tbuckley/cabot-search huggingface dataset:
Abstract B1: Radiotherapy promotes tumor-specific effector CD8+ T cells via DC activation.
Authors: Anurag K. Gupta, Hans Christian Probst, Van Vuong, Alexandro Landshammer, Sabine Muth, Hideo Yagita, Reto Schwendener, Martin Pruschy, Alexander Knuth, Maries van den Broek
Journal: Cancer Research (2013)

Abstract Radiotherapy is an important treatment for cancer. The main mode of action is thought to be the irreversible damage to tumor cell DNA, but there is evidence that irradiation mobilizes tumor-specific immunity and recent studies showed that the efficacy of high-dose radiotherapy depends on the presence of CD8+ T cells. We show here that the efficacy of radiotherapy given as a single, high dose (10 Gy) crucially depends on dendritic cells and CD8+ T cells, whereas CD4+ T cells or macrophages are dispensable. We show that local high-dose irradiation results in activation of tumor-associated dendritic cells that in turn support tumor-specific effector CD8+ T cells, thus identifying the mechanism that underlies radiotherapy-induced mobilization of tumor-specific immunity. We propose that – in the absence of irradiation – the activation status of dendritic cells rather than the amount of tumor-derived antigen is the bottleneck, which precludes efficient anti-tumor immunity. Citation Format: Anurag K. Gupta, Hans Christian Probst, Van Vuong, Alexandro Landshammer, Sabine Muth, Hideo Yagita, Reto Schwendener, Martin Pruschy, Alexander Knuth, Maries van den Broek. Radiotherapy promotes tumor-specific effector CD8+ T cells via DC activation. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B1.
Epidemiological studies of neurotoxic, reproductive, and carcinogenic effects of complex mixtures.
Authors: C M Shy
Journal: Environmental Health Perspectives (1993)

Neurotoxic, reproductive, and carcinogenic effects are potentially important health end points in epidemiological studies of complex mixtures, particularly when such mixtures contain volatile organic compounds or trace metals. Epidemiological studies of neurotoxicity often will require direct clinical, behavioral, and/or physiological testing of study subjects, because these effects are likely to be subtle and not identifiable as clearly defined diseases. Peripheral nervous system toxicity can be assessed by clinical neurologic examinations, by electrophysiological tests of nerve conduction, and by physiological tests of thresholds for neurosensory perception, though these tests require considerable standardization for use outside the clinical setting, and most of the available tests have not been assessed for their utility in detecting effects of neurotoxic exposures. Neurobehavioral effects of exposures to solvents, as examples of complex mixtures, have been studied widely; but batteries of tests are often used, and these have not been well standardized and are generally unfamiliar to most research investigators in this area. Recently standardized neurobehavioral test systems developed by the World Health Organization and by a U.S. group for use in field studies, show promise in detecting neurobehavioral effects at relatively low environmental exposures. Similarly, new and sensitive measures of disturbed reproductive function, such as time-to-conception and biochemical indices of early pregnancy loss, are affected by some low-concentration environmental agents; but those measures have not yet been applied to studies of complex mixtures.(ABSTRACT TRUNCATED AT 250 WORDS)
Neonatal Hyperbilirubinemia — What Are the Risks?
Authors: Jon F. Watchko
Journal: New England Journal of Medicine (2006)

Hyperbilirubinemia is the most common condition requiring evaluation and treatment of newborns, but for the vast majority of neonates, it is a benign, transitional phenomenon of no overt clinical significance. In a few infants, however, serum bilirubin may rise to hazardous levels that pose a direct threat of brain damage. Acute bilirubin encephalopathy, an uncommon disorder,1 may ensue, frequently evolving into kernicterus, a devastating chronic disabling condition characterized by the clinical tetrad of choreoathetoid cerebral palsy, central neural hearing loss, palsy of the vertical gaze, and tooth enamel hypoplasia as the result of bilirubin-induced cell toxicity.2 Originally described in newborns . . .
Isolated guinea pig coronary smooth muscle cells. Acetylcholine induces hyperpolarization due to sarcoplasmic reticulum calcium release activating potassium channels.
Authors: V Ganitkevich, G Isenberg
Journal: Circulation Research (1990)

Smooth muscle cells, dispersed from the circumflex coronary artery of the guinea pig, were studied with the whole-cell configuration of the patch-clamp. The resting potential of about -40 mV was superimposed by spikelike hyperpolarizations (SLHs) up to -20 mV amplitude. The SLHs resulted from spontaneous transient outward currents (spontaneous TOCs) measured under voltage-clamp (-40 or -50 mV). Acetylcholine (ACh; 10 microM) increased SLHs and TOCs in amplitude and frequency. Atropine blocked the ACh effects. ACh-induced SLHs or TOCs were suppressed by bath application of tetraethylammonium (1 or 10 mM) or by cell dialysis with cesium, suggesting that they result from induction of potassium currents. In cell-attached patches, induction of currents through 130-pS potassium channels was recorded when ACh was bath-applied. An ACh-induced increase in intracellular [Ca2+] is suggested as a second messenger since SHLs and TOCs were suppressed by cell dialysis of 10 mM EGTA. ACh induced SHLs and TOCs in the absence of extracellular calcium. Intracellular application of 5 mg/ml heparin blocked ACh-induced TOCs. When the intracellular calcium stores were depleted by pretreatment with caffeine, the ACh effects were suppressed. Similarly, ACh pretreatment reduced the caffeine-induced outward currents. The results suggested that ACh augments calcium release from the sarcoplasmic reticulum, and the released calcium activates maxi potassium channels. In the single cell, calcium-activated potassium channels generate TOCs and SLHs that sum up to a hyperpolarization of the multicellular tissue.
Effect of the Calcium Antagonist Felodipine as Supplementary Vasodilator Therapy in Patients With Chronic Heart Failure Treated With Enalapril
Authors: Jay N. Cohn, Susan Ziesche, Raphael Smith, Inder Anand, W. Bruce Dunkman, Henry Loeb, Guillermo Cintron, William Boden, Lawrence Baruch, Peter Rochin, Larrye Loss
Journal: Circulation (1997)

Background Despite therapy with diuretics, ACE inhibitors and digoxin morbidity and mortality in heart failure remain high and might respond favorably to an additional vasodilator. Methods and Results Male patients (n=450) with chronic heart failure (cardiac dysfunction and impaired exercise performance) on optimal current therapy (97% enalapril, 89% diuretics) were randomly assigned to double-blind treatment with felodipine extended release (5 mg BID) or placebo for 3 to 39 months (average, 18 months). Felodipine significantly reduced blood pressure and, at 3 months, increased ejection fraction (2.1% versus −0.1% units in the placebo group, P =.001) and reduced plasma atrial natriuretic peptide levels (−2.9 versus 26.9 pg/mL in the placebo group, P =.01) but did not improve exercise tolerance, quality of life, or the need for hospitalization. During long-term follow-up, the favorable effects on ejection fraction and atrial peptide did not persist, but felodipine prevented worsening exercise tolerance and quality of life. In the felodipine and placebo groups, mortality (13.8% versus 12.8%, respectively) and hospitalization (43% versus 42%) rates were similar, and a higher incidence of peripheral edema was the only apparent side effect of felodipine therapy. Conclusions Felodipine exerts a well-tolerated additional sustained vasodilator effect in patients with heart failure treated with enalapril, but the only possible long-term benefit was a trend for better exercise tolerance and less depression of quality of life in the second year of treatment. The drug appears to be safe but not clearly efficacious in patients with heart failure.
Modulation of in vitro proliferation kinetics and primitive hematopoietic potential of individual human CD34+CD38–/lo cells in G0
Authors: Edward F. Srour, Xia Tong, Ki Woong Sung, P. Artur Plett, Susan Rice, Joanne Daggy, Constantin T. Yiannoutsos, Rafat Abonour, Christie M. Orschell
Journal: Blood (2004)
THE DIASTATIC ACTIVITY OF THE BLOOD IN EXPERIMENTAL HYPERGLYCEMIA
Authors: Howard T. Karsner, Herbert L. Koeckert, Spencer A. Wahl
Journal: The Journal of Experimental Medicine (1921)

1. The diastatic activity of the blood is not materially changed by the subcutaneous injection of phlorhizin, uranyl nitrate, or adrenalin. 2. The diastatic activity of the blood is not affected by puncture of the floor of the fourth ventricle. 3. The diastatic activity of the blood is definitely increased by subcutaneous injections of morphia when a marked hyperglycemia is produced. The same phenomenon appears in asphyxia. 4. Complete pancreatectomy in dogs produces an increase in the diastatic activity of the blood. 5. The diastatic activity of the blood is not altered by the diet. 6. Ether anesthesia, alone, produces a very slight tendency to increase in the diastatic activity of the blood. 7. Repeated periodic small hemorrhages (4.5 cc.) produce no change in the diastatic activity of the blood until a definite color anemia results, when a slight tendency toward increase occurs simultaneously with the rise in blood sugar. 8. The diastatic activity of the blood is not proportional to the concentration of the sugar in the blood.
Lung Disease at Diagnosis in Infants with Cystic Fibrosis Detected by Newborn Screening
Authors: Peter D. Sly, Siobhain Brennan, Catherine Gangell, Nicholas de Klerk, Conor Murray, Lauren Mott, Stephen M. Stick, Philip J. Robinson, Colin F. Robertson, Sarath C. Ranganathan
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

The promise of newborn screening (NBS) for cystic fibrosis (CF) has not been fully realized, and the extent of improvement in respiratory outcomes is unclear. We hypothesized that significant lung disease was present at diagnosis.To determine the extent of lung disease in a geographically defined population of infants with CF diagnosed after detection by NBS.Fifty-seven infants (median age, 3.6 mo) with CF underwent bronchoalveolar lavage and chest computed tomography (CT) using a three-slice inspiratory and expiratory protocol.Despite the absence of respiratory symptoms in 48 (84.2%) of infants, a substantial proportion had lung disease with bacterial infection detected in 12 (21.1%), including Staphylococcus aureus (n = 4) and Pseudomonas aeruginosa (n = 3); neutrophilic inflammation (41. 4 x 10(3) cells/ml representing 18.7% of total cell count); proinflammatory cytokines, with 44 (77.2%) having detectable IL-8; and 17 (29.8%) having detectable free neutrophil elastase activity. Inflammation was increased in those with infection and respiratory symptoms; however, the majority of those infected were asymptomatic. Radiologic evidence of structural lung disease was common, with 46 (80.7%) having an abnormal CT; 11 (18.6%) had bronchial dilatation, 27 (45.0%) had bronchial wall thickening, and 40 (66.7%) had gas trapping. On multivariate analysis, free neutrophil elastase activity was associated with structural lung disease. Most children with structural lung disease had no clinically apparent lung disease.These data support the need for full evaluation in infancy and argue for new treatment strategies, especially those targeting neutrophilic inflammation, if the promise of NBS for CF is to be realized.
Lipodystrophy, pancreatitis, and eosinophilia.
Authors: P M Smith, M E Morgans, C G Clark, J E Lennard-Jones, O Gunnlaugsson, T A Jonasson
Journal: Gut (1975)

Two patients suffering from partial lipodystrophy, pancreatitis, and recurrent eosinophilia are described. In one patient the duodenum and the terminal ileum were narrowed, the appearances suggesting eosinophilic gastroenteritis: bilateral hydronephrosis was also present without ureteric obstruction. An association between lipodystrophy and renal disease is recognized; it is possible that there is also an association between lipodystrophy and pancreatitis, and eosinophilia with or without an intestinal lesion may be a further association.
Ticrynafen's Withdrawal From the Market
Authors: William R. Barclay
Journal: JAMA (1980)

Three articles in this issue ofThe Journal(pp 763, 764, and 766) describe adverse reactions to ticrynafen. This agent, which held great promise for the treatment of high blood pressure while at the same time lowering serum uric acid levels, has not proved to be an unmixed blessing. Recently, the manufacturer, Smith Kline &amp; French Laboratories, withdrew the drug from the market, because five persons died while they were taking the drug. These deaths may, of course, have been unrelated to the drug, and a careful reevaluation of ticrynafen by the company and the Food and Drug Administration may lead to its reintroduction. In any event physicians should be thoroughly familiar with the adverse effects of this agent should it be reintroduced, and, therefore, we are publishing the three reports on it that we have in hand. Much has been written and said about phase IV trials of a
Clinical audit in primary health care: towards quality assurance
Authors: R. Baker
Journal: BMJ (1995)

The approximate lethal intravenous dose of soluble salts of thorium, cerium, erbium, yttrium, praseodymium, and didymium is determined for rats. Massive intraperitoneal dosage of soluble salts of thorium, cerium, erbium, yttrium, and didymium, produce no effect upon the growth behavior of rat sarcoma 10. Intraperitoneal injection of praseodymium nitrate increases the incidence of tumor liquefaction in rat sarcoma 10, but does not affect the growth behavior of the Hyde rat carcinoma. Intraperitoneal injection of manganese acetate produces no effect upon the growth of the Hyde rat carcinoma. Intravenous injection of massive doses of lead acetate and of colloidal lead orthophosphate does not affect the growth behavior of the Hyde rat carcinoma.
Review: Statins reduce all-cause mortality in elderly patients with coronary heart disease
Authors: Daniel Sontheimer
Journal: Annals of Internal Medicine (2008)

Source Citation Afilalo J, Duque G, Steele R, et al. Statins for secondary prevention in elderly patients: a hierarchical Bayesian meta-analysis. J Am Coll Cardiol. 2008;51:37-45. 18174034
Chondrogenesis just ain’t what it used to be
Authors: Gerard Karsenty
Journal: Journal of Clinical Investigation (2001)

Most of the vertebrate skeleton forms by endochondral ossification, a multistep process that involves two successive cell-differentiation processes. Initially, following mesenchymal cell condensation, a cartilaginous scaffold forms that is later replaced by bone matrix. Under the control of transcription factors of the Sox family, these mesenchymal cells differentiate first into type II collagen–producing cells that proliferate until the shape of the future bone is established (1, 2). Subsequently, cells located at the center of this structure differentiate further to form hypertrophic chondrocytes, which synthesize a cartilaginous matrix that eventually calcifies. At the same time, the most mature hypertrophic chondrocytes undergo apoptosis, allowing the corresponding area to be invaded by blood vessels, and both multinucleate, matrix-resorbing cells and differentiated osteoblasts appear. The cartilaginous matrix is then degraded and replaced by a bone matrix secreted by osteoblasts.

Once this process is completed, the only cartilaginous structures remaining are the growth plate cartilages at the two distal ends of the bone. There, chondrocytes at each stage of differentiation — resting, proliferating, and hypertrophic chondrocytes — are arrayed in a linear succession from the most distal to the most medial regions. This growth plate cartilage therefore offers a powerful model for studying cell differentiation in situ.

Two mechanisms have been generally proposed to explain how chondrocytes and osteoblasts could emerge successively from the same mesenchymal condensation. First, two populations of progenitors might coexist within the condensations and differentiate along separate lineages into chondrocytes and osteoblasts. Alternatively, the same cells could differentiate along a single lineage, first generating chondrocytes, and later differentiating into osteoblasts. A second, related issue concerns the genetic regulation of the different steps of endochondral ossification, chondrogenesis, and bone morphogenesis. Mostly based on mouse genetic experiments, a number of recent studies, including the paper by Chung et al. (3) in a recent issue of the JCI, have established the cascade of events triggering each of these processes and have identified key factors required in their regulation (Figure ​(Figure11).



Figure 1

Molecular control of endochondral ossification. Transcription factors (Cbfa1 and others) promote the differentiation of the type II collagen–producing cells present in the skeletal mesenchymal condensations into Ihh-secreting hypertrophic chondrocytes. ...
Pressure-induced connective tissue synthesis in pulmonary artery segments is dependent on intact endothelium.
Authors: C A Tozzi, G J Poiani, A M Harangozo, C D Boyd, D J Riley
Journal: Journal of Clinical Investigation (1989)

Physiologic stimuli of connective tissue accumulation in pulmonary vascular remodeling are poorly defined. We postulated that increased pressure within central pulmonary arteries is a stimulus for connective tissue synthesis and the response is dependent on an intact endothelium. Mechanical tension equivalent to 50 mmHg pressure was applied for 4 h to isolated rat main pulmonary arteries (endothelium intact or removed), and incorporation of [14C]proline into collagen, [14C]valine into elastin, [3H]thymidine into DNA and pro alpha 1 (I) collagen mRNA levels were measured. In intact vessels, tension induced synthesis of collagen (3.1 +/- 0.4 vs. 2.3 +/- 0.5 [SEM] dpm X 10(2) [14C]-hydroxyproline/[mg protein.h]) (n = 10) and elastin (6.1 +/- 2.4 vs. 2.9 +/- 0.4 dpm X 10(3) [14C]valine/[mg protein.h]) (n = 5) (both P less than 0.05). Steady state mRNA levels of pro alpha 1 (I) collagen were also increased by tension (46 vs. 30 X 10(2) dpm hybridized/100 ng total RNA). However, the stimulus did not increase [3H]thymidine incorporation into DNA. In denuded vessels, tension had no effect on connective tissue synthesis or mRNA level of pro alpha 1 (I) collagen. Messenger RNA levels for v-sis were induced by tension in intact but not denuded vessels. Our findings establish that induction of vascular connective tissue synthesis by mechanical tension is dependent on an intact endothelium.
Rectilinear biphasic rather than monophasic waveforms for transthoracic cardioversion of patients with rheumatic heart disease and longstanding atrial fibrillation after corrective mitral valve procedures
Authors: Daniel Schutte, Carlos Libhaber, Karen Sliwa, Riaz Motara, Arthur Kibirige, John Kachope, Firanda Peters, Pinhas Sareli
Journal: Journal of the American College of Cardiology (2002)
Survival Patterns Among Lymphoma Patients With a Family History of Lymphoma
Authors: Lesley A. Anderson, Ruth M. Pfeiffer, Joshua S. Rapkin, Gloria Gridley, Lene Mellemkjaer, Kari Hemminki, Magnus Björkholm, Neil E. Caporaso, Ola Landgren
Journal: Journal of Clinical Oncology (2008)

Genetic factors are important in the etiology and pathogenesis of chronic lymphocytic leukemia (CLL), Hodgkin's lymphoma (HL), and non-Hodgkin's lymphoma (NHL). Only a few small studies have assessed clinical characteristics and prognosis for familial patients, with inconsistent findings.Using population-based registries from Sweden and Denmark, 7,749 patients with CLL, 7,476 patients with HL, and 25,801 patients with NHL with linkable first-degree relatives were identified. Kaplan-Meier curves were constructed to compare survival in patients with lymphoma with and without a family history of lymphoma. The risk of dying was assessed using adjusted Cox proportional hazard models.We found 85 patients with CLL (1.10%), 95 patients with HL (1.28%), and 206 patients with NHL (0.80%) with a family history of any lymphoma. Five-year mortality was similar for patients with CLL (hazard ratio [HR], 1.28; 95% CI, 0.95 to 1.72), HL (HR, 0.78; 95% CI, 0.49 to 1.25), and NHL (HR, 0.91; 95% CI, 0.74 to 1.12) versus without a family history of any lymphoma. Mortality was also similar for patients with versus without a family history of the same lymphoma. T-cell/anaplastic lymphoma patients with a family history of NHL had poorer outcome 5-years after diagnosis (HR, 5.38; 95% CI, 1.65 to 17.52). Results were similar for 10 years of follow-up.With the exception of T-cell/anaplastic lymphoma, survival patterns for patients with CLL, HL, and NHL with a family history of lymphoma were similar to those for sporadic patients, suggesting that most familial lymphomas do not have an altered clinical course. Our findings provide no evidence to modify therapeutic strategies for patients with CLL, HL, or NHL based solely on family history.
Neil Lessels Dallas
Authors: W. Jory
Journal: BMJ (2012)

Neil Lessels Dallas was born in Bradford and educated at Uppingham. He graduated from Trinity Hall, Cambridge, and completed his medical training at St Thomas’ Hospital in London. In the era of national service, Dallas served as a major in the Royal Army Medical Corps. His ophthalmic training was at Moorfields Hospital , after which he became consultant eye surgeon at the Bristol Eye and Frenchay Hospitals, one of a team of six …
Research: Solo or Symphony?
Authors: Samuel Vaisrub
Journal: JAMA (1977)

Until recently, science owed its major advances to gifted individuals working in the solitude of their studies or improvised ramshackle laboratories. With modern technological advances and with governmental support of various "crash" programs, the solo worker is now being replaced by organized institutional teams pursuing planned projects initiated by special committees. Attuned to public demand for quick, practical results, the grantors of grants are apt to favor applied research to the neglect of deeper probes into the nature of the unknown. Did this trend away from the spontaneous to the organized, from the fundamental to the applied, prove successful? Did it lead to great discoveries? Maintaining that it did not, that planned, organized, "contract" research is rarely followed by major advances, Burch<sup>1</sup>makes a plea for fostering "venture" research by creative individuals in the search of knowledge for the sake of knowledge. These individuals should be sought out, given