tbuckley/cabot-search huggingface dataset:
AB0304 Clinical and serological response to tocilizumab in patients with rheumatoid arthritis
Authors: C. Casu, E. Bruschi, C. Alpini, S. Marceglia, L. Giacomelli, O. Epis
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The role of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP) in the response to treatment for rheumatoid arthritis (RA) is not fully understood. Studies investigating changes in the levels of RF in response to synthetic and biological DMARDs have not been able to confirm a definitive relationship between decreased RF subtypes and clinical response, while studies investigating changes in anti-CCP levels have yielded conflicting results. In addition, to our knowledge the correlation between autoantibodies and tocilizumab treatment has been poorly investigated. <h3>Objectives</h3> This study investigates the relationship between the presence and levels of RF and anti-CCP and clinical response to tocilizumab in patients with RA. <h3>Methods</h3> This was an observational longitudinal study in 27 patients with active, long-standing RA despite previous treatment with &gt;2 DMARDs and/or steroids. Patients were treated with tocilizumab 8 mg/kg every 4 weeks. All patients were assessed using approved clinical scales (VES, PCR, HAQ, DAS28-VES, DAS28-PCR, CDAI, and SDAI). IgM-, IgA- and IgG-RFs and anti-CCP antibodies were assessed using ELISA at baseline, 3 months (T1), 6 months (T2), and 12 months (T3). <h3>Results</h3> All patients showed significant and sustained clinical response to tocilizmuab treatment. All clinical scales with the exception of HAQ significantly decreased. There was a significant correlation (p=0.03) between anti-CCP and SDAI changes from baseline at T1 and T2. Likewise there were no significant correlations between antibody count at T0 and changes in the DAS-28 VES at T1 and at T2. No significant relationship between clinical scales and antibody levels RF-IgG, IgA, IgM and anti-CCP levels were observed. <h3>Conclusions</h3> Tocilizumab is effective in treating the clinical symptoms of RA, and the efficacy of this molecule was not correlated with either RF or anti-CCP levels. There is now a growing body of evidence suggesting that markers associated with clinical response may not be the same biomarkers that predict risk of further joint damage <h3>References</h3> MIKULS TR, O'DELL JR, STONER JA, ET AL: Association of rheumatoid arthritis treatment response and disease duration with declines in serum levels of IgM rheumatoid factor and anti-cyclic citrullinated peptide antibody. Arthritis Rheum 2004; 50: 3776–82. KARSDAL MA, WOODWORTH T, HENRIKSEN K, ET AL: Biochemical markers of ongoing joint damage in rheumatoid arthritis--current and future applications, limitations and opportunities. Arthritis Res Ther 2011; 13: 215 TAKEUCHI T, TANAKA Y, AMANO K, ET AL: Clinical, radiographic and functional effectiveness of tocilizumab for rheumatoid arthritis patients-REACTION 52-week study. Rheumatology 2011; 50: 1908–15. <h3>Disclosure of Interest</h3> None Declared
Randomized phase III trial of 2nd line gemcitabine and paclitaxel chemotherapy in patients with advanced bladder cancer: short-term versus prolonged treatment [German Association of Urological Oncology (AUO) trial AB 20/99]
Authors: P. Albers, S.-I. Park, G. Niegisch, G. Fechner, U. Steiner, J. Lehmann, D. Heimbach, A. Heidenreich, R. Fimmers, R. Siener
Journal: Annals of Oncology (2010)
Preprocedural Statin Medication Reduces the Extent of Periprocedural Non–Q-Wave Myocardial Infarction
Authors: Joerg Herrmann, Amir Lerman, Dietrich Baumgart, Lothar Volbracht, Rainer Schulz, Clemens von Birgelen, Michael Haude, Gerd Heusch, Raimund Erbel
Journal: Circulation (2002)

Stenting-related myocardial injury has been recognized as a frequent and prognostically important event, the extent of which depends on microcirculatory impairment in association with platelet aggregation, inflammation, and increased oxidative stress. Recent studies underscored the non-lipid-lowering effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) with antithrombotic, antiinflammatory, and antioxidative aspects. Thus, we tested the hypothesis that preprocedural statin therapy is associated with a reduction in the extent of stenting-related myocardial injury.We stratified 296 consecutive patients who were undergoing stenting of a de novo stenosis according to the preprocedural status of statin therapy (229 statin-treated and 67 control patients). Incidence of periprocedural myocardial injury was assessed by analysis of creatine kinase (CK; upper limit of normal [ULN] 70 IU/L for women, 80 IU/L for men) and cardiac troponin T (cTnT; bedside test; threshold 0.1 ng/mL) before and 6, 12, and 24 hours after the intervention. Relative to control patients, the incidence of CK elevation >3x ULN was more than 90% lower in statin-treated patients (0.4% versus 6.0%, P=0.01). Statin therapy was the only factor independently associated with a lower risk of CK elevation >3x ULN (OR: 0.08, 95% CI: 0.01 to 0.75; P=0.03). The overall incidences of CK and cardiac troponin T elevation were slightly lower in statin-treated than in control patients (14.4% versus 20.9%, P=0.3, and 17.9% versus 22.4%, P=0.5, respectively).Preprocedural statin therapy is associated with a reduction in the incidence of larger-sized, stenting-related myocardial infarctions. Prospective, randomized trials are warranted to further assess this cardioprotective effect of statins in coronary intervention.
CCL28 Controls Immunoglobulin (Ig)A Plasma Cell Accumulation in the Lactating Mammary Gland and IgA Antibody Transfer to the Neonate
Authors: Eric Wilson, Eugene C. Butcher
Journal: The Journal of Experimental Medicine (2004)

The accumulation of immunoglobulin (Ig)A antibody-secreting cells (ASCs) in the lactating mammary gland leads to secretion of antibodies into milk and their passive transfer to the suckling newborn. This transfer of IgA from mother to infant provides transient immune protection against a variety of gastrointestinal pathogens. Here we show that the mucosal epithelial chemokine CCL28 is up-regulated in the mammary gland during lactation and that IgA ASCs from this tissue express CCR10 and migrate to CCL28. In vivo treatment with anti-CCL28 antibody blocks IgA ASC accumulation in the mammary gland, inhibiting IgA antibody secretion into milk and the subsequent appearance of antibody in the gastrointestinal tract of nursing neonates. We propose that CCL28 is a key regulator of IgA ASC accumulation in the mammary gland and thus controls the passive transfer of IgA antibodies from mother to infant.
Mapping Tumor Epitope Space by Direct Selection of Single-Chain Fv Antibody Libraries on Prostate Cancer Cells
Authors: Bin Liu, Fraser Conrad, Matthew R. Cooperberg, Dmitri B. Kirpotin, James D. Marks
Journal: Cancer Research (2004)

Abstract The identification of tumor-specific cell surface antigens is a critical step toward the development of targeted therapeutics for cancer. The epitope space at the tumor cell surface is highly complex, composed of proteins, carbohydrates, and other membrane-associated determinants including post-translational modification products, which are difficult to probe by approaches based on gene expression. This epitope space can be efficiently mapped by complementary monoclonal antibodies. By selecting human antibody gene diversity libraries directly on the surface of prostate cancer cells, we have taken a functional approach to identifying fully human, tumor-specific monoclonal antibodies without prior knowledge of their target antigens. Selection conditions have been optimized to favor tumor-specific antibody binding and internalization. To date, we have discovered &amp;gt;90 monoclonal antibodies that specifically bind and enter prostate cancer cells, with little or no binding to control cells. These antibodies are able to efficiently deliver intracellular payloads when attached to nanoparticles such as liposomes. In addition, a subset of the antibodies displayed intrinsic antiproliferative activity. These tumor-specific internalizing antibodies are likely to be useful for targeted therapeutics either alone or in combination with effector molecules. The antigens they bind constitute a tumor-specific internalizing epitope space that is likely to play a significant role in cancer cell homeostasis. Targeting components of this epitope space may facilitate development of immunotherapeutic and small molecule-based strategies as well as the use of other therapeutic agents that rely upon delivery to the interior of the tumor cell.
6-Shogaol induces apoptosis in human leukemia cells through a process involving caspase-mediated cleavage of eIF2α
Authors: Qun Liu, Yong-Bo Peng, Ping Zhou, Lian-Wen Qi, Mu Zhang, Ning Gao, E-Hu Liu, Ping Li
Journal: Molecular Cancer (2013)

6-Shogaol is a promising antitumor agent isolated from dietary ginger (Zingiber officinale). However, little is known about the efficacy of 6-shogaol on leukemia cells. Here we investigated the underlying mechanism of 6-shogaol induced apoptosis in human leukemia cells in vitro and in vivo.Three leukemia cell lines and primary leukemia cells were used to investigate the apoptosis effect of 6-shogaol. A shotgun approach based on label-free proteome with LC-CHIP Q-TOF MS/MS was employed to identify the cellular targets of 6-shogaol and the differentially expressed proteins were analyzed by bioinformatics protocols.The present study indicated that 6-shogaol selectively induced apoptosis in transformed and primary leukemia cells but not in normal cells. Eukaryotic translation initiation factor 2 alpha (eIF2α), a key regulator in apoptosis signaling pathway, was significantly affected in both Jurkat and U937 proteome profiles. The docking results suggested that 6-shogaol might bind well to eIF2α at Ser51 of the N-terminal domain. Immunoblotting data indicated that 6-shogaol induced apoptosis through a process involving dephosphorylation of eIF2α and caspase activation-dependent cleavage of eIF2α. Furthermore, 6-shogaol markedly inhibited tumor growth and induced apoptosis in U937 xenograft mouse model.The potent anti-leukemia activity of 6-shogaol found both in vitro and in vivo in our study make this compound a potential anti-tumor agent for hematologic malignancies.
Phenacetin Nephropathy, with Particular Reference to the Effect of Surgery
Authors: K. G. Koutsaimanis, H. E. de Wardener
Journal: BMJ (1970)

Sixteen patients suffering from phenacetin nephropathy were seen at one London hospital between June 1964 and January 1970. There were five deaths, three of them following a surgical operation. Phenacetin nephropathy occurs far more frequently than is generally considered. Unless patients are asked about the consumption of phenacetin routinely the diagnosis is usually missed. It is recommended that phenacetin and paracetamol should be available only on a doctor's prescription.
Pediatric Hospitalization as Crisis Intervention
Authors: RICHARD GALDSTON, MICHAEL C. HUGHES
Journal: American Journal of Psychiatry (1972)

The authors describe a follow-up clinic for pediatric patients who have been hospitalized; an attempt is made to transform the acute crisis of hospitalization into a therapeutic relationship aimed at ameliorating intrapsychic and intrafamily problems. This approach has been successful both with patients with demonstrable organic disease and those without such disease.
Influence of extracellular magnesium on capillary endothelial cell proliferation and migration.
Authors: S Banai, L Haggroth, S E Epstein, W Casscells
Journal: Circulation Research (1990)

We investigated the role of extracellular magnesium on capillary endothelial cell migration and proliferation, components of endothelial cell function that play an important role in angiogenesis and wound healing. Cell migration and proliferation were tested in six different MgSO4 concentrations and in various culture conditions. The Boyden chamber procedure was used to evaluate migration of bovine adrenal cortex capillary endothelial cells. We found that low magnesium concentration inhibited cell migration, but a dose-dependent increase in migration was observed when magnesium level was increased beyond the normal serum concentration (up to 2.4 mM magnesium; p less than 0.0001). Cell proliferation was also inhibited by very low magnesium concentration, an effect observed under all conditions studied. When cell proliferation was stimulated by acidic or basic fibroblast growth factors, it appeared that a ceiling was reached, an increasing magnesium concentration had no additional stimulatory effect. However, a dose-dependent increase in proliferation (p less than 0.005) was observed when magnesium concentration was increased above the normal serum level (0.8 mM) in culture conditions that did not cause marked cell proliferation. Thus, magnesium has an important role in endothelial cell migration and proliferation: very low extracellular magnesium concentrations inhibit and supranormal levels enhance both migration and proliferation. These results suggest that magnesium deficiency might adversely influence the healing and reendothelialization of vascular injuries and the healing of myocardial infarction and might also result in delayed or inadequate angiogenesis, effects potentially leading to infarct expansion and inadequate collateral development.
Respiratory effects of air pollution in chronic obstructive pulmonary disease: a three month prospective study
Authors: E. S. Harre, P. D. Price, R. B. Ayrey, L. J. Toop, I. R. Martin, G. I. Town
Journal: Thorax (1997)

BACKGROUND: A study was undertaken to investigate the relationship between air pollution levels and respiratory symptoms and peak expiratory flow rate (PEFR) in subjects with chronic obstructive pulmonary disease (COPD) living in Christchurch, New Zealand. METHODS: Forty subjects aged over 55 years with COPD completed twice daily diaries for three months during the winter of 1994. Subjects recorded respiratory symptoms, PEFR, outdoor activity, visits to doctor or hospital, and medication use. All were resident within a 5 km radius of the regional council9s air pollution monitoring site. Daily and hourly mean pollutant levels (particulates (PM10, nitrogen dioxide (NO2), sulphur dioxide (SO2) and carbon monoxide (CO)) were measured at the monitoring site. RESULTS: Pollution levels were generally low relative to those recorded in previous years. The New Zealand Ministry for the Environment guidelines for PM10 were exceeded on five occasions, and for CO six times. No association was found between PEFR and any of the pollution variables. A rise in the PM10 concentration equivalent to the interquartile range was associated with an increase in night time chest symptoms (relative risk 1.38, 95% CI 1.07 to 1.78). A rise in NO2 concentrations equivalent to the interquartile range was associated with increased reliever inhaler use (relative risk 1.42, 95% CI 1.13 to 1.79) and for 24 hour lag analysis with increased nebuliser use (relative risk 2.81, 95% CI 1.81 to 4.39). There was no increase in the relative risk of other symptoms in relation to pollution levels. CONCLUSIONS: These effects, demonstrated in a small susceptible group of subjects with COPD, indicate that adverse outcomes can be measured in response to pollution levels that are within current guidelines.
Ataluren as an Agent for Therapeutic Nonsense Suppression
Authors: Stuart W. Peltz, Manal Morsy, Ellen M. Welch, Allan Jacobson
Journal: Annual Review of Medicine (2012)

The interplay of translation and mRNA turnover has helped unveil how the regulation of gene expression is a continuum in which events that occur during the birth of a transcript in the nucleus can have profound effects on subsequent steps in the cytoplasm. Exemplifying this continuum is nonsense-mediated mRNA decay (NMD), the process wherein a premature stop codon affects both translation and mRNA decay. Studies of NMD helped lead us to the therapeutic concept of treating a subset of patients suffering from multiple genetic disorders due to nonsense mutations with a single small-molecule drug that modulates the translation termination process at a premature nonsense codon. Here we review both translation termination and NMD, and our subsequent efforts over the past 15 years that led to the identification, characterization, and clinical testing of ataluren, a new therapeutic with the potential to treat a broad range of genetic disorders due to nonsense mutations.
Reframing Women's Risk: Social Inequalities and HIV Infection
Authors: Sally Zierler, Nancy Krieger
Journal: Annual Review of Public Health (1997)

▪ Abstract Social inequalities lie at the heart of risk of HIV infection among women in the United States. As of December, 1995, 71,818 US women had developed AIDS-defining diagnoses. These women have been disproportionately poor, African-American, and Latina. Their neighborhoods have been burdened by poverty, racism, crack cocaine, heroin, and violence. To explain which women are at risk and why, this article reviews the epidemiology of HIV and AIDS among women in light of four conceptual frameworks linking health and social justice: feminism, social production of disease/political economy of health, ecosocial, and human rights. The article applies these alternative theories to describe sociopolitical contexts for AIDS' emergence and spread in the United States, and reviews evidence linking inequalities of class, race/ethnicity, gender, and sexuality, as well as strategies of resistance to these inequalities, to the distribution of HIV among women.
Ask(1) and you shall receive: A new link between antioxidants and cell death signaling
Authors: Mark J. Czaja
Journal: Hepatology (2003)

Hepatoprotection mediated by free radical scavenging molecules such as dimethyl sulfoxide (Me 2 SO) arose the question as to whether this effect involved one or several anti–apoptotic signals. Here, using primary cultures of rat hepatocytes and in vivo thioacetamide–induced liver failure, we showed that Me 2 SO failed to prevent any cleavage of initiator caspase–8 and –9 but constantly inhibited procaspase–3 maturation and apoptosis execution, pointing to an efficient inhibition of cleaved initiator caspase activities. Evidence was recently provided that apoptosis might require both caspase and ASK1/JNK–p38 activities. We demonstrated that this kinase pathway was strongly inhibited in the presence of Me 2 SO whereas overexpression of ASK1 was able to restore caspase–3 activity and apoptosis. Interestingly, we also found that GST M1/2 and GST A1/2 dropped under apoptotic conditions; furthermore transfection of GST M1, A1, or P1 to cells overexpressing ASK1, abolished caspase–3 activity and restored viability. This role of GSTs was further assessed by showing that their high expression level was tightly associated with inhibition of ASK1 activity in Me 2 SO–protected hepatocytes. Together, these results demonstrate that Me 2 SO–mediated hepatoprotection involves a dual inhibition of cleaved initiator caspase and ASK1/JNK–p38 activities. Furthermore, in highlighting the control of apoptosis by GSTs, these data provide new insights for analyzing the complex mechanisms of hepatoprotection.
PHARMACOLOGY OF NEUROTROPHIC FACTORS
Authors: Franz Hefti
Journal: The Annual Review of Pharmacology and Toxicology (1997)

▪ Abstract The field of neurotrophic factor pharmacology emerged during the past decade with the discovery that these proteins can counteract neuronal atrophy and death in the adult nervous system. These concepts are being tested in clinical trials. Therapeutic use of neurotrophic proteins seems practical for diseases of the peripheral nervous system (PNS), where they can be given by systemic administration. For diseases of the CNS, special administration strategies will have to be developed to deliver the neurotrophic factors into the brain. The development of small molecule mimetics represents an alternative approach that is actively pursued to provide brain-penetrant neurotrophics.
Subclassification of Diffuse Large B-Cell Lymphomas According to the Kiel Classification: Distinction of Centroblastic and Immunoblastic Lymphomas Is a Significant Prognostic Risk Factor
Authors: Marianne Engelhard, Günter Brittinger, Dieter Huhn, Heinrich H. Gerhartz, Peter Meusers, Wolfgang Siegert, Eckhard Thiel, Wolfgang Wilmanns, Ülker Aydemir, Stefan Bierwolf, Henrik Griesser, Markus Tiemann, Karl Lennert
Journal: Blood (1997)
Comparative Efficacy of Seven Psychotherapeutic Interventions for Patients with Depression: A Network Meta-Analysis
Authors: Jürgen Barth, Thomas Munder, Heike Gerger, Eveline Nüesch, Sven Trelle, Hansjörg Znoj, Peter Jüni, Pim Cuijpers
Journal: PLoS Medicine (2013)

Previous meta-analyses comparing the efficacy of psychotherapeutic interventions for depression were clouded by a limited number of within-study treatment comparisons. This study used network meta-analysis, a novel methodological approach that integrates direct and indirect evidence from randomised controlled studies, to re-examine the comparative efficacy of seven psychotherapeutic interventions for adult depression.We conducted systematic literature searches in PubMed, PsycINFO, and Embase up to November 2012, and identified additional studies through earlier meta-analyses and the references of included studies. We identified 198 studies, including 15,118 adult patients with depression, and coded moderator variables. Each of the seven psychotherapeutic interventions was superior to a waitlist control condition with moderate to large effects (range d = -0.62 to d = -0.92). Relative effects of different psychotherapeutic interventions on depressive symptoms were absent to small (range d = 0.01 to d = -0.30). Interpersonal therapy was significantly more effective than supportive therapy (d = -0.30, 95% credibility interval [CrI] [-0.54 to -0.05]). Moderator analysis showed that patient characteristics had no influence on treatment effects, but identified aspects of study quality and sample size as effect modifiers. Smaller effects were found in studies of at least moderate (Δd = 0.29 [-0.01 to 0.58]; p = 0.063) and large size (Δd = 0.33 [0.08 to 0.61]; p = 0.012) and those that had adequate outcome assessment (Δd = 0.38 [-0.06 to 0.87]; p = 0.100). Stepwise restriction of analyses by sample size showed robust effects for cognitive-behavioural therapy, interpersonal therapy, and problem-solving therapy (all d>0.46) compared to waitlist. Empirical evidence from large studies was unavailable or limited for other psychotherapeutic interventions.Overall our results are consistent with the notion that different psychotherapeutic interventions for depression have comparable benefits. However, the robustness of the evidence varies considerably between different psychotherapeutic treatments.
A FUNCTIONAL AND ANATOMICAL STUDY OF THE EXCRETION OF HEMOGLOBIN BY THE KIDNEY
Authors: Yoshu Fukuda, Jean Oliver
Journal: The Journal of Experimental Medicine (1923)

1. The anatomical and functional findings in hemoglobin excretion are best explained by the assumption of a filtration of this substance through the glomerulus and an additional excretion of it by the tubule cells. 2. Absorption of water aids in the concentrating process, and is most marked in the collecting tubules.
The Address Delivered in the Section of Otology
Authors: W. L. Purves
Journal: BMJ (1882)

examine both~the structures conveying and the structures receiving thc A N AD DR E SS motion p'erceptible to the optic nerve.But, when we turn from thes'e to the exact examination of ftmnc- DLVRDAT THE OP'ENING OF tional changes, my hopes of advance are much increased.T H E SE C T I 0 N 0 F 0 T 0 L 0 GY,For the purpose of exactly determining abnormal changes of func- THE SECTION OF OTOLOGY, ~~~ti o n , it is necessary that we should have some Istandards of the norma Alth An lnualJifccting-oft/ihe Br-itisk M3edical Association, power.In this respect, we are, as far as I know, sadly deficient.inz WVorcester-, Auigust zS8S2.What are the determinations at which we should sttive to arrive ?By WV.LAIDLAW PURVES, M\