tbuckley/cabot-search huggingface dataset:
Enhanced In Vitro Selective Toxicity of Chemotherapeutic Agents for Human Cancer Cells Based on a Metabolic Defect2
Authors: Peter H. Stern, Robert M. Hoffman
Journal: JNCI Journal of the National Cancer Institute (1986)

Journal Article Enhanced In Vitro Selective Toxicity of Chemotherapeutic Agents for Human Cancer Cells Based on a Metabolic Defect Get access Peter H. Stern, Peter H. Stern Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert M. Hoffman Robert M. Hoffman Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 76, Issue 4, April 1986, Pages 629–639, https://doi.org/10.1093/jnci/76.4.629 Published: 01 April 1986 Article history Received: 29 May 1985 Accepted: 12 November 1985 Published: 01 April 1986
TNFα-induced glucocorticoid resistance: Effect of steroidal and non-steroidal GR agonists, formoterol and inhibition of inflammatory signalling
Authors: Christopher Rider, Suharsh Shah, Anna Miller-Larsson, David Proud, Malcolm Johnson, Mark Giembycz, Robert Newton
Journal: European Respiratory Journal (2012)

Inhaled glucocorticoids (GCs) w/wo long-acting β 2 -adrenoceptor agonists (LABA) are the most effective treatment for asthma. However, GC insensitivity is a facet of severe asthma and COPD. We have examined TNFα-induced resistance to GC-dependent transcription by steroidal and non-steroidal GC receptor (GR) ligands in the absence and presence of a LABA, formoterol.   METHODS:  GC-dependent transcription was modeled by a simple 2×GRE-luciferase reporter in human bronchial epithelial BEAS-2B cells treated with TNFα (10 ng/ml) for 1 h prior to addition of GR ligands, and harvested after 6 h for luciferase assay.   RESULTS:  TNFα reduced by 43-54% the ability to drive 2×GRE-dependent transcription by dexamethasone, budesonide, fluticasone propionate or fluticasone furoate. The GCs des-ciclesonide, GW870086X, RU24858 and the non-steroidal GR agonist, GSK9027, all showed reduced maximal responses (E max ) with intrinsic activities 0.5-0.77 relative to dexamethasone. In each case, TNFα reduced E max  by a further 39-55%. Conversely, formoterol enhanced GRE-dependent transcription by each ligand and rescued the resistance induced by TNFα; these effects were proportional to the E max  of each drug. Statistically significant reversal of TNFα-induced resistance was observed with the c-jun N-terminal kinase inhibitor, JNK8, and PS-1145, an IκB kinase 2 (IKK2) inhibitor.   CONCLUSIONS:  TNFα induces GC resistance to steroidal GR ligands that are both full and partial agonists, as well as to a non-steroidal GR agonist. This effect is rescued by the addition of formoterol. It is possible that inhibition of inflammatory signalling may also reduce GC resistance.
Ultrasound guided transbronchial cryobiopsy in the diagnosis of peripheral lung lesions: A feasibility and safety trial
Authors: Ralf Eberhardt, Maren Schuhmann, Korkut Bostanci, Nicolas Kahn, Philipp A. Schnabel, Felix J.F. Herth
Journal: European Respiratory Journal (2011)

Background:  Peripheral lung lesions (PLL) can pose a diagnostic problem since they are often difficult to reach and only insufficient material can be obtained by transbronchial forceps biopsy. Endobronchial Ultrasound (EBUS) can be used for detection of PLL and in combination with a flexible cryoprobe (Erbe Medizintechnik, Germany) larger tissue samples can be taken. The purpose of this study was to evaluate the safety and feasibility of this technique.   Methods:  Patients with PPL up to 4cm in diameter were enrolled prospectively. After the PLL had been identified by EBUS we performed forceps as well as cryo biopsies under fluoroscopy through a guide-sheath. The order of the techniques used was randomised. The pathologist was blinded towards the biopsy technique. We evaluated and compared the diagnostic yield and sample size as well as the complication rate.   Results:  We were able to reach the lesion with EBUS guidance in 31 of 39 patients. The final diagnosis of the 31 patients was malignant in 25 and benign in 6 cases. In 74% we were able to make a definitive diagnosis with bronchoscopic sampling (23 of 31). In 19 cases the diagnosis was made with forceps as well as cryobiopsy, in 4 cases only through cryobiopsy. Samples obtained by cryobiposy were significantly larger. Complications observed during the procedure were 1 moderate bleed after cryobiopsy treated endoscopically. No pneumthorax occurred.   Discussion:  Transbronchial cryobiopsy with EBUS guidance is a safe technique and useful to obtain histological samples for diagnostic purposes. By obtaining larger tissue samples it may be possible to improve the bronchoscopic diagnostic yield for peripheral lung lesions.
Expression of Beta-Integrin Adhesion Molecules in Non-Hodgkin's Lymphoma: Correlation With Clinical and Evolutive Features
Authors: María-José Terol, Armando López-Guillermo, Francesc Bosch, Neus Villamor, María-Cinta Cid, Elías Campo, Emilio Montserrat
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To analyze beta-integrin expression in non-Hodgkin's lymphomas (NHLs) in order to assess its distribution among histologic subtypes and correlate with clinical features and outcome. PATIENTS AND METHODS: The expression of α2 through α6 and β1 common chains of very late activation antigen (VLA ) molecules and αL (CD11a) and β2 common (CD18) chains of leukocyte function-associated antigen 1 molecule were studied in 137 patients with NHL. Immunostaining was performed by a streptavidin-biotin alkaline phosphatase method, and integrin expression was semiquantitatively assessed. Correlation with clinical features was analyzed in 80 patients consecutively diagnosed as having immunocytoma (five cases), follicular lymphoma (19 cases), mantle-cell lymphoma (MCL; four cases), diffuse large-cell lymphoma (DLCL; 40 cases), lymphoblastic lymphoma (LL; six cases), anaplastic Ki-1–positive lymphoma (one case), and other peripheral T-cell lymphoma (five cases). RESULTS: MCL cells did not show α2 and α6 expression, whereas most expressed weak to moderate levels of α3, α4, and α5. LL mostly showed α2 to α5 expression, whereas α6 was observed in seven of 11 cases (higher proportion than that shown in other subgroups). Alpha chains of VLA molecules were present more frequently in T-cell than in B-cell lymphomas. Patients with moderate/strong α4, CD11a, and β2 common chain expression presented more frequently with advanced stage and bone marrow infiltration. Moderate/strong α4, α5, and β1 common chain expression correlated with extranodal involvement. In the subset of B-cell DLCL patients, negative/weak expression of α3 and α4 chains was related to a higher complete response rate. Moreover, negative or weak expression of α2, α3, α4, and β1 common chain had favorable significance for overall and failure-free survivals. CONCLUSION: In NHL, beta-integrin expression is related to histologic subtype. The expression pattern of these molecules probably influences disease dissemination and patients' prognoses.
Cigarette smoke augments MUC5AC mucin production via TLR3-EGFR pathway in airway epithelial cells
Authors: Kuninobu Kanai, Akira Koarai, Hisatoshi Sugiura, Tomohiro Ichikawa, Takashi Kikuchi, Keiichiro Akamatsu, Tsunahiko Hirano, Masanori Nakanishi, Kazuto Matsunaga, Yoshiaki Minakata, Masakazu Ichinose
Journal: European Respiratory Journal (2013)

Virus infections are a major cause of COPD exacerbations. Recently, toll-like receptor 3 (TLR3) has been shown to react to double-stranded RNA (dsRNA) and to be involved in the immune responses after viral infections. In the present study, we examined whether cigarette smoke, which is involved in the pathogenesis of COPD, enhances the mucin production via TLR3-epidermal growth factor receptor (EGFR) pathway in airway epithelial cells. The effect of cigarette smoke extract (CSE) on the production of a major airway mucin, MUC5AC, in NCI-H292 cells, a human pulmonary mucoepidermoid carcinoma cell line, after stimulation with polyinosine-polycytidylic acid [poly(I:C)], a synthetic analog of viral dsRNA and a ligand for TLR3, and the signal transduction were examined. CSE significantly potentiated the production of MUC5AC mucin in the epithelial cells after stimulation with poly(I:C) and the potentiation was inhibited by treatment with N-acetylcysteine, an antioxidant. CSE potentiated EGFR ligands (TGF-α and amphiregulin) production in the poly(I:C)-treated cells, and the CSE-augmented MUC5AC mucin production was inhibited by the neutralizing antibodies of EGFR or EGFR ligands. In addition, the augmented MUC5AC mucin production was inhibited by EGFR inhibitors (AG1378 and BIBX1382) or ERK inhibitor (U0126). These data suggest that cigarette smoke augments TLR3-stimulated mucin production in airway epithelial cells via EGFR and ERK signaling. Modulation of this pathway may be a therapeutic target for viral-induced mucin overproduction in exacerbations of COPD.
Vitamin B6 Metabolism in Chronic Alcohol Abuse
Authors: Lawrence Lumeng, Ting-Kai Li
Journal: Journal of Clinical Investigation (1974)

The plasma pyridoxal-5'-phosphate (PLP) level of alcoholic subjects has been compared with that of non-alcoholic individuals in order to ascertain the incidence of abnormal vitamin B(6) metabolism in chronic alcohol abuse. 66 alcoholic subjects were selected on the basis that they did not exhibit abnormal liver function tests and hematologic findings. 35 of them had plasma PLP concentrations less than 5 ng/ml, the lowest value encountered in 94 control subjects, indicating a high incidence of deranged PLP metabolism in alcoholic patients even when hepatic and hematologic abnormalities are absent. The biochemical basis for the altered PLP metabolism in chronic alcohol abuse was examined. Low plasma PLP levels in alcoholics were not accompanied by decreased pyridoxal kinase and pyridoxine phosphate oxidase activities in erythrocytes. Further studies with erythrocytes demonstrated that the cellular content of PLP is determined not only by the activities of these PLP-synthesizing enzymes but also by the activity of a phosphate-sensitive, membrane-associated, neutral phosphatase, which hydrolyzes phosphorylated B(6) compounds.Acetaldehyde, but not ethanol, impaired the net formation of PLP from pyridoxal, pyridoxine, and pyridoxine phosphate by erythrocytes. However, when the B(6)-phosphate phosphatase activity was inhibited by 80 mM phosphate, this effect of acetaldehyde was abolished. By the use of broken cell preparations, it was possible to demonstrate directly that the action of acetaldehyde is mediated by the phosphatase, resulting in an acceleration of the degradation of the phosphorylated B(6) compounds in erythrocytes.
High-dose versus low-dose cisplatin in advanced head and neck squamous carcinoma: a randomized study.
Authors: A Veronesi, V Zagonel, U Tirelli, E Galligioni, S Tumolo, L Barzan, M Lorenzini, R Comoretto, E Grigoletto
Journal: Journal of Clinical Oncology (1985)

From November 1981 to February 1983, 64 patients with advanced head and neck squamous carcinoma were randomly treated with either high-dose (120 mg/m2) or low-dose (60 mg/m2) cisplatin. Of the 62 eligible patients, 59 were evaluable: the response rate observed in patients receiving high-dose and low-dose cisplatin was 16.1% and 17.8%, respectively. Survival was superimposable in the two treatment arms. No evidence of dose dependency of cisplatin activity in advanced head and neck squamous carcinoma was noted in this randomized trial.
Dominant Mutations in the Autoimmune Regulator AIRE Are Associated with Common Organ-Specific Autoimmune Diseases
Authors: Bergithe E. Oftedal, Alexander Hellesen, Martina M. Erichsen, Eirik Bratland, Ayelet Vardi, Jaakko Perheentupa, E. Helen Kemp, Torunn Fiskerstrand, Marte K. Viken, Anthony P. Weetman, Sarel J. Fleishman, Siddharth Banka, William G. Newman, W.A.C. Sewell, Leila S. Sozaeva, Tetyana Zayats, Kristoffer Haugarvoll, Elizaveta M. Orlova, Jan Haavik, Stefan Johansson, Per M. Knappskog, Kristian Løvås, Anette S.B. Wolff, Jakub Abramson, Eystein S. Husebye
Journal: Immunity (2015)
Specificities of Antibodies Eluted from Human Cadaveric Renal Allografts
Authors: John J. McPhaul, Peter Stastny, Richard B. Freeman
Journal: Journal of Clinical Investigation (1981)

The purpose of the present experiments was to evaluate the role of circulating antibodies in the rejection of human renal allografts and to study the apparent target(s) for antibody binding. Eluates obtained from surgical biopsy and nephrectomy specimens of rejecting, cadaveric human renal allografts were tested for antibodies directed to structural antigens of normal kidney and for cytotoxic antibody activity against mononuclear cell populations. By indirect immunofluorescence 23 of 35 eluates contained immunoglobulin that bound to normal kidney. Staining was in smooth muscle only in 10 patients, in smooth muscle and other structures such as tubular basement membranes, proximal cells, or brush border in 9 patients, and in structures other than smooth muscle in 4 patients. All 16 eluates tested contained antibodies cytotoxic for cells derived from a panel of normal volunteers. Six were cytotoxic to T cells and 10 to B cell and monocyte-enriched preparations. Absorption of eluates with pooled buffy coat cells, platelet concentrates and packed, cultured B cells removed antibodies reactive with vascular wall smooth muscle and endothelium, but not antibodies to tubular basement membranes, proximal or distal tubular cells, brush border, or other structures of kidney sections. Two of five eluates containing antikidney antibodies were found to bind to rat kidneys in vivo. These results suggest that circulating antibodies participate in cadaveric renal allograft destruction and demonstrate that they can be recovered directly from the allograft. Moreover, the data indicate that there are different antibody populations involved: some clearly directed to allo-specific differences and others that are apparently kidney-specific.
Mucin Degradation in Human Colon Ecosystems
Authors: Lansing C. Hoskins, Erwin T. Boulding
Journal: Journal of Clinical Investigation (1981)

Recent work indicates that subpopulations of human fecal bacteria, averaging ∼1% of the total viable fecal flora, degrade the oligosaccharide side chains of hog gastric mucin, which structurally resembles human epithelial mucins. Here we report studies to determine whether degradation of mucin oligosaccharides is related to glycosidase production by bacteria growing in anaerobic fecal cultures. Triplicate cultures containing hog gastric mucin were inoculated with serially diluted feces from each of seven healthy subjects. When the stationary growth phase was attained, mucin oligosaccharide degradation and both cell-bound and extracellular activities of four glycosidases were measured in each culture. Cell-bound β-d-galactosidase, β-N-acetylglucosaminidase, and sialidase were present in bacteria growing at all levels of fecal inocula, including 10−11 g. In contrast, extracellular activities were present in every culture inoculated with 10−4−10−7 g feces, but were diminished or absent in cultures inoculated with 10−8−10−11 g feces. Bacterial autolysis was an unlikely cause of extracellular glycosidase activity, since p-nitrophenyl-α-l-fucosidase remained cell bound in cultures at every level of fecal inoculum. Degradation of mucin oligosaccharides was associated with extracellular, but not with cell-bound β-d-galactosidase, β-N-acetylglucosaminidase, and sialidase. Among the seven subjects, the estimated most probable numbers (MPN) of fecal bacteria producing extracellular β-d-galactosidase, β-N-acetylglucosaminidase, and sialidase ranged from 106−1010/g dry fecal wt, were comparable to the MPN of mucin-degrading bacteria, and were significantly smaller than the MPN of total fecal bacteria.
Shifting Boundaries in Professional Care
Authors: Anthony Hopkins, Juliet Solomon, Julia Abelson
Journal: Journal of the Royal Society of Medicine (1996)

The nature of the work undertaken by different health professionals and inter-professional boundaries are constantly shifting. The greater knowledge of users of health care, and the increasing technical and organizational complexity of modern medicine, have partly eroded the control of health professionals over the substance of their work. The definition of a field of work as lying within the province of any one profession is culturally rather than scientifically determined. It is evident that care of good quality should be delivered at the lowest possible cost. This might include delivery of care by a less trained person than heretofore, or by someone with limited but focused training. Sharing of skills is a more sensible subject for discussion than transfer of tasks. We review a number of studies which show the effectiveness of inter-professional substitution in various care settings, and also the effectiveness of substitution by those other than health professionals. The views of users of health services on inter-professional substitution need to be considered. Health professionals and others need to work together to devise innovative ways of delivering effective health care. The legal issues need clarification.
Survivorship: Cognitive Function, Version 1.2014
Authors: Crystal S. Denlinger, Jennifer A. Ligibel, Madhuri Are, K. Scott Baker, Wendy Demark-Wahnefried, Debra L. Friedman, Mindy Goldman, Lee Jones, Allison King, Grace H. Ku, Elizabeth Kvale, Terry S. Langbaum, Kristin Leonardi-Warren, Mary S. McCabe, Michelle Melisko, Jose G. Montoya, Kathi Mooney, Mary Ann Morgan, Javid J. Moslehi, Tracey O'Connor, Linda Overholser, Electra D. Paskett, Muhammad Raza, Karen L. Syrjala, Susan G. Urba, Mark T. Wakabayashi, Phyllis Zee, Nicole R. McMillian, Deborah A. Freedman-Cass
Journal: Journal of the National Comprehensive Cancer Network (2014)

Cognitive impairment is a common complaint among cancer survivors and may be a consequence of the tumors themselves or direct effects of cancer-related treatment (eg, chemotherapy, endocrine therapy, radiation). For some survivors, symptoms persist over the long term and, when more severe, can impact quality of life and function. This section of the NCCN Guidelines for Survivorship provides assessment, evaluation, and management recommendations for cognitive dysfunction in survivors. Nonpharmacologic interventions (eg, instruction in coping strategies; management of distress, pain, sleep disturbances, and fatigue; occupational therapy) are recommended, with pharmacologic interventions as a last line of therapy in survivors for whom other interventions have been insufficient.
Cannabidiol causes endothelium-dependent vasorelaxation of human mesenteric arteries via CB<sub>1</sub>activation
Authors: Christopher P. Stanley, William H. Hind, Cristina Tufarelli, Saoirse E. O'Sullivan
Journal: Cardiovascular Research (2015)

AimsThe protective effects of cannabidiol (CBD) have been widely shown in preclinical models and have translated into medicines for the treatment of multiple sclerosis and epilepsy. However, the direct vascular effects of CBD in humans are unknown.
An evaluation of the environmental and health effects of vehicle exhaust catalysts in the UK.
Authors: Emma J Hutchinson, Peter J G Pearson
Journal: Environmental Health Perspectives (2003)

Since 1993, all new gasoline-engine automobiles in the United Kingdom have been supplied with three-way vehicle exhaust catalytic converters (VECs) containing platinum, palladium, and rhodium, to comply with European Commission Stage I limits on emissions of regulated pollutants: carbon monoxide, hydrocarbons, and oxides of nitrogen. We conducted a physical and economic evaluation of the environmental and health benefits from a reduction in emissions through this mandated environmental technology against the costs, with reference to urban areas in Great Britain. We made both an ex post assessment--based on available data to 1998--and an ex ante assessment--projected to 2005, the year when full penetration of VECs into the fleet is expected. Substantial health benefits in excess of the costs of VECs were indicated: By 1998 the estimated net societal health benefits were approximately 500 million British pounds, and by 2005 they were estimated to rise to as much as 2 billion British pounds. We also found through environmental surveys that although lead in road dust has fallen by 50% in urban areas, platinum accumulations near roads have risen significantly, up to 90-fold higher than natural background levels. This rapid accumulation of platinum suggests further monitoring is warranted, although as yet there is no evidence of adverse health effects.
The serum CXCL13 level is associated with the Glasgow Prognostic Score in extranodal NK/T-cell lymphoma patients
Authors: Seok Jin Kim, Kyung Ju Ryu, Mineui Hong, Young Hyeh Ko, Won Seog Kim
Journal: Journal of Hematology & Oncology (2015)

The Glasgow Prognostic Score (GPS) measures inflammation and proves its prognostic value in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTL) which is commonly combined with inflammatory lesion. Given inflammatory chemokines play an important role in tumor progression, we hypothesized that chemokines might influence ENKTL aggressiveness through interaction with their receptors in the tumor tissue. We measured the serum levels of C-X-C motif ligand 13 (CXCL13) in 69 patients with ENKTL who received non-anthracycline-based chemotherapy and/or concurrent chemoradiotherapy because CXCL13 is thought to have a pro-tumor effect through interaction with its receptor, the C-X-C chemokine receptor 5 (CXCR5). We analyzed the association of serum CXCL13 with the GPS, and their prognostic relevance. The levels of CXCL13 were measured using a multiplex chemokine assay on archived frozen serum samples. Patients were categorized into high and low CXCL13 groups if they had CXCL13 levels above or below the median value of 29.1 pg/mL, respectively. The high CXCL13 group and grouping by the GPS showed a significant association with poor progression-free survival. The elevated serum levels of CXCL13 were also significantly associated with a high score of the GPS. High CXCL13 levels and GPS were significantly associated with high tumor burden predicting poor prognosis including stages III/IV, extranasal presentation, bone marrow invasion, and presence of Epstein-Barr virus (EBV) DNA in blood. Furthermore, serum CXCL13 and GPS discriminated patients at risk of treatment failure among patients with low tumor burden (stage I/II) and non-detectable EBV DNA. Serum levels of CXCL13 were associated with the prognostic value of GPS. Grouping by the serum CXCL13 might predict survival outcomes in patients with ENKTL, suggesting that it is a potential therapeutic target.