tbuckley/cabot-search huggingface dataset:
Identification of Patients With Prostate Cancer Who Benefit From Immediate Postoperative Radiotherapy: EORTC 22911
Authors: Theodorus H van Der Kwast, Michel Bolla, Hein van Poppel, Paul van Cangh, Kris Vekemans, Luigi da Pozzo, Jean-Francois Bosset, Karl H Kurth, Fritz H Schröder, Laurence Collette, Non Renseigné
Journal: Journal of Clinical Oncology (2007)

Purpose The randomized controlled European Organisation for Research and Treatment of Cancer (EORTC) trial 22911 studied the effect of radiotherapy after prostatectomy in patients with adverse risk factors. Review pathology data of specimens from participants in this trial were analyzed to identify which factors predict increased benefit from adjuvant radiotherapy. Patients and Methods After prostatectomy, 1,005 patients with stage pT3 and/or positive surgical margins were randomly assigned to a wait-and-see (n = 503) and an adjuvant radiotherapy (60 Gy conventional irradiation) arm (n = 502). Pathologic review data were available for 552 patients from 11 participating centers. The interaction between the review pathology characteristics and treatment benefit was assessed by log-rank test for heterogeneity (P &lt; .05). Results Margin status assessed by review pathology was the strongest predictor of prolonged biochemical disease-free survival with immediate postoperative radiotherapy (heterogeneity, P &lt; .01): by year 5, immediate postoperative irradiation could prevent 291 events/1,000 patients with positive margins versus 88 events/1,000 patients with negative margins. The hazard ratio for immediate irradiation was 0.38 (95% CI, 0.26 to 0.54) and 0.88 (95% CI, 0.53 to 1.46) in the groups with positive and negative margins, respectively. We could not identify a significant impact of the positive margin localization. Conclusion Provided careful pathology of the prostatectomy is performed, our results suggest that immediate postoperative radiotherapy might not be recommended for prostate cancer patients with negative surgical margins. These findings require validation on an independent data set.
In vitro studies of human pluripotential hematopoietic progenitors in polycythemia vera. Direct evidence of stem cell involvement.
Authors: R C Ash, R A Detrick, E D Zanjani
Journal: Journal of Clinical Investigation (1982)

Previous in vitro studies on committed hematopoietic progenitors have suggested that polycythemia vera (PV) is a clonal disorder arising in a pluripotential hematopoietic stem cell. In this study, recently developed technics for clonal assay of a human multipotential progenitor cell (CFU-GEMM) were used to assess the functional characteristics of CFU-GEMM in 19 PV patients. These studies showed: (a) increased numbers of detectable CFU-GEMM in blood and bone marrow samples of PV patients as compared with normals (P less than 0.002 and P less than 0.02, respectively); (b) erythropoietic differentiation of PV CFU-GEMM without exogenous erythropoietin (Ep) in culture (in marked contrast to CFU-GEMM of both normals and subjects with secondary erythrocytosis which require exogenous Ep for terminal hemoglobinization of their erythroid component), a property shown by experiments with an anti-Ep antiserum to be related to increased sensitivity of PV CFU-GEMM to Ep; (c) increased megakaryocyte formation by PV CFU-GEMM as compared with normals (P less than 0.025); and (d) a linear relationship, extrapolating to the origin, between CFU-GEMM detected and cells cultured. These studies demonstrate that at least two clinical features of PV, increased erythropoiesis and megakaryocytopoiesis, are reflected in corresponding functional characteristics of PV CFU-GEMM, and provide direct evidence of distinctive pluripotential stem cell activity in this disorder.
Effect of statin treatment for familial hypercholesterolaemia on life assurance: results of consecutive surveys in 1990 and 2002
Authors: H A W Neil, T Hammond, D Mant, S E Humphries
Journal: BMJ (2004)

<h3>Abstract</h3> During infection the host relies on pattern-recognition receptors to sense invading fungal pathogens to launch immune defense mechanisms. While fungal recognition and immune effector responses are organ and cell type specific, during disseminated candidiasis myeloid cells exacerbate collateral tissue damage. However, the complex interplay between protective antifungal immunity and immunopathology remains incompletely understood. The β-glucan receptor ephrin type-A 2 receptor (EphA2) is required to initiate mucosal inflammatory responses during oral <i>Candida</i> infection. Here we report that Epha2 promotes renal immunopathology during disseminated candidiasis. EphA2 deficiency leads to reduced renal inflammation and injury. Comprehensive analyses reveal that EphA2 limits IL-23 secretion in dendritic cells, while IL-23 signaling prevents ferroptotic myeloid cell death during infection. Further, ferroptosis aggravates inflammation during infection, while at the same time reducing the fungal killing capacity of macrophages. Thus, we identify ferroptotic cell death as a critical pathway of <i>Candida-</i>mediated renal immunopathology that opens a new avenue to tackle <i>Candida</i> infection and inflammation.
Regulation of Ca2+ channels by cAMP and cGMP in vascular smooth muscle cells.
Authors: T Ishikawa, J R Hume, K D Keef
Journal: Circulation Research (1993)

Whole-cell Ca2+ channel currents in rabbit portal vein cells were recorded using the amphotericin B-perforated patch-clamp technique at 35 degrees C. This technique allowed recording of stable inward currents in the absence of run-down for more than 30 minutes. Depolarizing voltage steps from a holding potential of -70 mV elicited voltage-dependent inward currents. The voltage dependence of inward currents measured in either 2.5 mmol/L Ba(2+)- or 2.5 mmol/L Ca(2+)-containing solution were very similar. However, maximum Ba2+ current (obtained at around +10 mV) was approximately 1.5-fold larger than maximum Ca2+ current. Changing the holding potential from -70 to -40 mV decreased inward currents but did not shift the voltage dependence significantly. Inward currents were also completely blocked by the dihydropyridine Ca2+ channel blocker, nicardipine (10 mumol/L), suggesting the presence of predominantly L-type Ca2+ channels in rabbit portal vein cells. Isoproterenol caused small increases in the amplitude of Ba2+ currents in a concentration-dependent manner (10 nmol/L to 1 mumol/L), which were reversed with propranolol. Forskolin (1 mumol/L) or 8-bromo-cAMP (0.1 mmol/L) also caused small increases in the amplitude of Ba2+ currents, suggesting that the stimulatory actions of isoproterenol are importantly linked to the production of cAMP. Higher concentrations of of isoproterenol (10 mumol/L) or forskolin (10 mumol/L) caused a transient increase in Ba2+ currents followed by f decrease in current amplitude. Higher doses of 8-bromo-cAMP (1 mmol/L) and low doses of 8-bromo-cGMP (0.1 mmol/L) inhibited Ba2+ currents, increased the rate of current inactivation, and produced a negative voltage shift in steady-state availability. These results indicate that low concentrations of intracellular cAMP produce modest increases in Ca2+ channel activity, whereas cGMP and higher concentrations of cAMP result in inhibition of Ca2+ channel activity in vascular smooth muscle cells. The observed similarities of cGMP and high concentrations of cAMP on Ba2+ current amplitude, kinetics, and steady-state inactivation suggest mediation by a common mechanism, possibly involving activation of cGMP-dependent protein kinase.
Bleomycin induces cellular senescence in alveolar epithelial cells
Authors: K. Aoshiba, T. Tsuji, A. Nagai
Journal: European Respiratory Journal (2003)

Cellular senescence is a state of irreversible growth arrest. In this paper the authors examined whether bleomycin, an agent that causes pulmonary fibrosis, induces the senescence of alveolar epithelial cells. Type II-like alveolar epithelial (A549) cells or rat primary type II cells were exposed to bleomycin and then evaluated for markers of cellular senescence. Bleomycin was also administered intratracheally in C57BL/6 mice. The authors found that exposure to bleomycin induced cellular senescence in A549 cells and rat primary type II cells. The senescence was characterised by a dose- and time-dependent increase in senescence-associated beta-galactosidase activity, senescence-associated changes in cell morphology, an increase in cell size and lysosomal mass, the overexpression of p21 protein, and irreversible growth arrest. The intratracheal injection of bleomycin in mice induced an increase in senescence-associated beta-galactosidase activity in type II epithelial cells, reaching a maximum at day 7. These results suggest that bleomycin induces a phenotype that is indistinguishable from that of senescence in alveolar epithelial cells. The induction of epithelial senescence by bleomycin may contribute to the pathway of impaired re-epithelialisation leading to pulmonary fibrosis.
Demosponge EST Sequencing Reveals a Complex Genetic Toolkit of the Simplest Metazoans
Authors: M. Harcet, M. Roller, H. Cetkovic, D. Perina, M. Wiens, W. E. G. Muller, K. Vlahovicek
Journal: Molecular Biology and Evolution (2010)

Sponges (Porifera) are among the simplest living and the earliest branching metazoans. They hold a pivotal role for studying genome evolution of the entire metazoan branch, both as an outgroup to Eumetazoa and as the closest branching phylum to the common ancestor of all multicellular animals (Urmetazoa). In order to assess the transcription inventory of sponges, we sequenced expressed sequence tag libraries of two demosponge species, Suberites domuncula and Lubomirskia baicalensis, and systematically analyzed the assembled sponge transcripts against their homologs from complete proteomes of six well-characterized metazoans—Nematostella vectensis, Caenorhabditis elegans, Drosophila melanogaster, Strongylocentrotus purpuratus, Ciona intestinalis, and Homo sapiens. We show that even the earliest metazoan species already have strikingly complex genomes in terms of gene content and functional repertoire and that the rich gene repertoire existed even before the emergence of true tissues, therefore further emphasizing the importance of gene loss and spatio-temporal changes in regulation of gene expression in shaping the metazoan genomes. Our findings further indicate that sponge and human genes generally show similarity levels higher than expected from their respective positions in metazoan phylogeny, providing direct evidence for slow rate of evolution in both "basal" and "apical" metazoan genome lineages. We propose that the ancestor of all metazoans had already had an unusually complex genome, thereby shifting the origins of genome complexity from Urbilateria to Urmetazoa.
Pancreatogram in cholestasis.
Authors: K R Palmer, P B Cotton, M Chapman
Journal: Gut (1984)

Endoscopic retrograde pancreatograms have been examined in patients presenting with cholestasis caused by either primary sclerosing cholangitis (13 subjects), or high cholangiocarcinomata (15 subjects), and in normal individuals (13 subjects). Pancreatograms were reported by two independent observers who had no knowledge of the diagnosis in any case and abnormalities were graded using a conventional scoring system. Pancreatograms were abnormal in 77% of cases of primary sclerosing cholangitis and in 60% of cholangiocarcinoma patients. These abnormalities usually consisted of side branch irregularities, although in five patients with primary sclerosing cholangitis and in two with cholangiocarcinoma, the main pancreatic duct was also markedly irregular.
Systemic Targeting of CpG-ODN to the Tumor Microenvironment with Anti–neu-CpG Hybrid Molecule and T Regulatory Cell Depletion Induces Memory Responses in BALB-neuT Tolerant Mice
Authors: Sanjay Sharma, Ana Lucia Dominguez, Soraya Zorro Manrique, Federica Cavallo, Shimon Sakaguchi, Joseph Lustgarten
Journal: Cancer Research (2008)

Abstract We have shown that neu transgenic mice are immunotolerant and that immunizations with dendritic cells (DC) pulsed with neu-derived antigens were not able to control tumor growth in these animals. We tested whether, by modulating the tumor microenvironment with Toll-like receptor ligands, it could be possible to induce the activation of antitumor responses in neu mice. Our results indicate that only intratumoral (i.t.) injections of CpG-ODN induce an antitumor response in neu mice. To target the CpG-ODN to the tumor site anywhere within the body, we chemically conjugated an anti–Her-2/neu monoclonal antibody (mAb) with CpG-ODN. The anti–neu-CpG hybrid molecule retained its ability to bind to Her-2/neu+ tumors, activate DCs, and induce antitumor responses. Our results indicated that injections of anti–neu-CpG induced the rejection of primary tumors in 100% of BALB/c mice and only in ∼30% of BALB-neuT mice. After challenging the BALB/c and BALB-neuT mice, we observed that BALB/c mice developed a protective memory response; in contrast, BALB-neuT mice succumbed to the challenge. After injections of anti–neu-CpG, T regulatory cells (T-reg) were drastically reduced at the tumor site, but a large number were still present in the lymphoid organs. When BALB-neuT mice were treated with anti–neu-CpG plus anti-GITR mAb, but not with anti-CD25 mAb, 100% of the BALB-neuT mice rejected the primary tumor and developed a protective memory response indicating the critical role of T-regs in regulating the repertoire against self antigens. Taken together, these results indicate that CpG-ODN–targeted therapy and depletion of T-regs optimally activate a primary response and generate a protective memory response against self-tumor antigens. [Cancer Res 2008;68(18):7530–40]
Complication of therapeutic endoscopic retrograde cholangiopancreatography
Authors: G I Papachristou, T H Baron
Journal: Gut (2007)

A 69-year-old man underwent endoscopic retrograde cholangiopancreatography for the evaluation of suspected hilar cholangiocarcinoma in the presence of primary sclerosing cholangitis. Cholangiography confirmed a hilar tight stricture. A 0.035-inch soft-tipped hydrophilic guidewire was advanced into the right intrahepatic biliary …
Continuous formation of nail along the bed
Authors: M. JOHNSON, S. SHUSTER
Journal: British Journal of Dermatology (1993)

To resolve the problem of whether nail is formed continuously along the length of the nail bed as well as by the germinal matrix, nail thickness was measured at six anatomical points along the length of 20 normal big toe-nails removed after injury. Nail water content was constant at 9-10% along the nail length, and the nails did not shrink with dehydration. Approximately 79% of nail thickness was contributed by the nail matrix, and 21% by the nail bed. The rate of nail production was constant at 0.13 mm/mm along the lunula and 0.027 mm/mm along the whole bed from the distal lunula to the point of separation at the onychodermal band; the fractional change in linear growth and thickness showed less variation than absolute change. The continuous production of nail by the bed provides a simple biological solution to the problem of attachment of a continuously moving plate. It provides a source of entry of drugs into the distal nail plate, and a rationale for the use of much shorter courses of antifungal drugs than previously believed possible.
A Specific STAT3-Binding Peptide Exerts Antiproliferative Effects and Antitumor Activity by Inhibiting STAT3 Phosphorylation and Signaling
Authors: Daejin Kim, In-Hyun Lee, Sunghyun Kim, Minsuk Choi, Hyungjun Kim, Sukyung Ahn, Phei Er Saw, Hyungsu Jeon, Yumi Lee, Sangyong Jon
Journal: Cancer Research (2014)

STAT3 promotes the survival, proliferation, metastasis, immune escape, and drug resistance of cancer cells, making its targeting an appealing prospect. However, although multiple inhibitors of STAT3 and its regulatory or effector pathway elements have been developed, bioactive agents have been somewhat elusive. In this report, we report the identification of a specific STAT3-binding peptide (APTSTAT3) through phage display of a novel "aptide" library. APTSTAT3 bound STAT3 with high specificity and affinity (∼231 nmol/L). Addition of a cell-penetrating motif to the peptide to yield APTSTAT3-9R enabled uptake by murine B16F1 melanoma cells. Treatment of various types of cancer cells with APTSTAT3-9R blocked STAT3 phosphorylation and reduced expression of STAT targets, including cyclin D1, Bcl-xL, and survivin. As a result, APTSTAT3-9R suppressed the viability and proliferation of cancer cells. Furthermore, intratumoral injection of APTSTAT3-9R exerted potent antitumor activity in both xenograft and allograft tumor models. Our results offer a preclinical proof-of-concept for APTSTAT3 as a tractable agent for translation to target the broad array of cancers harboring constitutively activated STAT3.
Biosynthesis of Pb44, the protective antigen of sporozoites of Plasmodium berghei.
Authors: N Yoshida, P Potocnjak, V Nussenzweig, R S Nussenzweig
Journal: The Journal of Experimental Medicine (1981)

In a previous paper (2) we identified a protective antigen (Pb44) of the surface membrane of sporozoites of Plasmodium berghei by means of a monoclonal antibody. Immunoprecipitation of extracts of mature salivary gland sporozoites, metabolically labeled with L[35S]methionine using the same monoclonal antibody, revealed three specific polypeptides: *Pb44, *Pb52, and *Pb54. Metabolically labeled *Pb44 is probably identical to the protective antigen previously identified by surface labeling. Both proteins have the same molecular weights and isoelectric points under denaturing conditions, and they share an epitope. Moreover, *Pb44 also seems to be located on the cell membrane. The results of pulse-chase experiments strongly suggest that *Pb52 is the precursor of *Pb44. The relationship between *Pb54 and the protective antigen is unknown. The three polypeptides seem to be strictly associated with only one of the developmental stage of the parasite. They were not detected in blood forms and were found in minute amounts in sporozoites from the midgut of mosquitoes. In contrast, in mature salivary gland sporozoites they constitute main products of protein synthesis.
Hospital-Onset Infections: A Patient Safety Issue
Authors: Julie Louise Gerberding
Journal: Annals of Internal Medicine (2002)

Hospital-onset infections, particularly those involving the urinary tract, lung, and bloodstream, are common and costly and cause substantial morbidity. This article analyzes the case of a 78-year-old man with lung cancer who died after developing hospital-onset pneumonia and urinary catheter–related infection during hospitalization for elective removal of a cerebellar metastasis. The field of infection control could benefit by adopting several approaches advocated by patient safety adherents, such as root-cause analysis. For example, hospital-onset infections that are implicated as attributable causes of death should perhaps be reviewed by local infection control teams regardless of the institution's overall infection rates. The patient safety movement can also learn from the traditions of infection control and hospital epidemiology. Specifically, applying infection control–based practices to safety problems may enhance safety. Such practices include establishing clear definitions of adverse events, standardizing methods for detecting and reporting events, creating appropriate rate adjustments for case-mix differences, instituting evidence-based intervention programs, and relying on skilled professionals to promote ongoing improvements in care. * This paper was prepared by Julie Louise Gerberding, MD, MPH, for the Quality Grand Rounds series. Sanjay Saint, MD, MPH, and Kaveh Shojania, MD, prepared the case for presentation.
Anti-desmocollin autoantibodies in nonclassical pemphigus
Authors: N. Ishii, K. Teye, S. Fukuda, R. Uehara, T. Hachiya, H. Koga, A. Tsuchisaka, S. Numata, B. Ohyama, C. Tateishi, D. Tsuruta, M. Furumura, S. Hattori, T. Kawakami, C. Ohata, T. Hashimoto
Journal: British Journal of Dermatology (2015)

Despite the established pathogenic role of anti‐desmoglein (Dsg) antibodies in classical pemphigus, the significance of autoantibodies to another desmosomal cadherin, desmocollin (Dsc) is at present unknown. No consistent immunoassay for immunoglobulin (Ig) G autoantibodies to Dscs has been developed. The aim of this study was to develop reliable assays to detect anti‐Dsc autoantibodies. We expressed soluble recombinant proteins (RPs) of human Dsc1–3 in mammalian cells and examined sera of various types of pemphigus, including 79 paraneoplastic pemphigus (PNP) sera, by novel enzyme‐linked immunosorbent assays (ELISAs) using the RPs. We also performed ELISAs of Dsc baculoproteins and used the complementary DNA (cDNA) transfection method, and compared the results with those of mammalian ELISAs. Through mammalian ELISAs, IgG autoantibodies to Dsc1, Dsc2 and Dsc3 were detected in 16·5%, 36·7% and 59·5% of PNP sera, respectively, and considerable numbers of pemphigus herpetiformis (PH) and pemphigus vegetans (PVeg) sera reacted strongly with Dsc1 and Dsc3. Mammalian ELISAs were highly specific and more sensitive than baculoprotein ELISAs or the cDNA transfection method. Several Dsc‐positive sera, particularly PH sera, showed no reactivity with Dsgs. The reactivity of PNP serum and PVeg serum with Dscs was not abolished by pre‐absorption with Dsg RPs. The results of these novel ELISAs indicated that IgG anti‐Dsc autoantibodies were frequently detected and potentially pathogenic in nonclassical pemphigus.
Inciting inflammation: the RAGE about tumor promotion
Authors: Michael Dougan, Glenn Dranoff
Journal: The Journal of Experimental Medicine (2008)

Mechanisms of innate and adaptive immunity play a pivotal role in the development of cancer. Chronic inflammation can drive tumor development, but antitumor immunity can also restrict or even prevent tumor growth. New data show that feed-forward signals downstream of the receptor for advanced glycation end-products (RAGE) can fuel chronic inflammation, creating a microenvironment that is ideal for tumor formation.
Clinical features, management, and short‐ and long‐term outcomes of patients with acute decompensated heart failure: phase I results of the <scp>HEARTS</scp> database
Authors: Khalid F. AlHabib, Abdelfatah A. Elasfar, Hussam Alfaleh, Tarek Kashour, Ahmad Hersi, Hanan AlBackr, Fayez Alshaer, Khalid AlNemer, Gamal A. Hussein, Layth Mimish, Ali Almasood, Waleed AlHabeeb, Saleh AlGhamdi, Mubrouk Alsharari, Esmail Chakra, Asif Malik, Raza Soomro, Abdullah Ghabashi, Mushabab Al‐Murayeh, Ahmed Abuosa
Journal: European Journal of Heart Failure (2014)
Modeling of exposure to carpet-cleaning chemicals preceding irritant-induced asthma in one patient.
Authors: R M Lynch
Journal: Environmental Health Perspectives (2000)

42-year-old woman experienced an acute asthma attack, seizures, and unconsciousness immediately after a carpet-cleaning and deodorizing job was conducted in her home. Exposure modeling estimates that she was exposed to approximately 3.4-17 mg/m(3) of sodium tripolyphosphate and more than 14 mg/m(3) volatile organic compounds immediately after the cleaning. I derived two separate exposure models for these estimates that evidenced good consistency of exposure estimates. Asthmatics and carpet-cleaning companies should be advised about safety during carpet-cleaning operations, including adequate warnings about excess risk for asthmatics, temporary removal from the home, reduced detergent levels within cleaners, and reduced overall levels of cleaning solutions used within the home. Further studies of carpet-cleaning exposures are indicated.