tbuckley/cabot-search huggingface dataset:
Detection of receptors for interleukin-6, interleukin-11, leukemia inhibitory factor, oncostatin M, and ciliary neurotrophic factor in bone marrow stromal/osteoblastic cells.
Authors: T Bellido, N Stahl, T J Farruggella, V Borba, G D Yancopoulos, S C Manolagas
Journal: Journal of Clinical Investigation (1996)

The functional receptor complexes assembled in response to interleukin-6 and -11 (IL-6 and IL-11), leukemia inhibitory factor (LIF), oncostatin M (OSM), and ciliary neurotrophic factor (CNTF), all involve the signal transducer gp130: IL-6 and IL-11 induce homodimerization of gp130, while the rest heterodimerize gp130 with other gp130-related beta subunits. Some of these cytokines (IL-6, IL-11, and CNTF) also require a specificity-determining alpha subunit not directly involved in signaling. We have searched for functional receptor complexes for these cytokines in cells of the bone marrow stromal/osteoblastic lineage, using tyrosine phosphorylation of the beta subunits as a detection assay. Collectively, murine calvaria cells, bone marrow-derived murine cell lines (+/+LDA11 and MBA13.2), as well as murine (MC3T3-E1) and human (MG-63) osteoblast-like cell lines displayed all the previously recognized alpha and beta subunits of this family of receptors. However, individual cell types had different constellations of alpha and beta subunits. In addition and in difference to the other cell types examined, MC3T3-E1 cells expressed a heretofore unrecognized form of gp130; and MG-63 displayed an alternative form (type II) of the OSM receptor. These findings establish that stromal/osteoblastic cells are targets for the actions of all the members of the cytokine subfamily that shares the gp130 signal transducer; and suggest that different receptor repertoires may be expressed at different stages of differentiation of this lineage.
Polo-like Kinase 1: A Potential Therapeutic Option in Combination with Conventional Chemotherapy for the Management of Patients with Triple-Negative Breast Cancer
Authors: Virginie Maire, Fariba Némati, Marion Richardson, Anne Vincent-Salomon, Bruno Tesson, Guillem Rigaill, Eléonore Gravier, Bérengère Marty-Prouvost, Leanne De Koning, Guillaume Lang, David Gentien, Aurélie Dumont, Emmanuel Barillot, Elisabetta Marangoni, Didier Decaudin, Sergio Roman-Roman, Alain Pierré, Francisco Cruzalegui, Stéphane Depil, Gordon C. Tucker, Thierry Dubois
Journal: Cancer Research (2012)

Breast cancers are composed of molecularly distinct subtypes with different clinical outcomes and responses to therapy. To discover potential therapeutic targets for the poor prognosis-associated triple-negative breast cancer (TNBC), gene expression profiling was carried out on a cohort of 130 breast cancer samples. Polo-like kinase 1 (PLK1) was found to be significantly overexpressed in TNBC compared with the other breast cancer subtypes. High PLK1 expression was confirmed by reverse phase protein and tissue microarrays. In triple-negative cell lines, RNAi-mediated PLK1 depletion or inhibition of PLK1 activity with a small molecule (BI-2536) induced an increase in phosphorylated H2AX, G(2)-M arrest, and apoptosis. A soft-agar colony assay showed that PLK1 silencing impaired clonogenic potential of TNBC cell lines. When cells were grown in extracellular matrix gels (Matrigel), and exposed to BI-2536, apoptosis was observed specifically in TNBC cancerous cells, and not in a normal cell line. When administrated as a single agent, the PLK1 inhibitor significantly impaired tumor growth in vivo in two xenografts models established from biopsies of patients with TNBC. Most importantly, the administration of BI-2536, in combination with doxorubicin + cyclophosphamide chemotherapy, led to a faster complete response compared with the chemotherapy treatment alone and prevented relapse, which is the major risk associated with TNBC. Altogether, our observations suggest PLK1 inhibition as an attractive therapeutic approach, in association with conventional chemotherapy, for the management of patients with TNBC.
Abstract 5514: Targeted liposomes in cancer therapy
Authors: Hari Chandana R. Mulamalla, Maria P. Lambros, Ying Huang
Journal: Cancer Research (2010)

Abstract The purpose of this project was to design a liposomal formulation which targets the SLC transporter. Daunorubicin, an anticancer drug, used as a model was encapsulated in the targeted liposomal formulation and the cellular uptake and cytotoxicity of targeted liposomal daunorubicin (TLD) as well as the mechanisms of cellular uptake were evaluated using the A549 lung cancer cell line. A quantity of 3×105/2ml cells of A549 were cultured in each well of 6 well plates in RPMI medium. The cells were treated with TLD, non targeted liposomal (NTL) daunorubicin and free, non-encapsulated daunorubicin containing 10µM and 5µM drug. They were incubated for 5-6 hours at 37oC and analyzed using flow cytometry and fluorescence imaging. The cytotoxicity of the formulations was determined using MTS assay. The IC50 was determined from the growth inhibition curves of cell viability. Furthermore, the mechanism of internalization of the TLD formulation was studied using inhibitors specific to each pathway of internalization. The results show that the cellular uptake TLD showed a significant increase of 2- fold compared to that of NTL and free drug for both concentrations (10µM and 5µM). These results were also consistent with the cytotoxicity study showing higher cytotoxicity of TLD compared to NTL and free drug, The IC50 of TDL showed a 2.3-fold and 3.4-fold decrease compared to NTL and free drug, respectively. Also the data showed decrease in the cellular uptake of TLD when the macropinocytosis pathway was inhibited. Depletion of cholesterol in the cellular wall also reduced the cellular uptake of the TLD formulation. The results indicate that our novel targeted liposomal formulation shows enhanced cellular uptake and cytotoxicity likely due to macropinocytosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5514.
Ectopic extramammary Paget's disease affecting the upper abdomen
Authors: Y. ONISHI, K. OHARA
Journal: British Journal of Dermatology (1996)

Summary We present 57-year-old man in whom ectopic extramammary Paget's disease (EMPD) affected the upper abdomen. Although the clinical appearance was suggestive of Bowen's disease or superficial basal cell epithelioma (BCE), the biopsy specimen showed EMPD histologically. Only 12 cases of ectopic EMPD have been reported (including this case). In our 20 year experience of 129 EMPD, this is the first ectopic case. Thus, the frequency of ectopic EMPD is 0–78% (one of 129) in our study. The male/female ratio in the reported 12 cases is 2 : 1. nearly the same as EMPD in general (2:1:1, in our 129 cases). The mean age of the 12 patients is 65.8 years, which is not significantly different from ordinary EMPD (66–;4 years, in our 129 cases). Comparing ectopic EMPD to ordinary EMPD, clinically and histologically. we could find no difference. As they appear to be the same disease, ectopic and ordinary EMPD may share similar origins and mechanisms of occurrence. We support the hypothesis that Paget's cells originate from the remaining pluripotential germinative cells which are able to differentiate into many kinds of secreting glands.
Excess collagen in hypertensive pulmonary arteries decreases vascular distensibility.
Authors: C A Tozzi, D L Christiansen, G J Poiani, D J Riley
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Increased vascular collagen content is a major feature of pulmonary vascular remodeling. The functional role of excess collagen in decreasing pulmonary vascular compliance has not been established. We determined whether there was a correlation between hydroxyproline content of rat pulmonary artery segments and elastance (EPA) of the pulmonary artery bed during development of hypoxic pulmonary hypertension (10% O2, 10 d) and normoxic recovery. EPA was measured by air-filled pressure-volume curves. After 10 d of hypoxia, hydroxyproline content increased approximately 2-fold in large segments (1,200-250 microns in diameter) but not significantly in small segments (> 250 microns). Elastance increased from 87 +/- 6 (SEM) to 145 +/- 8 mm Hg/ml (p < 0.05) within 5 d of hypoxia and returned to control value 3 wk after recovery. There was a correlation between collagen content and EPA in large segments during development of hypertension; no correlation was found during recovery from hypoxia. The ratio of hydroxyproline to total protein was unchanged in large segments after recovery from hypoxia but was increased in small segments after recovery. We conclude that increased collagen in large pulmonary arteries directly influences EPA during the development of hypoxic pulmonary hypertension.
Acute and Chronic Changes in the Microcirculation of the Liver in Inbred Strains of Mice Following Infection With Mouse Hepatitis Virus Type 3
Authors: Peggy J. Macphee, Vincent J. Dindzans, Lai-Sum Fung, Gary A. Levy
Journal: Hepatology (1985)

The acute and chronic effects of mouse hepatitis virus type 3 on the microcirculation of the liver in both semisusceptible C3HeB/FeJ and fully resistant A/J mice were studied. In the C3HeB/FeJ mice, abnormalities of microcirculatory flow were noted as early as 12 hr after infection and by 24 hr, localized avascular foci appeared. Disturbances were characterized by granular blood flow, sinusoidal microthrombi, distortion of sinusoids by edematous hepatocytes and necrotic lesions. Following the acute infection, Day 10, two patterns of chronic disease were observed. Eighty percent of the mice developed chronic granulomatous hepatitis whereas in the remaining 20% a more severe chronic aggressive hepatitis was observed which was characterized by ongoing hepatocellular necrosis and a marked mononuclear cell infiltrate. In both cases, in vivo microcirculatory abnormalities were found predominantly around visible lesions. Onset of the microcirculatory abnormalities was found to be concomitant with a rise in monocyte related procoagulant activity. Procoagulant activity rose acutely and remained elevated throughout the chronic phase but was higher in animals with severe disease. In contrast to the above, normal blood flow and histology were seen in the resistant A/J mice at all times following infection, and procoagulant activity remained at basal levels despite active viral replication as demonstrated by immunofluorescence studies and recovery of infectious virus. These observations suggest a role for monocyte procoagulant activity in the development of microcirculatory abnormalities following mouse hepatitis virus type 3 infection which may be important in the pathogenesis of the disease.
Convulsions, Hyperglycemia, and Glycosuria From Overdose of Nalidixic Acid
Authors: Mohammad A. Islam
Journal: JAMA (1965)

NALIDIXIC ACID (NegGram) is an antibacterial agent used in the treatment of urinary-tract infections. Nalidixic acid (1-ethyl-7-methyl-1,8-naphthyridin-4-one-3-carboxylic acid) is not related to sulfonamides, antibiotics, or nitrofurans. It may be an effective agent against some of the intractable gram-negative bacteria, including<i>Proteus, Escherichia coli, Aerobacter</i>, and<i>Klebsiella</i>. The average daily dose of nalidixic acid for a child of 6 to 14 years of age is 1 to 2 gm, and that for an adult, 2 to 4 gm. Reports of toxicity have been few, and the side effects of this drug have been considered minimal. The commoner toxic symptoms encountered with its use are nausea, vomiting, and drowsiness or weakness. Of 120 patients treated with this drug, Ward-Mcquaid et al<sup>1</sup>found only one with a skin rash, while another with duodenal ulcer had nausea. Barlow<sup>2</sup>in 1963 reported a maculopapular rash on the trunk and lower limbs of two
Autoantigen microarrays for multiplex characterization of autoantibody responses
Authors: William H. Robinson, Carla DiGennaro, Wolfgang Hueber, Brian B. Haab, Makoto Kamachi, Erik J. Dean, Sylvie Fournel, Derek Fong, Mark C. Genovese, Henry E. Neuman De Vegvar, Karl Skriner, David L. Hirschberg, Robert I. Morris, Sylviane Muller, Ger J. Pruijn, Walther J. van Venrooij, Josef S. Smolen, Patrick O. Brown, Lawrence Steinman, Paul J. Utz
Journal: Nature Medicine (2002)
Further Studies on the Normal Lymphocyte Transfer Test in Man
Authors: R. Harris, C. A. Clarke, A. L. Jones, P. M. Sheppard, D. Lehane, M. McCarthy, S. D. Lawler, H. S. Shatwell
Journal: BMJ (1966)

diluting fluid before counting, and tests for viability carried out by the dye-exclusion method.As has been said, a point of considerable importance lies in the exact technique used for intradermal injection.Variability in the depth of injection produces discrepant results, and negative reactions certainly follow inadvertent subcutaneous injections.The method recom- mended for Mantoux-testing (Irvine, 1954) has been adopted in the present work, and injections which do not immediately raise a bleb 6-8 mm. in diameter dimpled by hair follicles are at once repeated.All injections were given into the anterior surface of the upper forearm.In these experiments induration, more palpable than visible but corresponding to the " weal " of Moorhead and Patel (1964), has been measured as well as the erythema.The maximum induration usually occurred, as in previous experiments (Moorhead and Patel, 1964), on the second and eleventh days, and it is this and the erythema visible at these times which are recorded and subsequently referred to as the first and second reactions.No true weals-that is, transient urticaria-like reactions-were seen at 48 hours, though occasionally these occurred in the first 24 hours.2. Lymphocytes were killed by freezing as described below.
Work disability in adults with cystic fibrosis.
Authors: M Gillen, D Lallas, C Brown, E Yelin, P Blanc
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Greater numbers of persons with cystic fibrosis (CF) reach adulthood and, therefore, actively participate in the labor force. In this study, we estimated labor force participation rates and determined risk factors for work disability among persons with CF. We recruited 49 (73%) of 67 adults followed at one of two hospital-based CF centers. We ascertained employment history and CF-attributed work disability by structured questionnaire. Independently, we reviewed medical records for demographics and illness severity indicators. We analyzed potential risk factors for work disability by logistic regression analysis. All of those studied reported past or present labor force participation, consistent with high work motivation. Complete cessation of work attributed to CF was reported by 17 (35%; 95% CI, 21 to 49%). Although 23 (47%; 95% CI, 32 to 60%) of those surveyed stated that CF had affected career choice, only nine respondents had ever received career counselling and 16 had ever discussed job choice with their physicians. After adjusting for standard measures of disease severity by multiple logistic regression, age, adult diagnosis of CF, female gender, and single marital status, analyzed as a group, provided significant additional explanatory power to a predictive model of disability risk (model chi square [4 d.f.] = 11.5, p < 0.05). Health care professionals who design interventions targeted at work disability among persons with CF should address demographic factors as well as illness severity and should assess the vocational needs of persons with CF and the potential benefit of career counselling.
The Contribution of Activated Factor XIII to Fibrinolytic Resistance in Experimental Pulmonary Embolism
Authors: Guy L. Reed, Aiilyan K. Houng
Journal: Circulation (1999)

The resistance of thrombi to fibrinolysis induced by plasminogen activators remains a major impediment to the successful treatment of thrombotic diseases. This study examines the contribution of activated factor XIII (factor XIIIa) to fibrinolytic resistance in experimental pulmonary embolism.The fibrinolytic effects of specific inhibitors of factor XIIIa-mediated fibrin-fibrin cross-linking and alpha2-antiplasmin-fibrin cross-linking were measured in anesthetized ferrets with pulmonary emboli. Five experimental groups were treated with heparin (100 U/kg) and/or tissue plasminogen activator (TPA, 1 mg/kg) and the percent (mean+/-SD) lysis of emboli was determined: (1) control, normal factor XIIIa activity (14.1+/-4. 8% lysis); (2) inhibited factor XIIIa activity (42.7+/-7.4%); (3) normal factor XIIIa activity+TPA (32.3+/-7.7%); (4) inhibited factor XIIIa activity+TPA (76.0+/-11.9%); and (5) inhibited alpha2-antiplasmin-fibrin cross-linking+TPA (54.7+/-3.9%). Inhibition of factor XIIIa activity increased endogenous lysis markedly (group 1 versus 2; P<0.0001), to a level comparable to that achieved with TPA (group 2 versus 3; P<0.05). Among groups receiving TPA, selective inhibition of factor XIII-mediated alpha2-antiplasmin-fibrin cross-linking enhanced lysis (group 3 versus 5; P<0.0005). Complete inhibition of factor XIIIa also amplified lysis (group 3 versus 4; P<0.0001) and had greater effects than inhibition of alpha2-antiplasmin cross-linking alone (group 4 versus 5; P<0.0005). No significant fibrinogen degradation occurred in any group.Factor XIIIa-mediated fibrin-fibrin and alpha2-antiplasmin-fibrin cross-linking both caused experimental pulmonary emboli to resist endogenous and TPA-induced fibrinolysis. This suggests that factor XIIIa may play a critical role in regulating fibrinolysis in human thrombosis.
Prospective study of follow up alone in stage I teratoma of the testis.
Authors: G Read, R J Johnson, P M Wilkinson, B Eddleston
Journal: BMJ (1983)

In a prospective surveillance study of 45 patients with stage I teratoma of the testis 34 (76%) required no further treatment. Eleven patients relapsed but were salvaged by chemotherapy and radiotherapy. Seven patients relapsed within three months of the initial assessment and only one after more than 12 months. These preliminary results suggest that a follow up policy in stage I teratoma of the testis is possible but only in a regional centre with facilities for close monitoring of patients.
Epidermal origin of the amyloid in localized cutaneous amyloidosis
Authors: H. MAEDA, S. OHTA, Y. SAITO, H. NAMEKI, H. ISHIKAWA
Journal: British Journal of Dermatology (1982)

A case of localized cutaneous amyloidosis which developed after a lichen planus‐like skin reaction is reported. The amyloid consisted of amyloid fibrils enveloped by heparan sulphate granules. These amyloid fibrils reacted to anti‐human keratin antibody, indicating an epidermal origin for the fibrils.
Hip Protectors — A Breakthrough in Fracture Prevention
Authors: Laurence Rubenstein
Journal: New England Journal of Medicine (2000)

Hip fractures are one of the most devastating and costly problems commonly faced by elderly people. Each year in the United States, more than 300,000 people 65 years old or older are hospitalized because of hip fractures,1 and about a quarter of these people survive for less than one year because of the fracture or its complications.2 Of those who survive, most have substantial reductions in their ability to function in daily life and in their ability to walk, and a sizable minority are living in long-term care institutions by the end of the year after injury.2 Most previous attempts . . .
Community Engagement and the Ethics of Global, Translational Research: A Response to Sofaer and Eyal
Authors: John Lynch, Monica Mitchell
Journal: The American Journal of Bioethics (2010)

"Community Engagement and the Ethics of Global, Translational Research: A Response to Sofaer and Eyal." The American Journal of Bioethics, 10(8), pp. 37–38 This publication was supported by an Institutional Clinical and Translational Science Award, NIH/NCRR Grant #1UL1RR026314-01. Its contents are solely the responsibility of the authors and does not necessarily represent the views of the NIH.
Effect of a Nonionic Surface-Active Agent on Blood Viscosity and Platelet Adhesiveness
Authors: FREDERICK L. GROVER, MICHAEL W. HERON, MELVIN M. NEWMAN, BRUCE C. PATON
Journal: Circulation (1969)

The effects of Pluronic F68, a nonionic surface-active agent, on blood viscosity and platelet adhesiveness during extracorporeal circulation were investigated. Blood viscosity was significantly decreased. Platelet adhesiveness decreased markedly in six patients within ten minutes after intravenous injection. Pluronic F68 has many properties and actions which make it a useful additive to perfusion systems. Its potential in the treatment of diseases in which high viscosity or increased platelet adhesiveness are present deserves investigation.
On Bedside Teaching
Authors: Michael A. LaCombe
Journal: Annals of Internal Medicine (1997)

Actual teaching at the bedside during attending rounds, with emphasis on history taking and physical diagnosis, has declined from an incidence of 75% in the 1960s to an incidence of less than 16% today. Profound advances in technology, in imaging, and in laboratory testing and our fascination for these aspects of patient care, account for part of this decline, but faculty must also assume responsibility for the present lack of bedside teaching. If we are to reverse this trend, we will need to realize the barriers to bedside teaching, both real and imagined, and overcome them. And if we are to become effective bedside teachers, as were our mentors, we will need to sharpen our own physical diagnostic skills. We will need to learn how to be gentle with students and housestaff, how to better communicate with patients, and how to teach ethics and professionalism with the patient at hand.
THE ETIOLOGIC AGENTS OF VARICELLA AND HERPES ZOSTER
Authors: Thomas H. Weller, Helen M. Witton, E. John Bell
Journal: The Journal of Experimental Medicine (1958)

Fourteen strains of virus derived from the cutaneous lesions of cases of varicella and eight from patients with herpes zoster were propagated serially in primary explant cultures of human preputial or embryonic skin-muscle tissue. Infectious material could not be demonstrated in the fluid phase of infected cultures and inocula for passage therefore consisted of suspensions of infected tissue. Such tissue suspensions when stored in the frozen state did not regularly retain infectivity. The cytopathic process was focal and appeared to develop as the result of transfer of infectious material from cell to contiguous cell. Optimum development of the focal lesions in vitro related directly to conditions favoring optimum tissue growth and was further influenced by the spatial relationship of the tissue outgrowth. A variety of types of cells of human origin and several of monkey origin were susceptible to infection and responded with the formation of intranuclear inclusion bodies. The cellular response otherwise was variable, ranging from simple rounding with little change in size to the formation of large multinucleated cytoplasmic syncytia. Strains of virus recovered from patients with varicella and from patients with herpes zoster could not be distinguished on the basis of their cultural attributes.