tbuckley/cabot-search huggingface dataset:
Effect of Essential Fatty Acid Deficiency on Ultrastructure and Growth of Transplantable Mouse Hepatoma BRL&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: E H Leduc, J W Wilson
Journal: JNCI Journal of the National Cancer Institute (1964)

Journal Article Effect of Essential Fatty Acid Deficiency on Ultrastructure and Growth of Transplantable Mouse Hepatoma BRL Get access Elizabeth H. Leduc, Elizabeth H. Leduc Department of Biology, Brown University, Providence, Rhode Island Search for other works by this author on: Oxford Academic PubMed Google Scholar J. Walter Wilson J. Walter Wilson Department of Biology, Brown University, Providence, Rhode Island Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 33, Issue 4, October 1964, Pages 721–739, https://doi.org/10.1093/jnci/33.4.721 Published: 01 October 1964 Article history Received: 08 May 1964 Published: 01 October 1964
Pseudomonas aeruginosa and cyanide production
Authors: W. Lenney, F.J. Gilchrist
Journal: European Respiratory Journal (2011)

Infection and subsequent chronic infection of the cystic fibrosis (CF) lung with organisms such as Pseudomonas aeruginosa probably occurs at an early stage in the life of a child suffering from CF. Clinicians worldwide are eager to isolate the organism as early as possible in an attempt to treat the patient before any permanent damage occurs and hopefully to eliminate the organism completely from the respiratory tract for many years. Young children are usually unable to expectorate sputum for microbiological analysis and cough swabs are relatively insensitive. Induced sputum techniques are generally not well tolerated in children and bronchoscopic manoeuvres are very invasive, requiring a general anaesthetic. There has, therefore, been interest in discovering whether there are any surrogate markers which could be helpful as a specific indication of the presence of P. aeruginosa . It has been postulated that cyanide could be one such compound.

P. aeruginosa is one of a limited number of organisms which can synthesise cyanide 1. Synthesis occurs by the oxidative decarboxylation of glycine by a hydrogen cyanide synthase enzyme. This process also produces four electrons and four hydrogen ions per glycine molecule. Cyanide synthesis by P. aeruginosa occurs under microaerobic (O2<5%) conditions but is inactivated under both atmospheric oxygen and strictly anaerobic conditions 1, 2. Cyanide production by P. aeruginosa is maximised at temperatures between 34°C and 37°C 3. Studies which have investigated cyanogenesis in relation to P. aeruginosa using liquid or solid samples have assayed cyanide concentrations …
Designing prevention programmes to reduce incidence of dementia: prospective cohort study of modifiable risk factors
Authors: K. Ritchie, I. Carriere, C. W. Ritchie, C. Berr, S. Artero, M.-L. Ancelin
Journal: BMJ (2010)

<b>Objective</b> To estimate the percentage reduction in incidence of dementia that would be obtained if specific risk factors were eliminated. <b>Design</b> Prospective seven year cohort study. <b>Setting</b> General population, Montpellier, France. <b>Participants</b> 1433 people aged over 65 with a mean baseline age of 72.5 (SD 5.1) years. <b>Main outcome measures</b> Diagnosis of mild cognitive impairment or dementia established by a standardised neurological examination. <b>Results</b> Cox models were constructed to derive hazard ratios and determine confounding and interaction effects for potentially modifiable risk factors for dementia. Mean percentage population attributable fractions were calculated with 95% confidence intervals derived from bootstrapping for seven year incidence of mild cognitive impairment or dementia. The final model retained crystallised intelligence (population attributable fraction 18.11%, 95% confidence interval 10.91% to 25.42%), depression (10.31%, 3.66% to 17.17%), fruit and vegetable consumption (6.46%, 0.15% to 13.06%), diabetes (4.88%, 1.87% to 7.98%), and apolipoprotein E ε4 allele (7.11%, 2.44% to 11.98%). <b>Conclusions</b> Increasing crystallised intelligence and fruit and vegetable consumption and eliminating depression and diabetes are likely to have the biggest impact on reducing the incidence of dementia, outweighing even the effect of removing the principal known genetic risk factor. Although causal relations cannot be concluded with certainty, the study suggests priorities that may inform public health programmes.
The quest for universal health coverage: achieving social protection for all in Mexico
Authors: Felicia Marie Knaul, Eduardo González-Pier, Octavio Gómez-Dantés, David García-Junco, Héctor Arreola-Ornelas, Mariana Barraza-Lloréns, Rosa Sandoval, Francisco Caballero, Mauricio Hernández-Avila, Mercedes Juan, David Kershenobich, Gustavo Nigenda, Enrique Ruelas, Jaime Sepúlveda, Roberto Tapia, Guillermo Soberón, Salomón Chertorivski, Julio Frenk
Journal: The Lancet (2012)
HLA class II alleles and synovial fluid cytology in RA
Authors: L-S TEH
Journal: Annals of the Rheumatic Diseases (2001)

Rheumatoid arthritis (RA) is associated with HLA-DR4, which is encoded by the DRB1 gene. This genetic predisposition has been shown to lie within the sequence motif present in the third hypervariable region of the DRB1 gene.1 This sequence of amino acids has been called the “disease epitope” and can be encoded by DR4 subtypes as well as non-DR4 alleles; DR1 subtypes, DR10 and DR14 subtypes .1 Hence, it is also termed the shared epitope. In addition to imparting susceptibility to RA, HLA-DR4 has also been shown to be associated with the severity of the rheumatoid disease, including destructive erosive joint disease, rheumatoid factor positivity,2 and extra-articular manifestations, such as rheumatoid nodules, vasculitis, and Felty's syndrome.3 4HLA-DQ genes are in linkage disequilibrium with HLA-DR and subjects who are DR4 positive may either be DQB1*0301 or *0302 positive; certain extra-articular features of RA have been shown to be associated with HLA-DQB1*0301.4 5 

Synovial fluid cytology in RA is heterogeneous both with respect to total white cell count and to the proportions of polymorphs, lymphocytes, and ragocytes.6 Ragocytes are leucocytes containing intracytoplasmic granules and have been shown to be present in higher percentages in the joints of patients with RA.6Davis et al showed that when a patient with RA has a relapse affecting the same joint, the proportions of cell types remain similar, though the total white cell count may differ.7 The same study also found a significantly poorer outcome in patients with persistently high ragocyte counts as assessed by the necessity for subsequent joint replacement or synovectomy.

As both synovial cytology and genetic factors have been shown independently to …
Severe haemoptysis in patients with nonsmall cell lung carcinoma
Authors: Keyvan Razazi, Antoine Parrot, Antoine Khalil, Michel Djibre, Valerie Gounant, Jalal Assouad, Marie France Carette, Muriel Fartoukh, Jacques Cadranel
Journal: European Respiratory Journal (2014)

Severe haemoptysis due to nonsmall cell lung cancer (NSCLC) is considered a grim condition, and there is still scarce data on its characteristics and outcome, despite new imaging and treatment modalities. This retrospective study sought to describe the clinical characteristics, pathophysiology and outcome of NSCLC-related haemoptysis. We included 125 consecutive patients with severe haemoptysis (&gt;100 mL) at admission, 65 (52%) exhibiting squamous cell carcinoma. Tumour cavitation/necrosis was reported in 26 (21%) patients. 52 patients had received anticancer treatment, but none had received anti-angiogenic agents. Severe haemoptysis was related mainly to the bronchial artery (82%), and major pulmonary artery involvement was rare (6.4%). Interventional radiology was performed in 102 patients. Bleeding cessation was achieved in 108 (87%) out of 125 patients. The overall in-hospital and 1-year survival rates were 69% and 30%, respectively. Performance status (PS) ≥2 (OR 3.6, 95% CI 1.3–9.6), advanced stage (OR 8.6, 95% CI 2–37) and mechanical ventilation (OR 13, 95% CI 4.5–36) were independent predictors of in-hospital mortality. Performance status ≥2 (hazard ratio (HR) 2.4, 95% CI 1.5–3.7), advanced stage (HR 4, 95% CI 2.1–7.7), cancer progression (HR 2, 95% CI 1.01–2.7) and cavitation/necrosis (HR 1.7, 95% CI 1.21–3.2) were independently associated with 1-year mortality. Management of severe haemoptysis related to NSCLC should be improved, given our observed survival rates after hospital discharge.
Disease progression or pseudoprogression after concomitant radiochemotherapy treatment: Pitfalls in neurooncology
Authors: Alba A. Brandes, Alicia Tosoni, Federica Spagnolli, Giampiero Frezza, Marco Leonardi, Fabio Calbucci, Enrico Franceschi
Journal: Neuro-Oncology (2008)

Although radionecrosis has been exhaustively described in depth in the neurooncological literature, its diagnosis is still a challenging issue because its radiological pattern is frequently indistinguishable from that of tumor recurrence. This review discusses the causes of radionecrosis and the potential effect of adjuvant chemotherapy concomitant with radiotherapy on its rate and onset. The potential pitfalls in clinical studies attempting to make a differential diagnosis between radionecrosis and disease progression are also discussed.
Stage-Specific Characterization of the Vascular Endothelial Growth Factor Axis in Prostate Cancer: Expression of Lymphangiogenic Markers Is Associated with Advanced-Stage Disease
Authors: Varsha Kaushal, Perkins Mukunyadzi, Richard A. Dennis, Eric R. Siegel, Donald E. Johnson, Manish Kohli
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The vascular endothelial growth factor (VEGF) family plays a critical role in tumor angiogenesis and lymphangiogenesis. We characterized, at the mRNA and protein levels, the expression of VEGF-A and VEGF-D and their cognate receptors, VEGFR-1, VEGFR-2, and VEGFR-3 in early- and advanced-stage prostate cancer specimens. Experimental Design: The levels of VEGF-A and VEGF-D mRNA in early- and advanced-stage specimens were compared using an angiogenic gene array and were confirmed by quantitative real-time PCR. Receptor protein levels and activation status were determined by immunoblotting. Spatial expression of the proteins was evaluated using immunohistochemistry with fresh and archival tissues from benign prostatic hypertrophy specimens, early-stage prostate specimens, and advanced-stage metastatic specimens. Circulating plasma levels of these growth factors were measured using ELISAs. Results: We observed that expression patterns of VEGF isotypes corresponded to the prostate cancer stage: high expression of angiogenic growth factor VEGF-A was observed in early-stage prostate specimens, whereas high expression of lymphangiogenic growth factor VEGF-D was associated with advanced-stage metastatic disease. All VEGF receptors were present at variable levels in all specimens, but their activation states varied in a stage-specific manner. VEGFR-1 and, to a limited extent, VEGFR-2 were activated in early-stage specimens, whereas VEGFR-2 and VEGFR-3 were activated in advanced-stage specimens. Conclusions: Our results suggest that lymphangiogenic markers, such as VEGF-D and VEGFR-2 and VEGFR-3, may be better than angiogenic markers as targets of therapeutic intervention in advanced-stage prostate disease.
Energy cost of membrane depolarization in hog carotid artery.
Authors: J W Peterson, E Glück
Journal: Circulation Research (1982)

Past studies have shown that during stable stepwise activations of vascular smooth muscle with varying concentrations of high-K+, both cytoplasmic free-Ca++ and membrane depolarization vary. On the other hand, during stepwise activations with varying concentrations of external Ca++ in the presence of constant external Ca++ in the presence of constant external depolarizing high-K+, cytoplasmic free-Ca++ varies, while membrane depolarization remains relatively constant. In this study, the rates at which suprabasal energy metabolism (oxygen consumption and lactic acid production) increased with increasing isometric tension maintenance were measured under both circumstances. Suprabasal energy metabolism with increasing membrane depolarization (increasing external K+) exceeded that with constant depolarizing-[K+] and varying Ca++ by less than 2.5% at all levels of activation, which was not statistically significant (P greater than 0.70). We conclude therefore that the steady state metabolic energy cost of membrane depolarization per se during contractile activity in vascular smooth muscle from a tonic conducting vessel (hog carotid artery) is negligible. Although the possibility cannot be excluded, we find no metabolic evidence that increased cytoplasmic free-Ca++ itself activates an ATPase associated with Ca++ sequestration and/or extrusion beyond that present in the relaxed state. Activation of hog carotid artery with an isosmotic K+-for-Na+-substituted medium fails to stimulate aerobic glycolysis at all levels of K+ substitution. Experiments were performed at the muscle length optimal for isometric tension generation and at 37 degrees C.
Inactivation of the Osteopontin Gene Enhances Vascular Calcification of Matrix Gla Protein–deficient Mice
Authors: Mei Y. Speer, Marc D. McKee, Robert E. Guldberg, Lucy Liaw, Hsueh-Ying Yang, Elyse Tung, Gerard Karsenty, Cecilia M. Giachelli
Journal: The Journal of Experimental Medicine (2002)

Osteopontin (OPN) is abundantly expressed in human calcified arteries. To examine the role of OPN in vascular calcification, OPN mutant mice were crossed with matrix Gla protein (MGP) mutant mice. Mice deficient in MGP alone (MGP−/− OPN+/+) showed calcification of their arteries as early as 2 weeks (wk) after birth (0.33 ± 0.01 mmol/g dry weight), and the expression of OPN in the calcified arteries was greatly up-regulated compared with MGP wild-types. OPN accumulated adjacent to the mineral and colocalized to surrounding cells in the calcified media. Cells synthesizing OPN lacked smooth muscle (SM) lineage markers, SM α-actin and SM22α. However, most of them were not macrophages. Importantly, mice deficient in both MGP and OPN had twice as much arterial calcification as MGP−/− OPN+/+ at 2 wk, and over 3 times as much at 4 wk, suggesting an inhibitory effect of OPN in vascular calcification. Moreover, these mice died significantly earlier (4.4 ± 0.2 wk) than MGP−/− OPN+/+ counterparts (6.6 ± 1.0 wk). The cause of death in these animals was found to be vascular rupture followed by hemorrhage, most likely due to enhanced calcification. These studies are the first to demonstrate a role for OPN as an inducible inhibitor of ectopic calcification in vivo.
STUDIES ON THE LYMPHOCYTOSIS INDUCED IN MICE BY BORDETELLA PERTUSSIS
Authors: Stephen I. Morse
Journal: The Journal of Experimental Medicine (1965)

1. Intravenous injection into mice of phase I Bordetella pertussis vaccine resulted in a striking hyperleucocytosis with a predominating lymphocytosis. Intraperitoneal inoculation was less effective, and subcutaneous administration was inactive. 2. Active immunization prevented the hyperleucocytosis; passive immunization was less effective. 3. Reticuloendothelial blockage reduced the effect of the vaccine. 4. Extirpation of the spleen or thymus did not alter the leucocyte response. 5. Histologic studies suggested that the increase in circulating lymphocytes resulted from release of cells from lymphoid organs, including the thymus.
Myeloid-related proteins S100A8/S100A9 regulate joint inflammation and cartilage destruction during antigen-induced arthritis
Authors: P L E M van Lent, L Grevers, A B Blom, A Sloetjes, J S Mort, T Vogl, W Nacken, W B van den Berg, J Roth
Journal: Annals of the Rheumatic Diseases (2007)

To study the active involvement of Myeloid-related proteins S100A8 and S100A9 in joint inflammation and cartilage destruction during antigen-induced arthritis (AIA).Joint inflammation and cartilage destruction was measured with 99mTc uptake and histology. The role of S100A8/A9 was investigated by inducing AIA in S100A9-/- mice that also lack S100A8 at protein level, or after intra-articular injection of rS100A8 in mouse knee joints. Cartilage destruction was measured using immunolocalisation of the neoepitope VDIPEN or NITEGE. mRNA levels of matrix metalloproteinases (MMPs) and cytokines were measured using reverse transcriptase (RT)-PCR.Immunisation of S100A9-/- mice with the antigen mBSA induced normal cellular and humoral responses, not different from wild type (WT) controls. However, joint swelling measured at day 3 and 7 after AIA induction was significantly lower (36 and 70%, respectively). Histologically, at day 7 AIA, cellular mass was much lower (63-80%) and proteoglycan depletion from cartilage layers was significantly reduced (between 50-95%). Cartilage destruction mediated by MMPs was absent in S100A9-/- mice but clearly present in controls. MMP3, 9 and 13 mRNA levels were significantly lowered in arthritic synovia of S100A9-/-. In vitro stimulation of macrophages by the heterodimer S100A8/A9 or S100A8 elevated mRNA levels of MMP3, 9 and in particular MMP13. Intra-articular injection of S100A8 caused prominent joint inflammation and depletion of proteoglycans at day 1. Significant upregulation of mRNA levels of S100A8/A9, cytokines (interleukin 1 (IL1)), MMPs (MMP3, MMP13 and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)4) was found in the synovium and correlated with strong upregulation of NITEGE neoepitopes within the cartilage layers.S100A8/A9 regulate joint inflammation and cartilage destruction during antigen-induced arthritis.
Leptin- or troglitazone-induced lipopenia protects islets from interleukin 1beta cytotoxicity.
Authors: M Shimabukuro, K Koyama, Y Lee, R H Unger
Journal: Journal of Clinical Investigation (1997)

Interleukin 1beta (IL-1beta)-induced beta cell cytotoxicity has been implicated in the autoimmune cytotoxicity of insulin-dependent diabetes mellitus. These cytotoxic effects may be mediated by nitric oxide (NO). Since long-chain fatty acids (FFA), like IL-1beta, upregulate inducible nitric oxide synthase and enhance NO generation in islets, it seemed possible that islets might be protected from IL-1beta-induced damage by lowering their lipid content. We found that IL-1beta-induced NO production varied directly and islet cell viability inversely with islet triglyceride (TG) content. Fat-laden islets of obese rats were most vulnerable to IL-1beta, while moderately fat-depleted islets of food-restricted normal rats were less vulnerable than those of free-feeding normal rats. Severely lipopenic islets of rats made chronically hyperleptinemic by adenoviral leptin gene transfer resisted IL-1beta cytotoxicity even at 300 pg/ml, the maximal concentration. Troglitazone lowered islet TG in cultured islets from both normal rats and obese, leptin-resistant rats and reduced NO production and enhanced cell survival. We conclude that measures that lower islet TG content protect against IL-1beta-induced NO production and cytotoxicity. Leptin or troglitazone could provide in vivo protection against insulin-dependent diabetes mellitus.
Vasopressin versus Norepinephrine Infusion in Patients with Septic Shock
Authors: James A. Russell, Keith R. Walley, Joel Singer, Anthony C. Gordon, Paul C. Hébert, D. James Cooper, Cheryl L. Holmes, Sangeeta Mehta, John T. Granton, Michelle M. Storms, Deborah J. Cook, Jeffrey J. Presneill, Dieter Ayers
Journal: New England Journal of Medicine (2008)

Vasopressin is commonly used as an adjunct to catecholamines to support blood pressure in refractory septic shock, but its effect on mortality is unknown. We hypothesized that low-dose vasopressin as compared with norepinephrine would decrease mortality among patients with septic shock who were being treated with conventional (catecholamine) vasopressors.In this multicenter, randomized, double-blind trial, we assigned patients who had septic shock and were receiving a minimum of 5 microg of norepinephrine per minute to receive either low-dose vasopressin (0.01 to 0.03 U per minute) or norepinephrine (5 to 15 microg per minute) in addition to open-label vasopressors. All vasopressor infusions were titrated and tapered according to protocols to maintain a target blood pressure. The primary end point was the mortality rate 28 days after the start of infusions.A total of 778 patients underwent randomization, were infused with the study drug (396 patients received vasopressin, and 382 norepinephrine), and were included in the analysis. There was no significant difference between the vasopressin and norepinephrine groups in the 28-day mortality rate (35.4% and 39.3%, respectively; P=0.26) or in 90-day mortality (43.9% and 49.6%, respectively; P=0.11). There were no significant differences in the overall rates of serious adverse events (10.3% and 10.5%, respectively; P=1.00). In the prospectively defined stratum of less severe septic shock, the mortality rate was lower in the vasopressin group than in the norepinephrine group at 28 days (26.5% vs. 35.7%, P=0.05); in the stratum of more severe septic shock, there was no significant difference in 28-day mortality (44.0% and 42.5%, respectively; P=0.76). A test for heterogeneity between these two study strata was not significant (P=0.10).Low-dose vasopressin did not reduce mortality rates as compared with norepinephrine among patients with septic shock who were treated with catecholamine vasopressors. (Current Controlled Trials number, ISRCTN94845869 [controlled-trials.com].).
The C Allele of <i>ATM</i> rs11212617 Does Not Associate With Metformin Response in the Diabetes Prevention Program
Authors: Jose C. Florez, Kathleen A. Jablonski, Andrew Taylor, Kieren Mather, Edward Horton, Neil H. White, Elizabeth Barrett-Connor, William C. Knowler, Alan R. Shuldiner, Toni I. Pollin
Journal: Diabetes Care (2012)

OBJECTIVE The C allele at the rs11212617 polymorphism in the ataxia-telangiectasia–mutated (ATM) gene has been associated with greater clinical response to metformin in people with type 2 diabetes. We tested whether this variant modified the effect of metformin in the Diabetes Prevention Program (DPP), in which metformin reduced diabetes incidence by 31% in volunteers with impaired glucose tolerance. RESEARCH DESIGN AND METHODS We genotyped rs11212617 in 2,994 DPP participants and analyzed its effects on diabetes incidence and related traits. RESULTS Contrary to expectations, C carriers enjoyed no preventive advantage on metformin; their hazard ratio, compared with A carriers, was 1.17 ([95% CI 0.96–1.42], P = 0.13) under metformin. There were no significant differences by genotype in metformin’s effects on insulin sensitivity, fasting glucose, glycated hemoglobin, or disposition index. CONCLUSIONS The reported association of rs11212617 with metformin response was not confirmed for diabetes prevention or for effects on relevant physiologic parameters in the DPP.