tbuckley/cabot-search huggingface dataset:
Differential Action of the Bisphosphonates (3-Amino-1-Hydroxypropylidene)-1,1-Bisphosphonate (APD) and Disodium Dichloromethylidene Bisphosphonate (Cl2MDP) on Rat Macrophage-mediated Bone Resorption In Vitro
Authors: Pieter H. Reitsma, Steven L. Teitelbaum, Olav L. M. Bijvoet, Arnold J. Kahn
Journal: Journal of Clinical Investigation (1982)

The bisphosphonates (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) and disodium dichloromethylidene bisphosphonate (Cl2MDP) effectively inhibit the accelerated bone resorption associated with some skeletal disorders, e.g., Paget's disease. However, it has not been established whether these compounds exert their inhibitory effect by rendering the bone mineral more resistant to degradation, by diminishing the activity of resorbing cells, or through some combination of both activities. In this study, we have tested these possibilities using an in vitro resorption assay system consisting of elicited rat peritoneal macrophages co-cultured with particles of 45Ca-labeled, devitalized rat bone. This assay system permits the quantitative assessment of the action of APD and Cl2MDP on the two major phases of bone resorption (cell-substrate attachment and osteolysis) under circumstances where the drugs are present continuously or, most importantly for the issues in question, after the separate pretreatment of the particles or the resorbing cells.
The polynuclear platinum BBR3610 induces G2/M arrest and autophagy early and apoptosis late in glioma cells
Authors: Takashi Shingu, Vaibhav C. Chumbalkar, Ho-Shin Gwak, Keishi Fujiwara, Seiji Kondo, Nicholas P. Farrell, Oliver Bogler
Journal: Neuro-Oncology (2010)

BBR3610 is a polynuclear platinum compound, in which two platinums are linked by a spermine-like linker, and studies in a variety of cancers, including glioma, have shown that it is more potent than conventional platinums and works by different means. Identifying the mechanism of action of BBR3610 would help in developing the drug further for clinical use. Previous work showed that BBR3610 does not induce immediate apoptosis but results in an early G2/M arrest. Here, we report that BBR3610 induces early autophagy in glioma cells. Increased autophagy was also seen in intracranial xenografts treated with BBR3610. Interestingly, upon attenuation of autophagy by RNAi-mediated knockdown of ATG5 or ATG6/BECN1, no change in cell viability was observed, suggesting that the autophagy is neither an effective protection against BBR3610 nor an important part of the mechanism by which BBR3610 reduces glioma cell viability. This prompted a multimodal analysis of 4 cell lines over 2 weeks posttreatment with BBR3610, which showed that the G2/M arrest occurred early and apoptosis occurred later in all cell lines. The cells that survived entered a senescent state associated with mitotic catastrophe in 2 of the cell lines. Together, our data show that the response to treatment with a single agent is complex and changes over time.
ARTIFICIAL MAINTENANCE MEDIA FOR CELL AND ORGAN CULTIVATION
Authors: Lillian E. Baker, Alexis Carrel
Journal: The Journal of Experimental Medicine (1939)

Experiments have been described in which organs cultivated in the Lindbergh apparatus have been kept alive in artificial media for periods ranging from 3 days to 3 weeks, with life continuing in portions of some glands for from 35 to 62 days. The media used varied in composition from very simple and inexpensive ones in which some serum was used to a rather complex medium containing only that negligible amount of serum that is necessary as a solvent for vitamin A. The experiments performed demonstrate that artificial media can be used for organ cultivation, thus making it possible to study the behavior of human organs; to control the composition of the media at will; and to reduce the cost of experimentation.
TNF receptor superfamily member 13b (TNFRSF13B) hemizygosity reveals transmembrane activator and CAML interactor haploinsufficiency at later stages of B-cell development
Authors: Neil Romberg, Manmeet Virdee, Nicolas Chamberlain, Tyler Oe, Jean-Nicolas Schickel, Tiffany Perkins, Tineke Cantaert, Rima Rachid, Sally Rosengren, Regina Palazzo, Raif Geha, Charlotte Cunningham-Rundles, Eric Meffre
Journal: Journal of Allergy and Clinical Immunology (2015)
Tissue-Specific Induction of Intestinal ABCA1 Expression With a Liver X Receptor Agonist Raises Plasma HDL Cholesterol Levels
Authors: Liam R. Brunham, Janine K. Kruit, Terry D. Pape, John S. Parks, Folkert Kuipers, Michael R. Hayden
Journal: Circulation Research (2006)

ABCA1 controls the rate-limiting step in HDL particle formation and is therefore an attractive molecular target for raising HDL levels and protecting against atherosclerosis. Intestinal ABCA1 significantly and independently contributes to plasma HDL cholesterol levels in mice, suggesting that induction of intestinal ABCA1 expression may raise plasma HDL cholesterol levels. We evaluated the ability of a synthetic Liver X Receptor (LXR) agonist, GW3965, to raise plasma HDL cholesterol levels in control mice and mice with liver- or intestinal-specific deletion of the Abca1 gene. Oral treatment with GW3965 increased the expression of ABCA1 by approximately 6-fold (P=0.004) as well as other LXR target genes in the intestines of mice, with no change in the hepatic expression of these genes. This resulted in a significant approximately 48% elevation of plasma HDL cholesterol levels in wild-type mice (P<0.01) with no change in plasma triglycerides. A similar increase in HDL cholesterol was observed in mice lacking hepatic ABCA1, indicating that the increase in plasma HDL cholesterol was independent of hepatic ABCA1. This effect was completely abrogated in mice lacking intestinal ABCA1. These data indicate that intestinal ABCA1 may be an attractive therapeutic target for raising HDL levels while avoiding the hepatic lipogenesis and hypertriglyceridemia typical of systemic LXR activation.
Enzyme Replacement Therapy and Fabry Kidney Disease
Authors: David G. Warnock
Journal: Journal of the American Society of Nephrology (2007)

The advent of effective enzyme replacement therapy (ERT) has kindled considerable interest in Fabry disease; ERT offers the promise of altering the natural history of this unusual form of proteinuric chronic kidney disease (CKD). Fabry disease is a rare, X-linked, lysosomal storage disorder caused by deficient activity of the lysosomal enzyme -galactosidase A, with accumulation of its substrates (globotriaosylceramide and related glycosphingolipids), particularly in the vascular endothelial cells of the kidney and heart (1). Early manifestations typically include debilitating chronic acroparesthesias, episodic excruciating pain “crises,” hypohidrosis, and gastrointestinal complaints. Subsequently, kidney failure, heart disease, and strokes lead to early death, typically
Can Common Clinical Parameters Be Used to Identify Patients Who Will Need Insulin Treatment in Gestational Diabetes Mellitus?
Authors: Tania Pertot, Lynda Molyneaux, Kris Tan, Glynis P. Ross, Dennis K. Yue, Jencia Wong
Journal: Diabetes Care (2011)

OBJECTIVE To identify patients with gestational diabetes mellitus (GDM) who will need antenatal insulin treatment (AIT) by using a risk-prediction tool based on maternal clinical and biochemical characteristics at diagnosis. RESEARCH DESIGN AND METHODS Data from 3,009 women attending the Royal Prince Alfred Hospital GDM Clinic, Australia, between 1995 and 2010 were studied. A risk engine was developed from significant factors identified for AIT using a logistic regression model. RESULTS A total of 51% of GDM patients required AIT. Ethnicity, gestation at diagnosis, HbA1c, fasting and 60-min glucose at oral glucose tolerance test, BMI, and diabetes family history were significant independent determinants of AIT. Notably, only 9% of the attributable risk for AIT can be explained by the clinical factors studied. A modeled risk-scoring system was therefore a poor predictor of AIT. CONCLUSIONS Baseline maternal characteristics including HbA1c alone cannot predict the need for AIT in GDM. Lifestyle, compliance, or as yet unmeasured influences play a greater role in determining AIT.
Respiratory intermediate care units: a European survey: European Respiratory Society Task Force on epidemiology of respiratory intermediate care in Europe
Authors: A Corrado, C Roussos, N Ambrosino, M Confalonieri, A Cuvelier, M Elliott, M Ferrer, M Gorini, O Gurkan, J F Muir, L Quareni, D Robert, D Rodenstein, A Rossi, B Schoenhofer, A K Simonds, K Strom, A Torres, S Zakynthinos
Journal: European Respiratory Journal (2002)

⇓Severe chronic obstructive pulmonary disease (COPD) patients, especially those with chronic respiratory failure, may frequently require periods of intensive treatment, monitoring, nursing and, occasionally, ventilatory assistance in order to overcome acute exacerbations. Ventilatory assistance is only rarely provided in the conventional ward 1, therefore admission to an intensive care unit (ICU) is often needed 2. ICU, however, are very precious and expensive resources where nursing costs represent a major expense 3. Patients with acute on chronic respiratory failure may experience a prolonged stay in the ICU not only because of the severity of their illness which precipitates the underlying acute respiratory failure (ARF) 2, but also because of ICU-related complications 4. For these reasons the treatment of acute on chronically ill patients in these areas creates ethical 5 and economic concerns 6, 7.

It has been reported that ∼40% of the patients admitted to ICUs never received active intensive care, including mechanical ventilation 8–10. Only ∼40% of patients with ARF due to pulmonary disease needed to be invasively ventilated 11, 12. However, in some countries, such as the UK, with a severe ICU bed shortage, the vast majority of ICU admissions require mechanical ventilation.

A recent Italian survey carried out on 99 ICUs showed that COPD was the dominant underlying chronic disease in patients admitted to the Italian ICU, and the need for cardiorespiratory monitoring was the most frequent indication for admission (31.2%) 13.

These studies clearly indicate that in some centres there is an “overutilisation” of ICU resources for monitoring purposes, and that acute on chronic respiratory failure could be managed in many patients without invasive ventilation.

Patients with chronic respiratory failure, especially those with underlying COPD, very often suffer from a high frequency of …
Biomarkers of Airway Acidity and Oxidative Stress in Exhaled Breath Condensate from Grain Workers
Authors: Ron Do, Karen H. Bartlett, Helen Dimich-Ward, Winnie Chu, Susan M. Kennedy
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Grain workers report adverse respiratory symptoms due to exposures to grain dust and endotoxin. Studies have shown that biomarkers in exhaled breath condensate (EBC) vary with the severity of airway inflammation.The purpose of the study was to evaluate biomarkers of airway acidity (pH and ammonium [NH(4)(+)]) and oxidative stress (8-isoprostane) in the EBC of grain workers.A total of 75 workers from 5 terminal elevators participated. In addition to EBC sampling, exposure monitoring for inhalable grain dust and endotoxin was performed; spirometry, allergy testing, and a respiratory questionnaire derived from that of the American Thoracic Society were administered.Dust and endotoxin levels ranged from 0.010 to 13 mg/m(3) (median, 1.0) and 8.1 to 11,000 endotoxin units/m(3) (median, 610) respectively. EBC pH values varied from 4.3 to 8.2 (median, 7.9); NH(4)(+) values from 22 to 2,400 microM (median, 420); and 8-isoprostane values from 1.3 to 45 pg/ml (median, 11). Univariate and multivariable analyses revealed a consistent effect of cumulative smoking and obesity with decreased pH and NH(4)(+), and intensity of grain dust and endotoxin with increased 8-isoprostane. Duration of work on the test day was associated with decreased pH and NH(4)(+), whereas duration of employment in the industry was associated with decreased 8-isoprostane.Chronic exposures are associated with airway acidity, whereas acute exposures are more closely associated with oxidative stress. These results suggest that the collection of EBC may contribute to predicting the pathological state of the airways of workers exposed to acute and chronic factors.
Availability and Use of Palliative Care and End-of-Life Services for Pediatric Oncology Patients
Authors: Donna L. Johnston, Kim Nagel, Debra L. Friedman, Jane L. Meza, Craig A. Hurwitz, Sarah Friebert
Journal: Journal of Clinical Oncology (2008)

Palliative care prevents or relieves the symptoms caused by life-threatening medical conditions. Previous surveys have shown both underuse and lack of availability of these services for children with cancer throughout North America. We sought to investigate the current practices and resources surrounding palliative and end-of-life care among participating institutions of the Children's Oncology Group (COG).A survey regarding practices and resources was developed by the COG palliative care subcommittee and was sent to all 232 institutions to complete for the calendar year 2005.The survey was completed by 81% of the institutions. Per institution, there were a mean of 64.6 newly diagnosed patients and 17.7 patients experiencing relapse. A palliative care team was available in 58% of institutions, a pain service in 90%, a hospice in 60%, a psychosocial support team in 80%, and a bereavement program in 59%. Complementary and alternative medicine was available in 39% of institutions and in 95% of the COG institution's community. Most services, even when available, were not well used by patients.Despite the well-established benefit of pediatric palliative care, it is only offered in 58% of COG institutions caring for children with cancer. In an era where the benefit of palliative care has been clearly established, this number should approach 100%. Efforts should be directed toward understanding barriers to provision of such services, so that they are available and well used at all childhood cancer centers.
Breast cancer mortality in neighbouring European countries with different levels of screening but similar access to treatment: trend analysis of WHO mortality database
Authors: P. Autier, M. Boniol, A. Gavin, L. J. Vatten
Journal: BMJ (2011)

<b>Objective</b> To compare trends in breast cancer mortality within three pairs of neighbouring European countries in relation to implementation of screening. <b>Design</b> Retrospective trend analysis. <b>Setting</b> Three country pairs (Northern Ireland (United Kingdom) <i>v</i> Republic of Ireland, the Netherlands <i>v</i> Belgium and Flanders (Belgian region south of the Netherlands), and Sweden <i>v</i> Norway). <b>Data sources</b> WHO mortality database on cause of death and data sources on mammography screening, cancer treatment, and risk factors for breast cancer mortality. <b>Main outcome measures</b> Changes in breast cancer mortality calculated from linear regressions of log transformed, age adjusted death rates. Joinpoint analysis was used to identify the year when trends in mortality for all ages began to change. <b>Results</b> From 1989 to 2006, deaths from breast cancer decreased by 29% in Northern Ireland and by 26% in the Republic of Ireland; by 25% in the Netherlands and by 20% in Belgium and 25% in Flanders; and by 16% in Sweden and by 24% in Norway. The time trend and year of downward inflexion were similar between Northern Ireland and the Republic of Ireland and between the Netherlands and Flanders. In Sweden, mortality rates have steadily decreased since 1972, with no downward inflexion until 2006. Countries of each pair had similar healthcare services and prevalence of risk factors for breast cancer mortality but differing implementation of mammography screening, with a gap of about 10-15 years. <b>Conclusions</b> The contrast between the time differences in implementation of mammography screening and the similarity in reductions in mortality between the country pairs suggest that screening did not play a direct part in the reductions in breast cancer mortality.
B Cell–specific Transgenic Expression of Bcl2 Rescues Early B Lymphopoiesis but Not B Cell Responses in BOB.1/OBF.1-deficient Mice
Authors: Cornelia Brunner, Dragan Marinkovic, Jörg Klein, Tatjana Samardzic, Lars Nitschke, Thomas Wirth
Journal: The Journal of Experimental Medicine (2003)

Mice deficient for the transcriptional coactivator BOB.1/OBF.1 show several defects in B cell differentiation. Numbers of immature transitional B cells in the bone marrow are reduced and fewer B cells reach the periphery. Furthermore, germinal center B cells are absent and marginal zone (MZ) B lymphocytes are markedly reduced. Increased levels of B cell apoptosis in these mice prompted us to analyze expression and function of antiapoptotic proteins. Bcl2 expression is strongly reduced in BOB.1/OBF.1-deficient pre–B cells. When BOB.1/OBF.1-deficient mice were crossed with Bcl2-transgenic mice, B cell development in the bone marrow and numbers of B cells in peripheral lymphoid organs were normalized. However, neither germinal center B cells nor MZ B cells were rescued. Additionally, Bcl2 did not rescue the defects in signaling and affinity maturation found in BOB.1/OBF.1-deficient mice. Interestingly, Bcl2-transgenic mice by themselves show an MZ B cell defect. Virtually no functional MZ B cells were detected in these mice. In contrast, mice deficient for Bcl2 show a relative increase in MZ B cell numbers, indicating a previously undetected function of Bcl2 for this B cell compartment.
Threshold size for optimal passive pulmonary targeting and retention of rigid microparticles in rats
Authors: Hilliard L. Kutscher, Piyun Chao, Manjeet Deshmukh, Yashveer Singh, Peidi Hu, Laurie B. Joseph, David C. Reimer, Stanley Stein, Debra L. Laskin, Patrick J. Sinko
Journal: Journal of Controlled Release (2010)
NKB1: a natural killer cell receptor involved in the recognition of polymorphic HLA-B molecules.
Authors: V Litwin, J Gumperz, P Parham, J H Phillips, L L Lanier
Journal: The Journal of Experimental Medicine (1994)

Natural killer (NK) cells kill normal and transformed hematopoietic cells that lack expression of major histocompatibility complex (MHC) class I antigens. Lysis of HLA-negative Epstein Barr virus-transformed B lymphoblastoid cell lines (B-LCL) by human NK cell clones can be inhibited by transfection of the target cells with certain HLA-A, -B, or -C alleles. NK cell clones established from an individual demonstrate clonal heterogeneity in HLA recognition and a single NK clone can recognize multiple alleles. We describe a potential human NK cell receptor (NKB1) for certain HLA-B alleles (e.g., HLA-B*5101 and-B*5801) identified by the mAb DX9. NKB1 is a 70-kD glycoprotein that is expressed on a subset of NK cells and NK cell clones. DX9 monoclonal antibody (mAb) specifically inhibits the interaction between NK cell clones and B-LCL targets transfected with certain HLA-B alleles, but does not affect recognition of HLA-A or HLA-C antigens. An individual NK cell clone can independently recognize B-LCL targets transfected with HLA-B or HLA-C antigens; however, DX9 mAb only affects interaction with transfectants expressing certain HLA-B alleles. These findings demonstrate the existence of NK cell receptors involved in the recognition of HLA-B and imply the presence of multiple receptors for MHC on an individual NK clone.
IL-25 Elicits Innate Lymphoid Cells and Multipotent Progenitor Type 2 Cells That Reduce Renal Ischemic/Reperfusion Injury
Authors: Qingsong Huang, Zhiguo Niu, Jing Tan, Jun Yang, Yun Liu, Haijun Ma, Vincent W.S. Lee, Shuming Sun, Xiangfeng Song, Minghao Guo, Yiping Wang, Qi Cao
Journal: Journal of the American Society of Nephrology (2015)

IL-25 is an important immune regulator that can promote Th2 immune response-dependent immunity, inflammation, and tissue repair in asthma, intestinal infection, and autoimmune diseases. In this study, we examined the effects of IL-25 in renal ischemic/reperfusion injury (IRI). Treating IRI mice with IL-25 significantly improved renal function and reduced renal injury. Furthermore, IL-25 treatment increased the levels of IL-4, IL-5, and IL-13 in serum and kidney and promoted induction of alternatively activated (M2) macrophages in kidney. Notably, IL-25 treatment also increased the frequency of type 2 innate lymphoid cells (ILC2s) and multipotent progenitor type 2 (MPPtype2) cells in kidney. IL-25–responsive ILC2 and MPPtype2 cells produced greater amounts of Th2 cytokines that associated with the induction of M2 macrophages and suppression of classically activated (M1) macrophages in vitro. Finally, adoptive transfer of ILC2s or MPPtype2 cells not only reduced renal functional and histologic injury in IRI mice but also induced M2 macrophages in kidney. In conclusion, our data identify a mechanism whereby IL-25-elicited ILC2 and MPPtype2 cells regulate macrophage phenotype in kidney and prevent renal IRI.
ACTIBIND, a T2 RNase, Competes with Angiogenin and Inhibits Human Melanoma Growth, Angiogenesis, and Metastasis
Authors: Betty Schwartz, Oded Shoseyov, Vladislava O. Melnikova, Marya McCarty, Michael Leslie, Levava Roiz, Patricia Smirnoff, Guo-fu Hu, Dina Lev, Menashe Bar-Eli
Journal: Cancer Research (2007)

Abstract Melanoma is a very aggressive and highly angiogenic tumor in which standard treatments have had only limited success. Patients with advanced disease have a 5-year survival rate of 5%. In search for alternatives, we identified a natural product extracted from the fungus Aspergillus niger, termed ACTIBIND, that inhibits tumor growth and metastasis of melanoma in vivo. ACTIBIND, a T2 RNase, exerts antitumorigenic and antiangiogenic activities by competing with the angiogenic factor angiogenin (itself an RNase homologue). Thus, there was decreased expression and activity of the matrix metalloproteinase 2 in melanoma and vascular endothelial cells, decreased vascularization, and increased tumor cell apoptosis in vivo. ACTIBIND significantly inhibited angiogenesis in an in vivo angiogenesis assay with sponges containing angiogenin. In vitro, ACTIBIND was internalized by both melanoma and human umbilical vein endothelial cells, reached the cell nuclei, and inhibited the activity of angiogenin response elements in a dose-dependent manner. Collectively, our data indicate that ACTIBIND should be tested for its potential as a new antiangiogenic modality for the treatment of melanoma. [Cancer Res 2007;67(11):5258–66]
An Acellular Biologic Scaffold Promotes Skeletal Muscle Formation in Mice and Humans with Volumetric Muscle Loss
Authors: Brian M. Sicari, J. Peter Rubin, Christopher L. Dearth, Matthew T. Wolf, Fabrisia Ambrosio, Michael Boninger, Neill J. Turner, Douglas J. Weber, Tyler W. Simpson, Aaron Wyse, Elke H. P. Brown, Jenna L. Dziki, Lee E. Fisher, Spencer Brown, Stephen F. Badylak
Journal: Science Translational Medicine (2014)

Scaffolds composed of cell-free extracellular matrix promote de novo formation of functional skeletal muscle tissue in sites of volumetric muscle loss.