bluuebunny/crossref_metadata_2025_split huggingface dataset:
The additional risk of malignant mesothelioma in former workers and residents of Wittenoom with benign pleural disease or asbestosis
Authors: Reid A , de Klerk N , Ambrosini G , Olsen N , Pang S C , Musk A W 
Published: September 2005

Aims:To examine the hypothesis that people with benign pleural disease or asbestosis have an increased risk of malignant mesothelioma beyond that attributable to their degree of asbestos exposure.Methods:Former workers and residents of the crocidolite mining and milling town of Wittenoom are participating in a cancer prevention programme (n = 1988). The first plain chest radiograph taken at the time of recruitment into the cancer prevention programme was read for evidence of benign pleural disease and asbestosis, using the UICC classification. Crocidolite exposure of former workers was derived from employment records and records of dust measurements performed during the operation of the asbestos mine and mill between 1943 and 1966. Based on fibre counts, exposure for former residents was determined using duration of residence and period of residence (before and after a new mill was commissioned in 1957) and interpolation from periodic hygienic measures undertaken from personal monitors between 1966 and 1992. Cox proportional hazards modelling was used to relate benign pleural disease, asbestosis, asbestos exposure, and mesothelioma.Results:Between 1990 and 2002, there were 76 cases of mesothelioma (56 of the pleura and 20 of the peritoneum). Cases had more radiographic evidence of (all) benign pleural disease, pleural thickening, blunt/obliterated costophrenic angle, and asbestosis than non-cases. Adjusting for time since first exposure (log years), cumulative exposure (log f/ml-years), and age at the start of the programme, pleural thickening (OR = 3.1, 95% CI 1.2 to 7.6) and asbestosis (OR = 3.3, 95% CI 1.3 to 8.6) were associated with an increased risk of peritoneal mesothelioma. There was no increased risk for pleural mesothelioma.Conclusion:The presence of benign pleural disease, in particular pleural thickening, and asbestosis appears to increase the risk of mesothelioma of the peritoneum, but not of the pleura beyond that attributable to indices of asbestos exposure in this cohort of subjects exposed to crocidolite.
A search strategy for occupational health intervention studies
Authors: Verbeek J , Salmi J , Pasternack I , Jauhiainen M , Laamanen I , Schaafsma F , Hulshof C , van Dijk F 
Published: September 2005

Background:As a result of low numbers and diversity in study type, occupational health intervention studies are not easy to locate in electronic literature databases.Aim:To develop a search strategy that facilitates finding occupational health intervention studies in Medline, both for researchers and practitioners.Methods:A gold standard of articles was created by going through two whole volumes of 19 biomedical journals, both occupational health specialty and non-occupational health journals. Criteria for occupational health intervention studies were: evaluating an intervention with an occupational health outcome and a study design with a control group. Each journal was searched independently by two of the authors. Search terms were developed by asking specialists and counting word frequencies in gold standard articles.Results:Out of 11 022 articles published we found 149 occupational health intervention studies. The most sensitive single terms were work*[tw] (sensitivity 71%, specificity 88%) and effect*[tw] (sensitivity 75%, specificity 63%). The most sensitive string was (effect*[tw] OR control*[tw] OR evaluation*[tw] OR program*[tw]) AND (work*[tw] OR occupation*[tw] OR prevention*[tw] OR protect*[tw]) (sensitivity 89%, specificity 78%). The most specific single terms were “occupational health”[tw] (sensitivity 22%, specificity 98%) and effectiveness[tw] (sensitivity 22%, specificity 98%). The most specific string was (program[tw] OR “prevention and control”[sh]) AND (occupational[tw] OR worker*[tw]) (sensitivity 47%, specificity 98%).Conclusion:No single search terms are available that can locate occupational health intervention studies sufficiently. The authors’ search strings have acceptable sensitivity and specificity to be used by researchers and practitioners respectively. Redefinition and elaboration of keywords in Medline could greatly facilitate the location of occupational health intervention studies.
A NOVEL MECHANISM BASED ON ARTIFICIAL LOGICAL SPIDER WEB FOR REROUTING IN MPLS NETWORKS
Authors: YANG XINYU , SHI YI 
Published: September 2005

Multiprotocol label switching (MPLS) is a hybrid solution that combines the advantages of easy forwarding with the ability of guaranteeing quality-of-service (QoS). To deliver reliable service, MPLS requires traffic protection and recovery. Rerouting is one such recovery mechanism. In this paper, we propose a novel rerouting model called DDRAAS that is inspired by the spider and its web in nature. We try to establish an artificial logical spider web in the MPLS network to reorganise it into a structure that is more regular and simple. Based on this, we give the definition of the reroute area. Artificial spiders are then used to explore recovery paths dynamically in the reroute area. DDRAAS can be used to calculate the recovery paths in advance in order to protect the work path, while the improved DDRAAS can be a fast rerouting algorithm to calculate and establish recovery paths when faults occur. We have simulated our mechanism using the MPLS network simulator (MNS) and the performance metrics were compared to those of other proposals. The simulation results show that our mechanism is better in reducing packet loss, disorder and has faster rerouting speed. These improvements help to minimise the effects of link failure and/or congestion.
12/15-Lipoxygenase Regulates Intercellular Adhesion Molecule-1 Expression and Monocyte Adhesion to Endothelium Through Activation of RhoA and Nuclear Factor-κB
Authors: Bolick David T. , Orr A. Wayne , Whetzel Angela , Srinivasan Suseela , Hatley Melissa E. , Schwartz Martin A. , Hedrick Catherine C. 
Published: September 2005

Background—12/15-lipoxygenase (12/15-LO) activity leads to the production of the proinflammatory eicosanoids 12-S-hydroxyeicosatetraenoic acid (12SHETE) and 13-S-hydroxyoctadecadienoic acid. We have previously shown a 3.5-fold increase in endothelial intercellular adhesion molecule (ICAM)-1 expression in mice overexpressing the 12/15-LO gene. We examined whether 12/15-LO activity regulated endothelial ICAM-1 expression.Methods and Results—Freshly isolated aortic endothelial cells (EC) from 12/15-LO transgenic mice had significantly greater nuclear factor-κB (NF-κB) activation and ICAM mRNA expression compared with C57BL/6J control. 12/15-LO transgenic EC showed elevated RhoA activity, and inhibition of RhoA using either C3 toxin or the Rho-kinase inhibitor Y-27632 blocked NF-κB activation, ICAM-1 induction, and monocyte adhesion. Furthermore, we show that 12SHETE activates protein kinase Cα, which forms a complex with active RhoA and is required for NF-κB–dependent ICAM expression in response to 12SHETE.Conclusions—The 12/15-LO pathway stimulates ICAM-1 expression through the RhoA/protein kinase Cα-dependent activation of NF-κB. These findings identify a major signaling pathway in EC through which 12/15-LO contributes to vascular inflammation and atherosclerosis.
Low-Frequency Pycnocline Variability in the Northeast Pacific
Authors: Capotondi Antonietta , Alexander Michael A. , Deser Clara , Miller Arthur J. 
Published: September 2005

Abstract
The output from an ocean general circulation model (OGCM) driven by observed surface forcing is used in conjunction with simpler dynamical models to examine the physical mechanisms responsible for interannual to interdecadal pycnocline variability in the northeast Pacific Ocean during 1958–97, a period that includes the 1976–77 climate shift. After 1977 the pycnocline deepened in a broad band along the coast and shoaled in the central part of the Gulf of Alaska. The changes in pycnocline depth diagnosed from the model are in agreement with the pycnocline depth changes observed at two ocean stations in different areas of the Gulf of Alaska. A simple Ekman pumping model with linear damping explains a large fraction of pycnocline variability in the OGCM. The fit of the simple model to the OGCM is maximized in the central part of the Gulf of Alaska, where the pycnocline variability produced by the simple model can account for ∼70%–90% of the pycnocline depth variance in the OGCM. Evidence of westward-propagating Rossby waves is found in the OGCM, but they are not the dominant signal. On the contrary, large-scale pycnocline depth anomalies have primarily a standing character, thus explaining the success of the local Ekman pumping model. The agreement between the Ekman pumping model and OGCM deteriorates in a large band along the coast, where propagating disturbances within the pycnocline, due to either mean flow advection or boundary waves, appear to play an important role in pycnocline variability. Coastal propagation of pycnocline depth anomalies is especially relevant in the western part of the Gulf of Alaska, where local Ekman pumping-induced changes are anticorrelated with the OGCM pycnocline depth variations. The pycnocline depth changes associated with the 1976–77 climate regime shift do not seem to be consistent with Sverdrup dynamics, raising questions about the nature of the adjustment of the Alaska Gyre to low-frequency wind stress variability.
Observations of Inertial Wave Events near the Continental Slope off Goban Spur
Authors: van Aken Hendrik M. , Maas Leo R. M. , van Haren Hans 
Published: September 2005

Abstract
Near-inertial waves were observed during the Ocean Margin Exchange (OMEX-I) experiments with current meters over the continental slope near Goban Spur. The strongest inertial motion was observed in the bottom layer, about 50 m above the 1000-m isobath. There the waves were slightly (1.7%) superinertial and the bottom slope appeared to be critical for the near-inertial peak frequency, allowing the velocity vector to follow the sloping bottom. The vertical velocity component of this motion was responsible for the near-inertial spectral peak in the temperature spectrum, which was also observed in the bottom layer. Evidence was found supporting the speculative hypothesis that high-energy near-inertial wave events were produced during geostrophic adjustment in the variable deep eastern-boundary current over the slope near Goban Spur.
Use of interleukin 7 receptor-α knockout donor cells demonstrates the lymphoid independence of dendritic cells
Authors: Takeuchi Satoshi , Katz Stephen I. 
Published: September 2005

AbstractThe precise lineage of dendritic cells (DCs), including skin Langerhans cells (LCs), is unclear. Interleukin 7 (IL-7) and its receptor (IL-7Rα) are known to mediate lymphopoiesis, and IL-7 is also known to be essential for the generation of DCs from lymphoid-committed precursors in vitro. Thus, to determine the developmental lymphoid (or IL-7Rα) dependency of various DCs and to examine the importance of IL-7/IL-7Rα for DC development in vivo, we used IL-7Rα knockout (KO) donor cells to reconstitute DCs/LCs in sublethally irradiated recipients and compared the results to those obtained using wild-type (WT) donor cells. We found that lymphoid lineage cells (except natural killer [NK] cells), including thymocytes, were less efficiently reconstituted by IL-7Rα KO donor cells, whereas myeloid lineage cells and DCs/LCs were equally well reconstituted by both the IL-7Rα KO and WT donor cells. Overall, we conclude that IL-7Rα is not required for the development of DCs/LC in vivo.
Deletion of the selection cassette, but not cis-acting elements, in targeted Flk1-lacZ allele reveals Flk1 expression in multipotent mesodermal progenitors
Authors: Ema Masatsugu , Takahashi Satoru , Rossant Janet 
Published: September 2005

AbstractFlk1, the gene encoding the vascular endothelial growth factor receptor 2 (VEGFR-2), is a well-known marker for vascular and hematopoietic progenitors and is indispensable for normal hematopoiesis and vasculogenesis. Here we show that Flk1 expression in the early mouse embryo marks a broad spectrum of mesodermal progenitors exiting the primitive streak as well as later mesodermal cell types including some cardiomyocytes, portions of the somites, and all extraembryonic mesoderm cells. These findings made use of an Flk1-lacZ knock-in allele in which the neomycin selection cassette was removed, which resulted in full replication of the endogenous expression of Flk1. Targeted deletion of a region in intron 1 that has been proposed to direct endothelial expression produced no alteration in either endothelial or broader mesodermal expression of the Flk1-lacZ allele. Examination of lacZ expression in homozygotes for the Flk1lacZ neo-out allele revealed that lacZ-expressing mesodermal cells persisted in nonvascular regions. Thus, Flk1 expression marks progenitors with broad mesodermal potential but is not absolutely required for the development of all mesodermal lineages in which it is expressed.
The proteasome inhibitor bortezomib induces apoptosis in mantle-cell lymphoma through generation of ROS and Noxa activation independent of p53 status
Authors: Pérez-Galán Patricia , Roué Gaël , Villamor Neus , Montserrat Emili , Campo Elias , Colomer Dolors 
Published: September 2005

AbstractMantle-cell lymphoma (MCL) is a mature B-cell lymphoma with an aggressive course and generally poor prognosis. Conventional chemotherapy has little efficacy. Bortezomib is a novel, reversible, and highly specific proteasome inhibitor that appears as a new hope for MCL treatment. We have analyzed the in vitro sensitivity to bortezomib in 4 MCL cell lines and in primary tumor cells from 10 MCL patients. Bortezomib induced phosphatidylserine exposure, mitochondrial depolarization, ROS generation, Bax and Bak conformational changes, and caspase activation. In addition, ROS scavengers, but not pancaspase inhibitors, blocked all apoptosis hallmarks. Protein and mRNA-expression analysis, revealed marked up-regulation of the BH3-only protein Noxa, between 4 to 6 hours after bortezomib addition, independent of p53 status. However, this up-regulation was faster and higher in cells with functional p53. Noxa RNA interference markedly decreased sensitivity to bortezomib, pointing to this protein as a key mediator between proteasome inhibition and mitochondrial depolarization in MCL cells. Noxa interacts with the antiapoptotic protein Mcl-1 and promotes Bak release from Mcl-1, suggesting that up-regulation of Noxa might counteract Mcl-1 accumulation after bortezomib treatment. These findings should be useful to extend the therapeutic strategies in MCL patients and to improve their prognosis.
The principal eosinophil peroxidase product, HOSCN, is a uniquely potent phagocyte oxidant inducer of endothelial cell tissue factor activity: a potential mechanism for thrombosis in eosinophilic inflammatory states
Authors: Wang Jian-Guo , Mahmud Shawn A. , Thompson Jacob A. , Geng Jian-Guo , Key Nigel S. , Slungaard Arne 
Published: September 2005

AbstractIn vivo, bromide (Br–), nitrite (NO2–), and thiocyanate (SCN–) compete for oxidation by eosinophil peroxidase (EPO) and H2O2, yielding, respectively, HOBr, NO2·, and HOSCN. We have recently shown that SCN– is the strongly preferred substrate for EPO in vivo and that HOSCN, in contrast with other EPO-generated oxidants and HOCl, is a relatively weak, cell-permeant, sulfhydryl (SH)–reactive oxidant. We here show that HOSCN is a uniquely potent (up to 100-fold) phagocyte oxidant inducer of tissue factor (TF) activity in human umbilical vein endothelial cells (HUVECs). This induction is attributable to transcriptional up-regulation of TF gene expression dependent upon both activation of the p65/c-Rel TF-κB transcription factor and activity of the ERK1/2 kinase pathway upstream of Egr-1 and was markedly further enhanced in the presence of wortmannin, an inhibitor of the PI3 kinase/Akt pathway. HOSCN also markedly activates the proinflammatory p65/p50 NF-κB pathway. Based on these findings we hypothesize that HOSCN generated by adherent and infiltrating eosinophils may provoke the development of a prothrombotic and proinflammatory endothelial/endocardial phenotype that promotes the pronounced thrombotic diathesis characteristic of the hypereosinophilic syndrome.
Ocular adnexal lymphoma: a clinicopathologic study of a large cohort of patients with no evidence for an association with Chlamydia psittaci
Authors: Rosado Manuel F. , Byrne Gerald E. , Ding Feying , Fields Kenneth A. , Ruiz Phillip , Dubovy Sander R. , Walker Gale R. , Markoe Arnold , Lossos Izidore S. 
Published: September 2005

AbstractNon-Hodgkin lymphomas are among the most common primary tumors occurring in the ocular adnexa. Herein, we present a 14-year single-institution experience in 62 patients with primary ocular adnexal lymphomas (OALs). Association with Chlamydia psittaci infection is examined in 57 tumor specimens.Extranodal marginal zone lymphoma (EMZL) was the most frequent histologic subtype (89%). The majority of patients with EMZL (84%) presented with stage E-extranodal (IE), however only 16% had an advanced stage. All stage IE patients were treated with local radiotherapy, whereas patients with disseminated disease received systemic therapy with or without local irradiation. All but 1 patient with EMZL achieved complete remission (CR). During a median follow-up of 52 months (range, 3-153 months), the estimated 5-year overall survival (OS) and freedom from progression (FFP) were 96% and 79%, respectively. During the follow-up, 22% of patients relapsed, mainly in extranodal sites, and 4% transformed to diffuse large B-cell lymphoma. None of the patients exhibited local orbital failure in the radiation field. None of the OAL specimens harbored C psittaci DNA.Our study demonstrates that EMZLs, accounting for the majority of primary OALs, are characterized by an indolent natural history with frequent, continuous extranodal relapses. In South Florida, OALs are not associated with C psittaci infections.
PKCϵ controls protection against TRAIL in erythroid progenitors
Authors: Mirandola Prisco , Gobbi Giuliana , Ponti Cristina , Sponzilli Ivonne , Cocco Lucio , Vitale Marco 
Published: September 2005

Abstract
Apoptosis plays a central role in the regulation of the size of the hematopoietic stem cell pool as well as in the processes of cell differentiation along the various hematopoietic lineages. TRAIL is a member of the TNF family of cytokines with a known apoptogenic role against a variety of malignant cells and an emerging role in the modulation of normal hematopoiesis. Here we worked on the hypothesis that PKCϵ could act as a switch of the cellular response to TRAIL during erythropoiesis. We demonstrate that EPO-induced erythroid CD34 cells are insensitive to the apoptogenic effect of TRAIL at day 0 due to the lack of specific receptor expression. From day 3 onward, erythroid cells express surface death receptors and become sensitive to TRAIL up to day 7/8 when, notwithstanding death-receptor expression, the EPO-driven up-regulation of PKCϵ intracellular levels renders differentiating erythroid cells resistant to TRAIL likely via Bcl-2 up-regulation. Our conclusion is that in human CD34 cells, EPO promotes a series of events that, being finely regulated in their kinetics, restricts the sensitivity of these cells to TRAIL to a specific period of time, which therefore represents the “TRAIL window” for the negative regulation of erythroid-cell numbers.
Radiosensitising effect of electrochemotherapy with bleomycin in LPB sarcoma cells and tumors in mice
Authors: Kranjc Simona , Cemazar Maja , Grosel Alenka , Sentjurc Marjeta , Sersa Gregor 
Published: September 2005

Abstract

Background
Bleomycin is poorly permeant but potent cytotoxic and radiosensitizing drug. The aim of the study was to evaluate whether a physical drug delivery system – electroporation can increase radiosensitising effect of bleomycin in vitro and in vivo.

Methods
LPB sarcoma cells and tumors were treated either with bleomycin, electroporation or ionizing radiation, and combination of these treatments. In vitro, response to different treatments was determined by colony forming assay, while in vivo, treatment effectiveness was determined by local tumor control (TCD50). Time dependence of partial oxygen pressure in LPB tumors after application of electric pulses was measured by electron paramagnetic oxyimetry.

Results
Electroporation of cells in vitro increased radiosensitising effect of bleomycin for 1.5 times, in vivo radiation response of tumors was enhanced by 1.9 fold compared to response of tumors that were irradiated only. Neither treatment of tumors with bleomycin nor application of electric pulses only, affected radiation response of tumors. Application of electric pulses to the tumors induced profound but transient reduction of tumor oxygenation. Although tumor oxygenation after electroporation partially restored at the time of irradiation, it was still reduced at the level of radiobiologically relevant hypoxia.

Conclusion
Our study shows that application of electric pulses to cells and tumors increases radiosensitising effect of bleomycin. Furthermore, our results demonstrate that the radiobiologically relevant hypoxia induced by electroporation of tumors did not counteract the pronounced radiosensitising effect of electrochemotherapy with bleomycin.
Survey of oxaliplatin-associated neurotoxicity using an interview-based questionnaire in patients with metastatic colorectal cancer
Authors: Leonard Gregory D , Wright Maurice A , Quinn Mary G , Fioravanti Suzanne , Harold Nancy , Schuler Barbara , Thomas Rebecca R , Grem Jean L 
Published: September 2005

Abstract

Background
New chemotherapy regimens for patients with colorectal cancer have improved survival, but at the cost of clinical toxicity. Oxaliplatin, an agent used in first-line therapy for metastatic colorectal cancer, causes acute and chronic neurotoxicity. This study was performed to carefully assess the incidence, type and duration of oxaliplatin neurotoxicity.

Methods
A detailed questionnaire was completed after each chemotherapy cycle for patients with metastatic colorectal cancer enrolled in a phase I trial of oxaliplatin and capecitabine. An oxaliplatin specific neurotoxicity scale was used to grade toxicity.

Results
Eighty-six adult patients with colorectal cancer were evaluated. Acute neuropathy symptoms included voice changes, visual alterations, pharyngo-laryngeal dysesthesia (lack of awareness of breathing); peri-oral or oral numbness, pain and symptoms due to muscle contraction (spasm, cramps, tremors). When the worst neurotoxicity per patient was considered, grade 1/2/3/4 dysesthesias and paresthesias were seen in 71/12/5/0 and 66/20/7/1 percent of patients. By cycles 3, 6, 9, and 12, oxaliplatin dose reduction or discontinuation was needed in 2.7%, 20%, 37.5% and 62.5% of patients.

Conclusion
Oxaliplatin-associated acute neuropathy causes a variety of distressing, but transient, symptoms due to peripheral sensory and motor nerve hyperexcitability. Chronic neuropathy may be debilitating and often necessitates dose reductions or discontinuation of oxaliplatin. Patients should be warned of the possible spectrum of symptoms and re-assured about the transient nature of acute neurotoxicity. Ongoing studies are addressing the treatment and prophylaxis of oxaliplatin neurotoxicity.