bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lewis y antigen promotes the proliferation of ovarian carcinoma-derived RMG-I cells through the PI3K/Akt signaling pathway
Authors: Liu Juanjuan , Lin Bei , Hao Yingying , Qi Yue , Zhu Liancheng , Li Feifei , Liu Dawo , Cong Jianping , Zhang Shulan , Iwamori Masao 
Published: December 2009

AbstractBackgroundLewis y antigen is difucosylated oligosaccharide and is carried by glycoconjugates at cell surface. Elevated expression of Lewis y has been found in 75% of ovarian tumor, and the high expression level is correlated to the tumor's pathological staging and prognosis. This study was to investigate the effect and the possible mechanism of Lewis y on the proliferation of human ovarian cancer cells.MethodsWe constructed a plasmid encoding α1,2-fucosyltransferase (α1,2-FT) gene and then transfected it into ovarian carcinoma-derived RMG-I cells with lowest Lewis y antigen expression level. Effect of Lewis y on cell proliferation was assessed after transfection. Changes in cell survival and signal transduction were evaluated after α-L-fucosidase, anti-Lewis y antibody and phosphatidylinositol 3-kinase (PI3K) inhibitor treatment.ResultsOur results showed that the levels of α1,2-FT gene and Lewis y increased significantly after transfection. The cell proliferation of ovarian carcinoma-derived RMG-I cells sped up as the Lewis y antigen was increased. Both of α-L-fucosidase and anti-Lewis y antibody inhibited the cell proliferation. The phosphorylation level of Akt was apparently elevated in Lewis y-overexpressing cells and the inhibitor of PI3K, LY294002, dramatically inhibited the growth of Lewis y-overexpressing cells. In addition, the phosphorylation intensity and difference in phosphorylation intensity between cells with different expression of α1,2-FT were attenuated significantly by the monoantibody to Lewis y and by the PI3K inhibitor LY294002.ConclusionsIncreased expression of Lewis y antigen plays an important role in promoting cell proliferation through activating PI3K/Akt signaling pathway in ovarian carcinoma-derived RMG-I cells. Inhibition of Lewis y expression may provide a new therapeutic approach for Lewis y positive ovarian cancer.
Recent developments in podiatric prescribing in the UK and Australia
Authors: Gilheany Mark F , Borthwick Alan M 
Published: December 2009

AbstractRecent and substantial changes in access to restricted medicines by podiatrists in Australia are clearly consistent with healthcare policies aimed at reshaping the healthcare workforce. At the same time, prescribing and access to medicines by allied health professionals, including podiatrists, has been the focus of a recent scoping project by the UK Department of Health. In this commentary we explore the possible implications of these changes.
Local expression of tumor necrosis factor-receptor 1:immunoglobulin G can induce salivary gland dysfunction in a murine model of Sjögren's syndrome
Authors: Vosters Jelle L , Yin Hongen , Roescher Nienke , Kok Marc R , Tak Paul P , Chiorini John A 
Published: December 2009

Abstract
Introduction
Tumor necrosis factor is a pleiotropic cytokine with potent immune regulatory functions. Although tumor necrosis factor inhibitors have demonstrated great utility in treating other autoimmune diseases, such as rheumatoid arthritis, there are conflicting results in Sjögren's syndrome. The aim of this study was to assess the effect of a locally expressed tumor necrosis factor inhibitor on the salivary gland function and histopathology in an animal model of Sjögren's syndrome.

Methods
Using in vivo adeno associated viral gene transfer, we have stably expressed soluble tumor necrosis factor-receptor 1-Fc fusion protein locally in the salivary glands in the Non Obese Diabetic model of Sjögren's syndrome. Pilocarpine stimulated saliva flow was measured to address the salivary gland function and salivary glands were analyzed for focus score and cytokine profiles. Additionally, cytokines and autoantibody levels were measured in plasma.

Results
Local expression of tumor necrosis factor-receptor 1:immunoglobulin G fusion protein resulted in decreased saliva flow over time. While no change in lymphocytic infiltrates or autoantibody levels was detected, statistically significant increased levels of tumor growth factor-β1 and decreased levels of interleukin-5, interleukin-12p70 and interleukin -17 were detected in the salivary glands. In contrast, plasma levels showed significantly decreased levels of tumor growth factor-β1 and increased levels of interleukin-4, interferon-γ, interleukin-10 and interleukin-12p70.

Conclusions
Our findings suggest that expression of tumor necrosis factor inhibitors in the salivary gland can have a negative effect on salivary gland function and that other cytokines should be explored as points for therapeutic intervention in Sjögren's syndrome.
Combination effect of antithrombin and recombinant human soluble thrombomodulin in a lipopolysaccharide induced rat sepsis model
Authors: Iba Toshiaki , Nakarai Etsuro , Takayama Toshio , Nakajima Kenji , Sasaoka Tetsumasa , Ohno Yoichi 
Published: December 2009

Abstract
Introduction
Recombinant human soluble thrombomodulin (rhsTM) is newly developed for the treatment of DIC. The purpose of this study was to evaluate the efficacy of the concomitant administration of rhsTM and antithrombin (AT).

Methods
In the first series, rats were treated with either 62.5, 125, 250 or 500 IU/kg (n = 6, each) of AT or 0.125, 0.25, 0.5 or 1.0 mg/kg (n = 6, each) of rhsTM followed by lipopolysaccharide (LPS) injection. 8 h later, the fibrinogen level was examined. In the second series, TM group was pretreated with 0.25 mg/kg of rhsTM, AT group was pretreated with 125 IU/kg of AT, AT/TM group was pretreated with both AT and rhsTM, and control group was pretreated with saline (n = 7, each). The platelet count, fibrinogen, ALT, LDH and high-mobility group box 1 (HMGB1) levels were measured. In addition, histologic changes in liver were examined. In the third series, survival was calculated up to 24 h.

Results
Both AT and rhsTM produced a linear dose-response with regard to the fibrinogen level, with 125 IU/kg of AT and 0.25 mg/kg of rhsTM producing equivalent effects. The combined administration of AT and rhsTM significantly reduced the decrease in the platelet count and the fibrinogen level (P < 0.05, 0.01, respectively). The elevations in ALT and LDH were significantly suppressed in all treatment groups. The HMGB1 level and the histologic changes tended to indicate damage reduction. Survival was significantly better only in AT/TM group (P < 0.01).

Conclusions
The coadministration of AT and rhsTM might be effective for the treatment of severe sepsis.
Statin Use and Prognosis in Patients With Diffuse Large B-Cell Lymphoma and Follicular Lymphoma in the Rituximab Era
Authors: Nowakowski Grzegorz S. , Maurer Matthew J. , Habermann Thomas M. , Ansell Stephen M. , Macon William R. , Ristow Kay M. , Allmer Cristine , Slager Susan L. , Witzig Thomas E. , Cerhan James R. 
Published: December 2009

PurposeStatins have antilymphoma properties but have also been shown to inhibit the binding of rituximab to the CD20 antigen, resulting in reduced antitumor activity of rituximab in vitro. The clinical impact of statin use on the outcome of lymphoma patients treated with a rituximab-containing regimen is unknown.Patients and MethodsConsecutive patients with newly diagnosed, diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) were enrolled onto a registry and observed prospectively. The impact of statin use on patients' outcomes was analyzed.ResultsTwo hundred twenty-eight patients with DLBCL and 293 patients with FL were enrolled from September 2002 through June 2007; 21% of patients with DLBCL and 19% of patients with FL were on statins at diagnosis, and 20% and 17% remained on statins during lymphoma treatment, respectively. All patients with DLBCL and 39% of patients with FL received initial therapy containing rituximab. The median follow-up time was 47 months (range, 13 to 80 months). Statin use had no impact on the overall response rate (P = .67), overall survival (P = .76), or event-free survival (EFS) in patients with DLBCL (hazard ratio [HR] = 0.85; 95% CI, 0.43 to 1.68). Statin use at diagnosis was associated with improved EFS in patients with FL (HR = 0.45; 95% CI, 0.26 to 0.77), including subgroups treated with rituximab or a rituximab-containing regimen (HR = 0.38; 95% CI, 0.14 to 1.07) and patients who were observed only (HR = 0.38; 95% CI, 0.17 to 0.84).ConclusionThe concurrent use of statins during the treatment of patients with DLBCL and FL in the rituximab era did not adversely affect outcome. The apparent benefit of statin therapy on FL outcome requires further studies.
Safety and Efficacy of Romiplostim in Patients With Lower-Risk Myelodysplastic Syndrome and Thrombocytopenia
Authors: Kantarjian Hagop , Fenaux Pierre , Sekeres Mikkael A. , Becker Pamela S. , Boruchov Adam , Bowen David , Hellstrom-Lindberg Eva , Larson Richard A. , Lyons Roger M. , Muus Petra , Shammo Jamile , Siegel Robert , Hu Kuolung , Franklin Janet , Berger Dietmar P. 
Published: December 2009

Purpose To assess the safety and efficacy of romiplostim, a peptibody that increases platelet production, for treatment of thrombocytopenic patients with myelodysplastic syndromes (MDS). Patients and Methods Eligible patients had lower-risk MDS (International Prognostic Scoring System low or intermediate 1), a mean baseline platelet count ≤ 50 × 109/L, and were only receiving supportive care. Patients received three injections of 300, 700, 1,000, or 1,500 μg romiplostim at weekly intervals. After evaluation of platelet response at week 4, patients could continue to receive romiplostim in a treatment extension phase for up to 1 year. Results All 44 patients who enrolled completed the treatment phase; 41 patients continued into the extension phase. Median platelet counts increased throughout the study, from fewer than 30 × 109/L at baseline to 60, 73, 38, and 58 × 109/L at week 4 for the 300-, 700-, 1,000-, and 1,500 -μg dose cohorts, respectively. A durable platelet response (per International Working Group 2000 criteria for 8 consecutive weeks independent of platelet transfusions) was achieved by 19 patients (46%). The incidence of bleeding events and platelet transfusions was less common among patients who achieved a durable platelet response than those who did not (4.3 v 39.3 per 100 patient-weeks). Forty-three patients (98%) reported one or more adverse events. Treatment-related serious adverse events were reported in five patients (11%), all of whom were in the 1,500-μg dose cohort. Two patients progressed to acute myeloid leukemia during the study. No neutralizing antibodies to either romiplostim or endogenous thrombopoietin were seen. Conclusion Romiplostim appeared well-tolerated in this study and may be a useful treatment for patients with MDS and thrombocytopenia.
Phase III, Randomized, Open-Label Study of Daily Imatinib Mesylate 400 mg Versus 800 mg in Patients With Newly Diagnosed, Previously Untreated Chronic Myeloid Leukemia in Chronic Phase Using Molecular End Points: Tyrosine Kinase Inhibitor Optimization and Selectivity Study
Authors: Cortes Jorge E. , Baccarani Michele , Guilhot François , Druker Brian J. , Branford Susan , Kim Dong-Wook , Pane Fabrizio , Pasquini Ricardo , Goldberg Stuart L. , Kalaycio Matt , Moiraghi Beatriz , Rowe Jacob M. , Tothova Elena , De Souza Carmino , Rudoltz Marc , Yu Richard , Krahnke Tillmann , Kantarjian Hagop M. , Radich Jerald P. , Hughes Timothy P. 
Published: December 2009

Purpose To evaluate the safety and efficacy of initial treatment with imatinib mesylate 800 mg/d (400 mg twice daily) versus 400 mg/d in patients with newly diagnosed chronic myeloid leukemia in chronic phase. Patients and Methods A total of 476 patients were randomly assigned 2:1 to imatinib 800 mg (n = 319) or 400 mg (n = 157) daily. The primary end point was the major molecular response (MMR) rate at 12 months. Results At 12 months, differences in MMR and complete cytogenetic response (CCyR) rates were not statistically significant (MMR, 46% v 40%; P = .2035; CCyR, 70% v 66%; P = .3470). However, MMR occurred faster among patients randomly assigned to imatinib 800 mg/d, who had higher rates of MMR at 3 and 6 months compared with those in the imatinib 400-mg/d arm (P = .0035 by log-rank test). CCyR also occurred faster in the 800-mg/d arm (CCyR at 6 months, 57% v 45%; P = .0146). The most common adverse events were edema, gastrointestinal problems, and rash, and all were more common in patients in the 800-mg/d arm. Grades 3 to 4 hematologic toxicity also occurred more frequently in patients receiving imatinib 800 mg/d. Conclusion MMR rates at 1 year were similar with imatinib 800 mg/d and 400 mg/d, but MMR and CCyR occurred earlier in patients treated with 800 mg/d. Continued follow-up is needed to determine the clinical significance of earlier responses on high-dose imatinib.
Results of Dasatinib Therapy in Patients With Early Chronic-Phase Chronic Myeloid Leukemia
Authors: Cortes Jorge E. , Jones Dan , O'Brien Susan , Jabbour Elias , Ravandi Farhad , Koller Charles , Borthakur Gautam , Walker Brenda , Zhao Weiqiang , Shan Jianqin , Kantarjian Hagop 
Published: December 2009

Purpose Dasatinib is effective therapy for chronic myeloid leukemia (CML) after imatinib failure. In this study, we investigate the efficacy of dasatinib as initial therapy for patients with CML in early chronic phase. Patients and Methods Patients with newly diagnosed CML in early chronic phase were randomly assigned to receive dasatinib 100 mg once daily or 50 mg twice daily as initial therapy. Results Among 50 patients observed for at least 3 months, 49 patients (98%) achieved a complete cytogenetic response (CCyR), and 41 patients (82%) achieved a major molecular response (MMR). Responses occurred rapidly, with 94% of patients achieving CCyR by 6 months. There was no difference in response rate by treatment arm. The projected event-free survival rate at 24 months is 88%, and all patients are alive after a median follow-up time of 24 months. Grade ≥ 3 neutropenia and thrombocytopenia occurred in 21% and 10% of patients, respectively. Nonhematologic toxicity was usually grade 1 to 2. There was no significant difference in toxicity between the two arms, and the actual median dose at 12 months was 100 mg (range, 20 to 100 mg). Conclusion Dasatinib is an effective agent for the initial management of CML in early chronic phase, producing high rates of CCyR and MMR.
Recent loss of Gibraltar seagrasses
Authors: Bull James C. , Kenyon Emma J. , Edmunds Danny , Cook Kevan J. 
Published: December 2009

Abstract
Worldwide, seagrasses face threats including climate change, disease and anthropogenic disturbance, with populations at the extremes of species’ distributions likely presaging future problems elsewhere in their geographical ranges. At the geographic limits of two marine macrophytes (Zostera marina and Posidonia oceanica) and under intense urbanization, seagrasses around Gibraltar are particularly vulnerable. However, the last published survey of Gibraltar seagrass meadows, in 1993, showed both species were abundant. We resurveyed this area and were unable to locate any seagrass in Gibraltar waters. Extensive coastal development and land reclamation make much former seagrass habitat in Gibraltar waters unsuitable, presenting substantial hurdles to any future restoration efforts.
Prostate cancer screening: clinical impact of WHO calibration of Beckman Coulter Access® prostate-specific antigen assays
Authors: Fillée Catherine , Tombal Bertrand , Philippe Marianne 
Published: December 2009

Abstract

Background: The goal of this study was to evaluate the clinical impact of using the same total prostate-specific antigen (tPSA) and free PSA (fPSA) assays calibrated with World Health Organization (WHO) materials or with Hybritech Tandem-R calibrator.

Methods: From the initial correlation study that included 150 patients, the clinical impact of the WHO calibration was simulated using a large cohort (n=4548) of referred patients. Interim reports of the European Study of Screening for Prostate Cancer (ERSPC) were used to evaluate the clinical outcomes of patients and the risk of prostate cancer (PCa).

Results: WHO calibration of tPSA assays leads to a reduction of about 20% in measured results (tPSA WHO=0.81 tPSA Hybritech+0.04; fPSA WHO=0.78 fPSA Hybritech+0.00; %fPSA WHO=0.92 %fPSA Hybritech+0.00). The simulation showed that the WHO calibration is associated with a risk of missing 15% of PCa.

Conclusions: The discrepancies between the two calibrations lead to significant clinical misinterpretation with decreased detection of PCa if tPSA cut-off thresholds are not adjusted.
Clin Chem Lab Med 2010;48:285–8.
O-β-N-acetyl-D-glucosaminidase in erythrocytes of Italian air force acrobatic pilots
Authors: Corsi Massimiliano M. , Massaccesi Luca , Dogliotti Giada , Vianello Elena , Agrifoglio Marco , Palumbo Fabrizio , Goi Giancarlo 
Published: December 2009

Abstract

Background: Italian air force acrobatic pilots are occupationally susceptible to oxidative stress damage that can lead to overt signs and symptoms of hypoxia. We propose erythrocyte glycohydrolases as new, sensitive markers to assess oxidative stress.

Methods: We measured erythrocyte concentrations of β-D-glucuronidase (GCR), hexosaminidase, O-β-N-acetyl-D-glucosaminidase (O-GlcNAcase), plasma membrane fluidity and plasma hydroperoxides from 19 pilots and compared these to 40 matched healthy subjects.

Results: Plasma hydroperoxide concentrations and the erythrocyte ghosts' fluorescence anisotropy were significantly lower in the pilots. Concentrations of GCR, O-GlcNAcase and hexosaminidase in pilots were significantly different from controls, being lower, higher and higher, respectively.

Conclusions: Pilots, in spite of their oxidative stress, are better protected than controls, probably as a result of their physical training and proper diet. Our results confirm that erythrocytes, with their 120-day life span, are a useful model for investigating physiopathological conditions, and glycohydrolases are good markers for monitoring oxidative stress, even in healthy people.
Clin Chem Lab Med 2010;48:213–6.
Defining hyperandrogenism in polycystic ovary syndrome: measurement of testosterone and androstenedione by liquid chromatography–tandem mass spectrometry and analysis by receiver operator characteristic plots
Authors: Barth Julian H , Field Helen P , Yasmin Ephia , Balen Adam H 
Published: December 2009

ObjectiveHyperandrogenism is one of the diagnostic criteria for the polycystic ovary syndrome (PCOS) despite no agreed definition of hyperandrogenism. In part, this is due to the quality of testosterone immunoassays. We have developed liquid chromatography–tandem mass spectrometry methods for analysing testosterone and androstenedione (Ad) to study their reference ranges and diagnostic utility in PCOS.Design, setting and subjectsA consecutive series of 122 women attending a reproductive medicine clinic.MethodsBlood samples were taken during the early follicular phase for measurement of LH, FSH, oestradiol, Ad, testosterone and sex hormone-binding globulin (SHBG). Retrospective case note analysis was used to determine the clinical features and ultrasound findings.ResultsThe incidence of PCOS was 13.9%. The reference interval for testosterone was <1.8 nmol/l and for Ad was 1.4–7.4 nmol/l. There were significant differences in total testosterone (P=0.001), Ad (P<0.05) and free androgen index (FAI; P<0.0001) between the women with and without PCOS. Diagnostic performance using receiver operator characteristic plots showed area under the curve (AUC) for FAI 0.81, testosterone 0.75 and Ad 0.66. The AUC for the LH:FSH ratio was 0.72.ConclusionsOur analysis of a consecutive series of women attending a reproductive clinic has provided an appropriate series on which to construct reference ranges for key androgens in women. Secondly, it has allowed us to conclude that early follicular serum testosterone measured using tandem mass spectrometry, FAI and the LH:FSH ratio are valuable laboratory tests in the diagnosis of PCOS.
New Tools for Investigating the Comparative Biology of Caenorhabditis briggsae and C. elegans
Authors: Zhao Zhongying , Flibotte Stephane , Murray John I , Blick Daniel , Boyle Thomas J , Gupta Bhagwati , Moerman Donald G , Waterston Robert H 
Published: December 2009

Abstract
Comparative studies of Caenorhabditis briggsae and C. elegans have provided insights into gene function and developmental control in both organisms. C. elegans is a well developed model organism with a variety of molecular and genetic tools to study gene functions. In contrast, there are only very limited tools available for its closest relative, C. briggsae. To take advantage of the full potential of this comparative approach, we have developed several genetic and molecular tools to facilitate functional analysis in C. briggsae. First, we designed and implemented an SNP-based oligonucleotide microarray for rapid mapping of genetic mutants in C. briggsae. Second, we generated a mutagenized frozen library to permit the isolation of targeted deletions and used the library to recover a deletion mutant of cbr-unc-119 for use as a transgenic marker. Third, we used the cbr-unc-119 mutant in ballistic transformation and generated fluorescently labeled strains that allow automated lineaging and cellular resolution expression analysis. Finally, we demonstrated the potential of automated lineaging by profiling expression of egl-5, hlh-1, and pha-4 at cellular resolution and by detailed phenotyping of the perturbations on the Wnt signaling pathway. These additions to the experimental toolkit for C. briggsae should greatly increase its utility in comparative studies with C. elegans. With the emerging sequence of nematode species more closely related to C. briggsae, these tools may open novel avenues of experimentation in C. briggsae itself.
Drosophila Raf's N Terminus Contains a Novel Conserved Region and Can Contribute to Torso RTK Signaling
Authors: Ding Jian , Tchaicheeyan Oren , Ambrosio Linda 
Published: December 2009

Abstract
Drosophila Raf (DRaf) contains an extended N terminus, in addition to three conserved regions (CR1–CR3); however, the function(s) of this N-terminal segment remains elusive. In this article, a novel region within Draf's N terminus that is conserved in BRaf proteins of vertebrates was identified and termed conserved region N-terminal (CRN). We show that the N-terminal segment can play a positive role(s) in the Torso receptor tyrosine kinase pathway in vivo, and its contribution to signaling appears to be dependent on the activity of Torso receptor, suggesting this N-terminal segment can function in signal transmission. Circular dichroism analysis indicates that DRaf's N terminus (amino acids 1–117) including CRN (amino acids 19–77) is folded in vitro and has a high content of helical secondary structure as predicted by proteomics tools. In yeast two-hybrid assays, stronger interactions between DRaf's Ras binding domain (RBD) and the small GTPase Ras1, as well as Rap1, were observed when CRN and RBD sequences were linked. Together, our studies suggest that DRaf's extended N terminus may assist in its association with the upstream activators (Ras1 and Rap1) through a CRN-mediated mechanism(s) in vivo.