tbuckley/cabot-search huggingface dataset:
Implication of a Pro-Apoptotic Protein, Prostate Apoptosis Response-4 (Par-4) in Breast Cancer.
Authors: L. Ye, R. Mansel, W. Jiang
Journal: Cancer Research (2009)

Abstract Background: Par-4, Prostate Apoptosis Response-4, is pro-apoptotic in certain cell types and has been implicated in the development and progression of solid tumours. However, the role of Par-4 in breast cancer remains unclear. The current study investigated the role played by Par-4 in breast cancer.Methods: The expression of Par-4 was examined in a breast cancer cohort using quantitative real time PCR and immunohistochemistry (IHC). The biological functions of Par-4 in breast cancer cells were tested by creating breast cancer cell lines that had differential Par-4 expression. The cell functions were examined using a variety of in vitro assays, including growth, migration and invasion. The implication of Par-4 in breast cancer was further tested in an in vivo tumour model.Results: A marked decrease of both Par-4 mRNA and protein was seen in breast tumours compared with background tissues. Par-4 staining was cytoplasmic in both mammary epithelial cells and cancer cells in the tissues. The level of Par-4 transcripts in primary tumours was decreased in the patients with poor prognosis and worse clinical outcome. The overall survival was poor in the patients with lower Par-4 transcript level, p=0.0082 compared with the patients who had higher expression. Patients with higher expression level also had longer disease free survival (133.1 months (95% CI, 121.1-145.1 months)), p=0.0597 compared with patients who had lower expression (118.4 months (95% CI, 103.2-133.5 months)). Over-expression of Par-4 in MDA-MB-231 cells (MDA-MB-231Par4exp) resulted a reduction of cell growth, migration and invasion in vitro. The invaded cell number of MDA-MB-231Par4exp was 17.9±2.5, p&amp;lt;0.01 compared with both MDA-MB-231WT(30.8±2.6) and MDA-MB-231pEF(34.1±6.5) controls. This also led to a decreased in vivo tumour growth, in an athymic mice model.Conclusions: Taken together, decreased Par-4 expression in breast cancer correlates with poor prognosis and shorter survival. Par-4 suppresses growth, migration and invasiveness of breast cancer cells in vitro, and also inhibits in vivo tumour growth. It suggests that Par-4 plays critical roles in the progression of breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6155.
Testing Platelet Activation With a Shear-Dependent Platelet Function Test Versus Aggregation-Based Tests
Authors: Julio I. Osende, Valentin Fuster, Eli I. Lev, Daichi Shimbo, Ursula Rauch, Jonathan D. Marmur, Merwin Richard, David Varon, Juan Jose Badimon
Journal: Circulation (2001)

Background —Tests developed to monitor glycoprotein (GP) IIb/IIIa blockade do not properly reflect platelet function in vivo and need a baseline (pretreatment) value. Because GP IIb/IIIa is essential in platelet aggregation and thrombosis under shear conditions, a flow-dependent approach to monitor its inhibition can be used. Methods and Results —We compared a test based on flow-dependent platelet deposition, the Cone and Platelet Analyzer (CPA), with in vitro platelet aggregometry and the Rapid Platelet Function Assay (RPFA) on platelet function after GP IIb/IIIa inhibition. In vitro, increasing concentrations of abciximab (0% to 100% receptor occupancy) were tested. Ex vivo, platelet function was monitored with the CPA and with aggregometry for up to 1 week after abciximab administration. The CPA was better correlated with the percentage of free GP IIb/IIIa receptors than was aggregometry or the RPFA. Only the RPFA, when expressed as a ratio over baseline (pretreatment), was comparable to the CPA. Ex vivo, the CPA, but not aggregometry, showed prolonged platelet inhibition with gradual recovery from GP IIb/IIIa receptor blockade in the first week after abciximab administration. Conclusions —Platelet function assessment by shear-induced deposition is a reliable test to monitor a wide range of GP IIb/IIIa inhibition. Its accuracy does not require a baseline reference. The effects of GP IIb/IIIa blockade on platelet function should be examined under high shear conditions.
Treatment of displaced intracapsular hip fractures in older patients
Authors: J. E. Madsen
Journal: BMJ (2010)

Total hip arthroplasty is preferable to hemiarthroplasty in healthy patients

In the linked systematic review (doi:10.1136/bmj.c2332), Hopley and colleagues compare outcomes after total hip replacement versus hemiarthroplasty when treating displaced femoral neck fractures in older patients.1 Hip fractures cause considerable death and disability in elderly people. Worldwide, 1.6 million new hip fractures occurred in 2000, and these accounted for the loss of 2.35 million disability adjusted life years (DALYs) annually and 1.4% of the burden of disease in women in the Western world.2 The incidence of hip fractures is estimated to rise to more than six million in 2050, around half of which will be femoral neck fractures.3

Displaced femoral neck fractures in elderly people are treated by internal fixation or prosthetic replacement, with either a hemiarthroplasty replacing the femoral head and neck or a total hip arthroplasty which also includes acetabular replacement. These treatments are associated with different complication rates, function, and independency of living. Hemiarthroplasty produces consistently better function than internal fixation,4 5 6 and lower reoperation rates (10% v 40%).7 No significant differences …
Abstract LB-459: An essay concerning the molecular prediction of disease outcome in melanoma patients
Authors: Melanie Gschaider, Friederike Neumann, Bettina Peters, Florian Lenz, Micheal Cibena, Malgorzata Goiser, Ingrid Wolf, Jörg Wenzel, Cornelia Mauch, Wolfgang Schreiner, Stephan N. Wagner
Journal: Cancer Research (2012)

Abstract Melanoma is the most lethal form of skin cancer. Current prognostic clinical and histopathological parameters are insufficient to accurately predict the outcome of individual patients. Several studies have claimed gene expression signatures to predict survival or metastasis of primary melanoma patients. However, the reproducibility among these studies is disappointingly low and led to the development of guidelines on statistical analysis and reporting of gene expression data for cancer outcome. We carefully followed these guidelines when we used gene expression data from primary human melanoma samples to identify gene signatures predictive for disease outcome. The class comparison dataset was established using microarray data from non-metastatic and metastatic primary melanoma samples. The top 50 differentially expressed genes were identified by Significance Analysis of Microarrays and used in an independent gene expression data set of primary melanomas for prediction. Multivariate Cox regression analysis determined the classifier revealing the best predictive value. This classifier comprised the Duffy blood group chemokine receptor and the ribosomal protein S27-like and defined the cutoff positions for favorable and detrimental disease outcome, respectively. We report this classifier as an essay to provide molecular information supplementary to standard morphological prognostic factors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-459. doi:1538-7445.AM2012-LB-459
879 AGING AND ANTI HCV TREATMENT OUTCOME IN HCV INFECTED WOMEN WITH AND WITHOUT HIV INFECTION
Authors: P. Nasta, M. Giralda, C. Baiguera, S. Odolini, E. Chiari, A. Spinetti, S. Amadasi, G. Moioli, S. Zaltron, F. Castelli
Journal: Journal of Hepatology (2013)
Hereditary and acquired p53 gene mutations in childhood acute lymphoblastic leukemia.
Authors: Carolyn A. Felix, Marion M. Nau, Takashi Takahashi, Tetsuya Mitsudomi, Itsuo Chiba, David G. Poplack, Gregory H. Reaman, Diane E. Cole, John James Letterio, Jacqueline Whang-Peng, Turid Knutsen, John D. Minna
Journal: Journal of Clinical Investigation (1992)

The p53 gene was examined in primary lymphoblasts of 25 pediatric patients with acute lymphoblastic leukemia by the RNase protection assay and by single strand conformation polymorphism analysis in 23 of 25 cases. p53 mutations were found to occur, but at a low frequency (4 of 25). While all four mutations were identified by single strand conformation polymorphism, the comparative sensitivity of RNase protection was 50% (2 of 4). Heterozygosity was retained at mutated codons in 3 of 4 cases. One pedigree was consistent with the Li-Fraumeni syndrome, and bone marrow from both diagnosis and remission indicated a germline G to T transversion at codon 272 (valine to leucine). Although members of another family were affected with leukemia, a 2-bp deletion in exon 6 was nonhereditary. The other two nonhereditary p53 mutations included a T to G transversion at codon 270 (phenylalanine to cysteine) and a G to C transversion at codon 248 (arginine to proline). These data support the role of both hereditary and acquired p53 mutations in the pathogenesis and/or progression of some cases of childhood acute lymphoblastic leukemia.
Noninvasive vs invasive ventilation in COPD patients with severe acute respiratory failure deemed to require ventilatory assistance
Authors: Enzo Squadrone, Pamela Frigerio, Claudio Fogliati, Cesare Gregoretti, Giorgio Conti, Massimo Antonelli, Roberta Costa, Paola Baiardi, Paolo Navalesi
Journal: Intensive Care Medicine (2004)
Reduction of the size of infarction by allopurinol in the ischemic-reperfused canine heart.
Authors: S W Werns, M J Shea, S E Mitsos, R C Dysko, J C Fantone, M A Schork, G D Abrams, B Pitt, B R Lucchesi
Journal: Circulation (1986)

This study was performed to assess the effect of allopurinol in a canine preparation of myocardial infarction. Dogs underwent occlusion of the left circumflex coronary artery for 90 min, followed by reperfusion for 6 hr. Three groups were studied: (1) control, (2) dogs receiving 25 mg/kg allopurinol 18 hr before occlusion and 50 mg/kg 5 min before occlusion, and (3) dogs receiving allopurinol as above plus 5 mg/kg superoxide dismutase over 1 hr beginning 15 min before reperfusion. Infarct size expressed as a percentage of the area at risk was 40 +/- 4 in the control group, 22 +/- 5 in the allopurinol group (p less than .05 vs control), and 17 +/- 4 in the allopurinol plus superoxide dismutase group (p less than .05 vs control). The differences in infarct size were not due to differences in myocardial oxygen supply or demand. Neutrophil superoxide anion production was not altered by allopurinol treatment. The results suggest that myocardial xanthine oxidase may generate oxygen radicals that play a role in myocardial injury due to ischemia and reperfusion.
CD4+ T cells contribute to postischemic liver injury in mice by interacting with sinusoidal endothelium and platelets
Authors: Andrej Khandoga, Marc Hanschen, Julia S. Kessler, Fritz Krombach
Journal: Hepatology (2006)

The mechanisms by which T cells contribute to the hepatic inflammation during antigen-independent ischemia/reperfusion (I/R) are not fully understood. We analyzed the recruitment of T cells in the postischemic hepatic microcirculation in vivo and tested the hypothesis that T cells interact with platelets and activate sinusoidal endothelial cells, resulting in microvascular dysfunction followed by tissue injury. Using intravital videofluorescence microscopy, we show in mice that warm hepatic I/R (90/30-140 min) induces accumulation and transendothelial migration of CD4+, but not CD8+ T cells in sinusoids during early reperfusion. Simultaneous visualization of fluorescence-labeled CD4+ T cells and platelets showed that approximately 30% of all accumulated CD4+ T cells were colocalized with platelets, suggesting an interaction between both cell types. Although interactions of CD4+/CD40L−/− T cells with CD40L−/− platelets in wild-type mice were slightly reduced, they were almost absent if CD4+ T cells and platelets were from CD62P−/− mice. CD4 deficiency as well as CD40-CD40L and CD28-B7 disruption attenuated postischemic platelet adherence in the same manner as platelet inactivation with a glycoprotein IIb/IIIa antagonist and reduced neutrophil transmigration, sinusoidal perfusion failure, and transaminase activities. Treatment with an MHC class II antibody, however, did not affect I/R injury. In conclusion, we describe the type, kinetic, and microvascular localization of T cell recruitment in the postischemic liver. CD4+ T cells interact with platelets in postischemic sinusoids, and this interaction is mediated by platelet CD62P. CD4+ T cells activate endothelium, increase I/R-induced platelet adherence and neutrophil migration via CD40-CD40L and CD28-B7-dependent pathways, and aggravate microvascular/hepatocellular injury. (Hepatology 2006;43:306–315.)
Abstract LB-117: Myc phosphorylation suppresses transformation through novel regulatory regions.
Authors: Dharmendra Dingar, Amanda R. Wasylishen, Michelle Chan-Seng-Yue, Ling Huang, Christina Bros, William Tu, Natalie Meyer, Paul C. Boutros, Linda Z. Penn
Journal: Cancer Research (2013)

Abstract Myc is a proto-oncogenic transcription factor, whose expression is deregulated in numerous human tumours and over-expression in animal models can cause tumorigenesis. Myc is important in cancer initiation and progression and therefore to develop successful approaches targeting Myc, a better understanding of both the mechanisms of Myc regulation and subsequent deregulation in cancer is important. Identification of Myc post-translational modifications (PTMs) that are essential for its oncogenic activity remains largely unknown. Therefore, detecting those key PTMs and there effect on gene expression would shed more light on the mechanisms of Myc dependent tumorigenesis. In our study, we screened a panel of Myc phosphorylation mutants in MCF10A cells for their ability to promote anchorage-independent colony growth and we identified two previously uncharacterized mutants that increased Myc-dependent transformation: S71A/S81A and 340Cl-A (T343A, S344A, S347A, and S348A). We further confirmed that gain-of-function serine and threonine mutants potentiated transformation in SH-EP neuroblastoma cells and three-dimensional MCF10A acini. Additionally, to investigate the mechanism of increased transformation and mutants' selectivity for gene transcription, we conducted genome-wide mRNA expression analysis of MCF10A acini and identified 112 genes regulated by all MYC alleles, and 158 genes regulated by all three transforming phosphorylation mutants but not wild-type MYC. We performed genome-wide ChIP in MCF10A cells, integrated this with gene transcription data, and showed that the majority of genes with altered expression also have MYC binding in their promoter regions, further suggesting that these gene expression changes are directly regulated by Myc. In conclusion, phosphorylation of S71/S81 and 340Cl amino acid residues negatively regulates Myc dependent transformation, suggesting that better understanding of Myc regulation through the phosphorylation of these residues may provide opportunities to therapeutically target Myc. Citation Format: Dharmendra Dingar, Amanda R. Wasylishen, Michelle Chan-Seng-Yue, Ling Huang, Christina Bros, William Tu, Natalie Meyer, Paul C. Boutros, Linda Z. Penn. Myc phosphorylation suppresses transformation through novel regulatory regions. [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 LB-117. doi:10.1158/1538-7445.AM2013-LB-117
Automated External Defibrillators: Technical Considerations and Clinical Promise
Authors: Theodore S. Takata, Richard L. Page, Jose A. Joglar
Journal: Annals of Internal Medicine (2001)

Early defibrillation is the most important determinant of survival for victims of cardiac arrest due to ventricular fibrillation. The automated external defibrillator (AED) was developed as the result of the American Heart Association's Public Access Defibrillation initiative. The goal of this initiative is to place AEDs in strategic locations so that laypersons with minimal training could promptly defibrillate victims of cardiac arrest. Because of changes in design and the use of alternative waveforms for defibrillation, the modern AED is compact and portable, simple to use, and highly efficacious; in addition, it requires little maintenance. Automated external defibrillators have been used successfully by traditional and nontraditional responders as well as laypersons. In special environments, such as casinos and commercial aircraft, AEDs have performed particularly well. State and federal legislation has eased concerns about AED use by extending legal protection to AED users under Good Samaritan laws. Since the experience continues to be positive, AEDs are being used in increasingly diverse community locations, and public awareness is growing. The American Heart Association's initiative is progressing rapidly.
Loss of Medical Conscience In the Emergency Room
Authors: Preston J. Burnham
Journal: JAMA (1967)

To the Editor:—  A haze distinguishes between a procedure that is done in the operating room and the same procedure that  might as well  in the emergency room. The aims are the same: to  the best for the patient, consistent with high medical standards, with the means available and with concern for the patient's economy and time.  We can be extremists and take every patient with abrasion or gashed muscle to the operating room for absolute sterile precautions and cleanliness.  Or, we can reasonably use essentially the same precautions and techniques and perform the procedure more quickly in the emergency room.  Why, then, is it that many doctors lose their trained senses when they do it in the emergency room, and suture and otherwise treat raw tissues with bare hands, bare faces, and bare heads?
Medical Student Abuse
Authors: Val I. Robichaux
Journal: JAMA (1984)

<h3>To the Editor.—</h3> In reference to the recent article by Rosenberg and Silver,<sup>1</sup>isn't it remarkable that so few of the surveyed medical school deans thought that medical student abuse occurred at their respective institutions? One wonders if they remember their own medical education. I have never met a physician that has not at least witnessed abuse of medical students. How many of us have not seen the shy third-year clerk bullied, berated, and at times humiliated simply for the inability to deliver a polished case presentation or because he or she displayed less than encyclopedic knowledge when grilled by the department chairman on rounds? Because of an extended stint in the military, I did not start college until I was 28 years old. I will always remember my undergraduate years as one of the most enlightening and enjoyable periods of my life. Although I graduated from medical school
Cetirizine Effectively Relieves Both Ocular Allergy Symptoms and Nasal Allergy Symptoms In Subjects With Seasonal Allergic Rhinitis
Authors: Eduardo Urdaneta, Xiaoyan Tian, Mei-Miau Wu, Qiong Du, Kathleen B. Franklin, Mitesh Patel
Journal: Journal of Allergy and Clinical Immunology (2014)
PWE-074 Tissue Inhibitor Of Metalloproteinase (timp)-3 Reduces Pro-inflammatory Cytokine Production By Ulcerative Colitis Mucosa Cultured Ex Vivo
Authors: IM Bell, F Ammoscato, P Biancheri, R Curciarello, T Macdonald
Journal: Gut (2014)

<h3>Introduction</h3> Interleukin (IL)-1b, IL-6, IL-8 and tumour necrosis factor (TNF)-a, are elevated in the inflamed mucosa of patients with ulcerative colitis and play a central role in driving the pro-inflammatory immune response in this condition. TNF-a is cleaved from the cell surface by TNF-a converting enzyme (TACE), which is inhibited by tissue inhibitor of Metalloproteinase (TIMP)-3. We studied whether the addition of TIMP-3 to inflamed colonic biopsies from ulcerative colitis patients reduced the release of the pro-inflammatory cytokines TNF-a, IL-1b, IL-6 and IL-8. <h3>Methods</h3> Colonic biopsies were obtained from macroscopically inflamed areas of 4 patients with ulcerative colitis undergoing colonoscopy for a disease flare. Biopsies were then cultured <i><i>ex vivo</i></i> for 24 h in 300 ul of serum free HL-1 medium in the absence or presence of recombinant human TIMP-3 (100 ng/ml). The concentration of TNF-a, IL-1β, IL-6 and IL-8 were measured in culture supernatants by ELISA. <h3>Results</h3> Culture with TIMP-3 significantly reduced TNF-a production by inflamed ulcerative colitis biopsies cultured <i><i>ex vivo</i></i>(from 1365 ug/ml in the absence of TIMP-3 to 45 ug/ml after TIMP-3 addition). Furthermore, the addition of TIMP-3 significantly reduced IL-1b production by inflamed ulcerative colitis biopsies (from 776 to 261 ug/ml). There was a trend in the reduction of IL-6 (from 3018 to 2702 ug/ml), which did not reach statistic significance, and no significant change in IL-8 production (from 30812 to 29114.5 ug/ml). <h3>Conclusion</h3> TIMP-3 administration not only causes a reduction in TNF-a via TACE inhibition but also IL-1β. This raises the possibility of its use therapeutically in the treatment of ulcerative colitis. <h3>Disclosure of Interest</h3> None Declared.
IMMUNOLOGIC TOLERANCE AFTER SPECIFIC IMMUNIZATION
Authors: Marianne M. Dorner, Jonathan W. Uhr
Journal: The Journal of Experimental Medicine (1964)

Specific immunologic tolerance to bovine serum albumin (BSA) was induced in approximately one-half of the rabbits that had been primarily immunized and were prepared for a secondary antibody response to BSA. The state of tolerance lasted for several months in the majority of rabbits and was not easily terminated by immunization with human serum albumin followed by BSA.
Funding to Boost Mental Health Care
Authors: Bridget M. Kuehn
Journal: JAMA (2014)

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