tbuckley/cabot-search huggingface dataset:
Efficacy and safety of topical antifungals in the treatment of dermatomycosis: a systematic review
Authors: I. Rotta, A. Sanchez, P.R. Gonçalves, M.F. Otuki, C.J. Correr
Journal: British Journal of Dermatology (2012)

The analysis of comparative efficacy and safety of topical antifungals in the literature is restricted to the treatment of tinea pedis and onychomycosis. Therefore our objective was to evaluate and compare the efficacy and safety of topical antifungals used in the treatment of dermatomycosis, we performed a comprehensive search for randomized controlled trials (RCTs) in the following databases: Medline, Cochrane Central Register of Controlled Trials, EMBASE, Lilacs and International Pharmaceutical Abstracts, we identified studies that compared the use of topical antifungals with other antifungals or with placebo published up to July 2010 in English, Spanish or Portuguese. The quality of reporting was assessed according to the Jadad scale; only studies with a score of 3 or more were included. The outcomes evaluated were mycological cure at the end of treatment, sustained cure, occurrence of adverse events and tolerability, including withdrawals due to adverse events. A total of 104 RCTs satisfied the inclusion criteria, containing a total of 135 comparisons, with 55 out of 120 possible comparisons among the 16 drugs evaluated. Pooled data on efficacy showed that all the antifungals were better than placebo. There were no significant differences among antifungal classes. No differences were found in safety or tolerability in any direct comparison. Sensitivity analysis indicated the robustness of the findings. Our results indicate the clear superiority of topical antifungals over placebo but that there is no consistent difference among classes. Mixed treatment comparisons are necessary to rank antifungals, as direct comparisons among many of them are lacking.
842 SOFOSBUVIR SAFETY AND TOLERABILITY IN 741 PATIENTS TREATED FOR UP TO 24 WEEKS
Authors: K.V. Kowdley, T. Hassanein, E.J. Gane, R.H. Hyland, J. Ma, W.T. Symonds, J. Lalezari, E. Lawitz
Journal: Journal of Hepatology (2013)
Antithrombotic Treatment of Splanchnic Vein Thrombosis: Results of an International Registry
Authors: Walter Ageno, Nicoletta Riva, Soo-Mee Bang, Maria Teresa Sartori, Elvira Grandone, Jan Beyer-Westendorf, Giovanni Barillari, Matteo ND Di Minno, Rita Duce, Alessandra Malato, Rita Santoro, Daniela Poli, Peter Verhamme, Ida Martinelli, Pieter W. Kamphuisen, Adriano Alatri, Doyeun Oh, Elbio D. Amico, Sam Schulman, Francesco Dentali
Journal: Blood (2012)
Diagnosis of Renal Cancer by Molecular Urinalysis
Authors: C. F. Eisenberger, M. Schoenberg, C. Enger, S. Hortopan, S. Shah, N.-H. Chow, F. F. Marshall, D. Sidransky
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: Organ-confined renal malignancies can be cured in the majority of patients, whereas more extensive lesions have a poor prognosis. We sought to develop a noninvasive test for renal cancer detection based on a novel molecular approach. METHODS: Matched urine and serum DNA samples were obtained before surgery from 30 patients with clinically organ-confined solid renal masses (25 with malignant tumors and five with tumors of low malignant potential) and were subjected to microsatellite analysis. Serum samples and urine samples obtained from 16 individuals without clinical evidence of genitourinary malignancy served as controls. RESULTS: Nineteen (76%) of the 25 patients with malignant tumors were found to have one or more microsatellite DNA alterations in their urine specimen, and 15 (60%) were found to have alterations in their serum DNA by microsatellite analysis. In every case, the microsatellite changes in urine or serum were identical to those found in the primary tumor. Three of five patients with tumors of low malignant potential were found to have DNA alterations in their urine, but none displayed alterations in their serum. Moreover, microsatellite alterations were not identified in either the urine or the serum samples from normal control subjects and patients with hematuria due to nephrolithiasis (renal stones). CONCLUSION: These data suggest that microsatellite DNA analysis of urine specimens provides a potentially valuable tool for the early detection of resectable kidney cancer. Furthermore, microsatellite analysis of serum samples reveals evidence of circulating tumor-specific DNA in approximately half of these patients and may reflect the propensity of these tumors to spread to distant sites at an early stage.
Human monoclonal anti-keyhole limpet hemocyanin antibody-secreting hybridoma produced from peripheral blood B lymphocytes of a keyhole limpet hemocyanin-immune individual.
Authors: H C Lane, J H Shelhamer, H S Mostowski, A S Fauci
Journal: The Journal of Experimental Medicine (1982)

A human IgMk monoclonal antibody, 2F7, of predetermined specificity, has been produced by the fusion of human peripheral blood lymphocytes with the nonsecreting mouse myeloma line SP-1. The heterohybridoma has remained stable for over 8 mo, with culture supernatants containing up to 30 micrograms/ml of specific IgM. The antibody has been shown to be capable of inducing a blastogenic response in the absence of antigen in the peripheral blood lymphocytes of normal subjects immune to the antigen. The ability to choose an antigen, immunize a human subject to that antigen, and then use the peripheral blood lymphocytes from that subject to produce antigen-specific human monoclonal antibodies should be of great value in a wide variety of investigative, diagnostic, and therapeutic endeavors.U
Staphylococcal enterotoxin A has two cooperative binding sites on major histocompatibility complex class II.
Authors: K R Hudson, R E Tiedemann, R G Urban, S C Lowe, J L Strominger, J D Fraser
Journal: The Journal of Experimental Medicine (1995)

The superantigen staphylococcal enterotoxin A (SEA) binds to major histocompatibility complex (MHC) class II molecules at two sites on either side of the peptide groove. Two separate but cooperative interactions to the human class II molecule HLA-DR1 were detected. The first high affinity interaction to the DR1 beta chain is mediated by a zinc atom coordinated by H187, H225, and D227 in SEA and H81 in the polymorphic DR1 beta chain. The second low affinity site is to the DR1 alpha chain analogous to SEB binding and is mediated by residue F47 in SEA. Binding of one SEA to the DR1 beta chain enhances the binding of a second SEA molecule to the DR1 alpha chain. The zinc site is on the opposite side of the SEA molecule from residue F47 so that one SEA molecule can readily bind two class II molecules. Both binding sites on SEA are required for maximal activity. Thus, unlike, SEB, SEA requires two separate binding sites for optimal activity, which may allow it to stabilize SEA interaction with T cell receptors, as well as to activate the antigen-presenting cell by cross-linking MHC class II.
Modulation of β1-integrins on hemopoietic progenitor cells after allergen challenge in asthmatic subjects
Authors: Adriana E. Catalli, Jennifer V. Thomson, Irene M. Babirad, MyLinh Duong, Tracey M. Doyle, Karen J. Howie, Paul Newbold, Richard I. Craggs, Martyn Foster, Gail M. Gauvreau, Paul M. O'Byrne, Roma Sehmi
Journal: Journal of Allergy and Clinical Immunology (2008)
Distinct Roles of CSF-1 Isoforms in Lupus Nephritis
Authors: Julia Menke, Yasunori Iwata, Whitney A. Rabacal, Ranu Basu, E. Richard Stanley, Vicki R. Kelley
Journal: Journal of the American Society of Nephrology (2011)

Colony-stimulating factor-1 (CSF-1), the principal growth factor for macrophages, is increased in the kidney, serum, and urine of patients with lupus nephritis, and eliminating CSF-1 suppresses lupus in MRL-Fas(lpr) mice. CSF-1 has three biologically active isoforms: a membrane-spanning cell surface glycoprotein (csCSF-1), a secreted proteoglycan (spCSF-1), and a secreted glycoprotein (sgCSF-1); the role of each isoform in the circulation and kidney in autoimmune disease is not well understood. Here, we constructed mutant MRL-Fas(lpr) mice that only express csCSF-1 or precursors of the spCSF-1 and sgCSF-1 isoforms. Both csCSF-1 and spCSF-1 shifted monocytes toward proinflammatory, activated populations, enhancing their recruitment into the kidney during lupus nephritis. With advancing lupus nephritis, spCSF-1 was the predominant isoform responsible for increasing circulating CSF-1 and, along with the csCSF-1 isoform, for increasing intrarenal CSF-1. Thus, csCSF-1 appears to initiate and promote the local activation of macrophages within the kidney. Intrarenal expression of csCSF-1 and spCSF-1 increases with advancing nephritis, thereby promoting the intrarenal recruitment of monocytes and expansion of Ly6C(hi) macrophages, which induce apoptosis of the renal parenchyma. Taken together, these data suggest that the three CSF-1 isoforms have distinct biologic properties, suggesting that blocking both circulating and intrarenal CSF-1 may be necessary for therapeutic efficacy.
Epoetin Alfa Treatment Results in Clinically Significant Improvements in Quality of Life in Anemic Cancer Patients When Referenced to the General Population
Authors: David Cella, Martin J. Zagari, Christina Vandoros, Dennis D. Gagnon, Hans-Jürgen Hurtz, Johan W.R. Nortier
Journal: Journal of Clinical Oncology (2003)

Purpose: Anemia, highly common among cancer patients, is often an underlying cause of cancer-related fatigue and other quality-of-life (QOL) deficits. Although randomized clinical trials have shown that treatment with epoetin alfa increases hemoglobin levels, reduces fatigue, lessens transfusion requirements, and improves overall QOL, cancer-related anemia and fatigue remain undertreated. This is, in part, because scales and measures of QOL are still relatively unfamiliar to most clinicians and because population-based reference ranges are lacking, thus making clinical trial results difficult to interpret. Methods: To aid in the interpretation of QOL results from clinical trials, we administered the Functional Assessment of Cancer Therapy–Anemia (FACT-An) QOL instrument to a nationally representative sample of 1,400 people using an Internet survey panel in the United States. We then compared the FACT-An data from the Internet survey with the QOL data of a 375-patient randomized, double-blind clinical trial evaluating epoetin alfa versus placebo in anemic cancer patients. Results: FACT-An, as administered to the survey population, displayed good psychometric properties and was able to discriminate between respondents with histories of specified illnesses, including anemia and cancer, and those without. Comparison of the population norm and clinical trial data showed that treatment with epoetin alfa resulted in clinically meaningful as well as statistically significant improvements in QOL (P &lt; .01). Conclusion: Reliable population norm data are now available to aid in the interpretation of clinical trial results where the FACT-An questionnaire is administered. In the clinical trial, treatment with epoetin alfa overcame much of the QOL deficit seen in anemic cancer patients compared with the norm population sample.
Focal Ablation Targeted to the Index Lesion in Multifocal Localised Prostate Cancer: a Prospective Development Study
Authors: Hashim U. Ahmed, Louise Dickinson, Susan Charman, Shraddha Weir, Neil McCartan, Richard G. Hindley, Alex Freeman, Alex P. Kirkham, Mahua Sahu, Rebecca Scott, Clare Allen, Jan Van der Meulen, Mark Emberton
Journal: European Urology (2015)
Etanercept, infliximab, and leflunomide in established rheumatoid arthritis: clinical experience using a structured follow up programme in southern Sweden
Authors: P Geborek
Journal: Annals of the Rheumatic Diseases (2002)

<b>Objective:</b> To explore the feasibility of prospectively monitoring treatment efficacy and tolerability of infliximab, etanercept, and leflunomide over a two year period in patients with established rheumatoid arthritis (RA) in clinical practice using a structured protocol. <b>Methods:</b> All patients with RA at seven centres in southern Sweden, for whom at least two disease modifying antirheumatic drugs, including methotrexate, had failed or not been tolerated, who started treatment with either infliximab, etanercept, or leflunomide were included. They were evaluated at predefined times using a standardised protocol including items required for evaluating response to the American College of Rheumatology (ACR) or EULAR criteria. All adverse events were recorded using World Health Organisation terminology. Concomitant treatment and survival while receiving a drug were recorded. <b>Results:</b> During the study 166 patients were treated with etanercept, 135 with infliximab, and 103 with leflunomide. Treatment response as determined by the ACR and EULAR response criteria was similar for the tumour necrosis factor (TNF) blockers. The TNF blockers performed significantly better than leflunomide both as determined by the response criteria and by survival on drug analysis. Thus 79% and 75% continued to receive etanercept or infliximab compared with 22% of patients who started leflunomide after 20 months. The spectrum of side effects did not differ from those previously reported in the clinical trials. The initial two year experience of a protocol for postmarketing surveillance of etanercept, infliximab, and leflunomide shows that a structured protocol with central data handling can be used in clinical practice for documenting the performance of newly introduced drugs. <b>Conclusions:</b> Efficacy data for the TNF blockers comply with results in clinical trials, whereas leflunomide appeared to perform worse than in clinical trials. Prolonged monitoring is required to identify possible rare side effects.
PGC-1α Promotes the Growth of ErbB2/Neu–Induced Mammary Tumors by Regulating Nutrient Supply
Authors: Eva Klimcakova, Valérie Chénard, Shawn McGuirk, David Germain, Daina Avizonis, William J. Muller, Julie St-Pierre
Journal: Cancer Research (2012)

Cancer cells display an increased reliance on glycolysis despite the presence of sufficient oxygen levels to support mitochondrial functions. In this study, we asked whether ameliorating mitochondrial functions in cancer cells might limit their proliferative capacity. Specifically, we increased mitochondrial metabolism in a murine cellular model of ErbB2/Neu-induced breast cancer by ectopically expressing the transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a master regulator of mitochondrial metabolism. As predicted, ErbB2/Neu cells ectopically expressing PGC-1α displayed an increased level of mitochondrial metabolism and reduced proliferative capacity in vitro, compared with controls. In contrast, ErbB2/Neu cells ectopically expressing PGC-1α formed larger tumors in vivo. These tumors exhibited increased concentrations of glucose and the angiogenic factor VEGF as well as higher expression of ErbB2/Neu compared with controls. We discovered that ErbB2/Neu levels were sensitive to nutrient availability, such that reduced glucose concentrations resulted in diminished ErbB2/Neu protein levels. Therefore, our data indicate that PGC-1α prevents the nutrient-mediated downregulation of ErbB2/Neu in tumors by increasing glucose supply. Mechanistic investigations revealed that the regulation of ErbB2/Neu levels by glucose was mediated by the unfolded protein response (UPR). Incubation of ErbB2/Neu-induced breast cancer cells in limited glucose concentrations or with drugs that activate the UPR led to significant reductions in ErbB2/Neu protein levels. Also, ErbB2/Neu-induced tumors ectopically expressing PGC-1α displayed lowered UPR activation compared with controls. Together, our findings uncover an unexpected link between PGC-1α-mediated nutrient availability, UPR, and ErbB2/Neu levels.
Prolonged Inhibition of Glioblastoma Xenograft Initiation and Clonogenic Growth following <i>In Vivo</i> Notch Blockade
Authors: Qian Chu, Brent A. Orr, Samantha Semenkow, Eli E. Bar, Charles G. Eberhart
Journal: Clinical Cancer Research (2013)

Abstract Purpose: To examine the effects of clinically relevant pharmacologic Notch inhibition on glioblastoma xenografts. Experimental Design: Murine orthotopic xenografts generated from temozolomide-sensitive and -resistant glioblastoma neurosphere lines were treated with the γ-secretase inhibitor MRK003. Tumor growth was tracked by weekly imaging, and the effects on animal survival and tumor proliferation were assessed, along with the expression of Notch targets, stem cell, and differentiation markers, and the biology of neurospheres isolated from previously treated xenografts and controls. Results: Weekly MRK003 therapy resulted in significant reductions in growth as measured by imaging, as well as prolongation of survival. Microscopic examination confirmed a statistically significant reduction in cross-sectional tumor area and mitotic index in a MRK003-treated cohort as compared with controls. Expression of multiple Notch targets was reduced in the xenografts, along with neural stem/progenitor cell markers, whereas glial differentiation was induced. Neurospheres derived from MRK003-treated xenografts exhibited reduced clonogenicity and formed less aggressive secondary xenografts. Neurospheres isolated from treated xenografts remained sensitive to MRK003, suggesting that therapeutic resistance does not rapidly arise during in vivo Notch blockade. Conclusions: Weekly oral delivery of MRK003 results in significant in vivo inhibition of Notch pathway activity, tumor growth, stem cell marker expression, and clonogenicity, providing preclinical support for the use of such compounds in patients with malignant brain tumors. Some of these effects can persist for some time after in vivo therapy is complete. Clin Cancer Res; 19(12); 3224–33. ©2013 AACR.
Antigen-specific helper T cells required for dominant idiotype expression are not H-2 restricted
Authors: K Bottomly, DE Mosier
Journal: The Journal of Experimental Medicine (1981)

Two synergizing antigen-specific helper T (Th) cell populations are required for an optimal TEPC15 (T15)-dominated antiphosphorylcholine (PC) plaque- forming cell response . In these studies, the two Th cell sets are shown to differ in their requirements for recognition of self-major histocompatibility complex (MHC)-encoded determinants by testing the ability of Th cells from F(1) {arrow} parent bone marrow chimeras to collaborate with PC-specific B cells bearing MHC-encoded determinants of either parental haplotypes. Previous studies have shown that one antigen-specific Th cell population is required for T-dependent anti-PC responses and activates PC-specific B cells only if the hapten, PC, is physically linked to the priming antigen. This Th cell, referred to as ThMHC, induces anti-PC responses that are mainly non-T15 in character, and it appears to be identical to the conventional antigen- specific Th cell. In these experiments, using T cells from (A X B)F(1) {arrow} parent A chimeras, ThMHC cells requiring hapten-carrier association provide help for F(1) and parent A B cells but not for B cells from parent B, thus confirming that the activity of the conventional Th cell is H-2 restricted . The second antigen-specific Th cell population, whose function is measured in the presence of the ThMHC cell set, preferentially activates T15-bearing B cells. This Th cell set (ThId) is missing in mice expressing low levels of T15-bearing antibody and can be restored by the addition of antigen-specific T cells from donors expressing high levels of circulating T15 Id. These studies demonstrate that T cells from F(1) {arrow} parent chimeras that express substantial levels of T15-bearing anti-PC antibody could provide ThId cell activity for the selective activation of T15-bearing B cells of F(1) and both parental H-2 types. These results imply that whereas the activity of conventional, ThMHC, cells is clearly H-2 restricted, ThId cells from the same chimeric donors are not required to recognize antigen in association with self-MHC-encoded determinants for successful T-B collaboration .
Comment on: Wolpert et al. Dietary Fat Acutely Increases Glucose Concentrations and Insulin Requirements in Patients With Type 1 Diabetes: Implications for Carbohydrate-Based Bolus Dose Calculation and Intensive Diabetes Management. Diabetes Care 2013;36:810–816
Authors: Thomas M.S. Wolever
Journal: Diabetes Care (2013)

I read with great interest the recent article by Wolpert et al. (1) in which they compared postprandial responses elicited by low- and high-fat dinner test meals and concluded that dietary fat increases glucose levels and insulin requirements in people with type 1 diabetes. This is consistent with recent results …
Limited role of CD28-mediated signals in T helper subset differentiation.
Authors: D R Brown, J M Green, N H Moskowitz, M Davis, C B Thompson, S L Reiner
Journal: The Journal of Experimental Medicine (1996)

The role of CD28-mediated signals in T helper cell maturation is not fully understood. We tested the requirement for costimulation through CD28 in several systems of CD4+, T cell differentiation. In vivo priming of mice with genetic disruption of CD28 (CD28-/-) yielded normal levels of antigen-specific interferon gamma production but markedly diminished levels of interleukin 4 (IL-4) after in vitro restimulation. In response to the pathogenic microbe, Leishman a major, C57BL6 CD28-/- mice were fully capable of controlling infection and exhibited a normal T helper 1 response. BALB/c CD28-/- mice unexpectedly exhibited normal susceptibility to L. major. BALB/c CD28-/- mice developed high levels of IL-4 mRNA and protein induction in the draining lymph nodes. In addition, susceptibility of BALB/c CD28-/- mice was reversed by neutralization of IL-4 in vivo. We also activated transgenic CD28-bearing T cells from the BALB and C57BL background in vitro in the presence of CTLA4Ig. BALB cells had greater IL-4 producing capacity than C57BL cells in the absence of costimulation. Diverse factors including costimulatory signals, genetic polymorphism, and the nature of the immunogen all influence T helper phenotype commitment, but these results provide evidence that CD28 is not an absolute requirement for generating either Th1 or Th2 responses.
The Effects of Mustard Gas, Ionizing Radiation, Herbicides, Trauma, and Oil Smoke on US Military Personnel: The Results of Veteran Studies
Authors: Tim A. Bullman, Han K. Kang
Journal: Annual Review of Public Health (1994)

In recent decades, public health policy and practice have been increasingly challenged by globalization, even as global financing for health has increased dramatically. This article discusses globalization and its health challenges from a vantage of ...Read More