tbuckley/cabot-search huggingface dataset:
Lowering Bone Mineral Affinity of Bisphosphonates as a Therapeutic Strategy to Optimize Skeletal Tumor Growth Inhibition<i>In vivo</i>
Authors: Pierrick G.J. Fournier, Florence Daubiné, Mark W. Lundy, Michael J. Rogers, Frank H. Ebetino, Philippe Clézardin
Journal: Cancer Research (2008)

Abstract Bisphosphonates bind avidly to bone mineral and are potent inhibitors of osteoclast-mediated bone destruction. They also exhibit antitumor activity in vitro. Here, we used a mouse model of human breast cancer bone metastasis to examine the effects of risedronate and NE-10790, a phosphonocarboxylate analogue of the bisphosphonate risedronate, on osteolysis and tumor growth. Osteolysis was measured by radiography and histomorphometry. Tumor burden was measured by fluorescence imaging and histomorphometry. NE-10790 had a 70-fold lower bone mineral affinity compared with risedronate. It was 7-fold and 8,800-fold less potent than risedronate at reducing, respectively, breast cancer cell viability in vitro and bone loss in ovariectomized animals. We next showed that risedronate given at a low dosage in animals bearing human B02-GFP breast tumors reduced osteolysis by inhibiting bone resorption, whereas therapy with higher doses also inhibited skeletal tumor burden. Conversely, therapy with NE-10790 substantially reduced skeletal tumor growth at a dosage that did not inhibit osteolysis, a higher dosage being able to also reduce bone destruction. The in vivo antitumor activity of NE-10790 was restricted to bone because it did not inhibit the growth of subcutaneous B02-GFP tumor xenografts nor the formation of B16-F10 melanoma lung metastases. Moreover, NE-10790, in combination with risedronate, reduced both osteolysis and skeletal tumor burden, whereas NE-10790 or risedronate alone only decreased either tumor burden or osteolysis, respectively. In conclusion, our study shows that decreasing the bone mineral affinity of bisphosphonates is an effective therapeutic strategy to inhibit skeletal tumor growth in vivo. [Cancer Res 2008;68(21):8945–53]
Sputum purulence-guided antibiotic use in hospitalised patients with exacerbations of COPD
Authors: Néstor Soler, Mariano Esperatti, Santiago Ewig, Arturo Huerta, Carlos Agustí, Antoni Torres
Journal: European Respiratory Journal (2012)

In patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) needing hospitalisation, sputum purulence is associated with bacteria in the lower respiratory tract. We performed a prospective non-randomised interventional pilot study applying a sputum purulence-guided strategy of antibiotic treatment and investigating the relationship between sputum purulence and biomarkers. In hospitalised patients with acute exacerbation of COPD antibiotics were restricted to those with purulent sputum. The primary end-point was rate of therapeutic failure during hospitalisation. Secondary end-points were parameters reflecting short- and long-term outcomes. We included 73 patients, 34 with non-purulent sputum. No differences were observed on therapeutic failure criteria (9% non-purulent versus 10% purulent (p=0.51)). Serum C-reactive protein (CRP) was significantly increased in the purulent group at admission (11.6 versus 5.3, p=0.006) and at day 3 (2.7 versus 1.2, p=0.01). Serum procalcitonin (PCT) was similar between the groups. No differences were found in short-term outcomes. The exacerbation rate at 180 days was higher in the purulent group. These results support the hypothesis of performing a randomised trial using a sputum purulence-guided antibiotic treatment strategy in patients with acute exacerbations of COPD. CRP, but not PCT, may be a useful parameter to increase confidence of the absence of bacterial bronchial infection.
Papulopustular skin lesions are seen more frequently in patients with Behcet's syndrome who have arthritis: a controlled and masked study
Authors: E Diri
Journal: Annals of the Rheumatic Diseases (2001)

To determine the prevalence of acneiform skin lesions (comedones, papules, and pustules) in patients with Behçet's syndrome (BS) with arthritis.Study groups included 44 patients with BS with arthritis (32 men, 12 women, mean (SD) age 37.8 (8.9)), 42 patients with BS without arthritis (31 men, 11 women, mean age 35.5 (6.4)), 21 patients with active rheumatoid arthritis (five men, 16 women, mean age 48.8 (14)), and 33 healthy volunteers (28 men, five women, mean age 40.1 (8.1)). All probands and controls were examined by a rheumatologist and a dermatologist, in a prospective and masked protocol. An ophthalmological evaluation was performed if necessary. Skin lesions, including comedones, papules, and pustules, were counted and scored as 0: absent, 1: 1-5, 2: 6-10, 3: 11-15, 4: 16-20, and 5: >20.Although there was no significant difference between the four groups in the prevalence of comedones, the number of papules and pustules was significantly higher in patients with BS with arthritis (p=0.0037 for papules and p<0.0001 for pustules) than in the remaining three groups.Acneiform skin lesions (papules and pustules) seem to be more frequent in patients with BS with arthritis. This suggest that the arthritis seen in BS may possibly be related to acne associated arthritis.
Altered Dynamics of Intestinal Cell Maturation in <i>Apc1638N/+</i> Mice
Authors: Donghai Wang, Rossanna C. Pezo, Georgia Corner, Cristina Sison, Martin L. Lesser, Shailesh M. Shenoy, John M. Mariadason, Robert H. Singer, Leonard H. Augenlicht
Journal: Cancer Research (2010)

Abstract Novel imaging of active transcription sites in interphase nuclei of intestinal epithelial cells in situ showed that key genes associated with Wnt and Notch signaling were dynamically regulated as the cells underwent normal maturation during their migration along the mouse crypt-villus axis (CVA). However, oscillating patterns of activation of these genes were displaced along this axis in the histologically normal intestinal mucosa of Apc1638N/+ mice before tumor development. Gene expression profiling then showed that the normal reprogramming of cells along the CVA was dampened in the Apc1638N/+ mice, with an overrepresentation of c-myc target genes among those loci affected in the mutant mice. Moreover, in the Apc1638N/+ mice, there was a perturbed pattern of expression of lineage-specific markers along the CVA consistent with transcription site repression of the Math1 gene, and genes encoding enzymes of every step of the tricarboxylic acid cycle were downregulated in the crypt of Apc1638N/+ mice compared with WT, but not in the villus. These changes may alter energy metabolism and generate a pseudohypoxic state, suggested by elevated expression of Hif1α and its target genes. Thus, although intestinal tumors develop in Apc1638N/+ mice on focal loss or inactivation of the WT allele, our results show that in the Apc1638N/+ mouse, inheritance of only a single WT Apc allele perturbs the dynamic and complex reprogramming underlying normal cell maturation, which links epithelial function and homeostasis with architectural organization of the intestine. Cancer Res; 70(13); 5348–57. ©2010 AACR.
Basophils Play a Pivotal Role in Immunoglobulin-G-Mediated but Not Immunoglobulin-E-Mediated Systemic Anaphylaxis
Authors: Yusuke Tsujimura, Kazushige Obata, Kaori Mukai, Hideo Shindou, Masayuki Yoshida, Hideto Nishikado, Yohei Kawano, Yoshiyuki Minegishi, Takao Shimizu, Hajime Karasuyama
Journal: Immunity (2008)
THE QUANTITATIVE DETERMINATION OF INFLUENZA VIRUS AND ANTIBODIES BY MEANS OF RED CELL AGGLUTINATION
Authors: George K. Hirst
Journal: The Journal of Experimental Medicine (1942)

1. The agglutination titer for chicken red cells of freshly prepared or carefully stored suspensions of PR8 influenza virus, that is to say virus of maximum pathogenicity, was found to be proportional to the mouse lethal titer of the same preparations. 2. The agglutination titer of infected allantoic fluid procured in a standard way is relatively constant, regardless of the influenza strain used and its pathogenicity for mice. 3. Virus preparations inactivated by heat or storage may retain their agglutinating power. 4. Certain animal sera contain a partially heat-labile factor which, in low dilution, inhibits the agglutination of chicken red cells by influenza A and influenza B viruses. 5. The agglutination inhibition test, using ferret and human sera, gives qualitative data regarding influenza antibodies which are similar to the information obtained on the same sera by means of the virus neutralization test. 6. There is a definite relationship between the agglutination inhibition titer and the virus neutralization titer of a serum. On a logarithmic scale of both variables, this relationship is essentially linear within the range investigated. 7. The agglutination inhibition titer of immune ferret serum is inversely proportional to the amount of virus used in the test.
Cost benefit of out of hours endoscopy: the options
Authors: T. Heymann
Journal: Gut (2010)

The title of Professor Barkun's commentary on out of hours endoscopy1 caught my attention. He provides an excellent intelligible review of the evidence in favour of fairly early endoscopy for many patients who present with acute upper gastrointestinal (GI) haemorrhage, but he refers to cost only in linking early endoscopy to the potential for shorter hospital stays and so lower charges. I support the idea that suitably experienced endoscopists should be available out of hours to provide advice and endoscopy for patients who present with more severe GI haemorrhage just as colleagues in other specialities should be available to offer advice …
VASCULAR FUNCTION AND OCULAR INVOLVEMENT IN SARCOIDOSIS
Authors: Gerasimos Siasos, Theodore Paraskevopoulos, Dimitris Tousoulis, Elias Gialafos, Evangelos Oikonomou, Marina Zaromitidou, Stamatios Kioufis, Konstantinos Maniatis, Georgia Siasou, Nikolaos Gouliopoulos, Eleni Kokkou, Savvas Mazaris, Theodosia Konsola, Christodoulos I Stefanadis
Journal: Journal of the American College of Cardiology (2014)
Comparison of the effects of ranitidine, cimetidine and placebo on the 24 hour intragastric acidity and nocturnal acid secretion in patients with duodenal ulcer.
Authors: R P Walt, P J Male, J Rawlings, R H Hunt, G J Milton-Thompson, J J Misiewicz
Journal: Gut (1981)

Twenty-four hour intragastric acidity and nocturnal acid secretion were measured in 10 males with duodenal ulcer in four separate 24 hour studies, during which the subjects ate normal meals, had unrestricted physical activity, and consumed their customary quantities of tobacco. The medication consisted of either placebo, cimetidine 200 mg tds and 400 mg at night, or ranitidine 150 mg bd, or 200 mg bd. Ranitidine 150 mg bd decreased mean 24 hour hydrogen ion activity from 41.8 mmol/l to 13.1 mmol/l (-69%, P less than 0.001) and nocturnal acid output from 6.1 mmol/h to 0.6 mmol/h (-90%, P less than 0.01). This degree of inhibition was significantly greater than that due to cimetidine (P less than 0.001 for 24 hours acidity, less than 0.05 for night time acid output). Plasma concentrations of ranitidine were greater than the IC50 for more than eight hours after the 150 mg dose. Ranitidine 200 mg conferred no additional advantage. Ranitidine 150 mg bd should be tested in therapeutic trials.
The power Doppler twinkling artefact associated with periarticular calcification induced by intra-articular corticosteroid injection in patients with rheumatoid arthritis
Authors: Yasuo Nagafuchi, Shuji Sumitomo, Yoko Soroida, Takeyuki Kanzaki, Yukiko Iwasaki, Kazuya Michishita, Tomomi Iwai, Hitoshi Ikeda, Keishi Fujio, Kazuhiko Yamamoto
Journal: Annals of the Rheumatic Diseases (2013)

Intra-articular corticosteroid injections are widely used to treat rheumatoid arthritis (RA).1 Although they are useful in combination with other antirheumatic agents, some side effects have been reported including subcutaneous atrophy, septic arthritis, avascular necrosis, and rarely, periarticular calcification.2–4 We report here two RA cases that presented with periarticular calcification.

Case 1. A 51-year-old woman suffering from RA for 6 years was treated with methotrexate 16 mg weekly, abatacept 500 mg monthly and triamcinolone acetonide injection on the radial side of the right third proximal interphalangeal (PIP) joint approximately once a month (22 times for the third PIP joint in total). While disease activity scores for 28 joints maintained low disease activity, a hand radiograph showed progressive periarticular calcifications on the injected radial side (figure 1A–C). Joint ultrasonography revealed hyperechoic regions in the joint cavity with posterior power Doppler (PD) signals (figure 2A). Spectral Doppler sonography was performed to evaluate the nature of the PD signals, and an artefactual spectral signal without any definable flow pattern was observed (figure 2B). This finding was obviously different from the true RA synovitis finding detected on her right first metacarpophalangeal joint (figure 2C). …
Antibody-Dependent Lysis of Tumor Cells In Vivo. II. Elimination of Chromium-51 as a Measurement of Cytolysis&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;
Authors: J C Scornik, P A Klein
Journal: JNCI Journal of the National Cancer Institute (1978)

The effect of antibody on tumor cells was studied in vivo by measurement of the rate of elimination of 51Cr in A/J mice inoculated with labeled Ehrlich tumor cells. Mice receiving ip injections of tumor cells and normal serum eliminated 51Cr rapidly during the first 24 hours and at a much slower rate thereafter. This biphasic pattern of elimination was due to the fact that 51Cr predominantly labels small (less than 13,000 mol wt) intracellular molecules, which the mouse rapidly eliminates, whereas larger labeled molecules are eliminated slowly. Antibody to tumor cells significantly accelerated the elimination of 51Cr at concentrations that regularly suppressed tumor growth. Antibody also induced a faster elimination rate in mice treated with cobra venom factor but not in mice treated with silica or inoculated sc with the tumor cells. Unlabeled tumor cells inhibited antibody-induced 51Cr clearance in normal mice but not in proteose peptone-treated mice. These results suggested that peritoneal cells are required in the induction of antibody-dependent cytolysis in vivo. In addition, actively or passively alloimmunized mice exhibited a similar accelerated 51Cr elimination rate when inoculated with the appropriate labeled target cells.
Coping Resources, Coping Processes, and Mental Health
Authors: Shelley E. Taylor, Annette L. Stanton
Journal: Annual Review of Clinical Psychology (2007)

Coping, defined as action-oriented and intrapsychic efforts to manage the demands created by stressful events, is coming to be recognized both for its significant impact on stress-related mental and physical health outcomes and for its intervention potential. We review coping resources that aid in this process, including individual differences in optimism, mastery, self-esteem, and social support, and examine appraisal and coping processes, especially those marked by approach or avoidance. We address the origins of coping resources and processes in genes, early life experience, and gene-environment interactions, and address neural underpinnings of coping that may shed light on evaluating coping interventions. We conclude by outlining possible intervention strategies for improving coping processes.
SIGNALING NETWORKS IN LIVING CELLS
Authors: Michael A. White, Richard G.W. Anderson
Journal: The Annual Review of Pharmacology and Toxicology (2004)

Recent advances in cell signaling research suggest that multiple sets of signal transducing molecules are preorganized and sequestered in distinct compartments within the cell. These compartments are assembled and maintained by specific cellular machinery. The molecular ecology within a compartment creates an environment that favors the efficient and accurate integration of signaling information arriving from humoral, mechanical, and nutritional sources. The functional organization of these compartments suggests they are the location of signaling networks that naturally organize into hierarchical interconnected sets of molecules through their participation in different classes of interacting units. An important goal is to determine the contribution of the compartment to the function of these networks in living cells.
Treatment of Cancer During Pregnancy: The Need for Tailored Strategies
Authors: Hatem A. Azim, Fedro A. Peccatori
Journal: Journal of Clinical Oncology (2010)

TO THEEDITOR:Van Calsteren et al 1 recently reported a retrospective analysis of 215 patients with cancer who were diagnosed and managed during the course of pregnancy. They showed that managing patients with cancer during pregnancy is feasible and is not associated with an increased risk of fetal malformations. However,theauthorsstatedtheirconcernsregardingthehighincidence of preterm deliveries, which reached 54.2% in their series. They emphasized that preterm delivery is associated with high risk of medicalcomplications,whichcouldhaveseriousconsequenceson fetal morbidity and mortality. In an attempt to reduce this risk, they proposed delaying adjuvant therapy for patients with early breast cancer until fetal maturity, even if this would entail holding therapy up to 3 months. They referred to a mathematical model suggesting that delaying adjuvant therapy in gestational breast cancer could be an acceptable approach. 2 They also suggested that if chemotherapy is considered, delivery should be delayed until fetal maturity rather than fetal viability. We completely agree with the second proposition provided the proper selection of the agents administered during the course of gestation. Nevertheless, although we acknowledge that delaying adjuvant therapy for patients with breast cancer is reasonable in some cases, it remains questionable for many others as a result of the typically aggressive biology of gestational breast cancer. It has been shown that almost 50% of patients with breast cancer diagnosed during pregnancy are diagnosed with locally advanced, node-positivedisease. 3 Furthermore,delayingadjuvantchemotherapy beyond 3 weeks from surgery was shown to be detrimental in patients with endocrine unresponsive tumors. 4 Thus, chemotherapy should not be delayed in pregnant patients with breast cancer whoneedit.Theexceptionwouldbeforpatientsdiagnosedduring the first trimester, in which the incidence of fetal malformation is as high as 20%. 5 Of 83 patients diagnosed with gestational breast cancer, only six infants (7%) had a birth weight below the 10th percentile for gestational age. Other studies showed similar results as well. 6,7 Hence,itisnotclearthatpatientswithearlybreastcancerarethose at significant risk of preterm delivery if exposed to chemotherapy during the pregnancy course. We believe it is hard to generalize conclusions and caution should be taken when dealing with less aggressive settings (eg, adjuvant breast cancer), in which we could compromise their treatment for fear of a risk, which seems to be low anyway in their case. We have recently conducted a systematic review of literature on theuseofdifferentsystemictherapiesinthetreatmentofpatientswith
Trait and state anxiety in male and female cross-country runners.
Authors: F. H. Sanderson, T. Reilly
Journal: British Journal of Sports Medicine (1983)

The purpose of this study was to explore the relationships between state/trait anxiety and competitive cross-country performance for males and females. A-trait and A-state pre- and post-competition were monitored in 38 females and 26 males at major meetings. The females' A-trait was correlated with pre-race A-state (p less than .05) which was itself correlated significantly with race performance (p less than .05). A significant post-race A-state reduction occurred only with the better runners. The correlation between A-trait and pre-race A-state was also found in the male athletes (p less than .05) while A-trait significantly correlated with race performance (p less than .05). A-state was significantly reduced post-race, the greatest decrease being observed in the top performers. It is concluded that trait as well as transient dispositions are relevant when psychological determinants of performance are considered.
Randomized Trials in Oncology Stopped Early for Benefit
Authors: Ryan A. Wilcox, Benjamin Djulbegovic, Gordon H. Guyatt, Victor M. Montori
Journal: Journal of Clinical Oncology (2007)

atedwithimprovedsurvival(hazardratio[HR],0.55;95%CI,0.38 to0.80;P.002).Giventheimplausibilityoftheseresults(because ofthelargerthanexpectedeffectonmortalityanditsinconsistency with the reduction in the risk of relapse, the key postulated mechanism for improved survival), the investigators continued the trial despite the apparent difference in survival. After random assignment of more than 1,000 patients, a significant survival advantage for five courses of consolidation chemotherapy could not be demonstrated, with an HR of 1.09 (95% CI, 0.87 to 1.37; P .4). The apparently significant results observed after few end points (ie, deaths) had occurred may be explained by data analysis at a “random high,” when a disproportionate number of events had occurred in the experimental arm by chance. Had this trial been stopped early and its results used to justify an additional course of consolidation chemotherapy, subsequent patients with acute myeloid leukemia would have been exposed to a costly, potentially toxic and ineffective therapy. The extent to which medical oncology RCTs that are stopped early for benefit manifest problems of inadequate reporting and likely effect overestimations, remains uncertain. Therefore, we examinedindetailthemedicaloncologyRCTspreviouslyreportedin the larger systematic review. 1 We reviewed the study characteristics, features related to the decision to monitor and stop the study early (sample size, interim analyses, monitoring and stopping rules), the number of events, and the estimated treatment effects reportedinthe29RCTsinmedicaloncologythathadbeenstopped early for benefit (Appendix, online only).
On a Handy Method of Examining Morbid Nervous Tissues Microscopically
Authors: J. B. Tuke
Journal: BMJ (1874)

TIE BRITISH MEDICAL 7OURNAL.[Sept.5, I874the voyage to Africa, from which it has been our cood fortune to return, after much sickness, many adventures, and hairbreadth escapes.A few typographical errors have unfortunately crept in, which the indulgent reader will kindly overlook.As rough notes