we have termed lichen planoporitis.
Comparing Data Collected by Computerized and Written Surveys for Adolescence Health Research
Authors: Wu Ying , Newfield Susan A.
Published: December 2006

Background:  This study assessed whether data‐collection formats, computerized versus paper‐and‐pencil, affect response patterns and descriptive statistics for adolescent health assessment surveys. Youth were assessed as part of a health risk reduction program.

Methods:  Baseline data from 1131 youth were analyzed. Participants completed the questionnaire either by computer (n = 390) or by paper‐and‐pencil (n = 741).

Results:  The rate of returned surveys meeting inclusion requirements was 90.6% and did not differ by methods. However, the computerized method resulted in significantly less incompleteness but more identical responses. Multiple regression indicated that the survey methods did not contribute to problematic responses. The two survey methods yielded similar scale internal reliability and descriptive statistics for behavioral and psychological outcomes, although the computerized method elicited higher reports of some risk items such as carrying a knife, beating up a person, selling drugs, and delivering drugs.

Conclusions:  Overall, the survey method did not produce a significant difference in outcomes. This provides support for program personnel selecting survey methods based on study goals with confidence that the method of administration will not have a significant impact on the outcome.
ON TIME-DEPENDENT COLLAPSING BRANES AND FUZZY ODD-DIMENSIONAL SPHERES
Authors: PAPAGEORGAKIS C. , RAMGOOLAM S.
Published: December 2006

We study the time-dependent dynamics of a collection of N collapsing/expanding D0-branes in type IIA string theory. We show that the fuzzy-S3 and S5 provide time-dependent solutions to the matrix model of D0-branes and its DBI generalisation. Some intriguing cancellations in the calculation of the non-Abelian DBI matrix actions result in the fuzzy-S3 and S5 having the same dynamics at large-N. For the matrix model, we find analytic solutions describing the time-dependent radius, in terms of Jacobi elliptic functions. Investigation of the physical properties of these configurations shows that there are no bounces for the trajectory of the collapse at large-N. We also write down a set of useful identities for fuzzy-S3, fuzzy-S5 and general fuzzy odd-spheres.
Mechanisms ofegfrGene Transcription Modulation: Relationship to Cancer Risk and Therapy Response
Authors: Brandt Burkhard , Meyer-Staeckling Sönke , Schmidt Hartmut , Agelopoulos Konstantin , Buerger Horst
Published: December 2006

The epidermal growth factor receptor (EGFR) plays a crucial role in growth, differentiation, and motility of normal as well as cancer cells. For predictive cancer diagnostics and therapeutic targeting of EGFR, it is important to know how the expression level of EGFR is controlled and related to receptor signaling. A novel transcriptional regulation mechanism has been described that depends on the length of a CA repeat in intron 1 [CA simple sequence repeat 1 (CA SSR I)] of the EGFR gene. Thereby, the number of CA repeats is inversely correlated to pre-mRNA synthesis. Indirect evidence for the importance of this mechanism includes the preferential occurrence of amplifications in cancer tissue harboring short CA repeats in this sequence and the discovery of distinct alleles in young breast cancer patients with a family history of the disease and in Japanese breast cancer patients. It can be postulated that the length of the CA repeat influences DNA bendability and, in consequence, the binding of repressor proteins. In summary, it seems that the CA SSR I represents an inherited variable for response to anti-EGFR therapies that could be determined before therapy. Moreover, the potential for synergistic effects with other polymorphism [e.g., EGFR R497K (HER-1 497K) and CCND1 A870G] leading to a simultaneous increase of EGFR signaling activity and expression should be investigated. From a practical perspective, assessment of the CA SSR I number of CA dinucleotide repeats as a predictor for clinical outcome is very attractive because it is a constant feature that does not change over time and can be easily measured in normal and cancer tissues (blood cells, skin, and tumor biopsies) in an assay that is technically simple, objective, and even quantitative.
Systemic Anthrax Lethal Toxin Therapy Produces Regressions of Subcutaneous Human Melanoma Tumors in Athymic Nude Mice
Authors: Abi-Habib Ralph J. , Singh Ravibhushan , Leppla Stephen H. , Greene John J. , Ding Yan , Berghuis Bree , Duesbery Nicholas S. , Frankel Arthur E.
Published: December 2006

Purpose: Anthrax Lethal Toxin (LeTx), composed of protective antigen and lethal factor, catalytically cleaves mitogen-activated protein kinase (MAPK) kinases and inhibits the MAPK signaling pathways. The majority of metastatic melanomas possess the V599E BRAF mutation, which constitutively activates MAPK1/2 signaling. LeTx is cytotoxic to BRAF mutant melanoma cell lines in vitro, whereas most normal cells are resistant to this toxin. In this study, we determine the in vivo potency and safety of systemically administered LeTx.

Experimental Design: A s.c. xenograft melanoma model in athymic nude mice was treated with different i.p. doses of LeTx.

Results: In this study, we show that in vivo systemic LeTx treatment of s.c. xenograft melanoma tumors in athymic nude mice yields partial and complete tumor regressions with minor toxicity to mice. When animal toxicity was observed, we did not find any histologic evidence of tissue damage.

Conclusions: LeTx is one of the rare targeted agents to produce complete remissions of human melanomas in an animal model and thus warrants further preclinical development.
Tetradecylselenoacetic Acid, a PPAR Ligand With Antioxidant, Antiinflammatory, and Hypolipidemic Properties
Authors: Dyrøy Endre , Røst Therese H. , Pettersen Reidar J. , Halvorsen Bente , Gudbrandsen Oddrun A. , Ueland Thor , Muna Ziad , Müller Fredrik , Nordrehaug Jan E. , Aukrust Pål , Berge Rolf K.
Published: December 2006

Objective—

Antioxidants protect against oxidative stress and inflammation, which, in combination with hyperlipidemia, are important mediators of atherogenesis. Here we present a selenium-substituted fatty acid, tetradecylselenoacetic acid (TSA), which is hypothesized to have antioxidant, antiinflammatory, and hypolipidemic properties.

Methods and Results—

We show that TSA exerts antioxidant properties by delaying the onset of oxidation of human low density lipoprotein (LDL), by reducing the uptake of oxidized LDL in murine macrophages, and by increasing the mRNA level of superoxide dismutase in rat liver. TSA also showed antiinflammatory effects by suppressing the release of interleukin (IL)-2 and -4, and by increasing the release of IL-10 in human blood leukocytes. In addition, TSA decreased the plasma triacylglycerol level and increased the mitochondrial fatty acid β-oxidation in rat liver. In pigs, TSA seemed to reduce coronary artery intimal thickening after percutaneous coronary intervention. In HepG2 cells TSA activated all peroxisome proliferator-activated receptors (PPARs) in a dose-dependent manner.

Conclusions—

Our data suggest that TSA exert potent antioxidant, antiinflammatory, and hypolipidemic properties, potentially involving PPAR-related mechanisms. Based on these effects, it is tempting to hypothesize that TSA could be an interesting antiatherogenic approach to atherosclerotic disorders.