bluuebunny/crossref_metadata_2025 huggingface dataset:
1H, 19F, and 31P PGSE NMR Diffusion Studies on Chiral Organic Salts: Ion Pairing and the Dependence of a Diffusion Value on Diastereomeric Structure
Authors: Martínez‐Viviente Eloísa , Pregosin Paul S. , Vial Laurent , Herse Christelle , Lacour Jérôme
Published: April 2004

1H, 19F and 31P pulsed field gradient spin‐echo (PGSE) diffusion studies on chiral organic salts that contain hexacoordinate phosphate anions, namely tris(tetrachlorobenzenediolato)phosphate(V) (TRISPHAT) and bis(tetrachlorobenzenediolato)mono([1,1′]binaphthalenyl‐2,2′diolato)‐phosphate(V) (BINPHAT), are reported. The first example of the dependence of a diffusion value on diastereomeric structure is presented. Marked solvent and concentration effects on the diffusion constants (D) of these salts are noted and the question of ion pairing is discussed.
Clinical significance of non‐Candida fungal blood isolation in patients undergoing high‐risk allogeneic hematopoietic stem cell transplantation (1993–2001)
Authors: Safdar Amar , Singhal Seema , Mehta Jayesh
Published: April 2004

BACKGROUND

The clinical relevance of mold isolated from blood cultures, even in severely immunosuppressed allogeneic hematopoietic stem cell transplantation (HSCT) recipients, remains uncertain. The authors hypothesized that isolation of non‐Candida fungi from blood cultures in patients undergoing high‐risk HSCT would have clinical significance.

METHODS

The authors reviewed the records of 73 allogeneic HSCT recipients between January 1, 1993 and January 1, 2001 in whom fungal species were isolated from blood cultures.

RESULTS

Fifty‐two episodes of non‐Candida fungemia occurred in 48 patients (66%) after a median of 10 days (range, 2–341) after transplantation. All 48 patients had indwelling intravascular catheters, and 23 patients (48%) had profound neutropenia. Thirty‐five of 48 patients had received partially matched, related donor stem cell grafts (19 patients had 3‐antigen‐mismatched grafts); 35 patients had undergone T‐cell depleted transplantation and 9 patients were receiving treatment for acute graft‐versus‐host disease. In 5 of 48 patients (10%), death was attributed to fungemia that occurred 8–11 days after the initial fungal blood culture was obtained; all 5 patients were age > 30 years. No deaths occurred in the younger age group (n = 22 patients; P = 0.05). In the 24 patients who did not receive systemic antifungal therapy, 4 deaths (17%) were attributed to infections with Penicillium (n = 2 patients), Epicoccum (n = 1 patient), or Penicillium plus Cladosporium species (n = 1 patient). Of the 24 patients who received amphotericin B, only 1 patient (4%) died as a result of a probable hematogenous Aspergillus species infection; this difference in outcome, however, was not significant (P = 0.2).

CONCLUSIONS

Most of the non‐Candida fungal blood culture isolates in recipients of high‐risk, mismatched donor transplantation were clinically nonsignificant. However, because these low‐virulence saprophytes occasionally may cause life‐threatening disease, a reevaluation of the existing diagnostic paradigm is needed so that clinically significant fungemia may be differentiated from pseudofungemia. Cancer 2004. © 2004 American Cancer Society.
Breast carcinoma screening and risk perception among women at increased risk for breast carcinoma
Authors: Sabatino Susan A. , Burns Risa B. , Davis Roger B. , Phillips Russell S. , Chen Ya‐Hua , McCarthy Ellen P.
Published: April 2004

BACKGROUND

The Gail model is validated to estimate breast carcinoma risk. The authors assessed the association of Gail risk scores with screening and cancer risk perception.

METHODS

Using the 2000 National Health Interview Survey, the authors studied women ages 41–70 without a cancer history. Gail scores ≥ 1.66% defined increased risk. The authors used logistic regression to assess associations between breast carcinoma risk and previous and recent (≤ 1 year) mammography and clinical breast examination (CBE).

RESULTS

Of 6410 women, 15.7% had increased risk. High‐risk women more frequently reported previous mammograms (94% vs. 85%; P < 0.0001), previous CBE (93% vs. 88%; P < 0.0001), recent mammograms (70% vs. 54%; P < 0.0001), recent CBE (71% vs. 61%; P < 0.0001), and high cancer risk perception (20% vs. 9%; P < 0.0001). However, 30% of high‐risk women had not received a recent mammogram. After adjustment for sociodemographic factors, access to care factors, and cancer risk perception, high‐risk women remained more likely to have received recent mammography (adjusted odds ratio [OR], 1.45, 95% confidence interval [95% CI], 1.19–1.77), recent CBE (OR, 1.32; 95% CI, 1.08–1.61]), and previous mammography than average‐risk women. The authors observed an interaction between risk and age, with women ages 41–49 years more frequently reporting previous mammography (OR, 4.79; 95% CI, 1.55–4.81) than average‐risk, same‐age women. For women age ≥ 50 years, the odds of previous mammography were similar regardless of risk.

CONCLUSIONS

In a nationally representative sample, 15.7% of women had increased breast carcinoma risk using the Gail model. High‐risk women perceived higher cancer risk and more often received screening. However, nearly one in three high‐risk women did not receive recent screening and most of these women did not perceive increased risk. Cancer 2004. © 2004 American Cancer Society.
Members of the Wnt, Fz, and Frp gene families expressed in postnatal mouse cerebral cortex
Authors: Shimogori Tomomi , VanSant Janine , Paik Eun , Grove Elizabeth Ann
Published: April 2004

The functions of Wingless‐Int (Wnt) signaling, studied intensely in embryonic brain development, have been comparatively little investigated in the postnatal brain. We report remarkably patterned gene expression of Wnt signaling components in postnatal mouse cerebral cortex, lasting into young adulthood. Wnt genes are expressed in gene‐specific regional and lamina patterns in each of the major subdivisions of the cerebral cortex: the olfactory bulb (OB), the hippocampal formation, and the neocortex. Genes encoding Frizzled (Fz) Wnt receptors, or secreted Frizzled‐related proteins (sFrps), are also expressed in regional and lamina patterns. These findings suggest that Wnt signaling is active and regulated in the postnatal cortex and that different cortical cell populations have varying requirements for a Wnt signal. The OB, in particular, shows gene expression of a large variety of Wnt signaling components, making it a prime target for future functional studies. The penultimate components of the canonical Wnt pathway are the Tcf/Lef1 transcription factors, which regulate transcription of Wnt signaling target genes. Surprisingly, we found little Tcf/Lef1 expression in the postnatal neocortex. These observations suggest that noncanonical Wnt pathways predominate, which will require functional testing. However, Lef1 is widely expressed in the dorsal thalamus, and Wnt ligands and receptors are expressed, respectively, in cortical areas and thalamic nuclei that are interconnected. Thus, canonical Wnt signaling could be utilized in a major cortical input by Fz‐ and Lef1‐expressing thalamic cells that innervate the Wnt‐expressing cortex. J. Comp. Neurol. 473:496–510, 2004. © 2004 Wiley‐Liss, Inc.
A hybrid discontinuous Galerkin/interface method for the computational modelling of failure
Authors: Mergheim J. , Kuhl E. , Steinmann P.
Published: April 2004

The present contribution is concerned with the computational modelling of failure along well‐defined surfaces, which occur for example in the case of light‐weight composite materials. A hybrid method will be introduced which makes use of the discontinuous Galerkin method in combination with a finite element interface approach. As a natural choice interface elements are introduced along the known failure surface. The discontinuous Galerkin method is applied in the pre‐failure regime to avoid the unphysical use of penalty terms and instead to enforce the continuity of the solution along the interface weakly. Once a particular failure criterion is fulfilled, the behaviour of the interface is determined constitutively, depending on the displacement jump. The applicability of the proposed method is illustrated by means of two computational model problems. Copyright © 2004 John Wiley & Sons, Ltd.
An assessment of the average nodal volume formulation for the analysis of nearly incompressible solids under finite strains
Authors: Andrade Pires F. M. , de Souza Neto E. A. , de la Cuesta Padilla J. L.
Published: April 2004

This paper provides an assessment of the average nodal volume methodology originally proposed by Bonet and Burton (Commun. Numer. Meth. Engng. 1998; 14:437–449) for the analysis of finitely strained nearly incompressible solids. An implicit version of the average nodal pressure formulation is derived by re‐casting the original concept in terms of average nodal volume change ratio within the framework of the F‐bar method proposed by de Souza Neto et al. (Int. J. Solids Struct. 1996; 33: 3277–3296). In this context, a linear triangle for implicit plane strain and axisymmetric analysis of nearly incompressible solids under finite strains is obtained. An exact expression for the corresponding element stiffness matrix is presented. This allows the use of the full Newton–Raphson algorithm, ensuring quadratic rates of asymptotic convergence in the global equilibrium iterations. The performance of the procedure is thoroughly assessed by means of numerical examples. The results show that the nodal averaging technique substantially reduces the volumetric locking tendency of the linear triangle and allows an accurate prediction of deformed shapes and reaction forces in situations of practical interest. However, the formulation is found to produce considerable checkerboard‐type hydrostatic pressure fluctuations which poses severe limitations on its range of applicability. Copyright © 2004 John Wiley & Sons, Ltd.
A simple model for viscous regularization of elasto‐plastic constitutive laws with softening
Authors: Dias da Silva V.
Published: April 2004

An overlay‐type rheological model is presented, which is used to introduce viscosity in inviscid elasto‐plastic material laws with softening, in order to reduce the mesh‐dependency of Finite Element solutions. This model is intended to be an alternative to the well‐known visco‐plastic formulations of Perzyna and Duvaut–Lions. A time integration algorithm for the visco‐elastic model component is presented, being demonstrated in the paper, that it is unconditionally stable and oscillation‐free. The algorithm is tested in a problem with slip driven softening (von Mises material) and in a problem with decohesion driven softening (Cam‐Clay model). Figures showing the capability of the algorithm to regularize the solution are presented. Copyright © 2004 John Wiley & Sons, Ltd.
CD1d deficiency exacerbates inflammatory dermatitis in MRL‐lpr/lpr mice
Authors: Yang Jun‐Qi , Chun Taehoon , Liu Hongzhu , Hong Seokmann , Bui Hai , Van Kaer Luc , Wang Chyung‐Ru , Singh Ram Raj
Published: April 2004

Mechanisms responsible for the development of autoimmune skin disease in humans and animal models with lupus remain poorly understood. In this study, we have investigated the role of CD1d, an antigen‐presenting molecule known to activate natural killer T cells, in the development of inflammatory dermatitis in lupus‐susceptible MRL‐lpr/lpr mice. In particular, we have establishedMRL‐lpr/lpr mice carrying a germ‐line deletion of the CD1d genes. We demonstrate that CD1d‐deficient MRL‐lpr/lpr mice, as compared with wild‐type littermates, have more frequent and more severe skin disease, with increased local infiltration with mast cells, lymphocytes and dendritic cells, including Langerhans cells. CD1d‐deficient MRL‐lpr/lpr mice had increased prevalence of CD4+ T cells in the spleen and liver and of TCRα β +B220+ cells in lymph nodes. Furthermore, CD1d deficiency was associated with decreased T cell production of type 2 cytokines and increased or unchanged type 1 cytokines. These findings indicate a regulatory role of CD1d in inflammatory dermatitis. Understanding the mechanisms by which CD1d deficiency results in splenic T cell expansion and cytokine alterations, with increased dermal infiltration of dendritic cells and lymphocytes in MRL‐lpr/lpr mice, will have implications for the pathogenesis of inflammatory skin diseases.
Granulocyte colony‐stimulating factor promotes the generation of regulatory DC through induction of IL‐10 and IFN‐α
Authors: Rutella Sergio , Bonanno Giuseppina , Pierelli Luca , Mariotti Andrea , Capoluongo Ettore , Contemi Anna Maria , Ameglio Franco , Curti Antonio , de Ritis Daniela G. , Voso Maria Teresa , Perillo Alessandro , Mancuso Salvatore , Scambia Giovanni , Lemoli Roberto M. , Leone Giuseppe
Published: April 2004

We have recently demonstrated that G‐CSF promotes the generation of human T regulatory (TREG) type 1 cells. In this study, we investigated whether the immunomodulatory effects of G‐CSF might be mediated by DC. CD14+ monocytes were cultured with serum collected after clinical administration of G‐CSF (post‐G), which contained high amounts of IL‐10 and IFN‐α. Similar to incompletely matured DC, monocytes nurtured with post‐G serum acquired a DC‐like morphology, expressed high levels of costimulatory molecules and HLA‐DR, and exhibited diminished IL‐12p70 release and poor allostimulatory capacity. Importantly, post‐G DC‐like cells were insensitive to maturation stimuli. As shown by neutralization studies, IFN‐α and, even more pronounced, IL‐10 contained in post‐G serum inhibited IL‐12p70 release by post‐G DC‐like cells. Furthermore, phenotypic and functional features of post‐G DC‐like cells were replicated by culturing post‐G monocytes with exogenous IL‐10 and IFN‐α. Post‐G DC‐like cells promoted Ag‐specific hyporesponsiveness in naive allogeneic CD4+ T cells and orchestrated a TREG response that was dependent on secreted TGFβ1 and IL‐10. Finally, neutralization of IL‐10 and IFN‐α contained in post‐G serum translated into abrogation of the regulatory features of post‐G DC‐like cells. This novel mechanism of immune regulation effected by G‐CSF might be therapeutically exploited for tolerance induction in autoimmune disorders.
Environmental pollutant tributyltin promotes Th2 polarization and exacerbates airway inflammation
Authors: Kato Takuma , Uchikawa Ryuichi , Yamada Minoru , Arizono Naoki , Oikawa Saeko , Kawanishi Shosuke , Nishio Akiyoshi , Nakase Hiroshi , Kuribayashi Kagemasa
Published: April 2004

It has been shown that a relatively high dose of tributyltin (TBT), which is recognized as a particularly notable environmental pollutant, exerts immunotoxic effects such as thymic atrophy viainduction of T cell apoptosis. However, the effect of low doses of TBT on the immune responses remains unknown. Here we show that environmentally relevant doses of TBT promoted strong Th2 polarization via suppression and augmentation of Th1 and Th2 development, respectively, from naive CD4+ T cells primed with anti‐CD3 and splenic antigen‐presenting cells (APC). TBT‐induced Th2 polarization was indirect, working through APC via suppression of IL‐12 production by macrophages/DC and the augmentation of IL‐10 production by B cells. Th2 polarization was also induced in mice treatedwith TBT and immunized with OVA or infected with Nippostrongylus brasiliensis. Furthermore, airway inflammation in mice sensitized and challenged with OVA was exacerbated by the administration of TBT with concomitant augmentation of Th2‐type immunity. Our results highlight the fact that an important environmental pollutant TBT may present significant risk for the induction of allergic diseases via promotion of Th2 polarization.
Electrocatalytic Oxidation of Catechol at Multi‐Walled Carbon Nanotubes Modified Electrode
Authors: Xu Zhiai , Chen Xu , Qu Xiaohu , Dong Shaojun
Published: April 2004

In 0.05 mol/L phosphate buffer solution (pH 7.0), carbon nanotubes modified electrode exhibits rapid response, strong catalytic activity with high stability toward the electrochemical oxidation of catechol. The electrochemical behavior of catechol on both the multi‐walled and single‐walled carbon nanotubes modified electrode was investigated. The experimental conditions, such as pH of the solution and scan rate were optimized. The currents (measured by constant potential amperometry) increase linearly with the concentrations of catechol in the range of 2.0×10−5–1.2×10−3 mol/L. Moreover, at the multi‐walled carbon nanotubes modified electrode the electrochemical responses of catechol and ascorbic acid can be separated clearly.
Airborne dust deposition in the Okavango Delta, Botswana, and its impact on landforms
Authors: Krah M. , McCarthy T. S. , Annegarn H. , Ramberg L.
Published: April 2004

This study investigated the local‐scale generation and movement of dust in the seasonal swamps of the Okavango Delta, Botswana, with a view to examining possible transfer of material between ﬂood plains and islands. It was found that most of the dust load was carried in the lowest 3 m of the air column, and consisted mainly of amorphous silica, indicating that dust was generated largely on the ﬂood plains. Dust loads were found to be highest above the ﬂood plains and lowest over the interiors of islands, probably due to the bafﬂing effect of the island trees on wind velocity. The contrast in dust loads between islands and ﬂood plains suggests that there is a net transfer of dust from ﬂood plains to islands, but it was not possible to quantify this transfer. It is evident, however, that ﬂood plains experience net erosion and islands net aggradation. A strong seasonality in dust loads was observed, with the maximum dust loads coinciding with maximum wind velocity in October. This also coincides with peak seasonal ﬂooding in the delta, and only non‐inundated ﬂood plains are capable of generating dust. Years of low ﬂood therefore appear to be more dusty. There may also be transfer of material from higher‐lying to lower‐lying ﬂood plains, which may reduce the topographic contrast on the ﬂood plains. Copyright © 2004 John Wiley & Sons, Ltd.
Seasonal patterns of runoff and erosion responses to simulated rainfall in a badland area in Mediterranean mountain conditions (Vallcebre, southeastern Pyrenees)
Authors: Regüés D. , Gallart F.
Published: April 2004

Regolith surface characteristics and response were examined over a three‐year period in a badland area in a Mediterranean middle‐mountain zone near Vallcebre (Eastern Pyrenees). Preliminary work carried out in this area indicated clear seasonal patterns of regolith properties driven by frost heaving in winter and crusting and erosion in the rest of the year. Rainfall simulations were performed with a small portable nozzle simulator in order to study seasonal changes in runoff generation, erosion rates and raindrop effect on bulk density changes. The results showed large seasonal variations in runoff and erosion responses. Inﬁltration rates after runoff start were correlated with precipitation depth before runoff start; runoff generation was therefore related to regolith saturation only to a very limited extent. Erosion rates were more controlled by runoff rates than by the weakness of regolith against raindrop splash, and sediment grain size increased with concentration. The combined role of antecedent regolith moisture and bulk density explained most of the seasonal variability in inﬁltration, bulk density changes during rainfall and erosion rates, but some seasonal differences in sediment detachability were not explained by these variables and may be attributed to changes in roughness. Overall, runoff and erosion responses were relatively stable during spring and autumn, whereas wide variations in inﬁltration rates and sediment detachment occurred in winter and summer respectively. Experiments conducted in a single season would have produced poorly representative, if not erroneous, results. Copyright © 2004 John Wiley & Sons, Ltd.
Serum linoleic and total polyunsaturated fatty acids in relation to prostate and other cancers: A population‐based cohort study
Authors: Laaksonen David E. , Laukkanen Jari A. , Niskanen Leo , Nyyssönen Kristiina , Rissanen Tiina H. , Voutilainen Sari , Pukkala Eero , Hakkarainen Anna , Salonen Jukka T.
Published: April 2004

Dietary and serum fatty acid composition has been implicated in the pathogenesis of prostate and other cancers, but findings have been conflicting. Cohort studies reporting serum fatty acid composition are lacking. We assessed the association of fatty acid composition determined from dietary records and serum with incident cancer of the prostate and any site in a population‐based cohort of 2,002 middle‐aged Finnish men who were free of cancer at baseline and during the first 4 years of follow‐up. During 12.6 years of follow‐up, 46 men developed prostate cancer and 151 any cancer. Men with proportions of serum nonesterified [risk ratio (RR) 0.28; 95% confidence intervals (CI) 0.12–0.66] and esterified linoleic acid (RR 0.37; 95% CI = 0.16–0.86) and total polyunsaturated fatty acids (RR 0.30; 95% CI = 0.12–0.71) in the upper third were less than 1/3 as likely to develop prostate cancer during follow‐up. Adjustment for possible confounders like socioeconomic status, physical activity, obesity and insulin concentrations did not attenuate the association. Similar but weaker associations with any cancer were found. Dietary linoleic acid intake also tended to be inversely associated with incident prostate cancer (age‐adjusted RR for the upper vs. lower third 0.55; 95% CI = 0.26–1.14, p for the trend 0.097). Substitution of linoleic acid for saturated fat in middle‐aged men consuming a high saturated‐fat diet may decrease the risk of prostate and other cancers, although it is possible that some of the effect may be mediated by nutrients closely associated with vegetable fats. © 2004 Wiley‐Liss, Inc.
IGF‐I and breast cancer: A meta‐analysis
Authors: Shi Runhua , Yu Herbert , McLarty Jerry , Glass Jonathan
Published: April 2004

IGFs are peptide hormones involved in the regulation of cell proliferation, differentiation and apoptosis. IGFs are regulated by endocrine and paracrine mechanisms; however, their action in tissue is determined by circulating levels and local production of IGFs and IGF‐binding proteins (IGFBPs). Some, but not all, epidemiologic studies have associated high circulating levels of IGF‐I with increased risk of breast cancer among premenopausal women. To evaluate the overall association of IGF‐I and IGFBP‐3 levels with breast cancer risk, we performed a meta‐analysis on 16 publications of epidemiologic and clinical studies. Analyses were performed for all women as well as for pre‐ and postmenopausal women separately. Hedges' standardized mean differences (HSMDs) and odds ratios (ORs) were used to estimate the effect of IGF‐I and IGFBP‐3. Data analysis showed that circulating levels of IGF‐I were not significantly higher in breast cancer patients than in controls for all women and for the postmenopausal group (HSMD = 0.024 and 0.035, respectively; p > 0.40) but were significantly higher (HSMD = 0.170, p < 0.001) for the premenopausal group. ORs for breast cancer risk were 1.05 (95% CI 0.94–1.17), 0.93 (95% CI 0.80–1.10) and 1.39 (95% CI 1.16–1.66). The HSMD of IGFBP‐3 was 0.18 (p < 0.001), and the OR for breast cancer was 1.42 (95% CI 1.15–1.74) for premenopausal women. Our results support the suggested association between high IGF‐I and IGFBP‐3 levels and increased risk of breast cancer in premenopausal women. © 2004 Wiley‐Liss, Inc.
Allelic loss on chromosomes 2q21 and 19p 13.2 in oxyphilic thyroid tumors
Authors: Stankov Karmen , Pastore Alessandro , Toschi Luca , McKay James , Lesueur Fabienne , Kraimps Jean Louis , Bonneau Dominique , Gibelin Hélène , Levillain Pierre , Volante Marco , Papotti Mauro , Romeo Giovanni
Published: April 2004

Hürthle thyroid tumors are characterized by frequent numerical chromosomal aberrations, including aneuploidy or polyploidy, losses and gains of some chromosomal regions and DNA fragmentation. In recent years, great attention has been paid to the combined analysis of morphologic and genetic features of oxyphilic tumors and to the elucidation of their pathogenesis. We analyzed for loss of heterozygosity (LOH) of the candidate regions for TCO (thyroid tumor with cell oxyphilia) and NMTC1 (nonmedullary thyroid carcinoma 1), 2 loci already mapped on chromosomes 19p13.2 and 2q21, respectively. Matched normal and tumor DNA samples from 70 patients with sporadic oxyphilic thyroid tumors and 20 with sporadic follicular tumors were subjected to microsatellite analysis using 10 markers on 19p13.2 and 6 markers on 2q21. This approach led us to the observation of a more significant LOH in oxyphilic than in follicular tumors. Allelic loss in tumor samples was evenly distributed in both 19p13.2 and 2q21 regions, in accordance with the established linkage of TCO and NMTC1 for inherited tumors. In order to investigate the possible contribution of both susceptibility loci in oxyphilic tumors, the family that led to the original mapping of TCO locus was reanalyzed for the markers in the 2q21 region. This led to the exclusion of linkage with the NMTC1 locus and to the refutation of the digenic inheritance hypothesis at least in this family. © 2004 Wiley‐Liss, Inc.
Post‐translationally modified S12, absent in transformed breast epithelial cells, is not associated with the 26S proteasome and is induced by proteasome inhibitor
Authors: Thompson H. Garrett R. , Harris Joseph W. , Brody James P.
Published: April 2004

The 26S proteasome, consisting of the 20S core and 19S regulatory complexes, regulates intracellular protein concentration through proteolytic degradation of targeted substrates. Composition of the 19S regulatory complex as well as posttranslational modifications of the 19S subunits can effectively regulate the activity of the 26S proteasome. Aberrant activity of the 26S proteasome affects the cell cycle, apoptosis and other cellular processes related to cancer. Recent data show an additional proteasome‐independent role of 19S subunits in transcriptional regulation. S12 (Rpn8), the human homologue of mouse Mov‐34, is a non‐ATPase 19S regulatory subunit of the 26S proteasome. Previous studies have identified phosphorylated S12. In our study, we identify a modified S12 isoform (S12‐M) with distinct biochemical properties. The S12‐M isoform was found in 6 normal, but not 4 transformed, breast epithelial cell lines. Modification of S12 protein can be induced in vitro by addition of the proteasome inhibitor PSI. Modified and unmodified S12 have similar mass, but different isoelectric points, consistent with phosphorylation. In normal cells, unmodified S12 associates with the 26S proteasome, while modified S12‐M does not. Whereas transformed cell line nuclei contain neither S12 isoform, S12‐M is predominantly cytosolic in normal cells, with the unmodified S12 present in both the nuclei and cytosol. Together with the role of 19S subunits in transcriptional regulation, homology between S12 and eIF3 and TFIIH subunits, coelution with immunoproteasome subunits, and differential posttranslational modification and nuclear localization, these data suggest a differential nuclear function of modified and unmodified S12 in cancer. © 2004 Wiley‐Liss, Inc.
Alterations in tumor necrosis factor–induced endothelial cell procoagulant activity by hyperthermia
Authors: Carroll Nancy M. , Elaraj Dina M. , Puhlmann Markus , Weinreich David M. , Turner Ewa M. , Xu Hui , Alexander H. Richard
Published: April 2004

TNF is a cytokine with potent antitumor activity in murine models and when administered clinically via regional perfusion. There is substantial evidence that this antitumor activity depends in large part on TNF's procoagulant effect on tumor neovasculature, which is mediated by induction of endothelial cell tissue factor (TF), a component of the extrinsic clotting cascade. In regional perfusion of a cancer‐bearing limb or organ, TNF is always administered under hyperthermic temperatures; however, little is known about the effect of hyperthermia on TNF‐mediated procoagulant activity in endothelium. We examined the effects of hyperthermia on TNF‐mediated procoagulant activity in human umbilical vein endothelial cells (HUVECs). HUVECs were exposed to TNF at normothermic (37°C) and hyperthermic (41°C) temperatures for 90 min, then assayed for clotting activity, TF protein production and mRNA production of TF and tissue factor pathway inhibitor‐2 (TFPI‐2), an endogenous inducible inhibitor of TF activity in HUVECs. TNF treatment at 41°C significantly reduced clotting activity, TF protein and mRNA as well as TFPI‐2 mRNA compared to treatment at 37°C. These data show that hyperthermia significantly reduces the procoagulant effects of TNF on endothelial tissue compared to normothermia, which may have important clinical implications for the use of TNF in regional perfusion. © 2004 Wiley‐Liss, Inc.
Factors Affecting Macroinvertebrate Richness and Diversity in Portuguese Streams: a Two‐Scale Analysis
Authors: Graça Manuel A. S. , Pinto Paulo , Cortes Rui , Coimbra Nuno , Oliveira Simone , Morais Manuela , Carvalho Maria João , Malo Jorge
Published: April 2004

We analysed the spatial patterns in macroinvertebrate taxon richness and abundance at two scales: sampling unit and basin. We sampled 12 stream sites in three zones of Portugal, differing in climate geomorphology and water chemistry. At a sampling unit scale, substratum organic matter content, depth and the dominant size of substratum particles were correlated with numbers of taxa and individuals. We propose that the number of taxa at a small scale depends on the number of individuals, which in turn is the result of organic matter accumulation, hydrologic and substratum characteristics. The environmental parameters better explaining the large‐scale biological data were temperature, minimum size of substratum particles and pH. Regardless of the relative importance of variable types and mechanisms regulating stream invertebrates along the climatic gradient, rivers from the North and Centre appeared to be richer in taxa than the typically Mediterranean streams in the South.
Botulinum toxins in neurological disease
Authors: Comella Cynthia L. , Pullman Seth L.
Published: April 2004

Botulinum toxins are among the most potent neurotoxins known to humans. In the past 25 years, botulinum toxin has emerged as both a potential weapon of bioterrorism and as a powerful therapeutic agent, with growing applications in neurological and non‐neurological disease. Botulinum toxin is unique in its ability to target peripheral cholinergic neurons, preventing the release of acetylcholine through the enzymatic cleavage of proteins involved in membrane fusion, without prominent central nervous system effects. There are seven serotypes of the toxin, each with a specific activity at the molecular level. Currently, serotypes A (in two preparations) and B are available for clinical use, and have been shown to be safe and effective for the treatment of dystonia, spasticity, and other disorders in which muscle overactivity gives rise to symptoms. This review focuses on the pharmacology, electrophysiology, immunology, and application of botulinum toxin in selected neurological disorders. Muscle Nerve 29: 628–644, 2004
Prevalence and determinants of antibiotic resistance in faecal Escherichia coli among unselected patients attending general practitioners in Southwest Germany
Authors: Stürmer Til , Erb Andrea , Marre Reinhard , Brenner Hermann
Published: April 2004

Purpose

Widespread use of antibiotics is thought to be the main reason for the world‐wide increase in antibiotic resistance. Although a great majority of antibiotics are prescribed outside hospitals, little is known about the prevalence and determinants of antibiotic resistance in the general population.

Methods

Escherichia coli (E. coli) was cultured from and minimal inhibitory concentrations against six commonly prescribed antibiotic substances were tested in 750 stool samples of 484 unselected, consecutive outpatients aged 40–74 years attending general practitioners. Odds ratios (OR) and their 95% confidence intervals (CI) for the association between potential risk factors and the prevalence of antibiotic resistance were estimated using generalised estimating equations.

Results

Prevalence of E. coli resistance against ampicillin, doxycycline, cotrimoxazole or quinolones was 24%. Current antibiotic use was strongly associated with antibiotic resistance, adjusted OR: 11.1, 95%CI: 2.3–53, but antibiotic resistance was unaffected by antibiotic use stopped weeks before. Recent hospitalisations were the only other significant predictor of an increased prevalence of resistance.

Conclusions

The strong association between current use of antibiotics and colonisation with antibiotic resistant E. coli suggests a major role for selection of resistant strains while using antibiotics that seem to be quickly reversible, though. Copyright © 2003 John Wiley & Sons, Ltd.
Early onset of hyperkalemia in patients treated with low molecular weight heparin: a prospective study
Authors: Koren‐Michowitz Maya , Avni Batia , Michowitz Yoav , Moravski Gil , Efrati Shai , Golik Ahuva
Published: April 2004

Objective

Data on low molecular weight heparin (LMWH) and induction of hyperkalemia is scarce. Therefore, we conducted a prospective study evaluating potassium levels before and after three days of treatment with the LMWH Enoxaparin.

Methods

Patients treated with the LMWH Enoxaparin in the standard therapeutic dosages were included. Levels of potassium, sodium, urea, creatinine, AST, ALT bicarbonate, pH and platelet counts were examined before and after three days of LMWH treatment. Plasma renin activity (PRA) and aldosterone levels were examined in a subgroup of patients. Potassium levels were correlated with disease states and medications known to affect potassium homeostasis.

Results

Ninety‐seven consecutive patients were enrolled in the study, however, 12 patients were excluded from analysis; therefore 85 patients comprised the study group. The most common reason for exclusion (in 9 patients) was the absence of a second potassium result. We found an increase in potassium levels from 4.26±0.04 mmol/L at baseline to 4.43±0.04 mmol/L on the third day of treatment (mean±SE), with potassium levels exceeding 5.0 mmol/L in 9% of treated patients. There was no life threatening or symptomatic hyperkalemia. PRA and aldosterone levels did not change significantly during the treatment period. There was no correlation between the increase in potassium levels and diabetes mellitus or treatment with angiotensin converting enzymes inhibitors, angiotensin receptor blockers, β‐blockers and non‐potassium sparing diuretics.

Conclusions

Potassium levels increase on the third day of treatment with the LMWH Enoxaparin. This effect may be aldosterone independent. Copyright © 2003 John Wiley & Sons, Ltd.
Oral anticoagulants and the risk of osteoporotic fractures among elderly
Authors: Pilon Danielle , Castilloux Anne‐Marie , Dorais Marc , LeLorier Jacques
Published: April 2004

Purpose

Coumadin‐based oral anticoagulants are associated with a decrease in bone mass density, but their role in fracture risk is equivocal. Because the use of oral anticoagulants is prevalent among the elderly, as is the risk and morbidity of osteoporotic fractures, the association between osteoporotic fractures and oral anticoagulants needs to be clarified.

Method

We conducted a case‐control study on a 10% random sample of subjects aged 70 years and older enrolled in the Quebec universal health insurance plan between 1992 and 1994. Incident cases of a first osteoporotic fracture were identified by International Classification of Diseases, Ninth Revision codes. Exposure was defined as one or more prescriptions of oral anticoagulants dispensed before the osteoporotic fracture. Ten controls for each case, matched by age and date of osteoporotic fracture, were identified.

Results

Among 1523 cases, 48 (3.2%) were ever exposed to oral anticoagulants; among 15 205 controls, 461 (3.0%) were ever exposed (crude odds ratio: 1.0: 95% confidence interval: 0.7–1.5). These negative results persisted after adjusting for potential confounding variables and stratifying exposure into cumulative dose and treatment duration.

Conclusions

Coumadin‐based oral anticoagulants are not significantly associated with osteoporotic fractures among the elderly, providing reassurance for elderly patients on long‐term oral anticoagulants. Copyright © 2003 John Wiley & Sons, Ltd.
Drug switching patterns among patients with rheumatoid arthritis and osteoarthritis using COX‐2 specific inhibitors and non‐specific NSAIDs
Authors: Zhao Sean Z. , Wentworth Chuck , Burke Thomas A. , Makuch Robert W.
Published: April 2004

Purpose

To compare RA and OA patients' time‐to‐switch after newly initiating treatment with three most commonly used non‐specific (NS)‐NSAIDs and two COX‐2 inhibitors, celecoxib and rofecoxib.

Methods

Managed care enrollees newly prescribed celecoxib, rofecoxib, ibuprofen, naproxen or diclofenac were identified. Time to switch to a different NS‐NSAID or COX‐2 specific inhibitor was determined using time‐to‐event analysis and Cox proportional hazards models were used to estimate the odds ratio (OR) after controlling for potential confounders.

Results

The time to 25% of the cohort switching was longer for rofecoxib and celecoxib (159 and 205 days respectively) compared to the three NS‐NSAIDs (49–78 days). Patients were at the highest risk of switching within the first 100 days of therapy. After adjusting for potential confounding factors, the OR for switching to another NS‐NSAID or COX‐2 specific inhibitor ranged from 1.74 to 2.35 for the three NS‐NSAIDs compared to celecoxib (all comparisons, p < 0.01). Similar findings were obtained when comparing rofecoxib to each of the three NS‐NSAIDS (all comparisons, p < 0.01). When COX‐2 inhibitors combined were compared to NS‐NSAIDS combined, the OR for switching was 1.53 (95% confidence interval=1.42–1.65; p < 0.01) after adjusting for potential confounders.

Conclusions

Patients on the COX‐2 specific inhibitors (celecoxib and rofecoxib) were significantly less likely to switch their therapy than patients on NS‐NSAIDS (ibuprofen, naproxen and diclofenac). These results suggest that COX‐2 specific inhibitors may be a more effective treatment option when compared with NS‐NSAIDs in usual clinical practice. Copyright © 2003 John Wiley & Sons, Ltd.
Impact of mailed warning to prescribers on the co‐prescription of tramadol and antidepressants
Authors: Shatin Deborah , Gardner Jacqueline S. , Stergachis Andy , Blough David , Graham David
Published: April 2004

Purpose

An evaluation was made of the effectiveness in changing prescribing behavior of ‘Dear Health Professional (DHP)’ letters mailed by the manufacturer to physicians and other health professionals advising them of safety information on co‐prescribing of tramadol and antidepressants.

Methods

A retrospective cohort analysis of prescription claims of all plan members from 12 UnitedHealth Group‐affiliated health plans who received a first prescription for tramadol between 1 April 1995 and 31 December 1996. The prevalence of co‐prescribing of antidepressants and tramadol relative to the date of the ‘DHP’ communication was determined.

Results

9218 plan members received an initial prescription for tramadol within the observation period. Prior to the date of the ‘DHP’ communication 1061/4774 (22.2%) members received a prescription for an antidepressant within 30 days of their first prescription for tramadol. Following the date of the communication 844/4444 (19.0%) of members received an antidepressant within 30 days of their first prescription for tramadol. An overall decreasing linear trend in antidepressant co‐prescribing was evident over the observation period, but there was no statistically significant acceleration in the decrease following this communication.

Conclusions

The mailed ‘DHP’ advisory letter did not affect the rate of co‐prescribing of tramadol with antidepressants. Copyright © 2004 John Wiley & Sons, Ltd.
Use and adherence to beta‐blockers for secondary prevention of myocardial infarction: who is not getting the treatment?
Authors: Wei Li , Flynn Robert , Murray Gordon D. , MacDonald Thomas M.
Published: April 2004

Purpose

To characterise those who receive beta‐blocker therapy after MI and to estimate the effect of adherence to beta‐blocker use on subsequent mortality and recurrent MI.

Methods

A community‐based observational cohort study was done using a record linkage database. Patients were those discharged from hospitals after their first MI between January 1994 and December 1995 and who also survived for at least 1 year. The outcome was all cause mortality and recurrent MI. Results were adjusted for age, sex, social deprivation, airways disease, peripheral vascular disease (PVD), diabetes mellitus, cardiovascular drug use, steroid use and hospitalisation for cardiovascular disease using a logistic regression model and a Cox regression model.

Results

A total of 865 patients were included in this study. 386 (44.6%) were on beta‐blocker treatment during the year after MI. Beta‐blocker use was lower amongst high‐risk patients (older patients, patients with obstructive airway disease, PVD and those with a previous hospitalisation for heart failure). Mortality was lower in patients treated with beta‐blockers compared with those untreated. Good adherence (≥80%) was associated with a lower adjusted relative risk of mortality compared with unexposed patients (0.49, 95%CI 0.30–0.80, p < 0.01). Within the high‐risk subgroup of patients, the adjusted relative risk of mortality with good adherence was 0.40 (0.17–0.93, p = 0.03).

Conclusions

Beta‐blocker use was lower in older patients, patients with airways disease, PVD and heart failure, but these patients appeared to have the greatest benefit from beta‐blockers. Good adherence to beta‐blocker treatment after MI was associated with a lower risk of mortality. Copyright © 2004 John Wiley & Sons, Ltd.
Nonaqueous dispersion polymerization of styrene in methanol with the ionomer block copolymer poly[(4‐methylstyrene)‐co‐(4‐vinyltriethylbenzyl ammonium bromide)]‐b‐polyisobutene as a stabilizer
Authors: Ma Yuhong , Yang Wantai
Published: April 2004

The nonaqueous dispersion polymerization of styrene in methanol with poly[(4‐methylstyrene)‐co‐(4‐vinyltriethylbenzyl ammonium bromide)]‐b‐polyisobutene as a stabilizer was investigated. There was no observable inducing period or autoacceleration in the polymerization process. The conversion increased almost linearly with the polymerization time as high as 80%. The average sizes of the obtained polystyrene particles increased, and the size distributions of the polystyrene particles tended to become narrower, with increasing conversion. The mechanism of the dispersion polymerization in the presence of polyisobutene‐b‐poly[(4‐methylstyrene)‐co‐(4‐vinyltriethylbenzyl ammonium bromide)] was nucleation/growth. When the stabilizer/monomer ratio (w/w) was greater than 2.0%, the polystyrene dispersion was stable, and there was no observable polymer particle coagulation taking place during the whole polymerization process. The average diameter of the polymer particles can be mediated through changes in the polymerization conversion, monomer, and stabilizer. Nearly monodispersed polystyrene particles with average diameters of approximately 0.45–2.21 μm were obtained under optimal conditions. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 2678–2685, 2004
Photoinduced controlled/living free‐radical polymerization of 4‐methacryloyl‐1,2,2,6,6‐pentamethyl‐piperidenyl
Authors: Liu Xiaoxuan , Zhang Xiahong , Zhang Xinghong , Wu Guangguo , Yang Jianwen , Pang Laixing , Zeng Zhaohua , Chen Yonglie
Published: April 2004

The photoinduced solution polymerization of 4‐methacryloyl‐1,2,2,6,6‐pentamethyl‐piperidinyl (MPMP), used as a reactive hindered amine piperidinol derivative, was performed. The obtained MPMP homopolymer had a very narrow molecular weight distribution (1.06–1.39) according to gel permeation chromatography. The number‐average and weight‐average molecular weights increased linearly with the monomer conversion, this being characteristic of controlled/living free‐radical polymerizations. Electron spin resonance signals were detected in the MPMP homopolymer and in a polymer mixture solution, and they were assigned to nitroxide radicals, which were bound to the polymer chains and persisted at a level of 10−9 mol/L during the polymerization. Instead of the addition of mediated nitroxide radicals such as 2,2,6,6‐tetramethyl‐piperidinyl‐1‐oxy (TEMPO), those radicals (>NO ·) were formed in situ during the photopolymerization of MPMP, and so the reaction mechanism was understood as being similar to that of TEMPO‐mediated controlled/living free‐radical polymerization. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 2659–2665, 2004
Preparation of a new polymer containing photoluminescent pyrazoline unit in the main chain
Authors: Fang Qiang , Yamamoto Takakazu
Published: April 2004

A novel photoluminescent polymer (PPyne) containing a 2‐pyrazoline unit in the molecular main chain was prepared (for the first time) by polycondensation between a 2‐pyrazoline monomer [an adduct of 2,6‐bis(4‐bromobenzylidene)cyclohexanone with phenylhydrazine] and 2,5‐dihexyloxy‐p‐phenylene diboric ester in the presence of Pd(PPh3)4. PPyne had a number‐average molecular weight of 7800 and a polydispersity index of 1.99 and showed good solubility in common organic solvents. In toluene PPyne exhibited an intrinsic viscosity [η] of 0.42 dL g−1 at 30 °C. The polymer was photoluminescent (PL) in both the chloroform solution and the solid state; the quantum yield of PL in the solution was 40%. In the two states, PPyne gave the same ultraviolet–visible (UV–vis) peak at 368 nm and the same PL peak at 512 nm. DSC traces indicated that PPyne had a melting temperature of 168 °C, and thermogravimetric analysis revealed that the polymer had good thermal stability with a 5 wt % loss temperature of 376 °C under N2. Electrochemical oxidation of PPyne started at about 0.5 V versus Ag/AgNO3 and gave a peak at 0.98 V versus Ag/AgNO3 with a color change of the film from yellow to black green. The color change was followed by UV–vis spectroscopy. The corresponding reduction peak appeared at 0.80 V versus Ag/AgNO3. Treatment of PPyne with HCl led to dehydrogenating transformation of the polymer to a new cross‐conjugated polymer. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 2686–2697, 2004
The effect of annealing on the crystallization of poly(ethylene terephthalate)/polycarbonate blends
Authors: Kong Y. , Hay J. N.
Published: April 2004

The effect of annealing on the morphology and subsequent crystallization kinetics of poly (ethylene terephthalate)/polycarbonate blends have been investigated using differential scanning calorimetry (DSC), polarized light microscopy, and scanning electron microscopy (SEM). During annealing transesterification and phase coarsening occurred, and the final properties were compromizes between these two competing effects. Initially, the effect of phase separation dominated and the rate of cold crystallization of PET increased. Transesterification, however, became increasingly important and the rate of crystallization decreased progressively until finally the blend completely lost the ability to crystallize. At this stage in the reaction a single glass transition was observed and uniform glassy material observed in the SEM. The maximum crystallinity of the blend achieved on heating showed the same trend in first increasing and then decreasing with annealing time. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 2129–2136, 2004