tbuckley/cabot-search huggingface dataset:
Pulmonary mass in a 19-year-old male
Authors: Laura-Jane E Smith, David R Lawrence, Irfan Kayani, Arrigo Capitanio, Mary Falzon, Sam M Janes, Neal Navani
Journal: Thorax (2011)

Pulmonary mass in a 19-year-old male CLINICAL PRESENTATIONA 19-year-old student who had never smoked presented with a 6-month history of cough, wheeze, sputum production and generalised fatigue.His exercise tolerance was unaffected and he continued to play rugby competitively.He had a history of childhood asthma and received treatment with inhaled salbutamol with no effect.A chest x-ray revealed a round density at the base of the right lung.A CT chest was performed (figure 1) and subsequently a 68 Ga-DOTATATE (1,4,7,10-tetraazacyclododecane-N,N 9 ,N 99 ,N 999tetraacetic acid-d-Phe(1),Tyr(3)-octreotate) PET-CT (positron emission tomography-CT) was arranged, demonstrating that the mass had a maximum standardised uptake value of 6.6 (figure 2).He was referred for a right lower lobectomy.Histological evaluation of the lobectomy specimen demonstrated bland spindle cell proliferation with a prominent inflammatory infiltrate.Immunohistochemical staining was positive for vimentin, smooth muscle actin and cytokeratin AE1/AE3, and negative for desmin, caldesmon, calponin, ALK1 and CD34.
Proteasome alpha-type subunit C9 is a primary target of autoantibodies in sera of patients with myositis and systemic lupus erythematosus.
Authors: E Feist, T Dörner, U Kuckelkorn, G Schmidtke, B Micheel, F Hiepe, G R Burmester, P M Kloetzel
Journal: The Journal of Experimental Medicine (1996)

Autoantibodies occur in low frequencies among patients with myositis characterizing only distinct subsets of this disease. Most of these known antibodies are directed to enzymatically active complexes. The 20S proteasome represents an essential cytoplasmatic protein complex for intracellular nonlysosomal protein degradation, and is involved in major histocompatibility complex class I restricted antigen processing. In this study we investigated whether the 20S proteasome complex is an antibody target in myositis and in other autoimmune diseases. 34 sera of poly/dermatomyositis patients were assayed for antiproteasomal antibodies using enzyme-linked immunosorbent assay, immunoblot, and two-dimensional non-equilibrium pH gradient electrophoresis (NEPHGE). Sera was from patients with systemic lupus erythematosus (SLE), mixed connective tissue disease, and rheumatoid arthritis; healthy volunteers served as controls. In 62% (21/34) of the cases sera from patients with myositis and in 58% (30/52) of the cases sera from patients with SLE reacted with the 20S proteasome. These frequencies exceeded those of sera from patients with mixed connective tissue disease, rheumatoid arthritis, and healthy controls. The alpha-type subunit C9 of the 20S proteasome was determined to be the predominant target of the autoimmune sera in myositis and SLE. Lacking other frequent autoantibodies in myositis, the antiproteasome antibodies are the most common humoral immune response so far detected in this disease entity.
Long-Term Risk of Clinical Progression After Biochemical Recurrence Following Radical Prostatectomy: The Impact of Time from Surgery to Recurrence
Authors: Stephen A. Boorjian, R. Houston Thompson, Matthew K. Tollefson, Laureano J. Rangel, Eric J. Bergstralh, Michael L. Blute, R. Jeffrey Karnes
Journal: European Urology (2011)
Microfluidic Reactors for Diagnostics Applications
Authors: Stephanie E. McCalla, Anubhav Tripathi
Journal: Annual Review of Biomedical Engineering (2011)

Diagnostic assays are an important part of health care, both in the clinic and in research laboratories. In addition to improving treatments and clinical outcomes, rapid and reliable diagnostics help track disease epidemiology, curb infectious outbreaks, and further the understanding of chronic illness. Disease markers such as antigens, RNA, and DNA are present at low concentrations in biological samples, such that the majority of diagnostic assays rely on an amplification reaction before detection is possible. Ideally, these amplification reactions would be sensitive, specific, inexpensive, rapid, integrated, and automated. Microfluidic technology currently in development offers many advantages over conventional benchtop reactions that help achieve these goals. The small reaction volumes and energy consumption make reactions cheaper and more efficient in a microfluidic reactor. Additionally, the channel architecture could be designed to perform multiple tests or experimental steps on one integrated, automated platform. This review explores the current research on microfluidic reactors designed to aid diagnostic applications, covering a broad spectrum of amplification techniques and designs.
Pancreatic endocrine tumours: mutational and immunohistochemical survey of protein kinases reveals alterations in targetable kinases in cancer cell lines and rare primaries
Authors: V. Corbo, S. Beghelli, S. Bersani, D. Antonello, G. Talamini, M. Brunelli, P. Capelli, M. Falconi, A. Scarpa
Journal: Annals of Oncology (2011)

BackgroundKinases represent potential therapeutic targets in pancreatic endocrine tumours (PETs).Patients and methodsThirty-five kinase genes were sequenced in 36 primary PETs and three PET cell lines: (i) 4 receptor tyrosine kinases (RTK), epithelial growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), tyrosine-protein kinase KIT (KIT), platelet-derived growth factor receptor alpha (PDGFRalpha); (ii) 6 belonging to the Akt/mTOR pathway; and (iii) 25 frequently mutated in cancers. The immunohistochemical expression of the four RTKs and the copy number of EGFR and HER2 were assessed in 140 PETs.ResultsSomatic mutations were found in KIT in one and ATM in two primary neoplasms. Among 140 PETs, EGFR was immunopositive in 18 (13%), HER2 in 3 (2%), KIT in 16 (11%), and PDGFRalpha in 135 (96%). HER2 amplification was found in 2/130 (1.5%) PETs. KIT membrane immunostaining was significantly associated with tumour aggressiveness and shorter patient survival. PET cell lines QGP1, CM and BON harboured mutations in FGFR3, FLT1/VEGFR1 and PIK3CA, respectively.ConclusionsOnly rare PET cases, harbouring either HER2 amplification or KIT mutation, might benefit from targeted drugs. KIT membrane expression deserves further attention as a prognostic marker. ATM mutation is involved in a proportion of PET. The finding of specific mutations in PET cell lines renders these models useful for preclinical studies involving pathway-specific therapies.
Apoptosis
Authors: Brian O’Rourke
Journal: Circulation Research (1999)

A n explosion of information has recently emerged highlighting the role of mitochondria in the life and death of cells.The function of mitochondria as the arbiters of a complex signaling cascade urging the cell to its own orchestrated demise is one of a number of new findings fueling a renewed interest in this essential organelle.Perhaps in no other tissue is it more important to maintain mitochondrial function and prevent cell dropout than in cardiac muscle.Pump function quickly fails when the constant high-energy demand of contraction is not met by the efficient generation of ATP through mitochondrial oxidative phosphorylation, and if cell death is triggered in the adult heart, regardless of whether it is through necrotic or apoptotic pathways, there is no way to regenerate lost myocytes.
Association between DNA variant sites in the apolipoprotein A5 gene and coronary heart disease in Chinese
Authors: Hekun Liu, Sizhong Zhang, Jianyin Lin, Hai Li, Aimin Huang, Cuiying Xiao, Xuefei Li, Zhiguang Su, Chunting Wang, Daniel W. Nebert, Bing Zhou, Keqin Zheng, Jiajun Shi, Guixin Li, Dejia Huang
Journal: Metabolism (2005)
Detailed characterization of tumor infiltrating lymphocytes in two distinct human solid malignancies show phenotypic similarities
Authors: Magdalena Kovacsovics-Bankowski, Lana Chisholm, Jonna Vercellini, Christopher G Tucker, Ryan Montler, Daniel Haley, Philippa Newell, Jun Ma, Paul Tseng, Ronald Wolf, John T Vetto, Chet Hammill, Paul Hansen, Andrew D Weinberg
Journal: Journal for ImmunoTherapy of Cancer (2014)

<h3>Background</h3> We examined the phenotype and function of lymphocytes collected from the peripheral blood (PBL) and tumor (TIL) of patients with two different solid malignancies: colorectal cancer liver metastases (CRLM) and ovarian cancer (OVC). <h3>Methods</h3> Tumor and corresponding peripheral blood were collected from 16 CRLM and 22 OVC patients; immediately following resection they were processed and analyzed using a multi-color flow cytometry panel. Cytokine mRNA from purified PBL and TIL CD4<sup>+</sup> T cells were also analyzed by qPCR. <h3>Results</h3> Overall, we found similar changes in the phenotypic and cytokine profiles when the TIL were compared to PBL from patients with two different malignancies. The percentage of Treg (CD4<sup>+</sup>/CD25<sup>+</sup>/FoxP3<sup>+</sup>) in PBL and TIL was similar: 8.1% versus 10.2%, respectively in CRLM patients. However, the frequency of Treg in primary OVC TIL was higher than PBL: 19.2% versus 4.5% (p &lt;0.0001). A subpopulation of Treg expressing HLA-DR was markedly increased in TIL compared to PBL in both tumor types, CRLM: 69.0% versus 31.7% (p = 0.0002) and OVC 74.6% versus 37.0% (p &lt;0.0001), which suggested preferential Treg activation within the tumor. The cytokine mRNA profile showed that IL-6, a cytokine known for its immunosuppressive properties through STAT3 upregulation, was increased in TIL samples in patients with OVC and CRLM. Both TIL populations also contained a significantly higher proportion of activated CD8<sup>+</sup> T cells (HLA-DR<sup>+</sup>/CD38<sup>+</sup>) compared to PBL (CRLM: 30.2% vs 7.7%, (p = 0.0012), OVC: 57.1% vs 12.0%, (p &lt;0.0001)). <h3>Conclusion</h3> This study demonstrates that multi-color flow cytometry of freshly digested tumor samples reveals phenotypic differences in TIL vs PBL T cell sub-populations. The TIL composition in primary and metastatic tumors from two distinct histologies were remarkably similar, showing a greater proportion of activated/suppressive Treg (HLA-DR<sup>+</sup>, CD39<sup>+</sup>, CTLA-4<sup>+</sup> and Helios<sup>+</sup>) and activated cytotoxic T cells (CD8<sup>+</sup>/HLA-DR<sup>+</sup>/CD38<sup>+</sup>) when compared to PBL and an increase in IL-6 mRNA from CD4 TIL.
Galileo would have loved sports biomechanics, digitised ECG and his smartphone
Authors: Ben Clarsen, Hilde Moseby Berge
Journal: British Journal of Sports Medicine (2014)

Galileo Galilei (1564–1642) is often referred to as the father of modern science. Initially a medical student, his obsession with measurement soon turned him to physics, mathematics and astronomy. Galileo was the first to accurately measure time by harnessing the principles of the pendulum and his improvements of the telescope led to massive advances in the fields of physics and astronomy. In particular, he provided the first empirical evidence that the earth revolved around the sun, and not vice versa. The 17th century's ‘Steve Jobs’ figure, Galileo invented the microscope, thermometer and compass. Just as Jobs revolutionised our thinking towards mobile computing by promising ‘a thousand songs in your pocket’, Galileo rocked his world by saying ‘measure all that is measurable, and make measurable what is not.’

Is our digital revolution going be considered another ‘golden age’? For sports clinicians and scientists, technological advances are opening up possibilities we could previously only dream of, particularly when it comes to measuring what was previously …
Pulmonary rehabilitation and the BODE index in COPD
Authors: C. G. Cote, B. R. Celli
Journal: European Respiratory Journal (2005)

The BODE index, which integrates body mass index, airflow limitation (forced expiratory volume in one second), dyspnoea and 6-min walk distance, predicts mortality in chronic obstructive pulmonary disease (COPD). Pulmonary rehabilitation (PR) improves some components of BODE. It was hypothesised that changes in BODE may reflect the effects of PR. To test this, participation in PR was offered to 246 patients (BODE quartiles 2-4). The patients were divided as follows: no PR (130 who declined rehabilitation or who dropped out from PR), and PR (116 who completed PR). BODE was determined at entry, after PR, and at 1 and 2 yrs. Other outcomes were: length of stay (LOS) for respiratory-related hospitalisations and mortality. At entry, the two groups had similar age and comorbidity but different BODE. After PR, the BODE improved by 19% and returned to baseline after 2 yrs. The BODE worsened in the no PR group by 4% at 12 months and 18% at 2 yrs. Respiratory mortality at 2 yrs for PR was 7%, compared with 39% for no PR. LOS at 1 yr for COPD decreased 20% in PR, while it increased 25% in no PR. In conclusion, pulmonary rehabilitation participation improves BODE and is associated with better outcomes. The BODE index change after pulmonary rehabilitation provides valuable prognostic information.
Deletion of thioredoxin-interacting protein in mice impairs mitochondrial function but protects the myocardium from ischemia-reperfusion injury
Authors: Jun Yoshioka, William A. Chutkow, Samuel Lee, Jae Bum Kim, Jie Yan, Rong Tian, Merry L. Lindsey, Edward P. Feener, Christine E. Seidman, Jonathan G. Seidman, Richard T. Lee
Journal: Journal of Clinical Investigation (2011)

Classic therapeutics for ischemic heart disease are less effective in individuals with the metabolic syndrome. As the prevalence of the metabolic syndrome is increasing, better understanding of cardiac metabolism is needed to identify potential new targets for therapeutic intervention. Thioredoxin-interacting protein (Txnip) is a regulator of metabolism and an inhibitor of the antioxidant thioredoxins, but little is known about its roles in the myocardium. We examined hearts from Txnip-KO mice by polony multiplex analysis of gene expression and an independent proteomic approach; both methods indicated suppression of genes and proteins participating in mitochondrial metabolism. Consistently, Txnip-KO mitochondria were functionally and structurally altered, showing reduced oxygen consumption and ultrastructural derangements. Given the central role that mitochondria play during hypoxia, we hypothesized that Txnip deletion would enhance ischemia-reperfusion damage. Surprisingly, Txnip-KO hearts had greater recovery of cardiac function after an ischemia-reperfusion insult. Similarly, cardiomyocyte-specific Txnip deletion reduced infarct size after reversible coronary ligation. Coordinated with reduced mitochondrial function, deletion of Txnip enhanced anaerobic glycolysis. Whereas mitochondrial ATP synthesis was minimally decreased by Txnip deletion, cellular ATP content and lactate formation were higher in Txnip-KO hearts after ischemia-reperfusion injury. Pharmacologic inhibition of glycolytic metabolism completely abolished the protection afforded the heart by Txnip deficiency under hypoxic conditions. Thus, although Txnip deletion suppresses mitochondrial function, protection from myocardial ischemia is enhanced as a result of a coordinated shift to enhanced anaerobic metabolism, which provides an energy source outside of mitochondria.
ASCO 2011: Broadening the Horizons of Cancer Research
Authors: K. Crane
Journal: JNCI Journal of the National Cancer Institute (2011)

Clinical Oncology (ASCO) meetingthe world ' s largest conference dedicated to advancing research on cancerone session played the devil ' s advocate: Why is cancer research failing?Citing the sobering statistic that 900 people in the U.S. die of cancer every day, Lee Ellis, M.D. , of the University of Texas MD Anderson Cancer Center in Houston, and colleagues dedicated a panel discussion to understanding how cancer research can be improved.Part of the problem, Ellis said, starts with faulty mouse models.Because tumors in mice grow much faster than they do in humans, and agents target rapidly dividing cells, results may often end up positive in mice.He added that
p50 Nuclear Factor-κB Overexpression in Tumor-Associated Macrophages Inhibits M1 Inflammatory Responses and Antitumor Resistance
Authors: Alessandra Saccani, Tiziana Schioppa, Chiara Porta, Subhra K. Biswas, Manuela Nebuloni, Luca Vago, Barbara Bottazzi, Mario P. Colombo, Alberto Mantovani, Antonio Sica
Journal: Cancer Research (2006)

Abstract Tumor-associated macrophages (TAM) are a major inflammatory infiltrate in tumors and a major component of the protumor function of inflammation. TAM in established tumors generally have an M2 phenotype with defective production of interleukin-12 (IL-12) and high IL-10. Here, we report that defective responsiveness of TAM from a murine fibrosarcoma and human ovarian carcinoma to M1 activation signals was associated with a massive nuclear localization of the p50 nuclear factor-κB (NF-κB) inhibitory homodimer. p50 overexpression inhibited IL-12 expression in normal macrophages. TAM isolated from p50−/− mice showed normal production of M1 cytokines, associated with reduced growth of transplanted tumors. Bone marrow chimeras showed that p50 inactivation in hematopoietic cells was sufficient to result in reduced tumor growth. Thus, p50 NF-κB overexpression accounts for the inability of TAM to mount an effective M1 antitumor response capable of inhibiting tumor growth. (Cancer Res 2006; 66(23): 11432-40)
Reader's guide to critical appraisal of cohort studies: 1. Role and design
Authors: Paula A Rochon, Jerry H Gurwitz, Kathy Sykora, Muhammad Mamdani, David L Streiner, Susan Garfinkel, Sharon-Lise T Normand, M Geoffrey
Journal: BMJ (2005)

Cohort studies can provide valuable information unavailable from randomised trials, but readers need to be alert to possible flaws
Matched and Mismatched Allogeneic Stem-Cell Transplantation From Unrelated Donors Using Combined Graft-Versus-Host Disease Prophylaxis Including Rabbit Anti–T Lymphocyte Globulin
Authors: Jürgen Finke, Claudia Schmoor, Helmut Lang, Karin Potthoff, Hartmut Bertz
Journal: Journal of Clinical Oncology (2003)

With improved HLA-typing techniques, it is presently unclear what degree of identity is necessary for successful unrelated-donor stem-cell transplantation (UD SCT). Here, we describe the outcome after matched and mismatched UD SCT using a graft-versus-host disease (GVHD) prophylaxis including high-dose rabbit anti-T lymphocyte globulin (ATG).One hundred adult patients (median age, 37 years; range, 17 to 65 years) with hematologic malignancies underwent transplantation in early disease (first complete remission [CR1] or first chronic phase [CP1]; n = 34) or in advanced disease (second complete remission or second chronic phase, no remission, refractory; n = 66) with nondepleted bone marrow (n = 87) or peripheral-blood-derived (n = 13) stem cells from an HLA-A, HLA-B, HLA-DRB1*, or HLA-DQB1* identical (n = 75) or mismatched (one antigen, n = 21; two to three antigens, n = 4) unrelated donor. GVHD prophylaxis consisted of rabbit ATG before transplantation in addition to cyclosporine and short-course methotrexate.The cumulative incidence of acute GVHD degrees II- degrees IV was 21% (95% confidence interval [CI], 14% to 33%) and 20% (95% CI, 9% to 44%) and acute GVHD degrees III- degrees IV was 5.3% (95% CI, 2% to 14%) and 4% (95% CI, 0.6% to 28%) in HLA-matched and HLA-mismatched transplantations, respectively. The risk for extensive chronic GVHD was 43% (95% CI, 32% to 59%) and 44% (95% CI, 26% to 75%) for HLA-matched and HLA-mismatched patients, respectively. The risk of relapse at 4 years was 17% (95% CI, 7% to 43%) and 43% (95% CI, 31% to 60%) for CR1/CP1 and advanced disease patients, respectively. With a median follow-up of 1,068 days (range, 12 to 1,958 days), 3-year disease-free and overall survival for patients who underwent transplantation in CR1/CP1 was 63% (95% CI, 46% to 81%) and 75% (95% CI, 59% to 90%), respectively; and for patients with advanced disease, it was 34% (95% CI, 22% to 46%) and 39% (95% CI, 25% to 53%), respectively.A certain degree of one antigen mismatching may not compromise the outcome after UD SCT when using this rabbit ATG in addition to standard GVHD prophylaxis regimen.
Clinical manifestations of antiphospholipid syndrome (APS) with and without antiphospholipid antibodies (the so-called ‘seronegative APS’)
Authors: Jose Luis Rodriguez-Garcia, Maria Laura Bertolaccini, Maria Jose Cuadrado, Giovanni Sanna, Oier Ateka-Barrutia, Munther A Khamashta
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objectives</h3> Although the medical literature currently provides a growing number of isolated case reports of patients with clinically well-defined antiphospholipid syndrome (APS) and persistently negative antiphospholipid antibodies (aPL), there are no studies including a series of patients addressing the clinical features of this condition. <h3>Methods</h3> The authors assessed clinical manifestations of APS in 154 patients: 87 patients with seropositive APS and 67 patients with thrombosis and/or pregnancy morbidity persistently negative for aPL and presenting with at least two additional non-criteria manifestations of APS (the so-called 'seronegative APS', SN-APS). Patients were interviewed at the time of recruitment, and a retrospective file review was carried out. <h3>Results</h3> There were no significant differences in the frequency of thrombotic events or obstetric morbidity in patients with SN-APS versus patients with seropositive APS: deep vein thrombosis (31.4% vs 31.0%), pulmonary embolism (23.8% vs 28.7%), stroke (14.9% vs 17.2%), transient ischaemic attack (11.9% vs 10.3%), early spontaneous abortions (67.1% vs 52.1%), stillbirths (62.5% vs 59.4%), prematurity (28.1% vs 21.7%) or pre-eclampsia (28.1% vs 23.1%). <h3>Conclusions</h3> Classic and SN-APS patients show similar clinical profiles. The results suggest that clinical management in patients with APS should not be based only on the presence of conventional aPL.
Nitrite regulation of shock
Authors: A. Cauwels, P. Brouckaert
Journal: Cardiovascular Research (2010)

Severe sepsis and septic shock, which are among the most common causes of death in intensive care units worldwide, cause high morbidity, mortality, and social and economic costs. Therefore, developing successful therapies against sepsis is one of the most important challenges in critical care medicine. Death from septic shock is caused by refractory hypotension and multiple organ failure (MOF). Although excessive systemic vasodilation triggered by nitric oxide (NO) is believed to mediate the hypotension, several endogenous factors and phenomena are responsible for MOF, including tissue hypoperfusion and ischaemia, mitochondrial dysfunction, and other cytotoxic effects, all of which might be directly or indirectly antagonized by local NO. Hence, selective inhibition of the production of hypotension-causing NO in the macrocirculation and/or selective treatment with microvasculature-specific NO donors could theoretically constitute a successful therapy. Recently, the NO metabolite nitrite was recognized as an NO donor specifically in hypoxic/acidic conditions, which can be expected in the septic microvasculature. We recently showed that treatment with nitrite can protect mice against progressive hypothermia, mitochondrial dysfunction, organ damage, and even death induced by tumour necrosis factor or lipopolysaccharide. In this review, we discuss the rationale for using nitrite for the treatment of shock, the possible mechanisms of nitrite-mediated protection, and the lessons that can be drawn for possible future translation of the results from mouse models to the clinic.
New battlefields for costimulation
Authors: Natalia Martin-Orozco, Chen Dong
Journal: The Journal of Experimental Medicine (2006)

Costimulation regulates the activation of naive T cells as they first encounter antigens in the secondary lymphoid organs. But recently characterized costimulatory molecules of the B7 family appear to have roles beyond initial T cell activation. New evidence shows that negative costimulators expressed by tumors and normal tissues afford local protection from T cell-mediated attack.