tbuckley/cabot-search huggingface dataset:
Prevalence of Excessive Tearing in Women With Early Breast Cancer Receiving Adjuvant Docetaxel-Based Chemotherapy
Authors: Arlene Chan, Charles Su, Richard H. de Boer, Adam Gajdatsy
Journal: Journal of Clinical Oncology (2013)

To define the incidence and impact of tearing in patients receiving adjuvant docetaxel-based chemotherapy and assess for lacrimal duct obstruction (LDO) as a causative factor.Consecutive patients with early breast cancer recommended for docetaxel-based chemotherapy with no prior ocular symptoms were included. Before and after completion of chemotherapy, patients underwent lacrimal drainage evaluation by computed tomographic dacrocystography (CT-DCG) and ophthalmic assessment. Eye symptoms were assessed at baseline, during, and after completion of chemotherapy.Over a 22-month period, 100 patients were recruited. Asymptomatic LDO was present at baseline in 17% and 18% of patients, as assessed by ophthalmic review and CT-DCG, respectively. Overall, 86% of patients developed tearing, with no significant difference between those who did and did not have LDO (94% v 84%; P = .45). Blepharitis occurred in 37% and minor corneal epitheliopathy in 22% of patients, with neither condition predicting for the development of tearing. Impairment of visual activities was greatest after cycle one (70% of patients) but had decreased to < 5% by 4 months after treatment.Tearing occurs in the majority of patients receiving adjuvant docetaxel-based chemotherapy regimens and occurred similarly in patients with and without LDO. There was poor concordance between CT-DCG and ophthalmic examination in the detection of LDO. Tearing and other eye symptoms impaired visual activities, but in nearly all patients, both symptoms and functional impairment were mild and had resolved by 4 months after chemotherapy. Our study demonstrates docetaxel-related tearing is not caused by LDO, and as such, evaluation or stenting of the duct is not considered necessary.
Contribution to antimitochondrial antibody production: Cleavage of pyruvate dehydrogenase complex-E2 by apoptosis-related proteases
Authors: Shuji Matsumura, Judy Van De Water, Hiroto Kita, Ross L. Coppel, Takao Tsuji, Kazuhide Yamamoto, Aftab A. Ansari, Eric M. Gershwin
Journal: Hepatology (2002)

Patients with PBC produce a directed, specific response to a single immunodominant autoepitope of PDC-E2 within the inner lipoyl domain. In contrast, immunized animals react to multiple epitopes and rarely recognize the inner lipoyl domain. In other autoimmune diseases, apoptosis plays a critical role in antigen presentation; the caspases and granzyme B are the key proteases in the generation of autoepitopes. To determine the specific cleavage pattern of full-length recombinant PDC-E2, we performed in vitro digestion with caspases-3, -6, -8 and granzyme B. The resulting fragments were immunoblotted and probed with an extensive panel of monoclonal anti-PDC-E2 antibodies and sera from patients with PBC. Interestingly, on granzyme B digestion, PDC-E2 lost reactivity, suggesting the destruction of the immunodominant epitope. Because this site contains the major epitope for both B cells and T cells, it suggests that granzyme B is unlikely to be involved in generation of autoepitopes in primary biliary cirrhosis (PBC). In contrast, following treatment with the caspase enzymes, immunoreactive fragments were generated. Indeed, by confocal microscopy, activated caspase-3 is found in the marginal hepatocytes and bile ducts. Moreover, caspase-3 staining was strongest in the small intrahepatic bile ducts, the major site of tissue destruction in PBC. In conclusion, these data suggest that following apoptosis, the caspase family of proteolytic enzymes have the potential to generate immunogenic fragments that contribute to the autoantigen reservoir and the production of antimitochondrial antibodies. These findings are also consistent with the generation of an autoimmune response against an intracellular antigen that evades catabolism during apoptosis.
Evidence of a dominant role for low osmolality in the efficacy of cereal based oral rehydration solutions: studies in a model of secretory diarrhoea.
Authors: A V Thillainayagam, S Carnaby, J A Dias, M L Clark, M J Farthing
Journal: Gut (1993)

Clinical trials suggest that including naturally occurring complex carbohydrate in oral rehydration solutions (ORS) in place of glucose increases water absorption and reduces stool volume during acute diarrhoea. The mechanisms for this greater clinical efficacy has not been established. This study examined the ability of two hypotonic rice based ORS, RS-ORS (137 mOsm/kg) and RP-ORS (143 mOsm/kg), and HYPO-ORS (240 mOsm/kg) a glucose equivalent ORS, to effect water absorption by in vivo perfusion of normal and secreting rat small intestine. The results were compared with those for two widely used conventional hypertonic ORS, WHO-ORS (331 mOsm/kg) and UK-ORS (310 mOsm/kg). In the normal intestine, water absorption was similar from WHO-ORS (87.4 (45.1-124.6) microliters/min/g; median and interquartile range) and UK-ORS (57.6 (41.5-87)) but less than from the hypotonic solutions (p < 0.02); water absorption from RS-ORS (181.8 (168.5-193.8)) and RP-ORS (195.7 (179.3-207.9)) was similar but less than from HYPO-ORS (241.3 (230.6-279.7); p < 0.005). In the secreting intestine, all ORS reversed net secretion of fluid to net absorption; the hypotonic solutions, HYPO-ORS (105.2 (95.2-111)), RS-ORS (127.7 (118.3-169.4)) and RP-ORS (133.7 (122.1-174.5)), produced more water absorption (p < 0.005) than the hypertonic solutions WHO-ORS (47.1 (29-75.9)) and UK-ORS (24.9 (18.4-29.4)). The rice based ions promoted most water absorption in secreting intestine (p < 0.007). These data indicate that low osmolality is of primary importance in mediating the increased water absorption from cereal based ORS.
Results of the Two Incidence Screenings in the National Lung Screening Trial
Authors: Denise R. Aberle, Sarah DeMello, Christine D. Berg, William C. Black, Brenda Brewer, Timothy R. Church, Kathy L. Clingan, Fenghai Duan, Richard M. Fagerstrom, Ilana F. Gareen, Constantine A. Gatsonis, David S. Gierada, Amanda Jain, Gordon C. Jones, Irene Mahon, Pamela M. Marcus, Joshua M. Rathmell, JoRean Sicks
Journal: New England Journal of Medicine (2013)

The National Lung Screening Trial was conducted to determine whether three annual screenings (rounds T0, T1, and T2) with low-dose helical computed tomography (CT), as compared with chest radiography, could reduce mortality from lung cancer. We present detailed findings from the first two incidence screenings (rounds T1 and T2). We evaluated the rate of adherence of the participants to the screening protocol, the results of screening and downstream diagnostic tests, features of the lung-cancer cases, and first-line treatments, and we estimated the performance characteristics of both screening methods. At the T1 and T2 rounds, positive screening results were observed in 27.9% and 16.8% of participants in the low-dose CT group and in 6.2% and 5.0% of participants in the radiography group, respectively. In the low-dose CT group, the sensitivity was 94.4%, the specificity was 72.6%, the positive predictive value was 2.4%, and the negative predictive value was 99.9% at T1; at T2, the positive predictive value increased to 5.2%. In the radiography group, the sensitivity was 59.6%, the specificity was 94.1%, the positive predictive value was 4.4%, and the negative predictive value was 99.8% at T1; both the sensitivity and the positive predictive value increased at T2. Among lung cancers of known stage, 87 (47.5%) were stage IA and 57 (31.1%) were stage III or IV in the low-dose CT group at T1; in the radiography group, 31 (23.5%) were stage IA and 78 (59.1%) were stage III or IV at T1. These differences in stage distribution between groups persisted at T2. Low-dose CT was more sensitive in detecting early-stage lung cancers, but its measured positive predictive value was lower than that of radiography. As compared with radiography, the two annual incidence screenings with low-dose CT resulted in a decrease in the number of advanced-stage cancers diagnosed and an increase in the number of early-stage lung cancers diagnosed. (Funded by the National Cancer Institute; NLST ClinicalTrials.gov number, NCT00047385.).
The Two Faces of Janus: Sex Steroids as Mediators of Both Cell Proliferation and Cell Death
Authors: A. M. Soto, C. Sonnenschein
Journal: JNCI Journal of the National Cancer Institute (2001)

In this issue of the Journal, Song et al. (1) report that prolonged estrogen withdrawal in breast cancer cells results in the acquisition of an apoptotic response to 17 -estradiol; i.e., the very same hormone that mediates the proliferation of its target cells in the female genital tract and mammary glands is also able to trigger their death. In this editorial, we aim to integrate these experimental results, which are obviously relevant to the management of breast cancer, within a biologic perspective. The exploration of nature never ceases to surprise biologists. When adopting a narrow anthropocentric approach, we imagine nature as designed by a meticulous engineer. However, a more appropriate metaphor would be to imagine instead the workings of nature as the fruit of tinkering, or putting old devices to new uses. From this evolutionary perspective, it is conceivable that the same sex steroid hormones mediate the increase of cell numbers, the inhibition of cell proliferation, the inhibition of cell death, and the increase of cell death. In the 1970s, Bruchovsky et al. (2) showed that androgens, in addition to inhibiting cell death and inducing cell proliferation in the rat prostate in situ, inhibit prostate cell proliferation. The proliferative and inhibitory effects were dissociated temporarily; i.e., the latter event followed the former. Gorski and colleagues (3,4) described an equivalent effect by estrogens for the uterus and the pituitary gland.
Intercontinental comparison of patient cohorts: what can we learn from it?
Authors: P Schemmer, L Fischer, J Schmidt, M W Buchler
Journal: Gut (2007)

<h3>Objective</h3> The Collaborative Cross (CC) is a mouse population model with diverse and reproducible genetic backgrounds used to identify novel disease models and genes that contribute to human disease. Since spontaneous tumour susceptibility in CC mice remains unexplored, we assessed tumour incidence and spectrum. <h3>Design</h3> We monitored 293 mice from 18 CC strains for tumour development. Genetic association analysis and RNA sequencing were used to identify susceptibility loci and candidate genes. We analysed genomes of patients with gastric cancer to evaluate the relevance of genes identified in the CC mouse model and measured the expression levels of <i>ISG15</i> by immunohistochemical staining using a gastric adenocarcinoma tissue microarray. Association of gene expression with overall survival (OS) was assessed by Kaplan-Meier analysis. <h3>Results</h3> CC mice displayed a wide range in the incidence and types of spontaneous tumours. More than 40% of CC036 mice developed gastric tumours within 1 year. Genetic association analysis identified <i>Nf</i>κ<i>b1</i> as a candidate susceptibility gene, while RNA sequencing analysis of non-tumour gastric tissues from CC036 mice showed significantly higher expression of inflammatory response genes. In human gastric cancers, the majority of human orthologues of the 166 mouse genes were preferentially altered by amplification or deletion and were significantly associated with OS. Higher expression of the CC036 inflammatory response gene signature is associated with poor OS. Finally, ISG15 protein is elevated in gastric adenocarcinomas and correlated with shortened patient OS. <h3>Conclusions</h3> CC strains exhibit tremendous variation in tumour susceptibility, and we present CC036 as a spontaneous laboratory mouse model for studying human gastric tumourigenesis.
Tumor Stromal-Derived Factor-1 Recruits Vascular Progenitors to Mitotic Neovasculature, where Microenvironment Influences Their Differentiated Phenotypes
Authors: Manish Aghi, Kenneth S. Cohen, Rachael J. Klein, David T. Scadden, E. Antonio Chiocca
Journal: Cancer Research (2006)

Abstract Mechanisms underlying tumor vasculogenesis, the homing and engraftment of bone marrow–derived vascular progenitors, remain undefined. We hypothesized that tumor cell–secreted factors regulate vasculogenesis. We studied vasculogenic and nonvasculogenic intracranial murine gliomas. A PCR screen identified stromal-derived factor-1 (SDF-1/CXCL12) and vascular endothelial growth factor (VEGF) expression by vasculogenic glioma cells and spontaneously arising vasculogenic tumors in NF1+/−:Trp53+/− mice, but not by nonvasculogenic glioma cells. Enforced SDF-1, not VEGF, expression in nonvasculogenic cells caused vasculogenesis. Combined SDF-1 and VEGF expression augmented vasculogenesis over SDF-1 expression alone. Blocking SDF-1 receptor CXCR4 reduced short-term homing and long-term engraftment of vascular progenitors. Implanting tumor cells secreting SDF-1 was therefore necessary and sufficient to incorporate marrow-derived precursors into tumor endothelium. SDF-1 seemed to exert these effects by acting locally intratumorally and did not cause an efflux of marrow-derived progenitors into circulation. Tumor microenvironment determined additional fates of marrow-derived cells. Hypoxia, observed with ectopic s.c. murine tumors at levels approximating that of intracranial human glioblastoma, interacted with tumor-secreted SDF-1 to expand engrafted vascular progenitor differentiated phenotypes to include pericytes as well as endothelium. In contrast, less hypoxic orthotopic intracranial murine gliomas contained only marrow-derived endothelium without marrow-derived pericytes. Furthermore, we found that vasculogenesis is significant for tumors because it generates endothelium with a higher mitotic index than endothelium derived from local sources. Although CXCR4 blockade selectively targeted endothelium generated by vasculogenesis, completely inhibiting vessel formation may require combination therapy targeting locally derived and marrow-derived endothelium. (Cancer Res 2006; 66(18): 9054-64)
Not allowed to die.
Authors: W. S. Symmers
Journal: BMJ (1968)

Anti-idiotypic antibodies to four monoclonal IgM, one polyclonal IgM, and one polyclonal IgA rheumatoid factors were produced in rabbits and tested for cross reactivity with rheumatoid factors from nine patients with essential mixed cryoglobulinaemia, three patients with rheumatoid arthritis, four patients with systemic sicca syndrome, and one patient with systemic lupus erythematosus. Variable (3/16 to 10/16) cross reactivity for each anti-idiotypic antibody was observed which was not restricted by disease category, clonality, or isotype of the rheumatoid factor. These findings suggest that rheumatoid factor genes are highly conserved from the germ-line antibody repertoire.
Prognostic significance of received relative dose intensity in non-Hodgkin's lymphoma patients: Application to LNH-87 protocol
Authors: E. Lepage, C. Gisselbrecht, C. Haioun, C. Sebban, H. Tilly, A. Bosly, P. Morel, R. Herbrecht, F. Reyes, B. Coiffier
Journal: Annals of Oncology (1993)
Replication of association between FAM167A(C8orf13)-BLK region and rheumatoid arthritis in a Japanese population
Authors: I. Ito, A. Kawasaki, S. Ito, Y. Kondo, M. Sugihara, M. Horikoshi, T. Hayashi, D. Goto, I. Matsumoto, A. Tsutsumi, Y. Takasaki, H. Hashimoto, K. Matsuta, T. Sumida, N. Tsuchiya
Journal: Annals of the Rheumatic Diseases (2009)

Polymorphisms in the genomic region encoding B lymphoid tyrosine kinase ( BLK ) and family with sequence similarity 167, member A ( FAM167A , also referred to as C8orf13 ) at 8p23.1 have been associated with systemic lupus erythematosus (SLE) in Caucasian1 2 and Asian3 4 populations. A recent genome-wide study in a north American population showed new associations with rheumatoid arthritis (RA), among which was a single nucleotide polymorphism (SNP) rs2736340 in the intergenic region of BLK and FAM167A .5 In the HapMap Japanese samples (http://www.hapmap.org/index.html.ja), this SNP is in absolute linkage disequilibrium ( r 2=1) with rs13277113, previously associated with SLE.1,–,4 We have shown that the population frequency of the risk genotype rs13277113A/A and the OR for SLE …
(31) Case for diagnosis. Pustular dermatosis of scalp
Authors: J.L. Burton
Journal: British Journal of Dermatology (1977)

Journal Article (31) Case for diagnosis. Pustular dermatosis of scalp Get access J.L. Burton J.L. Burton Bristol Royal Infirmary Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 97, Issue s15, 1 December 1977, Pages 67–68, https://doi.org/10.1111/j.1365-2133.1977.tb14339.x Published: 01 December 1977
Mutations in the unfolded protein response regulator ATF6 cause the cone dysfunction disorder achromatopsia
Authors: Susanne Kohl, Ditta Zobor, Wei-Chieh Chiang, Nicole Weisschuh, Jennifer Staller, Irene Gonzalez Menendez, Stanley Chang, Susanne C Beck, Marina Garcia Garrido, Vithiyanjali Sothilingam, Mathias W Seeliger, Franco Stanzial, Francesco Benedicenti, Francesca Inzana, Elise Héon, Ajoy Vincent, Jill Beis, Tim M Strom, Günther Rudolph, Susanne Roosing, Anneke I den Hollander, Frans P M Cremers, Irma Lopez, Huanan Ren, Anthony T Moore, Andrew R Webster, Michel Michaelides, Robert K Koenekoop, Eberhart Zrenner, Randal J Kaufman, Stephen H Tsang, Bernd Wissinger, Jonathan H Lin
Journal: Nature Genetics (2015)
Focal nodular hyperplasia of the liver in men: is presentation the same in men and women?
Authors: A Luciani
Journal: Gut (2002)

Focal nodular hyperplasia (FNH) of the liver is a benign hepatic lesion relatively common in women. No studies specifically designed to describe the presentation and imaging findings in males have been published.The aims of this study were: (a) to describe the clinical and imaging findings in 18 men with FNH, and (b) to compare these data with those observed in 216 women with FNH observed during the same nine year period.According to a final diagnosis of FNH assessed either by pathological examination or by magnetic resonance (MR), the medical charts of 18 men with FNH observed at our institution were reviewed. In order to compare clinical and MR presentations, the files of 216 women with a total of 291 FNH lesions, investigated during the same nine year period, were reviewed.Eighteen FNH lesions, with a mean diameter of 37.5 mm, were demonstrated in the 18 male patients. A total of 291 lesions with a mean diameter of 63.4 mm were comparatively demonstrated in 216 female patients. Mean age at diagnosis was significantly higher in men (p<0.01) and mean FNH size was significantly smaller in men (p<0.001). Surgery was more frequently performed in men (72.2%) than in women (16.7%) (p<0.001).Our data indicate that FNH is rare in men and that the lesions are smaller and more often atypical than those in women.
Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke
Authors: Céline Bellenguez, Steve Bevan, Andreas Gschwendtner, Chris C A Spencer, Annette I Burgess, Matti Pirinen, Caroline A Jackson, Matthew Traylor, Amy Strange, Zhan Su, Gavin Band, Paul D Syme, Rainer Malik, Joanna Pera, Bo Norrving, Robin Lemmens, Colin Freeman, Renata Schanz, Tom James, Deborah Poole, Lee Murphy, Helen Segal, Lynelle Cortellini, Yu-Ching Cheng, Daniel Woo, Michael A Nalls, Bertram Müller-Myhsok, Christa Meisinger, Udo Seedorf, Helen Ross-Adams, Steven Boonen, Dorota Wloch-Kopec, Valerie Valant, Julia Slark, Karen Furie, Hossein Delavaran, Cordelia Langford, Panos Deloukas, Sarah Edkins, Sarah Hunt, Emma Gray, Serge Dronov, Leena Peltonen, Solveig Gretarsdottir, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Kari Stefansson, Giorgio B Boncoraglio, Eugenio A Parati, John Attia, Elizabeth Holliday, Chris Levi, Maria-Grazia Franzosi, Anuj Goel, Anna Helgadottir, Jenefer M Blackwell, Elvira Bramon, Matthew A Brown, Juan P Casas, Aiden Corvin, Audrey Duncanson, Janusz Jankowski, Christopher G Mathew, Colin N A Palmer, Robert Plomin, Anna Rautanen, Stephen J Sawcer, Richard C Trembath, Ananth C Viswanathan, Nicholas W Wood, Bradford B Worrall, Steven J Kittner, Braxton D Mitchell, Brett Kissela, James F Meschia, Vincent Thijs, Arne Lindgren, Mary Joan Macleod, Agnieszka Slowik, Matthew Walters, Jonathan Rosand, Pankaj Sharma, Martin Farrall, Cathie L M Sudlow, Peter M Rothwell, Martin Dichgans, Peter Donnelly, Hugh S Markus
Journal: Nature Genetics (2012)
Apelin, the Novel Endogenous Ligand of the Orphan Receptor APJ, Regulates Cardiac Contractility
Authors: István Szokodi, Pasi Tavi, Gábor Földes, Sari Voutilainen-Myllylä, Mika Ilves, Heikki Tokola, Sampsa Pikkarainen, Jarkko Piuhola, Jaana Rysä, Miklós Tóth, Heikki Ruskoaho
Journal: Circulation Research (2002)

The orphan receptor APJ and its recently identified endogenous ligand, apelin, exhibit high levels of mRNA expression in the heart. However, the functional importance of apelin in the cardiovascular system is not known. In isolated perfused rat hearts, infusion of apelin (0.01 to 10 nmol/L) induced a dose-dependent positive inotropic effect (EC 50 : 33.1±1.5 pmol/L). Moreover, preload-induced increase in dP/dt max was significantly augmented ( P &lt;0.05) in the presence of apelin. Inhibition of phospholipase C (PLC) with U-73122 and suppression of protein kinase C (PKC) with staurosporine and GF-109203X markedly attenuated the apelin-induced inotropic effect ( P &lt;0.001). In addition, zoniporide, a selective inhibitor of Na + -H + exchange (NHE) isoform-1, and KB-R7943, a potent inhibitor of the reverse mode Na + -Ca 2+ exchange (NCX), significantly suppressed the response to apelin ( P &lt;0.001). Perforated patch-clamp recordings showed that apelin did not modulate L-type Ca 2+ current or voltage-activated K + currents in isolated adult rat ventricular myocytes. Apelin mRNA was markedly downregulated in cultured neonatal rat ventricular myocytes subjected to mechanical stretch and in vivo in two models of chronic ventricular pressure overload. The present study provides the first evidence for the physiological significance of apelin in the heart. Our results show that apelin is one of the most potent endogenous positive inotropic substances yet identified and that the inotropic response to apelin may involve activation of PLC, PKC, and sarcolemmal NHE and NCX.
Isoniazid conjugated poly(lactide-co-glycolide): Long-term controlled drug release and tissue regeneration for bone tuberculosis therapy
Authors: Da Huang, Dawei Li, Tiantian Wang, Hong Shen, Pei Zhao, Baoxia Liu, Yezi You, Yuanzheng Ma, Fei Yang, Decheng Wu, Shenguo Wang
Journal: Biomaterials (2015)