tbuckley/cabot-search huggingface dataset:
Treatment With Nephrectomy Only for Small, Stage I/Favorable Histology Wilms’ Tumor: A Report From the National Wilms’ Tumor Study Group
Authors: Daniel M. Green, Norman E. Breslow, J. Bruce Beckwith, Michael L. Ritchey, Robert C. Shamberger, Gerald M. Haase, Giulio J. D’Angio, Elizabeth Perlman, Milton Donaldson, Paul E. Grundy, Robert Weetman, Max J. Coppes, Marcio Malogolowkin, Patricia Shearer, Peter Coccia, Morris Kletzel, Patrick R.M. Thomas, Roger Macklis, Gail Tomlinson, Vicki Huff, Robert Newbury, Douglas Weeks
Journal: Journal of Clinical Oncology (2001)

Children younger than 24 months with small (< 550 g), favorable histology (FH) Wilms tumors (WTs) were shown in a pilot study to have an excellent prognosis when treated with nephrectomy only.A study of nephrectomy only for the treatment of selected children with FH WT was undertaken. Stringent stopping rules were designed to insure closure of the study if the true 2-year relapse-free survival rate was 90% or lower.Seventy-five previously untreated children younger than 24 months with stage I/FH WTs for which the surgical specimen weighed less than 550 g were treated with nephrectomy only. Three patients developed metachronous, contralateral WT 1.1, 1.4, and 2.3 years after nephrectomy, and eight patients relapsed 0.3 to 1.05 years after diagnosis (median, 0.4 years; mean, 0.51 years). The sites of relapse were lung (n = 5) and operative bed (n = 3). The 2-year disease-free (relapse and metachronous contralateral WT) survival rate was 86.5%. The 2-year survival rate is 100% with a median follow-up of 2.84 years. The 2-year disease-free survival rate (excluding metachronous contralateral WT) was 89.2%, and the 2-year cumulative risk of metachronous contralateral WT was 3.1%.Children younger than 24 months treated with nephrectomy only for a stage I/FH WT that weighed less than 550 g had a risk of relapse, including the development of metachronous contralateral WT, of 13.5% 2 years after diagnosis. All patients who experienced relapse on this trial are alive at this time. This approach will be re-evaluated in a clinical trial using a less conservative stopping rule.
I just wanted to be a doctor
Authors: Tara Hunt
Journal: BMJ (2006)

W hen I decided at the ripe old age of 26 that I had had enough of waitressing, bar jobs, doing arts degrees just because they sounded fun, and teaching English as a foreign language, I thought maybe I was finally ready to make a proper career choice. Maybe, just maybe, the time had come to put away childish things. I went for coffee with a friend. She asked one pertinent question. What would you do if you could do anything you liked? Regardless of time, money, peer pressure, parental pressure, qualifications, intellectual, or physical capacity… what would you do if you could do anything? I pondered for quite some time. There were so many things I wanted to encompass. I wanted to do something good. Something that was worth doing. Something that was interesting. A good laugh. Something that gave me a sense of self respect. Something that made me want to get out of bed at some ungodly hour. Something that my mum would be proud of. I mean, it's such a big part of your life, your …
Class III β-Tubulin Expression and Benefit from Adjuvant Cisplatin/Vinorelbine Chemotherapy in Operable Non–Small Cell Lung Cancer: Analysis of NCIC JBR.10
Authors: Pascal Sève, Raymond Lai, Keyue Ding, Timothy Winton, Charles Butts, John Mackey, Charles Dumontet, Laith Dabbagh, Sarit Aviel-Ronen, Lesley Seymour, Marlo Whitehead, Ming-Sound Tsao, Frances A. Shepherd, Tony Reiman
Journal: Clinical Cancer Research (2007)

High class III beta-tubulin (bTubIII) expression in advanced non-small cell lung cancer is known to correlate with reduced response rates and inferior survival with anti-microtubule agents. JBR.10 showed a 12% and 15% improvement in 5-year recurrence-free survival (RFS) and overall survival (OS), respectively, with the addition of cisplatin and vinorelbine following resection of stage IB-II non-small cell lung cancer. We sought to determine the effect of bTubIII on patient outcome and benefit from adjuvant chemotherapy in the JBR.10 trial.We did a semiquantitative immunohistochemical assay for bTubIII on primary tumor tissue available from 265 of the 482 patients in JBR.10. Tumors were classified as bTubIII "low" or "high" using a validated method. We examined the prognostic effect of bTubIII in patients treated with or without chemotherapy and the survival benefit from chemotherapy in low versus high bTubIII subgroups.High bTubIII expression was associated with poorer RFS and OS in patients treated with surgery alone but not in patients treated with adjuvant chemotherapy. The RFS and OS benefits of adjuvant chemotherapy were greater in high versus low tubulin expressors. However, with Cox regression, the interaction between bTubIII status and chemotherapy treatment in predicting RFS or OS did not reach statistical significance.Chemotherapy seemed to overcome the negative prognostic effect of high bTubIII expression. Greater benefit from adjuvant chemotherapy was seen in patients with high bTubIII expression. This is contrary to what has been seen in the setting of advanced disease; possible reasons for this difference are being explored.
Studies on Renin
Authors: Erwin Haas, Harry Goldblatt, LaVera Lewis, Edwin C. Gipson
Journal: Circulation Research (1972)

Dog renin was produced with a yield of 1.1 Goldblatt units (GU)/g renal tissue and with a specific activity of 1.3 GU/mg protein, i.e., a specific activity 10-16 times higher than that of previous preparations. This renin, free of angiotensinase and of anaphylactoid substances, was used to study the effects of prolonged infusion of renin in normal conscious dogs and as a standard for the bioassay of renin. A simplified method was designed for the indirect assay of canine renin. After prolonged incubation, the angiotensin produced was determined by bioassay in the rat, and the final estimate was expressed as the concentration of renin, in terms of GU, with an accuracy of ± 12.8%. The lower sensitivity of the assay is 1.0 x 10 -5 GU/ml; this limit permits an estimate of the endogenous renin in 0.1 ml of normal dog serum or in 0.005 mg of normal canine renal tissue. The sensitivity of this bioassay is, therefore, within the range found in seven radioimmunoassays (0.26 x 10 -5 GU/ml to 6.2 x 10 -5 GU/ml), and compared with the previous direct bioassay of renin in the dog the sensitivity is approximately 100,000-fold greater. By reference to an internationally accepted unit of renin, the Goldblatt unit, it was possible to recalculate and compare directly the results obtained in seven laboratories on the concentration of renin in blood, renal lymph, and various other tissues. This unified method for the evaluation of renin assays has made possible the determination of the rate of release of renin from the kidneys and the minimum rate of infusion of renin capable of producing persistent appreciable elevation of blood pressure.
Plasminogen Is a Critical Determinant of Vascular Remodeling in Mice
Authors: Angela F. Drew, Heidi L. Tucker, Keith W. Kombrinck, Daniel I. Simon, Thomas H. Bugge, Jay L. Degen
Journal: Circulation Research (2000)

Abstract —Extracellular proteolysis is likely to be a feature of vascular remodeling associated with atherosclerotic and restenotic arteries. To investigate the role of plasminogen-mediated proteolysis in remodeling, polyethylene cuffs were placed around the femoral arteries of mice with single and combined deficiencies in plasminogen and fibrinogen. Neointimal development occurred in all mice and was unaffected by genotype. Significant compensatory medial remodeling occurred in the cuffed arteries of control mice but not in plasminogen-deficient mice. Furthermore, focal areas of medial atrophy were frequently observed in plasminogen-deficient mice but not in control animals. A simultaneous deficit of fibrinogen restored the potential of the arteries of plasminogen-deficient mice to enlarge in association with neointimal development but did not eliminate the focal medial atrophy. An intense inflammatory infiltrate occurred in the adventitia of cuffed arteries, which was associated with enhanced matrix deposition. Adventitial collagen deposition was apparent after 28 days in control and fibrinogen-deficient arteries but not in plasminogen-deficient arteries, which contained persistent fibrin. These studies demonstrate that plasmin(ogen) contributes to favorable arterial remodeling and adventitial collagen deposition via a mechanism that is related to fibrinogen, presumably fibrinolysis. In addition, these studies reveal a fibrin-independent role of plasminogen in preventing medial atrophy in challenged vessels. (Circ Res. 2000;87:133-139.)
Sarcoidosis is a Th1/Th17 multisystem disorder
Authors: M. Facco, A. Cabrelle, A. Teramo, V. Olivieri, M. Gnoato, S. Teolato, E. Ave, C. Gattazzo, G. P. Fadini, F. Calabrese, G. Semenzato, C. Agostini
Journal: Thorax (2010)

<h3>Background and aims</h3> Sarcoidosis is characterised by a compartmentalisation of CD4<sup>+</sup> T helper 1 (Th1) lymphocytes and activated macrophages in involved organs, including the lung. Recently, Th17 effector CD4<sup>+</sup> T cells have been claimed to be involved in the pathogenesis of granuloma formation. The objective of this study was to investigate the involvement of Th17 cells in the pathogenesis of sarcoidosis. <h3>Methods</h3> Peripheral and pulmonary Th17 cells were evaluated by flow cytometry, real-time PCR, immunohistochemistry analyses and functional assays in patients with sarcoidosis in different phases of the disease and in control subjects. <h3>Results</h3> Th17 cells were detected both in the peripheral blood (4.72±2.27% of CD4<sup>+</sup> T cells) and in the bronchoalveolar lavage (BAL) (8.81±2.25% of CD4<sup>+</sup> T lymphocytes) of patients with sarcoidosis and T cell alveolitis. Immunohistochemical analysis of lung and lymph node specimens showed that interleukin 17 (IL-17)<sup>+</sup>/CD4<sup>+</sup> T cells infiltrate sarcoid tissues surrounding the central core of the granuloma. IL-17 was expressed by macrophages infiltrating sarcoid tissue and/or forming the granuloma core (7.88±2.40% of alveolar macrophages). Analysis of some lung specimens highlighted the persistence of IL-17<sup>+</sup>/CD4<sup>+</sup> T cells in relapsed patients and their absence in the recovered cases. Migratory assays demonstrated the ability of the Th17 cell to respond to the chemotactic stimulus CCL20—that is, the CCR6 ligand (74.8±8.5 vs 7.6±2.8 migrating BAL lymphocytes/high-powered field, with and without CCL20, respectively). <h3>Conclusions</h3> Th17 cells participate in the alveolitic/granuloma phase and also to the progression towards the fibrotic phase of the disease. The recruitment of this cell subset may be driven by CCL20 chemokine.
Developing a domain-general framework for cognition: What is the best approach?
Authors: James L. McClelland, David C. Plaut, Stephen J. Gotts, Tiago V. Maia
Journal: Behavioral and Brain Sciences (2003)

We share with Anderson &amp; Lebiere (A&amp;L) (and with Newell before them) the goal of developing a domain-general framework for modeling cognition, and we take seriously the issue of evaluation criteria. We advocate a more focused approach than the one reflected in Newell's criteria, based on analysis of failures as well as successes of models brought into close contact with experimental data. A&amp;L attribute the shortcomings of our parallel-distributed processing framework to a failure to acknowledge a symbolic level of thought. Our framework does acknowledge a symbolic level, contrary to their claim. What we deny is that the symbolic level is the level at which the principles of cognitive processing should be formulated. Models cast at a symbolic level are sometimes useful as high-level approximations of the underlying mechanisms of thought. The adequacy of this approximation will continue to increase as symbolic modelers continue to incorporate principles of parallel distributed processing.
Efficient Identification of a Novel Cancer/Testis Antigen for Immunotherapy Using Three-Step Microarray Analysis
Authors: Takeshi Yokoe, Fumiaki Tanaka, Koshi Mimori, Hiroshi Inoue, Takahiro Ohmachi, Masato Kusunoki, Masaki Mori
Journal: Cancer Research (2008)

Abstract Advanced technology in molecular biology has provided us powerful tools for the diagnosis and treatment for cancer. We herein adopted a new methodology to identify a novel cancer/testis (CT) antigen with high frequency of expression in colorectal cancer as follows: (a) combining laser microdissection and cDNA microarray was used to analyze the gene expression profile of colorectal cancer cells; (b) genes overexpressed in testis and underexpressed in normal colon epithelium were analyzed using cDNA microarray; and (c) the gene expression profile of colorectal cancer cells was compared with that of normal testis. Using this methodology, we selected 38 candidates for CT antigen. Among these genes, we identified a novel CT antigen, serine/threonine kinase 31 (STK31), which was previously reported as a gene expressed in spermatogonia. Reverse transcription–PCR analysis showed that STK31 gene expression levels in cancer samples were significantly higher (P &amp;lt; 0.0001) than those in normal samples. The STK31 gene was frequently expressed not only in colorectal cancer but also in gastric and esophageal cancer. Moreover, STK31 peptide was able to elicit specific CTLs and induced CTLs lysed either peptide-loading or endogenously STK31-expressing target cells. These results showed that the new methodology in this study facilitated identification of CT antigens and that STK31 may be a candidate for cancer immunotherapy against gastrointestinal cancer. [Cancer Res 2008;68(4):1074–82]
Lactate dehydrogenase isoenzyme pattern in uninvolved mucosa of patients with colorectal carcinoma.
Authors: R Tayler, V H Cumberland, D W Piper
Journal: Gut (1977)

Colorectal mucosa from patients with colorectal carcinoma was compared with rectal mucosa from a control group. It was found that the LDH isoenzyme pattern of uninvolved mucosa proximal and distal to the carcinoma differed from that of normal tissue and resembled that of carcinoma tissue except in the case of the uninvolved mucosa proximal to the carcinoma of the sigmoid colon, which did not differ from normal mucosa.
Itopride in functional dyspepsia: results of two phase III multicentre, randomised, double-blind, placebo-controlled trials
Authors: N J Talley, J Tack, T Ptak, R Gupta, M Giguere
Journal: Gut (2007)

Functional dyspepsia (FD) is a common disorder but there is currently little efficacious drug therapy. Itopride, a prokinetic approved in several countries, showed promising efficacy in FD in a phase IIb trial. The aim of this study was to test the efficacy and safety of this drug in FD.Two similar placebo-controlled clinical trials were conducted (International and North America). Males and females, 18-65 years old, with a diagnosis of FD (Rome II) and the absence (by upper endoscopy) of any relevant structural disease were recruited. All were negative for Helicobacter pylori and, if present, heartburn could not exceed one episode per week. Following screening, patients were randomised to itopride 100 mg three times daily or identical placebo. The co-primary end points were: (1) global patient assessment (GPA) of efficacy; and (2) Leeds Dyspepsia Questionnaire (LDQ). Symptoms were evaluated at weeks 2, 4 and 8. Secondary measures of efficacy included Nepean Dyspepsia Index (NDI) quality of life.The GPA responder rates at week 8 on itopride versus placebo were similar in both trials (45.2% vs 45.6% and 37.8 vs 35.4%, respectively; p = NS). A significant benefit of itopride over placebo was observed for the LDQ responders in the International (62% vs 52.7%, p = 0.04) but not the North American trial (46.9% vs 44.8%). The safety and tolerability profile were comparable with placebo, with the exception of prolactin elevations, which occurred more frequently on itopride (18/579) than placebo (1/591).In this population with FD, itopride did not show a difference in symptom response from placebo.
Clinical characteristics and biochemical mechanisms of congenital hyperinsulinism associated with dominant KATP channel mutations
Authors: Sara E. Pinney, Courtney MacMullen, Susan Becker, Yu-Wen Lin, Cheryl Hanna, Paul Thornton, Arupa Ganguly, Show-Ling Shyng, Charles A. Stanley
Journal: Journal of Clinical Investigation (2008)

Congenital hyperinsulinism is a condition of dysregulated insulin secretion often caused by inactivating mutations of the ATP-sensitive K+ (KATP) channel in the pancreatic β cell. Though most disease-causing mutations of the 2 genes encoding KATP subunits, ABCC8 (SUR1) and KCNJ11 (Kir6.2), are recessively inherited, some cases of dominantly inherited inactivating mutations have been reported. To better understand the differences between dominantly and recessively inherited inactivating KATP mutations, we have identified and characterized 16 families with 14 different dominantly inherited KATP mutations, including a total of 33 affected individuals. The 16 probands presented with hypoglycemia at ages from birth to 3.3 years, and 15 of 16 were well controlled on diazoxide, a KATP channel agonist. Of 29 adults with mutations, 14 were asymptomatic. In contrast to a previous report of increased diabetes risk in dominant KATP hyperinsulinism, only 4 of 29 adults had diabetes. Unlike recessive mutations, dominantly inherited KATP mutant subunits trafficked normally to the plasma membrane when expressed in COSm6 cells. Dominant mutations also resulted in different channel-gating defects, as dominant ABCC8 mutations diminished channel responses to magnesium adenosine diphosphate or diazoxide, while dominant KCNJ11 mutations impaired channel opening, even in the absence of nucleotides. These data highlight distinctive features of dominant KATP hyperinsulinism relative to the more common and more severe recessive form, including retention of normal subunit trafficking, impaired channel activity, and a milder hypoglycemia phenotype that may escape detection in infancy and is often responsive to diazoxide medical therapy, without the need for surgical pancreatectomy.
Suppression of endothelin-1 secretion by lysophosphatidylcholine in oxidized low density lipoprotein in cultured vascular endothelial cells.
Authors: M Jougasaki, K Kugiyama, Y Saito, K Nakao, H Imura, H Yasue
Journal: Circulation Research (1992)

Oxidatively modified low density lipoprotein (oxidized LDL), an atherogenic lipoprotein that exists in the atherosclerotic arteries, has been shown to alter endothelial cell functions. In the present study, we examined the effects of oxidized LDL on the production of endothelin-1-like immunoreactivity (ET-1-LI) by the cultured vascular endothelial cells from porcine aorta and human umbilical vein. Incubation with oxidized LDL resulted in a dose-dependent suppression of ET-1-LI release by both endothelial cells. Oxidized LDL also inhibited thrombin-mediated stimulation of ET-1-LI secretion. However, native LDL had no effects on ET-1-LI secretion. A lipid extract from oxidized LDL, but not from native LDL, inhibited ET-1-LI secretion, indicating that the lipid component of oxidized LDL was required for the inhibition of ET-1-LI secretion. Oxidative modification of LDL was associated with degradation of a substantial amount of phosphatidylcholine to lysophosphatidylcholine (LPC). Pretreatment with defatted albumin, which is an acceptor for hydrophilic lipids including LPC, reduced LPC concentration in oxidized LDL to that in native LDL and simultaneously prevented the inhibitory effects of oxidized LDL on ET-1-LI secretion. Incubation with synthetic LPC (palmitoyl), but not with synthetic phosphatidylcholine (dipalmitoyl), suppressed ET-1-LI secretion by the endothelial cells. No cell death was observed during the incubations as judged by the trypan blue exclusion test, and protein synthesis of the endothelial cells was not affected by lipids or lipoproteins at a concentration at which suppression of ET-1-LI was observed. We concluded that LPC in oxidized LDL causes suppression of ET-1-LI release, which may counteract the vasoconstrictive properties of atherosclerotic arteries.
PET Imaging of Serotonin Type 2A Receptors in Late-Life Neuropsychiatric Disorders
Authors: Carolyn Cidis Meltzer, Julie C. Price, Chester A. Mathis, Phil J. Greer, Michael N. Cantwell, Patricia R. Houck, Benoit H. Mulsant, Doron Ben-Eliezer, Brian Lopresti, Steven T. DeKosky, Charles F. Reynolds
Journal: American Journal of Psychiatry (1999)

To determine whether there are abnormalities in the in vivo status of the serotonin type 2A (5-HT2A) receptor in late-life depression and Alzheimer's disease, the authors used positron emission tomography (PET) to assess patients with these two conditions and healthy subjects.PET was performed by using [18F]altanserin to evaluate 5-HT2A receptor binding in 11 elderly patients with depression (four men, seven women; mean age = 65.0 years, SD = 5.5); nine Alzheimer's disease patients, including three with concurrent depression (two men, seven women; mean age = 69.7 years, SD = 5.0); and 10 age-matched healthy subjects (four men, six women; mean age = 69.8 years, SD = 5.0). Partial-volume correction of regional specific binding estimates was performed by using a method based on magnetic resonance imaging.No significant abnormalities in [18F]altanserin binding (binding potential) were observed in the patients with late-life depression, and no effect of depression on binding potential was present within the Alzheimer's disease group. However, the patients with Alzheimer's disease had significantly lower binding than the normal subjects in several brain regions, including the anterior cingulate, prefrontal cortex, and sensorimotor cortex.These results suggest that the 5-HT2A receptor is differentially affected in late-life depression and Alzheimer's disease, a finding that has implications for the etiological basis of mood and cognitive features of neuropsychiatric disorders of late life.
Healthy Behavior Change and Cardiovascular Outcomes in Newly Diagnosed Type 2 Diabetic Patients: A Cohort Analysis of the ADDITION-Cambridge Study
Authors: Gráinne H. Long, Andrew J.M. Cooper, Nicholas J. Wareham, Simon J. Griffin, Rebecca K. Simmons
Journal: Diabetes Care (2014)

To examine whether improvements in health behaviors are associated with reduced risk of cardiovascular disease (CVD) in individuals with newly diagnosed type 2 diabetes.
Can Cognition Survive Heart Surgery?
Authors: Martin A. Samuels
Journal: Circulation (2006)

n this issue of Circulation, Jensen et al 1 report that cognitive difficulties were no fewer when off-pump (OPCAB) versus conventional (CCAB) coronary artery bypass grafting was used.This important investigation, a substudy of the Best Bypass Surgery Trial, is a randomized prospective controlled trial that compares OPCAB with CCAB.Although the numbers seem relatively small (ie, 120 elderly patients with a men age of 76 years), the study was carefully powered to show differences in cognitive function at a mean of 103 days of follow-up.Although one could quibble with the details of the neuropsychological tests chosen (mini-mental state examination as a screening test for dementia after randomization but before inclusion, visual verbal learning, concept shifting, Stroop color word interference test, letter-digit coding), the main result is unequivocal.The incidence of cognitive decline was roughly 8%, and no difference between OPCAB and CCAB was found.This disappointing result raises important questions about the mechanisms of neurological injury caused by cardiac surgery and what future strategies might entail.
A phase II trial of docetaxel in platinum pre-treated patients with advanced epithelial ovarian cancer: A Japanese Cooperative Study
Authors: N. Katsumata, R. Tsunematsu, K. Tanaka, Y. Terashima, S. Ogita, H. Hoshiai, I. Kohno, K. Hirabayashi, M. Yakushiji, K. Noda, T. Taguchi
Journal: Annals of Oncology (2000)