tbuckley/cabot-search huggingface dataset:
High incidence of Kaposi sarcoma–associated herpesvirus–related non-Hodgkin lymphoma in patients with HIV infection and multicentric Castleman disease
Authors: Eric Oksenhendler, Emmanuelle Boulanger, Lionel Galicier, Ming-Qing Du, Nicolas Dupin, Tim C. Diss, Rifat Hamoudi, Marie-Thérèse Daniel, Félix Agbalika, Chris Boshoff, Jean-Pierre Clauvel, Peter G. Isaacson, Véronique Meignin
Journal: Blood (2002)
Immunohistochemical detection and quantitation of P-glycoprotein in multiple drug-resistant human myeloma cells: association with level of drug resistance and drug accumulation
Authors: WS Dalton, TM Grogan, JA Rybski, RJ Scheper, L Richter, J Kailey, HJ Broxterman, HM Pinedo, SE Salmon
Journal: Blood (1989)
Is the sugar intestinal permeability test a reliable investigation for coeliac disease screening?
Authors: C Catassi, E Fabiani, I M Ratsch, A Bonucci, M Dotti, G V Coppa, P L Giorgi
Journal: Gut (1997)

The lactulose/mannitol (L/M) intestinal permeability test is a simple, non-invasive screening test for coeliac disease. The reliability of the L/M test has so far only been tested in selected groups of patients with coeliac disease.To evaluate the reliability of the L/M test in a group of patients with coeliac disease who had been diagnosed during mass serological screening of the general population.Twenty nine patients with coeliac disease detected by screening and 54 age matched coeliac disease free controls aged 11-15 years underwent an L/M test with 5 g lactulose and 2 g mannitol in isotonic aqueous solution. Urinary sugars were measured by high performance liquid chromatography.The median % urinary recovery of lactulose (lactulose UR) was significantly higher in patients with coeliac disease than in controls (0.63 v 0.18, p < 0.001). The mean mannitol % UR was lower in patients with coeliac disease than in controls (17.6 v 18.5) but the difference was not significant. The median urinary L%/M% ratio was significantly higher in patients with coeliac disease than in controls (0.038 v 0.014, p < 0.001). However, 16 of the 29 patients with coeliac disease showed an L%/M% ratio within normal limits (< 0.044).The L/M intestinal permeability test is not a valuable tool for screening of coeliac disease in the general population. The pattern of the urinary probe recovery suggests that many patients with coeliac disease could remain symptomless because the extent of their intestinal mucosal damage is small ("short" coeliac disease).
Structural Basis for the Ascending Limb of Left Ventricular Function
Authors: CHAIM YORAN, JAMES W. COVELL, JOHN ROSS
Journal: Circulation Research (1973)

Midwall sarcomere lengths near maximal have been reported at left ventricular end-diastolic pressures at the upper limits of normal, but an ascending limb of cardiac function can exist at much higher filling pressures. Accordingly, an analysis was made of sarcomere length distributions across the left ventricular wall over a range of end-diastolic pressures between 2 and 20 mm Hg. In 11 dogs, significant ascending limbs of ventricular function were documented at filling pressures between 2 and 12 mm Hg and between 12 and 20 mm Hg. Nine hearts were arrested and rapidly fixed in diastole with intracoronary glutaraldehyde perfusion, and tissues from five sites equally distributed across the left ventricular free wall were examined by electron microscopy. At filling pressures at the lower end of the normal range (2, 6, and 12 mm Hg), an uneven distribution of sarcomere lengths across the wall was noted: mean sarcomere lengths were shortest at the subendocardial layer, longest at a site between the subendocardial and the midwall layers, and then progressively shorter toward the epicardium. All differences were highly significant. At an end-diastolic pressure of 20 mm Hg, the difference in sarcomere lengths between layers was small; sarcomere lengths decreased only slightly from endocardium to epicardium. Despite maximal sarcomere lengths just inside the midwall in hearts fixed at 12 mm Hg (2.253µ), sarcomere lengths in other layers-the subendocardial and the subepicardial regions-were increased substantially from 2.129 and 2.183µ, respectively, at 12 mm Hg to 2.283 and 2.247µ at 20 mm Hg ( P &lt; 0.001 and P &lt; 0.002, respectively). Therefore, sarcomeres from all layers of the wall increase in length up to a filling pressure of 12 mm Hg; however, as filling pressure is increased further, only short sarcomeres from the subendocardial and the subepicardial layers are recruited. The latter mechanism forms the ultrastructural basis for the ascending limb of normal ventricular function at elevated left ventricular filling pressures.
Sporotrichoid phaeohyphomycosis due to Alternaria infectoria.
Authors: R. Gerdsen, M. Uerlich, G.S. De Hoog, T. Bieber, R. Horre
Journal: British Journal of Dermatology (2001)

We describe a cardiac transplant patient who had human cutaneous alternariosis with a sporotrichoid distribution of skin lesions. In this patient identification of the causative organism Alternaria infectoria was achieved by sequencing the rDNA internal transcribed spacer domain. Treatment with itraconazole led to clinical resolution within 4 months.
NEUROTROPHINS AND SYNAPTIC PLASTICITY
Authors: A. Kimberley McAllister, Lawrence C. Katz, Donald C. Lo
Journal: Annual Review of Neuroscience (1999)

▪ Abstract Despite considerable evidence that neuronal activity influences the organization and function of circuits in the developing and adult brain, the molecular signals that translate activity into structural and functional changes in connections remain largely obscure. This review discusses the evidence implicating neurotrophins as molecular mediators of synaptic and morphological plasticity. Neurotrophins are attractive candidates for these roles because they and their receptors are expressed in areas of the brain that undergo plasticity, activity can regulate their levels and secretion, and they regulate both synaptic transmission and neuronal growth. Although numerous experiments show demonstrable effects of neurotrophins on synaptic plasticity, the rules and mechanisms by which they exert their effects remain intriguingly elusive.
Autoimmunity to Chaperonins in the Pathogenesis of Arthritis and Diabetes
Authors: I R Cohen
Journal: Annual Review of Immunology (1991)

The immunology of the 65 kd heat shock protein (hsp65) is paradoxical. Microbial and mammalian hsp65 molecules are 50% identical in amino acid sequence and immunologically cross-reactive, so microbial hsp65 looks like self; yet hsp65 is a dominant antigen in infection. Immunity to hsp65 can cause autoimmune diabetes in mice and may be related to autoimmune arthritis in rats and humans, so immunity to hsp65 should be forbidden; yet healthy persons manifest T-cell responses to self-hsp65. The aim of this chapter is to explore the immunological dominance of hsp65 and its role in autoimmunity--benign and pernicious.
Efficacy of environmental measures to decrease the risk of hospital-acquired aspergillosis in patients hospitalised in haematology wards
Authors: P. Berthelot, P. Loulergue, H. Raberin, M. Turco, C. Mounier, R. Tran Manh Sung, F. Lucht, B. Pozzetto, D. Guyotat
Journal: Clinical Microbiology and Infection (2006)
Low- and high-dose fluticasone propionate in asthma; effects during and after treatment
Authors: N.H. Gershman, H.H. Wong, J.T. Liu, J.V. Fahy
Journal: European Respiratory Journal (2000)

The dose dependency of the effects of inhaled corticosteroids on markers of asthmatic airway inflammation have not been well studied. There is a need to study the dose/response effects on this inflammation. In order to determine the dose/response effects of fluticasone propionate (FP), 24 asthmatic subjects were randomized to low- (100 microg x day(-1)) or high-dose (1,000 microg x day(-1)) FP for six weeks followed by placebo for 3 weeks. During treatment, the median increase in forced expiratory volume in one second (FEV1)was 12% in the high-dose group (p&lt;0.05) and 10% in the low-dose group (p&lt;0.05) (p&gt;0.05 between groups); the median decrease in the percentage of sputum eosinophils was 93% in the high-dose group (p&lt;0.05) and 46% in the low-dose group (p&lt;0.05) (p&gt;0.05 between groups). Symptoms, salbutamol use, morning peak flow, provocative concentration of methacholine causing a 20% fall in FEV1 (PC20), sputum eosinophil cationic protein concentration and tryptase activity improved significantly in both groups (p&lt;0.05), but only the improvement in salbutamol use was greater in the high-dose group (p&lt;0.05). During the run-out, the improvements in FEV1 and PC20 were rapidly reversed in both groups, but the improvements in peak flow and tryptase activity persisted; the improvement in sputum eosinophil concentration persisted only in the high-dose group (p&lt;0.05). It was concluded that dose/response effects for FP are not easily demonstrable because low-dose FP is quite effective. For most outcomes, the effects of high- and low-dose FP are relatively short-lived after treatment is stopped. This finding raises questions about the extent to which inhaled corticosteroids are disease-modifying in asthma.
Optical Imaging of Cancer-Related Proteases Using Near-Infrared Fluorescence Matrix Metalloproteinase-Sensitive and Cathepsin B-Sensitive Probes
Authors: Ji Young Yhee, Sun Ah Kim, Heebeom Koo, Sohee Son, Ju Hee Ryu, In-Chan Youn, Kuiwon Choi, Ick Chan Kwon, Kwangmeyung Kim
Journal: Theranostics (2012)

Cathepsin B and matrix metalloproteinase (MMP) play key roles in tumor progression by controlled degradation of extracellular matrix. Consequently, these proteases have been attracted in cancer research, and many imaging probes utilizing these proteases have been developed. Our groups developed cathepsin B and MMP imaging nanoprobes based on polymer nanoparticle platform. Both cathepsin B and MMP imaging probes used near-infrared fluorescence (NIRF) dye and dark-quencher to for high sensitivity, and protease-sensitive peptide sequence in each probe authorized high specificity of the probes. We compared the bioactivities of cathepsin B and MMP sensitive probes in cancer-related environments to investigate the biological property of the probes. As a result, cathepsin B probe showed fluorescence recovery after the probe entered the cytoplasm. This property could be useful to evaluate the cytoplasmic targeted delivery by using probe-conjugated nanoparticles in vivo. On the other hand, MMP probe was superior in specificity in vivo and tissue study. This comparative study will provide precise information about peptide-based optical probes, and allow their proper application to cancer diagnosis.
Guest Authorship and Ghostwriting in Publications Related to Rofecoxib
Authors: Joseph S Ross, Kevin P Hill, David S Egilman, Harlan M Krumholz
Journal: JAMA (2008)

Authorship in biomedical publication provides recognition and establishes accountability and responsibility. Recent litigation related to rofecoxib provided a unique opportunity to examine guest authorship and ghostwriting, practices that have been suspected in biomedical publication but for which there is little documentation.To characterize different types and the extent of guest authorship and ghostwriting in 1 case study.Court documents originally obtained during litigation related to rofecoxib against Merck & Co Inc. Documents were created predominantly between 1996 and 2004. In addition, publicly available articles related to rofecoxib identified via MEDLINE.All documents were reviewed by one author, with selected review by coauthors, using an iterative process of review, discussion, and rereview of documents to identify information related to guest authorship or ghostwriting.Approximately 250 documents were relevant to our review. For the publication of clinical trials, documents were found describing Merck employees working either independently or in collaboration with medical publishing companies to prepare manuscripts and subsequently recruiting external, academically affiliated investigators to be authors. Recruited authors were frequently placed in the first and second positions of the authorship list. For the publication of scientific review papers, documents were found describing Merck marketing employees developing plans for manuscripts, contracting with medical publishing companies to ghostwrite manuscripts, and recruiting external, academically affiliated investigators to be authors. Recruited authors were commonly the sole author on the manuscript and offered honoraria for their participation. Among 96 relevant published articles, we found that 92% (22 of 24) of clinical trial articles published a disclosure of Merck's financial support, but only 50% (36 of 72) of review articles published either a disclosure of Merck sponsorship or a disclosure of whether the author had received any financial compensation from the company.This case-study review of industry documents demonstrates that clinical trial manuscripts related to rofecoxib were authored by sponsor employees but often attributed first authorship to academically affiliated investigators who did not always disclose industry financial support. Review manuscripts were often prepared by unacknowledged authors and subsequently attributed authorship to academically affiliated investigators who often did not disclose industry financial support.
β-Carotene Supplementation and Incidence of Cancer and Cardiovascular Disease: the Women's Health Study
Authors: I M Lee, N R Cook, J E Manson, J E Buring, C H Hennekens
Journal: JNCI Journal of the National Cancer Institute (1999)

In observational studies, individuals with high intakes of fruits and vegetables containing beta-carotene experience lower risks of developing cancer. However, the few randomized trials of beta-carotene supplementation show no overall benefits; some even suggest harm. This trial was designed to test the effects of beta-carotene supplementation in women.The Women's Health Study is a randomized, double-blind, placebo-controlled trial originally testing aspirin, vitamin E, and beta-carotene in the prevention of cancer and cardiovascular disease among 39 876 women aged 45 years or older. The beta-carotene component was terminated early after a median treatment duration of 2.1 years (range = 0.00-2. 72 years). Statistical tests were two-sided.Among women randomly assigned to receive beta-carotene (50 mg on alternate days; n = 19 939) or placebo (n =19 937), there were no statistically significant differences in incidence of cancer, cardiovascular disease, or total mortality after a median of 4.1 years (2.1 years' treatment plus another 2.0 years' follow-up). There were 378 cancers in the beta-carotene group and 369 cancers in the placebo group (relative risk [RR] = 1.03; 95% confidence interval [CI] = 0.89-1. 18). There were no statistically significant differences for any site-specific cancer or during years 1 and 2 combined and years 3 and up combined. For cardiovascular disease, there were no statistically significant differences for myocardial infarction (42 in the beta-carotene group versus 50 in the placebo group), stroke (61 versus 43), deaths from cardiovascular causes (14 versus 12), or the combined end point of these three events (116 versus 102; among women with more than one event, only the first was counted). Deaths from any cause were similar in the two groups (59 versus 55). Among smokers at baseline (13% of all women), there were no statistically significant differences in overall incidence of cancer (RR = 1.11; 95% CI = 0.78-1.58) or cardiovascular disease (RR = 1.01; 95% CI = 0. 62-1.63).Among apparently healthy women, there was no benefit or harm from beta-carotene supplementation for a limited period on the incidence of cancer and of cardiovascular disease.
Dual roles for immune metagenes in breast cancer prognosis and therapy prediction
Authors: Angela Alistar, Jeff W Chou, Srikanth Nagalla, Michael A Black, Ralph D’Agostino, Lance D Miller
Journal: Genome Medicine (2014)

Neoadjuvant chemotherapy for breast cancer leads to considerable variability in clinical responses, with only 10 to 20% of cases achieving complete pathologic responses (pCR). Biological and clinical factors that determine the extent of pCR are incompletely understood. Mounting evidence indicates that the patient's immune system contributes to tumor regression and can be modulated by therapies. The cell types most frequently observed with this association are effector tumor infiltrating lymphocytes (TILs), such as cytotoxic T cells, natural killer cells and B cells. We and others have shown that the relative abundance of TILs in breast cancer can be quantified by intratumoral transcript levels of coordinately expressed, immune cell-specific genes. Through expression microarray analysis, we recently discovered three immune gene signatures, or metagenes, that appear to reflect the relative abundance of distinct tumor-infiltrating leukocyte populations. The B/P (B cell/plasma cell), T/NK (T cell/natural killer cell) and M/D (monocyte/dendritic cell) immune metagenes were significantly associated with distant metastasis-free survival of patients with highly proliferative cancer of the basal-like, HER2-enriched and luminal B intrinsic subtypes.Given the histopathological evidence that TIL abundance is predictive of neoadjuvant treatment efficacy, we evaluated the therapy-predictive potential of the prognostic immune metagenes. We hypothesized that pre-chemotherapy immune gene signatures would be significantly predictive of tumor response. In a multi-institutional, meta-cohort analysis of 701 breast cancer patients receiving neoadjuvant chemotherapy, gene expression profiles of tumor biopsies were investigated by logistic regression to determine the existence of therapy-predictive interactions between the immune metagenes, tumor proliferative capacity, and intrinsic subtypes.By univariate analysis, the B/P, T/NK and M/D metagenes were all significantly and positively associated with favorable pathologic responses. In multivariate analyses, proliferative capacity and intrinsic subtype altered the significance of the immune metagenes in different ways, with the M/D and B/P metagenes achieving the greatest overall significance after adjustment for other variables.Gene expression signatures of infiltrating immune cells carry both prognostic and therapy-predictive value that is impacted by tumor proliferative capacity and intrinsic subtype. Anti-tumor functions of plasma B cells and myeloid-derived antigen-presenting cells may explain more variability in pathologic response to neoadjuvant chemotherapy than previously recognized.
Down-regulation of miR-675-5p contributes to tumor progression and development by targeting pro-tumorigenic GPR55 in non-small cell lung cancer
Authors: Dan He, Jun Wang, Chunfang Zhang, Bin Shan, Xiyun Deng, Bin Li, Yanwu Zhou, Wei Chen, Jidong Hong, Yang Gao, Zhuchu Chen, Chaojun Duan
Journal: Molecular Cancer (2015)

microRNAs are small noncoding RNAs that modulate a variety of cellular processes by regulating multiple targets, which can promote or inhibit the development of malignant behaviors. Accumulating evidence suggests that miR-675-5p plays important roles in human carcinogenesis. However, its precise biological role remains largely elusive. This study examined the role of miR-675-5p in non- small cell lung cancer (NSCLC). The expression of miR-675-5p was analyzed by real-time quantitative PCR (qRT-PCR). The effect of miR-675-5p on proliferation was evaluated through MTT and colony formation assays, and cell migration and invasion were evaluated through transwell assays. The expression of target proteins and downstream molecules was analyzed by western blotting and immunohistochemical staining. The luciferase reporter assay was used to assess the target genes of miR-675-5p in non-small cell lung cancer cells. The expression levels of miR-675-5p in NSCLC tissues were significantly reduced compared to those in adjacent non-cancerous tissues (P < 0.001). The expression of miR-675-5p in patients with non-small cell lung cancer had a negative correlation with lymph node metastasis (P < 0.01) and TNM stage (P < 0.05). Down-regulation of miR-675-5p promoted cell growth, proliferation, colony formation, invasion and migration, and promoted the tumorigenicity graft growth of nude mice in vivo (P < 0.01); whereas up-regulation of miR-675-5p had the contrary effects. The luciferase reporter assay showed that GPR55 was a direct target gene of miR-675-5p. Overexpression of miR-675-5p can lead to the down-regulation of GPR55 and its signaling pathway, whereas the effect can be reversed by down-regulation of miR-675-5p expression. miR-675-5p functions as a novel tumor suppressor in NSCLC and the anti-oncogenic activity may involve its inhibition of the target gene GPR55. These findings suggest the possibility for miR-675-5p as a therapeutic target in NSCLC.
Cyclooxygenase-2 Inhibition Induces Apoptosis Signaling via Death Receptors and Mitochondria in Hepatocellular Carcinoma
Authors: Michael A. Kern, Anke M. Haugg, Andreas F. Koch, Tobias Schilling, Kai Breuhahn, Henning Walczak, Binje Fleischer, Christian Trautwein, Christoph Michalski, Henning Schulze-Bergkamen, Helmut Friess, Wolfgang Stremmel, Peter H. Krammer, Peter Schirmacher, Martina Müller
Journal: Cancer Research (2006)

Abstract Inhibition of cyclooxygenase (COX)-2 elicits chemopreventive and therapeutic effects in solid tumors that are coupled with the induction of apoptosis in tumor cells. We investigated the mechanisms by which COX-2 inhibition induces apoptosis in hepatocellular carcinoma (HCC) cells. COX-2 inhibition triggered expression of the CD95, tumor necrosis factor (TNF)-R, and TNF-related apoptosis-inducing ligand (TRAIL)-R1 and TRAIL-R2 death receptors. Addition of the respective specific ligands further increased apoptosis, indicating that COX-2 inhibition induced the expression of functional death receptors. Overexpression of a dominant-negative Fas-associated death domain mutant reduced COX-2 inhibitor-mediated apoptosis. Furthermore, our findings showed a link between COX-2 inhibition and the mitochondrial apoptosis pathway. COX-2 inhibition led to a rapid down-regulation of myeloid cell leukemia-1 (Mcl-1), an antiapoptotic member of the Bcl-2 family, followed by translocation of Bax to mitochondria and cytochrome c release from mitochondria. Consequently, overexpression of Mcl-1 led to inhibition of COX-2 inhibitor-mediated apoptosis. Furthermore, blocking endogenous Mcl-1 function using a small-interfering RNA approach enhanced COX-2 inhibitor-mediated apoptosis. It is of clinical importance that celecoxib acted synergistically with chemotherapeutic drugs in the induction of apoptosis in HCC cells. The clinical relevance of these results is further substantiated by the finding that COX-2 inhibitors did not sensitize primary human hepatocytes toward chemotherapy-induced apoptosis. In conclusion, COX-2 inhibition engages different apoptosis pathways in HCC cells stimulating death receptor signaling, activation of caspases, and apoptosis originating from mitochondria. (Cancer Res 2006; 66(14): 7059-66)