tbuckley/cabot-search huggingface dataset:
Incidence and determinants of 1-month mortality after cancer-directed surgery
Authors: B.A. Mahal, G. Inverso, A.A. Aizer, D.R. Ziehr, A.S. Hyatt, T.K. Choueiri, K.E. Hoffman, J.C. Hu, C.J. Beard, A.V. D'Amico, N.E. Martin, P.F. Orio, Q.-D. Trinh, P.L. Nguyen
Journal: Annals of Oncology (2014)
Inhibitory actions of a high fibre diet on intestinal gas transit in healthy volunteers
Authors: S Gonlachanvit
Journal: Gut (2004)

Fibre treatment often produces gaseous symptoms which have been attributed to fermentation by colonic bacteria with increased gas production. Effects of fibre ingestion on intestinal gas flow are unexplored.We aimed to test the hypothesis that consumption of a high fibre diet retards gas transit.Ten healthy volunteers participated.To investigate the effects of fibre on gas dynamics, physiological gas mixtures were jejunally perfused at 12 ml/min x 2 hours after a standard diet for seven days with and without psyllium 30 g/day in a crossover fashion. Gas was collected from an intrarectal catheter to bypass the anus and evacuation was quantified in real time using a barostat.On initiating gas perfusion under control conditions, an initial lag phase with no gas expulsion was observed (1129 (274) seconds). Thereafter, gas evacuation from the rectum proceeded with cumulative volumes of 1429 (108) ml by the end of the second hour. Evacuation was pulsatile with passage of 20.9 (2.5) boluses, with mean volumes of 68.2 (5.0) ml. Fibre prolonged the lag time (2265 (304) seconds; p<0.05) and reduced cumulative gas evacuation volumes (1022 (80) ml; p<0.05). Decreased gas evacuation resulted from reductions in the numbers of bolus passages (14.2 (1.1); p<0.05) but not bolus volumes (70.7 (3.4) ml; p = 0.66).Consumption of a high fibre diet retards intestinal gas transit by decreasing bolus propulsion to the rectum. Thus, in addition to increasing gas production by colonic flora, fibre ingestion may elicit gaseous symptoms by promoting gas retention.
THE FIXATION OF ANTISEPTICS BY DRESSINGS AND TISSUES: ITS IMPORTANCE IN WOUND TREATMENT, WITH SPECIAL REFERENCE TO ACRIFLAVINE
Authors: J. G. Graham
Journal: BMJ (1928)

rXLMuIAx JO1Madding phenol is a drawback, and now recommend the following method: Incubate the agar serum for about two hours at 370 C. Then a 30 per cent.solution of peptone is taken, and 4 c.cm. of it is mlixed with 21 miniims of phenol (measured) for each ounce of the peptoned agar serum.No precipitate will he found in this peptone solution.*It is then poured into the agar serum, and mixed up with it, wlhen the colloidal solution remains perfectly clear.It is unnecessary to incubate further.It is best to use the patient's own serum, as it contains some appropriate antibody, more or less.When a case has been thoroughly exaimined, the diet, etc., arranged, and any endocrine defect attended to,' first try intravenous injection of peptone (5 per cent.) up to 21 or 3 c.cm.; if after a time, say four to five weeks, but little improvement is found, carefullv and slowly introduce into the vein peptoned agar serum (2 c.cm. iup to 3-or 4 c.cm.) when, in many cases, excellent results will be obtained.
Combined image and genomic analysis of high-grade serous ovarian cancer reveals PTEN loss as a common driver event and prognostic classifier
Authors: Filipe C Martins, Ines de Santiago, Anne Trinh, Jian Xian, Anne Guo, Karen Sayal, Mercedes Jimenez-Linan, Suha Deen, Kristy Driver, Marie Mack, Jennifer Aslop, Paul D Pharoah, Florian Markowetz, James D Brenton
Journal: Genome biology (2014)

Abstract Background TP53 and BRCA1/2 mutations are the main drivers in high-grade serous ovarian carcinoma (HGSOC). We hypothesise that combining tissue phenotypes from image analysis of tumour sections with genomic profiles could reveal other significant driver events. Results Automatic estimates of stromal content combined with genomic analysis of TCGA HGSOC tumours show that stroma strongly biases estimates of PTEN expression. Tumour-specific PTEN expression was tested in two independent cohorts using tissue microarrays containing 521 cases of HGSOC. PTEN loss or downregulation occurred in 77% of the first cohort by immunofluorescence and 52% of the validation group by immunohistochemistry, and is associated with worse survival in a multivariate Cox-regression model adjusted for study site, age, stage and grade. Reanalysis of TCGA data shows that hemizygous loss of PTEN is common (36%) and expression of PTEN and expression of androgen receptor are positively associated. Low androgen receptor expression was associated with reduced survival in data from TCGA and immunohistochemical analysis of the first cohort. Conclusion PTEN loss is a common event in HGSOC and defines a subgroup with significantly worse prognosis, suggesting the rational use of drugs to target PI3K and androgen receptor pathways for HGSOC. This work shows that integrative approaches combining tissue phenotypes from images with genomic analysis can resolve confounding effects of tissue heterogeneity and should be used to identify new drivers in other cancers.
Health-Related Quality of Life in Non–Small-Cell Lung Cancer: Methodologic Issues in Randomized Controlled Trials
Authors: Andrew Bottomley, Fabio Efficace, Ronald Thomas, Veerle Vanvoorden, Sam H. Ahmedzai
Journal: Journal of Clinical Oncology (2003)

Purpose: Non–small-cell lung cancer (NSCLC), a leading cause of cancer-related deaths in both developed and developing countries, heavily impacts patient health-related quality of life (HRQOL). Although recent research has found many positive and significant steps in randomized controlled trials (RCTs) in which HRQOL has been used as an outcome, questions remain regarding methodologic quality and impact value of HRQOL outcome assessments in some RCTs. To date, no detailed systematic review exists of HRQOL methodology in NSCLC RCTs. Methods: A systematic review using Cochrane methodology evaluated HRQOL components in RCTs. Identified studies were evaluated independently by three reviewers on a broad set of predetermined criteria. Results: Twenty-nine published RCTs (NSCLC patient samples total, N = 8,445) with an HRQOL component were identified. Although most trials exhibited good-quality research and useful HRQOL and clinical data, the weaknesses identified in some trials include such common limitations as no clear hypothesis, lack of a clear approach to missing data and data analysis, and limited presentation of results. Conclusion: Although it is clear that HRQOL is an important end point in NSCLC RCTs because the information helps to influence treatment recommendations, the identified weaknesses in conducting HRQOL measurement in NSCLC RCTs and the reporting of results need to be addressed.
Socioeconomic status, lung function and admission to hospital for COPD: results from the Copenhagen City Heart Study
Authors: E. Prescott, P Lange, J. Vestbo, None and the Copenhagen City Heart Study Group
Journal: European Respiratory Journal (1999)

This study analysed the effect of education and income on development of chronic obstructive pulmonary disease (COPD) assessing lung function and hospital admission. The study population consisted of 14,223 subjects, aged 20-90 yrs, randomly sampled from the population of Copenhagen in 1976. Association between socioeconomic factors and forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) at study entry was analysed by linear regression. The relation between socioeconomic factors and risk of admission to hospital for COPD from study entry until 1993 was assessed by register linkage. Education and income were independently associated with FEV1 and FVC. The age- and height-adjusted difference in FEV1 (mean+/-SEM) between the highest and lowest level of education and income was 259+/-31 mL in females and 400+/-39 mL in males. After additional adjustment for quantity and duration of smoking and inhalation, the difference was 220+/-31 mL and 363+/-39 mL in females and males, respectively. Results for FVC were of the same magnitude. Using a socioeconomic index which combined information on education and household income the association with lung function did not differ by age. A total of 219 females and 265 males were admitted to hospital for COPD during follow-up. Education and income were significantly associated with admission to hospital. After detailed adjustment for smoking the relative risks (95% confidence intervals) for medium and high versus low socioeconomic index in females were 0.74 (0.55-1.02) and 0.27 (0.10-0.73), respectively. Corresponding relative risks in males were 0.47 (0.36-0.63) and 0.35 (0.17-0.70). The results indicate that socioeconomic factors operating from early in life affect the adult risk of developing chronic obstructive pulmonary disease independently of smoking in both females and males.
Clinical and Theoretical Implications of 5-HT<sub>2</sub> and D<sub>2</sub> Receptor Occupancy of Clozapine, Risperidone, and Olanzapine in Schizophrenia
Authors: S Kapur, R B Zipursky, G Remington
Journal: American Journal of Psychiatry (1999)

Dopamine D2 receptor occupancy measurements provide a valid predictor of antipsychotic response, extrapyramidal side effects, and elevation of prolactin levels. The new antipsychotics clozapine, risperidone, and olanzapine obtain antipsychotic response with few extrapyramidal side effects and little prolactin elevation. The purpose of this study was to compare the D2 and serotonin 5-HT2 receptor occupancies of these drugs in patients receiving multiple-dose, steady-state regimens.Forty-four patients with schizophrenia (16 taking risperidone, 2-12 mg/day; 17 taking olanzapine, 5-60 mg/day; and 11 taking clozapine, 75-900 mg/day) had their D2 and 5-HT2 occupancies determined with the use of [11C]raclopride and [18F]setoperone, respectively, and positron emission tomography imaging.Clozapine showed a much lower D2 occupancy (16%-68%) than risperidone (63%-89%) and olanzapine (43%-89%). Risperidone and olanzapine gave equal D2 occupancies at doses of 5 and 20 mg/day, respectively. All three drugs showed greater 5-HT2 than D2 occupancy at all doses, although the difference was greatest for clozapine.Clozapine, at doses known to be effective in routine clinical settings, showed a D2 occupancy clearly lower than that of typical antipsychotics, while risperidone and olanzapine at their usual clinical doses gave the same level of D2 occupancy as low-dose typical antipsychotics. The results also suggest that some previous clinical comparisons of antipsychotics may have been confounded by different levels of D2 occupancy. Clinical comparisons of these drugs, matching for D2 occupancy, may provide a better measure of their true "atypicality" and will help in understanding the contribution of non-D2 receptors to antipsychotic effects.
VEGF Receptor Inhibitors Block the Ability of Metronomically Dosed Cyclophosphamide to Activate Innate Immunity–Induced Tumor Regression
Authors: Joshua C. Doloff, David J. Waxman
Journal: Cancer Research (2012)

Abstract In metronomic chemotherapy, frequent drug administration at lower than maximally tolerated doses can improve activity while reducing the dose-limiting toxicity of conventional dosing schedules. Although the antitumor activity produced by metronomic chemotherapy is attributed widely to antiangiogenesis, the significance of this mechanism remains somewhat unclear. In this study, we show that a 6-day repeating metronomic schedule of cyclophosphamide administration activates a potent antitumor immune response associated with brain tumor recruitment of natural killer (NK) cells, macrophages, and dendritic cells that leads to marked tumor regression. Tumor regression was blocked in nonobese diabetic/severe combined immunodeficient (NOD/SCID-γ) mice, which are deficient or dysfunctional in all these immune cell types. Furthermore, regression was blunted by NK cell depletion in immunocompetent syngeneic mice or in perforin-deficient mice, which are compromised for NK, NKT, and T-cell cytolytic functions. Unexpectedly, we found that VEGF receptor inhibitors blocked both innate immune cell recruitment and the associated tumor regression response. Cyclophosphamide administered at a maximum tolerated dose activated a transient, weak innate immune response, arguing that persistent drug-induced cytotoxic damage or associated cytokine and chemokine responses are required for effective innate immunity–based tumor regression. Together, our results reveal an innate immunity–based mechanism of tumor regression that can be activated by a traditional cytotoxic chemotherapy administered on a metronomic schedule. These findings suggest the need to carefully evaluate the clinical effects of combination chemotherapies that incorporate antiangiogenesis drugs targeting VEGF receptor. Cancer Res; 72(5); 1103–15. ©2012 AACR.
Insomnia related to sleep apnoea: effect of long-term auto-adjusting positive airway pressure treatment
Authors: Xuân-Lan Nguyên, Dominique Rakotonanahary, Joël Chaskalovic, Bernard Fleury
Journal: European Respiratory Journal (2012)

Insomnia related to sleep apnoea (IA) is highly prevalent, and its proper treatment is still debated. The aim of this study was to test the hypothesis that long-term auto-adjusting positive airway pressure (APAP) treatment improves IA symptoms. 80 patients (mean± sd age 54.9±10.6 yrs, respiratory disturbance index (RDI) 45.0±24.6 events·h −1 ) receiving APAP treatment were followed prospectively for 24 months. Somnolence and depression were assessed at baseline (T0) with the Epworth and the QD2A scales, respectively. Nightly APAP use was measured after 24 months of treatment (T24). The assessment of insomnia at T0 and T24 used the insomnia severity index (ISI). The combination of ISI T0 ≥15 and ISI T0 –ISI T24 ≥9 defined the APAP-responding insomnia (APAP-RI) group. A logistic regression analysis identified the factors independently associated with the APAP-RI group. The ISI (13.7±5.7 versus 8.2±6.3) decreased significantly from T0 to T24 (p = 0.0001) for the patients as a whole, with a mean decrease of 13.5±2.9. Among the 39 insomniac subjects (T0), 20 belonged to the APAP-RI group (51%). The Epworth score (OR 1.536, 95% CI 1.093–2.159; p = 0.01) and the RDI (OR 1.080, 95% CI 1.010–1.154; p = 0.02) increased the risk of belonging to the APAP-RI group. IA symptoms improved with APAP treatment, and improvement was associated with the initial severity of the disease and somnolence in our population.
High Prevalence of Autoantibodies to hLAMP-2 in Anti–Neutrophil Cytoplasmic Antibody–Associated Vasculitis
Authors: Renate Kain, Henko Tadema, Eoin F. McKinney, Alexandra Benharkou, Ricarda Brandes, Andrea Peschel, Virginie Hubert, Tjerk Feenstra, Gürkan Sengölge, Coen Stegeman, Peter Heeringa, Paul A. Lyons, Kenneth G.C. Smith, Cees Kallenberg, Andrew J. Rees
Journal: Journal of the American Society of Nephrology (2012)

The involvement of autoantibodies to human lysosome-associated membrane protein-2 (hLAMP-2) in anti–neutrophil cytoplasmic antibody (ANCA)–associated vasculitis is controversial because of the absence of confirmatory data subsequent to the initial reports of their high prevalence in this disease. We characterized three assays for anti-hLAMP-2 antibodies: ELISA and Western blotting assays using unglycosylated recombinant hLAMP-2 expressed in Escherichia coli, and an indirect immunofluorescence assay using stably transfected ldlD cells that expressed glycosylated full-length hLAMP-2 on the plasma membrane. The assays detected autoantibodies to hLAMP-2 in human sera reproducibly and with comparable sensitivity and the assays gave the same results in 80.5% of the test panel of 40 selected positive and negative sera. In untreated patients at presentation, the frequencies of autoantibodies to LAMP-2 were 89%, 91%, and 80%, respectively, among three groups of patients with ANCA-associated vasculitis from Vienna, Austria (n=19); Groningen, the Netherlands (n=50) and Cambridge, United Kingdom (n=53). Prevalence of LAMP-2 autoantibodies was similar in both those with myeloperoxidase-ANCA and proteinase 3-ANCA. Furthermore, we detected LAMP-2 autoantibodies in two ANCA-negative patients. LAMP-2 autoantibodies rapidly became undetectable after the initiation of immunosuppressive treatment and frequently became detectable again during clinical relapse. We conclude that when robust assays are used, circulating autoantibodies to hLAMP-2 can be detected in most European patients with ANCA-associated vasculitis. Large-scale prospective studies are now needed to determine whether they are pathogenic or merely an epiphenomenon.
TREM2 deficiency eliminates TREM2+ inflammatory macrophages and ameliorates pathology in Alzheimer’s disease mouse models
Authors: Taylor R. Jay, Crystal M. Miller, Paul J. Cheng, Leah C. Graham, Shane Bemiller, Margaret L. Broihier, Guixiang Xu, Daniel Margevicius, J. Colleen Karlo, Gregory L. Sousa, Anne C. Cotleur, Oleg Butovsky, Lynn Bekris, Susan M. Staugaitis, James B. Leverenz, Sanjay W. Pimplikar, Gary E. Landreth, Gareth R. Howell, Richard M. Ransohoff, Bruce T. Lamb
Journal: The Journal of Experimental Medicine (2015)

Variants in triggering receptor expressed on myeloid cells 2 (TREM2) confer high risk for Alzheimer’s disease (AD) and other neurodegenerative diseases. However, the cell types and mechanisms underlying TREM2’s involvement in neurodegeneration remain to be established. Here, we report that TREM2 is up-regulated on myeloid cells surrounding amyloid deposits in AD mouse models and human AD tissue. TREM2 was detected on CD45hiLy6C+ myeloid cells, but not on P2RY12+ parenchymal microglia. In AD mice deficient for TREM2, the CD45hiLy6C+ macrophages are virtually eliminated, resulting in reduced inflammation and ameliorated amyloid and tau pathologies. These data suggest a functionally important role for TREM2+ macrophages in AD pathogenesis and an unexpected, detrimental role of TREM2 in AD pathology. These findings have direct implications for future development of TREM2-targeted therapeutics.
Studies of the cell surface of mouse dendritic cells and other leukocytes
Authors: MC Nussenzweig, RM Steinman, JC Unkeless, MD Witmer, B Gutchinov, ZA Cohn
Journal: The Journal of Experimental Medicine (1981)

The surface of dendritic cells (DC) has been analyzed by means of monoclonal antibodies (Ab) and lactoperoxidase (LPO)-mediated radioiodination. Antigens and other exteriorily disposed polypeptides of purified spleen DC were compared with those of tissue macrophages (Mphi), monocytes, and other bone marrow-derived elements. Quantitative binding studies and autoradiography with (125)I-Ab established that DC expressed high levels of I-A and H-2D, 2 x 10(5) and 1 x 10(5) Ab binding sites per cell, respectively. DC from conventional, germ-free, and specific pathogen-free mice were all rich in Ia. Expression of Ia on B cells was 5-10 percent of that on DC and increased fivefold during lipopolysaccharide mitogenesis. More than 70-90 percent of purified Mphi and monocytes from specific pathogen-free mice were Ia negative, but increased levels of Ia were noted on cells from mice reared under conventional conditions. Thus large amounts of Ia on DC is a constitutive trait, whereas the expression of Ia by other cell types may be governed by the environmental and immunological status of the host. The 2.4G2 Fc receptor Ag was not detected on DC. Peritoneal and spleen Mphi had 10(5) 2.4G2 binding sites/cell, whereas monocytes and lymphocytes were less reactive (1 x 10(4)-3 x 10(4) binding sites/cell). Four other Mphi-related antigens were evaluated. Each had a distinctive tissue distribution and none bound exclusively to Mphi and monocytes. Neither 1.21J (Mac-1) nor F4/80 reacted with DC. Immunoprecipitation studies of externally ((125)I) and biosynthetically ([(35)S]methionine)dabeled cells confirmed the binding data. Sensitive binding assays with (125)I-Ab confirmed previous observations that DC lack Ig and Thy-1. Lyt-1 was also not found on DC, but 5-12 percent of the cells in purified DC preparations expressed both Lyt-2 and Ia. All DC expressed the leukocyte common antigens at levels similar to other leukocytes. The spectrum of surface polypeptides labeled by LPO-mediated iodination was different on Mphi, DC, and lymphocytes. Polypeptides migrating at molecular weights of 155,000, 85,000, and 62,000 appeared to be restricted to DC. These observations establish that the cell surface of DC differs considerably from other leukocytes, including the blood monocyte, and suggest that the DC is part of a unique Ia-rich leukocyte differentiation pathway.
AN ETIOLOGIC CONSIDERATION OF DONOVANIA GRANULOMATIS CULTIVATED FROM GRANULOMA INGUINALE (THREE CASES) IN EMBRYONIC YOLK
Authors: Katherine Anderson, W. A. DeMonbreun, E. W. Goodpasture
Journal: The Journal of Experimental Medicine (1945)

1. A microorganism identical with that originally described by Anderson has been cultivated in pure strain from two additional cases of granuloma inguinale by means of inoculating the yolk of chick embryos with uncontaminated human tissue containing Donovan bodies. 2. The morphological and cultural characteristics of the three isolated strains are described and discussed. 3. This microorganism has been cultivated in vitro only in media containing embryonic yolk. It failed to grow on any of a variety of artificial media. 4. It has not proved to be pathogenic for common experimental animals. 5. The Donovan body is reproduced in the epithelial cells of the yolk sac and in the yolk. The microorganism evidently reproduces both extracellularly and intracellularly. 6. The microorganism produces in culture antigens that elicit immune reactions in the skin and serum of granuloma inguinale patients. 7. This microorganism is judged to be a bacterium and the etiological agent of granuloma inguinale. 8. It is proposed that these strains of the bacterium be the type of a new genus, Donovania, in recognition of Donovan's original description of the pathognomonic bodies of granuloma inguinale; and that the specific name granulomatis be applied to designate its relationship to the characteristic lesion of the disease.