tbuckley/cabot-search huggingface dataset:
Stomal adenocarcinoma in Crohn's disease.
Authors: D J Sherlock, V Suarez, J G Gray
Journal: Gut (1990)

Malignant change occurring at the site of a stoma in two patients with proved Crohn9s disease is described. Patients with ulcerative colitis have an increased risk of colonic malignancy and Crohn9s disease is also associated with both small and large bowel carcinoma. Most previous reports of stomal carcinoma have been associated with ulcerative colitis although Crohn9s disease seems to carry a greater risk of associated small bowel carcinomas. This is the first report of stomal carcinoma complicating Crohn9s disease. Epithelial dysplasia is associated with gastrointestinal carcinomas in both ulcerative colitis and Crohn9s disease and a dysplasia-carcinoma sequence has been suggested as the origin of these tumours. In both our patients with stomal adenocarcinoma, dysplasia was identified in adjacent tissues, which suggests a similar mechanism. Malignant change should be suspected if epithelial dysplasia is discovered in a biopsy specimen from the mucosa of an ileostomy in Crohn9s disease, and this risk is increased if the dysplasia is of a high grade.
Is daily dose of IFN plus ribavirin more effective than standard IFN plus ribavirin regimen for HCV related liver disease? A prospective randomized study
Authors: M. De Luca, A. Ascione, C. Canestrini, G.G. Di Costanzo, F.P. Picciotto, F. Lampasi, W. Utech
Journal: Journal of Hepatology (2001)
Temporal trends in HIV-1 incidence and risk behaviours in men who have sex with men in Bangkok, Thailand, 2006–13: an observational study
Authors: Frits van Griensven, Timothy H Holtz, Warunee Thienkrua, Wannee Chonwattana, Wipas Wimonsate, Supaporn Chaikummao, Anchalee Varangrat, Tareerat Chemnasiri, Wichuda Sukwicha, Marcel E Curlin, Taraz Samandari, Anupong Chitwarakorn, Philip A Mock
Journal: The Lancet HIV (2015)
Neuropathic Pain: A Maladaptive Response of the Nervous System to Damage
Authors: Michael Costigan, Joachim Scholz, Clifford J. Woolf
Journal: Annual Review of Neuroscience (2009)

Neuropathic pain is triggered by lesions to the somatosensory nervous system that alter its structure and function so that pain occurs spontaneously and responses to noxious and innocuous stimuli are pathologically amplified. The pain is an expression of maladaptive plasticity within the nociceptive system, a series of changes that constitute a neural disease state. Multiple alterations distributed widely across the nervous system contribute to complex pain phenotypes. These alterations include ectopic generation of action potentials, facilitation and disinhibition of synaptic transmission, loss of synaptic connectivity and formation of new synaptic circuits, and neuroimmune interactions. Although neural lesions are necessary, they are not sufficient to generate neuropathic pain; genetic polymorphisms, gender, and age all influence the risk of developing persistent pain. Treatment needs to move from merely suppressing symptoms to a disease-modifying strategy aimed at both preventing maladaptive plasticity and reducing intrinsic risk.
Enoxaparin Prevents Death and Cardiac Ischemic Events in Unstable Angina/Non–Q-Wave Myocardial Infarction
Authors: Elliott M. Antman, Carolyn H. McCabe, Enrique P. Gurfinkel, Alexander G. G. Turpie, Peter J. L. M. Bernink, Diana Salein, Antonio Bayes de Luna, Kim Fox, Jean-Marc Lablanche, David Radley, Jerome Premmereur, Eugene Braunwald
Journal: Circulation (1999)

Background —Low-molecular-weight heparins are attractive alternatives to unfractionated heparin (UFH) for management of unstable angina/non–Q-wave myocardial infarction (UA/NQMI). Methods and Results —Patients (n=3910) with UA/NQMI were randomized to intravenous UFH for ≥3 days followed by subcutaneous placebo injections or uninterrupted antithrombin therapy with enoxaparin during both the acute phase (initial 30 mg intravenous bolus followed by injections of 1.0 mg/kg every 12 hours) and outpatient phase (injections every 12 hours of 40 mg for patients weighing &lt;65 kg and 60 mg for those weighing ≥65 kg). The primary end point (death, myocardial infarction, or urgent revascularization) occurred by 8 days in 14.5% of patients in the UFH group and 12.4% of patients in the enoxaparin group (OR 0.83; 95% CI 0.69 to 1.00; P =0.048) and by 43 days in 19.7% of the UFH group and 17.3% of the enoxaparin group (OR 0.85; 95% CI 0.72 to 1.00; P =0.048). During the first 72 hours and also throughout the entire initial hospitalization, there was no difference in the rate of major hemorrhage in the treatment groups. During the outpatient phase, major hemorrhage occurred in 1.5% of the group treated with placebo and 2.9% of the group treated with enoxaparin ( P =0.021). Conclusions —Enoxaparin is superior to UFH for reducing a composite of death and serious cardiac ischemic events during the acute management of UA/NQMI patients without causing a significant increase in the rate of major hemorrhage. No further relative decrease in events occurred with outpatient enoxaparin treatment, but there was an increase in the rate of major hemorrhage.
Triplex DNA-binding proteins are associated with clinical outcomes revealed by proteomic measurements in patients with colorectal cancer
Authors: Laura D Nelson, Christian Bender, Heiko Mannsperger, Daniel Buergy, Patryk Kambakamba, Giridhar Mudduluru, Ulrike Korf, Dennis Hughes, Michael W Van Dyke, Heike Allgayer
Journal: Molecular Cancer (2012)

Abstract Background Tri- and tetra-nucleotide repeats in mammalian genomes can induce formation of alternative non-B DNA structures such as triplexes and guanine (G)-quadruplexes. These structures can induce mutagenesis, chromosomal translocations and genomic instability. We wanted to determine if proteins that bind triplex DNA structures are quantitatively or qualitatively different between colorectal tumor and adjacent normal tissue and if this binding activity correlates with patient clinical characteristics. Methods Extracts from 63 human colorectal tumor and adjacent normal tissues were examined by gel shifts (EMSA) for triplex DNA-binding proteins, which were correlated with clinicopathological tumor characteristics using the Mann-Whitney U , Spearman’s rho, Kaplan-Meier and Mantel-Cox log-rank tests. Biotinylated triplex DNA and streptavidin agarose affinity binding were used to purify triplex-binding proteins in RKO cells. Western blotting and reverse-phase protein array were used to measure protein expression in tissue extracts. Results Increased triplex DNA-binding activity in tumor extracts correlated significantly with lymphatic disease, metastasis, and reduced overall survival. We identified three multifunctional splicing factors with biotinylated triplex DNA affinity: U2AF65 in cytoplasmic extracts, and PSF and p54nrb in nuclear extracts. Super-shift EMSA with anti-U2AF65 antibodies produced a shifted band of the major EMSA H3 complex, identifying U2AF65 as the protein present in the major EMSA band. U2AF65 expression correlated significantly with EMSA H3 values in all extracts and was higher in extracts from Stage III/IV vs. Stage I/II colon tumors (p = 0.024). EMSA H3 values and U2AF65 expression also correlated significantly with GSK3 beta, beta-catenin, and NF- B p65 expression, whereas p54nrb and PSF expression correlated with c-Myc, cyclin D1, and CDK4. EMSA values and expression of all three splicing factors correlated with ErbB1, mTOR, PTEN, and Stat5. Western blots confirmed that full-length and truncated beta-catenin expression correlated with U2AF65 expression in tumor extracts. Conclusions Increased triplex DNA-binding activity in vitro correlates with lymph node disease, metastasis, and reduced overall survival in colorectal cancer, and increased U2AF65 expression is associated with total and truncated beta-catenin expression in high-stage colorectal tumors.
Treatment of cancer with oral drugs: a position statement by the Spanish Society of Medical Oncology (SEOM)
Authors: R. Colomer, E. Alba, A. González-Martin, L. Paz-Ares, M. Martín, A. Llombart, Á. Rodríguez Lescure, J. Salvador, J. Albanell, D. Isla, M. Lomas, C.A. Rodríguez, J.M. Trigo, J.R. Germà, J. Bellmunt, J. Tabernero, R. Rosell, E. Aranda, R. Cubedo, J. Baselga
Journal: Annals of Oncology (2010)
Gene expression-based screening for inhibitors of PDGFR signaling
Authors: Alena A Antipova, Brent R Stockwell, Todd R Golub
Journal: Genome biology (2008)

Abstract Here we describe a proof-of-concept experiment designed to explore the possibility of using gene expression-based high-throughput screening (GE-HTS) to find inhibitors of a signaling cascade, using platelet derived growth factor receptor (PDGFR) signaling as the example. The previously unrecognized ability of aurintricarboxylic acid to inhibit PDGFR signaling, discovered through a screen of 1,739 compounds, demonstrates the feasibility and generalizability of GE-HTS for the discovery of small molecule modulators of any signaling pathway of interest.
Distribution and Clinical Significance of Heparan Sulfate Proteoglycans in Ovarian Cancer
Authors: E. June Davies, Fiona H. Blackhall, Jonathan H. Shanks, Guido David, Alan T. McGown, Ric Swindell, Richard J. Slade, Pierre Martin-Hirsch, John T. Gallagher, Gordon C. Jayson
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Heparan sulfate proteoglycans have been implicated in cancer cell growth, invasion, metastasis, and angiogenesis. This study was designed to compare their expression in normal ovary and ovarian tumors and then to examine their prognostic significance in ovarian cancer. Experimental Design: The expression of syndecan-1, -2, -3, and -4, glypican-1, and perlecan was assessed by immunohistochemistry in 147 biopsies that included normal ovary and benign, borderline, and malignant ovarian tumors. Clinical data, including tumor stage, performance status, treatment, and survival, were collected. Univariate and multivariate analyses were performed to evaluate prognostic significance. Results: The expression patterns of syndecan-1 and perlecan were altered in ovarian tumors compared with normal ovary. Syndecan-1 was not detected in normal ovary but was present in the epithelial and stromal cells of benign and borderline tumors and in ovarian adenocarcinomas. Perlecan expression was decreased in basement membranes that were disrupted by cancer cells but maintained in the basement membranes of blood vessels. Syndecan-2, -3, and -4, and glypican-1 were expressed in normal ovary and benign and malignant ovarian tumors. Stromal expression of syndecan-1 and glypican-1 were poor prognostic factors for survival in univariate analysis. Conclusion: We report for the first time distinct patterns of expression of cell surface and extracellular matrix heparan sulfate proteoglycans in normal ovary compared with ovarian tumors. These data reinforce the role of the tumor stroma in ovarian adenocarcinoma and suggest that stromal induction of syndecan-1 contributes to the pathogenesis of this malignancy.
Chromosomal location of structural genes encoding murine immunoglobulin lambda light chains. Genetics of murine lambda light chains.
Authors: P D'Eustachio, A L Bothwell, T K Takaro, D Baltimore, F H Ruddle
Journal: The Journal of Experimental Medicine (1981)

To determine the chromosomal localization of murine lambda light (L) chain structural genes, DNA from a panel of 11 mouse x hamster somatic cell hybrids was scored for the presence of sequences homologous to cloned lambda DNA probe molecules. Six of the hybrids had detectable lambda I and lambda II gene sequences. In all six, the full complement of murine sequences was present, and in its germline configuration. The remaining hybrids lacked any detectable murine lambda L chain gene sequences. The only mouse chromosome present in all of the positive hybrids and absent from the negative ones was number 16, allowing the assignment of lambda L chain structural genes to this chromosome. Together with the previous assignments of the kappa L chain genes to chromosome 6 and heavy chain genes to chromosome 12, this finding completes the mapping of Ig structural genes in the mouse at the chromosomal level.
Positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) for the staging of low-grade non-Hodgkin’s lymphoma (NHL)
Authors: G. Jerusalem, Y. Beguin, F. Najjar, R. Hustinx, M.F. Fassotte, P. Rigo, G. Fillet
Journal: Annals of Oncology (2001)
Multivalent Dendritic Molecules as Broad Spectrum Bacteria Agglutination Agents
Authors: Shuzhang Xiao, Lica Abu-Esba, Serhan Turkyilmaz, Alexander G. White, Bradley D. Smith
Journal: Theranostics (2013)

This study reports the first set of synthetic molecules that act as broad spectrum agglutination agents and thus are complementary to the specific targeting of antibodies.The molecules have dendritic architecture and contain multiple copies of zinc(II)-dipicolylamine (ZnDPA) units that have selective affinity for the bacterial cell envelope.A series of molecular structures were evaluated, with the number of appended ZnDPA units ranging from four to thirty-two.Agglutination assays showed that the multivalent probes rapidly cross-linked ten different strains of bacteria, regardless of Gram-type and cell morphology.Fluorescence microscopy studies using probes with four ZnDPA units indicated a high selectivity for bacteria agglutination in the presence of mammalian cells and no measurable effect on the health of the cells.The high bacterial selectivity was confirmed by conducting in vivo optical imaging studies of a mouse leg infection model.The results suggest that multivalent ZnDPA molecular probes with dendritic structures have great promise as selective, broad spectrum bacterial agglutination agents for infection imaging and theranostic applications.
Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline
Authors: Dawn L. Hershman, Christina Lacchetti, Robert H. Dworkin, Ellen M. Lavoie Smith, Jonathan Bleeker, Guido Cavaletti, Cynthia Chauhan, Patrick Gavin, Antoinette Lavino, Maryam B. Lustberg, Judith Paice, Bryan Schneider, Mary Lou Smith, Tom Smith, Shelby Terstriep, Nina Wagner-Johnston, Kate Bak, Charles L. Loprinzi
Journal: Journal of Clinical Oncology (2014)

To provide evidence-based guidance on the optimum prevention and treatment approaches in the management of chemotherapy-induced peripheral neuropathies (CIPN) in adult cancer survivors.A systematic literature search identified relevant, randomized controlled trials (RCTs) for the treatment of CIPN. Primary outcomes included incidence and severity of neuropathy as measured by neurophysiologic changes, patient-reported outcomes, and quality of life.A total of 48 RCTs met eligibility criteria and comprise the evidentiary basis for the recommendations. Trials tended to be small and heterogeneous, many with insufficient sample sizes to detect clinically important differences in outcomes. Primary outcomes varied across the trials, and in most cases, studies were not directly comparable because of different outcomes, measurements, and instruments used at different time points. The strength of the recommendations is based on the quality, amount, and consistency of the evidence and the balance between benefits and harms.On the basis of the paucity of high-quality, consistent evidence, there are no agents recommended for the prevention of CIPN. With regard to the treatment of existing CIPN, the best available data support a moderate recommendation for treatment with duloxetine. Although the CIPN trials are inconclusive regarding tricyclic antidepressants (such as nortriptyline), gabapentin, and a compounded topical gel containing baclofen, amitriptyline HCL, and ketamine, these agents may be offered on the basis of data supporting their utility in other neuropathic pain conditions given the limited other CIPN treatment options. Further research on these agents is warranted.
Hepatitis B virus precore mutants are identical in carriers from various ethnic origins and are associated with a range of liver disease severity
Authors: Ran Tur-Kaspa, Athalia Klein, Shlomit Aharonson
Journal: Hepatology (1992)

Hepatitis B virus carriers in Israel are mostly HBeAg negative, of whom 5% to 10% have circulating hepatitis B virus. Recently, a hepatitis B virus variant with a stop codon in the precore region was identified, and it was suggested that specific mutations are associated with fulminant or severe chronic active hepatitis. We have analyzed serum samples from HBeAg-positive and HBeAg-negative patients by polymerase chain reaction, using primers spanning the precore/core region. Nucleotide sequence analysis (by direct sequencing) from amplified hepatitis B virus DNA demonstrated that viral genomes from all HBeAg-negative patients contain G to A mutation (nucleotide 1896), leading to the formation of a stop codon. An additional G to A mutation was identified three nucleotides downstream (nucleotide 1899). These patients are of various ethnic origins, with no unique clinical characteristics and with normal liver histology, chronic hepatitis or cirrhosis. No mutation at the precore/core region was observed in the HBeAg-positive patients. In conclusion, the precore mutations identified in hepatitis B virus carriers in Israel are identical regardless of the carrier's ethnic origin and are associated with mild-to-severe liver disease.
Report of an International Workshop to Standardize Baseline Evaluation and Response Criteria for Primary CNS Lymphoma
Authors: Lauren E. Abrey, Tracy T. Batchelor, Andrés J.M. Ferreri, Mary Gospodarowicz, Elisa J. Pulczynski, Emanuele Zucca, Justine R. Smith, Agnieszka Korfel, Carole Soussain, Lisa M. DeAngelis, Edward A. Neuwelt, Brian Patrick O'Neill, Eckhard Thiel, Tamara Shenkier, Fransesc Graus, Martin van den Bent, John F. Seymour, Philip Poortmans, James O. Armitage, Franco Cavalli
Journal: Journal of Clinical Oncology (2005)

Standardized guidelines for the baseline evaluation and response assessment of primary CNS lymphoma (PCNSL) are critical to ensure comparability among clinical trials for newly diagnosed patients. The relative rarity of this tumor precludes rapid completion of large-scale phase III trials and, therefore, our reliance on the results of well-designed phase II trials is critical. To formulate this recommendation, an international group of experts representing hematologic oncology, medical oncology, neuro-oncology, neurology, radiation oncology, neurosurgery, and ophthalmology met to review current standards of reporting and to formulate a consensus opinion regarding minimum baseline evaluation and common standards for assessing response to therapy. The response guidelines were based on the results of neuroimaging, corticosteroid use, ophthalmologic examination, and CSF cytology. A critical issue that requires additional study is the optimal method to assess the neurocognitive impact of therapy and address the quality of life of PCNSL survivors. We hope that these guidelines will improve communication among investigators and comparability among clinical trials in a way that will allow us to develop better therapies for patients.
Causation, supervenience, and special sciences
Authors: Graham Macdonald
Journal: Behavioral and Brain Sciences (2004)

Ross &amp; Spurrett (R&amp;S) argue that Kim's reductionism rests on a restricted account of supervenience and a misunderstanding about causality. I contend that broadening supervenience does nothing to avoid Kim's argument and that it is difficult to see how employing different notions of causality helps to avoid the problem. I end by sketching a different solution.
In defence of Romberg’s test
Authors: John A Schaefer
Journal: Journal of the Royal Society of Medicine (2015)

As a retired neurologist, I read with great interest Michael O’Brien’s paper on the use and abuse of physical signs in neurology. I agree entirely with his emphasis on the history as the most important part of a neurological assessment; however, I felt I must write a short note in defence of an old stalwart, Romberg’s test. I have always emphasised over the years, particularly to students, the need to accumulate information about the patient before the formal examination. This includes such things as their behaviour in the waiting room and office, whether they were accompanied on their visit or not, their general appearance and their mobility around the office, including a good walk up and down the hall fully clothed, with modifications as needed such as heel-toe walking, standing on one or other leg, walking backwards and Romberg’s test. It is my experience that many patients with a disorder of proprioception are unaware that their balance is worse with the eyes closed. They take a bath not a shower, they do not go out at night and they sleep with some form of night light. This component of the overall evaluation I think helps in our ability to hopefully have a fairly firm diagnosis, or at worst, a small list of alternative diagnoses, before proceeding to the formal neurological examination, which can include, as needed, more sophisticated testing of the sensory nervous system. I would urge that we keep Romberg’s test as part of our clinical repertoire.
<i>In vivo</i> Targeting of Dead Tumor Cells in a Murine Tumor Model Using a Monoclonal Antibody Specific for the La Autoantigen
Authors: Fares Al-Ejeh, Jocelyn M. Darby, Katherine Pensa, Kerrilyn R. Diener, John D. Hayball, Michael P. Brown
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To investigate the potential of the La-specific monoclonal antibody (mAb) 3B9 as an in vivo tumor-targeting agent. Experimental Design: The murine EL4 lymphoma cell line was used for in vitro studies and the EL4 model in which apoptosis was induced with cyclophosphamide and etoposide was used for in vivo studies. In vitro studies compared 3B9 binding in the EL4 cell with that in its counterpart primary cell type of the thymocyte. For in vivo studies, 3B9 was intrinsically or extrinsically labeled with carbon-14 or 1,4,7,10-tetra-azacylododecane-N,N′,N″,N″″-tetraacetic acid–indium-111, respectively, and biodistribution of the radiotracers was investigated in EL4 tumor-bearing mice, which were treated or not with chemotherapy. Results: La-specific 3B9 mAb bound EL4 cells rather than thymocytes, and binding was detergent resistant. 3B9 binding to dead EL4 cells in vitro was specific, rapid, and saturable. Significantly, more 3B9 bound dead EL4 tumor explant cells after host mice were treated with chemotherapy, which suggested that DNA damage induced 3B9 binding. Tumor binding of 3B9 in vivo was antigen specific and increased significantly after chemotherapy. Tumor accumulation of 3B9 peaked at ∼50% of the injected dose per gram of tumor 72 h after chemotherapy and correlated with increased tumor cell death. Tumor/organ ratios of 3B9 biodistribution, which included the tumor/blood ratio, exceeded unity 48 or more hours after chemotherapy. Conclusions: La-specific mAb selectively targeted dead tumor cells in vivo, and targeting was augmented by cytotoxic chemotherapy. This novel cell death radioligand may be useful both for radioimmunoscintigraphy and radioimmunotherapy.