bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Modulation of Leukotriene B4 Synthesis and Degradation in Human Bronchoalveolar Lavage Cells by Lipopolysaccharide and Tobacco Smoke
Authors: Mao Jenny T. , Tashkin Donald P. , Tsu I-Hsien , Serio Kenneth J. 
Published: September 2008

Abstract
Leukotrienes have been implicated to play a prominent inductive role in carcinogenesis. We previously reported that bronchoalveolar lavage (BAL) cells from smokers manifested higher levels of leukotriene B4 (LTB4) production than ex-smokers. This study aims to elucidate the underlying mechanism(s). BAL cells from current and former smokers were exposed to lipopolysaccharide (LPS) for up to 7 days. LPS induced the release of LTB4 from BAL cells and down-regulated 5-lipoxygenase (5-LOX) mRNA expression in a dose-dependent manner, followed by a decrease in 5-LOX protein production and normalization of LTB4 levels. Exogenous LTB4 inhibited LPS-induced 5-LOX activity and accentuated the down-regulation of 5-LOX mRNA, whereas suppression of 5-LOX abrogated the LPS-induced changes, suggesting a negative feedback mechanism. LPS concomitantly induced expression and activity of the LTB4 metabolizing enzyme LTB4 ω-hydroxylase (LTB4OH) in ex-smokers' BAL cells, but not in smokers' BAL cells. In vitro smoke exposure of ex-smokers' BAL cells also abrogated the LPS-induced up-regulation of LTB4OH mRNA expression. Furthermore, ex-smokers' BAL cells expressed significantly higher LTB4OH mRNA levels than smokers' BAL cells. Such differential modulation of LTB4 synthesis and degradation by LPS in the setting of tobacco smoke exposure suggests that mechanisms responsible for sustained elevation of LTB4 levels in the lung microenvironment may contribute to the pathogenesis of tobacco-related respiratory diseases such as lung cancer. By regulating the balance of LTB4 in the lung, LTB4OH may function as a suppressor of lung carcinogenesis.
(−)-Epigallocatechin Gallate Suppresses Azoxymethane-Induced Colonic Premalignant Lesions in Male C57BL/KsJ-db/db Mice
Authors: Shimizu Masahito , Shirakami Yohei , Sakai Hiroyasu , Adachi Seiji , Hata Kazuya , Hirose Yoshinobu , Tsurumi Hisashi , Tanaka Takuji , Moriwaki Hisataka 
Published: September 2008

Abstract
Obesity and diabetes mellitus are risk factors for colon cancer. The activation of the insulin-like growth factor (IGF)/IGF-IR axis plays a critical role in this carcinogenesis. (−)-Epigallocatechin gallate (EGCG), the major constituent of green tea, seems to have both antiobesity and antidiabetic effects. This study examined the effects of EGCG on the development of azoxymethane-induced colonic premalignant lesions in C57BL/KsJ-db/db (db/db) mice, which are obese and develop diabetes mellitus. Male db/db mice were given four weekly s.c. injections of azoxymethane (15 mg/kg body weight) and then they received drinking water containing 0.01% or 0.1% EGCG for 7 weeks. At sacrifice, drinking water with EGCG caused a significant decrease in the number of total aberrant crypt foci, large aberrant crypt foci, and β-catenin accumulated crypts in these mice, all of which are premalignant lesions of the colon. The colonic mucosa of db/db mice expressed high levels of the IGF-IR, phosphorylated form of IGF-IR (p-IGF-IR), p-GSK-3β, β-catenin, cyclooxygenase-2, and cyclin D1 proteins, and EGCG in drinking water caused a marked decrease in the expression of these proteins. Treating these mice with EGCG also caused an increase in the serum level of IGFBP-3 while conversely decreasing the serum levels of IGF-I, insulin, triglyceride, cholesterol, and leptin. EGCG overcomes the activation of the IGF/IGF-IR axis, thereby inhibiting the development of colonic premalignant lesions in an obesity-related colon cancer model, which was also associated with hyperlipidemia, hyperinsulinemia, and hyperleptinemia. EGCG may be, therefore, useful in the chemoprevention or treatment of obesity-related colorectal cancer.
NAD+-Dependent 15-Hydroxyprostaglandin Dehydrogenase Regulates Levels of Bioactive Lipids in Non–Small Cell Lung Cancer
Authors: Hughes Duncan , Otani Taisuke , Yang Peiying , Newman Robert A. , Yantiss Rhonda K. , Altorki Nasser K. , Port Jeff L. , Yan Min , Markowitz Sanford D. , Mazumdar Madhu , Tai Hsin-Hsiung , Subbaramaiah Kotha , Dannenberg Andrew J. 
Published: September 2008

Abstract
Elevated levels of procarcinogenic prostaglandins (PG) are found in a variety of human malignancies including non–small cell lung cancer (NSCLC). Overexpression of cyclooxygenase-2 and microsomal prostaglandin synthase 1 occurs in tumors and contributes to increased PG synthesis. NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH), the key enzyme responsible for metabolic inactivation of PGs, is down-regulated in various malignancies. The main objective of this study was to elucidate the effect of loss of 15-PGDH on levels of bioactive lipids in NSCLC. We found that levels of cyclooxygenase-2 and microsomal prostaglandin synthase 1 were commonly increased whereas the amount of 15-PGDH was frequently decreased in NSCLC compared with adjacent normal lung. Reduced expression of 15-PGDH occurred in tumor cells and was paralleled by decreased 15-PGDH activity in tumors. Amounts of PGE1, PGE2, and PGF2α, known substrates of 15-PGDH, were markedly increased whereas levels of 13,14-dihydro-15-keto-PGE2, a catabolic product of PGE2, were markedly reduced in NSCLC compared with normal lung. Complementary in vitro and in vivo experiments were done to determine whether these changes in PG levels were a consequence of down-regulation of 15-PGDH in NSCLC. Similar to NSCLC, amounts of PGE1, PGE2, and PGF2α were markedly increased whereas levels of 13,14-dihydro-15-keto-PGE2 were decreased in the lungs of 15-PGDH knockout mice compared with wild-type mice or when 15-PGDH was silenced in A549 lung cancer cells. Collectively, these data indicate that 15-PGDH is commonly down-regulated in NSCLC, an effect that contributes to the accumulation of multiple bioactive lipids in NSCLC.
An Expanded Risk Prediction Model for Lung Cancer
Authors: Spitz Margaret R. , Etzel Carol J. , Dong Qiong , Amos Christopher I. , Wei Qingyi , Wu Xifeng , Hong Waun Ki 
Published: September 2008

Abstract
Risk prediction models are useful in clinical decision making. We have published an internally validated prediction tool for lung cancer based on easily obtainable epidemiologic and clinical data. Because the precision of the model was modest, we now estimate the improvement obtained by adding two markers of DNA repair capacity.
Assay data (host-cell reactivation and mutagen sensitivity) were available for 725 White lung cancer cases and 615 controls, all former or current smokers, a subset of cases and controls from the previous analysis. Multivariable models were constructed from the original variables with addition of the biomarkers separately and together. Pairwise comparisons of the area under the receiver operating characteristic curves (AUC) and 3-fold cross-validations were done.
For former smokers, the AUC and 95% confidence intervals were 0.67 (0.63–0.71) for the baseline model and 0.70 (0.66–0.74) for the expanded model. For current smokers, the comparable AUC values were 0.68 (0.64–0.72) and 0.73 (0.69–0.77). For both groups, the expanded models were statistically significantly better than the baseline models (P = 0.006 and P = 0.0048, respectively), although the increases in the concordance statistics were modest. We also recomputed 1-year absolute risks of lung cancer as described previously for two different risk profiles and showed that individuals who exhibited poor repair capacity or heightened mutagen sensitivity had increased absolute risks of lung cancer.
Addition of biomarker assays improved the sensitivity of the expanded models.
Development and Validation of a Lung Cancer Risk Prediction Model for African-Americans
Authors: Etzel Carol J. , Kachroo Sumesh , Liu Mei , D'Amelio Anthony , Dong Qiong , Cote Michele L. , Wenzlaff Angela S. , Hong Waun Ki , Greisinger Anthony J. , Schwartz Ann G. , Spitz Margaret R. 
Published: September 2008

Abstract
Because existing risk prediction models for lung cancer were developed in white populations, they may not be appropriate for predicting risk among African-Americans. Therefore, a need exists to construct and validate a risk prediction model for lung cancer that is specific to African-Americans. We analyzed data from 491 African-Americans with lung cancer and 497 matched African-American controls to identify specific risks and incorporate them into a multivariable risk model for lung cancer and estimate the 5-year absolute risk of lung cancer. We performed internal and external validations of the risk model using data on additional cases and controls from the same ongoing multiracial/ethnic lung cancer case-control study from which the model-building data were obtained as well as data from two different lung cancer studies in metropolitan Detroit, respectively. We also compared our African-American model with our previously developed risk prediction model for whites. The final risk model included smoking-related variables [smoking status, pack-years smoked, age at smoking cessation (former smokers), and number of years since smoking cessation (former smokers)], self-reported physician diagnoses of chronic obstructive pulmonary disease or hay fever, and exposures to asbestos or wood dusts. Our risk prediction model for African-Americans exhibited good discrimination [75% (95% confidence interval, 0.67–0.82)] for our internal data and moderate discrimination [63% (95% confidence interval, 0.57–0.69)] for the external data group, which is an improvement over the Spitz model for white subjects. Existing lung cancer prediction models may not be appropriate for predicting risk for African-Americans because (a) they were developed using white populations, (b) level of risk is different for risk factors that African-American share with whites, and (c) unique group-specific risk factors exist for African-Americans. This study developed and validated a risk prediction model for lung cancer that is specific to African-Americans and thus more precise in predicting their risks. These findings highlight the importance of conducting further ethnic-specific analyses of disease risk.
The impact of a hybrid online and classroom-based course on palliative care competencies of family medicine residents
Authors: Pereira J , Palacios M , Collin T , Wedel R , Galloway L , Murray A , Violato C , Lockyer J 
Published: September 2008

The University of Calgary offers a palliative care course that involves both classroom- and web-based learning for rural-based family medicine residents. This study assessed the impact of the course on palliative care-related competencies for two classes: 2004 and 2005. Instruments were developed to evaluate pre- versus post-course changes in knowledge (15-item quiz), attitudes (12-item survey), self-perceived comfort levels (19-item survey) and skills (3 long Objective Structured Clinical Examination stations (OSCEs), with accompanying standardised score sheets). In all, 16 and 20 residents participated in the 2004 and 2005 classes, respectively. Internal reliability values were acceptable to very good (Knowledge Quiz, Kuder-Richardson 20 = 0.5; Attitude Scale, α = 0.68–0.78; OSCE score sheets, α = 0.63–0.89; Self-Perceived Comfort Survey, α = 0.89–0.92). Inter-rater reliability values of the OSCE score sheets were α = 0.87 to 0.92. There was a significant improvement in the pre- versus post-course performances in OSCE 2 for 2004 and 2005 ( P = 0.01; P = 0.01; d = 1.42 and 1.94, respectively). Despite statistically insignificant changes in the other OSCEs, acceptable to large effect sizes were noted ( d = 0.4–1.34) for OSCE 1 in 2004 and OSCEs 3 in 2004 and 2005. Knowledge improved significantly pre-versus post-course in 2004 and 2005 ( t = 4.44 and 8.99; d = 2.29 and 2.24, respectively). Significant improvements and large effect sizes were noted in the comfort scales, but a ceiling effect was noted in the communication subscale. This hybrid course resulted in significant improvements across four domains, knowledge, attitudes, self-perceived comfort scale, and skills, in 2 consecutive classes.
Palliative care rehabilitation survey: a pilot study of patients’ priorities for rehabilitation goals
Authors: Schleinich MA , Warren S , Nekolaichuk C , Kaasa T , Watanabe S 
Published: September 2008

Rehabilitation in palliative care is often overlooked. Settings that do consider occupational or physical therapy for palliative care patients often consult to therapists with competing caseloads. Few therapists specialise in palliative care, but nearly all ask, ‘What needs doing’? and ‘How well am I doing that’? No existing instruments address their questions. The objective is to develop and test a questionnaire for identifying patient goals and priorities for rehabilitation in palliative care. A questionnaire representing 11 domains of the Canadian Model of Occupational Performance was designed and pilot tested at four palliative care sites. Each question reflected a typical rehabilitation intervention in palliative care. Patients were asked to rate how important each of these interventions was on a numerical rating scale (0, not important–10, extremely important). Open-ended questions captured verbatim comments regarding thoughts of rehabilitation. The questionnaire was tested for test-retest reliability with two interviews approximately 1 week apart. Forty patients participated in the first interview and 32 in the second. Eight of eleven domain sub-scores achieved an intra-class correlation coefficient of 0.6 or higher. The highest means were for the physical (8.2), institutional (7.8) and self-care (7.8) domains on the first interview and for the spiritual domain (7.9) on the second interview. Suggestions are provided to shorten the questionnaire and strengthen validity. This work furthers the understanding of the role of rehabilitation in palliative care. It also illustrates the feasibility of involving palliative care patients in research that contributes to setting standards and measuring quality of service.
Do case conferences between general practitioners and specialist palliative care services improve quality of life? A randomised controlled trial (ISRCTN 52269003)
Authors: Mitchell GK , Del Mar CB , O’Rourke PK , Clavarino AM 
Published: September 2008

Australian palliative care is delivered by general practitioners (GPs) and specialist palliative care teams. Patient outcomes should improve if they work in formal partnership. We conducted a multi-centred randomised controlled trial of specialist- GP case conferences, with the GP participating by teleconference, or usual care and communication methods. Primary outcome measure was global Quality of Life (QoL) scores at 3 weeks from intervention. Secondary measures included subscale QoL scores and carer burden. Two a priori intention-to-treat analyses were conducted using recruitment, and time of death, as fixed time points. There was no difference between groups in the magnitude of change in global QoL measures from baseline to any time point up to 9 weeks post-case conference, or at any time before death. The case conference group showed better maintenance of some physical and mental health measures of QoL in the 35 days before death. Case conferences may improve clinical relationships and care plans at referral, which are not implemented until severe symptoms develop. Case conferences between GPs and specialist palliative care services may be warranted for palliative care patients.
Evaluation of surface contamination in a hospital hematology—oncology pharmacy
Authors: Touzin Karine , Bussieres Jean-François , Langlois Éric , Lefebvre Michel 
Published: September 2008

Objective. To describe environmental contamination with hazardous drugs in a hospital pharmacy setting before and after reorganizing a hematology— oncology satellite pharmacy. Methods. This is a descriptive study of surface contamination with cyclophosphamide, ifosfamide, and methotrexate in two hematology—oncology satellite pharmacies. In order to measure surface contamination with hazardous drugs, samples from four distinct measurement sites within the pharmacy were taken in each of the two phases (pre-and postphases) using a sampling procedure and an analytical method modified from Larson et al. Results. A total of 133 samples from four measurement sites were taken and analyzed over the course of the study (specifically 60 prephase samples and 73 postphase samples). The study showed a significant increase in the number of positive samples (from 66.7% to 90.4%, p<0.001) from the pre- to the postphase. The increase, however, is only significant in terms of the location where completed preparations were placed after they had come out from under the hood (from 0/15 to 21/28, p<0.001) and the work surface (from 8/15 to 15/15, p = 0.006) and only in terms of ifosfamide. Furthermore, for the other sites studied, the number of positive samples remained unchanged between the pre- and postphase. A statistically significant difference between the pre- and postphase was observed in terms of ifosfamide for three of the four measurement sites studied and methotrexate for one of the four sites. Average concentrations were higher in the post phase in three of the four cases. Conclusion. This study describes environmental contamination with hazardous drugs in a hospital pharmacy setting before and after reorganizing a hematology—oncology satellite pharmacy. The study showed that a refitting of the hemato-oncology pharmacy is not a sufficient strategy to reduce the environmental contamination by ifosfamide because a significant increase in the number of positive samples from the pre- to the postphase have been observed. Many factors can contribute to influence the contamination of hazardous drugs such as the workflow and the training of the personal. Continuous environmental surveillance of hazardous drugs is required to document traces and help reduce risks. J Oncol Pharm Practice (2009) 15: 53—61.
Carbon dioxide formation during initial stages of photodegradation of poly(ethyleneterephthalate) (PET) films
Authors: Fernando S. S. , Christensen P. A. , Egerton T. A. , Eveson R. , Martins-Franchetti S. M. , Voisin D. , White J. R. 
Published: September 2008

Carbon dioxide (CO2) generation by ultraviolet irradiation of poly(ethyleneterephthalate) (PET) films in oxygen was monitored by in situ Fourier transform infrared spectroscopy. Typically, the CO2 absorbance increased by ∼100 × 10−4 in 180 min, with no evidence of hindrance by restricted diffusion of O2 into, or CO2 out of, the films. It was concluded that Fourier transform infrared spectrometry monitoring of CO2 conveniently, reliably and rapidly measures PET films photostability. Quantitative analysis of the CO2 evolved from progressively thinner films from successive stages of the biaxial film drawing process indicated that CO2 was generated within a few microns of the film surface and that the same amounts were generated from the irradiated surface of 540 μm cast, 150 μm uniaxially drawn and 85 μm biaxially drawn films. Although drawing increased film crystallinity, photoreactivity appeared to be unchanged. However, total CO2 formation followed the pattern PET cast<PET uniaxial<PET biaxial because ultraviolet irradiation attenuation reduced photo generation at the rear of thick films.
Lenalidomide down-regulates the CD20 antigen and antagonizes direct and antibody-dependent cellular cytotoxicity of rituximab on primary chronic lymphocytic leukemia cells
Authors: Lapalombella Rosa , Yu Bo , Triantafillou Georgia , Liu Qing , Butchar Jonathan P. , Lozanski Gerard , Ramanunni Asha , Smith Lisa L. , Blum William , Andritsos Leslie , Wang Da-Sheng , Lehman Amy , Chen Ching-Shih , Johnson Amy J. , Marcucci Guido , Lee Robert J. , Lee L. James , Tridandapani Susheela , Muthusamy Natarajan , Byrd John C. 
Published: September 2008

AbstractLenalidomide, an immunomodulatory agent that enhances antibody-dependent cellular cytotoxicity (ADCC), is currently being investigated as a therapy for chronic lymphocytic leukemia (CLL). The anti-CD20 antibody rituximab is active in CLL and represents a rational agent to combine with lenalidomide. We therefore examined whether lenalidomide combined with rituximab enhances direct apoptosis and ADCC in CLL cells. In contrast to previous reports using CD20-positive lymphoma cell lines, lenalidomide down-regulated CD20 surface antigen expression in CLL patient cells via enhanced internalization, without influencing transcription. The CD20 surface antigen internalization enhanced delivery of an oligonucleotide incorporated into anti-CD20 immunoliposomes. In addition, CD20 surface antigen down-modulation by lenalidomide in CLL was accompanied by diminished rituximab-mediated apoptosis and ADCC. These observations suggest a need for alternative sequencing strategies to avoid antagonism between lenalidomide and rituximab therapy in CLL. In addition, they suggest that lenalidomide therapy might be useful to enhance targeted delivery of RNAi-based therapies using CD20 immunoliposomes in B-cell malignancies.
WASP confers selective advantage for specific hematopoietic cell populations and serves a unique role in marginal zone B-cell homeostasis and function
Authors: Westerberg Lisa S. , de la Fuente Miguel A. , Wermeling Fredrik , Ochs Hans D. , Karlsson Mikael C. I. , Snapper Scott B. , Notarangelo Luigi D. 
Published: September 2008

AbstractDevelopment of hematopoietic cells depends on a dynamic actin cytoskeleton. Here we demonstrate that expression of the cytoskeletal regulator WASP, mutated in the Wiskott-Aldrich syndrome, provides selective advantage for the development of naturally occurring regulatory T cells, natural killer T cells, CD4+ and CD8+ T lymphocytes, marginal zone (MZ) B cells, MZ macrophages, and platelets. To define the relative contribution of MZ B cells and MZ macrophages for MZ development, we generated wild-type and WASP-deficient bone marrow chimeric mice, with full restoration of the MZ. However, even in the presence of MZ macrophages, only 10% of MZ B cells were of WASP-deficient origin. We show that WASP-deficient MZ B cells hyperproliferate in vivo and fail to respond to sphingosine-1-phosphate, a crucial chemoattractant for MZ B-cell positioning. Abnormalities of the MZ compartment in WASP−/− mice lead to aberrant uptake of Staphylococcus aureus and to a reduced immune response to TNP-Ficoll. Moreover, WASP-deficient mice have increased levels of “natural” IgM antibodies. Our findings reveal that WASP regulates both development and function of hematopoietic cells. We demonstrate that WASP deficiency leads to an aberrant MZ that may affect responses to blood-borne pathogens and peripheral B-cell tolerance.