tbuckley/cabot-search huggingface dataset:
AZD2171, a Pan-VEGF Receptor Tyrosine Kinase Inhibitor, Normalizes Tumor Vasculature and Alleviates Edema in Glioblastoma Patients
Authors: Tracy T. Batchelor, A. Gregory Sorensen, Emmanuelle di Tomaso, Wei-Ting Zhang, Dan G. Duda, Kenneth S. Cohen, Kevin R. Kozak, Daniel P. Cahill, Poe-Jou Chen, Mingwang Zhu, Marek Ancukiewicz, Maciej M. Mrugala, Scott Plotkin, Jan Drappatz, David N. Louis, Percy Ivy, David T. Scadden, Thomas Benner, Jay S. Loeffler, Patrick Y. Wen, Rakesh K. Jain
Journal: Cancer Cell (2007)
STUDIES ON THE PHYSICAL AND CHEMICAL PROPERTIES OF THE VIRUS OF FOOT-AND-MOUTH DISEASE
Authors: Peter K. Olitsky, Louis Boëz
Journal: The Journal of Experimental Medicine (1927)

No multiplication of the virus in vitro was observed. We have found, however, that the optimum conditions necessary for the preservation of the virus in artificial media are as follows: The hydrogen ion concentration of the medium should be 7.5 to 7.6, not only at the beginning, but, and more important, at the conclusion of the period of observation. A strict anaerobic atmosphere is also favorable, as is a temperature below 37°C. A semisolid structure of the medium appears to be advantageous and this can be effected by the use of ¼th per cent agar or 10 per cent gelatin. Of the two, the gelatin is more desirable, and of the latter the most effective material is gelatin from which the impurities have been most thoroughly removed, namely the gelatin employed by Loeb for his isoelectric determinations. This material is best adjusted to the proper hydrogen ion concentration (7.5–7.6) with potassium hydroxide and not with buffer phosphate. Gelatin is the simplest of protein media available and its employment is in keeping with the principle we have found that the requirements for life of the virus of foot-and-mouth disease are of the simplest. The addition of organic or complex protein substances, such as dextrose, broth, serum, lipoids, etc., to a simple basic medium interferes with the effectiveness of the latter. It is thus not surprising that we were unable to confirm the cultural results of Frosch and Dahmen for neither their medium nor its components or their method satisfies the essential conditions necessary to maintain artificially the life of the virus. Furthermore, from the standpoint of technique it was found necessary when comparing 2 or more media for their value in preserving the incitant, to employ all of them in a parallel experiment with the same sample of virus, for the factors of potency of the active agent, contamination, and changes in hydrogen ion concentration, if variable, may give rise to faulty interpretations. Moreover, activity in 3 successive subplants may be regarded as mere preservation but not multiplication of the virus. Finally, we discuss the status of the virus from the point of view of its fluid or particulate, and its animate or inanimate, characters.
Predicting bacterial cause in infectious conjunctivitis: cohort study on informativeness of combinations of signs and symptoms
Authors: Remco P Rietveld, Gerben ter Riet, Patrick J E Bindels, Jacobus H Sloos, Henk C P M van Weert
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To find an efficient set of diagnostic indicators that are optimally informative in the diagnosis of a bacterial origin of acute infectious conjunctivitis. <b>Design</b> Cohort study involving consecutive patients. Results of index tests and reference standard were collected independently from each other. <b>Setting</b> 25 Dutch health centres. <b>Participants</b> 184 adults presenting with a red eye and either (muco)purulent discharge or glued eyelid(s), not wearing contact lenses. <b>Main outcome measures</b> Probability of a positive bacterial culture, given different combinations of index test results; area under receiver operating characteristics curve. <b>Results</b> Logistic regression analysis showed optimal diagnostic discrimination for the combination of early morning glued eye(s), itch, and a history of conjunctivitis. The first of these indicators increased the likelihood of a bacterial cause, whereas the other two decreased it. The area under the receiver operating characteristics curve for this combination of symptoms was 0.74 (95% confidence interval 0.63 to 0.80). The overall prevalence of bacterial involvement of 32% could be lowered to 4% or raised to 77%, depending on the pattern of index test results. <b>Conclusion</b> A bacterial origin of complaints indicative of acute infectious conjunctivitis can be made much more likely or unlikely by the answers to three simple questions posed during clinical history taking (possibly by telephone). These results may have consequences for more targeted prescription of ocular antibiotics.
Copper Signaling Axis as a Target for Prostate Cancer Therapeutics
Authors: Rachid Safi, Erik R. Nelson, Satish K. Chitneni, Katherine J. Franz, Daniel J. George, Michael R. Zalutsky, Donald P. McDonnell
Journal: Cancer Research (2014)

Previously published reports indicate that serum copper levels are elevated in patients with prostate cancer and that increased copper uptake can be used as a means to image prostate tumors. It is unclear, however, to what extent copper is required for prostate cancer cell function as we observed only modest effects of chelation strategies on the growth of these cells in vitro. With the goal of exploiting prostate cancer cell proclivity for copper uptake, we developed a "conditional lethal" screen to identify compounds whose cytotoxic actions were manifested in a copper-dependent manner. Emerging from this screen was a series of dithiocarbamates, which, when complexed with copper, induced reactive oxygen species-dependent apoptosis of malignant, but not normal, prostate cells. One of the dithiocarbamates identified, disulfiram (DSF), is an FDA-approved drug that has previously yielded disappointing results in clinical trials in patients with recurrent prostate cancer. Similarly, in our studies, DSF alone had a minimal effect on the growth of prostate cancer tumors when propagated as xenografts. However, when DSF was coadministered with copper, a very dramatic inhibition of tumor growth in models of hormone-sensitive and of castrate-resistant disease was observed. Furthermore, we determined that prostate cancer cells express high levels of CTR1, the primary copper transporter, and additional chaperones that are required to maintain intracellular copper homeostasis. The expression levels of most of these proteins are increased further upon treatment of androgen receptor (AR)-positive prostate cancer cell lines with androgens. Not surprisingly, robust CTR1-dependent uptake of copper into prostate cancer cells was observed, an activity that was accentuated by activation of AR. Given these data linking AR to intracellular copper uptake, we believe that dithiocarbamate/copper complexes are likely to be effective for the treatment of patients with prostate cancer whose disease is resistant to classical androgen ablation therapies.
The Lettsomian Lectures ON THE CONDITIONS WHICH MODIFY THE CHARACTERS OF INFLAMMATIONS OF THE SKIN, AND THEIR INFLUENCE ON TREATMENT: Delivered before the Medical Society of London
Authors: H. R. Crocker
Journal: BMJ (1903)

The lock and key simile of E. Fischer affords perhaps the best analogy.The lock is the cell, the key is the amboceptor, and the hand which turns the key the complement.As a rule but one key (or at most a few similar ones, a small number compared with the total) will fit a given lock.But nearly any hand, it may be of a monkey or performing dog, can turn the key in the lock.o ~. . . . . . .
A peek into the future of sports medicine: the digital revolution has entered our pitch
Authors: Evert A Verhagen, B Clarsen, R Bahr
Journal: British Journal of Sports Medicine (2013)

The current wide-scale availability of the internet and connected mobile devices is revolutionising healthcare. Patients and practitioners have unprecedented access to health information; they communicate with each more than ever before. It seems as if new technology is appearing daily and with it comes the promise of greater (cost) efficiency and quality of medical practise.1 The sports medicine community is currently buzzing about ‘eHealth’, which may be defined as the practise of medicine supported by electronic processes and communication. The newest buzzword is ‘mHealth’, referring to eHealth driven by the use of mobile devices, not limited to smartphones. Indeed, we are seeing an increased use of readily available technologies such as SMS messaging, social media platforms, apps and online questionnaires in both clinical and research settings.

Grindem et al 2 illustrate how online technologies can aid clinical practice. Specifically they monitored return-to-sport after an anterior cruciate ligament (ACL) injury; one of the clinical ‘success’ measures of postinjury rehabilitation. Current methods that register sports activity after ACL injury are usually restricted to knee-demanding sports alone to limit the time-burden for patients and to ensure valid data collection. Participation …
Glucose-potassium-insulin infusions in the management of post-stroke hyperglycaemia: the UK Glucose Insulin in Stroke Trial (GIST-UK)
Authors: Christopher S Gray, Anthony J Hildreth, Peter A Sandercock, Janice E O'Connell, Donna E Johnston, Niall EF Cartlidge, John M Bamford, Oliver F James, K George MM Alberti
Journal: The Lancet Neurology (2007)
Human basophil histamine release is differently affected by inhibitors of calmodulin, diacylglycerol kinase and peptidyl prolyl cis‐trans isomerase in a secretagogue specific manner
Authors: H. Bergstrand, B. Lundquist
Journal: Allergy (1992)

Bergstrand H, Lundquist B. Human basophil histamine release is differently affected by inhibitors of calmodulin, diacylglycerol kinase and peptidyl prolyl cis‐trans isomerase in a secretagogue specific manner. To assess the role of calmodulin in human basophil histamine release, we triggered leukocytes with different secretagogues in the presence of putative inhibitors of calmodulin. Calcium ionophore‐induced histamine release was reduced or blocked by calmidazolium, CGS 9343B, felodipine, metofenazate, and Ro 22–4839. H 186/86, a felodipine‐related dihydropyridine derivative, blocked A23187‐but not ionomycin‐triggered histamine release, suggesting a difference in the mode of action of these ionophores. In contrast, leukocyte histamine release triggered by the purported protein kinase C (PKC) activator, l, 2‐isopropylidene‐3‐decanoyl‐ sn ‐glycerol (IpOCOC 9 ), was enhanced by calmidazolium, CGS 9349B and metofenazate but not affected by felodipine or Ro 22‐4839, whereas the response triggered by 4β‐phorbol 12‐myristate 13‐aeetate (PMA) was reduced by metofenazate and Ro 22‐4839 but not consistently affected by calmidazolium, CGS 9343B or felodipine. The PMA‐induced histamine release was enhanced by H 186/86. Anti‐IgE‐ and F mlp ‐induced responses were either unaffected or slightly enhanced by the examined calmodulin antagonists. In comparison with the calmodulin antagonists, R 59022, an inhibitor of diacylglycerol kinase, failed to reduce calcium ionophore‐triggered histamine release, whereas FK506, an inhibitor of peptidyl prolyl cis‐trans isomerase (PPI), reduced both anti‐IgE‐ and ionophore‐triggered responses. These results indicate that calmodulin constitutes an obligate link in signal transduction pathways leading to human leukocyte histamine release if the trigger is a calcium ionophore but not when responses are induced by anti‐IgE, F mlp or PMA; a calmodulin‐dependent component may rather balance responses induced by IpOCOC 9 . We also conclude that most employed stimuli, including IpOCOC 9 , trigger human basophil histamine release through partly distinet pathways.
International standards for newborn weight, length, and head circumference by gestational age and sex: the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project
Authors: José Villar, Leila Cheikh Ismail, Cesar G Victora, Eric O Ohuma, Enrico Bertino, Doug G Altman, Ann Lambert, Aris T Papageorghiou, Maria Carvalho, Yasmin A Jaffer, Michael G Gravett, Manorama Purwar, Ihunnaya O Frederick, Alison J Noble, Ruyan Pang, Fernando C Barros, Cameron Chumlea, Zulfiqar A Bhutta, Stephen H Kennedy
Journal: The Lancet (2014)
Prognostic Factors for Stage III Epithelial Ovarian Cancer: A Gynecologic Oncology Group Study
Authors: William E. Winter, G. Larry Maxwell, Chunqiao Tian, Jay W. Carlson, Robert F. Ozols, Peter G. Rose, Maurie Markman, Deborah K. Armstrong, Franco Muggia, William P. McGuire
Journal: Journal of Clinical Oncology (2007)

Purpose Conflicting results on prognostic factors for advanced epithelial ovarian cancer (EOC) have been reported because of small sample size and heterogeneity of study population. The purpose of this study was to identify factors predictive of poor prognosis in a similarly treated population of women with advanced EOC. Patients and Methods A retrospective review of demographic, pathologic, treatment, and outcome data from 1,895 patients with International Federation of Gynecology and Obstetrics stage III EOC who had undergone primary surgery followed by six cycles of intravenous platinum/paclitaxel was conducted. A proportional hazards model was used to assess the association of prognostic factors with progression-free survival (PFS) and overall survival (OS). Results Increasing age was associated with increased risks for disease progression (HR = 1.06; 95% CI, 1.02 to 1.11 for an increase every 10 years) and death (HR = 1.12; 95% CI, 1.06 to 1.18). Mucinous or clear-cell histology was associated with a worse PFS and OS compared with serous carcinomas. Patients with performance status (PS) 1 or 2 were at an increased risk for recurrence compared with PS 0 (HR = 1.12; 95% CI, 1.01 to 1.24). Compared with patients with microscopic residual disease, patients with 0.1 to 1.0 cm and &gt; 1.0 cm residual disease had an increased risk of recurrence (HR = 1.96; 95% CI, 1.70 to 2.26; and HR = 2.36; 95% CI, 2.04 to 2.73, respectively) and death (HR = 2.11; 95% CI, 1.78 to 2.49; P &lt; .001; and HR = 2.47; 95% CI, 2.09 to 2.92, respectively). Conclusion Age, PS, tumor histology, and residual tumor volume were independent predictors of prognosis in patients with stage III EOC. These data can be used to identify patients with poor prognosis and to design future tailored randomized clinical trials.
Involvement of p38 mitogen-activated protein kinase signaling in transformed growth of a cholangiocarcinoma cell line
Authors: L Tadlock
Journal: Hepatology (2001)

Although mitogen-activated protein kinase (MAPK) pathways play a key role in cell growth, their role in mediating the altered growth phenotype of transformed cells remains unclear. The p44/p42 MAPK signaling cascades are activated by mitogenic stimulation of human cholangiocytes. In contrast, the p38 MAPK pathway is activated by mitogen stimulation of malignant, but not nonmalignant cholangiocytes. Thus, our aims were to determine the role of p38 MAPK signaling in mediating the growth phenotype of transformed cholangiocytes. KMCH-1 malignant human cholangiocytes required the presence of serum for proliferation, but were able to grow in reduced serum conditions. Inhibition of p38 MAPK decreased serum-dependent proliferation of KMCH-1 cells. Furthermore, inhibition of p38 MAPK, but not of p44/p42 MAPK, reduced anchorage-independent growth of KMCH-1 cells. Although both p38 and p44/p42 MAPK are activated in response to mitogens, they have divergent effects on anchorage-independent growth. Inhibition of p38 MAPK, but not of p44/p42 MAPK signaling, decreased cell cycle progression and increased expression of the cyclin-dependent kinase inhibitor p21WAF1/CIPl. However, expression of p27KIP1 or p16INK4A was not altered by either pathway. Thus, mitogen activation of p38 MAPK decreases expression of p21WAF1/CIP1 and mediates growth independent of anchorage signals, whereas mitogen activation of p44/p42 MAPK mediates an anchorage signal-dependent growth pathway. These data provide a link between aberrant stress-activated cell signaling and the altered growth phenotype of transformed cells that may be important for the development of therapies to limit transformed cell growth.
Inhibition of the alternative complement pathway preserves photoreceptors after retinal injury
Authors: J. Harry Sweigard, Hidetaka Matsumoto, Kaylee E. Smith, Leo A. Kim, Eleftherios I. Paschalis, Yoko Okonuki, Alexandra Castillejos, Keiko Kataoka, Eiichi Hasegawa, Ryoji Yanai, Deeba Husain, John D. Lambris, Demetrios Vavvas, Joan W. Miller, Kip M. Connor
Journal: Science Translational Medicine (2015)

The alternative complement pathway is activated in response to retinal injury, and inhibiting this pathway prevents complement-mediated photoreceptor cell death.
Congenital dyserythropoietic anemia type II: epidemiology, clinical appearance, and prognosis based on long-term observation
Authors: Hermann Heimpel, Volker Anselstetter, Ladislav Chrobak, Jonas Denecke, Beate Einsiedler, Kerstin Gallmeier, Antje Griesshammer, Thorsten Marquardt, Gritta Janka-Schaub, Martina Kron, Elisabeth Kohne
Journal: Blood (2003)
Looking Beyond Survival: How Are We Looking at Survivorship?
Authors: Eva Grunfeld
Journal: Journal of Clinical Oncology (2006)

The prevalence of cancer survivors is increasing worldwide. This creates the imperative to look beyond cancer survival to cancer survivorship. This review explores cancer survivorship from an international perspective in two ways: from a cancer control perspective through a review of cancer control strategies and from a cancer care perspective through a review of clinical practice guidelines and research on cancer follow-up care.Many national cancer control strategies or cancer charities consider survivorship obliquely, primarily under the umbrellas of quality of life and rehabilitation. Few have well-developed policies or plans specifically directed at survivorship. Cancer follow-up care is recognized internationally as a pressing health care issue. Many countries have tested new and innovative models to deliver follow-up care. Similarly, many countries have developed guidelines that specifically address follow-up care. Few studies or guidelines address the broader, multifaceted aspects of cancer survivorship.This review suggests that research and recognition of cancer survivorship as a unique phase of the cancer care trajectory need to be improved. In many of the poorer countries of the world, the imperative remains the basics of cancer care: timely diagnosis, access to treatment, and alleviation of suffering.
The Molecular Pharmacology and Cell Biology of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Receptors
Authors: Claire L. Palmer, Lucy Cotton, Jeremy M. Henley
Journal: Pharmacological Reviews (2005)

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) are of fundamental importance in the brain. They are responsible for the majority of fast excitatory synaptic transmission, and their overactivation is potently excitotoxic. Recent findings have implicated AMPARs in synapse formation and stabilization, and regulation of functional AMPARs is the principal mechanism underlying synaptic plasticity. Changes in AMPAR activity have been described in the pathology of numerous diseases, such as Alzheimer9s disease, stroke, and epilepsy. Unsurprisingly, the developmental and activity-dependent changes in the functional synaptic expression of these receptors are under tight cellular regulation. The molecular and cellular mechanisms that control the postsynaptic insertion, arrangement, and lifetime of surface-expressed AMPARs are the subject of intense and widespread investigation. For example, there has been an explosion of information about proteins that interact with AMPAR subunits, and these interactors are beginning to provide real insight into the molecular and cellular mechanisms underlying the cell biology of AMPARs. As a result, there has been considerable progress in this field, and the aim of this review is to provide an account of the current state of knowledge.
A SYNTHETIC GLYCOLIPID WITH B-CELL MITOGENIC ACTIVITY
Authors: David L. Rosenstreich, Jean Asselineau, Stephan E. Mergenhagen, Alois Nowotny
Journal: The Journal of Experimental Medicine (1974)

A synthetic glycolipid, N-palmitoyl-D-glucosamine, (NPG) was found to be a potent B-cell mitogen, that stimulated spleen cells from nu/nu as well as from normal mice. The proper dispersion of the water insoluble preparation is critical for the elicitation of this mitogenic effect. Limulus lysate clotting assay indicated that the NPG preparation either contains only 0.001% endotoxin contamination, or that NPG itself is 10–5 times less active in this assay than purified endotoxic LPS. Since such low levels of endotoxin concentration are not mitogenic, it is concluded that synthetic N-palmitoyl-D-glucosamine, when properly dispersed, is itself a B-cell mitogen.
Effects of 1-Year Treatment with Cyclophosphamide on Outcomes at 2 Years in Scleroderma Lung Disease
Authors: Donald P. Tashkin, Robert Elashoff, Philip J. Clements, Michael D. Roth, Daniel E. Furst, Richard M. Silver, Jonathan Goldin, Edgar Arriola, Charlie Strange, Marcy B. Bolster, James R. Seibold, David J. Riley, Vivien M. Hsu, John Varga, Dean Schraufnagel, Arthur Theodore, Robert Simms, Robert Wise, Fred Wigley, Barbara White, Virginia Steen, Charles Read, Maureen Mayes, Ed Parsley, Kamal Mubarak, M. Kari Connolly, Jeffrey Golden, Mitchell Olman, Barri Fessler, Naomi Rothfield, Mark Metersky, Dinesh Khanna, Ning Li, Gang Li
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

The Scleroderma Lung Study enrolled 158 patients with scleroderma-related interstitial lung disease in a placebo-controlled trial of oral cyclophosphamide (CYC). Although treatment-related benefits in pulmonary function, skin scores, and patient-centered outcomes were demonstrated after 1 year of therapy, the duration of benefit beyond 1 year was unclear.A second year of follow-up was performed to determine if these effects persisted after stopping treatment.A detailed analysis of data obtained over the two years of the study was performed.Using a longitudinal joint model, we analyzed FVC, total lung capacity, transitional dyspnea index, Rodnan skin scores, and the Health Assessment Questionnaire-Disability Index during the second year, after adjusting for baseline values, baseline fibrosis score, and nonignorable missing data. Evaluable subjects (72 CYC; 73 placebo) included 93 who completed all visits plus 52 who completed at least 6 months of therapy and returned at 24 month or had their 24-month data imputed. The beneficial effects of CYC on pulmonary function and health status continued to increase through 18 months, after which they dissipated, whereas skin improvements dissipated after 12 months. In contrast, the positive effect on dyspnea persisted through 24 months. Adverse events were uncommon.One year of CYC improved lung function, skin scores, dyspnea, and health status/disability, effects which either persisted or increased further for several months after stopping therapy. However, except for a sustained impact on dyspnea, all of these effects waned and were no longer apparent at 24 months. Treatment strategies aimed at extending the positive therapeutic effects observed with CYC should be considered. Clinical trial registered with www.clinicaltrials.gov (NCT 000004563).