tbuckley/cabot-search huggingface dataset:
An evaluation of the rosette inhibition test in Crohn's disease
Authors: J. R. Clarke, E. R. Richens, M. J. Williams, K. R. Gough, R. J. Ancill
Journal: Gut (1974)

Serial rosette inhibition tests were performed on nine patients with Crohn9s disease undergoing immunosuppressive therapy in an attempt to estimate the minimum amount of drug necessary to maintain immunosuppression. The rosette inhibition titre was found to be higher in immunosuppressed patients than in normal subjects. However, there was no consistent correlation of the rosette inhibition titre with the degree of activity of the disease. The test is therefore not sufficiently discriminative to be used as a basis on which to control drug dosage.
ALTERED REACTIVITY TO EPINEPHRINE IN THE HYPERSENSITIVE RABBIT
Authors: Robert R. Gatling
Journal: The Journal of Experimental Medicine (1958)

A series of experiments are reported which illustrate and characterize an altered state of reactivity of the skin of the hypersensitive rabbit to epinephrine (and norepinephrine). The requirements for the production of the lesion are: a state of hypersensitivity, circulating antigen and antibody and focal deposition of epinephrine or norepinephrine. The size and intensity of the reaction appear to be directly related to the amount of epinephrine injected (within certain limits) and to the degree of hypersensitivity as measured by the Arthus reaction. Although circulating antigen is required, the precise quantity does not seem to be as critical as does the amount of circulating antibody; a certain minimum amount is necessary, however. Experimental evidence is given which indicates the utilization of antigen in the production of the lesion. Data tending to identify this lesion with the Arthus reaction are given. The possibility of an analogous relationship between the mechanism of this experimental lesion and the necrotizing arteritis of the collagen diseases is postulated.
The Effect of Continuous Glucose Monitoring in Well-Controlled Type 1 Diabetes
Journal: Diabetes Care (2009)

OBJECTIVE The potential benefits of continuous glucose monitoring (CGM) in the management of adults and children with well-controlled type 1 diabetes have not been examined. RESEARCH DESIGN AND METHODS A total of 129 adults and children with intensively treated type 1 diabetes (age range 8–69 years) and A1C &amp;lt;7.0% were randomly assigned to either continuous or standard glucose monitoring for 26 weeks. The main study outcomes were time with glucose level ≤70 mg/dl, A1C level, and severe hypoglycemic events. RESULTS At 26 weeks, biochemical hypoglycemia (≤70 mg/dl) was less frequent in the CGM group than in the control group (median 54 vs. 91 min/day), but the difference was not statistically significant (P = 0.16). Median time with a glucose level ≤60 mg/dl was 18 versus 35 min/day, respectively (P = 0.05). Time out of range (≤70 or &amp;gt;180 mg/dl) was significantly lower in the CGM group than in the control group (377 vs. 491 min/day, P = 0.003). There was a significant treatment group difference favoring the CGM group in mean A1C at 26 weeks adjusted for baseline (P &amp;lt; 0.001). One or more severe hypoglycemic events occurred in 10 and 11% of the two groups, respectively (P = 1.0). Four outcome measures combining A1C and hypoglycemia data favored the CGM group in comparison with the control group (P &amp;lt; 0.001, 0.007, 0.005, and 0.003). CONCLUSIONS Most outcomes, including those combining A1C and hypoglycemia, favored the CGM group. The weight of evidence suggests that CGM is beneficial for individuals with type 1 diabetes who have already achieved excellent control with A1C &amp;lt;7.0%.
Mitochondria as a source of mechanical signals in cardiomyocytes
Authors: A. Kaasik, M. Kuum, F. Joubert, J. Wilding, R. Ventura-Clapier, V. Veksler
Journal: Cardiovascular Research (2010)

The myofibrillar and nuclear compartments in cardiomyocytes are known to be sensitive to extracellular mechanical stimuli. Recently, we have shown that alterations in the mitochondrial ionic balance in cells in situ are associated with considerably increased mitochondrial volume. Theoretically, this swelling of mitochondria could impose mechanical constraints on the myofibrils and nuclei in their vicinity. Thus, we studied whether modulation of mitochondrial volume in cardiomyocytes in situ has a mechanical effect on the myofibrillar and nuclear compartments. We used the measurement of passive force developed by saponin-permeabilized mouse ventricular fibres as a sensor for compression of the myofibrils. Osmotic compression induced by dextran caused an increase in passive force. Similarly, mitochondrial swelling induced by drugs that alter ionic homeostasis (alamethicin and propranolol) markedly augmented passive force (confirmed by confocal microscopy). Diazoxide, a mitochondrial ATP-sensitive potassium channel opener known to cause moderate mitochondrial swelling, also increased passive force (by 28 ± 5% at 10% stretch, P < 0.01). This effect was completely blocked by 5-hydroxydecanoate (5-HD), a putative specific inhibitor of these channels. Mitochondrial swelling induced by alamethicin and propranolol led to significant nuclear deformation, which was visualized by confocal microscopy. Furthermore, diazoxide decreased nuclear volume, calculated using three-dimensional reconstructed images, in a 5-HD-dependent manner by 12 ± 2% (P < 0.05). This corresponds to an increase in intracellular pressure of 2.1 ± 0.3 kPa. This study is the first to demonstrate that mitochondria are able to generate internal pressure, which can mechanically affect the morphological and functional properties of intracellular organelles.
High expression of CD40 on B-cell precursor acute lymphoblastic leukemia blasts is an independent risk factor associated with improved survival and enhanced capacity to up-regulate the death receptor CD95
Authors: Anja Troeger, Ludmila Glouchkova, Birgit Ackermann, Gabriele Escherich, Roland Meisel, Helmut Hanenberg, Monique L. den Boer, Rob Pieters, Gritta E. Janka-Schaub, Ulrich Goebel, Hans-Juergen Laws, Dagmar Dilloo
Journal: Blood (2008)
Gefitinib Versus Placebo in Completely Resected Non–Small-Cell Lung Cancer: Results of the NCIC CTG BR19 Study
Authors: Glenwood D. Goss, Chris O'Callaghan, Ian Lorimer, Ming-Sound Tsao, Gregory A. Masters, James Jett, Martin J. Edelman, Rogerio Lilenbaum, Hak Choy, Fadlo Khuri, Katherine Pisters, David Gandara, Kemp Kernstine, Charles Butts, Jonathan Noble, Thomas A. Hensing, Kendrith Rowland, Joan Schiller, Keyue Ding, Frances A. Shepherd
Journal: Journal of Clinical Oncology (2013)

Survival of patients with completely resected non-small-cell lung cancer (NSCLC) is unsatisfactory, and in 2002, the benefit of adjuvant chemotherapy was not established. This phase III study assessed the impact of postoperative adjuvant gefitinib on overall survival (OS).Patients with completely resected (stage IB, II, or IIIA) NSCLC stratified by stage, histology, sex, postoperative radiotherapy, and chemotherapy were randomly assigned (1:1) to receive gefitinib 250 mg per day or placebo for 2 years. Study end points were OS, disease-free survival (DFS), and toxicity.As a result of early closure, 503 of 1,242 planned patients were randomly assigned (251 to gefitinib and 252 to placebo). Baseline factors were balanced between the arms. With a median of 4.7 years of follow-up (range, 0.1 to 6.3 years), there was no difference in OS (hazard ratio [HR], 1.24; 95% CI, 0.94 to 1.64; P = .14) or DFS (HR, 1.22; 95% CI, 0.93 to 1.61; P = .15) between the arms. Exploratory analyses demonstrated no DFS (HR, 1.28; 95% CI, 0.92 to 1.76; P = .14) or OS benefit (HR, 1.24; 95% CI, 0.90 to 1.71; P = .18) from gefitinib for 344 patients with epidermal growth factor receptor (EGFR) wild-type tumors. Similarly, there was no DFS (HR, 1.84; 95% CI, 0.44 to 7.73; P = .395) or OS benefit (HR, 3.16; 95% CI, 0.61 to 16.45; P = .15) from gefitinib for the 15 patients with EGFR mutation-positive tumors. Adverse events were those expected with an EGFR inhibitor. Serious adverse events occurred in ≤ 5% of patients, except infection, fatigue, and pain. One patient in each arm had fatal pneumonitis.Although the trial closed prematurely and definitive statements regarding the efficacy of adjuvant gefitinib cannot be made, these results indicate that it is unlikely to be of benefit.
Metabolic disorders in heart diseases with an inflammatory background
Authors: F. R. Boucher
Journal: Cardiovascular Research (2010)

This editorial refers to ‘The p65 subunit of NF-κB binds to PGC-1α, linking inflammation and metabolic disturbances in cardiac cells’, by D. Alvarez-Guardia et al ., pp. 449–458, this issue. 

Cardiac hypertrophy and heart failure are associated with nuclear factor-κB (NF-κB) activation and PPARγ coactivator-1α (PGC-1α) inhibition. In this issue of Cardiovascular Research , the study by Alvarez-Guardia et al .1 evidences a key step of cellular signalling and makes the link between these two major pathways.

The general term NF-κB traditionally refers to the ubiquitous p50/p65 heterodimer. The p65 subunit provides the gene regulatory function. NF-κB is retained in the cytoplasm complexed with IκBs such as IκBα. The IκB kinase complex (IKK), when activated by diverse upstream kinases, phosphorylates IκBs, inducing their degradation by the ubiquitin proteasome. Free NF-κB heterodimers then translocate to the nucleus ( Figure 1 ). A previous report has proposed that NF-κB-mediated inhibition of PGC-1α could explain the shift towards increased glycolysis under pathophysiological conditions with an inflammatory background.2 The mechanistic study by Alvarez-Guardia et al .1 was performed on AC16 cells resulting from the fusion of human primary ventricular cells with transformed fibroblasts and on heart extracts from mice overexpressing TNF-α. Co-immunoprecipitation experiments have allowed the authors to demonstrate that the p65 subunit of NF-κB is … 

*Corresponding author. Tel: +33 476 637 117; fax: +33 476 637 152, Email: Francois.Boucher{at}ujf-grenoble.fr
Decreased Expression of Kv4.2 and Novel Kv4.3 K <sup>+</sup> Channel Subunit mRNAs in Ventricles of Renovascular Hypertensive Rats
Authors: Koichi Takimoto, Danqing Li, Kenneth M. Hershman, Ping Li, Edwin K. Jackson, Edwin S. Levitan
Journal: Circulation Research (1997)

Abstract Hypertension-induced cardiac hypertrophy is associated with alterations in ventricular action potentials. To understand molecular mechanisms underlying this electrical abnormality, expression of cardiac voltage-gated K + channel subunit genes was examined in ventricles of renovascular hypertensive rats. While generating a rat Kv4.3 probe, we discovered a previously unreported 19–amino acid insertion in the C-terminal intracellular region of the channel subunit. RNase protection assays indicated that this novel isoform is predominant in rat lung and heart. Effects of renovascular hypertension were then determined by using renal artery clipping models: two-kidney, one clip (2K-1C) rats, a model of high-renin hypertension with a normal plasma volume, and one-kidney, one clip (1K-1C) rats, a model of normal renin with a raised plasma volume. Expression of Kv4.2 and Kv4.3 mRNAs was diminished by &gt;50% in ventricles of 2K-1C rats; however, no changes in the expression of Kv1.2, Kv1.4, Kv1.5, Kv2.1, or KvLQT1 mRNAs were detected. Similar downregulation of Kv4.2 and Kv4.3 mRNAs was detected in 1K-1C rats. Chronic administration of captopril, an angiotensin-converting enzyme inhibitor, blocked the development of hypertension and the suppression of Kv4 subfamily channel mRNA expression in 2K-1C rats. Furthermore, captopril administration to sham-operated rats significantly increased Kv4.2 mRNA. These results indicate that renovascular hypertension causes specific reductions in Kv4 subfamily channel mRNA expression and that this effect is likely to be mediated primarily by an increase in cardiac afterload.
Increased circulating pro-brain natriuretic peptide (PROBNP) and brain natriuretic peptide (BNP) in patients with cirrhosis. Relation to cardiovascular dysfunction and severity of disease
Authors: J.H. Henriksen, J.P. Goetze, S. Fuglsang, E. Christensen, F. Bendtsen, S. Moeller
Journal: Journal of Hepatology (2003)
Army Psychiatry in the Mid-'60s
Authors: WILLIAM J. TIFFANY, WILLIAM S. ALLERTON
Journal: American Journal of Psychiatry (1967)

In this presentation of contemporary Army psychiatry, the authors evaluate personnel utilization, innovations in residency training, and current research programs in the perspective of current trends in psychiatric practice. They point out that the concepts of preventive and community psychiatry have long-established tenure in military medicine.
Public Health Genetics: An Emerging Interdisciplinary Field for the Post-Genomic Era
Authors: Gilbert S. Omenn
Journal: Annual Review of Public Health (2000)

Public health genetics is an exciting interdisciplinary area that brings all the public health sciences to bear on the emerging challenge of interpreting the medical and public health significance of genetic variation within populations. Sequencing of the human genome will generate an avalanche of genetic information to be linked with information about microbial, chemical, and physical exposures; nutrition, metabolism, lifestyle behaviors, and medications. The public health genetics mini-symposium in this volume includes articles dealing with educational innovations, host-pathogen interactions in infectious diseases, nutrition/genetic interactions in cancers, and population screening for hemochromatosis. Additional topics addressed here are ecogenetics and risk assessment, the genetics of unhealthful behaviors, and ethical and policy issues. Finally, a set of principles for community-based health research in populations is presented as a public health-oriented counterpart to the principle of autonomy and the practice of informed consent that have become key elements of ethics in medical care and medical research with individuals.
The Promise of MicroRNA Replacement Therapy
Authors: Andreas G. Bader, David Brown, Matthew Winkler
Journal: Cancer Research (2010)

Abstract MicroRNAs (miRNA), a class of natural RNA-interfering agents, have recently been identified as attractive targets for therapeutic intervention. The rationale for developing miRNA therapeutics is based on the premise that aberrantly expressed miRNAs play key roles in the development of human disease, and that correcting these miRNA deficiencies by either antagonizing or restoring miRNA function may provide a therapeutic benefit. Although miRNA antagonists are conceptually similar to other inhibitory therapies, restoring the function of a miRNA by miRNA replacement is a less well characterized approach. Here, we discuss the specific properties of miRNA replacement and review recent examples that explored the therapeutic delivery of miRNA mimics in animal models of cancer. Cancer Res; 70(18); 7027–30. ©2010 AACR.
Phase III Study of Pemetrexed in Combination With Cisplatin Versus Cisplatin Alone in Patients With Malignant Pleural Mesothelioma
Authors: Nicholas J. Vogelzang, James J. Rusthoven, James Symanowski, Claude Denham, E. Kaukel, Pierre Ruffie, Ulrich Gatzemeier, Michael Boyer, Salih Emri, Christian Manegold, Clet Niyikiza, Paolo Paoletti
Journal: Journal of Clinical Oncology (2003)

Patients with malignant pleural mesothelioma, a rapidly progressing malignancy with a median survival time of 6 to 9 months, have previously responded poorly to chemotherapy. We conducted a phase III trial to determine whether treatment with pemetrexed and cisplatin results in survival time superior to that achieved with cisplatin alone.
Cc Chemokine Receptor 2 Is Critical for Induction of Experimental Autoimmune Encephalomyelitis
Authors: Brian T. Fife, Gary B. Huffnagle, William A. Kuziel, William J. Karpus
Journal: The Journal of Experimental Medicine (2000)

Experimental autoimmune encephalomyelitis (EAE) is a CD4+ T lymphocyte–mediated disease of the central nervous system (CNS) characterized by mononuclear cell infiltration, demyelination, and paralysis. We previously demonstrated a role for chemokines in acute and relapsing EAE pathogenesis. Presently, we investigated the role of CC chemokine receptor 2 (CCR2) in acute EAE. CCR2−/− mice did not develop clinical EAE or CNS histopathology, and showed a significant reduction in T cell– and CNS-infiltrating CD45highF4/80+ monocyte subpopulations. Peripheral lymphocytes from CCR2−/− mice produced comparable levels of interferon-gamma (IFN-γ) and interleukin (IL)-2 in response to antigen-specific restimulation when compared with control mice. Adoptively transferred myelin oligodendrocyte glycoprotein 35-55–specific T cells lacking expression of CCR2 were able to induce EAE, whereas CCR2−/− recipients of wild-type T cells failed to develop disease. These results suggest that CCR2 expression on host-derived mononuclear cells is critical for disease induction.
Molecular Characteristics of ERCC1-Negative versus ERCC1-Positive Tumors in Resected NSCLC
Authors: Luc Friboulet, Daniel Barrios-Gonzales, Frédéric Commo, Ken André Olaussen, Stephan Vagner, Julien Adam, Aïcha Goubar, Nicolas Dorvault, Vladimir Lazar, Bastien Job, Benjamin Besse, Pierre Validire, Philippe Girard, Ludovic Lacroix, Johanna Hasmats, Fabienne Dufour, Fabrice André, Jean-Charles Soria
Journal: Clinical Cancer Research (2011)

Excision repair cross-complementation group 1 (ERCC1) is a protein involved in repair of DNA platinum adducts and stalled DNA replication forks. We and others have previously shown the influence of ERCC1 expression upon survival rates and benefit of cisplatin-based chemotherapy in patients with resected non-small-cell lung cancer (NSCLC). However, little is known about the molecular characteristics of ERCC1-positive and ERCC1-negative tumors.We took advantage of a cohort of 91 patients with resected NSCLC, for which we had matched frozen and paraffin-embedded samples to explore the comparative molecular portraits of ERCC1-positive and ERCC1-negative tumors of NSCLC. We carried out a global molecular analysis including assessment of ERCC1 expression levels by using both immunohistochemistry (IHC) and quantitative reverse transcriptase PCR (qRT-PCR), genomic instability, global gene and miRNA expression, and sequencing of selected key genes involved in lung carcinogenesis.ERCC1 protein and mRNA expression were significantly correlated. However, we observed several cases with clear discrepancies. We noted that ERCC1-negative tumors had a higher rate of genomic abnormalities versus ERCC1-positive tumors. ERCC1-positive tumors seemed to share a common DNA damage response (DDR) phenotype with the overexpression of seven genes linked to DDR. The miRNA expression analysis identified miR-375 as significantly underexpressed in ERCC1-positive tumors.Our data show inconsistencies in ERCC1 expression between IHC and qRT-PCR readouts. Furthermore, ERCC1 status is not linked to specific mutational patterns or frequencies. Finally, ERCC1-negative tumors have a high rate of genomic aberrations that could consequently influence prognosis in patients with resected NSCLC.
Higher Levels of HDL Cholesterol Are Associated With a Decreased Likelihood of Albuminuria in Patients With Long-Standing Type 1 Diabetes
Authors: Mark E. Molitch, Demetra Rupp, Mercedes Carnethon
Journal: Diabetes Care (2006)

OBJECTIVE—The objective of this study was to determine whether high levels of HDL cholesterol are associated with a lower prevalence of albuminuria RESEARCH DESIGN AND METHODS—We analyzed the lipid profiles of patients with type 1 diabetes of ≥20 years duration in 42 patients with albuminuria (28 microalbuminuria and 14 macroalbuminuria) and 65 patients without increased albumin excretion before any interventions with either statins or ACE inhibitors. RESULTS—Several characteristics were similar in the two groups: sex, age, duration of diabetes, total cholesterol, LDL cholesterol, and triglycerides. By univariate analysis, significant differences (P &amp;lt; 0.01) were found in HDL cholesterol (albuminuria 1.42 mg/dl, no albuminuria 1.71 mg/dl, P &amp;lt; 0.01), HbA1c (A1C) (albuminuria 8.5%, no albuminuria 7.5%), and proportions with no, background, and proliferative retinopathy (albuminuria 2.4, 16.7, and 81%; no albuminuria 24.6, 52.3, and 23.1%, respectively). When adjusted for age and sex, a 0.26-mmol/l (10-mg/dl) increase in HDL cholesterol is associated with an odds ratio (OR) of 0.70 (95% CI 0.54–0.90) for having albuminuria. In a multivariate model that adjusted for age, sex, diabetes duration, and A1C, for every 0.54-mmol/l (21-mg/dl) increase in HDL cholesterol, patients are approximately half (OR 0.51 [95% CI 0.30–0.86]) as likely to have albuminuria, even after controlling for A1C. CONCLUSIONS—Higher HDL cholesterol levels may be protective against the development of albuminuria in patients with type 1 diabetes. Whether this is due to the HDL cholesterol levels or whether they serve as a marker for some other mechanism remains to be determined.
After Francis, what next for the NHS?
Authors: A. O'Dowd
Journal: BMJ (2013)

Following the landmark Francis report into what went wrong at Mid Staffordshire NHS Foundation Trust, a panel of experts gathered at a <i>BMJ</i> round table discussion held during the Nuffield Trust 2013 health policy summit last month to discuss how the report’s recommendations could change the NHS. <b>Adrian O’Dowd </b>reports.
A randomized phase III trial of oral S-1 plus cisplatin versus docetaxel plus cisplatin in Japanese patients with advanced non-small-cell lung cancer: TCOG0701 CATS trial
Authors: K Kubota, H Sakai, N Katakami, M Nishio, A Inoue, H Okamoto, H Isobe, H Kunitoh, Y Takiguchi, K Kobayashi, Y Nakamura, H Ohmatsu, S Sugawara, K Minato, M Fukuda, A Yokoyama, M Takeuchi, H Michimae, A Gemma, S Kudoh
Journal: Annals of Oncology (2015)

Platinum-based two-drug combination chemotherapy has been standard of care for patients with advanced nonsmall-cell lung cancer (NSCLC). The primary aim was to compare overall survival (OS) of patients with advanced NSCLC between the two chemotherapy regimens. Secondary end points included progression-free survival (PFS), response, safety, and quality of life (QoL).Patients with previously untreated stage IIIB or IV NSCLC, an Eastern Cooperative Oncology Group performance status of 0-1 and adequate organ function were randomized to receive either oral S-1 80 mg/m(2)/day on days 1-21 plus cisplatin 60 mg/m(2) on day 8 every 4-5 weeks, or docetaxel 60 mg/m(2) on day 1 plus cisplatin 80 mg/m(2) on day 1 every 3-4 weeks, both up to six cycles.A total of 608 patients from 66 sites in Japan were randomized to S-1 plus cisplatin (n = 303) or docetaxel plus cisplatin (n = 305). OS for oral S-1 plus cisplatin was noninferior to docetaxel plus cisplatin [median survival, 16.1 versus 17.1 months, respectively; hazard ratio = 1.013; 96.4% confidence interval (CI) 0.837-1.227]. Significantly higher febrile neutropenia (7.4% versus 1.0%), grade 3/4 neutropenia (73.4% versus 22.9%), grade 3/4 infection (14.5% versus 5.3%), and grade 1/2 alopecia (59.3% versus 12.3%) were observed in the docetaxel plus cisplatin than in the S-1 plus cisplatin. There were no differences found in PFS or response between the two arms. QoL data investigated by EORTC QLQ-C30 and LC-13 favored the S-1 plus cisplatin.Oral S-1 plus cisplatin is not inferior to docetaxel plus cisplatin and is better tolerated in Japanese patients with advanced NSCLC.UMIN000000608.