tbuckley/cabot-search huggingface dataset:
Abstract 5385: Effect of lenalidomide on antileukemia activity in vitro against adult T-cell leukemia (ATL)
Authors: Yukiko Kitagawa, Masao Matsuoka, Shohei Mitani
Journal: Cancer Research (2012)

Abstract Background: Lenalidomide is an FDA approved agent for del 5q myelodysplastic syndromes and in combination with dexamethasone for previously treated multiple myeloma. Recently, phase II clinical trial has shown its anti-tumor activity against recurrent and refractory T-cell lymphomas. However, the mechanism underlining its effect is poorly understood. Adult T-cell leukemia (ATL) is a mature T cell malignancy caused by Human T-cell leukemia virus type I (HTLV-I) that is endemic in southwestern Japan, the Caribbean islands and Central Africa, and it still remains as one of the most difficult malignancies to be cured. We have evaluated the anti-ATL activity of lenalidomide in vitro using HTLV-I positive cell lines. Methods: The effect of lenalidomide (10-3-102µM) and Fas antibody (25-400 ng/mL) was assessed on the proliferation of HTLV-I positive cell lines by CellTiter-Glo Luminescent Cell Viability Assay. The cytotoxic effect against HTLV-I positive cell lines of lenalidomide on IL-2 primed peripheral blood mononuclear cells (PBMNCs) as well as sorted CD56 positive and CD3 negative cells from IL-2 primed PBMNCs from healthy volunteers was studied by 51Cr releasing assay. Results: Lenalidomide alone did not inhibit cellular proliferation. Even 6 day incubation did not inhibit or stimulate proliferation of HTLV-1 positive cell lines. Cytotoxic activity of IL-2 primed PBMNCs from healthy volunteers against HTLV-I positive cell lines was enhanced by lenalidomide. Sorted NK cells have also shown enhanced cytotoxic activities on HTLV-1 positive cells. That effect was observed regardless of Tax or cellular FLICE-inhibitory protein (cFLIP) expression. Therefore, even Fas resistant HTLV-1 positive cell lines were succumbed to death by enhanced cytotoxicity by lenalidomide, whereas lenalidomide did not interact Fas inducing apoptotic pathways. Conclusions: These results have shown that lenalidomide enhances cytotoxic effects against HTLV-I positive cells, without direct anti-proliferative effect on those cell lines. That effect was mediated through CD56 positive and CD3 negative cells stimulated by lenalidomide. Further study is now on-going to elucidate the mechanism of those actions in an in vivo setting. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5385. doi:1538-7445.AM2012-5385
A Platform for Controlled Dual‐Drug Delivery to the Retina: Protective Effects against Light‐Induced Retinal Damage in Rats
Authors: Nobuhiro Nagai, Hirokazu Kaji, Hideyuki Onami, Yuki Katsukura, Yumi Ishikawa, Zhaleh Kashkouli Nezhad, Kaori Sampei, Satoru Iwata, Shuntaro Ito, Matsuhiko Nishizawa, Toru Nakazawa, Noriko Osumi, Yukihiko Mashima, Toshiaki Abe
Journal: Advanced Healthcare Materials (2014)

Controlled transscleral co-delivery of two drugs, edaravone (EDV) and unoprostone (UNO), using a platform that comprises a microfabricated reservoir, controlled-release cover, and drug formulations, which are made of photopolymerized poly(ethyleneglycol) dimethacrylates, shows synergistic retinal neuroprotection against light injury in rats when compared with single-drug-loaded devices. The device would offer a safer therapeutic method than intravitreal injections for retinal disease treatments. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Perception of what?
Authors: O. Löwhagen
Journal: European Respiratory Journal (2005)

Respiratory medicine: what is the diagnosis?To the Editors:Clues of the pressurised metered-dose inhaler in the left shirt pocket and the right upper lobe fibrosis should prompt the reader to consider the unifying diagnosis of allergic bronchopulmonary aspergillosis (fig.1).This 48-yr-old male had difficult-to-control asthma with elevated serum immunoglobulin E levels, presence of aspergillus immunoglobulin E antibodies, and the occurrence of central bronchiectasis, fibrosis and loss of volume in the right upper lobe on computed tomography of the thorax.The common causes of upper lobe fibrosis in the lungs are Tuberculosis, Extrinsic allergic alveolitis, Allergic bronchopulmonary aspergillosis, Radiation, and Sarcoidosis (TEARS).Other causes include ankylosing spondylitis, drugs, silicosis, and Langerhans' cell histiocytosis.The patient responded well to oral corticosteroid therapy and continues to be on maintenance prednisolone 2 yrs following the diagnosis.
Framing the debate between computational and dynamical approaches to cognitive science
Authors: Randall D. Beer
Journal: Behavioral and Brain Sciences (1998)

van Gelder argues that computational and dynamical systems are mathematically distinct kinds of systems. Although there are real experimental and theoretical differences between adopting a computational or dynamical perspective on cognition, and the dynamical approach has much to recommend it, the debate cannot be framed this rigorously. Instead, what is needed is careful study of concrete models to improve our intuitions.
Hemodynamic Studies of a Monoamine Oxidase Inhibitor, DL-Serine-N <sup>2</sup> -Isopropylhydrazide (RO 4-1038)
Authors: M. H. MAXWELL, H. C. GONICK, L. SCADUTO, M. L. PEARCE, C. R. KLEEMAN
Journal: Circulation (1962)

Hemodynamic studies were performed on 11 patients with severe diastolic hypertension before and after the chronic administration of the monoamine oxidase inhibitor, RO 4-1038. Although postural hypotension was more marked, the blood pressure decreased significantly in the supine position as well. The hypotensive effect was attributable almost solely to decreased total peripheral resistance and was unrelated to changes in cardiac output, blood volume, or sodium space. Renal plasma flow and glomerular filtration rate were unchanged. Evidence is presented which suggests that the decrease in blood pressure was not caused by adrenergic blockade. If RO 4-1038 is a representative monoamine oxidase inhibitor then its hemodynamic action is unique among the clinically useful hypotensive drugs.
Fatal Rectus Sheath Hematoma
Authors: Barbara S. Ducatman, Jurgen Ludwig, Richard D. Hurt
Journal: JAMA (1983)

Rectus sheath hematoma is an uncommon, often misdiagnosed, and usually self-limited condition. In a recent review of autopsy cases at the Mayo Clinic, Rochester, Minn, we found two patients in whom hemorrhages into the rectus sheaths were considered the immediate cause of death and one in whom the hemorrhage was considered a contributing cause of death. Rectus sheath hematoma should be included in the differential diagnosis of an abdominal mass of sudden onset, especially in patients who have been given anticoagulants. The condition may be fatal if the volume of the hemorrhage is large and if treatment is delayed.
Nephrons and Kidneys: A Quantitative Study of Developmental and Evolutionary Mammalian Renal Architectonics
Authors: L. J. McCormack
Journal: JAMA (1968)

One can only praise the elegant presentation of the development of the human nephron, found in this folio. The result of long-continued winnowing of the subject by Dr. Oliver is apparent in the concise and logical portrayal; this clarity becomes blurred only when extensive German passages are quoted; the author is more of a linguist than many of his readers. The study will be most appreciated by the serious student of "kidneys and nephrons." However, if the author's views are accepted, other texts pertaining to renal embryology, both abbreviated and extensive, will require complete revision. The incredible microdissections are most convincing, and as a consequence, one is forced to discard the time-honored concept of two structures within the kidney growing towards each other and uniting. Appreciation must be expressed to the Commonwealth Fund for its support; otherwise the tome might not have been issued in such a generous form. One
Effects of smoking on the urine excretion of oral<sup>51</sup>Cr EDTA in ulcerative colitis
Authors: C Benoni, H Prytz
Journal: Gut (1998)

Background —Smokers have a reduced risk and ex-smokers an increased risk of ulcerative colitis (UC). Stopping smoking often precedes onset and relapses. Smoking reduces the 24 hour urine excretion of oral chromium-51 labelled EDTA in healthy individuals. Aims —To estimate the effects of smoking on the urine excretion of oral 51 Cr EDTA in well characterised patients with UC. Subjects —Sixteen smoking and 16 non-smoking patients with UC in remission were studied. The non-smokers had never smoked. Most were taking 5-aminosalicylic acid. No patient took steroids or immunosuppressants. The control group comprised 25 smoking healthy volunteers and 25 who had never smoked. The median cigarette consumption was equal in the patients and volunteers. Methods —The 24 hour urine excretion of oral 51 Cr EDTA was measured and the results were correlated with smoking habits, number of cigarettes, and disease extent. Results —Patients with UC had significantly higher 24 hour urine recoveries than healthy controls (p=0.04). This difference was more pronounced when patients who smoked were compared with healthy smokers (p=0.005) No significant differences were found when comparing non-smoking patients with non-smoking controls or when comparing smoking and non-smoking patients. Urine recoveries did not correlate with number of cigarettes or disease extent. Smoking was more prevalent in patients with a more limited disease extent (p=0.033). Conclusions —Effects of smoking on the urine excretion of 51 Cr EDTA in health were abolished by the presence of UC. The protective effects of smoking in established UC are not due to a moderating effect of smoking on intestinal permeability.
Preconditioning preserves mitochondrial function and glycolytic flux during an early period of reperfusion in perfused rat hearts
Authors: K YABE, Y NASA, M SATO, R IIJIMA, S TAKEO
Journal: Cardiovascular Research (1997)

Objective: The purpose of the present study was to examine the effects of preconditioning on glycolysis and oxidative phosphorylation during reperfusion in perfused rat hearts. Methods: Preconditioning was induced by 5 min of ischemia and 5 min of reperfusion before 40 min of sustained ischemia and subsequent 30 min of reperfusion. Tissue energy metabolite levels, mitochondrial oxygen consumption capacity and adenine nucleotide translocator content of the perfused hearts were assessed at 40 min of ischemia, 5 and 30 min of reperfusion. Results: Preconditioning improved the postischemic recovery of rate X pressure product (92.5 ± 8.7 vs. 24.9 ± 1.2% for non-preconditioned group) and high-energy phosphate content (ATP and CrP; 39.5 ± 2.0 and 96.2 ± 4.9% of initial vs. 24.1 ± 0.9 and 56.1 ±4.3% of initial for the non-preconditioned group). The mitochondrial oxygen consumption capacity and the adenine nucleotide translocator content of the non-preconditioned heart were decreased by sustained ischemia and remained decreased throughout reperfusion. Preconditioning prevented these decreases. The tissue lactate level of the non-preconditioned heart was high throughout reperfusion (16.5-fold vs. basal), whereas in the preconditioned heart it returned to the basal level within a few minutes of reperfusion. Furthermore, the ratios of [fructose 1,6-bisphosphate]/([glucose 6-phosphate] + [fructose 6-phosphate]) at 5-min reperfusion were higher (2.2-fold) than those of the non-preconditioned heart. Conclusions: The results suggest that preconditioning preserves the capacity for normal mitochondrial function and the facilitation of glycolysis during reperfusion, which may play an important role in the improvement of postischemic contractile function and high-energy phosphate content.
Smoking Habits and Age in Relation to Pulmonary Changes
Authors: Oscar Auerbach, A. P. Stout, E. Cuyler Hammond, Lawrence Garfinkel
Journal: New England Journal of Medicine (1963)

IT has been reported that cigarette smoking is highly associated with coughing and shortness of breath1 and with the clinical finding of chronic bronchitis.2 Furthermore, it has been shown experimentally that exposure to cigarette smoke produces marked changes in the vascular system of the lungs of rats.3 This led us to suspect that the lung parenchyma of human beings might be directly affected by chronic irritation from tobacco smoke or indirectly affected as a result of changes in the bronchial tubes. Therefore, we undertook a histologic study of tissue from peripheral portions of the lungs. All the lungs in this . . .
HLA class I antigen expression as a measure of response to antiviral therapy of chronic hepatitis B
Authors: Robert G. Paul, Stanford T. Roodman, Carolyn R. Campbell, Carol J. Bodicky, Robert P. Perrillo
Journal: Hepatology (1991)

HLA class I antigen expression on peripheral blood mononuclear cells was evaluated by flow cytometry in 21 HBeAg-positive patients with chronic hepatitis B. Measurements were made before, during or after treatment with recombinant interferon-alpha-2b, either given alone or after a 6 wk course of prednisone. Immunohistochemical staining for human leukocyte class I antigen was also evaluated in 28 percutaneous liver biopsy specimens either obtained before or after therapy (N = 27) and during therapy in one instance. The amount of HLA class I antigen on peripheral blood mononuclear cells varied markedly among individual patients, but the overall results indicated that the level of inducible antigen did not correlate with increments of ALT during therapy or with a virological response to therapy. Hepatocyte staining for HLA class I antigen was observed in a minority of biopsy specimens (29%) and also did not appear to predict a response or correlate with the severity of histological disease. These data do not support current theories concerning pathogenetic mechanisms in chronic hepatitis B nor do they suggest that spontaneous display of HLA class I antigen on hepatocytes or interferon-induced expression of these antigens on peripheral blood mononuclear cells is a critical determinant for a response to therapy.
Methyl isocyanate: reproductive and developmental toxicology studies in Swiss mice.
Authors: B A Schwetz, B Adkins, M Harris, M Moorman, R Sloane
Journal: Environmental Health Perspectives (1987)

Studies were conducted in Swiss (CD-1) mice to evaluate the potential of inhaled vapors of methyl isocyanate (MIC) to affect reproduction and development. Inhaled MIC at concentrations of 0, 1, or 3 ppm, 6 hr per day during days 14 through 17 of gestation caused a significant increase in the number of dead fetuses at birth and caused a significant decrease in neonatal survival during lactation. In contrast, exposure of male and female mice to 1 or 3 ppm given 6 hr per day for 4 consecutive days had no effect on reproduction during mating trials conducted 1, 8, and 17 weeks after the exposure period. Similarly, there was no evidence of a dominant lethal effect in exposed male mice.
Hepatic cytochrome P450 down-regulation during aseptic inflammation in the mouse is interleukin 6 dependent
Authors: Elmar Siewert, Roque Bort, Reinhart Kluge, Peter C. Heinrich, José Castell, Ramiro Jover
Journal: Hepatology (2000)

Expression of cytochromes P450 (CYP) is markedly reduced during inflammatory processes. In vitro studies with hepatocytes have shown that cytokines generated during these processes down-regulate CYP. However, it is not clear to what extent each individual cytokine contributes to the overall reduced expression of the various CYP isoenzymes in vivo . Interleukin 6 (IL-6), a major player during inflammatory processes, is recognized as the most important cytokine modulating the hepatic expression of acute-phase protein (APP) genes. For this reason, we selected the IL-6 −/− mouse as a model to investigate the role of IL-6 in the down-regulation of hepatic CYP during experimental inflammation. Our results show that the reduction in messenger RNA (mRNA) levels of CYP1A2, CYP2A5, and CYP3A11 during turpentine-induced inflammation was abrogated in IL-6-deficient mice, confirming that IL-6 is an indispensable player for the down-regulation of hepatic CYP during aseptic inflammation. Moreover, the different CYP isoenzymes showed a variable grade of dependence on IL-6, CYP2A5 being the most sensitive one. In the case of CYP2E1, differences between IL-6 −/− and wild-type mice were no longer maintained after 24 hours, suggesting a delayed, rather than abrogated, CYP down-regulation in the absence of IL-6. As opposed to that, hepatic CYP repression took place in IL-6-deficient mice during lipopolysaccharide (LPS)-mediated inflammation. This contrasting behavior observed for CYP is surprisingly similar to the one seen for extracellular (serum amyloid A, β-fibrinogen) and intracellular (metallothionein-1) APPs and points to the fact that, in the model of bacterial inflammation (LPS), the effects of IL-6 on CYP down-regulation are likely to be substituted by other cytokines or mediators.
Procainamide Dosage Schedules, Plasma Concentrations, and Clinical Effects
Authors: Jan Koch-Weser
Journal: JAMA (1971)

The relationship of dosage to plasma concentration of procainamide varied greatly among 186 patients. This variation resulted from individual differences in completeness of absorption, distribution space, and elimination rate. Plasma concentrations correlated well with therapeutic and toxic effects. The usually effective antiarrhythmic concentration was 4 to 8 mg/liter; in occasional patients, 8 to 16 mg/liter was more effective. Toxic manifestations were very rare with concentrations of less than 12 mg/liter, but common with concentrations of more than 16 mg/liter. In most patients, procainamide hydrochloride in a daily dose of 50 mg/kg of body weight produces therapeutic plasma concentrations. Three-hour dosage intervals are required to prevent fluctuations of plasma level exceeding 50%. In urgent situations, a parenteral priming dose should be given. In patients with cardiac or renal failure and when usual doses fail or toxic manifestations appear, determinations of plasma levels are useful guides to dosage.
Effects of Dietary Carbohydrate and Fat Intake on Glucose and Lipoprotein Metabolism in Individuals With Diabetes Mellitus
Authors: Clarie B Hollenbeck, Ann M Coulston
Journal: Diabetes Care (1991)

The dietary treatment of individuals with diabetes remains a controversial issue. The major emphasis in recent years has been on the reduction of total fat and saturated fat and replacement with complex carbohydrate. The rationale for this approach is based on the premise that such diets will reduce the risk of coronary artery disease (CAD) by reducing total and low-density lipoprotein cholesterol concentrations. In this article, we review the available data and conclude that there is little evidence to support the notion that low-fat high-carbohydrate diets per se lead to any reduction in the risk for CAD in individuals with diabetes. The only data indicating that low-fat high-carbohydrate diets lead to beneficial effects on carbohydrate and lipoprotein metabolism are confounded either by the lack of suitable experimental control, by the fact that diets also differed in the type of dietary fat and amount of dietary cholesterol, or were enormously enriched in dietary fiber. When these factors are taken into consideration, there appears to be little evidence in support of the view that substituting carbohydrate for fat in the diets of individuals with diabetes results in any measurable beneficial effect. Indeed, it could be argued that the most characteristic defects in carbohydrate and lipoprotein metabolism are exacerbated in response to low-fat high-carbohydrate diets. Alternatively, the data presented herein strongly suggest that diets containing conventional quantities of fat, in which saturated fat is replaced by unsaturated fat and dietary cholesterol reduced, would result in the desired reductions to total and low-density lipoprotein cholesterol concentrations without the adverse effects of increased postprandial glucose and insulin concentrations, increased fasting and postprandial total and very-low-density lipoprotein triglyceride concentrations, and decreased fasting high-density lipoprotein cholesterol concentrations.
The Attending at the Funeral
Authors: Patrick Irvine
Journal: New England Journal of Medicine (1985)

It was during the busy Christmas season when I turned my car into the parking lot of the funeral home. This patient was my third to die in the past few weeks, and tonight was my second wake in three days.It was not easy to make the stop that evening. The holiday season is a difficult time for me to practice medicine; patients are more lonely and depressed, families are under greater stress, and tonight, the bittersweet juxtaposition of holiday joy and the sorrow of death were stressful. I had second thoughts as I got out of my car, . . .
Severe lichen planus clears with very low-dose cyclosporin
Authors: N.J. Levell, C.S. Munro, Janet M. Marks
Journal: British Journal of Dermatology (1992)

Journal Article Severe lichen planus clears with very low‐dose cyclosporin Get access N.J. Levell, N.J. Levell University Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne, U.K. Search for other works by this author on: Oxford Academic Google Scholar C.S. Munro, C.S. Munro University Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne, U.K. Search for other works by this author on: Oxford Academic Google Scholar Janet M. Marks Janet M. Marks University Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 127, Issue 1, 1 July 1992, Pages 66–67, https://doi.org/10.1111/j.1365-2133.1992.tb14836.x Published: 01 July 1992
The Need to Decide If All Estrogens Are Intrinsically Similar
Authors: Jonathan G. Moggs, John Ashby, Helen Tinwell, Fei Ling Lim, David J. Moore, Ian Kimber, George Orphanides
Journal: Environmental Health Perspectives (2004)

We used gene expression profiling to investigate whether the molecular effects induced by estrogens of different provenance are intrinsically similar. In this article we show that the physiologic estrogen 17-beta-estradiol, the phytoestrogen genistein, and the synthetic estrogen diethylstilbestrol alter the expression of the same 179 genes in the intact immature mouse uterus under conditions where each chemical has produced an equivalent gravimetric and histologic uterotrophic effect, using the standard 3-day assay protocol. Data are also presented indicating the limitations associated with comparison of gene expression profiles for different chemicals at times before the uterotrophic effects are fully realized. We conclude that the case has yet to be made for regarding synthetic estrogens as presenting a unique human hazard compared with phytoestrogens and physiologic estrogens. Key words: diethylstilbestrol, estrogen, gene expression, genistein, microarray, phytoestrogen, toxicogenomics, uterus.