tbuckley/cabot-search huggingface dataset:
High serum lactate dehydrogenase level predicts short survival after vincristine-doxorubicin-dexamethasone (VAD) salvage for refractory multiple myeloma
Authors: Miyuki Suguro, Yshinobu Kanda, Rie Yamamoto, Aki Chizuka, Tamae Hamaki, Tomohiro Matsuyama, Naoki Takezako, Akiyoshi Miwa, Atsushi Togawa
Journal: American Journal of Hematology (2000)

We evaluated possible prognostic factors just before salvage therapy with vincristine, doxorubicin, and dexamethasone (VAD) for 36 patients with refractory multiple myeloma. The median duration from diagnosis to the first VAD salvage was 14 months (range 2–76 months). Among parameters that have been shown to be associated with poor survival, a high serum lactate dehydrogenase (LDH) level was the sole significant predictor of survival. The median survival of patients with high LDH levels was 4 months, whereas that of patients with low LDH levels was 20 months. A multivariate analysis identified high LDH and high age as independent prognostic factors. More aggressive therapies might be indicated for high-LDH patients with refractory myeloma. Am. J. Hematol. 65:132–135, 2000. © 2000 Wiley-Liss, Inc.
Race and ancestry in biomedical research: exploring the challenges
Authors: Timothy Caulfield, Stephanie M Fullerton, Sarah E Ali-Khan, Laura Arbour, Esteban G Burchard, Richard S Cooper, Billie-Jo Hardy, Simrat Harry, Robyn Hyde-Lay, Jonathan Kahn, Rick Kittles, Barbara A Koenig, Sandra SJ Lee, Michael Malinowski, Vardit Ravitsky, Pamela Sankar, Stephen W Scherer, Béatrice Séguin, Darren Shickle, Guilherme Suarez-Kurtz, Abdallah S Daar
Journal: Genome Medicine (2009)

Abstract The use of race in biomedical research has, for decades, been a source of social controversy. However, recent events, such as the adoption of racially targeted pharmaceuticals, have raised the profile of the race issue. In addition, we are entering an era in which genomic research is increasingly focused on the nature and extent of human genetic variation, often examined by population, which leads to heightened potential for misunderstandings or misuse of terms concerning genetic variation and race. Here, we draw together the perspectives of participants in a recent interdisciplinary workshop on ancestry and health in medicine in order to explore the use of race in research issue from the vantage point of a variety of disciplines. We review the nature of the race controversy in the context of biomedical research and highlight several challenges to policy action, including restrictions resulting from commercial or regulatory considerations, the difficulty in presenting precise terminology in the media, and drifting or ambiguous definitions of key terms.
Effects of News Media Messages About Mass Shootings on Attitudes Toward Persons With Serious Mental Illness and Public Support for Gun Control Policies
Authors: Emma E. McGinty, Daniel W. Webster, Colleen L. Barry
Journal: American Journal of Psychiatry (2013)

In recent years, mass shootings by persons with serious mental illness have received extensive news media coverage. The authors test the effects of news stories about mass shootings on public attitudes toward persons with serious mental illness and support for gun control policies. They also examine whether news coverage of proposals to prevent persons with serious mental illness from having guns exacerbates the public's negative attitudes toward this group.The authors conducted a survey-embedded randomized experiment using a national sample (N=1,797) from an online panel. Respondents were randomly assigned to groups instructed to read one of three news stories or to a no-exposure control group. The news stories described, respectively, a mass shooting by a person with serious mental illness, the same mass shooting and a proposal for gun restrictions for persons with serious mental illness, and the same mass shooting and a proposal to ban large-capacity magazines. Outcome measures included attitudes toward working with or living near a person with serious mental illness, perceived dangerousness of persons with serious mental illness, and support for gun restrictions for persons with serious mental illness and for a ban on large-capacity magazines.Compared with the control group, the story about a mass shooting heightened respondents' negative attitudes toward persons with serious mental illness and raised support for gun restrictions for this group and for a ban on large-capacity magazines. Including information about the gun restriction policy in a story about a mass shooting did not heighten negative attitudes toward persons with serious mental illness or raise support for the restrictions.The aftermath of mass shootings is often viewed as a window of opportunity to garner support for gun control policies, but it also exacerbates negative attitudes toward persons with serious mental illness.
Conduction disturbances caused by high current density electric fields.
Authors: S Yabe, W M Smith, J P Daubert, P D Wolf, D L Rollins, R E Ideker
Journal: Circulation Research (1990)

During internal defibrillation, potential gradients greater than 100 V/cm occur near defibrillation electrodes. Such strong fields may cause deleterious effects, including arrhythmias. This study determined 1) the effects of such strong fields on the propagation of activation and 2) whether these effects were different for monophasic and biphasic shocks. Voltages and potential gradients during the shock, as well as activation sequences before and after the shock, were mapped from 117 epicardial electrodes placed over a 3 x 3-cm area on the right ventricle in six dogs. Pacing at a cycle length of 350 msec was given from a long narrow electrode on the right side of the mapped area to generate parallel activation isochrones. A monophasic shock, 10 msec in duration, or a biphasic shock with both phases 5 msec in duration was delivered 300 msec after the last paced stimulus via a mesh electrode on the left side of the mapped area as the cathode, with the anode on the right atrium. Shocks of 70-850 V were given, and the potential gradient and current density at each recording electrode were calculated from the measured potentials and fiber orientation by using a finite element method. Pacing was resumed 200 msec after the shock, and activation sequences were mapped for up to 5 minutes. Potential gradients ranged from 1 to 189 V/cm with high fields on the left side and low fields on the right side of the mapped area. Where the potential gradient was weak, the first activation sequence after the shock was similar to that before the shock, but activation blocked without conducting into areas where the gradient was greater than 64 +/- 4 (mean +/- SD) V/cm for monophasic and greater than 71 +/- 6 V/cm for biphasic shocks. These values are significantly different (p less than 0.003). The higher the potential gradient, the longer was the duration of block before conduction returned. Block duration, however, was generally shorter for biphasic than for monophasic waveforms of the same field strength. In conclusion, conduction block can follow either waveform, but biphasic waveforms cause less block than monophasic waveforms. This effect may partially explain the increased defibrillation efficacy of biphasic shocks.
Astroglia are a possible cellular substrate of angiotensin(1-7) effects in the rostral ventrolateral medulla
Authors: Fang Guo, Beihui Liu, Feige Tang, Samantha Lane, Ekaterina A. Souslova, Dmitriy M. Chudakov, Julian F.R. Paton, Sergey Kasparov
Journal: Cardiovascular Research (2010)

Angiotensin(1-7) (Ang1-7) acting at the level of the rostral ventrolateral medulla (RVLM) affects arterial pressure.The cellular substrate of Ang1-7 remains unknown.We sought to determine which cell types in RVLM could mediate its actions and whether these are altered in the spontaneously hypertensive rat (SHR). Methods and resultsAstrocytes, catecholaminergic (CA-ergic) and non-CA-ergic neurones were targeted with adenoviral vectors in organotypic slice cultures from Wistar rats and SHR.Astrocytic Ca 2+ signalling was monitored using a genetically engineered Ca 2+ sensor Case12.CA-ergic neurones expressed enhanced green fluorescent protein (EGFP) under control of the PRS × 8 promoter, whereas non-CA-neurones expressed EGFP under control of the synapsin-1 promoter.Neurones were recorded in whole cell mode while [Ca 2+ ] i was monitored using Rhod-2.RVLM astrocytes responded to Ang1-7 (200-1000 nM) with concentration-dependent [Ca 2+ ] i elevation.In SHR, the response to 1000 nM was significantly attenuated.The competitive Ang1-7 receptor antagonist A779, but not the AT 1 receptor blocker (losartan), suppressed Ang1-7-induced [Ca 2+ ] i elevations, which were also antagonized by blocking intracellular Ca 2+ stores.Ang1-7 evoked no consistent changes in [Ca 2+ ] i or membrane excitability in CA-ergic or non-CA-ergic neurones in either rat strain. ConclusionAstroglia are a plausible cellular target of Ang1-7 in RVLM.Our data suggest that astrocytic responsiveness to Ang1-7 is reduced in SHR.We hypothesise that Ang1-7 modulates astrocytic signalling which in vivo may affect local metabolism and microcirculation, resulting in changes in activity of RVLM pre-sympathetic neurones and hence blood pressure.
ECHOCARDIOGRAPHIC AND CLINICAL CORRELATES OF SPECIFIC EARLY REPOLARIZATION SUBTYPES ON ELECTROCARDIOGRAM
Authors: James B. Strait, Sameer Jamal, Abdulghani Saadi, Brett Sperry, Lindsay Mehring, Tania Singh, John Nayda, Toshiko Tanaka, Melissa David, Marco Canepa, Monika Moni, Luigi Ferrucci, Edward Lakatta
Journal: Journal of the American College of Cardiology (2012)
New onset asthma and respiratory symptoms are more prevalent in radiographers than in physiotherapists
Authors: O A Khair
Journal: Thorax (2003)

▴ Liss GM, Tarlo SM, Doherty J, et al . Physician diagnosed asthma, respiratory symptoms, and association with workplace tasks among radiographers in Ontario, Canada. Occup Environ Med2003;60:254–61 [OpenUrl][1][Abstract/FREE Full Text][2] This cross sectional questionnaire mail survey determined the prevalence of asthma and respiratory symptoms among radiographers (1754 … [1]: {openurl}?query=rft.jtitle%253DOccupational%2Band%2BEnvironmental%2BMedicine%26rft.stitle%253DOccup.%2BEnviron.%2BMed.%26rft.issn%253D1351-0711%26rft.aulast%253DLiss%26rft.auinit1%253DG%2BM%26rft.volume%253D60%26rft.issue%253D4%26rft.spage%253D254%26rft.epage%253D261%26rft.atitle%253DPhysician%2Bdiagnosed%2Basthma%252C%2Brespiratory%2Bsymptoms%252C%2Band%2Bassociations%2Bwith%2Bworkplace%2Btasks%2Bamong%2Bradiographers%2Bin%2BOntario%252C%2BCanada%26rft_id%253Dinfo%253Adoi%252F10.1136%252Foem.60.4.254%26rft_id%253Dinfo%253Apmid%252F12660373%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=oemed&resid=60/4/254&atom=%2Fthoraxjnl%2F58%2F6%2F514.atom
Expanding Nielsen's covert REM model, questioning Solms's approach to dreaming and REM sleep, and reinterpreting the Vertes &amp; Eastman view of REM sleep and memory
Authors: Robert D. Ogilvie, Tomoka Takeuchi, Timothy I. Murphy
Journal: Behavioral and Brain Sciences (2000)

Nielsen's covert REM process model explains much of the mentation found in REM and NREM sleep, but stops short of postulating an interaction of waking cognitive processes with the dream mechanisms of REM sleep. It ranks with the Hobson et al. paper as a major theoretical advance. The Solms article does not surmount the ever-present problem of defining dreams in a manner conducive to advancing dream theory. Vertes &amp; Eastman review the REM sleep and learning literature, but make questionable assumptions in doing so. [Hobson et al.; Nielsen; Solms; Vertes &amp; Eastman]
Transpleural gradient of 1,25-dihydroxyvitamin D in tuberculous pleuritis.
Authors: P F Barnes, R L Modlin, D D Bikle, J S Adams
Journal: Journal of Clinical Investigation (1989)

We used tuberculous pleuritis as a model to study the compartmentalization and potential immunoregulatory role of 1,25-dihydroxyvitamin D [1,25-(OH)2-D] in human granulomatous disease. In tuberculous pleuritis, mean concentrations of total 1,25-(OH)2-D were elevated in pleural fluid, compared to blood (67 pg/ml vs. 35 pg/ml). Concentrations of albumin, protein and 25-hydroxyvitamin D (25-OH-D) were lower in pleural fluid than blood, suggesting that accumulation of binding proteins does not explain the transpleural gradient of 1,25-(OH)2-D. The mean free 1,25-(OH)2-D concentration in pleural fluid was increased 5.3-fold over that in serum. 1,25-(OH)2-D3 inhibited PPD-induced proliferation of pleural fluid mononuclear cells, antigen-reactive lines and T lymphocyte clones derived from a single cell. Patient-derived PPD-reactive lines expressed a high-affinity intracellular binding moiety for 1,25-(OH)2-D3. Pleural fluid mononuclear cells and PPD-reactive lines did not metabolize 25-OH-D3 to 1,25-(OH)2-D3. The sum of these data suggests that concentration of 1,25-(OH)2-D in pleural fluid of tuberculosis patients is probably due to local hormone production by pleural tissue-based inflammatory cells that are not present in significant numbers in pleural fluid. Elevated concentrations of 1,25-(OH)2-D in pleural fluid may exert receptor-mediated inhibition of antigen-induced proliferation by pleural fluid lymphocytes. Inhibition of lymphocyte proliferation and lymphokine production may prevent tissue destruction from an uncontrolled inflammatory response.
THE TREATMENT OF RHEUMATIC DISEASES BY VACCINES
Authors: C. P. Ball
Journal: BMJ (1911)

M B I 05 even when in the tropics and covered with blankets.For the past year he had had " cold shivering sensations " down the back and legs.On one occasion, six years after the onset of the ,disease, his legs underwent most alarming vasomotor and sensory disturbances.While sitting at the breakfast table he noticed a " numb feeling " in the toes, which slowly spread up ,the legs to midway between the pubes and umbilicus.The lower limbs were absolutely paralysed and, he fancied, anaesthetic.When undressed and placed in bed his legs were seen to be of a diffase pale bluish colour, " as if mortification had set in," to use his words.The discoloration lasted two days, and on the first day he could not move the legs at all.On several occasions the legs, one or both, had been very swollen, -even up as far as the thighs, leaving " pitting " on digital compression.The oedema more or lpss subsided during the night, but recurred daily for weeks.,It was most marked when the perforating ulcers were most active.In fact, he came for treatment on the present occasion on account of inability to walk unaided, with extensive oedems and hyperaemia around a *deep ulcer on the sole of the right foot.-The presence of deep -pus was confidently diagnosed, but in response to fomentations and rest the condition rapidly subsided without any discharge.A. P., aged 58 years.One of the earliest symptoms was a sudden, extensive, painless, and unaccountable swelling of the whole of the right arm from the wrist to the root of the neck.'It was variously diagnosed (phlebitis, acute inflammatory changes, etc.), but gradually subsided under rest.Within a few months thereafter the condition recurred.In half an hour 'the limb became enormously swollen, and this time of a lemon colour of varying intensity and darker on the outside of the arm.This condition lasted several weeks and then left the shoulder-joint disorganized and dislocated.At times his feet burned and he was obliged to cool them outside the bedclothes.His feet were habitually inclined to swell.
Combined Anti-CD40 and Anti–IL-23 Monoclonal Antibody Therapy Effectively Suppresses Tumor Growth and Metastases
Authors: Bianca von Scheidt, Patrick S.K. Leung, Michelle C.R. Yong, Yu Zhang, Jennifer E. Towne, Mark J. Smyth, Michele W.L. Teng
Journal: Cancer Research (2014)

Abstract Tumor-induced immunosuppression remains one of the major obstacles to many potentially effective cancer therapies and vaccines. Host interleukin (IL)-23 suppresses the immune response during tumor initiation, growth, and metastases, and neutralization of IL-23 causes IL-12–dependent antitumor effects. Here, we report that combining agonistic anti-CD40 monoclonal antibodies (mAb) to drive IL-12 production and anti–IL-23 mAbs to counter the tumor promoting effects of IL-23 has greater antitumor activity than either agent alone. This increased antitumor efficacy was observed in several experimental and spontaneous lung metastases models as well as in models of de novo carcinogenesis. The combination effects were dependent on host IL-12, perforin, IFN-γ, natural killer, and/or T cells and independent of host B cells and IFN-αβ sensitivity. Interestingly, in the experimental lung metastases tumor models, we observed that intracellular IL-23 production was specifically restricted to MHC-IIhiCD11c+CD11b+ cells. Furthermore, an increase in proportion of these IL-23–producing cells was detected only in tumor models where IL-23 neutralization was therapeutic. Overall, these data suggest the clinical potential of using anti-CD40 (push) and anti–IL-23 mAbs (pull) to tip the IL-12/23 balance in established tumors. Cancer Res; 74(9); 2412–21. ©2014 AACR.
Sildenafil for treatment of lung fibrosis and pulmonary hypertension: a randomised controlled trial
Authors: Hossein Ardeschir Ghofrani, Ralph Wiedemann, Frank Rose, Ralph T Schermuly, Horst Olschewski, Norbert Weissmann, Andreas Gunther, Dieter Walmrath, Werner Seeger, Friedrich Grimminger
Journal: The Lancet (2002)
Influenza A resistance to oseltamivir
Authors: I Ismail
Journal: Thorax (2009)

Oseltamivir is a neuraminidase inhibitor used for the treatment and prophylaxis of influenza A infections. This study investigated the differences in demographics, epidemiology, clinical symptoms, severity of illness and clinical outcomes among patients infected with oseltamivir-resistant or oseltamivir-susceptible influenza A (H1N1) virus in the USA. Information about viral isolates and their subtypes, particularly …
Unnatural Amino Acids as Probes of Ligand-Receptor Interactions and Their Conformational Consequences
Authors: Stephan A. Pless, Christopher A. Ahern
Journal: The Annual Review of Pharmacology and Toxicology (2013)

G protein–coupled receptors and ion channels couple a wide range of external stimuli to cellular growth and division, metabolism, motility, and a myriad of intra- and intercellular signaling pathways. G protein–coupled receptors initiate complex, interrelated downstream signaling cascades, whereas rapid ionic flux through channels directly supports membrane excitability and mediates cellular functions through second messengers. Because of these characteristics, these ubiquitous transmembrane proteins are valuable therapeutic targets and have provided fertile ground for the development of leading-edge synthetic and chemical biological approaches. Here we summarize recent advances in the use of site-directed incorporation of unnatural amino acids and chemical probes to study ligand-receptor interactions, determine the location of binding sites, and examine the downstream conformational consequences of ligand binding in G protein–coupled receptors and ion channels.
Endothelial NADPH Oxidase-2 Promotes Interstitial Cardiac Fibrosis and Diastolic Dysfunction Through Proinflammatory Effects and Endothelial-Mesenchymal Transition
Authors: Colin E. Murdoch, Sanjay Chaubey, Lingfang Zeng, Bin Yu, Aleksander Ivetic, Simon J. Walker, Davy Vanhoutte, Stephane Heymans, David J. Grieve, Alison C. Cave, Alison C. Brewer, Min Zhang, Ajay M. Shah
Journal: Journal of the American College of Cardiology (2014)
Prediction of Late Disease Recurrence and Extended Adjuvant Letrozole Benefit by the HOXB13/IL17BR Biomarker
Authors: Dennis C. Sgroi, Erin Carney, Elizabeth Zarrella, Lauren Steffel, Shemeica N. Binns, Dianne M. Finkelstein, Jackie Szymonifka, Atul K. Bhan, Lois E. Shepherd, Yi Zhang, Catherine A. Schnabel, Mark G. Erlander, James N. Ingle, Peggy Porter, Hyman B. Muss, Katherine I. Pritchard, Dongsheng Tu, David L. Rimm, Paul E. Goss
Journal: JNCI Journal of the National Cancer Institute (2013)

Biomarkers to optimize extended adjuvant endocrine therapy for women with estrogen receptor (ER)–positive breast cancer are limited. The HOXB13/IL17BR (H/I) biomarker predicts recurrence risk in ER-positive, lymph node–negative breast cancer patients. H/I was evaluated in MA.17 trial for prognostic performance for late recurrence and treatment benefit from extended adjuvant letrozole. A prospective–retrospective, nested case-control design of 83 recurrences matched to 166 nonrecurrences from letrozole- and placebo-treated patients within MA.17 was conducted. Expression of H/I within primary tumors was determined by reverse-transcription polymerase chain reaction with a prespecified cutpoint. The predictive ability of H/I for ascertaining benefit from letrozole was determined using multivariable conditional logistic regression including standard clinicopathological factors as covariates. All statistical tests were two-sided. High H/I was statistically significantly associated with a decrease in late recurrence in patients receiving extended letrozole therapy (odds ratio [OR] = 0.35; 95% confidence interval [CI] = 0.16 to 0.75; P = .007). In an adjusted model with standard clinicopathological factors, high H/I remained statistically significantly associated with patient benefit from letrozole (OR = 0.33; 95% CI = 0.15 to 0.73; P = .006). Reduction in the absolute risk of recurrence at 5 years was 16.5% for patients with high H/I (P = .007). The interaction between H/I and letrozole treatment was statistically significant (P = .03). In the absence of extended letrozole therapy, high H/I identifies a subgroup of ER-positive patients disease-free after 5 years of tamoxifen who are at risk for late recurrence. When extended endocrine therapy with letrozole is prescribed, high H/I predicts benefit from therapy and a decreased probability of late disease recurrence.
An Activating β1 Integrin Mutation Increases the Conversion of Benign to Malignant Skin Tumors
Authors: Manuela Ferreira, Hironobu Fujiwara, Kazumasa Morita, Fiona M. Watt
Journal: Cancer Research (2009)

Identifying the physiologic relevance of cancer-associated genetic polymorphisms is a major challenge. Several changes in the coding sequence of beta integrin subunits have now been described in human tumors. One of these, T188Ibeta1, was identified as a heterozygous mutation in a poorly differentiated squamous cell carcinoma (SCC) and shown to activate extracellular matrix adhesion and inhibit keratinocyte differentiation in vitro. To study its contribution to tumor development, we overexpressed the mutant or wild-type (WT) human beta1 subunit in the basal layer of mouse epidermis using the keratin 14 promoter. The transgenic integrins were expressed at the cell surface and were functional, with the T188Ibeta1 subunit promoting cell spreading to a greater extent than WTbeta1. Epidermal proliferation and differentiation were unaffected and no expansion of the stem cell compartment was detected. During chemical carcinogenesis, both transgenes increased papilloma formation, but only the T188Ibeta1 transgene stimulated the conversion of papillomas to SCCs. Papillomas bearing the mutation showed increased Erk activity and reduced differentiation. SCCs expressing T188Ibeta1 were less well-differentiated than those expressing WTbeta1. These observations establish that the expression of a genetic variant in the I-like domain of beta1 integrins does not affect normal epidermal homeostasis, but increases tumor susceptibility and influences tumor type.