tbuckley/cabot-search huggingface dataset:
Responding to intimate partner and sexual violence against women
Authors: A. H. Sohal, D. James-Hanman
Journal: BMJ (2013)

New WHO guidelines outline what to do 

On 20 June the World Health Organization published its first clinical and policy evidence based guidelines on responding to intimate partner violence and sexual violence against women.1 These landmark guidelines draw from a WHO study of 24 097women in 10 countries.2 This study showed widespread lifetime physical and sexual violence by an intimate partner (15-71% prevalence among ever partnered women) and associated effects on health. Health outcomes associated with such violence include substantially increased risk of suicide attempts, suicidal thoughts, pain, dizziness, and vaginal discharge.3 The 2010 Global Burden of Disease Study ranked intimate partner violence fifth in terms of years lost owing to disability.4 In a study of Australian women of reproductive age (15-44 years), intimate partner violence was the largest risk factor for poor health (greater than smoking, alcohol, obesity, hypercholesterolaemia, and hypertension).5 Such violence is undoubtedly a major public health problem that requires a compassionate and effective health response.

The WHO guidelines offer 37 recommendations about the clinical care of women who have experienced intimate partner violence or sexual violence (or both), the training of healthcare providers, and the formulation of healthcare policy and service provision. They meet a crucial need to raise awareness of such violence as a health matter—rather than just a criminal justice, social, or personal problem—among healthcare providers, trainers, and policy makers. 

The WHO report …
Abstract 4367: Cigarette smoke condensate-induced oxidative DNA damage and its removal in cervical cancer cell lines
Authors: Afsoon Moktar, Manicka V. Vadhanam, Rajesh Singh, C. Gary Gairola, James W. Lillard, Ramesh C. Gupta
Journal: Cancer Research (2010)

Abstract Increased oxidative stress is implicated in the etiology of cancer. Exposure to cigarette smoke is well documented to increase oxidative stress in smoker tissues and probably plays a role in the incidence of cervical cancer. The cervical pre-cancerous lesions, initiated by HPV infection, generally regress in the absence of the known risk factors such as smoking. The oxidation of deoxyguanosine results in a highly mutagenic and extensively studied oxidative DNA lesion, 8-oxodeoxyguanosine (8-oxodG). The present study was performed to determine i) the effect of cigarette smoke condensate (CSC) on 8-oxodG formation in HPV-transfected cervical cell lines (ECT1/E6 E7); ii) the removal of the oxidative damage from HPV-positive (CaSki), HPV-negative (C33A) and ECT1/E6 E7 cells; and iii) the cell-cycle progression and apoptosis in the CSC-treated ECT1/E6 E7. We found that CSC induced 8-oxodG lesion in a dose- and time-dependent manner in the transfected cervical cell line. A 2.4-fold higher damage was observed in the HPV-positive tumor cell line compared to the HPV-negative cell line. Flow-cytometric and ImageStream (Amnis) analysis indicated that CaSki cells most efficiently removed the oxidative lesion in 48 h (93%). On the contrary, C33A cells did not reveal any significant removal of 8-oxodG up to 48 h. This difference could be explained by the presence of residual p53 activity in CaSki cells while the p53 is mutated in the C33A cell line. ECT1/E6 E7 cell line showed only a modest (22%) removal after 48 h. Interestingly, 8-oxodG was almost completely removed 72 h post-exposure in all the cervical cell lines. Furthermore, a dose-dependent increase in apoptosis was observed in ECT1/E6 E7 cells with an arrest at G0/G1 phase of cell cycle. We conclude that cigarette smoke induces oxidative stress with higher burden in HPV-positive cells; however, HPV exposure may not play a role in the kinetics of 8-oxodG removal (Supported from Agnes Brown Duggan Endowment and, in part, USPHS grant ES-011564). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4367.
Effects of <i>N</i>‐acetylcysteine on dense cell formation in sickle cell disease
Authors: Betty S. Pace, Archil Shartava, Ardie Pack‐Mabien, Mudhari Mulekar, Alfredo Ardia, Steven R. Goodman
Journal: American Journal of Hematology (2003)

Abstract The extent to which dense and irreversible sickle cells (ISCs) contribute to vaso‐occlusive episodes in sickle cell disease remains unclear. N ‐Acetylcysteine (NAC) inhibits dense cell and ISC formation in sickle erythrocytes in vitro and restores glutathione levels toward normal. A phase II double‐blind randomized clinical trial was completed to determine the efficacy of NAC in decreasing dense cell and ISC formation, and vaso‐occlusive episodes in sickle cell disease. Twenty‐one subjects with a history of at least two vaso‐occlusive episodes per year and 6% dense cells were enrolled. Four treatment groups were analyzed; NAC at a dose of 2,400 mg per day decreased the percent dense cells from 20.1 ± 2.9 to 12.6 ± 2.1 ( P &lt; 0.05) and increased red cell glutathione levels from 292.8 ± 74.5 to 576.7 ± 155.1 ( P &lt; 0.05). In addition, we observed a decrease in vaso‐occlusive episodes from 0.03 to 0.006 episodes per person‐days and a decreased in relative risk to R = 0.39. Although NAC did not significantly decrease the number of ISCs, there was a downward trend at all doses tested. In summary, NAC inhibited dense cell formation, restored glutathione levels toward normal, and decreased vaso‐occlusive episodes at a well‐tolerated dose of 2,400 mg per day. To determine the long‐term efficacy and safety of NAC, a multicenter phase III clinical trial is required. Am. J. Hematol. 73:26–32, 2003. © 2003 Wiley‐Liss, Inc.
Loss of TGFβ Receptor Type 2 Expression Impairs Estrogen Response and Confers Tamoxifen Resistance
Authors: Susann Busch, Andrew H. Sims, Olle Stål, Mårten Fernö, Göran Landberg
Journal: Cancer Research (2015)

One third of the patients with estrogen receptor α (ERα)-positive breast cancer who are treated with the antiestrogen tamoxifen will either not respond to initial therapy or will develop drug resistance. Endocrine response involves crosstalk between ERα and TGFβ signaling, such that tamoxifen nonresponsiveness or resistance in breast cancer might involve aberrant TGFβ signaling. In this study, we analyzed TGFβ receptor type 2 (TGFBR2) expression and correlated it with ERα status and phosphorylation in a cohort of 564 patients who had been randomized to tamoxifen or no-adjuvant treatment for invasive breast carcinoma. We also evaluated an additional four independent genetic datasets in invasive breast cancer. In all the cohorts we analyzed, we documented an association of low TGFBR2 protein and mRNA expression with tamoxifen resistance. Functional investigations confirmed that cell cycle or apoptosis responses to estrogen or tamoxifen in ERα-positive breast cancer cells were impaired by TGFBR2 silencing, as was ERα phosphorylation, tamoxifen-induced transcriptional activation of TGFβ, and upregulation of the multidrug resistance protein ABCG2. Acquisition of low TGFBR2 expression as a contributing factor to endocrine resistance was validated prospectively in a tamoxifen-resistant cell line generated by long-term drug treatment. Collectively, our results established a central contribution of TGFβ signaling in endocrine resistance in breast cancer and offered evidence that TGFBR2 can serve as an independent biomarker to predict treatment outcomes in ERα-positive forms of this disease.
Cytokines in implantation
Authors: T Chard
Journal: Human Reproduction Update (1995)

The process of implantation in the human involves 'invasion' of the maternal endometrium by the tro-phoblast surrounding the developing blastocyst, in response to which there is a cellular reaction in the endometrium. The overall situation has some features analogous to invasion by a tumour and some which are more characteristic of an inflammatory response. In addition, and also in common with cancer and inflammation, there is a release of biologically active molecules, including cytokines, at and around the implantation site. It is believed that these cytokines may play an important role in the successful establishment of the pregnancy; the evidence for this belief is examined in this review.
Abstract 5358: BRCA1 is a negative modulator of the PRC2 complex.
Authors: Xianzhou Zeng, Shuai Chen, Lan Wang, Haojie Huang
Journal: Cancer Research (2013)

Abstract The Polycomb repressive complex 2 (PRC2) is important for maintenance of stem cell pluripotency and suppression of cell differentiation by promoting histone H3 lysine 27 trimethylation (H3K27me3) and transcriptional repression of differentiation regulatory genes. Here we show that the tumor suppressor protein BRCA1 interacts with EZH2 and other components of PRC2 in mouse embryonic stem (ES) and human breast cancer cells. The BRCA1-binding region in EZH2 overlaps with the non-coding RNA (ncRNA)-binding domain, and BRCA1 expression inhibits the binding of EZH2 to the HOTAIR ncRNA. Decreased expression of BRCA1 causes EZH2 re-targeting genome wide and elevates H3K27me3 levels at PRC2 target loci in both mouse ES and human breast cancer cells. BRCA1 deficiency blocks ES cell differentiation and enhances breast cancer migration and invasion in an EZH2-dependent manner. These results reveal that BRCA1 is a key negative modulator of PRC2 and that loss of BRCA1 inhibits ES cell differentiation and enhances cancer aggressive phenotypes via augmented PRC2 function. Citation Format: Xianzhou Zeng, Shuai Chen, Lan Wang, Haojie Huang. BRCA1 is a negative modulator of the PRC2 complex. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5358. doi:10.1158/1538-7445.AM2013-5358
681. Hydrogel Encapsulation of Adenovirus-Transduced Cells Expressing BMP2 for Local Osteoinduction
Authors: Malavosklish Bikram, Christine Fouletier-Dilling, Andre M. Gobin, Alan R. Davis, Elizabeth A. Olmsted-Davis, Jennifer L. West
Journal: Molecular Therapy (2005)

The use of gene therapy as an alternative to autogenous bone grafting techniques commonly utilized to promote regeneration and healing have been very promising due to recent advances in recombinant adenoviral vectors encoding bone morphogenetic protein 2 (BMP2), which have been shown to induce bone formation via ex vivo cell transduction. However, major limitations to the delivery of transduced cells include targeted immune reactions towards the cells that result in increased clearance and a lack of immobilization of the cells within a specific tissue that can lead to spatially uncontrolled gene expression. One alternative is the encapsulation of ex vivo transduced BMP2 expressing cells within immunoprotective hydrogels. The poly(ethylene glycol)-based hydrogels used in these studies have permeability sufficient to allow diffusion of BMP2 out of the hydrogels but are impermeable to antibodies and immune cells. Thus, we have encapsulated human diploid lung fibroblasts (MRC-5) transduced with a chimeric adenovirus type 5 (Ad5) with a fiber gene of adenovirus type 35 encoding BMP2 (Ad5F35-BMP2) within PEG diacrylate (PEGDA) hydrogels to form tissue engineered scaffolds that offer immuno-protection. PEGDA hydrogels were polymerized in a 1:1 ratio of polymer:cell suspension into circular disks having diameter of |[sim]|11.5mm and thickness of |[sim]|0.5mm and maintained in culture for 14d. The conditioned media from the cultured disks were then assayed for BMP2 protein with an ELISA assay, which showed continued BMP2 production for the 14d period with peak protein levels occurring on day 5 that were comparable to control transduced plated cells at the same time interval (p>0.05). Cell viability was determined using Molecular Probes Live/Dead Staining Kit 24 h post encapsulation, which showed viabilities of |[sim]|74% and |[sim]|66% for encapsulated MRC-5 and transduced MRC-5 (tMRC-5) cells, respectively. The mechanical strength of the PEGDA hydrogels with encapsulated cells was investigated on an Instron 3342 mechanical tester at a crosshead speed of 1 mm/min, which showed that there was no significant difference in compressive modulus, 277kPa for hydrogel only and 270kPa for hydrogel with cells (p>0.05).
Regulatory T Cells Depress Immune Responses to Protective Antigens in Active Tuberculosis
Authors: Jean-Michel Hougardy, Sammy Place, Marc Hildebrand, Annie Drowart, Anne-Sophie Debrie, Camille Locht, Françoise Mascart
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: Tuberculosis (TB) remains a leading cause of death, and the role of T-cell responses to control Mycobacterium tuberculosis infections is well recognized. Patients with latent TB infection develop strong IFN-γ responses to the protective antigen heparin-binding hemagglutinin (HBHA), whereas patients with active TB do not.Objectives: We investigated the mechanism of this difference and evaluated the possible involvement of regulatory T (Treg) cells and/or cytokines in the low HBHA T-cell responses of patients with active TB.Methods: The impact of anti–transforming growth factor (TGF)-β and anti–IL-10 antibodies and of Treg cell depletion on the HBHA-induced IFN-γ secretion was analyzed, and the Treg cell phenotype was characterized by flow cytometry.Measurements and Main Results: Although the addition of anti–TGF-β or anti–IL-10 antibodies had no effect on the HBHA-induced IFN-γ secretion in patients with active TB, depletion of CD4+CD25highFOXP3+ T lymphocytes resulted in the induction by HBHA of IFN-γ concentrations that reached levels similar to those obtained for latent TB infection. No effect was noted on the early-secreted antigen target–6 or candidin T-cell responses.Conclusions: Specific CD4+CD25highFOXP3+ T cells depress the T-cell–mediated immune responses to the protective mycobacterial antigen HBHA during active TB in humans.
Effect of abciximab on myocardial microcirculation after successful primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction
Authors: Stephanie Lehrke, Henning Steen, Ralph Toelg, Uwe K. Wiegand, Ebangelos Giannitsis, Hugo A. Katus
Journal: Journal of the American College of Cardiology (2003)
Prostate-specific antigen: current status
Authors: M. K. Brawer
Journal: CA A Cancer Journal for Clinicians (1999)

Prostate-specific antigen (PSA) is the most important of all tumor markers in that it has significant applications in all aspects of the management of men with prostatic disease. Certainly, the most important utilization of PSA is for the early detection of this most ubiquitous of all human neoplasms. This article reviews the salient features of PSA, with particular emphasis on strategies to improve its utility in the diagnosis of prostate cancer. So-called PSA derivatives--including age-specific PSA, PSA velocity, and PSA density--are discussed. With the recognition of molecular forms of PSA, however, the ratio of free-to-total PSA, and now the complex form of PSA, have been shown to be more specific indicators of the presence of malignancy. Significant public interest and research efforts in prostate cancer have resulted in numerous advances over the past decade. The discovery of PSA and the development of assays to measure it will undoubtedly be recorded as one of the most important advances in the management of men with prostate cancer.
HLA-B27 binding of peptide from its own sequence and similar peptides from bacteria: implications for spondyloarthropathies
Authors: R.H. Scofield, B. Kurien, T. Gross, W.L. Warren, J.B. Harley, R.H. Scofield, J.B. Harley, R.H. Scofield, J.B. Harley
Journal: The Lancet (1995)
Cases of Fracture of the Base of the Skull: With Remarks
Authors: C. E. Prior
Journal: BMJ (1871)

<h3>Background</h3> Admission to hospital is associated with significant mortality.<sup>1</sup> Admission should prompt early consideration of ceilings of care (CoC) to ensure appropriate treatment provision. Delays in these decisions can lead to care mismatched with patient wishes, inappropriate escalation, delays in palliation, less time to come to terms with prognosis for patient and loved ones, as well as difficulties for staff out of hours. The post-take ward round (PTWR) often represents the most appropriate time to discuss CoC, as comprehensive patient information and consultant support are available. During the first wave of the Covid-19 pandemic, emphasis was put on early decision making and communication of CoC.<sup>2</sup> <h3>Aim</h3> To ascertain if one month after first lockdown, as the hospital was recovering and normalising, whether early decision-making regarding ceilings of care continued. <h3>Method</h3> PTWR proformas and Respect forms for 50 medical patients admitted to Alexandra Hospital Redditch during February 2020 were audited for CoC documentation. Due to the covid-19 pandemic, the UK went into lockdown from March to July 2020. Over one month later, in August 2020, a second audit of 50 patients was completed <h3>Results</h3> From pre-covid to one month after lockdown was lifted, CoC documentation at PTWR increased from 4% to 18%. For patients aged over 70, documentation increased from 6% to 23%. <h3>Discussion</h3> Results were likely heavily influenced by the unprecedented covid-19 pandemic. These results are likely due to more pro-active clinical decision making as a result of the acute crisis, awareness of bed pressures and a shift in perception of the importance of CoC. Potential alternative reasons include raised public awareness prompting patient-led discussions, or increased openness to care planning. Despite this, there is still room for further improvement in discussion and documentation of CoC as we continue to rebound from this crisis. <h3>References</h3> Moore E, Munoz-Arroyo R, Schofield L, <i>et al</i>. Death within 1 year among emergency medical admissions to Scottish hospitals: incident cohort study. <i>BMJ Open</i> 2018;<b>8</b>:e021432. doi: 10.1136/bmjopen-2017–021432 Coleman JJ, Botkai A, Marson EJ, Evison F, Atia J, Wang J, Gallier S, Speakman J, Pankhurst T. Bringing into focus treatment limitation and DNACPR decisions: how COVID-19 has changed practice. <i>Resuscitation</i> 2020 Oct;<b>155</b>:172–179. doi: 10.1016/j.resuscitation.2020.08.006. Epub 2020 Aug 20. PMID: 32827587; PMCID: PMC7438269.
Sixth plot of the carcinogenic potency database: results of animal bioassays published in the General Literature 1989 to 1990 and by the National Toxicology Program 1990 to 1993.
Authors: L S Gold, N B Manley, T H Slone, G B Garfinkel, B N Ames, L Rohrbach, B R Stern, K Chow
Journal: Environmental Health Perspectives (1995)

This paper presents two types of information from the Carcinogenic Potency Database (CPDB): (a) the sixth chronological plot of analyses of long-term carcinogenesis bioassays, and (b) an index to chemicals in all six plots, including a summary compendium of positivity and potency for each chemical (Appendix 14). The five earlier plots of the CPDB have appeared in this journal, beginning in 1984 (1-5). Including the plot in this paper, the CPDB reports results of 5002 experiments on 1230 chemicals. This paper includes bioassay results published in the general literature between January 1989 and December 1990, and in Technical Reports of the National Toxicology Program between January 1990 and June 1993. Analyses are included on 17 chemicals tested in nonhuman primates by the Laboratory of Chemical Pharmacology, National Cancer Institute. This plot presents results of 531 long-term, chronic experiments of 182 test compounds and includes the same information about each experiment in the same plot format as the earlier papers: the species and strain of test animal, the route and duration of compound administration, dose level and other aspects of experimental protocol, histopathology and tumor incidence, TD50 (carcinogenic potency) and its statistical significance, dose response, author's opinion about carcinogenicity, and literature citation. We refer the reader to the 1984 publications (1,6,7) for a detailed guide to the plot of the database, a complete description of the numerical index of carcinogenic potency, and a discussion of the sources of data, the rationale for the inclusion of particular experiments and particular target sites, and the conventions adopted in summarizing the literature. The six plots of the CPDB are to be used together since results of individual experiments that were published earlier are not repeated. Appendix 14 is designed to facilitate access to results on all chemicals. References to the published papers that are the source of experimental data are reported in each of the published plots. For readers using the CPDB extensively, a combined plot is available of all results from the six separate plot papers, ordered alphabetically by chemical; the combined plot in printed form or on computer tape or diskette is available from the first author. A SAS database is also available.
Nephrotic Syndrome Caused by Probenecid
Authors: Thomas F. Ferris, Walter S. Morgan, Howard Levitin
Journal: New England Journal of Medicine (1961)

THE nephrotic syndrome has been reported to occur in the course of therapy with a number of drugs including trimethadione,1 , 2 paramethadione,3 mercurial diuretics,4 tolbutamide5 and perchlorate,6 as well as in association with sensitivity to poison oak7 and bee sting.8 In the case reported below, the nephrotic syndrome appeared to be the result of a reaction to probenecid.¶ Although proteinuria and renal failure are known to occur in the course of chronic gout, the nephrotic syndrome has not heretofore been reported as a result of gouty nephritis or in association with probenecid therapy.Case ReportA 52-year-old man was first seen . . .
Synergistic roles of granzymes A and B in mediating target cell death by rat basophilic leukemia mast cell tumors also expressing cytolysin/perforin.
Authors: H Nakajima, H L Park, P A Henkart
Journal: The Journal of Experimental Medicine (1995)

We have studied the cytotoxic activity of rat basophilic leukemia (RBL) cells transfected with cDNAs for the cytotoxic T lymphocyte (CTL) granule components, cytolysin (perforin), granzyme A, and granzyme B. With red cell targets, cytolysin expression conferred potent hemolytic activity, which was not influenced by coexpression of granzymes. With tumor targets, RBL cells expressing cytolysin alone were weakly cytotoxic, but both cytolytic and nucleolytic activity were enhanced by coexpression of granzyme B. RBL cells expressing all three CTL granule components showed still higher cytotoxic activities, with apoptotic target death. Analysis of the cytotoxic activity of individual transfectant clones showed that cytolytic and nucleolytic activity correlated with granzyme expression but was independent of cytolysin expression within the range examined. A synergism between granzymes A and B was apparent when the triple transfectant was compared with RBL cells expressing cytolysin and one granzyme. These data implicate granzymes as the major mediators of tumor target damage by cytotoxic lymphocytes.