tbuckley/cabot-search huggingface dataset:
A 96-well plate cell-based assay to quantify undesired cytotoxic effects against quiescent non-dividing cells
Authors: Laura A. Rudolph-Owen, Kathleen Salvato, Hongsheng Cheng, Jiayi Wu, Murray J. Towle, Bruce A. Littlefield
Journal: Cancer Research (2004)

1157  A major issue in the development of new chemotherapeutic agents is the occurrence of undesired toxicity in normal tissues. In fact, toxicity against normal non-dividing cells within the context of affected organs is the most common reason that compounds fail in the clinic. Here we describe the development of an assay to measure cytotoxicity against quiescent, or non-dividing, cells. IMR-90 human lung fibroblasts were plated at 1.0 x 104 cells/well in 96-well plates and grown in EMEM + 10% FBS. After 5 days in culture, media for the now confluent cells was replaced with EMEM + 0.1% FBS for three days to ensure total quiescence. Quiescence was verified using [3H]-thymidine incorporation with signal to noise ratio calculated by the ability of aphidicolin to further reduce signal. Test compounds were plated at final concentrations of 0.03nM to 100uM, and cell viability determined by measuring intracellular ATP after 1-3 days using a luciferase-based monitoring system (ATPLite, Perkin Elmer). Several clinical and laboratory compounds were evaluated in the quiescent IMR-90 cytotoxicity assay including the clinical drugs paclitaxel, oxaliplatin, 5-FU, doxorubicin, etoposide, SN-38 (active metabolite of CPT-11), gemcitabine and mitomycin C, as well as the laboratory tools actinomycin D and cycloheximide. Results indicate that clinical agents which act solely within proliferative phases of the cell cycle show good cytotoxicity windows between cytotoxic effects on quiescent fibroblasts and growth inhibitory effects against proliferating cancer cells. For example, the mitotic blocker paclitaxel inhibits cancer cell growth at low nM concentrations, yet is not cytotoxic to quiescent fibroblasts until approximately 10 μM even after 72 hours. Interestingly, agents such as doxorubicin, mitomycin C, and actinomycin D, which act via direct interactions with nucleic acids, show time-dependent increases in cytotoxicity against quiescent fibroblasts. Overall, results from a spectrum of drugs tested in this assay indicate that agents with mechanisms which are not exclusive to the proliferative phases of the cell cycle will show cytotoxicity towards quiescent fibroblasts. Most assays currently in use examine both cell proliferation and cytotoxicity in dividing cells, whether malignant or nonmalignant. However, assays which can quantify cytotoxic effects against truly non-proliferating cells have not been described. Development of the quiescent IMR-90 cytotoxicity assay to quantify cytotoxicity in non-dividing cells provides an in vitro tool to gauge the likelihood of undesirable cytotoxicity against non-dividing cells. These data may help guide the decision to subject anticancer leads to in vivo evaluation and thus accelerate progression of only the most promising drug candidates toward clinical testing.
Epidemic influenza and general hospitals.
Journal: BMJ (1968)

PointersAspirin and Haemorrhage: Incidence of aspirin- taking correlated with lesion in 582 patients with gastro-duodenal haemorrhage.Positive aspirin history most common in acute gastric lesions (p.661).Alcohol may accentuate blood loss from aspirin ingestion (p.664).Fibrin Degradation Products in Pregnancy: Level of fibrin/fibrinogen degradation products found to rise during pregnancy, suggesting that fibrinolysis may not be decreased in late preg- nancy, as has been assumed previously (p.665).Hypercalciuria and Stones: Study of the characteristics of stone-formers' urine (p.668).Home Haemodialysis: Internal arteriovenous fistula preferred by patients to external shunt.No medical complications in a total experience of 30 patient-months (p.671).Electrocardiogram in Diagnosis: In only 25% of 77 episodes of myocardial infarction was the initial E.C.G. tracing diagnostic.Early accu- rate diagnosis of slight attacks is best made by clinical examination and E.C.G. reporting by the same doctor (p.673).Home Treatment: Patients with myocardial
Relation between sympathetic outflow and vascular resistance in the calf during perturbations in central venous pressure. Evidence for cardiopulmonary afferent regulation of calf vascular resistance in humans.
Authors: S FVissing, UScherrer, R GVictor
Journal: Circulation Research (1989)

Vascular studies in humans have advanced the concept that, during orthostatic stress, cardiopulmonary afferents reflexly regulate vascular resistance in the forearm but exert surprisingly little if any effects on vascular resistance in the calf. In contrast, neurophysiological studies have indicated that unloading of cardiopulmonary afferents during lower body negative pressure evokes comparable increases in sympathetic outflow to the muscles of both the forearm and the calf. The aim of this study, therefore, was to determine if alterations in central venous pressure over the physiological range trigger reflex changes in muscle sympathetic outflow that not only are statistically significant but also are large enough to alter vascular resistance in the calf. To accomplish this aim, we measured calf blood flow with plethysmography and simultaneously performed microelectrode recordings of sympathetic outflow to calf muscles in conscious humans during maneuvers designed to alter the loading conditions of the ...
Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without congestive heart failure. A substudy of the Studies of Left Ventricular Dysfunction (SOLVD).
Authors: G SFrancis, CBenedict, D EJohnstone, P CKirlin, JNicklas, C SLiang, S HKubo, ERudin-Toretsky, SYusuf
Journal: Circulation (1990)

Neuroendocrine activation is known to occur in patients with congestive heart failure, but there is uncertainty as to whether this occurs before or after the presence of overt symptoms. In the Studies of Left Ventricular Dysfunction (SOLVD), a multicenter study of patients with ejection fractions of 35% or less, we compared baseline plasma norepinephrine, plasma renin activity, plasma atrial natriuretic factor, and plasma arginine vasopressin in 56 control subjects, 151 patients with left ventricular dysfunction (no overt heart failure), and 81 patients with overt heart failure before randomization. Median values for plasma norepinephrine (p = 0.0001), plasma atrial natriuretic factor (p less than 0.0001), plasma arginine vasopressin (p = 0.006), and plasma renin activity (p = 0.03) were significantly higher in patients with left ventricular dysfunction than in normal control subjects. Neuroendocrine values were highest in patients with overt heart failure. Plasma renin activity was normal in patients wit...
Automated quantitative coronary arteriography: morphologic and physiologic validation in vivo of a rapid digital angiographic method.
Authors: G BMancini, S BSimon, M JMcGillem, M TLeFree, H ZFriedman, R AVogel
Journal: Circulation (1987)

Quantitative coronary arteriography has been shown to be useful in assessing the extent of coronary disease, its functional significance, and its response to therapeutic interventions. Most current methods rely either on hand-drawn arterial contours or automatic edge-detection algorithms applied to 35 mm cineangiograms. To assess the performance in vivo of a new, fully automatic, rapid coronary quantitation program, dogs were instrumented with precision-drilled, plastic cylinders to create intraluminal stenoses in the left anterior descending and/or circumflex arteries, as well as with high-fidelity micromanometers and electromagnetic flow probes. Stenosis diameters ranged from 0.83 to 1.83 mm. Biplane, on-line, digital coronary angiograms and cineangiograms were recorded during standard selective coronary arteriography in the closed-chest preparation. The on-line digital images were analyzed in nonsubtracted and subtracted modes. Cineangiograms were digitized to allow coronary quantitation by the same co...
The importance of the determination of the myocardial area at risk in the evaluation of the outcome of acute myocardial infarction in patients.
Authors: A JFeiring, M RJohnson, J MKioschos, P TKirchner, M LMarcus, C WWhite
Journal: Circulation (1987)

On the basis of animal studies, we postulated that the size of the perfusion field (risk area) of an occluded coronary artery would be an important determinant of outcome in patients with acute myocardial infarction. To test this hypothesis, we measured size of the risk area in 27 patients with acute myocardial infarction by the intracoronary injection of 99mTc-macroaggregated albumin and gated nuclear imaging. After injection of the albumin spheres (5.3 +/- 1.4 hr after the onset of chest pain) streptokinase was administered and in 16 of 27 patients (59%) effective thrombolysis was achieved. Since none of the patients had evidence of a prior acute myocardial infarction, the 3 day nuclear left ventricular ejection fraction (LVEF) was considered an index of infarct size. Response to thrombolysis was analyzed according to success or failure of reperfusion and the size of the risk area (small risk area less than 25%, large risk area greater than 25% of left ventricular surface area). Standard clinical indexe...
Beta-adrenergic agonists stimulate the oxidative pentose phosphate pathway in the rat heart.
Authors: H GZimmer, HIbel, USuchner
Journal: Circulation Research (1990)

The oxidative pentose phosphate pathway is poorly developed in the rat heart compared with other organs, since the activity of glucose-6-phosphate dehydrogenase (G-6-PDH), the first and rate-limiting enzyme of the oxidative pentose phosphate pathway, is low. As a consequence, the available pool of 5-phosphoribosyl-1-pyrophosphate and the rate of adenine nucleotide biosynthesis are limited. Isoproterenol, 24 hours after subcutaneous administration at 0.1, 1, and 25 mg/kg, stimulated the activity of G-6-PDH in whole hearts dose-dependently from 4.3 +/- 0.16 (control) to 6.6 +/- 0.35, 10.3 +/- 0.82, and 11.5 +/- 0.56 units/g protein, respectively. The activity of 6-phosphogluconate dehydrogenase, another of the enzymes in the oxidative pentose phosphate pathway, remained unchanged. G-6-PDH activity started to increase 12 hours after isoproterenol application, when the glycogenolytic and functional response was over, and reached a peak value between 24 and 48 hours. This stimulating effect was also demonstrat...
Developmental changes in calcium currents of rabbit ventricular cells.
Authors: TOsaka, R WJoyner
Journal: Circulation Research (1991)

We investigated the postnatal development of L-type Ca2+ current (ICa) in enzymatically isolated adult (AD) and newborn (NB) (1-3-day-old) rabbit ventricular cells using the whole-cell, patch-clamp method. ICa was recorded with Cs(+)-rich pipettes and a Na(+)- and K(+)-free bath solution at 36 degrees C to eliminate other currents. ICa density (obtained by normalizing ICa to the cell capacitance) was significantly higher in AD cells than in NB cells at potential levels between 0 and +50 mV with 1.8 mM Ca2+ as the charge carrier. There was no shift in the current-voltage relation between AD and NB cells. The maximum ICa density was 9.9 +/- 2.0 pA/pF at 14 +/- 5 mV in AD cells (n = 11) compared with 5.6 +/- 2.0 pA/pF at 13 +/- 5 mV in NB cells (n = 7) (mean +/- SD). Time to half inactivation (T 1/2) showed a nearly U-shaped relation to membrane potentials from -10 to +30 mV with the shortest T 1/2 at the potential giving the maximum ICa density in both groups. T 1/2 at 0 and +10 mV was slightly but signific...
在系统评价中没有荟萃分析（游泳）的合成：报告指南
Authors: 迈尔里 Campbell., 乔安妮E. McKenzie., 阿曼达 Sowden., srinivasa vittal katikireddi., 苏e brennan., 西蒙 Ellis., Jamie Hartmann-Boyce, Rebecca Ryan., Sasha Shepperd., 詹姆斯托马斯, Vivian Welch., 希拉里汤姆森
Journal: BMJ (2020)

在系统的解释中，缺乏对Meta分析的数据，常用的替代合成方法是常用的，但很少报道这些方法。这种方法中缺乏透明度可以对审查结果的有效性倾诉。已经制定了没有元分析（SWIM）指南的合成，以指导在使用替代合成方法对效果估计的替代合成方法的审查中进行清除报告。本文介绍了综合干预效果的定量数据的游泳指南的开发，并提出了九个游泳报告项目，并伴随着解释和示例。
Role of Fluorescence Confocal Microscopy for Rapid Evaluation of Endoscopic Ultrasound Fine Needle Biopsy in Pancreatic Solid Lesions
Authors: S Stigliano, D Biasutto, FM Di Matteo
Journal: Endoscopy (2021)

Aims Endoscopic ultrasound fine needle biopsy (EUS FNB) is the standard procedure for the diagnosis of pancreatic lesions. Fluorescence Confocal microscopy (FCM) allows imaging of tissues in the fresh state, requiring minimal preparation without damage or loss of tissue. FCM could provide rapid information about the adequacy of the sample obtained during EUS-FNB with minimal preparation obviating at the unavailability of rapid onset evaluation (ROSE) and reducing the number of needle passes with the risk of adverse events. No data exists on FCM in the field of micro-histological specimens. We aimed at assess the diagnostic performance of FCM in predicting histological adequacy of EUS-FNB samples in pancreatic solid lesions and at assess the agreement between FCM evaluation and final histology.
Blood flow distribution within skeletal muscle during exercise in the presence of chronic heart failure: effect of milrinone.
Authors: HDrexler, FFaude, SHöing, HJust
Journal: Circulation (1987)

Recent studies suggest that, in the presence of heart failure, the capability of skeletal muscle to utilize delivered flow may be impaired due to maldistribution of blood flow within working muscle. Similarly, this mechanism could explain the failure of drugs to improve maximal oxygen consumption (VO2max) immediately. Accordingly, we assessed muscular blood flow distribution (ml/min/g, radioactive microspheres, 15 +/- 5 micron) among and within working muscle, VO2max, and arterial lactate in a rat preparation of myocardial infarction and heart failure (infarct size 36.0 +/- 3.3% of the left ventricle, n = 9), and in sham-operated animals (n = 11). Data were obtained at maximal treadmill exercise during alternate infusions of milrinone and saline. Total skeletal muscle blood flow during exercise was significantly lower in the infarction group (p less than .05 vs sham); reduced blood flow was primarily attributed to decreased flow to oxidative working muscle such as soleus and the red portion of gastrocnemi...
114P Nivolumab plus ipilimumab as first-line treatment for patients with advanced non-small cell lung cancer: A systematic review
Authors: J. Tandiono, S. Chen, E. Marcella, B. Susanto, R.S. Heriyanto, F. Wijovi, A. Tancherla, A. Kurniawan
Journal: Journal of Thoracic Oncology (2021)
Female Immunity Protects from Cutaneous Squamous Cell Carcinoma
Authors: Timothy Budden, Caroline Gaudy-Marqueste, Sarah Craig, Yuan Hu, Charles H. Earnshaw, Shilpa Gurung, Amelle Ra, Victoria Akhras, Patrick Shenjere, Ruth Green, Lynne Jamieson, John Lear, Luisa Motta, Carlos Caulín, Deemesh Oudit, Simon J. Furney, Amaya Virós
Journal: Clinical Cancer Research (2021)

Cancer susceptibility and mortality are higher in males, and the mutational and transcriptomic landscape of cancer differs by sex. The current assumption is that men are at higher risk of epithelial cancers as they expose more to carcinogens and accumulate more damage than women. We present data showing women present with less aggressive primary cutaneous squamous cell carcinoma (cSCC) and early strong immune activation.We explored clinical and molecular sexual disparity in immunocompetent and immunosuppressed patients with primary cSCC (N = 738, N = 160), advanced-stage cSCC (N = 63, N = 20) and FVB/N mice exposed to equal doses of DMBA, as well as in human keratinocytes by whole-exome, bulk, and single-cell RNA sequencing.We show cSCC is more aggressive in men, and immunocompetent women develop mild cSCC, later in life. To test whether sex drives disparity, we exposed male and female mice to equal doses of carcinogen, and found males present with more aggressive, metastatic cSCC than females. Critically, females activate cancer immune-related expression pathways and CD4 and CD8 T-cell infiltration independently of mutations, a response that is absent in prednisolone-treated animals. In contrast, males increase the rate of mitosis and proliferation in response to carcinogen. Women's skin and keratinocytes also activate immune-cancer fighting pathways and immune cells at UV radiation-damaged sites. Critically, a compromised immune system leads to high-risk, aggressive cSCC specifically in women.This work shows the immune response is sex biased in cSCC and highlights female immunity offers greater protection than male immunity.
Lithium chloride promotes osteogenesis and suppresses apoptosis during orthodontic tooth movement in osteoporotic model via regulating autophagy
Authors: Li Huang, Xing Yin, Jun Chen, Ruojing Liu, Xiaoyue Xiao, Zhiai Hu, Yan He, Shujuan Zou
Journal: Bioactive Materials (2021)

Osteoporosis is a widely distributed disease that may cause complications such as accelerated tooth movement, bone resorption, and tooth loss during orthodontic treatment. Promoting bone formation and reducing bone resorption are strategies for controlling these complications. For several decades, the autophagy inducer lithium chloride (LiCl) has been explored for bipolar . In this study, we investigated the autophagy-promoting effect of LiCl on bone remodeling under osteoporotic conditions during tooth movement. Ovariectomy was used to induce osteoporosis status in vivo. The results showed that LiCl rejuvenated autophagy, decreased apoptosis, and promoted bone formation, thus protecting tooth movement in osteoporotic mice. Furthermore, in vitro experiments showed that LiCl reversed the effects of ovariectomy on bone marrow-derived mesenchymal stem cells (BMSCs) extracted from ovariectomized mice, promoting osteogenesis and suppressing apoptosis by positively regulating autophagy. These findings suggest that LiCl can significantly decrease adverse effects of osteoporosis on bone remodeling, and that it has great potential significance in the field of bone formation during tooth movement in osteoporosis patients.
Neutral endopeptidase in the heart. Neutral endopeptidase inhibition prevents isoproterenol-induced myocardial hypoperfusion in rats by reducing bradykinin degradation.
Authors: GPiedimonte, J ANadel, C SLong, J IHoffman
Journal: Circulation Research (1994)

Peptide mediators may play a role in the control of myocardial perfusion. We found immunohistochemical evidence of the peptide-degrading enzyme neutral endopeptidase (NEP) in cultured rat myocytes. Therefore, we examined the effect of an NEP inhibitor, phosphoramidon, on myocardial perfusion in rats after (1) stimulating sensory nerves with capsaicin and (2) inducing myocardial hypoperfusion with isoproterenol, with or without pretreatment with selective antagonists of the substance P (NK1) and bradykinin (B2) receptors. Three to five sequential determinations of myocardial blood flow were made in anesthetized rats by injecting 100,000 radionuclide-labeled microspheres suspended in 70% dextrose into the left ventricle. Phosphoramidon doubled coronary blood flow in response to a dose of capsaicin that was ineffective in the absence of the inhibitor. Isoproterenol (50 mg/kg IP) caused an immediate fall in blood pressure and coronary blood flow; after 20 minutes, flow had returned to normal but pressure was ...
Response of the systemic and pulmonary circulation to converting-enzyme inhibition (captopril) at rest and during exercise in hypertensive patients.
Authors: RFagard, CBulpitt, PLijnen, AAmery
Journal: Circulation (1982)

Twenty sodium-replete patients with hypertension were allocated either to a placebo or to a captopril treatment group. Each patient was investigated in rest-recumbent (RR) and rest-sitting (RS) positions and during an uninterrupted, graded, submaximal exercise test (up to the anaerobic threshold) before treatment, and with a similar protocol 75 minutes after treatment with captopril or placebo on the same morning. Captopril decreased brachial intraarterial pressure by 7/4 mm Hg at RR, by 16/10 mm Hg at RS, and by 19/10 mm Hg during exercise (p less than 0.001), based on a decrease of systemic vascular resistance (p less than 0.001). Slight increases of cardiac output and of heart rate were noted at rest; cardiac output was not significantly affected during exercise, but the increase of heart rate of 2.4 beats/min was significant (p less than 0.01). Captopril decreased pulmonary artery (p less than 0.05) and capillary wedge pressures (p less than 0.001), with unchanged pulmonary vascular resistance. The da...
A collaborative study of infective endocarditis in the 1970s. Emphasis on infections in patients who have undergone cardiovascular surgery.
Authors: E LKaplan, HRich, WGersony, JManning
Journal: Circulation (1979)

Twenty-six major cardiovascular centers participated in a cooperative study of all cases of infective endocarditis occurring during a single calendar year to obtain an overview of infective endocarditis. The study was designed to learn which patients appear to be at highest risk to develop this infection after palliative or reparative cardiovascular surgery. Of 278 patients developing infective endocarditis during the year at these medical centers, 63 (23%) had had previous cardiovascular surgery and 215 had not. Seventy percent of the 278 patients had recognized congenital or acquired heart disease before developing the infection. Rheumatic heart disease accounted for over half of the patients with underlying structural heart disease. A majority (55%) of the 63 patients who had been operated on before developing endocarditis had prosthetic valves inserted. Of those who did not require prosthetic valves, the majority had congenital heart disease with systemic artery-to-pulmonary artery shunts. Although th...
Effects of nitroglycerin on regional myocardial ischemia induced by atrial pacing in dogs.
Authors: J LGerry, H VSchaff, C HKallman, J TFlaherty
Journal: Circulation Research (1981)

The exact mechanism or mechanisms by which nitroglycerin exerts its beneficial effect on pacing-induced regional myocardial ischemia has not been ellucidated previously. In an open-chest, anesthetized canine preparation a fixed, flow limiting stenosis was applied to the left anterior descending (LAD) coronary artery and heart rate was increased by atrial pacing. Mass spectrometry was used to measure myocardial oxygen (PmO2) and carbon dioxide (PmCO2) tensions. Myocardial blood flow was measured by the radioactive microsphere technique. Application of the stenosis resulted in regional decreases in PmO2 and increases in PmCO2 of greater magnitude in the subendocardial than in the subepicardial layer. Atrial pacing resulted in a further decrease in PmO2 and increase in PmCO2 as well as a reduction in subendocardial blood flow. Nitroglycerin (TNG) infusion reduced mean arterial pressure 20 mm Hg, resulting in a 14 mm Hg reduction in PmCO2 in the more ischemic subendocardial layer (P less than 0.05). Myocardia...