bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mature results of the M. D. Anderson Cancer Center risk-adapted transplantation strategy in mantle cell lymphoma
Authors: Tam Constantine S. , Bassett Roland , Ledesma Celina , Korbling Martin , Alousi Amin , Hosing Chitra , Kebraei Partow , Harrell Robyn , Rondon Gabriela , Giralt Sergio A. , Anderlini Paolo , Popat Uday , Pro Barbara , Samuels Barry , Hagemeister Frederick , Medeiros L. Jeffrey , Champlin Richard E. , Khouri Issa F. 
Published: January 2009

Abstract
In this study, we analyzed the long-term outcome of a risk-adapted transplantation strategy for mantle cell lymphoma in 121 patients enrolled in sequential transplantation protocols. Notable developments over the 17-year study period were the addition of rituximab to chemotherapy and preparative regimens and the advent of nonmyeloablative allogeneic stem cell transplantation (NST). In the autologous transplantation group (n = 86), rituximab resulted in a marked improvement in progression-free survival for patients who received a transplant in their first remission (where a plateau emerged at 3-8 years) but did not change the outcomes for patients who received a transplant beyond their first remission. In the NST group, composed entirely of patients who received a transplant beyond their first remission, durable remissions also emerged in progression-free survival at 5 to 9 years. The major determinants of disease control after NST were the use of a peripheral blood stem cell graft and donor chimerism of at least 95%, whereas the major determinant of death was immunosuppression for chronic graft-versus-host disease. Our results show that long-term disease-free survival in mantle cell lymphoma is possible after rituximab-containing autologous transplantation for patients in first remission and after NST for patients with relapsed or refractory disease.
Leukotriene B4release by human lung macrophagesviareceptor- not voltage-operated Ca2+channels
Authors: Finney-Hayward T. K. , Bahra P. , Li S. , Poll C. T. , Nicholson A. G. , Russell R. E. K. , Ford P. A. , Westwick J. , Fenwick P. S. , Barnes P. J. , Donnelly L. E. 
Published: January 2009

Increased numbers of macrophages and neutrophils in the lung is a key feature of chronic obstructive pulmonary disease (COPD). The major neutrophil chemotactic agent in the airways of COPD patients is leukotriene (LT)B4and is released by macrophages. The present study examines the role and mechanism of Ca2+in platelet-activating factor (PAF)-stimulated LTB4release from human lung macrophages.Macrophages were isolated from lung tissue of subjects undergoing lung resection surgery and monocyte-derived macrophages (MDM) were obtained from nonsmokers, smokers without obstruction and COPD patients. Cells were stimulated with PAF and LTB4release and [Ca2+]iwas measured.Lung macrophages and MDM released LTB4following stimulation with PAF (mean effective concentration: 0.08±0.06 μM (n = 5)versus0.17±0.12 μM (n = 17), respectively). Compared with MDM, lung macrophages released approximately eight-fold more LTB4. Neither smoking nor COPD altered MDM responses. PAF-stimulated LTB4release was abrogated by ethylene glycol tetraacetic acid suggesting a role for extracellular Ca2+. This was substantiated by using store-operated channel blockers econazole, SK&F96365 and Gd3+. However, econazole and SK&F96365 were more effective in MDM than lung macrophages. Neither LOE908 nor nifedipine could attenuate this response.These data suggest that platelet-activating factor-stimulated leukotriene B4release from human lung macrophages is mediated, in part, by Ca2+influx through receptor- but not voltage-operated Ca2+channels.
Role of lymphotoxin-α in cigarette smoke-induced inflammation and lymphoid neogenesis
Authors: Demoor T. , Bracke K. R. , Maes T. , Vandooren B. , Elewaut D. , Pilette C. , Joos G. F. , Brusselle G. G. 
Published: January 2009

In chronic obstructive pulmonary disease (COPD), chronic inflammation is accompanied by peribronchial lymphoid aggregates. Lymphotoxin (LT)-α, crucial in secondary lymphoid organogenesis, may be involved in lymphoid neogenesis.We examined cigarette smoke (CS)-induced pulmonary lymphoid neogenesis and inflammationin vivoin LTα knockout (LTα-/-) and wild-type (WT) mice and studied the expression of lymphoid chemokines by lung fibroblastsin vitro.T-cell numbers (in bronchoalveolar lavage fluid (BALF) and lungs) and lymphoid aggregate numbers were significantly higher in air-exposed LTα-/-mice than in WT animals, and increased upon chronic CS exposure in both genotypes. In contrast, local immunoglobulin A responses upon chronic CS exposure were attenuated in LTα-/-mice. CXC chemokine ligand (CXCL) 13 and CC chemokine ligand (CCL) 19 mRNA in total lung and CXCL13 protein level in BALF increased upon CS exposure in WT, but not in LTα-/-mice.In vitrolymphotoxin-β receptor (LTβR) stimulation induced CXCL13 and CCL19 mRNA in WT lung fibroblasts. Furthermore,in vitroexposure to CS extract upregulated CXCL13 mRNA expression in WT, but not in LTβR-/-, lung fibroblasts.In this murine model of COPD, CS induces pulmonary expression of lymphoid chemokines CXCL13 and CCL19 in a LTαβ–LTβR-dependent fashion. However, LTα is not required for CS-induced pulmonary lymphocyte accumulation and neogenesis of lymphoid aggregates.
A multiway analysis for identifying high integrity bovine BACs
Authors: Ratnakumar Abhirami , Barris Wesley , McWilliam Sean , Brauning Rudiger , McEwan John C , Snelling Warren M , Dalrymple Brian P 
Published: January 2009

AbstractBackgroundIn large genomics projects involving many different types of analyses of bacterial artificial chromosomes (BACs), such as fingerprinting, end sequencing (BES) and full BAC sequencing there are many opportunities for the identities of BACs to become confused. However, by comparing the results from the different analyses, inconsistencies can be identified and a set of high integrity BACs preferred for future research can be defined.ResultsThe location of each bovine BAC in the BAC fingerprint-based genome map and in the genome assembly were compared based on the reported BESs, and for a smaller number of BACs the full sequence. BACs with consistent positions in all three datasets, or if the full sequence was not available, for both the fingerprint map and BES-based alignments, were deemed to be correctly positioned. BACs with consistent BES-based and fingerprint-based locations, but with conflicting locations based on the fully sequenced BAC, appeared to have been misidentified during sequencing, and included a number of apparently swapped BACs. Inconsistencies between BES-based and fingerprint map positions identified thirty one plates from the CHORI-240 library that appear to have suffered substantial systematic problems during the end-sequencing of the BACs. No systematic problems were identified in the fingerprinting of the BACs. Analysis of BACs overlapping in the assembly identified a small overrepresentation of clones with substantial overlap in the library and a substantial enrichment of highly overlapping BACs on the same plate in the CHORI-240 library. More than half of these BACs appear to have been present as duplicates on the original BAC-library plates and thus should be avoided in subsequent projects.ConclusionOur analysis shows that ~95% of the bovine CHORI-240 library clones with both a BAC fingerprint and two BESs mapping to the genome in the expected orientations (~27% of all BACs) have consistent locations in the BAC fingerprint map and the genome assembly. We have developed a broadly applicable methodology for checking the integrity of BAC-based datasets even where only incomplete and partially assembled genomic sequence is available.
Prevalence, evaluation and management of overactive bladder in primary care
Authors: Cheung Wellman W , Khan Nadia H , Choi Karmina K , Bluth Martin H , Vincent Miriam T 
Published: January 2009

Abstract

Background
Patients with overactive bladder (OAB) are under-diagnosed in the primary care setting. Primary care physicians (PCP) approach to the patient and appropriate patient disclosure may contribute to under-diagnosis.

Methods
An outpatient primary care setting was used to determine the prevalence and characteristics of OAB. Patients who visited the family medicine outpatient clinic were invited to answer a self-administered questionnaire. It included questions on evidence of lower urinary tract symptoms (modified Overactive Bladder-Validated 8-question Screener [OAB-V8]), relevant medical and surgical history, and demographic data. Relationship between OAB and other independent variables were analyzed using chi-square and risk ratio (RR) analysis.

Results
Of 325 questionnaires distributed, 311 were returned completed. Patients ranged from 18 to 97 years, the majority women (74.0%) and African American (74.3%). OAB was present in 60.5% of men and 48.3% of women (p = 0.058). OAB was significantly associated with obesity (BMI > = 30) in women (p = 0.018, RR = 1.72), specifically obese premenopausal women (age < 55 years) (p = 0.011, RR = 1.98).

Conclusion
OAB prevalence is more than double and higher in men than previously reported. The relative risk for OAB is significantly greater in obese premenopausal women.
Total laparoscopic hysterectomy versus abdominal hysterectomy in the treatment of patients with early stage endometrial cancer: A randomized multi center study
Authors: Bijen Claudia BM , Briët Justine M , de Bock Geertruida H , Arts Henriëtte JG , Bergsma-Kadijk Johanna A , Mourits Marian JE 
Published: January 2009

Abstract

Background
Traditionally standard treatment for patients with early stage endometrial cancer (EC) is total abdominal hysterectomy and bilateral salpingo oophorectomy (TAH+BSO) with or without lymph node dissection through a vertical midline incision. While TAH is an accepted effective treatment, it is highly invasive, visibly scarring and associated with morbidity. An alternative treatment is the same operation by laparoscopy. Though in several studies total laparoscopic hysterectomy (TLH+ BSO) seems a safe and feasible alternative approach in early stage endometrial cancer patients, there are no randomized data available yet. Furthermore, a randomized controlled trial with surgeons trained in laparoscopy is warranted in order to implement this technique in a safe manner. The aim of this study is to compare the treatment related morbidity, cost-effectiveness and quality of life in early stage endometrial cancer patients treated by laparoscopy versus the standard open approach.

Methods
A multi centre randomized clinical phase 3 trial, including 5 university hospitals and 15 regional hospitals in the Netherlands. Only gynecologists trained in performing a TLH are allowed to participate. Inclusion criteria: Patients with a clinical stage I endometrioid adenocarcinoma or complex atypical hyperplasia are randomized in a 2:1 allocation to receive TLH or TAH. The main outcome measure is the rate of major complications, as assessed by an independent clinical review board. In total, 275 patients are required to have 80% power at α-0.05 to detect a significant difference of 15% complication rate. Secondary outcome measures are 1) costs and cost-effectiveness, 2) minor complications, and 3) quality of life. All data from this multi center study are reported using case record forms. Data regarding quality of life, pain, body Image, sexuality and additional homecare are assessed with self reported questionnaires.

Discussion
A randomized multi center study in early stage endometrial cancer patients with inclusion criteria for patients and surgeons is designed and ongoing. Results will be presented at the end of 2009.

Trial Registration

Dutch trial register number NTR821.
EZH2 and BMI1 inversely correlate with prognosis and TP53 mutation in breast cancer
Authors: Pietersen Alexandra M , Horlings Hugo M , Hauptmann Michael , Langerød Anita , Ajouaou Abderrahim , Cornelissen-Steijger Paulien , Wessels Lodewijk F , Jonkers Jos , Vijver Marc J van de , van Lohuizen Maarten 
Published: January 2009

Abstract
Introduction
PolycombGroup (PcG) proteins maintain gene repression through histone modifications and have been implicated in stem cell regulation and cancer. EZH2 is part of Polycomb Repressive Complex 2 (PRC2) and trimethylates H3K27. This histone mark recruits the BMI1-containing PRC1 that silences the genes marked by PRC2. Based on their role in stem cells, EZH2 and BMI1 have been predicted to contribute to a poor outcome for cancer patients.

Methods
We have analysed the expression of EZH2 and BMI1 in a well-characterised dataset of 295 human breast cancer samples.

Results
Interestingly, although EZH2 overexpression correlates with a poor prognosis in breast cancer, BMI1 overexpression correlates with a good outcome. Although this may reflect transformation of different cell types, we also observed a functional difference. The PcG-target genes INK4A and ARF are not expressed in tumours with high BMI1, but they are expressed in tumours with EZH2 overexpression. ARF expression results in tumour protein P53 (TP53) activation, and we found a significantly higher proportion of TP53 mutations in tumours with high EZH2. This may explain why tumours with high EZH2 respond poorly to therapy, in contrast to tumours with high BMI1.

Conclusions
Overall, our data highlight that whereas EZH2 and BMI1 may function in a 'linear' pathway in normal development, their overexpression has different functional consequences for breast tumourigenesis.
Loss of Betaglycan Contributes to the Malignant Properties of Human Granulosa Tumor Cells
Authors: Bilandzic Maree , Chu Simon , Farnworth Paul G. , Harrison Craig , Nicholls Peter , Wang Yao , Escalona Ruth M. , Fuller Peter J. , Findlay Jock K. , Stenvers Kaye L. 
Published: January 2009

AbstractBetaglycan is a type III TGFβ receptor that modulates cellular sensitivity to inhibins and TGFβ. Previous studies have suggested that betaglycan acts as a tumor suppressor in certain human epithelial cancers. However, the roles of betaglycan in ovarian granulosa cell tumors (GCTs) are poorly understood. The objective of this study was to determine whether human GCTs exhibit betaglycan expression and, if so, what impact this receptor has on tumor biology. Real-time PCR was used to quantify betaglycan transcripts in human GCTs (n = 17) and normal premenopausal ovaries (n = 11). This analysis established that GCTs exhibited a significant 2-fold lower mean betaglycan mRNA level as compared with the normal ovary (P &lt; 0.05). Similarly, two human GCT cell lines, KGN and COV434, exhibited low betaglycan expression and poor responsiveness to TGFβ and inhibin A in luciferase reporter assays, which was restored by stable transfection of wild-type betaglycan. Betaglycan significantly increased the adhesion of COV434 (P &lt; 0.05) and KGN (P &lt; 0.0001) cells, decreased cellular invasion through Matrigel, and inhibited wound healing. Expression of mutant forms of betaglycan that are defective in TGFβ and/or inhibin binding in each GCT cell line revealed that the inhibitory effects of betaglycan on wound healing were most strongly linked to the inhibin-binding region of betaglycan. Furthermore, knockdown of INHA mRNA expression abrogated the betaglycan-mediated inhibition of wound healing and invasion, whereas both INHA silencing and TGFβ neutralization abolished the betaglycan-mediated increase in adhesion to substrate. These data suggest that loss of betaglycan contributes to the pathogenesis of GCTs.
Glutathione dysregulation and the etiology and progression of human diseases
Authors: Ballatori Nazzareno , Krance Suzanne M. , Notenboom Sylvia , Shi Shujie , Tieu Kim , Hammond Christine L. 
Published: January 2009

AbstractGlutathione (GSH) plays an important role in a multitude of cellular processes, including cell differentiation, proliferation, and apoptosis, and as a result, disturbances in GSH homeostasis are implicated in the etiology and/or progression of a number of human diseases, including cancer, diseases of aging, cystic fibrosis, and cardiovascular, inflammatory, immune, metabolic, and neurodegenerative diseases. Owing to the pleiotropic effects of GSH on cell functions, it has been quite difficult to define the role of GSH in the onset and/or the expression of human diseases, although significant progress is being made. GSH levels, turnover rates, and/or oxidation state can be compromised by inherited or acquired defects in the enzymes, transporters, signaling molecules, or transcription factors that are involved in its homeostasis, or from exposure to reactive chemicals or metabolic intermediates. GSH deficiency or a decrease in the GSH/glutathione disulfide ratio manifests itself largely through an increased susceptibility to oxidative stress, and the resulting damage is thought to be involved in diseases, such as cancer, Parkinson's disease, and Alzheimer's disease. In addition, imbalances in GSH levels affect immune system function, and are thought to play a role in the aging process. Just as low intracellular GSH levels decrease cellular antioxidant capacity, elevated GSH levels generally increase antioxidant capacity and resistance to oxidative stress, and this is observed in many cancer cells. The higher GSH levels in some tumor cells are also typically associated with higher levels of GSH-related enzymes and transporters. Although neither the mechanism nor the implications of these changes are well defined, the high GSH content makes cancer cells chemoresistant, which is a major factor that limits drug treatment. The present report highlights and integrates the growing connections between imbalances in GSH homeostasis and a multitude of human diseases.
Two aspartic proteinases secreted by the pathogenic yeast Candida parapsilosis differ in expression pattern and catalytic properties
Authors: Hrušková-Heidingsfeldová Olga , Dostál Jiří , Majer Filip , Havlíková Jana , Hradilek Martin , Pichová Iva 
Published: January 2009

Abstract
Secreted aspartic proteinases (Sap) play a role in the virulence of pathogenic Candida spp. Candida parapsilosis possesses three genes encoding these enzymes: SAPP1, SAPP2, and SAPP3. We analyzed the expression of the SAPP1 and SAPP2 genes and the production of Sapp1p and Sapp2p proteinases in the presence of different nitrogen sources. While the SAPP2 transcript was present under all of the conditions tested, expression of SAPP1 was induced only by the presence of exogenous protein as the sole nitrogen source. The concentration of Sapp1p in the medium upon induction was at least one order of magnitude higher than the concentration of Sapp2p in all media tested in this study. Enzymological characterization of purified Sapp1p and Sapp2p demonstrated that Sapp2p has a more restricted substrate specificity and significantly lower catalytic activity than Sapp1p. Homology models of Sapp1p and Sapp2p revealed structural motifs that may be responsible for the differences between these two enzymes. Our results indicate that C. parapsilosis secretes a low level of Sapp2p proteinase with narrow substrate specificity and low proteolytic activity under most conditions, while expression and secretion of a higher amount of catalytically efficient Sapp1p enzymes is triggered in the presence of exogenous protein serving as a nitrogen source.
Central nervous system: cholesterol turnover, brain development and neurodegeneration
Authors: Dietschy John M. 
Published: January 2009

Abstract
The average amount of cholesterol in the whole animal equals approximately 2100 mg/kg body weight, and 15% and 23% of this sterol in the mouse and human, respectively, is found in the central nervous system. There is no detectable uptake across the blood-brain barrier of cholesterol carried in lipoproteins in the plasma, even in the newborn. However, high rates of de novo cholesterol synthesis in the glia and neurons provide the sterol necessary for early brain development. Once a stable brain size is achieved in the adult, cholesterol synthesis continues, albeit at a much lower rate, and this synthesis is just balanced by the excretion of an equal amount of sterol, either as 24(S)-hydroxycholesterol or, presumably, as cholesterol itself.
Structure-function relationship of the human antimicrobial peptide LL-37 and LL-37 fragments in the modulation of TLR responses
Authors: Molhoek E. Margo , den Hertog Alice L. , de Vries Anne-Marij B.C. , Nazmi Kamran , Veerman Enno C.I. , Hartgers Franca C. , Yazdanbakhsh Maria , Bikker Floris J. , van der Kleij Desiree 
Published: January 2009

Abstract
Cathelicidins are effector molecules of the innate host defense system that establish an antimicrobial barrier at epithelial interfaces. The human cathelicidin LL-37, in addition to its antimicrobial activity, also exhibits immunomodulatory effects, such as inhibition of pro-inflammatory responses to bacterial LPS in human monocytic cells. In this report, we demonstrate that LL-37 almost completely prevents the pro-inflammatory cytokine release by human peripheral blood mononuclear cells (PBMCs) following stimulation with Toll-like receptor (TLR)4 and TLR2/1 agonists while leaving TLR2/6, TLR5, TLR7 and TLR8 responses unchanged. Modulation of the TLR response by LL-37 occurred at least partly through the MAP kinase pathway via inhibition of p38 phosphorylation. By using an LL-37 library with overlapping sequences, we identified the mid-region of LL-37, comprising amino acids 13–31, as the active domain for the modulation of TLR responses. The mechanism of immunomodulation of LL-37 and LL-37 fragments is lipopoly-saccharide binding. Correlations between the capacity of LL-37 fragments to modulate TLR responses and their physico-chemical properties revealed that cationicity and hydrophobicity are essential for the modulation of LL-37-mediated TLR responses.