tbuckley/cabot-search huggingface dataset:
Increased Cyclooxygenase-2 Expression Is Associated With Chemotherapy Resistance and Poor Survival in Cervical Cancer Patients
Authors: G. Ferrandina, L. Lauriola, M. G. Distefano, G. F. Zannoni, M. Gessi, F. Legge, N. Maggiano, S. Mancuso, A. Capelli, G. Scambia, F. O. Ranelletti
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To investigate the expression of cyclooxygenase (COX-2) and its association with clinicopathologic parameters and clinical outcome in patients with cervical cancer. PATIENTS AND METHODS: The study included 84 patients with stage IB to IVA cervical cancer. Patients with early-stage cases (n = 21) underwent radical surgery, whereas patients with locally advanced cervical cancer (LACC) (n = 63) were first administered neoadjuvant cisplatin-based treatment and subjected to surgery in case of response. Immunohistochemical analysis was performed on paraffin-embedded sections with rabbit antiserum against COX-2. RESULTS: COX-2–integrated density values in the overall population ranged from 1.2 to 82.3, with mean ± SE values of 27.4 ± 2.4. According to the chosen cutoff value, 36 (42.9%) of 84 patients were scored as COX-2 positive. COX-2 levels were shown to be highly associated with tumor susceptibility to neoadjuvant treatment. COX-2 showed a progressive increase from mean ± SE values of 19.9 ± 8.0 in complete responders through 31.5 ± 3.5 in partial responses to 44.8 ± 3.9 in patients who were not responsive (P = .0054). When logistic regression was applied, only advanced stage and COX-2 positivity retained independent roles in predicting a poor chance of response to treatment. COX-2–positive patients had a shorter overall survival (OS) rate than COX-2–negative patients. In patients with LACC, the 2-year OS rate was 38% in COX-2–positive versus 85% in COX-2–negative patients (P = .0001). In the multivariate analysis, only advanced stage and COX-2 positivity retained independent negative prognostic roles for OS. CONCLUSION: The assessment of COX-2 status could provide additional information to identify patients with cervical cancer with a poor chance of response to neoadjuvant treatment and unfavorable prognosis.
Transforming Growth Factor β Subverts the Immune System into Directly Promoting Tumor Growth through Interleukin-17
Authors: Jeong-Seok Nam, Masaki Terabe, Mi-Jin Kang, Helen Chae, Nga Voong, Yu-an Yang, Arian Laurence, Aleksandra Michalowska, Mizuko Mamura, Scott Lonning, Jay A. Berzofsky, Lalage M. Wakefield
Journal: Cancer Research (2008)

Abstract Overexpression of the immunosuppressive cytokine transforming growth factor β (TGF-β) is one strategy that tumors have developed to evade effective immunesurveillance. Using transplantable models of breast and colon cancer, we made the unexpected finding that CD8+ cells in tumor-bearing animals can directly promote tumorigenesis, by a mechanism that is dependent on TGF-β. We showed that CD8+ splenocytes from tumor-bearing mice expressed elevated interleukin (IL)-17 when compared with naive mice, and that CD8+ T cells could be induced to make IL-17 on addition of TGF-β and IL-6 in vitro. Treatment of mice with anti–TGF-β antibodies in vivo reduced IL-17 expression both in the tumor and the locoregional lymph nodes. Although IL-17 has not previously been shown to act as a survival factor for epithelial cells, we found that IL-17 suppressed apoptosis of several tumor cell lines in vitro, suggesting that this altered T-cell polarization has the potential to promote tumorigenesis directly, rather than indirectly through inflammatory sequelae. Consistent with this hypothesis, knockdown of the IL-17 receptor in 4T1 mouse mammary cancer cells enhanced apoptosis and decreased tumor growth in vivo. Thus, in addition to suppressing immune surveillance, tumor-induced TGF-β may actively subvert the CD8+ arm of the immune system into directly promoting tumor growth by an IL-17–dependent mechanism. [Cancer Res 2008;68(10):3915–23]
Isometric relaxation of rat myocardium at end-systolic fiber length.
Authors: A W Wiegner, S H Bing
Journal: Circulation Research (1978)

In a "physiologically sequenced" contraction (PSC), which loads the isolated muscle preparation in a manner which approximates that of the intact heart, isometric relaxation precedes isotonic relaxation and occurs at minimum ("end-systolic") length. We studied the effects of inital muscle length, load, temperature, calcium, and isoproterenol on the isometric relaxation phase of physiologically sequenced contractions to define the determinants of the rate of isometric relaxation of rat left ventricular myocardium. At the baseline temperature (28 degrees C), relaxation was found to be nonexponential, and the maximum rate of decline of force (-dF/dtmax) was used to evaluate changes in relaxation. Three factors, shortening, end-systolic length, and total load, were examined as possible mechanical determinants of -dF/dtmax. We found that -dF/dtmax is linearly related to end-systolic muscle length for lengths below 94% of Lmax; -dF/dtmax is also strongly related to total load for lightly loaded contractions, but peaks at loads of approximately 80% of peak developed force and declines thereafter. Shortening is poorly correlated with -dF/dtmax. The slope of the linear portion of the relation between -dF/dtmax and end-systolic length appears to be independent of muscle-loading conditions and sensitive to factors known to alter relaxation.
Used infant mattresses and sudden infant death syndrome in Scotland: case-control study
Authors: David Tappin, Hazel Brooke, Russell Ecob, Angus Gibson
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective:</b> To examine the proposition that a used infant mattress is associated with an increased risk of sudden infant death syndrome. <b>Design:</b>Case-control study. <b>Setting:</b> Scotland (population 5.1 million, with about 53 000 births a year). <b>Participants:</b> 131 infants who died of sudden infant death syndrome between 1 January 1996 and 31 May 2000 and 278 age, season, and obstetric unit matched control infants. <b>Main outcome measures:</b> Routine use of an infant mattress previously used by another child and place of last sleep. <b>Results:</b> Routine use of an infant mattress previously used by another child was significantly associated with an increased risk of sudden infant death syndrome (multivariate odds ratio 3.07, 95% confidence interval 1.51 to 6.22). Use of a used infant mattress for last sleep was also associated with increased risk (6.10, 2.31 to 16.12). The association was significantly stronger if the mattress was from another home (4.78, 2.08 to 11.0) than if it was from the same home (1.64, 0.64 to 4.2). <b>Conclusion:</b> A valid significant association exists between use of a used infant mattress and an increased risk of sudden infant death syndrome, particularly if the mattress is from another home. Insufficient evidence is available to judge whether this relation is cause and effect. <h3>What is already known about this topic</h3> The major risk factors for sudden infant death syndrome are sleeping prone and parental smoking One study has suggested that the syndrome is associated with sleeping on an infant mattress previously used by another child <h3>What this study adds</h3> New case-control data show that the association between a previously used infant mattress and sudden infant death syndrome is valid When source of used mattress is categorised, the association is significant only if the mattress is from another home Insufficient evidence is available to judge whether this is a cause and effect relation
Is there a sex bias in prescribing anti-tumour necrosis factor medications to patients with rheumatoid arthritis? A nation-wide cross-sectional study
Authors: Elizabeth V Arkema, Martin Neovius, Joel K Joelsson, Julia F Simard, Ronald F van Vollenhoven
Journal: Annals of the Rheumatic Diseases (2012)

To determine whether men and women with rheumatoid arthritis are prescribed anti-tumour necrosis factor (anti-TNF) treatment at different levels of disease activity.Data from the Swedish national biologics registry ARTIS were used to analyse characteristics of patients' disease at the start of the first anti-TNF treatment. Means for men and women were compared using t-tests, and non-normally distributed covariates were compared using the Wilcoxon rank-sum test. Linear regression models, adjusted for age and calendar year, were used to investigate the association between sex and each disease activity measurement.Women were younger and had longer disease duration at treatment start than men. Tender joint count, erythrocyte sedimentation rate, patient's global assessment, patient-reported pain and health assessment questionnaire scores were significantly higher in women, whereas men had a higher level of C-reactive protein (p<0.05 for all comparisons). Swollen joint count and physician's global assessment did not differ by sex.For women with rheumatoid arthritis, treatment with anti-TNF therapy was initiated at a higher level of subjective disease activity than for men, but at the same level of physician-reported disease activity. These data imply that patients' subjectively experienced disease activity may be discounted in the treatment decision.
Interleukin 17F Level and Interferon Beta Response in Patients With Multiple Sclerosis
Authors: Hans-Peter Hartung, Lawrence Steinman, Douglas S. Goodin, Giancarlo Comi, Stuart Cook, Massimo Filippi, Paul O’Connor, Douglas R. Jeffery, Ludwig Kappos, Robert Axtell, Volker Knappertz, Timon Bogumil, Susanne Schwenke, Ed Croze, Rupert Sandbrink, Christopher Pohl
Journal: JAMA Neurology (2013)

High serum levels of interleukin 17F (IL-17F) at baseline have been associated with suboptimal response to interferon beta in patients with relapsing-remitting multiple sclerosis.To further investigate the role of IL-17F in predicting treatment response to interferon beta-1b in patients with relapsing-remitting multiple sclerosis using the Singulex Erenna IL-17F immunoassay.Serum samples were analyzed from 239 randomly selected patients treated with interferon beta-1b, 250 μg, for at least 2 years in the Betaferon Efficacy Yielding Outcomes of a New Dose Study.Treatment with interferon beta-1b, 250 μg, for at least 2 years.Levels of IL-17F at baseline and month 6 as well as the difference between the IL-17F levels at month 6 and baseline were compared between the following: (1) patients with less disease activity vs more disease activity; (2) patients with no disease activity vs some disease activity; and (3) responders vs nonresponders.Levels of IL-17F measured at baseline and month 6 did not correlate with lack of response to treatment after 2 years using clinical and magnetic resonance imaging criteria. Relapses and new lesions on magnetic resonance imaging were not associated with pretreatment serum IL-17F levels. When patients with neutralizing antibodies were excluded, the results did not change. All patients with levels of IL-17F greater than 200 pg/mL were associated with poor response with some clinical or radiological activity.An increase of IL-17F before and early after treatment with interferon beta-1b was not associated with poor response. These data do not support the value of IL-17F as a treatment response indicator for therapy of patients with multiple sclerosis with interferon beta, although high levels of IL-17F greater than 200 pg/mL may predict nonresponsiveness.
Genome-wide meta-analyses identify multiple loci associated with smoking behavior
Authors: Helena Furberg, Yunjung Kim, Jennifer Dackor, Eric Boerwinkle, Nora Franceschini, Diego Ardissino, Luisa Bernardinelli, Pier M. Mannucci, Francesco Mauri, Piera A. Merlini, Devin Absher, Themistocles L. Assimes, Stephen P. Fortmann, Carlos Iribarren, Joshua W. Knowles, Thomas Quertermous, Luigi Ferrucci, Toshiko Tanaka, Joshua C. Bis, Curt D. Furberg, Talin Haritunians, Barbara McKnight, Bruce M. Psaty, Kent D. Taylor, Evan L. Thacker, Peter Almgren, Leif Groop, Claes Ladenvall, Michael Boehnke, Anne U. Jackson, Karen L. Mohlke, Heather M. Stringham, Jaakko Tuomilehto, Emelia J. Benjamin, Shih Jen Hwang, Daniel Levy, Sarah Rosner Preis, Ramachandran S. Vasan, Jubao Duan, Pablo V. Gejman, Douglas F. Levinson, Alan R. Sanders, Jianxin Shi, Esther H. Lips, James D. McKay, Antonio Agudo, Luigi Barzan, Vladimir Bencko, Simone Benhamou, Xavier Castellsagué, Cristina Canova, David I. Conway, Eleonora Fabianova, Lenka Foretova, Vladimir Janout, Claire M. Healy, Ivana Holcátová, Kristina Kjaerheim, Pagona Lagiou, Jolanta Lissowska, Ray Lowry, Tatiana V. MacFarlane, Dana Mates, Lorenzo Richiardi, Peter Rudnai, Neonilia Szeszenia-Dabrowska, David Zaridze, Ariana Znaor, Mark Lathrop, Paul Brennan, Stefania Bandinelli, Timothy M. Frayling, Jack M. Guralnik, Yuri Milaneschi, John R B Perry, David Altshuler, Roberto Elosua, Sek Kathiresan, Gavin Lucas, Olle Melander, Christopher J. O'Donnell, Veikko Salomaa, Stephen M. Schwartz, Benjamin F. Voight, Brenda W. Penninx, Johannes H. Smit, Nicole Vogelzangs, Dorret I. Boomsma, Eco J C De Geus, Jacqueline M. Vink, Gonneke Willemsen, Stephen J. Chanock, Fangyi Gu, Susan E. Hankinson, David J. Hunter, Albert Hofman, Henning Tiemeier, Andre G. Uitterlinden, Cornelia M. Van Duijn, Stefan Walter, Daniel I. Chasman, Brendan M. Everett, Guillaume Paré, Paul M. Ridker, Ming D. Li, Hermine H. Maes, Janet Audrain-Mcgovern, Danielle Posthuma, Laura M. Thornton, Caryn Lerman, Jaakko Kaprio, Jed E. Rose, John P A Ioannidis, Peter Kraft, Dan Yu Lin, Patrick F. Sullivan
Journal: Nature Genetics (2010)
Challenges of Guarantee-Time Bias
Authors: Anita Giobbie-Hurder, Richard D. Gelber, Meredith M. Regan
Journal: Journal of Clinical Oncology (2013)

The potential for guarantee-time bias (GTB), also known as immortal time bias, exists whenever an analysis that is timed from enrollment or random assignment, such as disease-free or overall survival, is compared across groups defined by a classifying event occurring sometime during follow-up. The types of events associated with GTB are varied and may include the occurrence of objective disease response, onset of toxicity, or seroconversion. However, comparative analyses using these types of events as predictors are different from analyses using baseline characteristics that are specified completely before the occurrence of any outcome event. Recognizing the potential for GTB is not always straightforward, and it can be challenging to know when GTB is influencing the results of an analysis. This article defines GTB, provides examples of GTB from several published articles, and discusses three analytic techniques that can be used to remove the bias: conditional landmark analysis, extended Cox model, and inverse probability weighting. The strengths and limitations of each technique are presented. As an example, we explore the effect of bisphosphonate use on disease-free survival (DFS) using data from the BIG (Breast International Group) 1-98 randomized clinical trial. An analysis using a naive approach showed substantial benefit for patients who received bisphosphonate therapy. In contrast, analyses using the three methods known to remove GTB showed no statistical evidence of a reduction in risk of a DFS event with bisphosphonate therapy.
Hypoalbuminaemia and gastric mass
Authors: K Honein
Journal: Gut (2005)

Aim: Neutrophil migration in the intestine depends on chemotaxis of neutrophils to CXC chemokines produced by epithelial cells.The goal of this project was to determine if acute induction of a CXC chemokine gradient originating from intestinal epithelial cells is sufficient to induce neutrophil influx into intact intestinal tissue.Methods and results: The authors developed a double transgenic mouse model with doxycycline induced human IL-8 expression restricted to intestinal epithelial cells.Doxycycline treatment of double transgenic mice for three days resulted in a 50-fold increase in the caecal IL-8 concentration and influx of neutrophils into the lamina propria.Although neutrophils entered the paracellular space between epithelial cells, complete transepithelial migration was not observed.Doxycycline treatment also increased the water content of the caecal and colonic stool, indicating dysfunctional water transport.However, the transmural electrical resistance was not decreased.Neutrophils recruited to the intestinal epithelium did not show evidence of degranulation and the epithelium remained intact as judged by histology.Conclusions: This conditional transgenic model of chemokine expression provides evidence that acute induction of IL-8 in the intestinal epithelium is sufficient to trigger neutrophil recruitment to the lamina propria, but additional activation signals are needed for full activation and degranulation of neutrophils, mucosal injury, and complete transepithelial migration.
THE PERSISTENCE OF BOVINE γ-GLOBULIN INJECTED AS AN ANTIGEN INTO RABBITS
Authors: Philip D. McMaster, Heinz Kruse, Ernest Sturm, Joshua L. Edwards
Journal: The Journal of Experimental Medicine (1954)

A sensitive biological test has been used to detect the persistence of minute traces of a foreign protein, bovine γ-globulin, in the blood and livers of rabbits intravenously injected with it, as an antigen. At various intervals after injecting these rabbits (donors) serum or liver tissue was transferred from them to the peritoneal cavities of normal or unilaterally adrenalectomized mice (recipients) with the aim of rendering the latter hypersensitive to the antigen that might be persisting in the transferred materials; a state of affairs detectable, 2 days later, by the appearance of signs of reversed passive anaphylaxis when the recipient mice were intravenously challenged with a strong anti-bovine γ-globulin rabbit serum. The protein persisted in the blood of the donor rabbits, in readily demonstrable amounts for 1 month, and in the blood of one animal, in minute traces, or as long as 6 weeks. It was detectable in the livers for 8 weeks. The persistence of bovine γ-globulin in rabbits, which form circulating antibodies to it well, is not as long as that in mice, which form antibodies to it poorly, since in previous work with the mouse the antigen was found (1) in the blood after 8 weeks and in the liver for 14 weeks. Nevertheless the antigen persists in the rabbit much longer than is generally supposed. Indeed it can be found in the liver all through the period in which circulating antibody is demonstrable in the blood. Explanations for the phenomenon have been suggested. Its significance in relation to the mechanisms of antibody formation is obvious.
Heat Shock Protein 70 Surface-Positive Tumor Exosomes Stimulate Migratory and Cytolytic Activity of Natural Killer Cells
Authors: Robert Gastpar, Mathias Gehrmann, Maria A. Bausero, Alexzander Asea, Catharina Gross, Josef A. Schroeder, Gabriele Multhoff
Journal: Cancer Research (2005)

Abstract Detergent-soluble membrane vesicles are actively released by human pancreas (Colo−/Colo+) and colon (CX−/CX+) carcinoma sublines, differing in their capacity to present heat shock protein 70 (Hsp70)/Bag-4 on their plasma membranes. Floating properties, acetylcholine esterase activity, and protein composition characterized them as exosomes. An enrichment of Rab-4 documented their intracellular transport route from early endosomes to the plasma membrane. After solubilization, comparable amounts of cytosolic proteins, including tubulin, Hsp70, Hsc70, and Bag-4, but not ER-residing Grp94 and calnexin, were detectable in tumor-derived exosomes. However, with respect to the exosomal surface, only Colo+/CX+ but not Colo−/CX− derived exosomes were Hsp70 membrane positive. Therefore, concomitant with an up-regulated cell surface density of activation markers, migration and Hsp70 reactivity of natural killer (NK) cells was stimulated selectively by Hsp70/Bag-4 surface-positive exosomes, but not by their negative counterparts and tumor cell lysates. Moreover, the exosome-mediated lytic activity of NK cells was blockable by Hsp70-specific antibody. As already shown for TKD stimulation, NK cells preincubated with Hsp70 surface-positive exosomes initiated apoptosis in tumors through granzyme B release. In summary, our data provide an explanation how Hsp70 reactivity in NK cells is induced by tumor-derived exosomes.
Critical care outreach team's effect on patient outcome: More information is needed
Authors: Michael R Parker
Journal: BMJ (2004)

EDITOR—The average hospital mortality in patients admitted to intensive care units in England is 30%, of which around 8% occurs after discharge from intensive care.1 In the study by Ball et al the retrospective control group had a median predicted hospital mortality of 20.4%, and yet 19% died after discharge from intensive care.2 No details …
Immunoglobulin allotype gene polymorphisms in systemic sclerosis: interactive effect of MHC class II and KM genes on anticentromere antibody production
Authors: H. Kameda, J. P Pandey, J. Kaburaki, H. Inoko, M. Kuwana
Journal: Annals of the Rheumatic Diseases (1998)

<h3>OBJECTIVE</h3> To examine potential interactions between immunoglobulin (Ig)allotype gene polymorphisms and susceptibility to systemic sclerosis (SSc) as well as serological expression in SSc patients. <h3>METHODS</h3> IgG heavy chain allotypes G1M(f, z), G2M(n+, n-), G3M(b, g) and Ig light chain allotype KM(1, (1, 2), 3) were genotyped in 105 Japanese SSc patients and 47 race matched normal controls using polymerase chain reaction (PCR) based methods. Associations of each Ig allotype with SSc related antinuclear antibodies were examined in combination with or without MHC class II alleles. <h3>RESULTS</h3> GM/KM genotypic and allelic frequencies were similar in SSc patients and in normal controls. Frequencies of G1M(f) and G2M(n+) were significantly decreased in anticentromere antibody (ACA) positive SSc patients compared with ACA negative SSc patients (p = 0.04 and 0.02, respectively). Conversely, the presence of DQB1*0501 and KM(1, 2) significantly increased the risk of ACA positivity. <h3>CONCLUSION</h3> Ig allotype gene polymorphisms were not associated with susceptibility to SSc. Instead, the results suggested that MHC class II and KM genes are associated with autoimmune responses by interactively promoting the production of ACA.