tbuckley/cabot-search huggingface dataset:
S127 Chemotherapy sensitises Malignant pleural mesothelioma cells to undergo MSC-TRAIL induced apoptosis: Abstract S127 Table 1.
Authors: KK Kolluri, E Sage, ZQ Yuan, A Gaingreco, SM Janes
Journal: Thorax (2013)

<h3>Introduction</h3> Malignant pleural mesothelioma (MPM) is a highly aggressive, incurable, chemoresistant tumour. Recent studies have shown that Mesenchymal stem cells (MSC) can home to and incorporate into the tumour stroma. Their tumour tropism can be used to deliver Tumour necrosis factor related apoptosis inducing ligand (TRAIL), a transmembrane protein that selectively induces apoptosis in transformed cells. However, not all tumours are sensitive to TRAIL. TRAIL works through triggering the extrinsic apoptotic pathway while conventional chemotherapeutic agents act by triggering the intrinsic apoptotic pathway. We hypothesised the crosstalk between these two pathways could be exploited by combining chemotherapy and MSC-TRAIL in MPM tumour cell lines. <h3>Methods</h3> MSC were engineered to express TRAIL using a lentiviral plasmid vector. A Tetracycline (Tet)-inducible system was used as a backbone to control the expression of TRAIL. Apoptosis induced by recombinant TRAIL, MSC-TRAIL in MPM cell lines on combination with Vorinostat, a chemotherapeutic agent, was measured by Annexin-V/DAPI based flow cytometry. <h3>Results</h3> The combination of recombinant TRAIL and Vorinostat act synergistically to induce apoptosis in MPM cell lines. Recombinant TRAIL and Vorinostat, as monotherapies induce 7.17% and 51.35% apoptosis in an MPM cell line JU77 respectively. In CRL2081 and ONE58 cell lines, recombinant TRAIL induces 56.75% and 13.41% apoptosis while Vorinostat leads to 78.95% and 43.97% apoptosis respectively. The combination of recombinant TRAIL and Vorinostat shows an increased amount of apoptosis in JU77, CRL2081 and ONE58 cell lines at 80.77%, 96.6% and 77.27% respectively (Table 1). Similar synergistic affect was observed when TRAIL expressing MSCs were co-cultured with Vorinostat treated MPM cell lines. MSC-TRAIL induced apoptosis in JU77 (48.73%), CRL2081 (57.63%) and ONE58(53.8%). Combined treatment of Vorinostat and MSC-TRAIL significantly increased apoptosis to 77.7% in JU77, 90.93% in CRL2081 and 77.8% in ONE58 cells (Table 1). <h3>Conclusion</h3> The combination of Vorinostat and recombinant TRAIL acts synergistically to induce apoptosis in malignant plural mesothelioma cells. Similar affect is observed with the combination of MSC-TRAIL and Vorinostat. This study indicates that Mesenchymal stem cells can be used as vectors for delivery of TRAIL and upon combination with Vorinostat, could be a potential therapy for malignant pleural mesothelioma.
Cell-Specific Defect in Monocyte Function During Tumor Growth2
Authors: Sigurd J. Normann, Ernst Sorkin
Journal: JNCI Journal of the National Cancer Institute (1976)

Inbred DA rats bearing a syngeneic 7,12-dimethyl-benz[a]anthracene-induced neoplasm had an early impairment of chronic inflammation as measured by the numbers of monocytes elicited in a 3-day peritoneal exudative response to a sterile peptone injection. Furthermore, an advanced malignant tumor was associated with a complete block in the rats' capacity to mobilize monocytes, despite the fact that white blood cell counts on peripheral blood showed increased numbers of monocytes and polymorphonuclear leukocytes (PMN) during tumor growth. In contrast to the defect in chronic inflammation, a normal or increased acute inflammatory reponse was observed during tumor growth as measured by the 9-hour peritoneal PMN response to a sodium caseinate injection. Quantitative chemotaxis measurements in vitro made with these same peritoneal exudate cells revealed severe impairment of macrophage chemotaxis but normal migration of PMN. Generation of macrophage chemotactic signals from blood of rats with advanced tumors was not impaired. Since the resident cells of the peritoneal cavity were, chemotactically, a poor-responding population, this defective response in vitro appeared to correlate with the cell defect observed in vivo in the monocyte inflammatory response to peptone.
Congenital Aneurysm of the Right Aortic Sinus Associated with Coarctation of the Aorta and Subacute Bacterial Endocarditis
Authors: Israel Steinberg, Nathaniel Finby
Journal: New England Journal of Medicine (1955)

ANEURYSMS of the aortic sinus (of Valsalva) are rare. Jones and Langley,1 in their classic paper, reviewed the literature in 1949 and reported a total of 43 cases proved by autopsy and added 4 of their own. Of these, 25 were of congenital origin; the remainder were acquired. In 1951 Venning2 described 3 additional cases. Falholt and Thomsen,3 in 1953, reported a case with a congenital aneurysm of the right aortic sinus diagnosed by retrograde aortography, and totaled the number of congenital cases in the literature as 34. Another autopsy was recorded recently by Basabe, Hojman and Rósemblit.4 Fifteen cases . . .
Stroke and Alcohol Consumption
Authors: Jaswinder S. Gill, Alexander V. Zezulka, Martin J. Shipley, Surinder K. Gill, D. Gareth Beevers
Journal: New England Journal of Medicine (1986)

We conducted a retrospective case-control study to investigate a possible association between alcohol intake and stroke. Reported recent alcohol consumption and biochemical and hematologic markers of alcohol intake were examined for 230 patients with stroke (20 to 70 years old) and compared with concurrently collected data on controls matched for age, sex, and race. A single estimate of current intake was used as a measure of alcohol consumption. Among men, the relative risk of stroke (adjusted for hypertension, cigarette smoking, and medication) was lower in light drinkers (those consuming 10 to 90 g of alcohol weekly) than in nondrinkers (relative risk, 0.5), but was four times higher in heavy drinkers (consuming greater than or equal to 300 g weekly) than in nondrinkers. Because very few women in our study drank heavily, we were unable to determine whether heavy alcohol intake influenced the risk of stroke in women. With increasing serum concentrations of the biochemical markers of alcohol intake (aspartate aminotransferase, uric acid, and gamma-glutamyl transferase), we observed similar trends in the relative risk of stroke. Only the erythrocyte mean cell volume did not follow this pattern. We conclude that heavy alcohol consumption is an important and underrecognized independent risk factor for stroke in men, but our data are not adequate to settle the issue for women. Our conclusions are qualified by our reliance on reported recent alcohol consumption as the primary measure of intake.
Pervasive Effects of Aging on Gene Expression in Wild Wolves
Authors: Pauline Charruau, Rachel A. Johnston, Daniel R. Stahler, Amanda Lea, Noah Snyder-Mackler, Douglas W. Smith, Bridgett M. vonHoldt, Steven W. Cole, Jenny Tung, Robert K. Wayne
Journal: Molecular Biology and Evolution (2016)

Gene expression levels change as an individual ages and responds to environmental conditions. With the exception of humans, such patterns have principally been studied under controlled conditions, overlooking the array of developmental and environmental influences that organisms encounter under conditions in which natural selection operates. We used high-throughput RNA sequencing (RNA-Seq) of whole blood to assess the relative impacts of social status, age, disease, and sex on gene expression levels in a natural population of gray wolves (Canis lupus). Our findings suggest that age is broadly associated with gene expression levels, whereas other examined factors have minimal effects on gene expression patterns. Further, our results reveal evolutionarily conserved signatures of senescence, such as immunosenescence and metabolic aging, between wolves and humans despite major differences in life history and environment. The effects of aging on gene expression levels in wolves exhibit conservation with humans, but the more rapid expression differences observed in aging wolves is evolutionarily appropriate given the species' high level of extrinsic mortality due to intraspecific aggression. Some expression changes that occur with age can facilitate physical age-related changes that may enhance fitness in older wolves. However, the expression of these ancestral patterns of aging in descendant modern dogs living in highly modified domestic environments may be maladaptive and cause disease. This work provides evolutionary insight into aging patterns observed in domestic dogs and demonstrates the applicability of studying natural populations to investigate the mechanisms of aging.
Surgical Treatment of Cardiospasm
Authors: Emerson H. Drake
Journal: New England Journal of Medicine (1962)

THE medical condition known under the names of cardiospasm, achalasia and a multitude of other pseudonyms is now fairly well recognized to consist primarily of a functional obstruction of the lower esophagus that is apparently caused by a failure of relaxation of the circular muscle fibers in this area. This, in turn, has been correlated with a decrease in the number of ganglion cells in the intramural plexuses of the esophageal wall; the cause of this condition remains unexplained.Mild attacks of cardiospasm may come on at irregular intervals, being stimulated by cold, nervous tension or other circumstances. This relatively . . .
Multiple Sites for Bone-Marrow Puncture, with Particular Reference to Children
Authors: Jack J. Rheingold, Louis Weisfuse, William Dameshek
Journal: New England Journal of Medicine (1949)

EXAMINATION of the bone marrow in hematologic disorders by means of puncture aspiration has become in this laboratory and in many others a routine study that is often invaluable in diagnosis. Although the sternum is the usual site of such puncture, several investigators have suggested other areas. Thus Van den Berghe and Blitstein1 and Rubenstein2 have stressed the value of the iliac-crest puncture, amd more recently Loge3 and Huss, Gilbert and Liebow4 have advocated the spinous process as a site for obtaining a specimen of the bone marrow. Since alternative sites are often desirable we have investigated their value during . . .
Neurologic Crises in Hereditary Tyrosinemia
Authors: Grant Mitchell, Jean Larochelle, Marie Lambert, Jean Michaud, André Grenier, Hélène Ogier, Marie Gauthier, Jacques Lacroix, Michel Vanasse, Albert Larbrisseau, Khazal Paradis, Andrée Weber, Yolande Lefevre, Serge Melançon, Louis Dallaire
Journal: New England Journal of Medicine (1990)

Hereditary tyrosinemia results from an inborn error in the final step of tyrosine metabolism. The disease is known to cause acute and chronic liver failure, renal Fanconi's syndrome, and hepatocellular carcinoma. Neurologic manifestations have been reported but not emphasized as a common problem. In this paper, we describe neurologic crises that occurred among children identified as having tyrosinemia on neonatal screening since 1970. Of the 48 children with tyrosinemia, 20 (42 percent) had neurologic crises that began at a mean age of one year and led to 104 hospital admissions. These abrupt episodes of peripheral neuropathy were characterized by severe pain with extensor hypertonia (in 75 percent), vomiting or paralytic ileus (69 percent), muscle weakness (29 percent), and self-mutilation (8 percent). Eight children required mechanical ventilation because of paralysis, and 14 of the 20 children have died. Between crises, most survivors regained normal function. We found no reliable biochemical marker for the crises (those we evaluated included blood levels of tyrosine, succinylacetone, and hepatic aminotransferases). Urinary excretion of delta-aminolevulinic acid, a neurotoxic intermediate of porphyrin biosynthesis, was elevated during crises but also during the asymptomatic periods. Electrophysiologic studies in seven patients and neuromuscular biopsies in three patients showed axonal degeneration and secondary demyelination. We conclude that episodes of acute, severe peripheral neuropathy are common in hereditary tyrosinemia and resemble the crises of the neuropathic porphyrias.
Controlled Study of Androgen Therapy in Anemia of Patients on Maintenance Hemodialysis
Authors: Ernesto D. Hendler, John A. Goffinet, Stephen Ross, Robert E. Longnecker, Vjera Bakovic
Journal: New England Journal of Medicine (1974)

A double-blind crossover study was designed to determine the effect of androgen therapy on the anemia of patients with chronic renal failure treated with maintenance hemodialysis. Nandrolone decanoate, 100 mg intramuscularly per week, or placebo was administered to 14 patients treated in a center and eight treated at home. During the five-month period of androgen administration mean red-cell mass rose from 946 to 1173 ml (p < 0.001 ), and mean hematocrit from 23 to 27 per cent (p < 0.005). Seventeen of the 21 patients who completed the study improved. There was no improvement in red-cell mass or hematocrit when placebo was given. Blood-transfusion requirements fell from 0.35 to 0.16 units per patient per month (p < 0.05) during the use of androgen. No adverse side effects were observed. It is concluded that nandrolone decanoate has a beneficial effect on anemia in most patients treated with maintenance hemodialysis. (N Engl J Med 291: 1046–1051, 1974)
Subtotal Gastrectomy for Bleeding Duodenal Ulcer in Childhood
Authors: Thomas H. Green, W. Hardy Hendren
Journal: New England Journal of Medicine (1960)

PEDIATRICIANS, as well as interested surgeons, radiologists and, more recently, child psychiatrists, periodically acknowledge that peptic ulcer occurs more often in childhood than is generally appreciated and that it should be included in the differential diagnosis of vague abdominal pain and gastrointestinal symptoms in infants and children. No attempt will be made to review the fairly sizable literature that has accumulated during the past two or three decades. Those interested in so doing will find the major contributions and many of the collected case reports summarized in the review articles by Tashiro and Kobayashi1 in 1935, Bird, Limper and Mayer . . .
Magnetic Resonance Imaging of Angiographically Occult Runoff Vessels in Peripheral Arterial Occlusive Disease
Authors: Rodney S. Owen, Jeffrey P. Carpenter, Richard A. Baum, Leonard J. Perloff, Constantin Cope
Journal: New England Journal of Medicine (1992)

Bypass grafting to arteries of the lower leg has become standard surgical management of advanced peripheral vascular disease. Its success depends on identifying suitable distal vessels. Preoperative preparation includes imaging of the arteries of the lower leg, usually by conventional contrast arteriography. An alternative procedure, magnetic resonance (MR) angiography, has been successfully employed in patients with various cardiovascular diseases, but its possible value in patients with peripheral vascular disease has received little attention.
Abnormalities of Tryptophan Metabolism and Plasma Pyridoxal Phosphate in Hodgkin's Disease
Authors: Bruce A. Chabner, Vincent T. DeVita, David M. Livingston, Vincent T. Oliverio
Journal: New England Journal of Medicine (1970)

Plasma levels of pyridoxal phosphate and the metabolism of L-tryptophan were studied in 43 patients with Hodgkin's disease. Evidence for deficiency of pyridoxal phosphate was found on both tests; plasma levels were depressed in eight of 14 untreated patients tested, and 14 of 21 untreated patients excreted increased quantities of at least one of the intermediary compounds in the tryptophan degradative pathway. Both tests gave abnormal results most frequently in patients with advanced or symptomatic disease. In contrast, both tests were within normal limits in 14 patients in complete remission after chemotherapy for advanced disease. All eight patients with low plasma pyridoxal phosphate levels were anergic, of interest in view of the immunosuppressive effects of experimental pyridoxine deficiency. There was little evidence to implicate pyridoxal phosphate deficiency in the anemia of Hodgkin's disease.
Apelin: an antithrombotic factor that inhibits platelet function
Authors: Frédéric Adam, Abdel-Majid Khatib, Jose Javier Lopez, Camille Vatier, Sabrina Turpin, Adeline Muscat, Fabienne Soulet, Anne Aries, Isaac Jardin, Régis Bobe, Alain Stepanian, Dominique de Prost, Cédric Dray, Juan Antonio Rosado, Philippe Valet, Bruno Feve, Geraldine Siegfried
Journal: Blood (2015)
Granulocyte Transfusions for the Prevention of Infection in Patients Receiving Bone-Marrow Transplants
Authors: Reginald A. Clift, Jean E. Sanders, E. Donnall Thomas, Barbara Williams, C. Dean Buckner
Journal: New England Journal of Medicine (1978)

Prophylaxis by granulocyte transfusions against infection associated with granulocytopenia was studied in 69 patients receiving bone-marrow transplants for the therapy of hematologic neoplasia or aplastic anemia. Patients were randomized to receive or not to receive granulocyte transfusions when their circulating granulocyte levels fell to less than 200 per cubic millimeter during the period between transplantation and the development of graft function. During the first 21 posttransplant days, there were two local infections and no septicemias in 29 transfused patients. Seven local infections and 10 septicemias developed among the 40 controls. This protection was afforded by granulocytes collected by reversible leukoadhesion as well as by cells collected by continuous-flow centrifugation.
Assessing Quality of Care from the Medical Record
Authors: W. J. Fessel, E. E. Van Brunt
Journal: New England Journal of Medicine (1972)

Abstract Quality of medical care may be assessed on the basis of either the outcome of care or the process by which the care was given. To compare these two criteria, records and outcome were studied of patients with two common conditions, appendicitis and myocardial infarction. In three different hospitals the records of patients with the diagnosis of acute appendicitis had considerable disparity in the frequency of documentation of commonly sought symptoms or signs of this condition; yet at each hospital the disease was diagnosed with the same accuracy. Similarly, recorded data of patients with acute myocardial infarction showed no relation to various outcomes, including length of time lost from work, occurrences of angina, congestive heart failure, myocardial reinfarct and death. Thus, the orthodox method of audit for quality of medical care, based upon chart review of the recorded process of care, may be incomplete and misleading.
Prevention of Traffic Accidents
Authors: A C Macías Rodríguez, D J Feria Lorenzo, F J Mena Navarro
Journal: New England Journal of Medicine (1966)

To inform nursing professionals about their role in the prevention of traffic accidents, a grave health-related problem, is the purpose of this article. To begin with, factors which can deteriorate one's capacity to drive vehicles, and over which nursing professionals can intervene, will be presented. These factors include alcohol, other drugs, medicines, individual morbidity, the factor of aging and the use of security devices. A special reference will be made about widely used medicines. Finally the role that a nurse can fulfill will be explained. This role can be directed to various sections of the general public, be of varying natures, be exercised with greater or lesser ease, and lastly can have more or less effect upon those to whom it is destined.
Online pediatric oncology education: A novel teaching tool for oncology residents
Authors: P. Gfeller, R. Harrison, K. J. Goddard
Journal: Journal of Clinical Oncology (2006)

9048 Background: Deficiencies in pediatric oncology training for residents have been identified internationally. A lack of training in pediatric oncology during residency is correlated with impaired outcomes for pediatric patients. There is a clear need for novel teaching tools to supplement training in pediatric oncology. Purpose: The goal of this project was to develop a series of multimedia web-based learning modules for the interactive instruction and review of pediatric oncology. A needs-based assessment of pediatric oncology training in Canadian radiation oncology residency programs was used to guide web-site development. Methods: A needs-based analysis was conducted via a web-based survey sent to all Canadian radiation oncology program directors and residents. The survey was designed to identify the limitations of current training curriculum in pediatric oncology. A multidisciplinary team, including pathologists, radiologists, medical physicists, radiation and medical oncologists, developed the web site curriculum. The site was designed using teaching modules to focus on pediatric tumour sites. Modules were developed using a common format, divided into chapters detailing specific tumour types. Each chapter reviewed relevant epidemiology, anatomy, pathology, radiology, and treatment for the tumor type. A self-assessment tool was included at the end of the modules. User satisfaction surveys were used for feedback. Results: 100% (10/10) of Canadian radiation oncology program directors and 66% (69/106) of Canadian residents responded to the survey. 56% (59/106) of resident respondents felt that teaching in pediatric radiation oncology was inadequate and 56% (20/36) of senior residents felt unprepared for questions in pediatric oncology on qualifying board exams. 90% (105/116) of respondents felt that a web-based teaching tool would be useful. The first module, pediatric neuro-oncology, has been completed. Results indicate users find this module useful for supplementing traditional training. Conclusions: There are no other interactive teaching tools in pediatric oncology. This unique web-based educational program will allow self-directed study in the area of pediatric oncology, providing more effective learning of this challenging yet essential area of study. No significant financial relationships to disclose.