tbuckley/cabot-search huggingface dataset:
The G-Protein–Coupled Receptor CLR Is Upregulated in an Autocrine Loop with Adrenomedullin in Clear Cell Renal Cell Carcinoma and Associated with Poor Prognosis
Authors: Leonid L. Nikitenko, Russell Leek, Stephen Henderson, Nischalan Pillay, Helen Turley, Daniele Generali, Sarah Gunningham, Helen R. Morrin, Andrea Pellagatti, Margaret C.P. Rees, Adrian L. Harris, Stephen B. Fox
Journal: Clinical Cancer Research (2013)

Abstract Purpose: The G-protein–coupled receptor (GPCR) calcitonin receptor-like receptor (CLR) and its ligand peptide adrenomedullin (encoded by ADM gene) are implicated in tumor angiogenesis in mouse models but poorly defined in human cancers. We therefore investigated the diagnostic/prognostic use for CLR in human tumor types that may rely on adrenomedullin signaling and in clear cell renal cell carcinoma (RCC), a highly vascular tumor, in particular. Experimental Design: In silico gene expression mRNA profiling microarray study (n = 168 tumors) and cancer profiling cDNA array hybridization (n = 241 pairs of patient-matched tumor/normal tissue samples) were carried out to analyze ADM mRNA expression in 13 tumor types. Immunohistochemistry on tissue microarrays containing patient-matched renal tumor/normal tissues (n = 87 pairs) was conducted to study CLR expression and its association with clinicopathologic parameters and disease outcome. Results: ADM expression was significantly upregulated only in RCC and endometrial adenocarcinoma compared with normal tissue counterparts (P &amp;lt; 0.01). CLR was localized in tumor cells and vessels in RCC and upregulated as compared with patient-matched normal control kidney (P &amp;lt; 0.001). Higher CLR expression was found in advanced stages (P &amp;lt; 0.05), correlated with high tumor grade (P &amp;lt; 0.01) and conferred shorter overall survival (P &amp;lt; 0.01). Conclusions: In human tissues ADM expression is upregulated in cancer type–specific manner, implicating potential role for adrenomedullin signaling in particular in RCC, where CLR localization suggests autocrine/paracrine mode for adrenomedullin action within the tumor microenvironment. Our findings reveal previously unrecognized CLR upregulation in an autocrine loop with adrenomedullin in RCC with potential application for this GPCR as a target for future functional studies and drug development. Clin Cancer Res; 19(20); 5740–8. ©2013 AACR.
Effects of Monounsaturated and Polyunsaturated Fatty Acids (v-3 and v-6) on Brca1 Protein Expression in Breast Cell Lines
Authors: Dominique J. Bernard-Gallon, Jean-Claude Maurizis, Pascale G. Rio, PHILIPPE BOUGNOUX, Yves-Jean Bignon
Journal: JNCI Journal of the National Cancer Institute (1998)
Operate on My Stomach Cancer? Oh, No—Not You, or Not Yet!
Authors: Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2004)

Operate on My Stomach Cancer?Oh, No-Not You, or Not Yet! TO THE EDITOR: Gastric cancer is more common in men than in women. 1 Interestingly, this applies in all endemic and nonendemic areas, but the reason for this phenomenon remains unclear.Because we do not know the genetic basis for the increased susceptibility of men, one may speculate that female hormones provide some degree of protection; alternatively, do men not expose themselves to more carcinogens (smoking, food, alcohol, and so on) than do women?In a recent article by Kattan et al, 2 they indicate that there were more women (63.5%) than men in their database.I suspect that this is a typographical error; however, if it is not, I wonder about the explanation for this unusual distribution.In their nomogram, the men have a slightly worse prognosis than the women.This is likely due to more frequent proximal localization of the primary in men than in women.Nonetheless, the most important statement in their article is not that the increasing number of metastatic nodes imparts a worse outcome in terms of overall survival (this is well known), but that the lower number of examined nonmetastatic nodes resulted in a poor outcome.The number of examined nonmetastatic nodes was previously recognized as an independent prognostic factor. 3In the nomogram, patients who had zero to 10 examined nonmetastatic nodes incurred more points (thus worse survival time) than those in whom 30 examined nodes were nonmetastatic.Is there not a strong message here?Simply stated, the evidence supports the notion that more nodes one removes, the better off is the patient.In a recent article by Le Voyer et al, 4 it was demonstrated that the number of lymph nodes examined in 3,411 patients undergoing colon cancer surgery was an independent prognostic variable and survival of patients increased as more nodes were examined.Thus, this concept may apply to all gastrointestinal cancers.Most patients in the United States with newly diagnosed, local-regional gastric or gastroesophageal cancer have a cancer that is T3, N Ն 1, or both.An increase in the T stage correlates with an increase in the percentage of N Ն 1 stage. 5,6The more lymph nodes one examines, the more metastatic nodes that are likely to be found. 7,8There is also a strong correlation between the T stage and the frequency of N2 nodal group involvement, as defined by the Japanese classification. 5,7,8Can one make a compelling argu-
CATHETER ABLATION IN SUPRAVENTRICULAR TACHYCARDIA
Authors: Sanjay Deshpande, M.D, Mohammad Jazayeri, M.D, Anwer Dhala, M.D, Zalmen Blanck, M.D, Jasbir Sra, M.D, Siobhan Bremner, R.N., MPH, Masood Akhtar, M.D
Journal: Annual Review of Medicine (1995)

▪ Abstract The evolution of catheter ablation for the treatment of supraventricular tachycardias represents a major advance in the management of cardiac arrhythmias. Excellent results in the majority of patients undergoing the procedure, together with a low rate of early complications and a brief hospitalization, make catheter ablation a highly cost-effective permanent cure. At present, however, its place in relation to alternate therapies in the management of supraventricular tachycardias has not been clearly established owing to unresolved risk-benefit issues. Continuing technical advances will likely enable catheter ablation to be successfully applied to a broader range of cardiac arrhythmias.
Occupational asthma due to heated freon.
Authors: G B Field
Journal: Thorax (1985)

Occupational asthma due to heated fr-eon Sir,-I read with interest the report of a case of occupa- tional asthma due to heated freon by Dr J-L Malo and others (August 1984;39:628-9).I recently treated a refrigeration mechanic who developed acute asthmatic symptoms in almost identical circumstances.He had no past history of asthma.His symptoms and clinical signs of airway narrowing gradually resolved over the next 24 hours.Fluorinated chlorohydrocarbon refrigerants decompose on exposure to a naked flame or hot surface and may evolve highly irritant gases such as hydrochloric acid, chlorine, and phosgene.'These gases all cause tissue dam- age in the bronchial tree if inhaled in sufficient concentra- tion.The clinical manifestations of tissue damage are often delayed and, in the case of phosgene, typically occur after a latent period of five to eight hours.2It seems probable that the bronchoconstriction observed by Dr Malo and others in their asthmatic patient was initially a reaction to non- specific irritation and later a reaction to damage to the bronchial mucosa.The dual reaction can therefore be explained on the basis of mucosal injury without the need to invoke antigenic or other hypersensitivity mechanisms.No reaction would be expected to unheated freon, which does not release these toxic decomposition products.
Nutrition and fitness: mental health, ageing, and the implementation of a healthy diet and physical activity lifestyle
Authors: D Hughes
Journal: British Journal of Sports Medicine (2006)

Edited by A P Simopoulos. Published by Karger, Basel, Switzerland, 2005, £111.58, 182 pp, hardcover. ISBN 3805579454

In the fifth century BC, the Hippocratic physicians wrote “If there is any deficiency in food or exercise, the body will fall sick”. For those who are yet to be convinced of the role that sport and exercise medicine (SEM) can play in improving the general health of the population, this volume is mandatory reading. The book is a publication of part of the proceedings of the 5th International Conference on Nutrition and Fitness, held in Athens in June …
Regulation of Blood Pressure by Sympathetic Nerve Fibers and Adrenal Medulla in Normotensive and Hypertensive Rats
Authors: Jacques de Champlain, Marie Reine van Ameringen
Journal: Circulation Research (1972)

The respective roles of the sympathetic nerve fibers and adrenal medulla in the regulation of blood pressure and heart rate were studied in normotensive and hypertensive rats. Chemical sympathectomy alone, by treatment with 6-OH-DA, or bilateral adrenalectomy reduced blood pressure only slightly in normotensive animals. In animals made hypertensive with deoxycorticosterone (DOCA) and saline, each of these procedures reduced blood pressure to a greater extent than in normotensive animals, but the blood pressure remained at hypertensive levels. The combination of both procedures resulted in a greater fall in blood pressure than could have been predicted from individual effects, suggesting that the removal of one component of the sympathetic system can be compensated for by a hyperactivity of the remaining component. After chemical sympathectomy, adrenalectomy produced a rapid and marked fall in blood pressure in both normotensive and hypertensive animals and the blood pressure stabilized around 50 mm Hg within 1 hour after adrenalectomy. Since the basal blood pressure was identical in normotensive and hypertensive animals after removal of both components of the sympathetic system, this suggests that the most likely factor which would account for an elevated blood pressure in rats treated with DOCA and sodium is a synergic hyperactivity of the sympathetic fibers and adrenal medulla.
Reduced sulfation of muc5b is linked to xerostomia in patients with Sjogren syndrome
Authors: C Alliende, Y-J Kwon, M Brito, C Molina, S Aguilera, P Perez, L Leyton, A F G Quest, U Mandel, E Veerman, M Espinosa, H Clausen, C Leyton, R Romo, M-J Gonzalez
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objectives:</h3> MUC5B contains sulfated and sialylated oligosaccharides that sequester water required for moisturising the oral mucosa. Xerostomia, in patients with Sjögren syndrome, is generally associated with reduced quantities, rather than altered properties, of saliva. Here, we determined the amount of MUC5B (mRNA and protein) as well as sulfation levels in salivary glands of patients with normal or altered unstimulated salivary flow. Localisation of MUC5B and sulfated MUC5B, as well as total levels sulfated groups were determined and compared with acini basal lamina disorganisation. <h3>Patients and methods:</h3> In all, 18 patients with normal or altered unstimulated salivary flow and 16 controls were studied. MUC5B mRNA and protein were evaluated in salivary glands by semiquantitative RT-PCR and Western blot analysis. MUC5B sulfation was determined by Western blotting. MUC5B and sulfo-Lewis<sup>a</sup> antigen localisation were assessed by immunohistochemistry. The total amount of sulfated oligosaccharides was determined microdensitometrically. <h3>Results:</h3> No significant differences were detected in MUC5B mRNA and protein levels between controls and patients, while sulfo-Lewis<sup>a</sup> antigen levels were lower in patients. The number of sulfo-Lewis<sup>a</sup> positive mucous acini was reduced in patients but no correlation was observed between lower levels of sulfation and unstimulated salivary flow. Microdensitometric data confirmed the presence of reduced sulfated oligosaccharides levels in mucous acini from patients with highly disorganised basal lamina. <h3>Conclusion:</h3> Disorganisation of the basal lamina observed in patients with Sjögren syndrome may lead to dedifferentiation of acinar mucous cells and, as a consequence, alter sulfation of MUC5B. These changes are suggested to represent a novel mechanism that may explain xerostomia in these patients.
Increased Susceptibility of Poly(ADP-Ribose) Polymerase-1 Knockout Cells to Antitumor Triazoloacridone C-1305 Is Associated with Permanent G2 Cell Cycle Arrest
Authors: Józefa Węsierska-Gądek, Daniela Schloffer, Marieta Gueorguieva, Maria Uhl, Andrzej Skladanowski
Journal: Cancer Research (2004)

Triazoloacridone C-1305 is a novel inhibitor of DNA topoisomerase II, which exhibits potent antitumor activity toward solid tumors. In this study, antiproliferative action of C-1305 and its close analog C-1533 was investigated in nontransformed mouse fibroblasts and two mutant cell lines in which the PARP-1 gene was specifically disrupted. Unexpectedly, C-1305 very strongly affected proliferation of cells lacking poly(ADP-ribose) polymerase-1 (PARP-1), whereas the action of less active compound C-1533 toward normal and PARP-1-negative cells was comparable. The IC(50) concentration of C-1305 determined for PARP-1 knockout cells was approximately 150-fold lower than that determined for cells with functional PARP-1. Both studied triazoloacridones exhibited very low direct cytotoxicity as evidenced by accumulation of 7-amino-actinomycin D, and only low levels of apoptosis were observed after a 24-h exposure to studied drugs. Analysis of DNA damage induced by C-1305 by the Comet assay showed that this drug induced very low levels of DNA strand breaks. C-1305 strongly affected cell cycle progression in normal and PARP-1 mutant cells and arrested both cell types in G(2)-M phase. However, the G(2)-M arrest induced by C-1305 was greatly prolonged in PARP-1-deficient cells as compared with normal fibroblasts. Together, these results show that mouse cells lacking PARP-1 are extremely sensitive to C-1305, a new topoisomerase II inhibitor. This is in striking contrast with previous reports in which PARP-1-deficient cells were shown to be resistant to classical topoisomerase II inhibitors. Our data also suggest that the PARP-1 status might be essential for the maintenance of the G(2) arrest induced by C-1305.
Lipoxins and other arachidonate derived mediators in bronchial asthma
Authors: C Chavis, I Vachier, P Godard, J Bousquet, P Chanez
Journal: Thorax (2000)

Leukotrienes and lipoxins, arachidonate derived mediators from the lipoxygenase (LO) pathways, are associated with bronchial asthma.1-3 They have been detected in vivo in bronchoalveolar lavage (BAL) fluid4-6 and are biosynthesised in vitro by human alveolar macrophages (AM) and polymorphonuclear cells (PMN) after non-specific stimulation.7 Lipoxins were first isolated by Serhan et al 8 9 who incubated granulocytes with 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE). Lipoxin synthesis was also achieved by the addition of other exogenous substrates to cell cultures.8 10 11 In contrast, lipoxin synthesis by co-cultures of two different cell types does not require the addition of any exogenous substrates.11-13 The biosynthesis of lipoxins was shown to be the result of a cellular cooperation mechanism between two different cell types. The enzymatic mechanism of transcellular metabolism involves the action of at least two different lipoxygenases (fig 1). Thus, lipoxins may be generated following receptor mediated activation of either co-incubated PMN and platelets,13 or ionophore stimulation of PMN alone after exposure to exogenous 15(S)-HETE.14



Figure 1 
Transcellular metabolism.



As shown previously,15 AM from asthmatic patients display high levels of 5-LO activity. 15(S)-HETE is considered to be specific to human epithelium airways and endothelial cells.16-18Human epithelial and endothelial cells are unable to produce lipoxins from endogenous 15(S)-HETE16 19 but they are surrounded by several cell types which show 5-LO activity. Moreover, lipoxins have been identified in the BAL fluid of patients with lung disease20 and in stimulated whole blood.21Because of these observations, and assuming that peripheral blood cells were activated before trafficking to the airways, we have investigated whether AM and peripheral blood cells display sufficient LO activity to transform 15(S)-HETE and have determined whether the generation of lipoxins and their precursors is related to the severity of asthma and can be …
Liberals and conservatives can show similarities in negativity bias
Authors: Mark J. Brandt, Geoffrey Wetherell, Christine Reyna
Journal: Behavioral and Brain Sciences (2014)

Abstract Negativity bias may underlie the development of political ideologies, but liberals and conservatives are likely to respond to threats similarly. We review evidence from research on intolerance, motivated reasoning, and basic psychological threats that suggest liberals and conservatives are more similar than different when confronting threatening groups, situations, and information.
YB-1, the E2F Pathway, and Regulation of Tumor Cell Growth
Authors: Annette Lasham, Weini Samuel, Helen Cao, Rachna Patel, Reena Mehta, J. Lewis Stern, Glen Reid, Adele G. Woolley, Lance D. Miller, Michael A Black, Andrew N. Shelling, Cristin G. Print, Antony W. Braithwaite
Journal: JNCI Journal of the National Cancer Institute (2011)

Y-box binding factor 1 (YB-1) has been associated with prognosis in many tumor types. Reduced YB-1 expression inhibits tumor cell growth, but the mechanism is unclear. YB-1 mRNA levels were compared with tumor grade and histology using microarray data from 771 breast cancer patients and with disease-free survival and distant metastasis–free survival using data from 375 of those patients who did not receive adjuvant therapy. Microarrays were further searched for genes that had correlated expression with YB-1 mRNA. Small interfering RNA (siRNA) was used to study the effects of reduced YB-1 expression on growth of three tumor cell lines (MCF-7 breast, HCT116 colon, and A549 lung cancer cells), on tumorigenesis by A549 cells in nude mice, and on global transcription in the three cancer cell lines. Reporter gene assays were used to determine whether YB-1 siRNAs affected the expression of E2F1, and chromatin immunoprecipitation was used to determine whether YB-1 bound to various E2F promoters as well as E2F1-regulated promoters. All P values were from two-sided tests. YB-1 levels were elevated in more aggressive tumors and were strongly associated with poor disease-free survival and distant metastasis–free survival. YB-1 expression was often associated with the expression of genes with E2F sites in their promoters. Cells expressing YB-1 siRNA grew substantially more slowly than control cells and formed tumors less readily in nude mice. Transcripts that were altered in cancer cell lines with YB-1 siRNA included 32 genes that are components of prognostic gene expression signatures. YB-1 regulated expression of an E2F1 promoter–reporter construct in A549 cells (eg, relative E2F1 promoter activity with control siRNA = 4.04; with YB-1 siRNA = 1.40, difference= −2.64, 95% confidence interval = −3.57 to −1.71, P < .001) and bound to the promoters of several well-defined E2F1 target genes. YB-1 expression is associated with the activity of E2F transcription factors and may control tumor cell growth by this mechanism.
Dexamethasone in patients with acute lung injury from acute monocytic leukaemia
Authors: E. Azoulay, E. Canet, E. Raffoux, E. Lengline, V. Lemiale, F. Vincent, A. de Labarthe, A. Seguin, N. Boissel, H. Dombret, B. Schlemmer
Journal: European Respiratory Journal (2011)

The use of steroids is not required in myeloid malignancies and remains controversial in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). We sought to evaluate dexamethasone in patients with ALI/ARDS caused by acute monocytic leukaemia (AML FAB-M5) <i>via</i> either leukostasis or leukaemic infiltration. Dexamethasone (10 mg every 6 h until neutropenia) was added to chemotherapy and intensive care unit (ICU) management in 20 consecutive patients between 2005 and 2008, whose data were compared with those from 20 historical controls (1994–2002). ICU mortality was the primary criterion. We also compared respiratory deterioration rates, need for ventilation and nosocomial infections. 17 (85%) patients had hyperleukocytosis, 19 (95%) had leukaemic masses, and all 20 had severe pancytopenia. All patients presented with respiratory symptoms and pulmonary infiltrates prior to AML FAB-M5 diagnosis. Compared with historical controls, dexamethasone-treated patients had a significantly lower ICU mortality rate (20% <i>versus</i> 50%; p=0.04) and a trend for less respiratory deterioration (50% <i>versus</i> 80%; p=0.07). There were no significant increases in the rates of infections with dexamethasone. In conclusion, in patients with ALI/ARDS related to AML FAB-M5, adding dexamethasone to conventional chemotherapy seemed effective and safe. These results warrant a controlled trial of dexamethasone <i>versus</i> placebo in AML FAB-M5 patients with noninfectious pulmonary infiltrates.
Immunotherapy of Murine Leukemia. II. Effect of Passive Serum Therapy on Friend Murine Leukemia Virus-Induced Hematologic and Coagulation Parameters&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Fred Sanfilippo, Kuo-Jang Kao, Salvatore V. Pizzo, Jeffrey J. Collins
Journal: JNCI Journal of the National Cancer Institute (1980)

Journal Article Immunotherapy of Murine Leukemia. II. Effect of Passive Serum Therapy on Friend Murine Leukemia Virus-Induced Hematologic and Coagulation Parameters Get access Fred Sanfilippo, Fred Sanfilippo 5 3Department of Pathology, Duke University Medical Center, Durham, N.C. 27710.4Department of Microbiology and Immunology, Duke University Medical Center. 5Address reprints requests to Dr. Sanfilippo, P.O. Box 3712, Duke University Medical Center. Search for other works by this author on: Oxford Academic PubMed Google Scholar Kuo-Jang Kao, Kuo-Jang Kao 3Department of Pathology, Duke University Medical Center, Durham, N.C. 27710. Search for other works by this author on: Oxford Academic PubMed Google Scholar Salvatore V. Pizzo, Salvatore V. Pizzo 3Department of Pathology, Duke University Medical Center, Durham, N.C. 27710.6Department of Biochemistry, Duke University Medical Center. Search for other works by this author on: Oxford Academic PubMed Google Scholar Jeffrey J. Collins Jeffrey J. Collins 4Department of Microbiology and Immunology, Duke University Medical Center.7Department of Surgery, Duke University Medical Center.8Scholar of the Leukemia Society of America, Inc. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 64, Issue 3, March 1980, Pages 547–553, https://doi.org/10.1093/jnci/64.3.547 Published: 01 March 1980 Article history Received: 12 March 1979 Accepted: 17 August 1979 Published: 01 March 1980
Improving outcomes from community-acquired pneumonia: we need to be more sophisticated about cause and effect
Authors: G. W. Waterer, D. Lopez
Journal: European Respiratory Journal (2011)

Quality of care indicators are being introduced in many countries for many diseases, in an attempt by the funders of healthcare to ensure optimal outcomes are being achieved. However, the extent to which an improvement in performance, in one or more of these indicators, actually improves the outcomes of patients with community-acquired pneumonia (CAP) remains very unclear.

In the current issue of the European Respiratory Journal , Menendez et al. [1] publish their analysis of the relationship between various measures of quality of care in patients with CAP and clinical outcomes in a large multicentre Spanish study. The three quality measures they focused on were: adherence to antibiotic guidelines, delivery of the first dose of antibiotics within 6 h of presentation, and measurement of oxygenation at presentation. Consistent with the findings of other groups, adherence to antibiotic guidelines was associated with a shorter length of stay in patients without organ failure. In patients with more severe sepsis, mortality was also better in those who received guideline-concordant antibiotics within the first 6 h, but not in those who …