tbuckley/cabot-search huggingface dataset:
Cancer Immunotherapy Using a Bispecific NK Receptor Fusion Protein that Engages both T Cells and Tumor Cells
Authors: Tong Zhang, Charles L. Sentman
Journal: Cancer Research (2011)

Abstract T-cell immunotherapy is a promising strategy to treat cancer, but its efficacy, complexity, and costs may pose challenges. In this study, we report the results of an investigation of a new approach to selectively activate a T-cell attack against tumor cells. The immunotherapeutic approach we developed utilizes a bifunctional fusion protein that binds tumor cells through NK (natural killer)–activating receptor NKG2D and that recruits and stimulates T cells through an anti-CD3 single-chain variable fragment (scFv-NKG2D). In vitro, this scFv-NKG2D fusion protein engaged both T cells and tumor cells, stimulating T cells to produce IFN-γ, and cytotoxicity against NKG2D ligand–positive tumor cells. In vivo, expression of scFv-NKG2D by NKG2D ligand–positive tumor cells reduced tumor burden and, in some cases, led to tumor-free survival. Administration of scFv-NKG2D in vivo also promoted survival in a murine lymphoma model. Tumor-free mice were resistant to rechallenge with cognate tumor cells, suggesting that a host-specific immunologic memory response had been generated. Host adaptive immunity including γδ T cells was required for scFv-NKG2D–mediated therapeutic efficacy. ScFv-NKG2D also inhibited the growth of NKG2D ligand–negative B16F10 tumors, reduced the percentage of myeloid-derived suppressor cells and regulatory T cells, and increased the infiltration of T cells, suggesting that scFv-NKG2D may target these immune suppressive cells. Together, these results establish scFv-NKG2D as a promising biological fusion protein to induce effective antitumor immunity. Cancer Res; 71(6); 2066–76. ©2011 AACR.
Changes in brain adenosine during bicuculline-induced seizures in rats. Effects of hypoxia and altered systemic blood pressure.
Authors: H R Winn, J E Welsh, R Rubio, R M Berne
Journal: Circulation Research (1980)

We analyzed brain tissue in 139 rats for adenosine and its metabolites, inosine and hypoxanthine, during the initial 120 seconds of seizures induced by bicuculline. We also measured ATP, ADP, AMP, phosphocreatine (PCr), and lactate. We divided the rats into four groups by adjustment of their preictal arterial oxygen tension: group I, PaO2 &gt; 200 mm Hg; group II PaO2 = 50 mm Hg; and group III: PaO2 = 100 mm Hg. We treated a fourth group whose PaO2 = 100 mm Hg with phentolamine to block the 44% rise in blood pressure which occurred with the onset of seizures. PaCO2 was maintained between 30 anf 40 mm Hg in all groups. Brain tissue was sampled rapidly after 0, 10, 20, 30, 60, and 120 seconds of seizures by the freeze-blow technique. With normoxia (PaO2 = 100 mm Hg) or hyperoxia (PaO2 &gt; 200 mm Hg), adenosine increased within ten seconds of the onset of seizures and remained elevated even after 120 seconds. Elevations in inosine and hypoxanthine were delayed compared to the increases in adenosine. A reduction in PaO2 (50 mm Hg) or systemic blood pressure during seizures caused a further augmentation in the increase in brain adenosine levels. During the seizure period, transient changes in adenine nucleotides and energy charge were observed, but PCr remained depressed and lactate continued to rise. The rapid and sustained increase in cerebral adenosine levels, temporally paralleling the changes in cerebral blood flow, supports the role for adenosine in the regulation of cerebral blood flow.
The origin and function of mirror neurons: The missing link
Authors: Angelika Lingnau, Alfonso Caramazza
Journal: Behavioral and Brain Sciences (2014)

Abstract We argue, by analogy to the neural organization of the object recognition system, that demonstration of modulation of mirror neurons by associative learning does not imply absence of genetic adaptation. Innate connectivity defines the types of processes mirror neurons can participate in while allowing for extensive local plasticity. However, the proper function of these neurons remains to be worked out.
Phase II Study of Temozolomide and Thalidomide in Patients With Metastatic Neuroendocrine Tumors
Authors: Matthew H. Kulke, Keith Stuart, Peter C. Enzinger, David P. Ryan, Jeffrey W. Clark, Alona Muzikansky, Michele Vincitore, Ann Michelini, Charles S. Fuchs
Journal: Journal of Clinical Oncology (2006)

Standard, intravenous chemotherapy regimens for neuroendocrine tumors have been associated with limited response rates and significant toxicity. We evaluated the efficacy of an oral regimen of temozolomide and thalidomide in patients with metastatic carcinoid, pheochromocytoma, or pancreatic neuroendocrine tumors.Twenty-nine patients were treated with a combination of temozolomide, administered at a dose of 150 mg/m2 for 7 days, every other week, and thalidomide at doses of 50 to 400 mg daily. Patients were followed for evidence of toxicity, biochemical response, radiologic response, and survival.Treatment with temozolomide and thalidomide was associated with an objective biochemical (chromogranin A) response rate of 40%, and a radiologic response rate of 25% (45% among pancreatic endocrine tumors, 33% among pheochromocytomas, and 7% among carcinoid tumors). The median duration of response was 13.5 months, 1-year survival was 79%, and 2-year survival was 61%. The median administered dose of temozolomide was 150 mg/m(2), and the median administered dose of thalidomide was 100 mg daily. Grade 3-4 toxicities were uncommon, with the exception of grade 3-4 lymphopenia, which developed in 69% of the patient population. Opportunistic infections occurred in three patients (10%) during the time of lymphopenia, and included single cases of Pneumocystis carinii pneumonia, disseminated varicella zoster virus, and herpes simplex virus.Orally administered temozolomide and thalidomide seems to be an active regimen for the treatment of neuroendocrine tumors. In this 29-patient study, this regimen appeared more active in pancreatic endocrine tumors than in carcinoid tumors.
NeMeSys: a biological resource for narrowing the gap between sequence and function in the human pathogen Neisseria meningitidis
Authors: Christophe Rusniok, David Vallenet, Stéphanie Floquet, Helen Ewles, Coralie Mouzé-Soulama, Daniel Brown, Aurélie Lajus, Carmen Buchrieser, Claudine Médigue, Philippe Glaser, Vladimir Pelicic
Journal: Genome biology (2009)

Abstract Background Genome sequences, now available for most pathogens, hold promise for the rational design of new therapies. However, biological resources for genome-scale identification of gene function (notably genes involved in pathogenesis) and/or genes essential for cell viability, which are necessary to achieve this goal, are often sorely lacking. This holds true for Neisseria meningitidis , one of the most feared human bacterial pathogens that causes meningitis and septicemia. Results By determining and manually annotating the complete genome sequence of a serogroup C clinical isolate of N. meningitidis (strain 8013) and assembling a library of defined mutants in up to 60% of its non-essential genes, we have created NeMeSys, a biological resource for Neisseria meningitidis systematic functional analysis. To further enhance the versatility of this toolbox, we have manually (re)annotated eight publicly available Neisseria genome sequences and stored all these data in a publicly accessible online database. The potential of NeMeSys for narrowing the gap between sequence and function is illustrated in several ways, notably by performing a functional genomics analysis of the biogenesis of type IV pili, one of the most widespread virulence factors in bacteria, and by identifying through comparative genomics a complete biochemical pathway (for sulfur metabolism) that may potentially be important for nasopharyngeal colonization. Conclusions By improving our capacity to understand gene function in an important human pathogen, NeMeSys is expected to contribute to the ongoing efforts aimed at understanding a prokaryotic cell comprehensively and eventually to the design of new therapies.
Iodixanol inhibits exogenous surfactant therapy in rats with acute respiratory distress syndrome
Authors: J. Kesecioglu, M.J. Schultz, J.J. Haitsma, G.J. den Heeten, B. Lachmann
Journal: European Respiratory Journal (2002)

Optimal alveolar distribution of exogenous surfactant is an important determinant of its beneficial effect. This distribution can be determined by suspending surfactant in a radiological contrast medium before intratracheal instillation, followed by radiological imaging. Iodixanol is reported to be a safe contrast medium that causes no lung injury when instilled intratracheally. In this study, the effects of surfactant suspended in saline were compared with surfactant suspended either in 4:1 saline-iodixanol (64 mg iodine·mL −1 ) or in 1:1 saline-iodixanol (160 mg iodine·mL −1 ), on oxygenation and lung mechanics in a rat model of adult respiratory distress syndrome (ARDS) induced by lung lavage. After the induction of ARDS, surfactant instillation improved oxygenation, total lung volume at inflation with a distending pressure of 35 cmH 2 O, lung volume at transpulmonary pressure of 5 cmH 2 O and Gruenwald index. The effects of surfactant suspended in 4:1 saline-iodixanol were similar to those of surfactant alone. However, instillation of surfactant suspended in 1:1 saline-iodixanol resulted in significantly lower values in all measured parameters. Surface tension was the lowest in surfactant suspended in saline alone and addition of iodixanol led to an increase in surface tension in a dose-dependent manner. In conclusion, iodixanol at the higher dose caused an inhibition of the exogenous surfactant effect, characterized as a lack of improvement in oxygen tension in arterial blood, low total lung compliance, volume at 5 cmH 2 O end-expiration and Gruenwald index. This effect of iodixanol was probably due to its high surface tension, especially if a high concentration was used. Surfactant suspended in a lower concentration of iodixanol seems a better alternative, allowing for radiological imaging of the distribution of surfactant when intratracheally instilled.
The Efficiency of Cellular Energy Transduction and Its Implications for Obesity
Authors: Mary-Ellen Harper, Katherine Green, Martin D. Brand
Journal: Annual Review of Nutrition (2008)

We assess the existence, mechanism, and functions of less-than-maximal coupling efficiency of mitochondrial oxidative phosphorylation and its potential as a target for future antiobesity interventions. Coupling efficiency is the proportion of oxygen consumption used to make adenosine triphosphate (ATP) and do useful work. High coupling efficiency may lead to fat deposition; low coupling efficiency to a decrease in fat stores. We review obligatory and facultative energy expenditure and the role of a futile cycle of proton pumping and proton leak across the mitochondrial inner membrane in dissipating energy. Basal proton conductance is catalyzed primarily by the adenine nucleotide translocase but can be mimicked by chemical uncouplers. Inducible proton conductance is catalyzed by specific uncoupling proteins. We discuss the opportunities and pitfalls of targeting these processes as a treatment for obesity by decreasing coupling efficiency and increasing energy expenditure, either directly or through central mechanisms of energy homeostasis.
Anakinra treatment for systemic juvenile idiopathic arthritis and adult onset Still disease
Authors: P. Woo
Journal: Annals of the Rheumatic Diseases (2007)

Why attend?c Join over 1000 healthcare professionals from over 40 countries worldwide c Learn from experienced leaders and improvement experts c Find out what is current in quality and safety c Gain new skills and tools for creating change in your organisation c Take home practical solutions for improvement methods c Network with like-minded colleagues This is a premier event for those dedicated to improving quality and safety in healthcare.Our focus is on practical, take-home ideas that will leave you inspired to implement valuable, lasting change on your return to the workplace.
Population-Based Case-Control Study of Chinese Herbal Products Containing Aristolochic Acid and Urinary Tract Cancer Risk
Authors: M.-N. Lai, S.-M. Wang, P.-C. Chen, Y.-Y. Chen, J.-D. Wang
Journal: JNCI Journal of the National Cancer Institute (2009)

BackgroundConsumption of Chinese herbs that contain aristolochic acid (eg, Mu Tong) has been associated with an increased risk of urinary tract cancer.
Are eligibility criteria for over the counter statins appropriate?
Authors: D Graham Mackenzie, Sarah H Wild, Philip Rutledge
Journal: BMJ (2006)

EDITOR—Low dose statins are now available for purchase over the counter by people at moderate risk of coronary heart disease (10 year risk of coronary heart disease 10-15%). Eligible people are identified using an assessment of age, sex, and number of risk factors for coronary heart disease as described in guidelines from the Royal Pharmaceutical Society of Great Britain.1 The guidelines also recommend that blood pressure and cholesterol should be checked to identify people at high risk who should see their general practitioner, but these tests are not always available …
Thromboembolism After Total Hip Reconstruction
Authors: Charles M. Evarts, Ralph J. Alfidi
Journal: JAMA (1973)

Twenty-five patients undergoing total hip replacement received low doses of heparin sodium. Phlebography was used for the diagnosis of deep venous thrombosis. Five thousand international units (IU) of heparin were given subcutaneously two hours preoperatively, 5,000 IU postoperatively the night of surgery, and every 12 hours for the next seven to ten days. Venous thrombosis developed in seven of 25 patients. Pulmonary embolism occurred in six patients. Until further studies are forthcoming, the utmost caution is urged in the use of low doses of heparin as a prophylactic agent after total hip reconstruction.
Fibroblast growth factor-1 improves cardiac functional recovery and enhances cell survival after ischemia and reperfusion
Authors: Meindert Palmen, Mat J.A.P. Daemen, Leon J. De Windt, Jodil Willems, Willem R.M. Dassen, Sylvia Heeneman, Rene Zimmermann, Marc Van Bilsen, Pieter A. Doevendans
Journal: Journal of the American College of Cardiology (2004)
Mass ECG screening of young athletes
Authors: Roy J Shephard
Journal: British Journal of Sports Medicine (2008)

A recent article by Wilson and colleagues1 proposes the mandatory ECG screening of athletes as a means of reducing the risk of sudden cardiac death in this population. The idea of such screening originated with the studies of Dr Corrado and his colleagues in Italy.2 The concept has subsequently received support from several European groups, Dr Corrado being involved in some of these: the International Olympic Committee Medical Commission,3 the European Society of Cardiology4 and the Federation Internationale de Football Association (FIFA).5

A proper starting point for a consideration of this issue is Bayes’ theorem. This theorem makes clear that mass screening cannot be effective and will inevitably lead to a high proportion of false positive results if one is using a fallible test procedure when attempting to detect a rare risk. Wilson and associates1 attempted to increase the frequency of their positive outcomes by assessing the frequency with which their ECGs detected certain “abnormalities” such as the Wolff–Parkinson–White (WPW) syndrome, thought to be associated with an increased risk of sudden death. One …
Speckled hyperpigmentation, palmo-plantar punctate keratoses and childhood blistering: a clinical triad, with variable associations.
Authors: J. M. BOSS, C.N.A. MATTHEWS, R. D. G. PEACHEY, R. SUMMERLY
Journal: British Journal of Dermatology (1981)

Journal Article Speckled hyperpigmentation, palmo‐plantar punctate keratoses and childhood blistering: a clinical triad, with variable associations: A REPORT OF TWO FAMILIES Get access J. M. BOSS, J. M. BOSS Departments of Dermatology, Bristol Royal Infirmary, Bristol and North Staffordshire Hospital Centre, Stoke‐on‐Trent Search for other works by this author on: Oxford Academic Google Scholar C.N.A. MATTHEWS, C.N.A. MATTHEWS Departments of Dermatology, Bristol Royal Infirmary, Bristol and North Staffordshire Hospital Centre, Stoke‐on‐Trent Search for other works by this author on: Oxford Academic Google Scholar R. D. G. PEACHEY, R. D. G. PEACHEY Departments of Dermatology, Bristol Royal Infirmary, Bristol and North Staffordshire Hospital Centre, Stoke‐on‐Trent Reprint requests: Dr R. D. G. Peachey, Bristol Royal Infirmary, Bristol, BS2 8HW. Search for other works by this author on: Oxford Academic Google Scholar R. SUMMERLY R. SUMMERLY Departments of Dermatology, Bristol Royal Infirmary, Bristol and North Staffordshire Hospital Centre, Stoke‐on‐Trent Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 105, Issue 5, 1 November 1981, Pages 579–585, https://doi.org/10.1111/j.1365-2133.1981.tb00803.x Published: 01 November 1981 Article history Accepted: 02 January 1981 Published: 01 November 1981
Cost-Effectiveness of Cardiac Resynchronization Therapy in Patients with Symptomatic Heart Failure
Authors: Graham Nichol, Padma Kaul, Ella Huszti, John F.P. Bridges
Journal: Annals of Internal Medicine (2004)

Heart failure is a common, costly, and debilitating illness. Resynchronization of ventricular contraction in patients with heart failure improves ejection fraction. The long-term morbidity and costs associated with such cardiac resynchronization therapy remain unclear.To assess the incremental cost-effectiveness of cardiac resynchronization therapy.Markov model with Monte Carlo simulation. Future costs and effects were discounted at 3%.Effects data were obtained from a concurrent systematic review. Health-related quality-of-life and cost data were obtained from publicly available data or from surveys.Patients with reduced ventricular function and prolonged QRS.Lifetime.U.S. health care system.Cardiac resynchronization therapy versus medical therapy.Quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness.Medical therapy yielded a median of 2.64 (interquartile range, 2.47 to 2.82) discounted QALYs and a median discounted lifetime cost of 34,400 dollars (interquartile range, 31,100 dollars to 37,700 dollars). Cardiac resynchronization therapy was associated with a median incremental cost of 107,800 dollars(interquartile range, 79,800 dollars to 156,500 dollars) per additional QALY.Results were sensitive to changes in several variables, including the relative risk for death or hospitalization.These results apply to patients who meet the inclusion criteria of the currently completed trials.The incremental cost per QALY for cardiac resynchronization is similar to that of other commonly used interventions but is sensitive to changes in several key variables. Resynchronization therapy should not be considered in patients with comorbid illness that shortens life expectancy.
FURTHER REMARKS ON THE TREATMENT OF ASTHMA BY PEPTONE
Authors: A. G. Auld
Journal: BMJ (1918)

Auditory nerve fibers (ANFs) encode pure tones through two modes of coding, spike time or spike rate, depending on the tone frequency. In response to a low-frequency tone, ANF firing is phase locked to the sinusoidal waveform. Because time coding vanishes with an increase in the tone frequency, high frequency tone coding relies on the spike rate of the ANFs. Adding a continuous broadband noise to a tone compresses the rate-intensity function of ANFs, and shifts its dynamic range towards higher intensities. Thus, the ANFs with elevated threshold/low-spontaneous rate (SR) are thought to contribute to behavioral tone detection in noise. However, this theory relies on the discharge rate of the ANFs. The direct comparison with the masking threshold through spike timing, irrespectively of the spontaneous rate, has not so far been investigated. Taking advantage of a unique proxy to quantify the spike synchrony (<i>i.e.</i> the shuffle autocorrelogram), we show in female gerbils that high-SR ANFs are more adapted to encode low-frequency thresholds through temporal code, giving them a strong robustness in noise. By comparing behavioral thresholds measured using prepulse inhibition of the acoustical startle reflex with population thresholds calculated from ANFs pooled per octave band, we show that threshold based spike timing provides a better estimate of behavioral thresholds in the low-frequency range, whereas the high-frequency behavioral thresholds rely on the spiking rate, particularly in noise. This emphasizes the complementarity of temporal and rate modes to code tone-in-noise thresholds over a large range of frequencies. <b>SIGNIFICANCE STATEMENT</b> There is a general agreement that high-threshold/low-spontaneous rate (SR) auditory nerve fibers (ANFs) are of the prime importance to operate tone detection in noise. However, this theory is based on the discharge rate of the fibers. Comparing the behavioral thresholds and single ANF thresholds shows this is only true in the high-frequency range of tone stimulations. In the low-frequency range of tones (up to 2.7 kHz in gerbil), the most sensitive ANFs (high-SR fibers) carry neural information through a spike-timing mode, even in noise when tones do not induce a noticeable increment in the spike rate. This emphasizes the interplay between spike-time and spike-rate modes in the auditory nerve to encode tone-in-noise threshold over a large range of tone frequencies.
Phase II Trial of Procarbazine, Lomustine, and Vincristine as Initial Therapy for Patients With Low-Grade Oligodendroglioma or Oligoastrocytoma: Efficacy and Associations With Chromosomal Abnormalities
Authors: Jan C. Buckner, Dean Gesme, Judith R. O’Fallon, Julie E. Hammack, Scott Stafford, Paul D. Brown, Roland Hawkins, Bernd W. Scheithauer, Bradley J. Erickson, Ralph Levitt, Edward G. Shaw, Robert Jenkins
Journal: Journal of Clinical Oncology (2003)

The purpose of this article is to determine the response rate and toxicity of PCV administered before radiation therapy in patients with newly diagnosed LGO/LGOA and to explore correlations between response with 1p/19q deletions and aberrant p53 expression.Despite prolonged survival of patients with low-grade oligodendroglioma (LGO) and oligoastrocytoma (LGOA), the majority will succumb to progressive disease. Because procarbazine, lomustine (CCNU), and vincristine (PCV) is active in patients with recurrent LGO/LGOA, we hypothesized that it would be beneficial as primary therapy.Adult patients with residual tumor on magnetic resonance imaging scan following biopsy or subtotal resection of LGO/LGOA received up to six cycles of PCV. Radiation therapy (59.4 or 54.0 Gy) began within 10 weeks of completing chemotherapy or immediately if there was evidence of tumor progression on PCV. Tumor tissue was analyzed by fluorescent in situ hybridization for 1p and 19q deletion and by immunohistochemistry for p53 expression.Eight of 28 (29%) and 13 of 25 (52%) eligible patients demonstrated tumor regression as assessed by the treating physician and a blinded central neuroradiology reviewer, respectively. Myelosuppression was the predominant toxicity. Loss of 1p and 19q were associated with LGO but not LGOA (P =.009), were inversely associated with p53 detection, and were not associated with response to PCV (possibly because of the small sample size).PCV produces tumor regressions in a meaningful proportion of patients with LGO/LGOA. Toxicity, especially myelosuppression, is significant. Loss of 1p and 19q seems limited to patients with pure LGO and is inversely related to p53 alterations.