tbuckley/cabot-search huggingface dataset:
Superior biologic activity of the recombinant bee venom allergen hyaluronidase expressed in baculovirus-infected insect cells as compared with Escherichia coli☆☆☆★★★
Authors: Lyudmila N. Soldatova, Reto Crameri, Michael Gmachl, David M. Kemeny, Margit Schmidt, Margrit Weber, Ulrich R. Mueller
Journal: Journal of Allergy and Clinical Immunology (1998)
Enhancement of the Therapeutic Index: From Nonmyeloablative and Myeloablative toward Pretargeted Radioimmunotherapy for Metastatic Prostate Cancer
Authors: Sally J. DeNardo, Carol M. Richman, Huguette Albrecht, Patricia A. Burke, Arut Natarajan, Aina Yuan, Jeff P. Gregg, R.T. O'Donnell, Gerald L. DeNardo
Journal: Clinical Cancer Research (2005)

Abstract Purpose: New strategies that target selected molecular characteristics and result in an effective therapeutic index are needed for metastatic, hormone-refractory prostate cancer. Experimental Design: A series of preclinical and clinical studies were designed to increase the therapeutic index of targeted radiation therapy for prostate cancer. 111In/90Y-monoclonal antibody (mAb), m170, which targets aberrant sugars on abnormal MUC1, was evaluated in androgen-independent prostate cancer patients to determine the maximum tolerated dose and efficacy of nonmyeloablative radioimmunotherapy and myeloablative combined modality radioimmunotherapy with paclitaxel. To enhance the tumor to liver therapeutic index, a cathepsin degradable mAb linkage (111In/90Y-peptide-m170) was used in the myeloablative combined modality radioimmunotherapy protocol. For tumor to marrow therapeutic index improvement in future studies, anti-MUC1 scFvs modules were developed for pretargeted radioimmunotherapy. Anti-MUC1 and anti-DOTA scFvs were conjugated to polyethylene glycol scaffolds tested on DU145 prostate cancer cells and prostate tissue arrays, along with mAbs against MUC1 epitopes. Results: The nonmyeloablative maximum tolerated dose of 90Y-m170 was 0.74 GBq/m2 for patients with not more than 10% axial skeleton involvement. Metastatic prostate cancer was targeted in all 17 patients; mean radiation dose was 10.5 Gy/GBq and pain response occurred in 7 of 13 patients reporting pain. Myeloablative combined modality radioimmunotherapy with 0.4 GBq/m2 of 90Y-peptide-m170 and paclitaxel showed therapeutic effects in 4 of 6 patients and 30% less radiation to the liver per unit of activity. Neutropenia was dose limiting without marrow support and patient eligibility was a major limitation to dose escalation. Hypoglycosylated MUC1 epitopes were shown to be abundant in prostate cancer and to increase with disease grade. Anti-MUC1 scFvs binding to prostate cancer tissue and live cells were developed into di-scFv binding modules. Conclusions: The therapeutic index enhancement for prostate radioimmunotherapy was achieved in clinical studies by the addition of cathepsin cleavable linkers to 90Y-conjugated mAbs and the use of paclitaxel. However, the need for marrow support in myeloablative combined modality radioimmunotherapy restricted eligible patients. Therefore, modular pretargeted radioimmunotherapy, aiming at improving the tumor to marrow therapeutic index, is being developed.
Expansion and long-range differentiation of the NKT cell lineage in mice expressing CD1d exclusively on cortical thymocytes
Authors: Datsen G. Wei, Hyunji Lee, Se-Ho Park, Lucie Beaudoin, Luc Teyton, Agnès Lehuen, Albert Bendelac
Journal: The Journal of Experimental Medicine (2005)

Unlike conventional major histocompatibility complex–restricted T cells, Vα14-Jα18 NKT cell lineage precursors engage in cognate interactions with CD1d-expressing bone marrow–derived cells that are both necessary and sufficient for their thymic selection and differentiation, but the nature and sequence of these interactions remain partially understood. After positive selection mediated by CD1d-expressing cortical thymocytes, the mature NKT cell lineage undergoes a series of changes suggesting antigen priming by a professional antigen-presenting cell, including extensive cell division, acquisition of a memory phenotype, the ability to produce interleukin-4 and interferon-γ, and the expression of a panoply of NK receptors. By using a combined transgenic and chimeric approach to restrict CD1d expression to cortical thymocytes and to prevent expression on other hematopoietic cell types such as dendritic cells, macrophages, or B cells, we found that, to a large extent, expansion and differentiation events could be imparted by a single-cognate interaction with CD1d-expressing cortical thymocytes. These surprising findings suggest that, unlike thymic epithelial cells, cortical thymocytes can provide unexpected, cell type–specific signals leading to lineage expansion and NKT cell differentiation.
Establishment of Antitumor Memory in Humans Using in Vitro–Educated CD8 <sup>+</sup> T Cells
Authors: Marcus O. Butler, Philip Friedlander, Matthew I. Milstein, Mary M. Mooney, Genita Metzler, Andrew P. Murray, Makito Tanaka, Alla Berezovskaya, Osamu Imataki, Linda Drury, Lisa Brennan, Marisa Flavin, Donna Neuberg, Kristen Stevenson, Donald Lawrence, F. Stephen Hodi, Elsa F. Velazquez, Michael T. Jaklitsch, Sara E. Russell, Martin Mihm, Lee M. Nadler, Naoto Hirano
Journal: Science Translational Medicine (2011)

Although advanced-stage melanoma patients have a median survival of less than a year, adoptive T cell therapy can induce durable clinical responses in some patients. Successful adoptive T cell therapy to treat cancer requires engraftment of antitumor T lymphocytes that not only retain specificity and function in vivo but also display an intrinsic capacity to survive. To date, adoptively transferred antitumor CD8(+) T lymphocytes (CTLs) have had limited life spans unless the host has been manipulated. To generate CTLs that have an intrinsic capacity to persist in vivo, we developed a human artificial antigen-presenting cell system that can educate antitumor CTLs to acquire both a central memory and an effector memory phenotype as well as the capacity to survive in culture for prolonged periods of time. We examined whether antitumor CTLs generated using this system could function and persist in patients. We showed that MART1-specific CTLs, educated and expanded using our artificial antigen-presenting cell system, could survive for prolonged periods in advanced-stage melanoma patients without previous conditioning or cytokine treatment. Moreover, these CTLs trafficked to the tumor, mediated biological and clinical responses, and established antitumor immunologic memory. Therefore, this approach may broaden the availability of adoptive cell therapy to patients both alone and in combination with other therapeutic modalities.
Fibrinolysis and fibrinogenolysis in liver disease
Authors: Hoyu Takahashi, Wataru Tatewaki, Ken Wada, Hiroe Niwano, Akira Shibata
Journal: American Journal of Hematology (1990)

Abstract Patients with liver disease frequently have hemostatic abnormalities which include accelerated fibrinolysis. In order to assess the fibrinolytic state in liver disease, plasma levels of fibrinogenolysis products (FgDP), fibrinolysis products (FbDP), and fibrino‐genolysis plus fibrinolysis products (TDP) were measured with newly developed enzyme‐linked immunosorbent assays based on monoclonal antibodies in 36 patients with liver disease (six patients with acute hepatitis, seven with chronic hepatitis, ten with liver cirrhosis, 11 with hepatocellular carcinoma, and two with intrahepatic cholestasis). As compared with healthy subjects, mean plasma levels of FbDP (1,083 ± SD 1,254 vs. 236 ± 100 ng/ml, P = 0.005) and TDP (1,773 ± 1,814 vs. 669 ± 212 ng/ml, P = 0.001) were significantly elevated in patients with liver disease, whereas FgDP was normal (389 ± 202 vs. 396 ± 132 ng/ml, P = 0.87). Plasma FbDP correlated very well with TDP (r = 0.986, P &lt; 0.00001) in liver disease. In addition, FbDP and TDP but not FgDP correlated with plasma concentrations of thrombin‐antithrombin III complex. When plotted by the disease categories, the magnitude of elevations of FbDP and TDP was the most prominent in acute hepatitis followed by hepatocellular carcinoma. These findings indicate that activation of fibrinolysis occurs following thrombin generation, but increased primary fibrinogenolysis is rare in liver disease.
PILOT VALIDATION OF THE CLINICAL USE PHYSICAL ACTIVITY QUESTIONNAIRE FOR PREGNANCY (CPAQPREG)
Authors: JJ Power, GM Evans, K Tsintzas
Journal: British Journal of Sports Medicine (2013)

Aim The Clinical Use Physical Activity Questionnaire for Pregnancy (CPAQpreg) is proposed as a rapid, simple and accurate method to identify pregnant women whose levels of physical activity fail to meet those recommended by the Royal College of Obstetricians and Gynaecologists (RCOG). 1 Methods A pilot validation of CPAQpreg was performed at Leeds General Infirmary, UK. Each participant completed CPAQpreg and the Pregnancy Physical Activity Questionnaire (PPAQ). PPAQ has previously been validated for use in pregnancy but is both time consuming and difficult to interpret. 2 Total amounts of physical activity (MET minutes/week −1 ) were calculated for each questionnaire and subdivided by intensity; moderate, vigorous and combined (moderate+vigorous). Each participant was classified as active or inactive in accordance with RCOG physical activity guidance. Results A total of 191 participants completed the minimum data set (86.8% response rate). The prevalence of inactivity was 29.8%. CPAQpreg showed excellent levels of agreement with PPAQ in the identification of inactive individuals (Cohen's Kappa=0.758, p&lt;0.001) with a high sensitivity (96.5%, 95%CI 86.8–99.4) and high specificity (85.8%, 95% CI 78.5–91.0) Correlation between questionnaires for combined (moderate+vigorous) intensity physical activity was good (Spearman's correlation coefficient =0.072 p&lt;0.01) but wide levels of agreement (−9772 to 5104 MET minutes/week −1 ) and a negative bias (−2335 MET minutes/week −1 ) were shown on Bland Altman plots. Conclusions The CPAQpreg showed excellent levels of agreement with the PPAQ in the identification of inactive pregnant women. Further studies comparing the CPAQpreg with an objective measure would further enhance its validity and support the recommendation that the CPAQpreg is used at every contact between pregnant women and healthcare providers to identify inactive individuals quickly and accurately.
Hyperplastic Gastric Tumors with Spasmolytic Polypeptide–Expressing Metaplasia Caused by Tumor Necrosis Factor-α–Dependent Inflammation in Cyclooxygenase-2/Microsomal Prostaglandin E Synthase-1 Transgenic Mice
Authors: Masanobu Oshima, Hiroko Oshima, Akihiro Matsunaga, Makoto Mark Taketo
Journal: Cancer Research (2005)

Abstract We showed recently that Helicobacter infection induces expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in the mouse stomach, and that transgenic mice expressing both cyclooxygenase-2 and microsomal prostaglandin E synthase-1 (K19-C2mE mice) develop hyperplastic gastric tumors with inflammatory histopathology. To investigate possible roles of proinflammatory cytokines and acquired immunity in the gastric hyperplasia of K19-C2mE mice, we introduced knockout mutations for tumor necrosis factor-α (TNF-α; Tnf), interleukin-1 receptor-α chain (Il1r1), and Rag2 genes, respectively. Among the compound mutants, only the Tnf (−/−) K19-C2mE mice showed significant suppression of hyperplastic tumors with reduced cell proliferation. In contrast, tumorigenesis remained unaffected in either compound mutants of K19-C2mE containing Il1r1 or Rag2 mutation, indicating that neither interleukin-1β signaling nor T cell/B cell response was required for the development of hyperplastic tumors. Importantly, spasmolytic polypeptide/trefoil factor 2–expressing metaplasia (SPEM) in the K19-C2mE stomach was also suppressed in the Tnf (−/−) K19-C2mE mice, indicating that TNF-α–dependent inflammation is responsible for SPEM development. Because gastric metaplasia to the SPEM lineage is considered as a preneoplastic lesion of gastric cancer, it is possible that inhibition of TNF-α–dependent inflammation, together with eradication of Helicobacter, can be an effective prevention strategy for gastric cancer.
Abuse of Elders: Physicians Are Confused
Authors: Carolyn L. Clark-Daniels
Journal: JAMA (1988)

<h3>To the Editor.—</h3> In 1976, Alabama passed a statute (the Adult Protective Services Act) to prohibit the abuse, neglect, and exploitation of adults and mandate the reporting of mistreatment. Alabama focused its mandatory reporting requirements on all "practitioners of the healing arts." To evaluate the efficacy of the statute, the Center for the Study of Aging at the University of Alabama conducted in July 1987 a three-wave mail survey of Alabama physicians to assess their knowledge of the law and their responses to elder abuse. The random sample consisted of 336 internists, family practitioners, and general practitioners in Alabama stratified by specialty and city size. The response rate was 46%. The physicians responded to a series of statements concerning abuse using a five-point Likert scale ranging from "definitely not true" to "definitely true." The results show that after 12 years, Alabama physicians are confused about the law and about the
Protective Role of Pulmonary Nitric Oxide in the Acute Phase of Endotoxemia in Rats
Authors: Ryszard J. Gryglewski, Pawel P. Wolkow, Wojciech Uracz, Ewa Janowska, Joanna B. Bartus, Oleg Balbatun, Stephen Patton, Viktor Brovkovych, Tadeusz Malinski
Journal: Circulation Research (1998)

Abstract —We present for the first time direct continuous assay of NO concentration (porphyrinic sensor) in the lung parenchyma of Sprague-Dawley rats in vivo during endotoxemia. Intravenous infusion of lipopolysaccharide (LPS, 2 mg · kg −1 · min −1 for 10 minutes) stimulated an acute burst of NO from constitutive NO synthase (NOS) that peaked 10 to 15 minutes after the start of LPS infusion, mirroring a coincident peak drop in arterial pressure. NO concentration declined over the next hour to twice above pre-LPS infusion NO levels, where it remained until the rats died, 5 to 6 hours after LPS infusion. The chronic drop in arterial pressure observed from 70 minutes to 6 hours after the start of LPS infusion was not convincingly mirrored by a chronic increase in NO concentration, even though indirect NO assay (Griess method, assaying NO decay products NO 2 − /NO 3 − ) showed that NO production was increasing as a result of continuous NO release by inducible NOS. A NOS inhibitor, N ω -nitro- l -arginine (L-NNA, 10 mg/kg IV) injected 45 minutes before LPS infusion, resulted in sudden death accompanied by macroscopically/microscopically diagnosed symptoms similar to acute respiratory distress syndrome &lt;25 minutes after the start of LPS infusion. Pharmacological analysis of this L-NNA+LPS model by replacing L-NNA with 1-amino-2-hydroxy-guanidine (selective inhibitor of inducible NOS) or by pretreatment with S -nitroso- N -acetyl-penicillamine (NO donor), camonagrel (thromboxane synthase inhibitor), or WEB2170 (platelet-activating factor receptor antagonist) indicated that in the early acute phase of endotoxemia, LPS stimulated the production of cytoprotective NO, cytotoxic thromboxane A 2 , and platelet-activating factor.
Single portal pressure measurement predicts survival in cirrhotic patients with recent bleeding
Authors: D Patch, A Armonis, C Sabin, K Christopoulou, L Greenslade, A McCormick, R Dick, A K Burroughs
Journal: Gut (1999)

Height of portal pressure correlates with severity of alcoholic cirrhosis. Portal pressure indices are not however used routinely as predictors of survival.To examine the clinical value of a single portal pressure measurement in predicting outcome in cirrhotic patients who have bled.A series of 105 cirrhotic patients who consecutively underwent hepatic venous pressure measurement were investigated. The main cause of cirrhosis was alcoholic (64.8%) and prior to admission all patients had bled from varices.During the follow up period (median 566 days, range 10-2555), 33 patients died, and 54 developed variceal haemorrhage. Applying Cox regression analysis, hepatic venous pressure gradient, bilirubin, prothrombin time, ascites, and previous long term endoscopic treatment were the only statistically independent predictors of survival, irrespective of cirrhotic aetiology. The predictive value of the pressure gradient was much higher if the measurement was taken within the first or the second week from the bleeding and there was no association after 15 days. A hepatic venous pressure gradient of at least 16 mm Hg appeared to identify patients with a greatly increased risk of dying.Indirectly measured portal pressure is an independent predictor of survival in patients with both alcoholic and non-alcoholic cirrhosis. In patients with a previous variceal bleeding episode this predictive value seems to be better if the measurement is taken within the first two weeks from the bleeding episode. A greater use of this technique is recommended for the prognostic assessment and management of patients with chronic liver disease.
Dissociation of coronary vascular tolerance and neurohormonal adjustments during long-term nitroglycerin therapy in patients with stable coronary artery disease
Authors: Thomas Münzel, Thomas Heitzer, Sabine Kurz, David G. Harrison, Clemens Luhman, Linda Pape, Manfred Olschewski, Hanjörg Just
Journal: Journal of the American College of Cardiology (1996)
The CXCL7/CXCR1/2 Axis Is a Key Driver in the Growth of Clear Cell Renal Cell Carcinoma
Authors: Renaud Grépin, Mélanie Guyot, Sandy Giuliano, Marina Boncompagni, Damien Ambrosetti, Emmanuel Chamorey, Jean-Yves Scoazec, Sylvie Negrier, Hélène Simonnet, Gilles Pagès
Journal: Cancer Research (2013)

Abstract Mutations in the von Hippel–Lindau gene upregulate expression of the central angiogenic factor VEGF, which drives abnormal angiogenesis in clear cell renal cell carcinomas (ccRCC). However, the overexpression of VEGF in these tumors was not found to correlate with overall survival. Here, we show that the proangiogenic, proinflammatory cytokine CXCL7 is an independent prognostic factor for overall survival in this setting. CXCL7 antibodies strongly reduced the growth of ccRCC tumors in nude mice. Conversely, conditional overexpression of CXCL7 accelerated ccRCC development. CXCL7 promoted cell proliferation in vivo and in vitro, in which expression of CXCL7 was induced by the central proinflammatory cytokine interleukin (IL)-1β. ccRCC cells normally secrete low amounts of CXCL7; it was more highly expressed in tumors due to high levels of IL-1β there. We found that a pharmacological inhibitor of the CXCL7 receptors CXCR1 and CXCR2 (SB225002) was sufficient to inhibit endothelial cell proliferation and ccRCC growth. Because CXCR1 and CXCR2 are present on both endothelial and ccRCC cells, their inhibition affected both the tumor vasculature and the proliferation of tumor cells. Our results highlight the CXCL7/CXCR1/CXCR2 axis as a pertinent target for the treatment of ccRCC. Cancer Res; 74(3); 873–83. ©2013 AACR.
Breast Cancer–Associated <i>Abraxas</i> Mutation Disrupts Nuclear Localization and DNA Damage Response Functions
Authors: Szilvia Solyom, Bernadette Aressy, Katri Pylkäs, Jeffrey Patterson-Fortin, Jaana M. Hartikainen, Anne Kallioniemi, Saila Kauppila, Jenni Nikkilä, Veli-Matti Kosma, Arto Mannermaa, Roger A. Greenberg, Robert Winqvist
Journal: Science Translational Medicine (2012)

A germline mutation in the Abraxas gene impairs BRCA1 DNA damage response function and is associated with familial breast cancer.
Cellular mechanisms of long-term depression in the cerebellum
Authors: F. Crépel, N. Hemart, D. Jaillard, H. Daniel
Journal: Behavioral and Brain Sciences (1996)

Long-term depression (LTD) of synaptic transmission at parallel fibre-Purkinje cell synapses is thought to be a cellular substrate of motor learning in the cerebellum. This use-dependent change in synaptic efficacy is induced by conjunctive stimulation of Parallel fibres and climbing fibres. Researchers agree that the induction of LTD requires, as an initial step, a calcium influx via voltage-gated Ca2+ channels into a Purkinje cell, together with activation of ionotropic (AMPA) and probably metabotropic subtypes of glutamate receptors of this cell. Indeed, due to the lack of specific antagonist, the final demonstration of the contribution of metabotropic receptors in the LTD induction process, under functional conditions, remains unanswered. The debate is now focused on the second-messenger processes leading to LTD of synaptic transmission at parallel fibre-Purkinje cell synapses, after the calcium influx into the cell. All researchers agree that a calcium-dependent cascade of events including activation of protein kinase C is necessary for LTD induction. In contrast, the recruitment in the LTD induction of another cascade, also triggered by Ca2+, that is, through synthesis of nitric oxide and cyclic GMP, remains controversial.On the other hand, growing evidence suggests that these chains of reaction underlying LTD might ultimately lead to a genuine change in the functional characteristics of AMPA receptors at the parallel fibre-Purkinje cell synapses.
Time course of change in oxygen saturation and peak expiratory flow in children admitted to hospital with acute asthma.
Authors: W Mihatsch, G C Geelhoed, L I Landau, P N LeSouef
Journal: Thorax (1990)

The time course for recovery of the arterial oxygen saturation (SaO2) in acute childhood asthma is unknown. Serial measurements of SaO2 were made in 47 children during an acute attack of asthma that required admission to hospital. Adequate serial peak expiratory flow (PEF) measurements were possible in 28 children (mean age 8.3 years; group A), but not in the other 19 children (mean age 3.2 years; group B). Measurements of PEF and SaO2 were recorded twice daily before and 30 minutes after they had received salbutamol by nebuliser. Initial SaO2 values (mean (SD) %) were similar in groups A and B at 92.2 (3.5) and 92.4 (2.9). For the children in group A, PEF plateaued 36 hours after admission and SaO2 plateaued 12 hours later. Mean PEF improved after each dose of nebulised salbutamol during the first 36 hours, whereas mean SaO2 increased only after the first dose. SaO2 increased more rapidly in group B. Length of hospital stay was not related to initial SaO2 or PEF values. These data suggest that in children admitted to hospital for acute asthma arterial oxygen saturation is low at admission, recovers more slowly than airway function, reflects bronchodilatation with salbutamol only when SaO2 is low, and recovers more rapidly in younger children than in older children.