tbuckley/cabot-search huggingface dataset:
Motility and Adhesiveness in Human Neutrophils
Authors: C. Wayne Smith, James C. Hollers
Journal: Journal of Clinical Investigation (1980)

Human peripheral blood neutrophils obtained from healthy adults were examined in vitro. We assessed the effects of sequential stepwise increases in the concentration of the chemotactic dipeptide N-formyl-l-methionyl-l-phenylalanine (f-Met-Phe) on neutrophil attachment to serum-coated glass, detachment from serum-coated glass and the distribution on the cell surface of binding sites for albumin-coated latex beads. The initial exposure to f-Met-Phe resulted in increased adhesiveness and binding of latex beads in a random pattern over the cell surface. The second exposure to f-Met-Phe resulted in decreased adherence, detachment of neutrophils from serum-coated glass, and movement of binding sites for latex beads to the uropod. Enhanced adhesiveness and redistribution of binding sites were blocked by 0.1 mM N-α-p-tosyl-l-lysine chloromethyl ketone, a concentration that did not reduce the change in cellular shape caused by f-Met-Phe. Cytochalasin B (5 μg/ml) blocked the redistribution of binding sites as well as the change in shape. The third exposure to f-Met-Phe was given along with the latex beads. The stimulus was stopped after 2 min by fixing cells in suspension with glutaraldehyde. If the third exposure was at a concentration higher than the second, the beads were bound in the region of the lamellipodia in 70% of the cells. If lower, binding to the lamellipodia was found in a significantly smaller proportion of cells (13%). The results support the concept that neutrophils develop a polarized distribution of f-Met-Phe-induced adhesion sites in response to increasing concentrations of f-Met-Phe, and these sites flow from the region of the lamellipodia to the uropod.
Siah2 in pulmonary hypertension and right ventricular hypertrophy
Authors: Daniela Haag, Dorothea M. Peters, Bakytbek Kojonazarov, Simone Kraut, Hossein A. Ghofrani, Ralph T. Schermuly, Werner Seeger, Friedrich Grimminger, Andreas Möller, M. Lienhard Schmitz, Norbert Weissmann
Journal: European Respiratory Journal (2013)

Pulmonary hypertension (PH) is a disease of multifactorial etiology, which has a poor prognosis. It results in right heart hypertrophy which can culminate in decompensation and death. This study investigated the role of seven in absentia homologue 2 (Siah2) ubiquitin ligase in the pathogenesis of pulmonary vascular and right ventricular (RV) remodelling. Siah2 regulates Hypoxia-inducible factor-1α (HIF-1α) which plays a pivotal role in the pathogenesis of PH and RV hypertrophy by influencing cell metabolism, proliferation, survival and tissue vascularisation. Siah2 knockout (ko) mice and wildtype (wt) controls were examined in a model of hypoxia-induced PH and in pulmonary artery banding (PAB) which induces RV pressure overload independently of pulmonary vascular changes. Hypoxia-treated mice were kept in 10% O2 for 4 weeks. PAB-operated mice received a clip on the pulmonary artery and were examined after 3 weeks. Hypoxic Siah2 ko mice showed reduced RV hypertrophy and improved RV function (determined by echocardiography) compared to wt mice; however, both showed similarly increased pulmonary vascular remodelling. Siah2 ko PAB mice showed less RV hypertrophy and a partially conserved RV function. Fibrosis in the RV, determined by quantification of collagen, was significantly reduced in PAB Siah2 ko mice compared to wt mice. However, Siah2 mRNA expression was not altered in hypoxic lungs and RVs as well as in PAB-RVs of wt mice. Protein- and mRNA-expression of vegfa, a target gene of HIF1α important for neoangiogenesis, did not show any regulation in both models. In conclusion, even though Siah2 crucially influences cardiac function, it does not seem to play a role in the pulmonary pathology of PH.
Genetic Study of Modified Susceptibility to Tumor Transplants in Reciprocal Resistant Backcross Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Barbara H. Sanford
Journal: JNCI Journal of the National Cancer Institute (1963)

Striking differences in susceptibility to transplantation of a mammary tumor from an A/St mouse were noted in reciprocal resistant backcross progeny in this study involving 653 resistant backcross mice from 4 types of matings. The offspring of the cross between (A × C3H)F1 females and resistant C3H males developed significantly more tumors than did the progeny of resistant females crossed to F1 males; there was also a significant difference between the offspring of reciprocal F1 females. Lethal takes in backcross mice receiving transplants of tumor from F1 passage were compared with takes in similar hosts receiving tumor serially transplanted only in A/St. This comparison suggests differences among the 4 backcross types in response to a further variable influencing compatibility. The consistent difference in the graft susceptibility of hosts with essentially identical genotypes is pursued from two points of view: changes in the tumor due to type of passage, and differences in the hosts due to antigenic expression or immunological responsiveness.
GP cancer referral delays may explain UK's low cancer survival rates
Authors: A. O'Dowd
Journal: BMJ (2015)

Lower cancer survival rates in the United Kingdom than in other similar countries could be due to delays in general practitioners referring patients for tests, claims a new study published in BMJ Open .1 

However, GP representatives have said that British GPs are getting better at spotting possible cancer symptoms more quickly and taking action but that they need more resources to continue doing so.

Considerable differences in cancer survival rates have been noted between countries with similar health systems, and poor outcomes could be caused by late presentation of cases, diagnostic delays, and differences in treatment, or combinations of these, the report said. Cancer survival is relatively high in Australia, Canada, and Sweden, intermediate in Norway, and …
Nickel skin levels in different occupations and an estimate of the threshold for reacting to a single open application of nickel in nickel-allergic subjects
Authors: D.J. Gawkrodger, C.W. McLeod, K. Dobson
Journal: British Journal of Dermatology (2011)

Journal Article Nickel skin levels in different occupations and an estimate of the threshold for reacting to a single open application of nickel in nickel‐allergic subjects Get access D.J. Gawkrodger, D.J. Gawkrodger Department of Dermatology, Royal Hallamshire Hospital, Sheffield S10 2JF, U.K David J. Gawkrodger. E‐mail: david.gawkrodger@sth.nhs.uk Search for other works by this author on: Oxford Academic Google Scholar C.W. McLeod, C.W. McLeod Department of Analytical Chemistry, University of Sheffield, Sheffield S3 7HF, U.K Search for other works by this author on: Oxford Academic Google Scholar K. Dobson K. Dobson Department of Dermatology, Royal Hallamshire Hospital, Sheffield S10 2JF, U.K Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 166, Issue 1, 1 January 2012, Pages 82–87, https://doi.org/10.1111/j.1365-2133.2011.10644.x Published: 01 January 2012 Article history Accepted: 12 September 2011 Published: 01 January 2012
Feasibility of Home Delivery (Hd) of Maintenance Pemetrexed (Pem) Therapy for Advanced Nonsquamous Non Small Cell Lung Cancer (Adv Nsqnsclc)
Authors: R. Lal, Y. Summers, R. Shah, B. Crosse, J. Thompson, M.C. Nicolson, V. Potter, C.M. Visseren-Grul, A. Vikström, M. Lorenzo, Y. D'Yachkova, N. Bourayou, G. Hillerdal
Journal: Annals of Oncology (2014)
Enzymatic Defenses of the Mouse Heart Against Reactive Oxygen Metabolites
Authors: James H. Doroshow, Gershon Y. Locker, C. E. Myers
Journal: Journal of Clinical Investigation (1980)

The endogenous defenses of the mouse heart against reactive oxygen metabolites were investigated. The activities of three enzymes capable of detoxifying activated oxygen were determined in both the heart and liver; cardiac muscle contains 150 times less catalase and nearly four times less superoxide dismutase than liver. Glutathione peroxidase activities were, however, similar to the two tissues. Assay of glutathione peroxidase in the heart after 6 wk of selenium depletion with both hydrogen peroxide and cumene hydroperoxide as substrates revealed a >80% drop in enzyme activity and gave no indication that murine cardiac tissue contains nonselenium-dependent glutathione peroxidase. The selenium-deficient state, which was characterized by markedly decreased cardiac glutathione peroxidase levels, led to significantly enhanced doxorubicin toxicity at a dose of 15 mg/kg i.p. Doxorubicin administration in selenium-sufficient animals resulted in a dose-dependent decrease in cardiac glutathione peroxidase activity; the decrease in enzyme activity lasted 72 h after 15 mg/kg i.p. In contrast, cardiac superoxide dismutase and hepatic superoxide dismutase and glutathione peroxidase were unaffected by this dose of doxorubicin. These results suggest that the major pathway in cardiac tissue for detoxification of reactive oxygen metabolites is via the concerted action of superoxide dismutase and selenium-dependent glutathione peroxidase. The latter enzyme may be depleted by a selenium-deficient diet or doxorubicin treatment, leaving the heart with limited mechanisms for disposing of hydrogen peroxide or lipid peroxides.
An Atlas of Congenital Heart Disease.
Authors: Norman J. Sissman
Journal: Annals of Internal Medicine (1963)

Despite the vast experience accumulated during the past decade with all aspects of the lives and deaths of patients with congenital heart disease, there is still room for the clarification and direction that careful, informed, imaginative analysis of the results of pathological examination of postmortem material can give to the clinical management of these patients. Dr. Sherman has made a notable contribution in this area with the present volume.  The atlas was compiled from 503 specimens collected in the Museum of Congenital Heart Disease at the Children9s Hospital in Pittsburgh since 1954.
The Bare Lymphocyte Syndrome and the Regulation of MHC Expression
Authors: Walter Reith, Bernard Mach
Journal: Annual Review of Immunology (2001)

The bare lymphocyte syndrome (BLS) is a hereditary immunodeficiency resulting from the absence of major istocompatibility complex class II (MHCII) expression. Considering the central role of MHCII molecules in the development and activation of CD4 + T cells, it is not surprising that the immune system of the patients is severely impaired. BLS is the prototype of a “disease of gene regulation.” The affected genes encode RFXANK, RFX5, RFXAP, and CIITA, four regulatory factors that are highly specific and essential for MHCII genes. The first three are subunits of RFX, a trimeric complex that binds to all MHCII promoters. CIITA is a non-DNA-binding coactivator that functions as the master control factor for MHCII expression. The study of RFX and CIITA has made major contributions to our comprehension of the molecular mechanisms controlling MHCII genes and has made this system into a textbook model for the regulation of gene expression.
Safety of Aprotinin Use and Re-Use in Pediatric Cardiothoracic Surgery
Authors: Robert D. B. Jaquiss, Nancy S. Ghanayem, Michael C. Zacharisen, Kathleen A. Mussatto, James S. Tweddell, S. Bert Litwin
Journal: Circulation (2002)

Background Hypersensitivity reactions to aprotinin have been reported in adult cardiac surgical patients undergoing initial and re-exposure to the medication. This study describes the incidence and impact of aprotinin hypersensitivity reactions in children undergoing cardiothoracic surgery. Methods and Results In this retrospective review of our entire experience with aprotinin (n=865), 681 first exposures, 150 second exposures, and 34 third or higher exposures were examined. Reactions were classified as mild (generalized cutaneous erythema, Type A) or severe (unexplained cardiopulmonary instability after aprotinin exposure, Type B). Records of patients sustaining a reaction were reviewed to assess the impact of the reaction on outcome and to survey reaction management strategies. Reactions occurred in 7 of 681 first exposures (1.0%), of which 2 were Type A and 5 were Type B. In second exposures, there were reactions in 2 of 150 (1.3%), of which both were Type B. In 34 third or higher exposures, there was only 1 reaction (2.9%), which was Type B. Reactions were no more likely on second, third, or higher exposure than on initial exposure. Skin testing had a negative predictive value of 98.9% and a positive predictive value of 20%. Anti-aprotinin IgE was undetectable in 7 of 8 reactor cases tested. No adverse sequelae were attributed to aprotinin reaction. Conclusions The risk of hypersensitivity reactions to aprotinin is low in children undergoing cardiothoracic surgery, even with multiple exposures to the medication. Reactions are more likely with re-exposure, and risk increases with multiple exposures. Neither skin testing nor assays for IgE identified reactors.
Regional-Arterial Chemotherapy or Arterial Embolization in the Management of Various Stages of Colon Cancer
Authors: Y. Z. Patt, C. Charnsangavej, A. Boddie, G. M. Mavligit, M. Soski, S. Wallace
Journal: Liver Cancer (1985)

It is estimated that more than 120,000 new cases of colon and rectal cancer will occur in the United States during 1984, and approximately 50,000 patients will succumb to this disease [1]. As many as 60% of patients dying from colon cancer succumb to liver disease. Moreover, liver metastases might be the first evidence of recurrent disease in 60% of these patients [2]. The liver became, therefore, a target for regional arterial therapy, and investigators have developed arterial therapy programs using percutaneously placed hepatic arterial catheters [3,4] or implantable infusion systems [5,6] designed to deliver high concentrations of chemotherapy to the hepatic circulation.
Experience with Nalbuphine, a New Opioid Analgesic, in Acute Myocardial Infarction
Authors: R A Greenbaum, G Kaye, P D Mason
Journal: Journal of the Royal Society of Medicine (1987)

A total of 141 patients admitted to hospital with a diagnosis of suspected myocardial infarction were randomized to treatment with intravenous diamorphine (71) or nalbuphine (70). Myocardial infarction was subsequently confirmed in 109 patients. Both drugs provided good analgesia. Heart rate, blood pressure, respiratory rate, peak flow and minute volume were measured over a three-hour study period. Except for a slight fall in systolic blood pressure in the nalbuphine-treated group, there were no statistically significant differences between the groups. The nalbuphine-treated group had higher levels of aspartate aminotransferase and hydroxybutyric acid dehydrogenase but not creatine phosphokinase. The haemodynamic outcome and mortality at three months of the two groups were similar. It is concluded that nalbuphine provides effective analgesia coupled with few adverse circulatory or respiratory effects.
Efficacy and safety of subcutaneous tabalumab in patients with systemic lupus erythematosus: results from ILLUMINATE-1, a 52-week, phase III, multicentre, randomised, double-blind, placebo-controlled study
Authors: D A Isenberg, M Petri, K Kalunian, Y Tanaka, M B Urowitz, R W Hoffman, M Morgan-Cox, N Iikuni, M Silk, D J Wallace
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objectives</h3> Evaluate efficacy and safety of tabalumab, a human IgG4 monoclonal antibody that binds and neutralises membrane and soluble B-cell activating factor (BAFF) versus placebo plus standard of care (SoC) in patients with systemic lupus erythematosus (SLE). <h3>Methods</h3> This phase III, 52-week study randomised 1164 patients with moderate-to-severe SLE (Safety of Estrogens in Lupus Erythematosus National Assessment—SLE Disease Activity Index ≥6 at baseline). Patients received SoC plus subcutaneous injections of tabalumab or placebo, starting with a loading dose (240 mg) at week 0 and followed by 120 mg every two weeks (120 Q2W, n=387), 120 mg every four weeks (120 Q4W, n=389) or placebo Q2W (n=388). Primary endpoint: proportion of patients achieving SLE Responder Index 5 (SRI-5) response at week 52. <h3>Results</h3> Similar proportions of patients in each group achieved SRI-5 response at week 52 (120 Q2W: 31.8%; 120 Q4W: 35.2% and placebo: 29.3%). Key secondary endpoints were not met. In a sensitivity analysis not excluding patients who decreased antimalarials or immunosuppressants, SRI-5 response was achieved with 120 Q4W (37.0% vs 29.8% placebo; p=0.021), but not 120 Q2W (34.1%; p=0.171). Significant reductions in anti-dsDNA antibodies, increases in C3 and C4, and reductions in total B cells and immunoglobulins were observed with tabalumab. No differences were observed between treatment groups in percentage of deaths (120 Q2W: 0.8%; 120 Q4W: 0.5%; placebo: 0.5%), serious adverse events (AEs) (range 11.1–14.4%) or treatment-emergent AEs (range 81.1–82.3%). <h3>Conclusions</h3> Tabalumab had biological activity—changes in anti-dsDNA, complement, B cells and immunoglobulins—consistent with BAFF pathway inhibition. Key clinical efficacy endpoints did not achieve statistical significance. Safety profiles were similar with tabalumab and placebo. <h3>Trial registration number</h3> NCT01196091.
Telomere/telomerase interplay in virus‐driven and virus‐independent lymphomagenesis: pathogenic and clinical implications
Authors: Riccardo Dolcetti, Anita De Rossi
Journal: Medicinal Research Reviews (2010)

Abstract Telomerase is a ribonucleoprotein complex critically involved in extending and maintaining telomeres. Unlike the majority of somatic cells, in which hTERT and telomerase activity are generally silent, normal lymphocytes show transient physiological hTERT expression and telomerase activity according to their differentiation/activation status. During lymphomagenesis, induction of persistent telomerase expression and activity may occur before or after telomere shortening, as a consequence of the different mechanisms through which transforming factors/agents may activate telomerase. Available data indicate that the timing of telomerase activation may allow the distinction of two different lymphomagenetic models: (i) an early activation of telomerase via exogenous regulators of hTERT, along with an increased lymphocyte growth and a subsequent selection of cells with increased transforming potential may characterize several virus‐related lymphoid malignancies; (ii) a progressive shortening of telomeres, leading to genetic instability which favors a subsequent activation of telomerase via endogenous regulators may occur in most virus‐unrelated lymphoid tumors. These models may have clinically relevant implications, particularly for the tailoring of therapeutic strategies targeting telomerase. © 2010 Wiley Periodicals, Inc. Med Res Rev
The clinical evaluation of patients with Pseudomonas aeruginosa detected in respiratory specimens
Authors: Kei Nakashima, Yoshihito Ostuka, Haruki Kobayashi, Naoko Kastsurada, Nobihiro Asai, Hideki Makino, Masafumi Misawa, Yoshihiro Ohkuni, Norihiro Kaneko, Masahiro Aoshima
Journal: European Respiratory Journal (2012)

[Introduction] The present study aims to clarify the clinical picture of patients with Pseudomonas aeruginosa detected in respiratory specimens. [Methods] Medical records of patients with Pseudomonas aerguinosa detected in respiratory specimens from April 2010 to March 2011 at Kameda Medical Center were reviewed retrospectively. The following variables were reviewed: patient background, duration of hospitalization, drug susceptibility, outcomes.[Results] One hundred patients were detected with P. aeruginosa in respiratory specimens totally. Mean age was 75.0 y.o. Sixty seven patients were male, 33 were female. Twenty eight patients have chronic respiratory disease. Fifty three patients were detected through microbial substitution. Period from admission to detection of P. aeruginosa was 53.6 days. Period from antimicrobial initiation to detection was 40.6 days. The numbers of antimicrobial agents were 3.5 on average. MDRP were detected in 6 patients with hematological disorders. Sixty three patients have polymicrobial detection. S.marcescens, MRSA, MSSA, K.pneumoniae were detected in 12, 12, 11, 11 patients frequently. Fifty nine were judged as colonization. Forty one were causative organism of pneumonia. Three were CAP, 7 were NHCAP (Nursing and healthcare associated pneumonia) and 31 were HAP. Duration of hospitalization was 81.5 days on average, 14 patients were died. [Conclusions]P.aeruginosa were detected in patients with chronic respiratory disease and long hospitalization. More than half of detections were bacterial colonization. HAP were frequent and P.aeruginosa caused the prolonged hospitalization and poor prognosis.
Nivolumab and Urelumab Enhance Antitumor Activity of Human T Lymphocytes Engrafted in Rag2−/−IL2Rγnull Immunodeficient Mice
Authors: Miguel F. Sanmamed, Inmaculada Rodriguez, Kurt A. Schalper, Carmen Oñate, Arantza Azpilikueta, Maria E. Rodriguez-Ruiz, Aizea Morales-Kastresana, Sara Labiano, Jose L. Pérez-Gracia, Salvador Martín-Algarra, Carlos Alfaro, Guillermo Mazzolini, Francesca Sarno, Manuel Hidalgo, Alan J. Korman, Maria Jure-Kunkel, Ignacio Melero
Journal: Cancer Research (2015)

Abstract A current pressing need in cancer immunology is the development of preclinical model systems that are immunocompetent for the study of human tumors. Here, we report the development of a humanized murine model that can be used to analyze the pharmacodynamics and antitumor properties of immunostimulatory monoclonal antibodies (mAb) in settings where the receptors targeted by the mAbs are expressed. Human lymphocytes transferred into immunodeficient mice underwent activation and redistribution to murine organs, where they exhibited cell-surface expression of hCD137 and hPD-1. Systemic lymphocyte infiltrations resulted in a lethal CD4+ T cell–mediated disease (xenograft-versus-host disease), which was aggravated when murine subjects were administered clinical-grade anti-hCD137 (urelumab) and anti-hPD-1 (nivolumab). In mice engrafted with human colorectal HT-29 carcinoma cells and allogeneic human peripheral blood mononuclear cells (PBMC), or with a patient-derived gastric carcinoma and PBMCs from the same patient, we found that coadministration of urelumab and nivolumab was sufficient to significantly slow tumor growth. Correlated with this result were increased numbers of activated human T lymphocytes producing IFNγ and decreased numbers of human regulatory T lymphocytes in the tumor xenografts, possibly explaining the efficacy of the therapeutic regimen. Our results offer a proof of concept for the use of humanized mouse models for surrogate efficacy and histology investigations of immune checkpoint drugs and their combinations. Cancer Res; 75(17); 3466–78. ©2015 AACR.
Partial Characterization of a Fetal Lung Antigen Associated With Human Bronchogenic Carcinoma
Authors: E Sega, G Citro, P G Natali
Journal: JNCI Journal of the National Cancer Institute (1979)

The Initial stage of metastasis formation, l.e., the entry of metastatic cells from a malignant subcutaneously growing myelogenous tumor into the circulation, was observed by means of transmission electron microscopy and scanning electron microscopy in Long-Evans rats. The transmural passage of malignant cells occurred through the walls of intact venules within the tumor. The malignant cell penetrated the endothelial cell body by making a temporary migration pore. The migration pore closed after the malignant cell entered the vascular lumen. The endothelial vascular lining remained continuous. The entry of malignant cells Into the circulation was not the result of the general invasive and destructive properties of malignant tumor cells, but the consequence of a specific action of the tumor cells on the ablumlnal plasma membrane of the endothellum.