tbuckley/cabot-search huggingface dataset:
Human melanoma cells selected for resistance to apoptosis by prolonged exposure to tumor necrosis factor-related apoptosis-inducing ligand are more vulnerable to necrotic cell death induced by cisplatin.
Authors: Xu Dong Zhang, Jing Jing Wu, Susan Gillespie, Jodie Borrow, Peter Hersey
Journal: Clinical Cancer Research (2006)

Abstract PURPOSE: Heterogeneous sensitivity of melanoma cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis may lead to outgrowth of TRAIL-resistant cells and limit successful treatment by TRAIL. The present study aims to better understand the biological characteristics of melanoma cells resistant to TRAIL-induced apoptosis. EXPERIMENTAL DESIGN: We generated TRAIL-resistant melanoma cells by prolonged exposure to TRAIL and characterized the cells in terms of their sensitivity to killing induced by a panel of cytotoxic agents using biological and biochemical methods. RESULTS: TRAIL-resistant melanoma cells are cross-resistant to apoptosis induced by another death ligand FasL, the DNA-damaging agent cisplatin, the histone deacetylase inhibitor suberic bishydroxamate, and the antimicrotubule Vinca alkaloid, vincristine. The apoptotic signaling seemed to be inhibited upstream of mitochondrial apoptotic events and was associated with decreased expression of multiple apoptotic mediators, including pro-caspase-8, Fas-associated death domain, Bid, Bim, p53, and the products of its proapoptotic target genes. Despite being resistant to apoptosis, TRAIL-resistant melanoma cells were more vulnerable to cisplatin-induced nonapoptotic cell death. This was characterized by lack of DNA fragmentation, delayed externalization of phosphatidylserine, caspase and p53 independence, and severe mitochondrial disruption, and was preceded by poly(ADP)ribose polymerase (PARP) activation and depletion of intracellular ATP, indicative of necrotic cell death. Inhibition of PARP activity partially converted the mode of cell death from necrosis to apoptosis. CONCLUSIONS: TRAIL-resistant melanoma cells are cross-resistant to apoptosis induced by various apoptotic stimuli but are more sensitive to nonapoptotic cell death induced by cisplatin. Exploration of chemotherapy-induced nonapoptotic cell death may provide an alternative strategy in overcoming resistance of melanoma cells to TRAIL-induced apoptosis.
The Minisatellite MSB1, in the Fungus Botrytis cinerea, Probably Mutates by Slippage
Authors: T. Giraud, D. Fortini, C. Levis, Y. Brygoo
Journal: Molecular Biology and Evolution (1998)

A minisatellite was identified in the intron of the ATP synthase of the filamentous fungus Botrytis cinerea, and it was named MSB1. This is the second fungal minisatellite described to date. Its 37-bp repeat unit is AT-rich, and it is found at only one locus in the genome. The introns of 47 isolates of Botrytis species were sequenced. The number of tandem repeats varied only from 5 to 11, but there were many repeat variants. The structure of MSB1 is peculiar: the variants are in the same physical order in all individuals, and this order follows the most parsimonious tree. These original characteristics, together with a total lack of recombination between alleles of the flanking regions, suggest that MSB1 probably mutates by slippage. MSB1 was found in the intron of the ATP synthase of all of the Botrytis species analyzed, but the repeat unit was not found in any other genus examined, including Sclerotinia, which is the genus closest to Botrytis.
The prehistory of number concept
Authors: Karenleigh A. Overmann, Thomas Wynn, Frederick L. Coolidge
Journal: Behavioral and Brain Sciences (2011)

Abstract Carey leaves unaddressed an important evolutionary puzzle: In the absence of a numeral list, how could a concept of natural number ever have arisen in the first place? Here we suggest that the initial development of natural number must have bootstrapped on a material culture scaffold of some sort, and illustrate how this might have occurred using strings of beads.
Bronchial Interleukin-5 and Eotaxin Expression in Nasal Polyposis
Authors: CATHERINE LAMBLIN, FLORENCE BOLARD, PHILIPPE GOSSET, ANNE TSICOPOULOS, THIERRY PEREZ, JEAN DARRAS, ANNE JANIN, ANDRÉ BERNARD TONNEL, QUTAYBA HAMID, BENOIT WALLAERT
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

An eosinophilic bronchial inflammation was previously demonstrated in patients with nasal polyposis (NP) and asymptomatic bronchial hyperresponsiveness (BHR) similar to that observed in asthmatic patients with NP, whereas patients with NP without BHR did not. The aim of the study was to investigate the contribution of interleukin 5 (IL-5) and eotaxin to the pathogenesis of BHR associated with NP. Eleven patients with NP without BHR (Group A), 8 patients with NP and asymptomatic BHR (Group B), and 9 patients with NP and asthma (Group C) were included. Bronchial biopsies were studied for IL-5 and eotaxin immunoreactivity and IL-5 mRNA expression. IL-5 levels were determined in bronchial lavage (BL). Compared with Groups A and B, Group C patients exhibited higher numbers of IL-5 protein+ cells, IL-5 mRNA+ cells, and eotaxin+ cells in bronchial submucosa. Compared with Group A, Group B patients showed an increased number of IL-5 protein+ cells, whereas the number of IL-5 mRNA+ cells and eotaxin+ cells was similar. IL-5 levels in BL were increased only in Group C. Our study provides evidence of IL-5 involvement in bronchial eosinophilia and in the pathogenesis of asymptomatic BHR associated with NP, whereas both IL-5 and eotaxin are involved in asthma associated with NP.
HIV-Specific Differences in Outcome of Squamous Cell Carcinoma of the Anal Canal: A Multicentric Cohort Study of HIV-Positive Patients Receiving Highly Active Antiretroviral Therapy
Authors: Christoph Oehler-Jänne, Florence Huguet, Sawyna Provencher, Burkhardt Seifert, Laura Negretti, Marc-Oliver Riener, Marta Bonet, Abdelkarim S. Allal, I. Frank Ciernik
Journal: Journal of Clinical Oncology (2008)

To define clinical outcome after definitive chemoradiotherapy (CRT) of anal carcinoma in HIV-infected patients treated with highly active antiretroviral therapy (HAART).A multicentric cohort comparison of 40 HIV-positive patients with HAART and 81 HIV-negative patients treated with radiotherapy (RT) or CRT was retrospectively performed. Local disease control (LC), relapse-free survival (RFS), overall survival (OS), cancer-specific survival (CSS), toxicity, and prognostic factors were investigated.HIV-positive patients were younger (mean age, 48 v 62 years; P < .0005), predominantly male (93% v 25%; P < .0005), and with early-stage (P = .06) and large-cell histology (90% v 67%; P = .005) disease. RT or CRT resulted in complete response in 92% (HIV positive) and 96% (HIV negative) of cases. Five-year OS was 61% (95% CI, 44% to 78%) in HIV-positive and 65% (95% CI, 53% to 77%) in HIV-negative patients (median follow-up, 36 months). Five-year LC was 38% (95% CI, 5% to 71%) in HIV-positive and 87% (95% CI, 79% to 95%) in HIV-negative patients (P = .008) compromising CSS and sphincter preservation. Grade 3/4 acute skin (35% v 17% [HIV negative]; P = .04) and hematologic (33% v 12% [HIV negative]; P = .08) toxicity together approximated 50% in HIV-positive patients. RFS in HIV-positive patients was associated with RT dose (P = .08) and severe acute skin toxicity (P = .04).Long-term LC and acute toxicity represent major clinical challenges in HIV-positive patients with anal carcinoma. Even if fluoropyrimidine-based CRT is feasible and may result in similar response rates and OS as in HIV-negative patients, improved treatment strategies with better long-term outcome are warranted.
Contribution of inflammation to the pathology of idiopathic pulmonary arterial hypertension in children
Authors: S Hall, P Brogan, S G Haworth, N Klein
Journal: Thorax (2009)

Idiopathic pulmonary arterial hypertension (IPAH) is an incurable disease of multifactorial origin. Inflammation is frequently observed in IPAH, but its role in the pathobiology is unclear. In this study the distribution, nature and number of inflammatory cells in periarterial infiltrates in lungs of children with IPAH, pulmonary arterial hypertension associated with congenital heart disease (APAH) and in normal lung tissue were characterised and compared using immunohistochemistry The influence of treatment with combined prostacyclin and endothelin receptor blockers was also studied. In children with IPAH, both treated and untreated, but not in children with APAH or normal children, extensive periarterial infiltrates were present comprising macrophages and T lymphocytes with S100A4- and bone morphogenetic protein receptor type-2 (BMPR2)-positive cells. Although rarely co-expressing macrophage-specific antigens, BMPR2-positive cells were frequently closely associated with macrophages and lymphocytes. They were more abundant around peripheral arteries of children with IPAH than in APAH or normal lungs (15.1 (3.5), 2.3 (0.9) and 2.3 (0.9) cells/mm external elastic lamina, respectively; p&lt;0.01 for IPAH vs APAH or normal lungs). Prostacyclin with endothelin receptor blockade resulted in a significant reduction in endothelial cell activation as indicated by human leucocyte antigen (HLA)-DR expression (treated 17% vs untreated 100%, p&lt;0.002). This study shows that pulmonary inflammation is present in the lungs of children with IPAH. This may indicate a role for inflammation in the pathobiology of IPAH and provide the rationale for novel therapeutic intervention.
Local and systemic effects of an allogeneic tumor cell vaccine combining transgenic human lymphotactin with interleukin-2 in patients with advanced or refractory neuroblastoma
Authors: Raphaël F. Rousseau, Ann E. Haight, Charlotte Hirschmann-Jax, Eric S. Yvon, Donna R. Rill, Zhuyong Mei, Susan C. Smith, Shannon Inman, Kristine Cooper, Pat Alcoser, Bambi Grilley, Adrian Gee, Edwina Popek, Andrew Davidoff, Laura C. Bowman, Malcolm K. Brenner, Douglas Strother
Journal: Blood (2003)
Identification of immunodominant VP1 linear epitope of enterovirus 71 (EV71) using synthetic peptides for detecting human anti-EV71 IgG antibodies in western blots
Authors: D.G.W. Foo, R.X. Ang, S. Alonso, V.T.K. Chow, S.H. Quak, C.L. Poh
Journal: Clinical Microbiology and Infection (2008)
Brackets (parentheses) in formulas
Authors: D. G. Altman, J. M. Bland
Journal: BMJ (2011)

Each year, new health sciences postgraduate students in York are given a simple maths test. Each year the majority of them fail to calculate 20 – 3 × 5 correctly. According to the conventional rules of arithmetic, division and multiplication are done before addition and subtraction, so 20 − 3 × 5 = 20 − 15 = 5. Many students work from left to right and calculate 20 − 3 × 5 as 17 × 5 = 85. If that was what was actually meant, we would need to use brackets: (20 − 3) × 5 = 17 × 5 = 85. Brackets tell us that the enclosed part must be evaluated first. That convention is part of various mnemonic acronyms which indicate the order of operations, such as BODMAS (Brackets, Of (that is, power of), Divide, Multiply, Add, Subtract) and PEMDAS (Parentheses, Exponentiation, Multiplication, Division, Addition, Subtraction).1 

Schoolchildren learn the basic rules about how to construct and interpret mathematical formulas.1 The conventions exist to ensure that there is absolutely no ambiguity, as mathematics (unlike prose) has …
C-reactive Protein: A Physiological Activator of Interleukin 6 Receptor Shedding
Authors: Simon A. Jones, Daniela Novick, Sankichi Horiuchi, Naoki Yamamoto, Alexander J. Szalai, Gerald M. Fuller
Journal: The Journal of Experimental Medicine (1999)

The soluble interleukin 6 receptor (sIL-6R) circulates at elevated levels in various diseases. This suggests that inflammatory mediators control sIL-6R release. Through examination of human neutrophils, it was found that the acute phase reactant C-reactive protein (CRP) activates a threefold increase in sIL-6R production. Maximal release occurred after 30–60 min exposure to CRP (50 μg/ml), and was mimicked by peptides corresponding to amino acid residues 174– 185 and 201–206 of native CRP. A third peptide fragment (77–82) had no effect. Differential mRNA splicing did not account for the CRP-mediated release of sIL-6R, since this isoform was not detected in conditioned media. Furthermore, stimulation of neutrophils with CRP or with peptides 174–185 or 201–206 promoted a loss of membrane-bound IL-6R, suggesting release by proteolytic shedding. The metalloprotease inhibitor TAPI had only a marginal effect on CRP-mediated sIL-6R release, suggesting that shedding occurs via a mechanism distinct from that previously reported. It well established that IL-6 stimulates the acute phase expression of CRP. Our current findings demonstrate a novel relationship between these two mediators, since CRP may affect IL-6–mediated inflammatory events by enabling formation of the sIL-6R/IL-6 complex.
Bacterial Histamine Release by Immunological and Non‐Immunological Lectin‐Mediated Reactions
Authors: C. Jensen, S. Norn, P. Stahl Skov, F. Espersen, Chr. Koch, H. Permin
Journal: Allergy (1984)

The mechanisms of bacteria‐induced histamine release were examined in vitro in human leukocytes and rat mast cells. Three types of bacterial responders were found. In persons with IgE‐bearing basophilocytes bacterial histamine release could be triggered by two different mechanisms, an IgE‐dependent mechanism where removal of IgE abolished the release and a non‐immunological mechanism where this was not the case. In responders with no IgE‐bearing cells bacterial histamine release was caused by a non‐immunological mechanism. The non‐immunological mechanism was further substantiated by release in isolated mast cells from germ‐free rats. These experiments suggest a direct interaction between bacteria and target cell, and experiments with multi‐washed bacteria and bacteria cell wall preparations indicate the possibility of the bacteria wall interacting with the target cell. It is probable that the non‐immunological mechanism depends on lectin‐mediated reactions, since bacteria‐induced histamine release was inhibited by lectin‐binding sugars as is release caused by plant lectins.
ENDOTHELIAL-DEPENDENT MECHANISMS IN CHRONIC INFLAMMATORY LEUKOCYTE RECRUITMENT
Authors: Francis W. Luscinskas, Ph.D, Michael A. Gimbrone
Journal: Annual Review of Medicine (1996)

▪ Abstract Peripheral blood leukocytes interact with the vascular endothelium in a wide range of physiologic and pathophysiologic situations. A current working concept is that activation of vascular endothelium is an important event during the inflammatory response, conferring spatial and temporal localization and leukocyte-type selectivity to the recruitment process. This chapter highlights recent advances in our understanding of the endothelial-dependent molecular mechanisms that mediate recruitment of mononuclear leukocytes (lymphocytes and monocytes) and discusses these advances in the context of chronic inflammatory diseases and their potential therapeutic interventions.
Phosphorylation and Putative ER Retention Signals Are Required for Protein Kinase A-Mediated Potentiation of Cardiac Sodium Current
Authors: Jingsong Zhou, Hyeon-Gyu Shin, Jianxun Yi, Wangzhen Shen, Christine P. Williams, Katherine T. Murray
Journal: Circulation Research (2002)

Activation of protein kinase A (PKA) increases Na+ current derived from the human cardiac Na+ channel, hH1, in a slow, nonsaturable manner. This effect is prevented by compounds that disrupt plasma membrane recycling, implying enhanced trafficking of channels to the cell membrane as the mechanism responsible for Na+ current potentiation. To investigate the molecular basis of this effect, preferred consensus sites (serines 483, 571, and 593) and alternative sites phosphorylated by PKA in the rat heart isoform (serines 525 and 528) were removed in the I-II interdomain linker, a region in the channel previously implicated in the PKA response. Our results demonstrate that the presence of either serine 525 or 528 is required for Na+ current potentiation. The role of amino acid sequences that can mediate channel-protein interactions was also examined. Removal of a PDZ domain-binding motif at the carboxy terminus of hH1 did not alter the PKA response. The I-II interdomain linker of the channel contains 3 sites (479RKR481, 533RRR535, and 659RQR661) with the sequence RXR, a motif known to mediate retention of proteins in the endoplasmic reticulum (ER). The PKA-mediated increase in Na+ current was abolished when all 3 sites were eliminated, with RRR at position 533 to 535 primarily responsible for this effect. These results demonstrate that both alpha-subunit phosphorylation and the presence of putative ER retention signals are required for the PKA-mediated increase in cardiac Na+ current, an effect that likely involves interaction of the I-II interdomain linker with other proteins or regions of the channel.
Long-term results of conventional-dose salvage chemotherapy in patients with refractory and relapsed Hodgkin’s disease (Croatian experience)
Authors: I. Radman, N. Bašić, B. Labar, J. Kovačević, I. Aurer, V. Bogdanić, S. Zupančić-Šalek, D. Nemet, J. Jakić-Razumović, M. Mrsić, F. Šantek, L. Grgić-Markulin, D. Boban
Journal: Annals of Oncology (2002)
Interactions between liver allografts and lymphocytotoxic alloantibodies in inbred rats
Authors: Didier Houssin, Blanche Bellon, Marie-Dominique Brunaud, Jean Gugenheim, Abdellatif Settaf, Francesco Meriggi, Jean Emond
Journal: Hepatology (1986)

Several clinical and experimental findings suggest that liver allografts are less sensitive than other organ allografts to lymphocytotoxic antibodies. In this experimental study in hypersensitized inbred rat recipients, rejection of liver allografts was delayed compared to that of heart allografts. Furthermore, there was a marked decrease in the level of cytotoxic antibodies after liver allografting but not after heart allografting in these animals. The decrease in the level of antibodies also occurred after donor-specific extracorporeal liver hemoperfusion in hypersensitized recipients. Whether the decrease was caused by a massive absorption of antibodies on the liver or related to excretion of major histocompatibility complex antigens in a soluble form remains to be demonstrated. These results support the hypothesis that the liver has a privileged position in regard to rejection and are consistent with clinical observations made following ABO incompatible or crossmatch positive liver transplantations.
Lung and blood T-cell receptor repertoire in extrinsic allergic alveolitis
Authors: J Wahlstrom, M Berlin, R Lundgren, O Olerup, H Wigzell, A Eklund, J Grunewald
Journal: European Respiratory Journal (1997)

Patients with extrinsic allergic alveolitis (EAA) have accumulations of T-lymphocytes in their lungs. CD8+ lung T-cells, in particular, have been implicated in the pathogenesis of EAA. The objective of the present study was to analyse the T-cell receptor (TCR) V alpha and V beta gene usage of CD4+ and CD8+ lung and peripheral blood lymphocytes (PBLs) before and after treatment. Twelve patients with clinical signs of extrinsic allergic alveolitis were studied at disease onset, and nine of the 12 were also studied after treatment and clinical recovery. Lung cells, obtained by bronchoalveolar lavage (BAL), and paired PBL samples were analysed by flow cytometry using a panel of anti-TCR V monoclonal antibodies. The changes in TCR V gene usage were most pronounced in BAL CD8+ cells, as compared to the BAL CD4+, PBL CD8+ and PBL CD4+ subsets. At disease onset, 10 of the 12 patients had lung restricted expansions of CD8+ T-cells using a particular V alpha or V beta gene segment, and 8 of the 12 patients had CD8+ T-cell expansions in PBL. For the patients in whom a follow-up was possible, a majority of the expansions in the lungs were normalized, whereas most of the expansions in PBL remained. An over-representation of human leucocyte antigen (HLA)-DR2 (15) was detected, particularly among patients with farmer's lung. An increased selected T-cell receptor V gene usage may follow specific interactions between T-cells and antigens. In extrinsic allergic alveolitis, we determined that such expansions occur most frequently in the lung CD8+ T-cells. Since most expansions of lung CD8+ T-cells normalized with clinical improvement, these are further implicated in the pathogenesis of extrinsic allergic alveolitis.
Isokinetic profile of wrist and forearm strength in elite female junior tennis players
Authors: T S Ellenbecker, E P Roetert, S Riewald
Journal: British Journal of Sports Medicine (2006)

In tennis, injuries to the elbow and wrist occur secondary to the repetitive nature of play and are seen at increasingly young ages. Isokinetic testing can be used to determine muscular strength levels, but dominant/non-dominant and agonist/antagonist relations are needed for meaningful interpretation of the results.To determine whether there are laterality differences in wrist extension/flexion (E/F) and forearm supination/pronation (S/P) strength in elite female tennis players.32 elite female tennis players (age 12 to 16 years) with no history of upper extremity injury underwent bilateral isokinetic testing using a Cybex 6000 dynamometer. Peak torque and single repetition work values for wrist E/F and forearm S/P were measured at speeds of 90 degrees/s and 210 degrees/s, with random determination of the starting extremity. Repeated measures analysis of variance was used to determine differences between extremities for peak torque and single repetition work values.Significantly greater (p<0.01) dominant arm wrist E/F and forearm pronation strength was measured at both testing speeds. Significantly less (p<0.01) dominant side forearm supination strength was measured at both testing speeds.Greater dominant arm wrist E/F and forearm pronation strength is common and normal in young elite level female tennis players. These strength relations indicate sport specific muscular adaptations in the dominant tennis playing extremity. The results of this study can guide clinicians who work with young athletes from this population. Restoring greater dominant side wrist and forearm strength is indicated after an injury to the dominant upper extremity in such players.
Treatment of Arterial Occlusive Disease of the Lower Extremities
Authors: A D Whittemore, N P Couch, J A Mannick
Journal: Annual Review of Medicine (1985)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Evaluation of allergen-microarray–guided dietary intervention as treatment of eosinophilic esophagitis
Authors: Bram D. van Rhijn, Berber J. Vlieg-Boerstra, Serge A. Versteeg, Jaap H. Akkerdaas, Ronald van Ree, Ingrid Terreehorst, Aline B. Sprikkelman, Joanne Verheij, Andreas J.P.M. Smout, Albert J. Bredenoord
Journal: Journal of Allergy and Clinical Immunology (2015)