tbuckley/cabot-search huggingface dataset:
Systemic and immunotoxicity of silver nanoparticles in an intravenous 28 days repeated dose toxicity study in rats
Authors: Wim H. De Jong, Leo T.M. Van Der Ven, Annemarie Sleijffers, Margriet V.D.Z. Park, Eugene H.J.M. Jansen, Henk Van Loveren, Rob J. Vandebriel
Journal: Biomaterials (2013)

Because of its antibacterial activity nanosilver is one of the most commonly used nanomaterials. It is increasingly used in a variety of both medical and consumer products resulting in an increase in human exposure. However, the knowledge on the systemic toxicity of nanosilver is relatively limited. To determine the potential systemic toxicity of silver nanoparticles (Ag-NP) with different sizes (20 nm and 100 nm) a 28-days repeated dose toxicity study was performed in rats using intravenous administration. The toxic effect of the 20 nm Ag-NP was performed using the bench mark dose (BMD) approach. Treatment with a maximum dose of 6 mg/kg body weight was well tolerated by the animals. However, both for 20 nm and 100 nm Ag-NP growth retardation was observed during the treatment. A severe increase in spleen size and weight was present which was due to an increased cell number. Both T and B cell populations showed an increase in absolute cell number, whereas the relative cell numbers remained constant. At histopathological evaluation brown and black pigment indicating Ag-NP accumulation was noted in spleen, liver, and lymph nodes. Ag-NP was also detected incidentally in other organs. Clinical chemistry indicated liver damage (increased alkaline phosphatase, alanine transaminase, and aspartate transaminase) that could not be confirmed by histopathology. Hematology showed a decrease in several red blood cell parameters. The most striking toxic effect was the almost complete suppression of the natural killer (NK) cell activity in the spleen at high doses. Other immune parameters affected were: decreased interferon-γ and interleukin (IL)-10 production by concanavalin-A stimulated spleen cells, increased IL-1β and decreased IL-6, IL-10 and TNF-α production by lipopolysaccharide stimulated spleen cells, increase in serum IgM and IgE, and increase in blood neutrophilic granulocytes. For the spleen weight a critical effect dose of 0.37 mg/kg body weight (b.w.) could be established. The lowest critical effect dose (CED) for a 5% change compared to control animals was observed for thymus weight (CED05 0.01 mg/kg b.w.) and for functional immune parameters, i.e. decrease in NK cell activity (CED05 0.06 mg/kg b.w.) and LPS stimulation of spleen cells (CED05 0.04 mg/kg b.w.). These results show that for nanosilver the most sensitive parameters for potential adverse responses were effects on the immune system.
Belt and Bottom Bias in 'Beeper Obliterans'
Authors: Patrice N. Stevenson
Journal: JAMA (1992)

<h3>To the Editor.</h3> —I read with interest the recent letter by Drs Izenberg and Dowshen<sup>1</sup>characterizing their observations of the natural history of "beeper obliterans." I would submit that this syndrome as outlined (the periodic emission of beeping tones secondary to the impingement of an increasing abdominal girth on the test button of a pager-beeper) appears to be a peculiarly male affliction. Given the difference in the general propensity of fat to be deposited at the belt (beeper) line in males and somewhat more distally in females, obesity of equal magnitude may not cause equal beeper dysfunction. Also, the transient condition of "gestational beeper obliterans" should be recognized as an accelerated passage from stages 0 to 4 in a mere 40 weeks.
A Prospective Study of Posttransfusion Hepatitis
Authors: David J. Gocke
Journal: JAMA (1972)

Transfusion of blood containing Australia antigen (Au) was followed by development of hepatitis, Au antigenemia, or both in 52% of recipients. Another 23% of Au recipients exhibited an immune response. However, transfusion of Au-<i>negative</i>blood was associated with anticteric hepatitis in 16% and icteric hepatitis in 2% of the recipients. The typical Au recipient with hepatitis was Au positive during the acute phase and had a severe clinical illness. In the recipient of Au-negative blood, hepatitis was characterized by Au-negative tests in the acute phase and a mild illness. On the basis of these data, estimates of the relation of Au to the overall problem of posttransfusion hepatitis suggest that Au accounts for approximately 25% of icteric cases. Twenty percent of patients who developed Au antigenemia following transfusion became carriers of the antigen. Patients who became Au carriers tended to have mild or anicteric hepatitis, while those with severe, icteric attacks reverted to the Aunegative state. The frequency of Au antigen in commercial donor blood was 13-fold greater than in volunteer blood.
Abstract 3665: Enzymatic depletion of pericellular HA from tumor cell surface sensitizes Erbitux dependent immune cell-mediated cytotoxicity
Authors: Netai C. Singha, Ping Jiang, Gregory I. Frost, H Michael Shepard
Journal: Cancer Research (2011)

Abstract Hyaluronan (HA), a ubiquitous high-molar-mass linear glycosaminoglycan (GAG) plays a critical role in cell adhesion, motility, growth and differentiation. HA accumulation is associated with many human cancers. Human tumor cells can form HA rich pericellular matrix which might favor tumor growth by preventing the access of host immune cells to malignant cells. Monoclonal antibody (MAb) based therapeutics are emerging as an important component of therapy for human malignancies. Despite the very high specificity of monoclonal antibodies, resistance to MAb therapy is common. Antibody Dependent Cell-mediated Cytotoxicity (ADCC) is an important effector for the clinical efficacy of MAbs and relies on effective interaction between the Fc domain of antigen bound antibody and FcγRIII positive immune cells. We hypothesize that pericellular HA coating may contribute to resistance of HA-rich malignant cells to MAb mediated therapy by preventing efficient access of effector cells to their tumor targets. Enzymatic depletion of HA with PEGPH20 hyaluronidase could potentially sensitize such tumors to MAb mediated therapy. remove ell surface and ated therapy by preventing tumor cells contact EGFR positive breast carcinoma cell line MDA-MB-231luc and genetically engineered HAS2 over expressing MDA-MB-231HAS2 were used to investigate the role of HA-rich pericellular matrix in inhibition of ADCC. ADCC assay was performed by incubating Calcein AM labeled monolayer cells with monoclonal antibody (1h at 37°C) followed by co-incubation of recombinant human IL-2 (rhIL-2) activated human peripheral blood mononuclear cells (PBMC, 5h at 37°C, 5% CO2) with or without PEGPH20. Live cells from each treatment were assessed by fluorescence readings at Ex/Em 488nm/537nm (SpectraMax M2e plate reader) at the end of the assay. Percentages of cell killing were calculated against control. The student's t test was used to compare the difference between treatments. Particle exclusion assay demonstrated that HAS2 over expressing MDA-MB-231HAS2 cells formed a pericellular coat that inhibited access of the rhIL-2 activated PBMC to tumor cells. Incubation with PEGPH20 removed the HA-rich pericellular matrix and promoted contact of PBMC to tumor cells. Incubation of Erbitux with rhIL-2 activated PBMC induced a dose dependent killing of both MDA-MB-231luc and MDA-MB-231HAS2 cells. PEGPH20 increased ADCC by 10% on MDA-MB-231luc (HAlow) and 25% on MDA-MB-231HAS2 (HAhigh) tumor cells. Our results show that the HA-rich pericellular matrix on adherent tumor cells inhibits ADCC and PEGPH20 depletion of this coat sensitizes the tumor cells to ADCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3665. doi:10.1158/1538-7445.AM2011-3665
Child wellbeing and inequalities in rich countries
Authors: M E Black, H E Jeffery
Journal: BMJ (2007)

A recent Unicef report ranked the wellbeing of children in 21 rich countries.1 The report aggregated national data on more than 40 indicators from credible sources in six dimensions—material wellbeing (related to income, poverty, material goods), health and safety, educational wellbeing, family and peer relationships, behaviours and risks, and subjective wellbeing (how the child sees his or her self). The press had a field day when the report was published,2 because the United States and the United Kingdom were in the bottom five countries for five of the dimensions. The UK ranked 12th in health and the US ranked 12th in education; questions were rightly asked about how this could happen and what the government was going to do about it.
Managing urinary incontinence in older people
Authors: S. Thirugnanasothy
Journal: BMJ (2010)

#### Summary points

Urinary incontinence is defined by the International Continence Society as involuntary urinary leakage.1 The condition is common among older people. It affects more than a fifth of people aged over 85 years, according to a recent cohort study,2 although this is probably an underestimate. Urinary incontinence has both physical and psychological consequences, including damage to skin, urinary tract infections, an increased risk of falls, avoidance of going far from home, and a feeling of alienation.3 Urinary incontinence can also be difficult for carers to manage, and a cohort study of about 6000 patients found that urinary incontinence was second only to dementia as a reason for admission to long term care.4

In the United Kingdom, the 2001 report National Service Framework for Older People highlighted a need for continence services to be integrated across primary, acute, and specialist care.5 A recent national audit of continence care for older people found that urinary incontinence is poorly managed both in the community and in secondary care. Fundamental assessments such as rectal examination and measurement of …
The genomic landscape of small intestine neuroendocrine tumors
Authors: Michaela S. Banck, Rahul Kanwar, Amit A. Kulkarni, Ganesh K. Boora, Franziska Metge, Benjamin R. Kipp, Lizhi Zhang, Erik C. Thorland, Kay T. Minn, Ramesh Tentu, Bruce W. Eckloff, Eric D. Wieben, Yanhong Wu, Julie M. Cunningham, David M. Nagorney, Judith A. Gilbert, Matthew M. Ames, Andreas S. Beutler
Journal: Journal of Clinical Investigation (2013)

Small intestine neuroendocrine tumors (SI-NETs) are the most common malignancy of the small bowel. Several clinical trials target PI3K/Akt/mTOR signaling; however, it is unknown whether these or other genes are genetically altered in these tumors. To address the underlying genetics, we analyzed 48 SI-NETs by massively parallel exome sequencing. We detected an average of 0.1 somatic single nucleotide variants (SNVs) per 106 nucleotides (range, 0-0.59), mostly transitions (C>T and A>G), which suggests that SI-NETs are stable cancers. 197 protein-altering somatic SNVs affected a preponderance of cancer genes, including FGFR2, MEN1, HOOK3, EZH2, MLF1, CARD11, VHL, NONO, and SMAD1. Integrative analysis of SNVs and somatic copy number variations identified recurrently altered mechanisms of carcinogenesis: chromatin remodeling, DNA damage, apoptosis, RAS signaling, and axon guidance. Candidate therapeutically relevant alterations were found in 35 patients, including SRC, SMAD family genes, AURKA, EGFR, HSP90, and PDGFR. Mutually exclusive amplification of AKT1 or AKT2 was the most common event in the 16 patients with alterations of PI3K/Akt/mTOR signaling. We conclude that sequencing-based analysis may provide provisional grouping of SI-NETs by therapeutic targets or deregulated pathways.
Human Vγ9Vδ2-T cells efficiently kill influenza virus-infected lung alveolar epithelial cells
Authors: Hong Li, Zheng Xiang, Ting Feng, Jinrong Li, Yinping Liu, Yingying Fan, Qiao Lu, Zhongwei Yin, Meixing Yu, Chongyang Shen, Wenwei Tu
Journal: Cellular and Molecular Immunology (2013)
Occupational and environmental reproductive hazards education and resources for communities of color.
Authors: A Dula, S Kurtz, M L Samper
Journal: Environmental Health Perspectives (1993)

Little research has been published on the occupational and environmental hazards affecting people of color. Even less is known about the hazards that affect women of color. Although women of color have always been aggressive participants in the work force, their labor activity has increased dramatically over the last decade. Current job placement patterns suggest that women of color are concentrated in the lowest-paying and most hazardous jobs. In this paper, we specifically focus on occupational and environmental reproductive health concerns. We write with the understanding that reproductive hazards can affect pregnant women, nonpregnant women, and men, as well as the health and development of young children. Emphasis is placed primarily on African American women, because information on Hispanic, Native American, and Asian women is very limited. We discuss the participation of women of color in the labor force, using the U.S. Department of Labor categories. We review specific occupational hazards associated with each category of work and briefly discuss environmental hazards, noting that communities of color are at a disproportionate risk of exposure. Finally, we present the consensus report of the Community Education Working Group from the Woods Hole Conference on Occupational and Environmental Reproductive Hazards.
Exercise stimulates the mitogen-activated protein kinase pathway in human skeletal muscle.
Authors: D Aronson, M A Violan, S D Dufresne, D Zangen, R A Fielding, L J Goodyear
Journal: Journal of Clinical Investigation (1997)

Physical exercise can cause marked alterations in the structure and function of human skeletal muscle. However, little is known about the specific signaling molecules and pathways that enable exercise to modulate cellular processes in skeletal muscle. The mitogen-activated protein kinase (MAPK) cascade is a major signaling system by which cells transduce extracellular signals into intracellular responses. We tested the hypothesis that a single bout of exercise activates the MAPK signaling pathway. Needle biopsies of vastus lateralis muscle were taken from nine subjects at rest and after 60 min of cycle ergometer exercise. In all subjects, exercise increased MAPK phosphorylation, and the activity of its downstream substrate, the p90 ribosomal S6 kinase 2. Furthermore, exercise increased the activities of the upstream regulators of MAPK, MAP kinase kinase, and Raf-1. When two additional subjects were studied using a one-legged exercise protocol, MAPK phosphorylation and p90 ribosomal S6 kinase 2, MAP kinase kinase 1, and Raf-1 activities were increased only in the exercising leg. These studies demonstrate that exercise activates the MAPK cascade in human skeletal muscle and that this stimulation is primarily a local, tissue-specific phenomenon, rather than a systemic response to exercise. These findings suggest that the MAPK pathway may modulate cellular processes that occur in skeletal muscle in response to exercise.
Could nephrotoxicity due to colistin be ameliorated with the use of N-acetylcysteine?
Authors: Ezgi Ozyilmaz, Fatma Ayerden Ebinc, Ulver Derici, Ozlem Gulbahar, Guleser Goktas, Cigdem Elmas, I. Kivilcim Oguzulgen, Sukru Sindel
Journal: Intensive Care Medicine (2010)
Proliferation centers in chronic lymphocytic leukemia: correlation with cytogenetic and clinicobiological features in consecutive patients analyzed on tissue microarrays
Authors: M Ciccone, C Agostinelli, G M Rigolin, P P Piccaluga, F Cavazzini, S Righi, M T Sista, O Sofritti, L Rizzotto, E Sabattini, G Fioritoni, S Falorio, C Stelitano, A Olivieri, I Attolico, M Brugiatelli, P L Zinzani, E Saccenti, D Capello, M Negrini, A Cuneo, S Pileri
Journal: Leukemia (2011)
All together now
Authors: Wendy Moore
Journal: BMJ (2008)

In celebrating the 60th anniversary of the World Health Organization this year, it is humbling to reflect that for most of human history international cooperation has been notable by its absence.

Early races and cultures were more likely to persecute each other as the perceived carriers of lethal diseases than to join forces in mutual opposition. The Mongols pioneered germ warfare when they catapulted plague-ridden corpses into the besieged Black Sea port of Caffa in 1347, thereby launching the Black Death on its devastating sweep through Europe. When syphilis was first observed in 1495, each successive nation of sufferers named the scourge after their closest enemies, so that the French called it “the Neapolitan …
OT2-01-04: Cardiac Safety of Anthracycline-Containing Adjuvant Chemotherapy of Early Breast Cancer: OSCAR/ABC Ongoing, Observational, Multicentric Study.
Authors: E Ricevuto, V Cocciolone, M Zilli, MT Scognamiglio, B Pistilli, G Di Menna, M Mancini, K Cannita, MI Adinolfi, MG Ferrandina, A Pancotti, F Recchia, L Latini, C Ficorella, S Iacobelli
Journal: Cancer Research (2011)

Abstract BACKGROUND: Among the different chemotherapeutic options available for adjuvant treatment of early breast cancer (EBC), anthracycline-containing regimens represent prevalent choices. OSCAR/ABC is an observational, prospectic, multicentric study aimed at evaluating, in the clinical practice, the relevance of cardiac dysfunction and congestive heart failure (CHF) associated to “free choice”, anthracycline-containing adjuvant regimens and to identify patients at increased cardiac risk. PATIENTS AND METHODS: patients candidate to receive adjuvant anthracycline-containing chemotherapy, will be enrolled in the study. Data on demographic and clinical characteristics of patients (age, cardio-vascular comorbidity) tumor features (TNM, histotype, ER and PgR status, Ki67, and HER2 status), type of adjuvant regimen and tolerability of treatment will be collected and centrally registered at the Consorzio Interuniversitario Nazionale per ***1a Bio-Oncologia (CINBO) using e-CRFs. Data on type, sites and doses of radiotherapy performed will be collected, to evaluate the possible impact on cardiac function. Primary aim of the study is to evaluate the prevalence of cardiac dysfunction and CHF among the whole population enrolled, particularly according to risk criteria and type of administered chemotherapy. Cardiac dysfunction is defined as limiting cardio-vascular toxicity (≥ Grade 3 dyspnea, arrhytmia, hypertension) and/or asymptomatic LVEF reduction ≥20% (if &amp;gt;50% at the baseline) or ≥10% (if ≤50% at baseline); CHF is defined as clinical diagnosis and/or symptomatic LVEF reduction ≥20% (if &amp;gt;50% at the baseline) or ≥10% (if ≤50% at baseline). Assessment of cardiac risk involves the evaluation of age (&amp;lt; vs ≥ 65 years), cardio-vascular comorbidities (requiring treatment or not) and Left-Ventricular Ejection Fraction LVEF (&amp;gt; vs ≤ 55%) at diagnosis. Clinical and instrumental cardiac evaluation (ECG, Ecocardiography) will be performed at study entry, on-treatment and up to 5 years thereafter. Secondary objective of the study is to evaluate the clinical properness of different adjuvant anthracyclines-containing chemotherapy options, with regard to prevalence of therapeutic regimens, safety, efficacy (DFS and OS) and costs analysis. Cardiac safety and general toxicity on-treatment will be evaluated according to NCI criteria. The expected enrollment is 1,200 patients in 36 months. From September 2010 to May 2011, 7 of the 13 Centers involved in the study are active, with 65 enrolled patients. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-01-04.
The effect of anthralin (dithranol) on mitochondria
Authors: P. MORLIÉRE, L. DUBERTRET, T. SA E. MELO, C. SALET, M. FOSSE, R. SANTUS
Journal: British Journal of Dermatology (2006)

Journal Article The effect of anthralin (dithranol) on mitochondria Get access P. MORLIÉRE, P. MORLIÉRE Laboratoire de Dermatologie, Hôpital Henri Mondor, 94010 Creteil, France Dr P. Morliére, Laboratoire de Dermatologie, Hôpital Henri Mondor, 94010 Creteil, France. Search for other works by this author on: Oxford Academic Google Scholar L. DUBERTRET, L. DUBERTRET Laboratoire de Dermatologie, Hôpital Henri Mondor, 94010 Creteil, France Search for other works by this author on: Oxford Academic Google Scholar T. SA E. MELO, T. SA E. MELO Laboratoire de Physico‐Chimie de I'Adaptation Biologique, UA 481 du CNRS, Museum National d'Histoire Naturelle, 43, rue Cuvier, 75231 Paris Cedex 05, France Search for other works by this author on: Oxford Academic Google Scholar C. SALET, C. SALET Laboratoire de Biophysique, INSERM U201 and UA481 du CNRS, Museum National d'Histoire Naturelle, 61, rue Buffon, 75005 Paris, France Search for other works by this author on: Oxford Academic Google Scholar M. FOSSE, M. FOSSE Laboratoire de Dermatologie, Hôpital Henri Mondor, 94010 Creteil, France Search for other works by this author on: Oxford Academic Google Scholar R. SANTUS R. SANTUS Laboratoire de Physico‐Chimie de I'Adaptation Biologique, UA 481 du CNRS, Museum National d'Histoire Naturelle, 43, rue Cuvier, 75231 Paris Cedex 05, France Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 112, Issue 5, 1 May 1985, Pages 509–515, https://doi.org/10.1111/j.1365-2133.1985.tb15258.x Published: 01 May 1985 Article history Accepted: 25 September 1984 Published: 01 May 1985
Coronary Artery Spasm
Authors: Vinod Raxwal, Kamal Gupta
Journal: Circulation (2006)

A 50-year-old male patient presented with severe chest pain and right arm tightness.On arrival, he was hypotensive and had an initial slow atrial fibrillation with acute ST-segment elevation across the anterior and inferior leads (Figure 1).This required external pacing as well as atropine.The patient underwent urgent diagnostic coronary angiography that revealed a severely diseased, small-caliber right coronary artery with 100% distal cutoff before its bifurcation (Figure 2); 25% distal left main coronary artery stenosis with a diffusely diseased left anterior descending coronary artery from the ostium to the apex; and a circumflex artery with 50% proximal stenosis (Figure 3).Intracoronary nitroglycerin and nicardipine were injected, which resulted in complete resolution of stenosis (Figure 4 andFigure 5).The ST-segment elevation on the ECG subsequently resolved, and the patient returned to sinus rhythm.The patient had a peak troponin value of 0.29 and preserved left ventricular function with no wall motion abnormalities.
THE IN VITRO DIFFERENTIATION OF MONONUCLEAR PHAGOCYTES
Authors: Zanvil A. Cohn, Belinda Benson
Journal: The Journal of Experimental Medicine (1965)

Mouse mononuclear phagocytes cultivated in 50 per cent newborn calf serum medium pinocytize actively and form large numbers of phase-dense granules as well as three hydrolytic enzymes. When such cells are then placed in 1 per cent newborn calf serum they illustrate (a) a low level of pinocytic activity, (b) a shrinkage in granule size, and (c) a loss in cell protein, acid phosphatase, beta-glucuronidase, and cathepsin. Examination of the extracellular medium revealed no detectable hydrolase activity. The reintroduction of cells into high levels of serum again resulted in granule and enzyme formation. Cells rapidly incorporated fluorescein-conjugated calf serum proteins into the phase-dense granules. The fluorescence of labeled granules was lost during an 18 hour period in non-fluorescein-containing medium. Crystalline egg white lysozyme was concentrated in the macrophages. Approximately 80 per cent of the cell-associated enzyme was lost during a 24 hour washout period in either 1 or 50 per cent serum medium. No enzymatic activity could be recovered in the medium. Colloidal gold was taken up and concentrated in macrophage granules. Quantitative assays revealed this particle to be conserved during a 24 hour washout period.