tbuckley/cabot-search huggingface dataset:
Impact of sepsis on risk of postoperative arterial and venous thromboses: large prospective cohort study
Authors: J. D. Donze, P. M. Ridker, S. R. G. Finlayson, D. W. Bates
Journal: BMJ (2014)

Objectives To evaluate the impact of preoperative sepsis on risk of postoperative arterial and venous thromboses. Design Prospective cohort study using the National Surgical Quality Improvement Program database of the American College of Surgeons (ACS-NSQIP). Setting Inpatient and outpatient procedures in 374 hospitals of all types across the United States, 2005-12. Participants 2 305 380 adults who underwent surgical procedures. Main outcome measures Arterial thrombosis (myocardial infarction or stroke) and venous thrombosis (deep venous thrombosis or pulmonary embolism) in the 30 days after surgery. Results Among all surgical procedures, patients with preoperative systemic inflammatory response syndrome or any sepsis had three times the odds of having an arterial or venous postoperative thrombosis (odds ratio 3.1, 95% confidence interval 3.0 to 3.1). The adjusted odds ratios were 2.7 (2.5 to 2.8) for arterial thrombosis and 3.3 (3.2 to 3.4) for venous thrombosis. The adjusted odds ratios for thrombosis were 2.5 (2.4 to 2.6) in patients with systemic inflammatory response syndrome, 3.3 (3.1 to 3.4) in patients with sepsis, and 5.7 (5.4 to 6.1) in patients with severe sepsis, compared with patients without any systemic inflammation. In patients with preoperative sepsis, both emergency and elective surgical procedures had a twofold increased odds of thrombosis. Conclusions Preoperative sepsis represents an important independent risk factor for both arterial and venous thromboses. The risk of thrombosis increases with the severity of the inflammatory response and is higher in both emergent and elective surgical procedures. Suspicion of thrombosis should be higher in patients with sepsis who undergo surgery.
Re: Quantitative Association Between HER-2/neu and Steroid Hormone Receptors in Hormone Receptor-Positive Primary Breast Cancer
Authors: F. Spyratos, C. Bouchet, M. Ferrero-Pous, M. Tubiana-Hulin, K. Hacene
Journal: JNCI Journal of the National Cancer Institute (2003)

Recent clinical data (1) suggest that c-erbB-2 overexpression/amplification might be associated with tamoxifen resistance in patients with estrogen receptor (ER)-positive tumors. This association is controversial, however, and the question of the efficacy of hormone therapy in these patients is still a matter of debate. In a recent issue of the Journal, Konecny et al. (2) provided some answers to this question. After considering c-erbB-2, ER, and progesterone receptors (PRs) as continuous variables, they reported that patients with higher levels of c-erbB-2 overexpression had statistically significantly lower ER and PR levels than patients with lower levels of c-erbB-2 overexpression. They suggested that this finding might explain the relative resistance of c-erbB-2– positive, hormone receptor–positive tumors to hormone therapy.
Decreased levels of nucleotide pyrophosphatase phosphodiesterase 1 are associated with cartilage calcification in osteoarthritis and trigger osteoarthritic changes in mice
Authors: J Bertrand, Y Nitschke, M Fuerst, S Hermann, M Schäfers, J Sherwood, G Nalesso, W Ruether, F Rutsch, F Dell'Accio, T Pap
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> To analyse the function of nucleotide pyrophosphatase phosphodiesterase (NPP1), a member of the pyrophosphate pathway, in osteoarthritis (OA). <h3>Methods</h3> mRNA expression of NPP1, ANK ankylosing protein and tissue non-specific alkaline phosphatase was assessed by quantitative PCR. NPP1 protein levels were analysed in mouse and human cartilage samples. Bone metabolism was analysed by F18-positron emission tomography-scanning and µCT in ttw/ttw mice. Ttw/ttw mice are mice carrying a loss-of-function mutation in NPP1. Calcification of articular cartilage was assessed using von Kossa staining and OA severity using the Mankin score. Cartilage remodelling was investigated by type X collagen immunohistochemistry. <h3>Results</h3> Expression of NPP1, but not the other members of this pathway, inversely correlated with cartilage calcification and OA severity in mouse and humans. Proinflammatory cytokines downregulated the expression of NPP1, demonstrating an influence of inflammation on matrix calcification. Ttw/ttw mutant mice, carrying a loss-of-function mutation in NPP1, exhibit increased bone formation process in joints compared with wild types. Ttw/ttw mice also developed spontaneous OA-like changes, evaluated by histological analysis and in vivo imaging. Ectopic calcifications were associated with increased expression of collagen X in the cartilage. <h3>Conclusion</h3> The authors conclude that OA is characterised by the reactivation of molecular signalling cascades involving proinflammatory cytokines, thereby regulating the pyrophosphate pathway which consequently leads to cartilage ossification, at least in part resembling endochondral ossification.
The azaspirane SKF 105685 ameliorates renal allograft rejection in rats.
Authors: P Y Fan, C R Albrightson, D N Howell, C Best, A M Badger, T M Coffman
Journal: Journal of the American Society of Nephrology (1993)

The azaspirane SKF 105685 (N,N-dimethyl-8, 8-dipropyl-2-azaspiro (4.5) decane-2-propanamine dihydrochloride) has been shown to attenuate or reverse the course of immunologic disease in several animal models, possibly through the induction of nonspecific suppressor activity. To investigate its effects on immune-mediated renal disease, SKF 105685 was administered by gavage to rats with kidney allografts. Six days after transplantation, GFR (inulin clearance, 1.46 +/- 0.27 versus 0.41 +/- 0.15 mL/min per kg; P < 0.005) and RPF (p-aminohippurate clearance, 5.48 +/- 0.98 versus 1.99 +/- 0.72 mL/min per kg; P < 0.01) were significantly higher in SKF 105685-treated rats compared with vehicle-treated control rats. In addition, mononuclear inflammatory cell infiltrates were significantly reduced in SKF 105685-treated animals compared with controls. Treatment also reduced renal production of thromboxane B2 (81 +/- 22 versus 424 +/- 76 pg/min per mg of protein; P < 0.0005), prostaglandin E2 (612 +/- 165 versus 2,059 +/- 351 pg/min per mg of protein; P < 0.005), and 6-keto prostaglandin F1 alpha (217 +/- 56 versus 943 +/- 186 pg/min per mg of protein; P < 0.005), but interleukin-1 beta mRNA levels within kidney allografts were not affected by treatment. Thus, the azaspirane SKF 105685 is a novel immunosuppressive agent that substantially ameliorates renal allograft rejection in the rat. Although the mechanism of action is unknown, the beneficial effects of SKF 105685 in rejection may relate to its ability to induce suppressor activity and/or its effects on eicosanoid production.
High Potassium Intake Enhances the Inhibitory Effect of 11,12-EET on ENaC
Authors: Peng Sun, Dao-Hong Lin, Peng Yue, Houli Jiang, Katherine H. Gotlinger, Michal L. Schwartzman, John R. Falck, Mohan Goli, Wen-Hui Wang
Journal: Journal of the American Society of Nephrology (2010)

High dietary potassium stimulates the renal expression of cytochrome P450 (CYP) epoxygenase 2C23, which metabolizes arachidonic acid (AA). Because the AA metabolite 11,12-epoxyeicosatrienoic acid (11,12-EET) can inhibit the epithelial sodium channel (ENaC) in the cortical collecting duct, we tested whether dietary potassium modulates ENaC function. High dietary potassium increased 11,12-EET in the isolated cortical collecting duct, an effect mimicked by inhibiting the angiotensin II type I receptor with valsartan. In patch-clamp experiments, a high potassium intake or treatment with valsartan enhanced AA-induced inhibition of ENaC, an effect mediated by a CYP-epoxygenase-dependent pathway. Moreover, high dietary potassium and valsartan each augmented the inhibitory effect of 11,12-EET on ENaC. Liquid chromatography/mass spectrometry showed that the rate of EET conversion to dihydroxyeicosatrienoic acids (DHET) was lower in renal tissue obtained from rats on a high-potassium diet than from those on a control diet, but this was not a result of altered expression of soluble epoxide hydrolase (sEH). Instead, suppression of sEH activity seemed to be responsible for the 11,12-EET-mediated enhanced inhibition of ENaC in animals on a high-potassium diet. Patch-clamp experiments demonstrated that 11,12-DHET was a weak inhibitor of ENaC compared with 11,12-EET, whereas 8,9- and 14,15-DHET were not. Furthermore, inhibition of sEH enhanced the 11,12-EET-induced inhibition of ENaC similar to high dietary potassium. In conclusion, high dietary potassium enhances the inhibitory effect of AA and 11,12-EET on ENaC by increasing CYP epoxygenase activity and decreasing sEH activity, respectively.
DISRUPTION OF INFLUENZA VIRUS
Authors: David A. J. Tyrrell, Frank L. Horsfall
Journal: The Journal of Experimental Medicine (1954)

1. The hemagglutinating capacity, enzymic activity, and infectivity of several influenza viruses were destroyed by repeated freezing and thawing of dialyzed allantoic fluids containing them. 2. Influenza virus degraded by freezing and thawing, by treatment with 5 M urea, or by heating at 65 degrees C. still combined with homologous antibody and was demonstrable by blocking of the hemagglutination-inhibition and virus neutralization reactions. 3. After 50 cycles of freezing and thawing, much of the blocking antigen activity was not sedimented by centrifugation at 120,000 g for 2 hours, and electron microscopy showed complete disruption of the virus particles. So called soluble blocking antigen was obtained from four strains of influenza A, the Lee strain of influenza B, mumps, and Newcastle disease viruses. 4. Soluble blocking antigens from influenza A viruses were highly strain-specific; gave little or no reaction in complement-fixation tests; stimulated but little antibody production in rabbits and did not induce immunity in mice; caused reactivation of infective virus in neutral mixtures of homologous virus and immune serum. 5. Repeatedly frozen and thawed influenza virus preparations did not interfere with the propagation of infective virus in the allantoic sac. The blocking antigen activity they contained was precipitated by half saturated ammonium sulfate, destroyed by trypsin, chymotrypsin, or heating at 56 degrees C. for 30 minutes, but was unaffected by desoxyribonuclease or ribonuclease. 6. These findings are in accord with the view that soluble blocking antigen obtained from influenza virus particles on disruption by repeated freezing and thawing is protein in nature and represents the essential antigenic material of the intact virus.
Transgenic Expression of the Activating Natural Killer Receptor Ly49H Confers Resistance to Cytomegalovirus in Genetically Susceptible Mice
Authors: Seung-Hwan Lee, Ahmed Zafer, Yves de Repentigny, Rashmi Kothary, Michel L. Tremblay, Philippe Gros, Pascale Duplay, John R. Webb, Silvia M. Vidal
Journal: The Journal of Experimental Medicine (2003)

Natural resistance to infection with mouse cytomegalovirus (MCMV) is controlled by a dominant locus, Cmv1. Cmv1 is linked to the Ly49 family of natural killer receptors on distal chromosome 6. While some studies localized Cmv1 as distal to the Ly49 gene cluster, genetic and functional analysis identified Ly49h as a pivotal factor in resistance to MCMV. The role of these two independent genomic domains in MCMV resistance was evaluated by functional complementation using transgenesis of bacterial artificial chromosomes (BAC) in genetically susceptible mice. Phenotypic and genetic characterization of the transgenic animals traced the resistance gene to a single region spanning the Ly49h gene. The appearance of the Ly49H protein in NK cells of transgenic mice coincided with the emergence of MCMV resistance, and there was a threshold Ly49H protein level associated with full recovery. Finally, transgenic expression of Ly49H in the context of either of the two independent susceptibility alleles, Cmv1sBALB or Cmv1sFVB, conferred resistance to MCMV infection. These results demonstrate that Ly49h is necessary and sufficient to confer MCMV resistance, and formally demonstrate allelism between Cmv1 and Ly49h. This panel of transgenic animals provides a unique resource to study possible pleiotropic effect of Cmv1.
The effect of obesity on lung function
Authors: António Paes-Cardoso, José-Manuel Reis-Ferreira, Álvaro Moreira-da-Silva
Journal: European Respiratory Journal (2013)

The authors describe lung function abnormalities in patients with different severity grades of obesity and respiratory symptoms, but with no specific pathology or relevant respiratory past history. Lung function tests (LFT) in 163 patients had no statistically significant relationship (p>0.05) with body mass index (BMI) in obese people (BMI>30kg/m 2 , average 36.88kg/m 2  ±5.18), although either FVC (p=0.01), FEV1 (p=0.007) and RV (p=0.025) were correlated to waist circumference (WC). In morbidly obese subpopulation (BMI>40kg/m 2 ), there was no significant correlation of IMC with parameters of ventilatory mechanics; only alveolo-capillary diffusion (DLCO, p=0.039 but not DLCO/VA, p=0.06) was clearly correlated to WC. Waist circumference appears with more significant impact on LFT than BMI.  As conclusion, although our results proved the effect of obesity in lung function, perhaps the techniques usually adopted may not be sensitive enough to estimate this effect, expressing the complexity of obesity in this setting.
Distribution of renin activity and angiotensinogen in rat brain. Effects of dietary sodium chloride intake on brain renin.
Authors: C P Genain, G R Van Loon, T A Kotchen
Journal: Journal of Clinical Investigation (1985)

The purpose of this study was to investigate the biochemistry and the regulation of the brain renin-angiotensin system in the Sprague-Dawley rat. Renin activity and angiotensinogen concentrations (direct and indirect radioimmunoassays) were measured in several brain areas and in neuroendocrine glands. Regional renin activities were measured in separate groups of rats on high and low NaCl diets. Mean tissue renin activities ranged from 2.2 +/- 0.6 to 54.4 +/- 19.7 fmol/mg protein per h (mean of 7 +/- SD), with the highest amounts in pineal, pituitary, and pons-medulla. NaCl depletion increased renin activity in selected regions; based on estimates of residual plasma contamination (despite perfusion of brains with saline), increased renin activity of pineal gland and posterior pituitary was attributed to higher plasma renin. To eliminate contamination by plasma renin, 16-h-nephrectomized rats were also studied. In anephric rats, NaCl depletion increased renin activity by 92% in olfactory bulbs and by 97% in anterior pituitary compared with NaCl-replete state. These elevations could not be accounted for by hyperreninemia. Brain renin activity was low and was unaffected by dietary NaCl in amygdala, hypothalamus, striatum, frontal cortex, and cerebellum. In contrast to renin, highest angiotensinogen concentrations were measured in hypothalamus and cerebellum. Overall, angiotensinogen measurements with the direct and the indirect assays were highly correlated (n = 56, r = 0.96, P less than 0.001). We conclude that (a) NaCl deprivation increases renin in olfactory bulbs and anterior pituitary of the rat, unrelated to contamination by plasma renin; and (b) the existence of angiotensinogen, the precursor of angiotensins, is demonstrated by direct radioimmunoassay throughout the brain and in neuroendocrine glands.
Rupture Rate of Large Abdominal Aortic Aneurysms in Patients Refusing or Unfit for Elective Repair
Authors: Frank A. Lederle
Journal: JAMA (2002)

Among patients with abdominal aortic aneurysm (AAA) who have high operative risk, repair is usually deferred until the AAA reaches a diameter at which rupture risk is thought to outweigh operative risk, but few data exist on rupture risk of large AAA.To determine the incidence of rupture in patients with large AAA.Prospective cohort study in 47 Veterans Affairs medical centers.Veterans (n = 198) with AAA of at least 5.5 cm for whom elective AAA repair was not planned because of medical contraindication or patient refusal. Patients were enrolled between April 1995 and April 2000 and followed up through July 2000 (mean, 1.52 years).Incidence of AAA rupture by strata of initial and attained diameter.Outcome ascertainment was complete for all patients. There were 112 deaths (57%) and the autopsy rate was 46%. Forty-five patients had probable AAA rupture. The 1-year incidence of probable rupture by initial AAA diameter was 9.4% for AAA of 5.5 to 5.9 cm, 10.2% for AAA of 6.0 to 6.9 cm (19.1% for the subgroup of 6.5-6.9 cm), and 32.5% for AAA of 7.0 cm or more. Much of the increased risk of rupture associated with initial AAA diameters of 6.5-7.9 cm was related to the likelihood that the AAA diameter would reach 8.0 cm during follow-up, after which 25.7% ruptured within 6 months.The rupture rate is substantial in high-operative-risk patients with AAA of at least 5.5 cm in diameter and increases with larger diameter.
Decreased Obesity and Atherosclerosis in Human Paraoxonase 3 Transgenic Mice
Authors: Diana M. Shih, Yu-Rong Xia, Xu-Ping Wang, Susanna S. Wang, Noam Bourquard, Alan M. Fogelman, Aldons J. Lusis, Srinivasa T. Reddy
Journal: Circulation Research (2007)

Paraoxonase 3 (PON3) is a member of the PON family, which includes PON1, PON2, and PON3. Recently, PON3 was shown to prevent the oxidation of low-density lipoprotein in vitro. To test the role of PON3 in atherosclerosis and related traits, 2 independent lines of human PON3 transgenic (Tg) mice on the C57BL/6J (B6) background were constructed. Human PON3 mRNA was detected in various tissues, including liver, lung, kidney, brain, adipose, and aorta, of both lines of Tg mice. The human PON3 mRNA levels in the livers of PON3 Tg mice were 4- to 7-fold higher as compared with the endogenous mouse Pon3 mRNA levels. Human PON3 protein and activity were detected in the livers of Tg mice as well. No significant differences in plasma total, high-density lipoprotein, and very-low-density lipoprotein/low-density lipoprotein cholesterol and triglyceride and glucose levels were observed between the PON3 Tg and non-Tg mice. Interestingly, atherosclerotic lesion areas were significantly smaller in both lines of male PON3 Tg mice as compared with the male non-Tg littermates on B6 background fed an atherogenic diet. When bred onto the low-density lipoprotein receptor knockout mouse background, the male PON3 Tg mice also exhibited decreased atherosclerotic lesion areas and decreased expression of monocyte chemoattractant protein-1 in the aorta as compared with the male non-Tg littermates. In addition, decreased adiposity and lower circulating leptin levels were observed in both lines of male PON3 Tg mice as compared with the male non-Tg mice. In an F2 cross, adipose Pon3 mRNA levels inversely correlated with adiposity and related traits. Our study demonstrates that elevated PON3 expression significantly decreases atherosclerotic lesion formation and adiposity in male mice. PON3 may play an important role in protection against obesity and atherosclerosis.
Bone-Derived Stem Cells Repair the Heart After Myocardial Infarction Through Transdifferentiation and Paracrine Signaling Mechanisms
Authors: Jason M. Duran, Catherine A. Makarewich, Thomas E. Sharp, Timothy Starosta, Fang Zhu, Nicholas E. Hoffman, Yumi Chiba, Muniswamy Madesh, Remus M. Berretta, Hajime Kubo, Steven R. Houser
Journal: Circulation Research (2013)

Autologous bone marrow-derived or cardiac-derived stem cell therapy for heart disease has demonstrated safety and efficacy in clinical trials, but functional improvements have been limited. Finding the optimal stem cell type best suited for cardiac regeneration is the key toward improving clinical outcomes.
Regulation of Immunity Toward Allogeneic Tumors in Mice. II. Effect of Antiserum and Antiserum Fractions on Cellular and Humoral Response&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Takasugi, M., Hildemann, W. H.
Journal: JNCI Journal of the National Cancer Institute (1969)

Journal Article Regulation of Immunity Toward Allogeneic Tumors in Mice. II. Effect of Antiserum and Antiserum Fractions on Cellular and Humoral Response Get access M. Takasugi, M. Takasugi Department of Medical Microbiology and Immunology, University of California, Los Angeles, California 90024 Search for other works by this author on: Oxford Academic PubMed Google Scholar W. H. Hildemann W. H. Hildemann Department of Medical Microbiology and Immunology, University of California, Los Angeles, California 90024 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 43, Issue 4, October 1969, Pages 857–867, https://doi.org/10.1093/jnci/43.4.857 Published: 01 October 1969 Article history Received: 04 April 1969 Accepted: 20 June 1969 Published: 01 October 1969
Influenza in North Lincolnshire
Authors: T. B. F. Eminson
Journal: BMJ (1891)

caeum, and in this region there was well-marked tenderness.After being put to bed and treated with hot bottles, poultices, etc., he quickly recovered, but some tenderness over the ceecum remained for a day or two.There was no rise of tem- perature.Ile left the hospital in four days, well but very weak.The two hospital cases were very alarming, and as eollapsed as though they had been violently kicked over the solar plexus; but in all the abdominal pain was a marked pre- cursor of the attack, and the collapse its principal feature; while the severe depression that followed was common to all the four cases, though only in two of them was there any evi- dence of the bronchial irritation from whiclh so many of our influenza patients have suffered.These cases do, I think, furnislh additional evidence that, as Dr. Graves of Dublin and Dr. Blakiston of Birmingham affirmed long ago, influenza is an affection of the nervous system, with its concomitant derangements in the organs of digestion, circulation, etc., while the seat of incidence of the poison may be determined by at present unknown causes.
Switching to adalimumab for psoriasis patients with a suboptimal response to etanercept, methotrexate, or phototherapy: Efficacy and safety results from an open-label study
Authors: Bruce E. Strober, Yves Poulin, Francisco A. Kerdel, Richard G. Langley, Yihua Gu, Shiraz R. Gupta, Martin M. Okun, Kim A. Papp
Journal: Journal of the American Academy of Dermatology (2011)