tbuckley/cabot-search huggingface dataset:
Cytoprotective Effects of Hypoxia against Cisplatin-Induced Tubular Cell Apoptosis
Authors: Jinzhao Wang, Mangatt P. Biju, Mong-Heng Wang, Volker H. Haase, Zheng Dong
Journal: Journal of the American Society of Nephrology (2006)

Hypoxia that is caused by vascular defects or disruption is commonly associated with renal diseases. During cisplatin nephrotoxicity, hypoxic regions are identified in the outer medulla and the renal cortex. However, the regulation of cisplatin injury by hypoxia is unclear. Previous work has demonstrated the cytoprotective effects of hypoxia against apoptotic injury. This study further examines the cytoprotective mechanisms in models of cisplatin-induced tubular cell apoptosis. In cultured renal tubular cells, 20 microM cisplatin induced approximately 60% apoptosis within 16 h. The rate of apoptosis was suppressed to < 20%, when the incubation was conducted under hypoxia (2% O2). Mitochondrial events of apoptosis, namely Bax accumulation and cytochrome c release, also were ameliorated. During cisplatin treatment, cell ATP was maintained in both normoxic and hypoxic cells. Hypoxic incubation lowered extracellular pH, but prevention of the pH decrease did not restore cisplatin-induced apoptosis. The cytoprotective effects of hypoxia also were independent of hypoxia-inducible factor 1 (HIF-1). Cobalt, as hypoxia, activated HIF-1 yet did not suppress cisplatin-induced apoptosis. Moreover, hypoxia suppressed cisplatin-induced apoptosis in HIF-1-deficient mouse embryonic stem cells and renal proximal tubular cells. Conversely, mitochondrial inhibitors, particularly inhibitors of respiration complex III (antimycin A and myxothiazol), mimicked hypoxia in apoptosis suppression. The effects of hypoxia and mitochondrial inhibitors were not additive. It is interesting that both hypoxia and complex III inhibitors ameliorated cisplatin-induced p53 activation. Therefore, the cytoprotective effects of hypoxia are independent of changes in cell ATP, pH, or HIF but may involve mitochondrial inhibition and the suppression of p53.
A phase II study of bevacizumab, oxaliplatin, and docetaxel in locally advanced and metastatic gastric and gastroesophageal junction cancers
Authors: B.F. El-Rayes, M. Zalupski, T. Bekai-Saab, L.K. Heilbrun, N. Hammad, B. Patel, S. Urba, A.F. Shields, U. Vaishampayan, S. Dawson, K. Almhanna, D. Smith, P.A. Philip
Journal: Annals of Oncology (2010)
EndoPredict improves the prognostic classification derived from common clinical guidelines in ER-positive, HER2-negative early breast cancer
Authors: P. Dubsky, M. Filipits, R. Jakesz, M. Rudas, C.F. Singer, R. Greil, O. Dietze, I. Luisser, E. Klug, R. Sedivy, M. Bachner, D. Mayr, M. Schmidt, M.C. Gehrmann, C. Petry, K.E. Weber, R. Kronenwett, J.C. Brase, M. Gnant
Journal: Annals of Oncology (2012)

In early estrogen receptor (ER)-positive/HER2-negative breast cancer, the decision to administer chemotherapy is largely based on prognostic criteria. The combined molecular/clinical EndoPredict test (EPclin) has been validated to accurately assess prognosis in this population. In this study, the clinical relevance of EPclin in relation to well-established clinical guidelines is assessed.We assigned risk groups to 1702 ER-positive/HER2-negative postmenopausal women from two large phase III trials treated only with endocrine therapy. Prognosis was assigned according to National Comprehensive Cancer Center Network-, German S3-, St Gallen guidelines and the EPclin. Prognostic groups were compared using the Kaplan-Meier survival analysis.After 10 years, absolute risk reductions (ARR) between the high- and low-risk groups ranged from 6.9% to 11.2% if assigned according to guidelines. It was at 18.7% for EPclin. EPclin reassigned 58%-61% of women classified as high-/intermediate-risk (according to clinical guidelines) to low risk. Women reclassified to low risk showed a 5% rate of distant metastasis at 10 years.The EPclin score is able to predict favorable prognosis in a majority of patients that clinical guidelines would assign to intermediate or high risk. EPclin may reduce the indications for chemotherapy in ER-positive postmenopausal women with a limited number of clinical risk factors.
On Blaps Mortisaga as a Human Parasite
Authors: T. S. Cobbold
Journal: BMJ (1877)

THE BRITISH MED ICAL '7OURNAL.[April 7, T877.with the skull is well heard in the left ear, and increased by closure of the meatus.He thinks he can hear it in the right ear, but it is not increased by closing the meatus.He has continuous tinnitus in the right ear.When at his best, the noise is like a " dull buzzing"; but,
Improved outcomes of pediatric dilated cardiomyopathy with utilization of heart transplantation
Authors: Anna E. Tsirka, Kathryn Trinkaus, Su-Chiung Chen, Steven E. Lipshultz, Jeffrey A. Towbin, Steven D. Colan, Vernat Exil, Arnold W. Strauss, Charles E. Canter
Journal: Journal of the American College of Cardiology (2004)
Is Baseline Quality of Life Useful for Predicting Survival With Hormone-Refractory Prostate Cancer? A Pooled Analysis of Three Studies of the European Organisation for Research and Treatment of Cancer Genitourinary Group
Authors: Laurence Collette, George van Andel, Andrew Bottomley, Gosse O.N. Oosterhof, Walter Albrecht, Theo M. de Reijke, Sophie D. Fossà
Journal: Journal of Clinical Oncology (2004)

Purpose Patients with symptomatic metastatic hormone-resistant prostate cancer (HRPC) survive a median of 10 months and are often regarded as a homogeneous group. Few prognostic factors have been identified so far. We examined whether baseline health-related quality of life (HRQOL) parameters assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) were independent prognostic factors of survival and whether they bring extra precision to the predictions achievable with models based on clinical and biochemical factors only. Patients and Methods Data of 391 symptomatic (bone) metastatic HRPC patients from three randomized EORTC trials were used in multivariate Cox proportional hazards models. The significance level was set at α = .05. Results Of the 391 patients, 371 died, most of prostate cancer. Bone scan result, performance status, hemoglobin level, and insomnia and appetite loss as measured by the EORTC QLQ-C30 were independent predictors of survival. This model's area under the receiver operating curve was 0.65 compared with 0.63 without the two HRQOL factors. Conclusion Certain HRQOL sores, at baseline, seem to be predictors for duration of survival in HRPC. However, such measurements do not add to the predictive ability of models based only on clinical and biochemical factors.
Disease activity indexes in rheumatoid arthritis; a prospective, comparative study with thermography.
Authors: M D Devereaux, G R Parr, D P Thomas, B L Hazleman
Journal: Annals of the Rheumatic Diseases (1985)

There are many difficulties associated with the assessment of disease activity in rheumatoid arthritis. Infrared thermography has been used to quantify joint inflammation. The heat distribution index (HDI) is reproducible, sensitive, quantifiable, and not subject to circadian variation or interobserver error. In this study the HDIs for both elbows, wrists, knees, and ankles were summated and compared with other parameters of disease activity. There were 167 sets of observations in 20 patients with classical, seropositive, rheumatoid arthritis followed up over 12 months. There was a significant correlation (p less than 0.001) for thermography with the Ritchie articular index, Mallya score, grip strength, morning stiffness, erythrocyte sedimentation rate, and pain score. Significant correlations (p less than 0.05) for thermography with these parameters were found in individual patients. The summated HDI is a suitable, objective method for the assessment of response to therapy in patients with rheumatoid arthritis.
Human adipose-derived mesenchymal stem cells reduce inflammatory and T cell responses and induce regulatory T cells in vitro in rheumatoid arthritis
Authors: E Gonzalez-Rey, M A Gonzalez, N Varela, F O’Valle, P Hernandez-Cortes, L Rico, D Büscher, M Delgado
Journal: Annals of the Rheumatic Diseases (2009)

Objectives: Adult mesenchymal stem cells were recently found to suppress effector T cell and inflammatory responses and have emerged as attractive therapeutic candidates for immune disorders. In rheumatoid arthritis (RA), a loss in the immunological self-tolerance causes the activation of autoreactive T cells against joint components and subsequent chronic inflammation. The aim of this study is to characterise the immunosuppressive activity of human adipose-derived mesenchymal stem cells (hASCs) on collagen-reactive T cells from patients with RA. Methods: The effects of hASCs on collagen-reactive RA human T cell proliferation and cytokine production were investigated, as well as effects on the production of inflammatory mediators by monocytes and fibroblast-like synoviocytes from patients with RA. Results: hASCs suppressed the antigen-specific response of T cells from patients with RA. hASCs inhibited the proliferative response and the production of inflammatory cytokines by collagen-activated CD4 and CD8 T cells. In contrast, the numbers of IL10-producing T cells and monocytes were significantly augmented upon hASC treatment. The suppressive activity of hASCs was cell-to-cell contact dependent and independent. hASCs also stimulated the generation of FoxP3 protein-expressing CD4 + CD25 + regulatory T cells, with the capacity to suppress collagen-specific T cell responses. Finally, hASCs downregulated the inflammatory response and the production of matrix-degrading enzymes by synovial cells isolated from patients with RA. Conclusions: The present work identifies hASCs as key regulators of immune tolerance, with the capacity to suppress T cell and inflammatory responses and to induce the generation/activation of antigen-specific regulatory T cells.
<i>RRIG1</i> Mediates Effects of Retinoic Acid Receptor β2 on Tumor Cell Growth and Gene Expression through Binding to and Inhibition of RhoA
Authors: Zheng D. Liang, Scott M. Lippman, Tsung-Teh Wu, Reuben Lotan, Xiao-Chun Xu
Journal: Cancer Research (2006)

Abstract The expression of retinoic acid receptor β2 (RAR-β2) is frequently lost in various cancers and their premalignant lesions. However, the restoration of RAR-β2 expression inhibits tumor cell growth and suppresses cancer development. To understand the molecular mechanisms responsible for this RAR-β2-mediated antitumor activity, we did restriction fragment differential display-PCR and cloned a novel retinoid receptor–induced gene 1 (RRIG1), which is differentially expressed in RAR-β2-positive and RAR-β2-negative tumor cells. RRIG1 cDNA contains 2,851 bp and encodes a protein with 276 amino acids; the gene is localized at chromosome 9q34. Expressed in a broad range of normal tissues, RRIG1 is also lost in various cancer specimens. RRIG1 mediates the effect of RAR-β2 on cell growth and gene expression (e.g., extracellular signal–regulated kinase 1/2 and cyclooxygenase-2). The RRIG1 protein is expressed in the cell membrane and binds to and inhibits the activity of a small GTPase RhoA. Whereas induction of RRIG1 expression inhibits RhoA activation and f-actin formation and consequently reduces colony formation, invasion, and proliferation of esophageal cancer cells, antisense RRIG1 increases RhoA activity and f-actin formation and thus induces the colony formation, invasion, and proliferation of these cells. Our findings therefore show a novel molecular pathway involving RAR-β2 regulation of RRIG1 expression and RRIG1-RhoA interaction. An understanding of this pathway may translate into better control of human cancer. (Cancer Res 2006; 66(14): 7111-8)
Sphingosine kinase 1 expressed by endothelial colony-forming cells has a critical role in their revascularization activity
Authors: Stéphane Poitevin, Daniel Cussac, Aurélie S. Leroyer, Virginie Albinet, Gabrielle Sarlon-Bartoli, Benjamin Guillet, Lucas Hubert, Nathalie Andrieu-Abadie, Bettina Couderc, Angelo Parini, Françoise Dignat-George, Florence Sabatier
Journal: Cardiovascular Research (2014)

Cell therapy based on endothelial colony-forming cells (ECFCs) is a promising option for ischaemic cardiovascular diseases. A better understanding of the mechanisms by which these cells promote revascularization remains a critical challenge to improving their therapeutic potential. We aimed to identify the critical mechanisms involved in the revascularization activity of ECFCs by using the paracrine properties of mesenchymal stem cells (MSC).Conditioned medium from human bone marrow-derived MSCs (MSC-CM) increased the angiogenic activity of cord blood ECFCs in vitro (proliferation, migration, and pseudo-tube formation), the survival of ECFCs in mice (Matrigel Plug assay), and the capacity of ECFCs to promote the recovery of blood perfusion in mice with hindlimb ischaemia. Furthermore, the capillary density in ischaemic gastrocnemius muscle was significantly increased in mice transplanted with the ECFCs pre-treated with the MSC-CM. The enhancement of ECFCs activity involved the up-regulation of sphingosine kinase 1 (SphK1) expression and activity. The inhibition of SphK1 in ECFCs by using an inhibitor or a siRNA knockdown of SphK1 prevented the stimulation of the ECFCs induced by the MSC-CM. The improvement of ECFC activity by MSC-CM also involved the up-regulation of sphingosine-1-phosphate receptor 1 (S1P1) and a S1P/S1P1/3-dependent mechanism. Finally, we showed that the stimulation of ECFCs with exogenous S1P increased angiogenesis and promoted blood perfusion in hindlimb ischaemia.The up-regulation of SphK1 and S1P-dependent pathways is critical for the angiogenic/vasculogenic activity of ECFCs. The identification of this pathway provides attractive targets to optimize cell-based therapy for revascularization in ischaemic diseases.
Pseudo-obstruction of the Large Bowel
Authors: K. B. Orr
Journal: BMJ (1970)

There is supporting evidence that bradyarrhythmias and ventricular fibrillation are the cause of most of the early deaths following infarction.In order to reduce this very high prehospital mortality, it is suggested that the general practitioner should visit the patient as soon as possible, cutting down the admission delay, and that he should try to treat not only pain and dysrhythmias, but also left ventricular failure with digoxin and frusemide if it is severe, or with frusemide alone if it is mild.The accompanying letter should contain information about the medical history of the patient, and the treatment given to the patient at home, with drugs, dosage, route of administration, and the exact time given.
Metal complexes of Meloxicam and Isoxicam decrease viability and proliferation of virus-transformed cancer cells
Authors: T. Zhivkova, R. Alexandrova, L. Dyakova, M. Georgieva, G. Miloshev, D.-C. Culita, G. Marinescu, L. Patron, M. Alexandrov
Journal: Annals of Oncology (2015)
Pathologic Findings at Risk-Reducing Salpingo-Oophorectomy: Primary Results From Gynecologic Oncology Group Trial GOG-0199
Authors: Mark E. Sherman, Marion Piedmonte, Phuong L. Mai, Olga B. Ioffe, Brigitte M. Ronnett, Linda Van Le, Iouri Ivanov, Maria C. Bell, Stephanie V. Blank, Paul DiSilvestro, Chad A. Hamilton, Krishnansu S. Tewari, Katie Wakeley, Noah D. Kauff, S. Diane Yamada, Gustavo Rodriguez, Steven J. Skates, David S. Alberts, Joan L. Walker, Lori Minasian, Karen Lu, Mark H. Greene
Journal: Journal of Clinical Oncology (2014)

Risk-reducing salpingo-oophorectomy (RRSO) lowers mortality from ovarian/tubal and breast cancers among BRCA1/2 mutation carriers. Uncertainties persist regarding potential benefits of RRSO among high-risk noncarriers, optimal surgical age, and anatomic origin of clinically occult cancers detected at surgery. To address these topics, we analyzed surgical treatment arm results from Gynecologic Oncology Group Protocol-0199 (GOG-0199), the National Ovarian Cancer Prevention and Early Detection Study.This analysis included asymptomatic high-risk women age ≥ 30 years who elected RRSO at enrollment. Women provided risk factor data and underwent preoperative cancer antigen 125 (CA-125) serum testing and transvaginal ultrasound (TVU). RRSO specimens were processed according to a standardized tissue processing protocol and underwent central pathology panel review. Research-based BRCA1/2 mutation testing was performed when a participant's mutation status was unknown at enrollment. Relationships between participant characteristics and diagnostic findings were assessed using univariable statistics and multivariable logistic regression.Invasive or intraepithelial ovarian/tubal/peritoneal neoplasms were detected in 25 (2.6%) of 966 RRSOs (BRCA1 mutation carriers, 4.6%; BRCA2 carriers, 3.5%; and noncarriers, 0.5%; P < .001). In multivariable models, positive BRCA1/2 mutation status (P = .0056), postmenopausal status (P = .0023), and abnormal CA-125 levels and/or TVU examinations (P < .001) were associated with detection of clinically occult neoplasms at RRSO. For 387 women with negative BRCA1/2 mutation testing and normal CA-125 levels, findings at RRSO were benign.Clinically occult cancer was detected among 2.6% of high-risk women undergoing RRSO. BRCA1/2 mutation, postmenopausal status, and abnormal preoperative CA-125 and/or TVU were associated with cancer detection at RRSO. These data can inform management decisions among women at high risk of ovarian/tubal cancer.
Monitoring global health: time for new solutions
Authors: Christopher J L Murray, Alan D Lopez, Suwit Wibulpolprasert
Journal: BMJ (2004)

<i>Improved global health monitoring requires new technologies and methods, strengthened national capacity, norms and standards, and gold standard global reporting. The World Health Organization9s many functions limit its capacity for global reporting, and a new global health monitoring organisation is needed to provide independent gold standard health information to the world</i>
A young boy with a large hemifacial plaque with histopathologic features of trichoepithelioma
Authors: Dennis H. Oh, Alfred T. Lane, Andrew E. Turk, Sabine Kohler
Journal: Journal of the American Academy of Dermatology (1997)

Trichoepitheliomas commonly appear as sporadic solitary lesions or, more rarely, as multiple lesions that are often dominantly inherited. We describe an 8-year-old boy with multiple facial papules that coalesced into a large plaque. This presentation of multiple trichoepitheliomas may represent an unusual type of nevus.
Dynamic and Widespread lncRNA Expression in a Sponge and the Origin of Animal Complexity
Authors: Federico Gaiti, Selene L. Fernandez-Valverde, Nagayasu Nakanishi, Andrew D. Calcino, Itai Yanai, Milos Tanurdzic, Bernard M. Degnan
Journal: Molecular Biology and Evolution (2015)

Long noncoding RNAs (lncRNAs) are important developmental regulators in bilaterian animals. A correlation has been claimed between the lncRNA repertoire expansion and morphological complexity in vertebrate evolution. However, this claim has not been tested by examining morphologically simple animals. Here, we undertake a systematic investigation of lncRNAs in the demosponge Amphimedon queenslandica, a morphologically simple, early-branching metazoan. We combine RNA-Seq data across multiple developmental stages of Amphimedon with a filtering pipeline to conservatively predict 2,935 lncRNAs. These include intronic overlapping lncRNAs, exonic antisense overlapping lncRNAs, long intergenic nonprotein coding RNAs, and precursors for small RNAs. Sponge lncRNAs are remarkably similar to their bilaterian counterparts in being relatively short with few exons and having low primary sequence conservation relative to protein-coding genes. As in bilaterians, a majority of sponge lncRNAs exhibit typical hallmarks of regulatory molecules, including high temporal specificity and dynamic developmental expression. Specific lncRNA expression profiles correlate tightly with conserved protein-coding genes likely involved in a range of developmental and physiological processes, such as the Wnt signaling pathway. Although the majority of Amphimedon lncRNAs appears to be taxonomically restricted with no identifiable orthologs, we find a few cases of conservation between demosponges in lncRNAs that are antisense to coding sequences. Based on the high similarity in the structure, organization, and dynamic expression of sponge lncRNAs to their bilaterian counterparts, we propose that these noncoding RNAs are an ancient feature of the metazoan genome. These results are consistent with lncRNAs regulating the development of animals, regardless of their level of morphological complexity.
Cytogenetics of Childhood Acute Myeloid Leukemia: United Kingdom Medical Research Council Treatment Trials AML 10 and 12
Authors: Christine J. Harrison, Robert K. Hills, Anthony V. Moorman, David J. Grimwade, Ian Hann, David K.H. Webb, Keith Wheatley, Siebold S.N. de Graaf, Eva van den Berg, Alan K. Burnett, Brenda E.S. Gibson
Journal: Journal of Clinical Oncology (2010)

Karyotype is an independent indicator of prognosis in acute myeloid leukemia (AML) that is widely applied to risk-adapted therapy. Because AML is rare in children, the true prognostic significance of individual chromosomal abnormalities in this age group remains unclear.This cytogenetic study of 729 childhood patients classified them into 22 subgroups and evaluated their incidence and risk.Rearrangements of 11q23 were the most frequent abnormality found in approximately 16% of patients, with 50% of these in infants. The outcome for all patients with 11q23 abnormalities was intermediate; no difference was observed for those with t(9;11)(p21-22;q23). The core binding factor leukemias with the translocations t(8;21)(q22;q22) and inv(16)(p13q22) occurred at incidences of 14% and 7%, respectively, predominantly in older children, and their prognosis was favorable. An adverse outcome was observed in patients with monosomy 7, abnormalities of 5q, and t(6;9)(p23;q34). Abnormalities of 3q and complex karyotypes, in the absence of favorable-risk features, have been associated with an adverse outcome in adults, but the results were not significant in this childhood series. However, the presence of 12p abnormalities predicted a poor outcome.Because the spectrum of chromosomal changes and their risk association seem to differ between children and adults with AML, biologic differences are emerging, which will contribute to the redefinition of risk stratification for different age groups in the future.
Isolation of Homeodomain–Leucine Zipper Genes from the Moss Physcomitrella patens and the Evolution of Homeodomain–Leucine Zipper Genes in Land Plants
Authors: Keiko Sakakibara, Tomoaki Nishiyama, Masahiro Kato, Mitsuyasu Hasebe
Journal: Molecular Biology and Evolution (2001)

Homeobox genes encode transcription factors involved in many aspects of developmental processes.The homeodomain-leucine zipper (HD-Zip) genes, which are characterized by the presence of both a homeodomain and a leucine zipper motif, form a clade within the homeobox superfamily and were previously reported only from vascular plants.Here we report the isolation of 10 HD-Zip genes (named Pphb1-Pphb10) from the moss Physcomitrella patens.Based on a phylogenetic analysis of the 10 Pphb genes and previously reported vascular plant HD-Zip genes, all of the Pphb genes except Pphb3 belong to three of the four HD-Zip subfamilies (HD-Zip I, II, and III), indicating that these subfamilies originated before the divergence of the vascular plant and moss lineages.Pphb3 is sister to the HD-Zip II subfamily and has some distinctive characteristics, including the difference of the a 1 and d 1 sites of its leucine zipper motif, which are well conserved in each HD-Zip subfamily.Comparison of the genetic divergence of representative HD-Zip I and II genes showed that the evolutionary rate of HD-Zip I genes was faster than that of HD-Zip II genes.