tbuckley/cabot-search huggingface dataset:
Stomatococcus mucilaginosus in patients with bronchiectasis
Authors: Walid Hadid, Zhihong Yuan, Dipti Panchal, Mansoor Syed, Ruxana Sadikot
Journal: European Respiratory Journal (2013)

Bronchiectasis is a debilitating, airways disease characterized by a vicious cycle of inflammation and bacterial colonization. Infections contribute to development of recurrent exacerbations and premature death. We found that 9% of patients with bronchiectasis were colonized with  Stomatococcus mucilaginosa (SM),  in their lower respiratory tract as determined from bronchoalveolar lavage (BAL). SM is a gram positive human pathogen found in oral cavity which has been reported to cause severe infections in immunocompromised patients. We hypothesized that  SM  is a low grade pathogen which may predispose individuals with bronchiectasis to other infections such as PA. To define the pathogenic profile of SM we performed  in vivo  studies in wild type mice. Similar to  P.aeruginosa  SM induced a neutrophilic influx with production of cytokines and chemokines in the lungs when given intratracheally (10 10  cfu/ml). SM induced COX-2 in the lungs with production of PGE 2 . Furthermore, inhibition of COX-2 with NS-398 (specific inhibitor of COX-2) showed an enhanced clearance of SM with improved survival in mice that were treated with SM and PA103. The induction of COX-2 by SM was TLR2 dependent in vivo.  In vitro  studies in macrophages showed that treatment of cells with SM (MOI of 100) resulted in induction of pro-inflammatory cytokines, chemokines, enzymes (COX-2) and lipid mediators. Induction of COX-2 and production of PGE 2  in macrophages by SM was dependent on MAP Kinase signaling pathway. In conclusion our data for the first time provide novel insights into the pathogenic role of SM which is often ignored as a contaminant. Our data strongly suggest that SM from lower respiratory tract should not be considered an innocent bystander.
Comparison of Angiotensin II Antagonist and Antiserum Infusion with Nephrectomy in the Rat with Two-Kidney Goldblatt Hypertension
Authors: HERBERT THURSTON, JOHN D. SWALES
Journal: Circulation Research (1974)

Factors responsible for maintaining blood pressure were studied in rats with one renal artery constricted and the contralateral kidney intact. Rats with short-term (&lt; 3 weeks) and chronic (&gt; 4 months) hypertension were infused with angiotensin II antiserum until the pressor effect of exogenous angiotensin II was blocked. The blood pressure response to an infusion of an angiotensin antagonist (1-Sar-8-Ala-angiotensin II) was then recorded. Blood pressure was also measured following subsequent unilateral nephrectomy (ischemic kidney). Antiserum produced a small, sustained, nonsignificant fall in mean blood pressure, whereas the antagonist produced a major reduction. In rats with short-term hypertension, the antagonist reduced blood pressure to normal or near-normal levels. In rats with chronic hypertension, mean blood pressure fell but still remained above the upper limit of the normal range. Removal of the ischemic kidney produced a fall in blood pressure to a mean level close to that obtained after antagonist infusion. Mean cumulative sodium balance in the rats with short-term hypertension was slightly negative. On the basis of this and previously reported work, it is suggested that angiotensin II is generated at a vascular site which is inaccessible to antibody but readily accessible to antagonist. Moreover, since the effects of angiotensin II antagonist and nephrectomy do not differ significantly, it seems that the ischemic kidney sustains hypertension in this two-kidney model through activity of the renin-angiotensin system, although extrarenal factors assume greater importance when blood pressure remains elevated for longer periods.
The High Frequency of <i>De novo</i> Promoter Methylation in Synchronous Primary Endometrial and Ovarian Carcinomas
Authors: Daniela Furlan, Ileana Carnevali, Barbara Marcomini, Roberta Cerutti, Emanuele Dainese, Carlo Capella, Cristina Riva
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The methylation status of hMLH1, CDKN2A, and MGMT was investigated in a panel of synchronous cancers of the ovary and endometrium, fulfilling the clinicopathologic criteria for independent primary tumors to define the possible role of epigenetic mechanisms in the development of these cancers. Experimental Design: Bisulfite-converted DNA from 31 tumors (13 endometrial and 18 ovarian carcinomas) and from matched normal tissue of 13 patients was analyzed by a methylation-specific PCR assay at the CpG-rich 5′ regions of all three genes. In all tumors, we also investigated the presence of microsatellite instability and hMLH1 immunohistochemical expression in relation to hMLH1 hypermethylation status. Results: Methylation of hMLH1, CDKN2A, and MGMT was detected in 39%, 41%, and 48% of endometrial and ovarian tumors, respectively. hMLH1 hypermethylation was observed in all tumors of five patients, and it was invariably associated with loss of hMLH1 protein and presence of microsatellite instability. CDKN2A and MGMT methylation was randomly detected among both endometrial (45% and 24% of cases, respectively) and ovarian carcinomas (39% and 39% of cases, respectively). Concordant methylation at two or three genes was observed in 35% of cases. Conclusions: Epigenetic inactivation of hMLH1, CDKN2A, and MGMT may be a common and early event in the development of synchronous primary endometrial and ovarian carcinomas and may qualify as a marker of a field cancerization encompassing the ovary and endometrium. Detection of MGMT hypermethylation may be useful to define a set of gynecologic malignancies with a specific sensitivity to alkylating chemotherapy.
Modification of the Effects of Hypertension on Lysosomes and Connective Tissue in the Rat Aorta
Authors: HARVEY WOLINSKY, SIDNEY GOLDFISCHER, BERNICE SCHILLER, LISA E. KASAK
Journal: Circulation Research (1974)

The relationship of Iysosomes to the vascular effects of hypertension and the possible modification of these effects by anti-inflammatory agents (methylprednisolone and aspirin), vitamin E, and estrogen were studied. Each of these agents was given to a group of hypertensive rats; untreated hypertensive rats and normotensive rats served as controls. Vessel wall morphology and dimensions of aortas from hypertensive rats were unaffected by treatment. Usual connective tissue accumulations seen in hypertensive vessels were suppressed to normotensive levels in the methylprednisolone- and estrogen-treated hypertensive groups. Two lysosomal enzymes, acid phosphatase and N -acetyl-β- d -glucosaminidase (NAGA), increased over normal levels in hypertensive vessels from 1.03 ± 0.08 ( SE ) to 2.04 ± 0.19 µmoles/aortic pair hour -1 and from 1.10 ± 0.24 to 4.57 ± 0.38 µmoles/aortic pair hour -1 for the respective enzymes. Normal enzyme levels in estrogen-treated hypertensive rats (1.14 ± 0.15 µmoles/aortic pair hour -1 for acid phosphatase and 2.04 ± 0.44 µmoles/aortic pair hour -1 for NAGA) and intermediate levels in methylprednisolone-treated hypertensive rats (1.35 ± 0.10 µmoles/ aortic pair hour -1 for acid phosphatase and 2.48 ± 0.54 µmoles/aortic pair hour -1 for NAGA) were found. Other treated groups showed the usual elevations associated with hypertension. These group differences were also seen after cytochemical staining for lysosomal acid phosphatase and NAGA. The parallel changes in aortic connective tissue and lysosomal enzymes in hypertension and their modification by two drugs suggest that these events are related.
Clinical-Translational Approaches to the Nm23-H1 Metastasis Suppressor
Authors: Patricia S. Steeg, Christine E. Horak, Kathy D. Miller
Journal: Clinical Cancer Research (2008)

Abstract Nm23-H1 significantly reduces metastasis without effects on primary tumor size and was the first discovered metastasis suppressor gene. At least three mechanisms are thought to contribute to the metastasis-suppressive effect of Nm23-H1: (a) its histidine kinase activity toward ATP-citrate lyase, aldolase C, and the kinase suppressor of ras, with the last inactivating mitogen-activated protein kinase signaling; (b) binding proteins that titer out “free” Nm23-H1 and inhibit its ability to suppress metastasis; and (c) altered gene expression downstream of Nm23-H1, particularly an inverse association with the lysophosphatidic acid receptor endothelial differentiation gene-28 (EDG2). Most metastasis suppressor genes, including Nm23-H1, affect metastatic colonization, which is the outgrowth of tumor cells in distant locations; therefore, they are of high translational interest. A phase II trial is ongoing to test the hypothesis that a compound, high-dose medroxyprogesterone acetate (MPA), used as an unconventional gluocorticoid, will stimulate breast cancer cells to reexpress Nm23-H1 and limit subsequent metastatic colonization.
Use of a Novel Technique of Cutaneous Lavage for Diagnosis of Lyme Disease Associated With Erythema Migrans
Authors: None Wormser
Journal: JAMA (1992)

<h3>Objective.</h3> —Determining the microbial cause of cellulitis is often difficult. In this study, a novel two-needle lavage technique was used to culture<i>Borrelia burgdorferi</i>from the skin of suspected erythema migrans lesions. <h3>Design.</h3> —The yield of lavage cultures for B burgdorferi was compared with that of a 2-mm skin biopsy sample. <h3>Setting.</h3> —A Lyme disease diagnostic center located in an area in which Lyme disease is epidemic. <h3>Patients.</h3> —Forty-five patients with suspected erythema migrans who had not been treated with antimicrobial agents. <h3>Intervention.</h3> —Cutaneous lavage of the advancing edge of a suspected primary erythema migrans lesion was done for all 45 participants, 33 of whom also had a skin biopsy of the same lesion at an identical (14) or an adjacent (19) site. <h3>Main Outcome Measures.</h3> —Growth of<i>B burgdorferi</i>in in vitro culture. <h3>Results.</h3> —Lavage fluid cultures grew<i>B burgdorferi</i>in 13 (29%) of the 45 cases (95% confidence interval [Cl], 16% to 44%). Among the 33 cases in which both lavage and skin biopsy cultures were done, the yield of lavage culture was less than that of biopsy culture (<i>P</i>&lt;.09, 12/33 vs 20/33). If contaminated cultures are excluded, this difference is significant (<i>P</i>&lt;.05, 12/30 vs 20/27). <h3>Conclusion.</h3> —Cutaneous lavage is a new diagnostic technique for recovery of<i>B burgdorferi</i>from erythema migrans lesions that has potential applicability to other types of cutaneous infections. (<i>JAMA</i>. 1992;268:1311-1313)
Chloride Intracellular Channel-4 Is a Determinant of Native Collateral Formation in Skeletal Muscle and Brain
Authors: Dan Chalothorn, Hua Zhang, Jennifer E. Smith, John C. Edwards, James E. Faber
Journal: Circulation Research (2009)

The capacity of the collateral circulation to lessen injury in occlusive vascular disease depends on the density and caliber of native (preexisting) collaterals, as well as their ability to outwardly remodel in ischemia. Native collateral conductance varies widely among healthy individuals, yet little is known about what specifies collateral formation. Chloride intracellular channel (CLIC)4 protein is required for endothelial cell hollowing, a process necessary for vessel formation during embryogenesis and ischemia. Whether CLIC4 has other physiological roles in vascular biology is uncertain. We studied collateral formation and remodeling in mice deficient in CLIC1 and CLIC4. Vascular responses to femoral artery ligation were similar in Clic1 −/− and wild-type mice. In contrast, immediately after ligation perfusion dropped more in Clic4 −/− than wild-type mice, suggesting fewer preexisting collaterals, a finding confirmed by angiography, greater ischemia, and worse recovery of perfusion; however, collateral remodeling was unaffected. Likewise, native cerebral collateral density in Clic4 −/− (but not Clic1 −/− ) mice was reduced, resulting in severe infarctions. This was associated with impaired perinatal formation and stabilization of nascent collaterals. Clic4 hemizygous mice had intermediate deficits in the above parameters, suggesting a gene-dose effect. Ischemia augmented CLIC1 and CLIC4 expression similarly in wild-type mice. However, CLIC1 increased 3-fold more in Clic4 −/− mice, suggesting compensation. Despite greater ischemia in Clic4 −/− mice, hypoxia-inducible factor-1α, vascular endothelial growth factor (VEGF) and angiopoietin-2 increased less compared to wild-type, suggesting CLIC4 exerts influences upstream of hypoxia-inducible factor-1α-VEGF signaling. Hence, CLIC4 represents the second gene that, along with VEGF shown by us previously, specifies native collateral formation.
Effect of immunisation against angiotensin II with CYT006-AngQb on ambulatory blood pressure: a double-blind, randomised, placebo-controlled phase IIa study
Authors: Alain C Tissot, Patrik Maurer, Juerg Nussberger, Robert Sabat, Thomas Pfister, Stanislav Ignatenko, Hans-Dieter Volk, Hans Stocker, Philipp Müller, Gary T Jennings, Frank Wagner, Martin F Bachmann
Journal: The Lancet (2008)
EAACI Food Allergy and Anaphylaxis Guidelines: diagnosis and management of food allergy
Authors: A. Muraro, T. Werfel, K. Hoffmann-Sommergruber, G. Roberts, K. Beyer, C. Bindslev-Jensen, V. Cardona, A. Dubois, G. duToit, P. Eigenmann, M. Fernandez Rivas, S. Halken, L. Hickstein, A. Høst, E. Knol, G. Lack, M. J. Marchisotto, B. Niggemann, B. I. Nwaru, N. G. Papadopoulos, L. K. Poulsen, A. F. Santos, I. Skypala, A. Schoepfer, R. Van Ree, C. Venter, M. Worm, B. Vlieg-Boerstra, S. Panesar, D. de Silva, K. Soares-Weiser, A. Sheikh, B. K. Ballmer-Weber, C. Nilsson, N. W. de Jong, C. A. Akdis
Journal: Allergy (2014)

Food allergy can result in considerable morbidity, impact negatively on quality of life, and prove costly in terms of medical care. These guidelines have been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Guidelines for Food Allergy and Anaphylaxis Group, building on previous EAACI position papers on adverse reaction to foods and three recent systematic reviews on the epidemiology, diagnosis, and management of food allergy, and provide evidence-based recommendations for the diagnosis and management of food allergy. While the primary audience is allergists, this document is relevant for all other healthcare professionals, including primary care physicians, and pediatric and adult specialists, dieticians, pharmacists and paramedics. Our current understanding of the manifestations of food allergy, the role of diagnostic tests, and the effective management of patients of all ages with food allergy is presented. The acute management of non-life-threatening reactions is covered in these guidelines, but for guidance on the emergency management of anaphylaxis, readers are referred to the related EAACI Anaphylaxis Guidelines.
Periampullary adenoma causing pancreatitis.
Authors: S H White, N A Nazarian, A M Smith, T W Balfour
Journal: BMJ (1981)

first hour, haemoglobin 13 1 g dl, and white cell count 11 5 109'1.Antinuclear and anti-heart-muscle antibodics were absent and complement concentration normal.Chest x-ray films showed slight cardiac enlargement, and on echocardiography a small amount of pericardial effusion was detected.Treatment with aspirin 2 g daily was started with rapid clinical improvement.Two wecks latcr the echocardiogram was normal.He had first suffered from fever and chest pain two years previously; the symptoms had begun 10 days after an influenza vaccination with A/Texas/l/ 77/(H.N.)4 A/USSR,'9,77,(H,N,), and B,Hong Kong 5 72 (Vaccigrip- Institut Marieux).A clinical diagnosis of acute benign pcricarditis had been confirmed by echocardiography, and the symptoms had complctely resolved after a month of stcroid trcatment.
MORPHOLOGY AND PEROXIDASE CYTOCHEMISTRY OF MOUSE PROMONOCYTES, MONOCYTES, AND MACROPHAGES
Authors: Ralph van Furth, James G. Hirsch, Martha E. Fedorko
Journal: The Journal of Experimental Medicine (1970)

Mouse promonocytes have been identified and studied in cultures of bone marrow cells. These cells have a diameter of 14-20 micro, and in stained preparations reveal a large, indented or folded nucleus, and basophilic, finely granular cytoplasm. The living promonocyte viewed by phase contrast shows additional features: nucleoli, small dense bodies, and vesicles in the cytoplasm adjacent to the nuclear hilus, and slight membrane ruffling. Prominent ultrastructural components of promonocytes include a well developed Golgi apparatus, small numbers of centrosomal granules and vacuoles, extensive ribosomal aggregates, and finger-like projections of the cell surface. Promonocytes engage in pinocytosis and phagocytosis, but they are less active in these functions than are peripheral blood monocytes of peritoneal macrophages. Promonocytes are positive for peroxidase, the reaction product being localized to granules most of which are centrally situated in the cell. Monocytes in blood or in inflammatory peritoneal exudates display much smaller numbers of peroxidase-positive granules, and various types of mature mouse macrophages are peroxidase negative.
Selective serotonin reuptake inhibitors
Authors: Harm W J van Marwijk, Herman J Adèr
Journal: BMJ (2005)

Editor—Geddes and Cipriani fear that regulatory bodies overrate the importance of placebo controlled trials.1 We disagree. The placebo controlled randomised trial is still the best test of efficacy available, although several improvements in conventional methodology are necessary to prevent selection biases.2 However, selection bias owing to a placebo washout period has not yet been tackled.

Although no doctor uses a placebo washout in real life practice, most antidepressant trials use such a period before randomisation. To demonstrate their effect: say, 200 patients are available, and 20 placebo responders are excluded before randomisation. The remaining 180 patients are then randomised to treatment with antidepressant or placebo. However, as it is not known whether all placebo responders in the antidepressant arm would have recovered if they had been given antidepressants, the direction of this differential selection may favour antidepressants.

Other necessary methodological improvements are: more use of “active” placebos to allow better blinding as they contain substances that mimic the specific side effects of antidepressants3; better concealment of allocation;4 independent outcome assessment4; independent funding4; inclusion of relevant groups such as general practice patients and elderly people; and the use of the preferred more conservative intention to treat analyses.5

Most known biases inflate the effects of antidepressants. Intention to treat analyses would, for example, decrease the risk difference between antidepressant drugs and placebo from 28% to 19%.2 A large, independently funded, good quality general practice trial of antidepressants versus placebo is much needed now, without placebo washouts.
Mega-Trials for Blockbusters
Authors: John P. A. Ioannidis
Journal: JAMA (2013)

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Brief Report: Endothelial‐Specific X‐Box Binding Protein 1 Deficiency Limits Tumor Necrosis Factor–Induced Leukocyte Recruitment and Vasculitis
Authors: Athanasios Ziogas, Michael H. Muders, Matina Economopoulou, David Sprott, Sylvia Grossklaus, Gabriele Siegert, Gustavo B. Baretton, Ioannis Mitroulis, Triantafyllos Chavakis
Journal: Arthritis & Rheumatology (2015)

Endothelial cell activation by tumor necrosis factor (TNF) and associated leukocyte infiltration are hallmarks of vasculitis. The aim of this study was to investigate the potential role of the cellular stress-associated endothelial X-box binding protein 1 (XBP-1) transcription factor in TNF-induced endothelial cell inflammation and vasculitis.Mice with an endothelial cell-specific XBP-1 deficiency were used in a modified local Shwartzman reaction (LSR) model of TNF-induced small vessel vasculitis. To address the contribution of XBP-1 to the TNF-mediated inflammatory response in endothelial cells, we examined the activation of XBP-1 expression by TNF as well as the effect of XBP-1 knockdown in endothelial cells on TNF-induced signaling, proinflammatory gene expression, and leukocyte-endothelial cell adhesion.The active spliced form of XBP-1 in endothelial cells was triggered by TNF. In addition, endothelial XBP-1 contributed to the sustained TNF-triggered NF-κB-dependent transcriptional activation of proinflammatory molecules, which was associated with leukocyte-endothelial cell adhesion. In the LSR model, endothelial cell-specific XBP-1-deficient mice displayed significantly less vascular damage, accompanied by reduced perivascular neutrophil infiltration, as compared with wild-type mice.Endothelial XBP-1 is activated by TNF and regulates leukocyte-endothelial cell adhesion in vitro as well as neutrophil infiltration and vascular damage in murine vasculitis.
Mortality After Radical Prostatectomy or External Beam Radiotherapy for Localized Prostate Cancer
Authors: R. M. Hoffman, T. Koyama, K.-H. Fan, P. C. Albertsen, M. J. Barry, M. Goodman, A. S. Hamilton, A. L. Potosky, J. L. Stanford, A. M. Stroup, D. F. Penson
Journal: JNCI Journal of the National Cancer Institute (2013)

No randomized trials have compared survival outcomes for men with localized prostate cancer (PC) being treated with radical prostatectomy (RP) or external beam radiotherapy (EBRT). The goal of the study, therefore, was to estimate the association of RP (compared with EBRT) with overall and PC mortality.We analyzed an observational cohort from the population-based Prostate Cancer Outcomes Study, which included men aged 55 to 74 years diagnosed with localized PC between October 1994 and October 1995 who underwent either RP (n = 1164) or EBRT (n = 491) within 1 year of diagnosis. Patients were followed until death or study end (December 31, 2010). Overall and disease-specific mortality were assessed with multivariable survival analysis, with propensity scores to adjust for potential treatment selection confounders (demographics, comorbidities, and tumor characteristics). All statistical tests were two-sided.After 15 years of follow-up, there were 568 deaths, including 104 from PC. RP was associated with statistically significant advantages for overall (hazard ratio [HR] = 0.60, 95% confidence interval [CI] = 0.53 to 0.70, P <.0001.) and disease-specific mortality (HR = 0.35, 95% CI = 0.26 to 0.49, P <.0001.). Mortality benefits for RP were also observed within treatment propensity quintiles, when subjects were pair-matched on propensity scores, and in subgroup analyses based on age, tumor characteristics, and comorbidity.Population-based observational data on men diagnosed with localized PC in the mid-1990s suggest a mortality benefit associated with RP vs EBRT. Possible explanations include residual selection bias or a true survival advantage. Results might be less applicable for men facing treatment decisions today.