tbuckley/cabot-search huggingface dataset:
Minimal Residual Disease in Gastric Cancer: Evidence of an Independent Prognostic Relevance of Urokinase Receptor Expression by Disseminated Tumor Cells in the Bone Marrow
Authors: Markus Maria Heiss, Erich H. Simon, Bianca C.M. Beyer, Klaus Uwe Gruetzner, Anwar Tarabichi, Rudolf Babic, Friedrich Wilhelm Schildberg, Heike Allgayer
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To study the invasion-related molecule urokinase-type plasminogen activator receptor (u-PAR) expressed by disseminated tumor cells as a biologic predictor of poor survival in a large prospective series of patients with gastric cancer. PATIENTS AND METHODS: In 156 gastric cancer patients (prospective series), disseminated tumor cells in the bone marrow and the u-PAR expressed by these tumor cells were determined by cytokeratin (CK) 18 immunocytochemistry and u-PAR/CK18 double immunocytochemistry. RESULTS: In contrast to the mere detection of disseminated tumor cells at primary surgery, the additional evidence of u-PAR on these cells correlated significantly with pathologic T stage (P = .0474) and the expression of u-PAR (P = .0093) and plasminogen-activator inhibitor 1 (P = .0145) in the primary tumor (immunohistochemistry, χ 2 ). Kaplan-Meier analysis revealed no association with prognosis for the mere detection of disseminated tumor cells. In contrast, a significant association was seen between detection of u-PAR on these cells and shorter disease-free (P &lt; .0001) and overall survival (P &lt; .0001). Multivariate analysis revealed that u-PAR on disseminated tumor cells at the time of primary surgery is an independent prognostic factor for disease-free (95% confidence interval [CI], 1.72 to 3.21; P = .024) and overall survival (P = .0049; relative risk, 2.89; 95% CI, 1.92 to 4.30). CONCLUSION: This is the first large study to show that u-PAR, detected on disseminated tumor cells in the bone marrow, is an independent prognostic parameter in gastric cancer, in contrast to the mere detection of minimal residual disease (MRD). u-PAR may be a promising marker to define a critical subpopulation of disseminated tumor cells and a target to eliminate MRD. Molecular phenotyping of MRD is critical for defining its individual clinical relevance.
Computed Tomographic Pulmonary Angiography vs Ventilation-Perfusion Lung Scanning in Patients With Suspected Pulmonary Embolism
Authors: David R. Anderson, Susan R. Kahn, Marc A. Rodger, Michael J. Kovacs, Tim Morris, Andrew Hirsch, Eddy Lang, Ian Stiell, George Kovacs, Jon Dreyer, Carol Dennie, Yannick Cartier, David Barnes, Erica Burton, Susan Pleasance, Chris Skedgel, Keith O’Rouke, Philip S. Wells
Journal: JAMA (2007)

Ventilation-perfusion (V(dot)Q(dot) lung scanning and computed tomographic pulmonary angiography (CTPA) are widely used imaging procedures for the evaluation of patients with suspected pulmonary embolism. Ventilation-perfusion scanning has been largely replaced by CTPA in many centers despite limited comparative formal evaluations and concerns about CTPA's low sensitivity (ie, chance of missing clinically important pulmonary embuli).To determine whether CTPA may be relied upon as a safe alternative to V(dot)Q(dot scanning as the initial pulmonary imaging procedure for excluding the diagnosis of pulmonary embolism in acutely symptomatic patients.Randomized, single-blinded noninferiority clinical trial performed at 4 Canadian and 1 US tertiary care centers between May 2001 and April 2005 and involving 1417 patients considered likely to have acute pulmonary embolism based on a Wells clinical model score of 4.5 or greater or a positive D-dimer assay result.Patients were randomized to undergo either V(dot)Q(dot scanning or CTPA. Patients in whom pulmonary embolism was considered excluded did not receive antithrombotic therapy and were followed up for a 3-month period.The primary outcome was the subsequent development of symptomatic pulmonary embolism or proximal deep vein thrombosis in patients in whom pulmonary embolism had initially been excluded.Seven hundred one patients were randomized to CTPA and 716 to V(dot)Q(dot scanning. Of these, 133 patients (19.2%) in the CTPA group vs 101 (14.2%) in the V(dot)Q(dot scan group were diagnosed as having pulmonary embolism in the initial evaluation period (difference, 5.0%; 95% confidence interval [CI], 1.1% to 8.9%) and were treated with anticoagulant therapy. Of those in whom pulmonary embolism was considered excluded, 2 of 561 patients (0.4%) randomized to CTPA vs 6 of 611 patients (1.0%) undergoing V(dot)Q(dot scanning developed venous thromboembolism in follow-up (difference, -0.6%; 95% CI, -1.6% to 0.3%) including one patient with fatal pulmonary embolism in the V(dot)Q(dot group.In this study, CTPA was not inferior to V(dot)Q(dot scanning in ruling out pulmonary embolism. However, significantly more patients were diagnosed with pulmonary embolism using the CTPA approach. Further research is required to determine whether all pulmonary emboli detected by CTPA should be managed with anticoagulant therapy.isrctn.org Identifier: ISRCTN65486961.
Burden of childhood tuberculosis in 22 high-burden countries: a mathematical modelling study
Authors: Peter J Dodd, Elizabeth Gardiner, Renia Coghlan, James A Seddon
Journal: The Lancet Global Health (2014)

BackgroundConfirmation of a diagnosis of tuberculosis in children (aged <15 years) is challenging; under-reporting can result even when children do present to health services. Direct incidence estimates are unavailable, and WHO estimates build on paediatric notifications, with adjustment for incomplete surveillance by the same factor as adult notifications. We aimed to estimate the incidence of infection and disease in children, the prevalence of infection, and household exposure in the 22 countries with a high burden of the disease.MethodsWithin a mechanistic mathematical model, we combined estimates of adult tuberculosis prevalence in 2010, with aspects of the natural history of paediatric tuberculosis. In a household model, we estimated household exposure and infection. We accounted for the effects of age, BCG vaccination, and HIV infection. Additionally, we tested sensitivity to key structural assumptions by repeating all analyses without variation in BCG efficacy by latitude.FindingsThe median number of children estimated to be sharing a household with an individual with infectious tuberculosis in 2010 was 15 319 701 (IQR 13 766 297–17 061 821). In 2010, the median number of Mycobacterium tuberculosis infections in children was 7 591 759 (5 800 053–9 969 780), and 650 977 children (424 871–983 118) developed disease. Cumulative exposure meant that the median number of children with latent infection in 2010 was 53 234 854 (41 111 669–68 959 804). The model suggests that 35% (23–54) of paediatric cases of tuberculosis in the 15 countries reporting notifications by age in 2010 were detected. India is predicted to account for 27% (22–33) of the total burden of paediatric tuberculosis in the 22 countries. The predicted proportion of tuberculosis burden in children for each country correlated with incidence, varying between 4% and 21%.InterpretationOur model has shown that the incidence of paediatric tuberculosis is higher than the number of notifications, particularly in young children. Estimates of current household exposure and cumulative infection suggest an enormous opportunity for preventive treatment.FundingUNITAID and the US Agency for International Development.
Change in cartilage morphometry: a sample of the progression cohort of the Osteoarthritis Initiative
Authors: D J Hunter, J Niu, Y Zhang, S Totterman, J Tamez, C Dabrowski, R Davies, M-P Hellio Le Graverand, M Luchi, Y Tymofyeyev, C R Beals
Journal: Annals of the Rheumatic Diseases (2008)

The performance characteristics of hyaline articular cartilage measurement on magnetic resonance imaging (MRI) need to be accurately delineated before widespread application of this technology. Our objective was to assess the rate of natural disease progression of cartilage morphometry measures from baseline to 1 year in knees with osteoarthritis (OA) from a subset of participants from the Osteoarthritis Initiative (OAI).Subjects included for this exploratory analysis are a subset of the approximately 4700 participants in the OAI Study. Bilateral radiographs and 3T MRI (Siemans Trio) of the knees and clinical data were obtained at baseline and annually in all participants. 160 subjects from the OAI Progression subcohort all of whom had both frequent symptoms and, in the same knee, radiographic OA based on a screening reading done at the OAI clinics were eligible for this exploratory analysis. One knee from each subject was selected for analysis. 150 participants were included. Using sagittal 3D DESSwe (double echo, steady-state sequence with water excitation) MR images from the baseline and 12 follow-up month visit, a segmentation algorithm was applied to the cartilage plates of the index knee to compute the cartilage volume, normalised cartilage volume (volume normalised to bone surface interface area), and percentage denuded area (total cartilage bone interface area denuded of cartilage).Summary statistics of the changes (absolute and percentage) from baseline at 1 year and the standardised response mean (SRM), ie, mean change divided by the SD change were calculated. On average the subjects were 60.9 years of age and obese, with a mean body mass index of 30.3 kg/m2. The SRMs for cartilage volume of various locations are: central medial tibia -0.096; central medial femur -0.394; and patella -0.198. The SRMs for normalised cartilage volume of the various locations are central medial tibia -0.044, central medial femur -0.338 and patella -0.193. The majority of participants had a denuded area at baseline in the central medial femur (62%) and central medial tibia (60%). In general, the SRMs were small.These descriptive results of cartilage morphometry and its change at the 1-year time point from the first substantive MRI data release from the OAI Progression subcohort indicate that the annualised rates of change are small with the central medial femur showing the greatest consistent change.
An Inflammatory Polypeptide Complex from <i>Staphylococcus epidermidis</i>: Isolation and Characterization
Authors: Christopher Mehlin, Catherine M. Headley, Seymour J. Klebanoff
Journal: The Journal of Experimental Medicine (1999)

Staphylococcus epidermidis releases factors that activate the HIV-1 long terminal repeat, induce cytokine release, and activate nuclear factor κB in cells of macrophage lineage. The active material had a mass of 34,500 daltons, was inactivated by proteases and partitioned into the phenol layer on hot aqueous phenol extraction, and thus was termed phenol-soluble modulin (PSM). High performance liquid chromatography (HPLC) of crude PSM yielded two peaks of activity designated PSM peak 1 and peak 2. MALDI-TOF (matrix-assisted laser desorption ionization-time of flight) mass spectroscopy indicated the presence of two components in peak 1, which were designated PSMα and PSMβ. Peak 2 contained a single component, designated PSMγ. Separation of PSMα and PSMβ in peak 1 could be achieved by a second HPLC procedure. The structure of each component was determined by amino acid sequence analysis and identification and sequencing of their genes. PSMα, PSMβ, and PSMγ were 22-, 44-, and 25-amino acid, respectively, strongly hydrophobic polypeptides. PSMγ was identified as Staphylococcus epidermidis delta toxin, whereas PSMα and PSMβ exhibited more distant homology to previously described staphylococcal toxins. They appeared to exist as a complex or aggregate with activity greater than the component parts. The properties of the S. epidermidis PSMs suggest that they may contribute to the systemic manifestations of Gram-positive sepsis.
Joint hypermobility in adults referred to rheumatology clinics.
Authors: A J Bridges, E Smith, J Reid
Journal: Annals of the Rheumatic Diseases (1992)

Joint hypermobility is a rarely recognised aetiology for focal or diffuse musculoskeletal symptoms. To assess the occurrence and importance of joint hypermobility in adult patients referred to a rheumatologist, we prospectively evaluated 130 consecutive new patients for joint hypermobility. Twenty women (15%) had joint hypermobility at three or more locations (greater than or equal to 5 points on a 9 point scale). Most patients with joint hypermobility had common musculoskeletal problems as the reason for referral. Two patients referred with a diagnosis of rheumatoid arthritis were correctly reassigned a diagnosis of hypermobility syndrome. Three patients with systemic lupus erythematosus had diffuse joint hypermobility. There was a statistically significant association between diffuse joint hypermobility and osteoarthritis. Most patients (65%) had first degree family members with a history of joint hypermobility. These results show that joint hypermobility is common, familial, found in association with common rheumatic disorders, and statistically associated with osteoarthritis. The findings support the hypothesis that joint hypermobility predisposes to musculoskeletal disorders, especially osteoarthritis.
Effect of Nitroxoline on Angiogenesis and Growth of Human Bladder Cancer
Authors: Joong Sup Shim, Yoshiyuki Matsui, Shridhar Bhat, Benjamin A. Nacev, Jing Xu, Hyo-eun C. Bhang, Surajit Dhara, Kee Chung Han, Curtis R. Chong, Martin G. Pomper, Alan So, Jun O. Liu
Journal: JNCI Journal of the National Cancer Institute (2010)

Angiogenesis plays an important role in tumor growth and metastasis; therefore, inhibition of angiogenesis is a promising strategy for developing new anticancer drugs. Type 2 methionine aminopeptidase (MetAP2) protein is likely a molecular target of angiogenesis inhibitors. Nitroxoline, an antibiotic used to treat urinary tract infections, was identified from a high-throughput screen of a library of 175 000 compounds for MetAP2 inhibitors and from a parallel screen using the Johns Hopkins Drug Library to identify currently used clinical drugs that can also inhibit human umbilical vein endothelial cells (HUVEC) proliferation. To investigate the mechanism of action of nitroxoline, inhibition of MetAP2 activity and induction of senescence were assessed in HUVEC. To test the antiangiogenic activity of nitroxoline, endothelial tube formation in Matrigel and microvessel formation in Matrigel plugs in vivo were assessed. Antitumor efficacy of nitroxoline was evaluated in mouse models of human breast cancer xenograft (n = 10) and bladder cancer orthotopic xenograft (n = 11). Furthermore, the mechanism of action of nitroxoline was investigated in vivo. Nitroxoline inhibited MetAP2 activity in vitro (half maximal inhibitory concentration [IC50] = 54.8 nM, 95% confidence interval [CI] = 22.6 to 132.8 nM) and HUVEC proliferation (IC50 = 1.9 μM, 95% CI = 1.54 to 2.39 μM). Nitroxoline inhibited MetAP2 activity in HUVEC in a dose-dependent manner and induced premature senescence in a biphasic manner. Nitroxoline inhibited endothelial tube formation in Matrigel and reduced microvessel density in vivo. Mice (five per group) treated with nitroxoline showed a 60% reduction in tumor volume in breast cancer xenografts (tumor volume on day 30, vehicle vs nitroxoline, mean = 215.4 vs 86.5 mm3, difference = 128.9 mm3, 95% CI = 32.9 to 225.0 mm3, P = .012) and statistically significantly inhibited growth of bladder cancer in an orthotopic mouse model (tumor bioluminescence intensities of vehicle [n = 5] vs nitroxoline [n = 6], P = .045). Nitroxoline shows promise as a potential therapeutic antiangiogenic agent.
Outcomes of Combined Cardiovascular Risk Factor Management Strategies in Type 2 Diabetes: The ACCORD Randomized Trial
Authors: Karen L. Margolis, Patrick J. O’Connor, Timothy M. Morgan, John B. Buse, Robert M. Cohen, William C. Cushman, Jeffrey A. Cutler, Gregory W. Evans, Hertzel C. Gerstein, Richard H. Grimm, Edward W. Lipkin, K.M.Venkat Narayan, Matthew C. Riddle, Ajay Sood, David C. Goff
Journal: Diabetes Care (2014)

To compare effects of combinations of standard and intensive treatment of glycemia and either blood pressure (BP) or lipids in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.
Anthrax toxins suppress T lymphocyte activation by disrupting antigen receptor signaling
Authors: Silvia Rossi Paccani, Fiorella Tonello, Raffaella Ghittoni, Mariarita Natale, Lucia Muraro, Mario Milco D'Elios, Wei-Jen Tang, Cesare Montecucco, Cosima T. Baldari
Journal: The Journal of Experimental Medicine (2005)

Anthrax is an infection caused by pathogenic strains of Bacillus anthracis, which secretes a three-component toxic complex consisting of protective antigen (PA), edema factor (EF), and lethal factor (LF). PA forms binary complexes with either LF or EF and mediates their entry into host cells. Although the initial phases of bacterial growth occur in the lymph node, the host fails to mount an effective immune response. Here, we show that LT and ET are potent suppressors of human T cell activation and proliferation triggered through the antigen receptor. Both LT and ET inhibit the mitogen-activated protein and stress kinase pathways, and both toxins inhibit activation of NFAT and AP-1, two transcription factors essential for cytokine gene expression. These data identify a novel strategy of immune evasion by B. anthracis, based on both effector subunits of the toxic complex, and targeted to a key cellular component of adaptive immunity.
The Infant Gut Microbiome Mediates the Association Between Breastfeeding and Allergic-like Response to Pets in Children
Authors: Alexandra R. Sitarik, Suzanne Havstad, Albert M. Levin, Kei Fujimura, Ganesa R. Wegienka, Edward M. Zoratti, Dennis R. Ownby, Haejin Kim, Homer A. Boushey, Susan V. Lynch, Christine Cole Johnson
Journal: Journal of Allergy and Clinical Immunology (2015)
Place your bet and show us your hand
Authors: H.C. Williams
Journal: British Journal of Dermatology (2015)

Journal Article Place your bet and show us your hand Get access H.C. Williams H.C. Williams Department of Dermatology Queen's Medical Centre Nottingham U.K Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 173, Issue 4, 1 October 2015, Pages 1104–1105, https://doi.org/10.1111/bjd.13944 Published: 01 October 2015
S100A7 Enhances Mammary Tumorigenesis through Upregulation of Inflammatory Pathways
Authors: Mohd W. Nasser, Zahida Qamri, Yadwinder S. Deol, Janani Ravi, Catherine A. Powell, Prashant Trikha, Reto A. Schwendener, Xue-Feng Bai, Konstantin Shilo, Xianghong Zou, Gustavo Leone, Ronald Wolf, Stuart H. Yuspa, Ramesh K. Ganju
Journal: Cancer Research (2011)

S100A7/psoriasin, a member of the epidermal differentiation complex, is widely overexpressed in invasive estrogen receptor (ER)α-negative breast cancers. However, it has not been established whether S100A7 contributes to breast cancer growth or metastasis. Here, we report the consequences of its expression on inflammatory pathways that impact breast cancer growth. Overexpression of human S100A7 or its murine homologue mS100a7a15 enhanced cell proliferation and upregulated various proinflammatory molecules in ERα-negative breast cancer cells. To examine in vivo effects, we generated mice with an inducible form of mS100a7a15 (MMTV-mS100a7a15 mice). Orthotopic implantation of MVT-1 breast tumor cells into the mammary glands of these mice enhanced tumor growth and metastasis. Compared with uninduced transgenic control mice, the mammary glands of mice where mS100a7a15 was induced exhibited increased ductal hyperplasia and expression of molecules involved in proliferation, signaling, tissue remodeling, and macrophage recruitment. Furthermore, tumors and lung tissues obtained from these mice showed further increases in prometastatic gene expression and recruitment of tumor-associated macrophages (TAM). Notably, in vivo depletion of TAM inhibited the effects of mS100a7a15 induction on tumor growth and angiogenesis. Furthermore, introduction of soluble hS100A7 or mS100a7a15 enhanced chemotaxis of macrophages via activation of RAGE receptors. In summary, our work used a powerful new model system to show that S100A7 enhances breast tumor growth and metastasis by activating proinflammatory and metastatic pathways.
Pegylated Arginine Deiminase Treatment of Patients With Metastatic Melanoma: Results From Phase I and II Studies
Authors: Paolo A. Ascierto, Stefania Scala, Giuseppe Castello, Antonio Daponte, Ester Simeone, Alessandro Ottaiano, Gerardo Beneduce, Vincenzo De Rosa, Francesco Izzo, Maria Teresa Melucci, C. Mark Ensor, Archie W. Prestayko, Frederick W. Holtsberg, John S. Bomalaski, Mike A. Clark, Niramol Savaraj, Lynn G. Feun, Theodore F. Logan
Journal: Journal of Clinical Oncology (2005)

Purpose Individuals with metastatic melanoma have a poor prognosis. Many human melanomas are auxotrophic for arginine, and arginine is not an essential amino acid in humans. We hypothesized that this auxotrophy may be therapeutically exploited. A novel amino acid–degrading enzyme (arginine deiminase) conjugated to polyethylene glycol (ADI-SS PEG 20,000 mw) was used to lower plasma arginine in individuals with metastatic melanoma. Patients and Methods Two cohort dose-escalation studies were performed. A phase I study in the United States enrolled 15 patients, and a phase I to II study in Italy enrolled 24 patients. The Italian patients also received two subsequent cycles of treatment, each consisting of four once-weekly injections of 160 U/m 2 . The goals of these studies were to determine pharmacokinetics (PK), pharmacodynamics (PD), safety, and the antitumor activity of ADI-SS PEG 20,000 mw. Results PK and PD studies indicated that a dose of 160 U/m 2 lowered plasma arginine from a resting level of approximately 130 μmol/L to less than 2 μmol/L for at least 7 days; nitric oxide levels also were lowered. There were no grade 3 or 4 toxicities directly attributable to the drug. Six of 24 phase I to II patients responded to treatment (five partial responses and one complete response; 25% response rate) and also had prolonged survival. Conclusion Elimination of all detectable plasma arginine in patients with metastatic melanoma was well tolerated and may be effective in the treatment of this cancer. Further testing of ADI-SS PEG 20,000 mw in a larger population of individuals with metastatic melanoma is warranted.
Prinzmetal angina. Normal arteries and multifocal electrocardiographic changes
Authors: L. J. Haywood
Journal: JAMA (1976)

A 40-year-old man with severe angina had electrocardiographic changes typical of Prinzmetal angina during his attacks of chest pain. ST segment elevations in leads II, III, and aVF occurred intermittently with elevations in leads I and aVL, and with T wave flattening in V1, suggesting myocardial ischemia in areas supplied by the right coronary artery and by the circumflex branch of the left coronary artery. However, the coronary arteries appeared normal when arteriograms were made, suggesting that a reversible event caused the attacks.
Variation Among Primary Care Physicians in Prostate-Specific Antigen Screening of Older Men
Authors: Elizabeth Jaramillo, Alai Tan, Liu Yang, Yong-Fang Kuo, James S. Goodwin
Journal: JAMA (2013)

No organization recommends prostate-specific antigen (PSA) screening in men older than 75 years. Nevertheless, testing rates remain high.1,2 We hypothesized that primary care physicians (PCPs) would vary substantially in PSA screening rates and that much of the variance in whether an older man received a PSA test would depend on which PCP he saw.