tbuckley/cabot-search huggingface dataset:
Tumor cell behaviour modulation by mesenchymal stromal cells
Authors: Lucia Kucerova, Miroslava Matuskova, Kristina Hlubinova, Veronika Altanerova, Cestmir Altaner
Journal: Molecular Cancer (2010)

Human mesenchymal stromal cells (MSC) hold a promise for future cell-based therapies due to their immunomodulatory properties and/or secretory activity. Nevertheless non-neoplastic tumor compartment could also originate from MSC. We aimed to show whether multipotent MSC derived from human adipose tissue (AT-MSC) could create tumor cell-protective milieu and affect tumor cell behaviour in vitro and in vivo. Here we have demonstrated tumor-promoting effect of AT-MSC on human melanoma A375 cells. AT-MSC coinjection mediated abrogation of tumor latency and supported subcutaneous xenotransplant growth from very low melanoma cell doses. Tumor incidence was also significantly increased by AT-MSC-derived soluble factors. AT-MSC supported proliferation, suppressed apoptosis and modulated melanoma cell responses to cytotoxic drugs in vitro. Expression and multiplex cytokine assays confirmed synergistic increase in VEGF that contributed to the AT-MSC-mediated support of A375 xenotransplant growth. Production of G-CSF and other factors implicated in formation of supportive proinflammatory tumor cell microenvironment was also confirmed. SDF-1α/CXCR4 signalling contributed to tumor-promoting effect of systemic AT-MSC administration on A375 xenotransplants. However, no support was observed for human glioblastoma cells 8MGBA co-injected along with AT-MSC that did not sustain tumor xenotransplant growth in vivo. Tumor-inhibiting response could be attributed to the synergistic action of multiple cytokines produced by AT-MSC on glioblastoma cells. Herein we provide experimental evidence for MSC-mediated protective effect on melanoma A375 cells under nutrient-limiting and hostile environmental conditions resulting from mutual crosstalk between neoplastic and non-malignant cells. This tumor-favouring effect was not observed for the glioblastoma cells 8MGBA. Collectively, our data further strengthen the need for unravelling mechanisms underlying MSC-mediated modulation of tumor behaviour for possible future MSC clinical use in the context of malignant disease.
The Prophylactic and Curative Treatment of Plague
Authors: A. Lustig, G. Galeotti
Journal: BMJ (1901)

|FAW. 26, 1wo.and filtered.This mordantwvill keep for a considerable period of time.The cover glasses are prepared by washing them in a stroig solution of hydrochloric acid.They are taken fromn the acid, wiped witlh a clean cloth, and thorouglhly heated over a bunsen flamiie.A conivenielt way of doing this is to place tllem oni a slide upon a tripod, and apply the fillame.On a cover glass whiclh hias been suffliciently lheated, the film spreads witlh perfect evenness.The tr-aces of acid whiclh are left on the glass mnake it easier to avoid stubsequient precipitation of inordanlt or stainl.Time bacilli are placed oni the cover slip and fixed.The imiordant is then filtered, poured on the preparation, and lheated till steam is given off.Boiling should be avoided, as it leads to precipitation.The preparation slhould be kept at this tem-lperature forthlree minutes.It is then well washed in distilled water, and the staini is added, and' heated in the same way for thr ee or four miiinuites.The stain is mnade by adding i c.em. of a saturated alcoholic solution of gentian violet to lo c.em. of a saturated solution of ammonia alum.This is filtered and poured on the preparation.IThis method can be applied generally.I have found it pdticularly applicable to bacilli of the typhoid and B. coiiii-group.It has been used in the laboratory also for the stainingSli of the flagella of B. cholerte asiat., B. tetani, V. aquatilis, etc.The flagella are clearly defined and of moderate thickness.The advantage of the method is the certainty and rapidity with which results are obtained.Anyone who carries out the instructions given above will after a very little experience obtain without fail successful preparations.
long-term effect of combined vitamins e and c on coronary and peripheral endothelial function
Authors: Scott Kinlay, Dominik Behrendt, James C Fang, Danielle Delagrange, Jason Morrow, Joseph L Witztum, Nader Rifai, Andrew P Selwyn, Mark A Creager, Peter Ganz
Journal: Journal of the American College of Cardiology (2004)
Biochemical and Pharmacological Properties of SANORG 32701
Authors: J.M. Herbert, J.P. He´rault, A. Bernat, R.G.M. van Amsterdam, G.M.T. Vogel, J.C. Lormeau, M. Petitou, D.G. Meuleman
Journal: Circulation Research (1996)

SANORG 32701 is a new sulfated pentasaccharide obtained by total chemical synthesis. It is an analogue of the “synthetic pentasaccharide” (SR 90107/ORG 31540), which represents the antithrombin III (AT-III) binding site of heparin. Like SR 90107, it shows high affinity for human AT-III ( K d =3.7±0.7 nmol/L) and is a potent catalyst of its inhibitory effect with regard to factor Xa (1100±31 versus 850±27 anti-Xa U/mg for SR 90107). SANORG 32701 inhibited thrombin generation occurring via both the extrinsic and intrinsic pathways in vitro. After intravenous or subcutaneous administration to rabbits or rats, SANORG 32701 displayed prolonged anti–factor Xa activity and inhibition of thrombin generation ex vivo. SANORG 32701 was slowly eliminated, showing elimination half-lives between 2.8 and 4.9 hours with different doses. SANORG 32701 displayed antithrombotic activity by virtue of its potentiation of the anti–factor Xa activity of AT-III. It strongly inhibited thrombus formation in an experimental model of thromboplastin-induced venous thrombosis in rats (intravenously) and rabbits (subcutaneously) (ED 50 values were 25.5±4.1 and 91±12.7 nmol/kg, respectively). SANORG 32701 inhibited the accretion of fibrinogen I 125 to a preformed thrombus in the rabbit jugular vein and significantly reduced thrombus growth occurring after electrical stimulation of the rabbit carotid artery. In the rabbit, intravenous injection of SANORG 32701 enhanced tissue plasminogen activator (TPA)–induced thrombolysis, suggesting that concomitant use of SANORG 32701 during TPA therapy may be helpful in preventing thrombus accretion, thus facilitating clot lysis. In the rat, SANORG 32701 potently inhibited thrombus formation induced on a silk thread in an arteriovenous shunt and in the vena cava. Compared with standard heparin, SANORG 32701 (1000 nmol/kg IV) caused only minimal bleeding enhancement and exhibited a favorable antithrombotic activity/bleeding risk ratio, therefore showing that it might be considered as a promising compound in the treatment and prevention of various thrombotic diseases.
Ambulatory Treatment of Type 2 Diabetes in the U.S., 1997–2012
Authors: Lydia W. Turner, David Nartey, Randall S. Stafford, Sonal Singh, G. Caleb Alexander
Journal: Diabetes Care (2013)

OBJECTIVE Type 2 diabetes is increasingly common and associated with substantial morbidity and mortality. This study examines trends in the patterns and costs of drug treatment of type 2 diabetes from 1997 to 2012. RESEARCH DESIGN AND METHODS We conducted descriptive analyses of cross-sectional data using the IMS Health National Disease and Therapeutic Index, a nationally representative audit of ambulatory physician practices in the U.S. We focused on visits for diabetes among patients 35 years of age or older. We used the IMS Health National Prescription Audit of pharmacy dispensing to derive information about drug expenditures. RESULTS Ambulatory diabetes visits increased from 23 million treatment visits in 1997 (95% CI 21-25) to 35 million (32-37) in 2007 and declined to 31 million visits by 2012 (27-31). Between 1997 and 2012 biguanide use increased, from 23% (20-26) to 53% (50-56) of treatment visits. Glitazone use grew from 6% (4-8) in 1997 (41% [39-43] of all visits in 2005), but declined to 16% (14-18) by 2012. Since 2005, dipeptidyl peptidase-4 (DPP-4) inhibitor use increased steadily, representing 21% (18-23) of treatment visits by 2012. Glucagon-like peptide 1 (GLP-1) agonists accounted for 4% of treatment visits in 2012. Visits where two or more drug compounds were used increased nearly 40% from 1997 to 2012. Between 2008 and 2012, drug expenditures increased 61%, driven primarily by use of insulin glargine and DPP-4 inhibitors. CONCLUSIONS Declining sulfonylurea and glitazone use has been offset by increases in DPP-4 inhibitor use and, to a lesser degree, use of GLP-1 agonists. Treatment of diabetes has grown in complexity while older treatments continue to be replaced or supplemented by newer therapies.
High-Dose Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia: High Rates of Rapid Cytogenetic and Molecular Responses
Authors: Jorge E. Cortes, Hagop M. Kantarjian, Stuart L. Goldberg, Bayard L. Powell, Francis J. Giles, Meir Wetzler, Luke Akard, John M. Burke, Robert Kerr, Mansoor Saleh, August Salvado, Karen McDougall, Maher Albitar, Jerald Radich
Journal: Journal of Clinical Oncology (2009)

Long-term clinical outcome data have established imatinib 400 mg/d as standard front-line treatment for newly diagnosed patients with chronic myeloid leukemia (CML).The Rationale and Insight for Gleevec High-Dose Therapy (RIGHT) trial is a multicenter study of imatinib 400 mg twice a day as initial therapy in 115 patients (70% Sokal low risk) with newly diagnosed CML in chronic phase who were observed for both molecular and cytogenetic responses for up to 18 months. Eighty-three patients (72%) completed the study, 10 patients (9%) discontinued the study because of adverse events, and six patients (5%) discontinued because of unsatisfactory therapeutic effect.Polymerase chain reaction analysis demonstrated rapid kinetics of major molecular response (MMR), with 48% of patients achieving MMR by 6 months, 54% by 12 months, and 63% by 18 months. Corresponding complete molecular response rates were 39%, 44%, and 55%, respectively. Median dose-intensity was 98%. Overall, 79% of patients who received at least 90% dose-intensity achieved MMR. The most frequent adverse events included myelosuppression, rash, fatigue, and musculoskeletal symptoms.This study suggests that imatinib 400 mg twice a day results in more rapid reduction in tumor burden than imatinib 400 mg/d with minimal added toxicity.
Reducing INDEL calling errors in whole genome and exome sequencing data
Authors: Han Fang, Yiyang Wu, Giuseppe Narzisi, Jason A ORawe, Laura T Jimenez Barrón, Julie Rosenbaum, Michael Ronemus, Ivan Iossifov, Michael C Schatz, Gholson J Lyon
Journal: Genome Medicine (2014)

INDELs, especially those disrupting protein-coding regions of the genome, have been strongly associated with human diseases. However, there are still many errors with INDEL variant calling, driven by library preparation, sequencing biases, and algorithm artifacts.We characterized whole genome sequencing (WGS), whole exome sequencing (WES), and PCR-free sequencing data from the same samples to investigate the sources of INDEL errors. We also developed a classification scheme based on the coverage and composition to rank high and low quality INDEL calls. We performed a large-scale validation experiment on 600 loci, and find high-quality INDELs to have a substantially lower error rate than low-quality INDELs (7% vs. 51%).Simulation and experimental data show that assembly based callers are significantly more sensitive and robust for detecting large INDELs (>5 bp) than alignment based callers, consistent with published data. The concordance of INDEL detection between WGS and WES is low (53%), and WGS data uniquely identifies 10.8-fold more high-quality INDELs. The validation rate for WGS-specific INDELs is also much higher than that for WES-specific INDELs (84% vs. 57%), and WES misses many large INDELs. In addition, the concordance for INDEL detection between standard WGS and PCR-free sequencing is 71%, and standard WGS data uniquely identifies 6.3-fold more low-quality INDELs. Furthermore, accurate detection with Scalpel of heterozygous INDELs requires 1.2-fold higher coverage than that for homozygous INDELs. Lastly, homopolymer A/T INDELs are a major source of low-quality INDEL calls, and they are highly enriched in the WES data.Overall, we show that accuracy of INDEL detection with WGS is much greater than WES even in the targeted region. We calculated that 60X WGS depth of coverage from the HiSeq platform is needed to recover 95% of INDELs detected by Scalpel. While this is higher than current sequencing practice, the deeper coverage may save total project costs because of the greater accuracy and sensitivity. Finally, we investigate sources of INDEL errors (for example, capture deficiency, PCR amplification, homopolymers) with various data that will serve as a guideline to effectively reduce INDEL errors in genome sequencing.
Heterozygous splice mutation in <i>PIK3R1</i> causes human immunodeficiency with lymphoproliferation due to dominant activation of PI3K
Authors: Carrie L. Lucas, Yu Zhang, Anthony Venida, Ying Wang, Jason Hughes, Joshua McElwee, Morgan Butrick, Helen Matthews, Susan Price, Matthew Biancalana, Xiaochuan Wang, Michael Richards, Tamara Pozos, Isil Barlan, Ahmet Ozen, V. Koneti Rao, Helen C. Su, Michael J. Lenardo
Journal: The Journal of Experimental Medicine (2014)

Class IA phosphatidylinositol 3-kinases (PI3K), which generate PIP3 as a signal for cell growth and proliferation, exist as an intracellular complex of a catalytic subunit bound to a regulatory subunit. We and others have previously reported that heterozygous mutations in PIK3CD encoding the p110δ catalytic PI3K subunit cause a unique disorder termed p110δ-activating mutations causing senescent T cells, lymphadenopathy, and immunodeficiency (PASLI) disease. We report four patients from three families with a similar disease who harbor a recently reported heterozygous splice site mutation in PIK3R1, which encodes the p85α, p55α, and p50α regulatory PI3K subunits. These patients suffer from recurrent sinopulmonary infections and lymphoproliferation, exhibit hyperactive PI3K signaling, and have prominent expansion and skewing of peripheral blood CD8+ T cells toward terminally differentiated senescent effector cells with short telomeres. The PIK3R1 splice site mutation causes skipping of an exon, corresponding to loss of amino acid residues 434–475 in the inter-SH2 domain. The mutant p85α protein is expressed at low levels in patient cells and activates PI3K signaling when overexpressed in T cells from healthy subjects due to qualitative and quantitative binding changes in the p85α–p110δ complex and failure of the C-terminal region to properly inhibit p110δ catalytic activity.
Chitosan/Poly(ɛ-caprolactone) blend scaffolds for cartilage repair
Authors: Sara C. Neves, Liliana S. Moreira Teixeira, Lorenzo Moroni, Rui L. Reis, Clemens A. Van Blitterswijk, Natália M. Alves, Marcel Karperien, João F. Mano
Journal: Biomaterials (2010)
Interleukin-12: A Proinflammatory Cytokine with Immunoregulatory Functions that Bridge Innate Resistance and Antigen-Specific Adaptive Immunity
Authors: Giorgio Trinchieri
Journal: Annual Review of Immunology (1995)

Interleukin-12 (IL-12) is a heterodimeric cytokine produced mostly by phagocytic cells in response to bacteria, bacterial products, and intracellular parasites, and to some degree by B lymphocytes. IL-12 induces cytokine production, primarily of IFN-γ, from NK and T cells, acts as a growth factor for activated NK and T cells, enhances the cytotoxic activity of NK cells, and favors cytotoxic T lymphocyte generation. In vivo IL-12 acts primarily at three stages during the innate resistance/adaptive immune response to infection: 1. Early in the infection, IL-12 is produced and induces production from NK and T cells of IFN-γ , which contributes to phagocytic cell activation and inflammation; 2. IL-12 and IL-12- induced IFN-γ favor Thl cell differentiation by priming CD4 + T cells for high IFN-γ production; and 3. IL-12 contributes to optimal IFN-γ production and to proliferation of differentiated Th l cells in response to antigen. The early preference expressed in the immune response depends on the balance between IL-12, which favors Thl responses, and IL-4, which favors Th2 responses. Thus,IL-12 represents a functional bridge between the early nonspecific innate resistance and the subsequent antigen-specific adaptive immunity.
Diagnosis of pulmonary Langerhans cell histiocytosis by CT-guided core biopsy of lung: a report of three cases
Authors: S. Mukhopadhyay, S. M. Eckardt, E. M. Scalzetti
Journal: Thorax (2010)

A pathological diagnosis of pulmonary Langerhans cell histiocytosis (PLCH) usually requires a surgical lung biopsy. To date, diagnosis of PLCH by core needle biopsy has not been reported. Three cases are presented of PLCH diagnosed by CT-guided core biopsy in adult female smokers found to have multiple small bilateral lung nodules. The nodules biopsied were 5 mm, 7 mm and 1 cm in size, and showed interstitial expansion by Langerhans cells and eosinophils. CT-guided core biopsy should be considered as one of the less invasive techniques by which a pathological diagnosis of PLCH can be established.
Association between change in high density lipoprotein cholesterol and cardiovascular disease morbidity and mortality: systematic review and meta-regression analysis
Authors: M. Briel, I. Ferreira-Gonzalez, J. J You, P. J Karanicolas, E. A Akl, P. Wu, B. Blechacz, D. Bassler, X. Wei, A. Sharman, I. Whitt, S. Alves da Silva, Z. Khalid, A. J Nordmann, Q. Zhou, S. D Walter, N. Vale, N. Bhatnagar, C. O'Regan, E. J Mills, H. C Bucher, V. M Montori, G. H Guyatt
Journal: BMJ (2009)

To investigate the association between treatment induced change in high density lipoprotein cholesterol and total death, coronary heart disease death, and coronary heart disease events (coronary heart disease death and non-fatal myocardial infarction) adjusted for changes in low density lipoprotein cholesterol and drug class in randomised trials of lipid modifying interventions.Systematic review and meta-regression analysis of randomised controlled trials.Medline, Embase, Central, CINAHL, and AMED to October 2006 supplemented by contact with experts in the field.In teams of two, reviewers independently determined eligibility of randomised trials that tested lipid modifying interventions to reduce cardiovascular risk, reported high density lipoprotein cholesterol and mortality or myocardial infarctions separately for treatment groups, and treated and followed participants for at least six months.Using standardised, pre-piloted forms, reviewers independently extracted relevant information from each article. The change in lipid concentrations for each trial and the weighted risk ratios for clinical outcomes were calculated.The meta-regression analysis included 108 randomised trials involving 299 310 participants at risk of cardiovascular events. All analyses that adjusted for changes in low density lipoprotein cholesterol showed no association between treatment induced change in high density lipoprotein cholesterol and risk ratios for coronary heart disease deaths, coronary heart disease events, or total deaths. With all trials included, change in high density lipoprotein cholesterol explained almost no variability (<1%) in any of the outcomes. The change in the quotient of low density lipoprotein cholesterol and high density lipoprotein cholesterol did not explain more of the variability in any of the outcomes than did the change in low density lipoprotein cholesterol alone. For a 10 mg/dl (0.26 mmol/l) reduction in low density lipoprotein cholesterol, the relative risk reduction was 7.2% (95% confidence interval 3.1% to 11%; P=0.001) for coronary heart disease deaths, 7.1% (4.5% to 9.8%; P<0.001) for coronary heart disease events, and 4.4% (1.6% to 7.2%; P=0.002) for total deaths, when adjusted for change in high density lipoprotein cholesterol and drug class.Available data suggest that simply increasing the amount of circulating high density lipoprotein cholesterol does not reduce the risk of coronary heart disease events, coronary heart disease deaths, or total deaths. The results support reduction in low density lipoprotein cholesterol as the primary goal for lipid modifying interventions.
Melanoma Epidemic: An Analysis of Six Decades of Data From the Connecticut Tumor Registry
Authors: Alan C. Geller, Richard W. Clapp, Arthur J. Sober, Lou Gonsalves, Lloyd Mueller, Cindy L. Christiansen, Waqas Shaikh, Donald R. Miller
Journal: Journal of Clinical Oncology (2013)

Purpose Melanoma is the most commonly fatal form of skin cancer, with nearly 50,000 annual deaths worldwide. We sought to assess long-term trends in the incidence and mortality of melanoma in a state with complete and consistent registration. Methods We used data from the Connecticut Tumor Registry, the original National Cancer Institute SEER site, to determine trends in invasive melanoma (1950-2007), in situ melanoma (1973-2007), tumor thickness (1993-2007), mortality (1950-2007), and mortality to incidence (1950-2007) among the 19,973 and 3,635 Connecticut residents diagnosed with invasive melanoma (1950-2007) and who died as a result of melanoma (1950-2007), respectively. Main outcome measures included trends in incidence and mortality by age, sex, and birth cohort. Results In the initial period (1950-1954), a diagnosis of invasive melanoma was rare, with 1.9 patient cases per 100,000 for men and 2.6 patient cases per 100,000 for women. Between 1950 and 2007, overall incidence rates rose more than 17-fold in men (1.9 to 33.5 per 100,000) and more than nine-fold in women (2.6 to 25.3 per 100,000). During these six decades, mortality rates more than tripled in men (1.6 to 4.9 per 100,000) and doubled in women (1.3 to 2.6 per 100,000). Mortality rates were generally stable or decreasing in men and women through age 54 years. Conclusion Unremitting increases in incidence and mortality of melanoma call for a nationally coordinated effort to encourage and promote innovative prevention and early-detection efforts.
Effects of formoterol and salmeterol on cytokine release from monocyte-derived macrophages
Authors: L.E. Donnelly, S.J. Tudhope, P.S. Fenwick, P.J. Barnes
Journal: European Respiratory Journal (2009)

Pulmonary macrophages are a target for inhaled therapies. Combinations of long-acting β 2 -agonists (LABA) and glucocorticosteroids have been developed for asthma and chronic obstructive pulmonary disease (COPD). This study examined two LABA, salmeterol and formoterol, and the glucocorticosteroid, budesonide, on cytokine release from monocyte-derived macrophages (MDM) to determine whether anti-inflammatory effects observed in patients are due to inhibition of macrophages. MDM were incubated in the absence or presence of LABA or budesonide prior to stimulation with lipopolysaccharide (LPS). Tumour necrosis factor (TNF)-α, granulocyte macrophage-colony stimulating factor (GM-CSF) and CXC chemokine ligand (CXCL)8 were measured by ELISA. Formoterol and salmeterol inhibited LPS-stimulated release of TNF-α (mean effective concentration (EC 50 ) 2.4±1.8 and 3.5±2.7 nM, respectively; n = 11–16), GM-CSF (EC 50 24.6±2.1 and 52.4±40.8 nM, respectively, n = 11–12) but not CXCL8 from LPS-stimulated MDM. Budesonide inhibited release of all three cytokines (EC 50 TNF-α: 1.2±0.4 nM; GM-CSF: 0.4±0.2 nM; CXCL8: 0.4±0.1 nM; n = 3–4). Formoterol but not salmeterol elevated cAMP in these cells. These effects were attenuated by β-adrenoceptor antagonists, propranolol and ICI118551. Salmeterol (10 −7 M) also inhibited formoterol-induced cAMP and formoterol-mediated attenuation of cytokine release. Combining budesonide (0.3 nM) with formoterol, inhibited TNF-α release additively. LABA may inhibit inflammatory cytokine release from macrophages in a cAMP-independent manner and act additively with budesonide.