tbuckley/cabot-search huggingface dataset:
A Study of Five Cancer Families.
Authors: Henry T. Lynch
Journal: Annals of Internal Medicine (1966)

s1 May 1966A Study of Five Cancer Families.Henry T. Lynch, M.D., Margery W. Shaw, M.D., Charles W. Magnuson, M.D., Arthur L. Larsen, M.D., Anne J. Krush, M.S.Henry T. Lynch, M.D.Search for more papers by this author, Margery W. Shaw, M.D.Search for more papers by this author, Charles W. Magnuson, M.D.Search for more papers by this author, Arthur L. Larsen, M.D.Search for more papers by this author, Anne J. Krush, M.S.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-64-5-1177_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptHereditary factors are clear in several types of malignancies, which include familial polyposis coli, retinoblastomas, xeroderma pigmentosum, neurofibromatosis, Gardner's syndrome, and the basal cell nevus syndrome. There is no simple genetic interpretation for most other carcinomas. Studies have shown, however, that there is a higher frequency of similar types of tumors in close relatives of propositi than is found in the general population. Studies made of five "cancer families" at the University of Nebraska are of interest from the following standpoints: (1) wide distribution of anatomic sites of the malignant neoplasms; (2) occurrence of malignancies through three and four generations... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Omaha, Nebraska, and Ann Arbor, Michigan PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1966Volume 64, Issue 5Page: 1177-1178KeywordsBasal cellsGenetics Issue Published: 1 May 1966 PDF DownloadLoading ...
Suppressor function of peripheral blood mononuclear cells in normal individuals and in patients with systemic lupus erythematosus.
Authors: B Bresnihan, H E Jasin
Journal: Journal of Clinical Investigation (1977)

Normal peripheral blood mononuclear cells demonstrated increased DNA synthesis and secretion of newly synthesized protein when suboptimal concentrations of Concanavalin A (Con A) were added to the cultures after 24-h incubation in vitro. Cells stimulated by Con A, 1 mug/ml, after 24-h incubation demonstrated 3.0 times more tritiated thymidine incorporation, and 4.4 times more 14C-amino acid incorporation into newly synthesized secreted protein, than cells stimulated at 0 h (P less than 0.001). The acquisition of increased responsiveness was not abrogated by washing and resuspending the cells in fresh medium. Since the increased responsiveness could be inhibited by the addition to the cultures of small numbers of cells previously activated by Con A it is suggested that the enhanced reactivity acquired in culture represents the loss of a subpopulation of suppressor cells that modulate the T-lymphocyte response. Cells from nine patients with active, untreated systemic lupus erythematosus demonstrated normal responses to optimal concentrations of Con A added at 0 h, but an impaired response to Con A, 1 mug/ml. When these cells were incubated for 24 h, a significant increased response to Con A was not observed. This observation suggests that patients with active SLE lack circulating suppressor cells. When seven SLE patients were again studied after corticosteroid therapy had led to clinical improvement, the response to Con A, 1 mug/ml, added after 24-h incubation was similar to that observed in normal controls, suggesting that suppressor function in SLE returns as disease activity declines.
HER2+ circulating tumor cells (CTCs): a more sensitive and specific marker for CTCs positivity than total CTCs count in early breast cancer.
Authors: M Ignatiadis, V Durbecq, S Markowicz, C Chaboteaux, G Rouas, B Mounia, B Benjamin, F Liebens, V Georgoulias, D Mavrudis, M Piccart, C Sotiriou
Journal: Cancer Research (2009)

Abstract Abstract #5023 Background: CTCs have been detected using the CellSearch System in early and metastatic breast cancer (BC). However, no studies have been reported for the detection of HER2+ CTCs using the CellSearch System. In this study we aimed to analyze CTCs for HER2 expression in different stages of BC progression from ductal/lobular carcinoma in situ (DCIS/LCIS) to early and metastatic BC. Patients and Methods: 20ml of peripheral blood per woman was analyzed from healthy women, DCIS/LCIS or early BC patients, whereas 7.5ml of blood was analyzed from metastatic BC patients. The presence of CTCs as well as HER2 expression was assessed with the CellSearchSystem (Veridex, USA). After immunomagnetic enrichment with an anti-Epcam-antibody, cells were labeled with anti-cytokeratin (8,18,19), anti-HER2 and anti-CD45 antibodies. CTCs were defined as Cytokeratin-positive/CD45-negative cells, whereas HER2+ CTCs were defined as Cytokeratin-positive/CD45-negative/HER2-positive cells. Results: The presence of CTCs and HER2+ CTCs in healthy women, DCIS/LCIS, early and metastatic BC is depicted in table.&amp;#x2028; &amp;#x2028; Since 1 and 2 CTCs were detected in 7 (14.8%) and 4 (8.5%) of 47 healthy women, respectively, &amp;gt;1CTC or &amp;gt;2CTCs were selected as cutoffs for further analysis. Using the above cutoffs, 7 (18.9%) and 5 (13.5%) of 37 patients with early BC were considered CTC-positive, respectively. Since no HER2+ CTCs were detected in any of the 47 healthy women, a cutoff of ≥1 HER2+ CTCs was chosen. With this cutoff, more women with early BC [11 (29.7%) of 37 women] were considered CTC-positive. Conclusion: HER2+ CTCs seems to be a more sensitive and specific marker for CTCs' positivity than total CTCs counts in early breast cancer. Clinical relevance of the above cutoff for CTCs positivity using HER2+ CTCs detection will be performed in ongoing clinical trials of HER2 positive early breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5023.
A systematic review of topical corticosteroid withdrawal (“steroid addiction”) in patients with atopic dermatitis and other dermatoses
Authors: Tamar Hajar, Yael A. Leshem, Jon M. Hanifin, Susan T. Nedorost, Peter A. Lio, Amy S. Paller, Julie Block, Eric L. Simpson
Journal: Journal of the American Academy of Dermatology (2015)
Evaluating "payback" on biomedical research from papers cited in clinical guidelines: applied bibliometric study
Authors: J. Grant
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objectives:</b> To develop a methodology for evaluating the impact of research on health care, and to characterise the papers cited on clinical guidelines. <b>Design:</b> The bibliographic details of the papers cited in 15 clinical guidelines, developed in and for the United Kingdom, were collated and analysed with applied bibliometric techniques. <b>Results:</b> The median age of papers cited in clinical guidelines was eight years; most papers were published by authors living in either the United States (36%) or the United Kingdom (25%)—this is two and a half times more than expected as about 10% of all biomedical outputs are published in the United Kingdom; and clinical guidelines do not cite basic research papers. <b>Conclusion:</b> Analysis of the evidence base of clinical guidelines may be one way of tracking the flow of knowledge from the laboratory to the clinic. Moreover, such analysis provides a useful, clinically relevant method for evaluating research outcomes and different strategies in research and development.
Efforts to reduce US trainees' hours were ineffective, study says
Authors: J. H. Tanne
Journal: BMJ (2008)

Attempts to reduce the number of hours worked by physicians in residency training failed to improve their working and sleeping hours, and fatigue related errors were unchanged, a study to evaluate the effects of limiting working hours in US medical centres has found.

The prospective study reported the experience of 220 residents at three major US paediatric centres—the Children’s Hospital in Boston, the Children’s National Medical Center in Washington, DC, and Lucile Packard Children’s Hospital of Stanford Medical School in Palo Alto, California—before and after new rules on working hours were implemented ( Pediatrics 2008;122:250-8).

“The study did not show that errors occurred despite reduced hours; rather, it showed that the effort to …
Activated neutrophils secrete stored alpha 1-antitrypsin.
Authors: P Pääkkö, M Kirby, R M du Bois, A Gillissen, V J Ferrans, R G Crystal
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Neutrophil elastase (NE), a potent serine protease, is stored in primary granules of neutrophils and released following neutrophil activation. Alpha-1-antitrypsin (alpha 1-AT), the major inhibitor of NE, is synthesized by mature neutrophils. In the context of the maintenance of tissue homeostasis, we hypothesized that neutrophils may be able to store alpha 1-AT, thus having it available for release concordantly with NE. Immunofluorescence and quantitative flow-cytometric studies of neutrophils and monocytes labeled with fluorescein-conjugated alpha 1-AT-antibody demonstrated larger amounts of cytoplasmic alpha 1-AT in neutrophils than in monocytes. [35S]methionine-labeling and anti-alpha 1-AT immunoprecipitation analysis showed that although both neutrophils and monocytes synthesize alpha 1-AT, the proportion of newly synthesized intracellular alpha 1-AT was much higher in neutrophils than in monocytes. Flow-cytometric analysis showed that in the presence of surface stimulation with cytochalasin B followed by formyl-methionyleucylphenylalanine (fMLP), mean intracellular alpha 1-AT was decreased in stimulated neutrophils compared with that in resting cells, suggesting that the stored alpha 1-AT was rapidly released following surface triggering. Evaluation of surface-stimulated neutrophils by [35S]methionine labeling and anti-alpha 1-AT immunoprecipitation demonstrated increased secretion of alpha 1-AT compared with that of resting neutrophils, with some of the secreted alpha 1-AT capable of forming complexes with NE. Thus, neutrophils respond to surface stimulation not only by secreting NE but also by secreting its inhibitor, alpha 1-AT, suggesting that these cells have an inherent mechanism for damping the local effects of NE, their most powerful proteolytic enzyme.
Bowlby's disease?
Authors: M J Mitchinson
Journal: BMJ (1971)

Haemophagocytic lymphohistiocytosis (HLH) is one of the rare haematological syndromes more commonly reported in infants/children than adults. This disease is known for its aggressive dysregulated immune response affecting the host rapidly, causing multiorgan dysfunction and thus carries a high mortality. The disease still remains cryptic in this current decade despite all the developments in the ever-evolving field of haematology. Due to its rare occurrence and being more frequent in infants and the paediatric population, the literature lacks enough data to standardise therapies. Such events in adults and the elderly are invariably related to an underlying insult such as infections, other autoimmune or rheumatological diseases or drugs. We describe an interesting case of a middle-aged Caucasian woman who presented with fever, pancytopenia and hepatitis, who was eventually diagnosed with HLH just in time to receive the life-saving specific treatment as per available guidelines.
Cardiac Active Principles in Blood Plasma
Authors: Chandler McC. Brooks, STEPHAN HAJDU, EDWARD LEONARD
Journal: Circulation (1961)

A study of isolated frog hearts suggests that the amphibian heart is provided normally with a substance that maintains contractility and that disappears slowly from the heart during perfusion with saline solution. A search for substances that might fulfill this role in the frog heart has led to the isolation of many materials that have some degree of cardiotonic activity, but no conclusion can yet be reached about which, if any, of these substances is present in. the intact frog heart. The search has led, however, to the discovery of 2 substances of mammalian origin that are as potent as the cardiac glycosides with respect to their inotropic action on frog heart. One of these is a phospholipid called lysolecithin, the other is a system of 3 plasma globulins called "cardioglobulin A, B, and C." The concentration of cardioglobulin C in man is increased in essential hypertension and aortic stenosis, 2 unrelated conditions that have in common the development of increased left ventricular isometric tension in systole. Conversely, cardioglobulin C is decreased in a group of patients with idiopathic congestive heart failure. The discovery of these substances is relevant to the question whether isolated mammalian cardiac tissue becomes hypodynamic in physiologic saline because of the loss of a system that helps maintain normal myocardial contractility. We have noted that most of the studies on isolated strips of mammalian cardiac tissue fail to answer this question, since the strips were probably hypodynamic because of impaired oxygenation or nonphysiologie saline media. Studies from our laboratory indicate that a slow decline in contractility on prolonged washing does occur in isolated mammalian heart tissue, despite good oxygenation and a normal environment with respect to inorganic ions. This can be prevented or reversed by perfusion with mammalian plasma. Along similar lines, it is of interest that, although the decline of performance characteristics of in situ mammalian hearts may be due to many factors, the decline can be prevented by perfusing the coronary system of the in situ heart with blood from a healthy donor animal. The problem, then, has 2 aspects. On the one hand, we must discover the physiologic significance of the potent glycoside-like substances already isolated from mammalian tissue; on the other, we must investigate the beneficial effects of plasma on heart strips or of donor dog blood on in situ hearts. Do these actions occur because of an effect on myocardial metabolism or do they come about because of a plasma substance that enhances myocardial contractility directly?
Pretreatment with EPO reduces the injury and dysfunction caused by ischemia/reperfusion in the mouse kidney in vivo
Authors: Nimesh S.A. Patel, Edward J. Sharples, Salvatore Cuzzocrea, Prabal K. Chatterjee, Domenico Britti, Muhammad M. Yaqoob, Christoph Thiemermann
Journal: Kidney International (2004)
An oxygen conserving nasal cannula.
Authors: J C Moore-Gillon, R J George, D M Geddes
Journal: Thorax (1985)

Oxygen administration via a nasal cannula incorporating a small collapsible reservoir (Oxymizer, Chad Therapeutics Inc, California) was compared with delivery via a standard nasal cannula. Twelve patients with chronic, stable hypoxaemia (arterial oxygen tension less than 60 mm Hg (8.0 kPa)) were studied. Transcutaneous oxygen and carbon dioxide tensions were recorded by skin electrodes and oxygen saturation by ear oximetry. Baseline measurements during the breathing of air were compared with those made during the breathing of oxygen at flow rates of 0.5, 1.0, and 2.0 l/min via each device. Increases in saturation and transcutaneous oxygen tension were significantly greater at each flow rate with the reservoir device than with the conventional cannula. To produce similar improvements in oxygenation the reservoir device required an oxygen flow rate about half that of the conventional cannula. Use of the reservoir device may reduce the inconvenience and perhaps the cost of supplying domiciliary oxygen, and prolong the time during which patients may rely on a portable cylinder.
Determinants and outcomes associated with decisions to deny or to delay intensive care unit admission in Morocco
Authors: Maha Louriz, Khalid Abidi, Mostafa Akkaoui, Naoufel Madani, Kamal Chater, Jihane Belayachi, Tarek Dendane, Amine Ali Zeggwagh, Redouane Abouqal
Journal: Intensive Care Medicine (2012)
Novel rearrangements at the immunoglobulin D locus. Inversions and fusions add to IgH somatic diversity.
Authors: K D Meek, C A Hasemann, J D Capra
Journal: The Journal of Experimental Medicine (1989)

IgH rearrangements (VH-D, D-JH) are central to the generation of antibody diversity. The majority of the diversity seen in the third hypervariable region is generated by the D segment and at the joints formed by both junctional and N segment variation during D-JH and VH-D rearrangements. The mechanisms that regulate rearrangement are thought to obey the 12/23 rule, wherein D-D or VH-JH rearrangements are precluded. Here, we present evidence that D-D fusions do in fact occur, either as direct or inverted rearrangements. The fused D segments so generated may be fully capable of proceeding in subsequent D-JH and VH-D rearrangements. The resultant VH-D-D-JH recombinations add another dimension to the potential repertoire of IgH V regions by increasing the level of combinatorial diversity and by providing additional sites for N region variation.
18F NaF Brain Metastasis Uptake in a Patient with Melanoma
Authors: Robert P. Jones, Andrei Iagaru
Journal: Clinical Nuclear Medicine (2014)

A 57-year-old man with a history of metastatic melanoma and sclerotic bone lesions seen on CT was referred for 18F NaF PET/CT evaluation of active skeletal metastases. While the bone lesions had no uptake and were therefore thought to represent sequela of previously treated disease, an unexpected area of 18F NaF uptake was identified in the left temporal lobe. Concurrent contrast-enhanced brain MRI re-demonstrated a large metastasis, also seen on previous MRI scans done at another institution.
Noninvasive detection of intracardiac thrombosis: 131-I fibrinogen cardiac survey.
Authors: J H Frisbie, D E Tow, A A Sasahara, E M Barsamian, A F Parisi
Journal: Circulation (1976)

Cardiac survey following administration of 131-1 autologous fibrinogen is a noninvasive technique for the detection of intracardiac thrombosis. Fibrinogen is isolated from plasma by a rapid salting-out method with ammonium sulfate and is iodinated with chloramine T. The purity of 131-fibrinogen, expressed as clottable radioactivity, is greater than 90%. Cardiac survey consisting of serial gamma camera imaging or rectilinear scanning after intravenous administration of 131-I fibrinogen was conducted in dogs with freshly induced thromobosis of the left atrial appendage. An accumulation of radioactivity was detectable in the area of the left atrium and confirmed in each of nine dogs sacrificed. Similarly, 20 patients with heart disease predisposing to intracardiac thrombosis were surveyed. Eight of nine patients with positive studies and 11 of 11 with negative studies were confirmed subsequently at surgery or autopsy. Cardiac survey with 131-I fibrinogen is a simple and noninvasive method of detecting intracardiac thrombosis.
A STUDY OF THE NITROGEN METABOLISM AND OF ACIDOSIS AFTER THE TRANSPLANTATION OF A URETER INTO THE DUODENUM IN DOGS
Authors: Kingo Goto
Journal: The Journal of Experimental Medicine (1918)

1. The present work was undertaken to study the metabolism in the dog after a ureter-intestinal transplantation. Four dogs, Nos. I, 2, 5, and 7, were originally operated upon. Two, Nos. 2 and 7, showed kidney infection; the other two were not infected, and in these the metabolism was studied; one of the latter (No. 1) showed marked hydronephrosis and hydroureter. 2. Both after the transplantation of the right ureter into the intestine and the ligation of the right ureter, there is generally a moderately increased output of nitrogen in the urine and, in the former instance especially, a retention of nitrogen in the blood, but no change in carbon dioxide content in the blood. The significance of this is probably an increased tissue catabolism, the cause of which is doubtful without further work. 3. After removal of the left kidney subsequent to transplantation of the right ureter into the duodenum, renal insufficiency and resulting retention developed. The non-protein and urea nitrogen in the blood steadily increased and the carbon dioxide content of the blood diminished to the level characteristic of a moderate acidosis. No ketones were found in the blood The dogs died 5 to 10 days after the nephrectomy under conditions characteristic of suspended renal activity-deep respiration, unconsciousness, and sopor.
What's hot for recombination
Authors: Loraine Symington
Journal: Trends in Genetics (1997)

In the past decade we have witnessed remarkable progress in the identification, biochemical characterization and structural analysis of proteins that catalyze recombination.One of the themes at tht'; meeting was how these proteins cooperate to promote recombination more efficiently.Stephen Kowatczykowski (Univ. of California, USA) presented evidence that the translocating RecBCD complex facilitates loading of the RecA protein onto tt,e 3' end created by attenuation of the RecBCD nuclease activity at chi.This preferential loading of RecA by RecBCD contributes to the recombination stimulatory properties of chi sites.Michael Cox (Univ. of Wisconsin, USA) showed that the RecO and RecR proteins stabilize the RecA filament on single-stranded DNA by preventing disassembly of RecA from the 5' end, and ReeF and RecR block extension of the RecA filament on duplex DNA adjacent to a single-stranded region.These biochemical data fit with the proposed role of RecFOR in daughterstrand gap repair.The final stages of recombination involve resolution of Holliday junctions by either the ' RuvABC complex or RecG.Stephen West (ICRF, UK) showed physical interaction between RuvB and RuvC, and enhanced cleavage of a model four-way junction by RuvC in the presence of RuvA and RuvB.Genes in the RAD52 epistasis group were first identified in yeast by their requirement for ionizing radiation resistance.Mammalian homologs have been identified for RAD50, 1641951, RAD52, RAD54 and MREI 1. Surprisingly, the mouse Rad51 gene is essential for viability, but no clues for the essential function(s) were provided at this meeting.Four other mammalian genes have been found that encode proteins with significant similarity to Rad51p (David Schild, Lawrence Berkeley Natl Lab., USA; Eric Kmiec, Thomas Jefferson Univ., USA), but their functions, while cleady not redundant with RAD51, remain unknown.RAD51 (yeast or human) inefficiently promotes strand exchange in vitro.RPA (a single-stranded DNAbinding protein) stimulates the strand