tbuckley/cabot-search huggingface dataset:
Biochemical actions of glucocorticoids on macrophages in culture. Specific inhibition of elastase, collagenase, and plasminogen activator secretion and effects on other metabolic functions.
Authors: Z Werb
Journal: The Journal of Experimental Medicine (1978)

The effects of glucocorticoids on biochemical functions of macrophages from man, mouse, rabbit, and guinea pig were examined. Secretion of plasminogen activator by human peripheral blood monocytes was decreased by 50% with 1 nM dexamethasone. Differentiation of murine monocytic and granulocytic colonies in agar from bone marrow precursors was decreased by 50% at 7 days with 20 nM dexamethasone. Secretion of elastase, collagenase, and plasminogen activator by resident and thioglycollate-elicited mouse peritoneal macrophages was decreased by dexamethasone, cortisol, and triamcinolone acetonide (1--1,000 nM), but not by progesterone, estradiol, and dihydrotestosterone (1,000 nM); in contrast, secretion of lysozyme was not affected by glucocorticoids or other steroids. The inhibition of macrophage secretion by dexamethasone was both time and dose dependent. Effects were detected within 1--6 h after addition of the glucocorticoids, became maximum by 24 h, and were reversed during a similar time period after removal of the hormones. The extent of inhibition of macrophage secretion increased with increasing glucocorticoid concentration. Half-maximum inhibition of secretion of elastase, collagenase, and plasminogen activator was seen at dexamethasone concentrations (1--10 nM) similar to those that half-saturated the specific glucocorticoid receptors in these cells. At high concentrations of dexamethasone (100--1,000 nM) the secretion of plasminogen activator was inhibited to a greater extent (greater than 95%) than the secretion of elastase (60--80%). Progesterone alone had no effect on secretion, but it blocked the inhibitory effects of dexamethasone and cortisol. Secretion of collagenase, neutral proteinases, and plasminogen activator by elicited rabbit alveolar macrophages was inhibited with glucocorticoids (0.1--100 nM) but not with progesterone or sex steroids. Secretion of a neutral elastinolytic proteinase by guinea pig alveolar macrophages was also inhibited by dexamethasone. These data support the regulatory role of glucocorticoids on macrophage functions at physiological concentrations.
Transfusion-associated acute graft-versus-host disease in a heart transplant recipient
Authors: M.A. SOLA, A. ESPAN̄A, P. REDONDO, M.A. IDOATE, A.L. FERNANDEZ, R. LLORENS, E. QUINTANILLA
Journal: British Journal of Dermatology (2006)

Summary We report a heart transplant recipient who developed graft-versus-host disease (GVHD) following blood transfusion. We consider that heart transplant recipients should be included in the category of immunosuppressed patients who may develop this disease after being treated with blood products. We also consider that, at the present time, irradiation of blood products is the only useful method of avoiding development of GVHD in these patients.
STUDIES ON THE HEMOLYTIC STREPTOCOCCUS OF HUMAN ORIGIN
Authors: Champ Lyons, Hugh K. Ward
Journal: The Journal of Experimental Medicine (1935)

1. Anantiserum which specifically protects mice against a virulent culture (M variant) of the hemolytic streptococcus contains specific opsonin. Phagocytosis of the organisms can be observed in the peritoneum of the protected mouse. 2. An antiserum prepared by injecting an animal with the living M variant specifically opsonizes both the F and the M variant of the strain. 3. Evidence is presented which indicates the probable identity of the specific opsonin and the anti-M precipitin of Lancefield (7). Agglutination appears to be dependent upon a different antibody. 4. It is possible to type the hemolytic streptococci by means of specific opsonins, and the opsonic method has certain advantages over agglutination, precipitation, and mouse protection tests. It is evident from what little has been done that there are many types. 5. The serum of infants contains no opsonin for the virulent hemolytic streptococci, but the serum of adults may contain specific opsonins for certain strains. Inasmuch as no opsonins were demonstrable in two polyvalent antibacterial sera examined, the possibilities of therapeutic transfusion are discussed.
The Prediction of Diabetic Neuropathic Foot Ulceration Using Vibration Perception Thresholds: A prospective study
Authors: Matthew J Young, John L Breddy, Aristidis Veves, Andrew J M Boulton
Journal: Diabetes Care (1994)

OBJECTIVE To assess the ability of vibration perception threshold (VPT) to predict the development of diabetic foot ulceration. RESEARCH DESIGN AND METHODS A prospective follow-up study of consecutive patients with vibration perception measured by biothesiometry from April 1988 to March 1989. Patients were stratified in various risk groups. RESULTS Patients with a VPT &amp;lt;15 V had a cumulative incidence of foot ulceration of 2.9% compared with 19.8% in patients with a VPT &amp;gt;25 V, odds ratio (OR) 7.99 (3.65–17.5, 95% confidence intervals), P &amp;lt; 0.01. The incidence of ulceration increased with duration of diabetes, but even with this effect removed, the excess of ulceration persisted, OR 6.82 (2.75–16.92), P &amp;lt; 0.01. CONCLUSIONS VPT is an effective predictor of the risk of foot ulceration in diabetes and therefore could be used to target foot-care education to those patients most likely to benefit and, thereby, possibly improve its effectiveness.
Endothelial cell O-glycan deficiency causes blood/lymphatic misconnections and consequent fatty liver disease in mice
Authors: Jianxin Fu, Holger Gerhardt, J. Michael McDaniel, Baoyun Xia, Xiaowei Liu, Lacramioara Ivanciu, Annelii Ny, Karlien Hermans, Robert Silasi-Mansat, Samuel McGee, Emma Nye, Tongzhong Ju, Maria I. Ramirez, Peter Carmeliet, Richard D. Cummings, Florea Lupu, Lijun Xia
Journal: Journal of Clinical Investigation (2008)

Mucin-type O-glycans (O-glycans) are highly expressed in vascular ECs. However, it is not known whether they are important for vascular development. To investigate the roles of EC O-glycans, we generated mice lacking T-synthase, a glycosyltransferase encoded by the gene C1galt1 that is critical for the biosynthesis of core 1-derived O-glycans, in ECs and hematopoietic cells (termed here EHC T-syn(-/-) mice). EHC T-syn(-/-) mice exhibited embryonic and neonatal lethality associated with disorganized and blood-filled lymphatic vessels. Bone marrow transplantation and EC C1galt1 transgene rescue demonstrated that lymphangiogenesis specifically requires EC O-glycans, and intestinal lymphatic microvessels in EHC T-syn(-/-) mice expressed a mosaic of blood and lymphatic EC markers. The level of O-glycoprotein podoplanin was significantly reduced in EHC T-syn(-/-) lymphatics, and podoplanin-deficient mice developed blood-filled lymphatics resembling EHC T-syn(-/-) defects. In addition, postnatal inactivation of C1galt1 caused blood/lymphatic vessel misconnections that were similar to the vascular defects in the EHC T-syn(-/-) mice. One consequence of eliminating T-synthase in ECs and hematopoietic cells was that the EHC T-syn(-/-) pups developed fatty liver disease, because of direct chylomicron deposition via misconnected portal vein and intestinal lymphatic systems. Our studies therefore demonstrate that EC O-glycans control the separation of blood and lymphatic vessels during embryonic and postnatal development, in part by regulating podoplanin expression.
Are Patients With Renal Failure Good Candidates for Percutaneous Coronary Revascularization in the New Device Era?
Authors: Mark H. Rubenstein, Lari C. Harrell, Boris V. Sheynberg, Heribert Schunkert, Hasan Bazari, Igor F. Palacios
Journal: Circulation (2000)

Background —Patients with end-stage renal disease undergoing conventional balloon angioplasty have reduced procedural success and increased complication rates. This study was designed to determine the immediate and long-term outcomes of patients with varying degrees of renal failure undergoing percutaneous coronary intervention in the current device era. Methods and Results —We compared the immediate and long-term outcomes of 362 renal failure patients (creatinine &gt;1.5 mg/dL) with those of 2972 patients with normal renal function who underwent percutaneous coronary intervention between 1994 and 1997. Patients with renal failure were older and had more associated comorbidities. They had reduced procedural success (89.5% versus 92.9%, P =0.007) and greater in-hospital combined major event (death, Q-wave myocardial infarction, emergent CABG; 10.8% versus 1.8%; P &lt;0.0001) rates. Renal failure was an independent predictor of major adverse cardiac events (MACEs) (OR, 3.41; 95% CI, 1.84 to 6.22; P &lt;0.00001). Logistic regression analysis identified shock, peripheral vascular disease, balloon angioplasty strategy, and unstable angina as independent predictors of in-hospital MACEs in the renal group. Compared with 362 age- and sex-matched patients selected from the control group, patients with renal failure had a lower survival rate (27.7% versus 6.1%, P &lt;0.0001) and a greater MACE rate (51% versus 33%, P &lt;0.001) at long-term follow-up. Cox regression analysis identified age and PTCA strategy as independent predictors of long-term MACEs in the renal group. Finally, within the renal failure population, the dialysis and nondialysis patients experienced remarkably similar immediate and long-term outcomes. Conclusions —Although patients with renal failure can be treated with a high procedural success rate in the new device era, they have an increased rate of major events both in hospital and at long-term follow-up. Nevertheless, utilization of stenting and debulking techniques improves immediate and long-term outcomes.
Carcinoid myopathy and treatment with cyproheptadine (Periactin)
Authors: E. M. Berry, C. Maunder, M. Wilson
Journal: Gut (1974)

A case of the carcinoid syndrome associated with a proximal myopathy is reported. Histology showed advanced atrophy of type II muscle fibres but no inflammation. Perinuclear acid phosphatase was increased. Electron microscopy revealed persistence of the Z-line until the muscle fibre had been severely disrupted. Similar lesions have been observed in the hereditary muscular dystrophy in mice, and also in these animals and in rats when injected with 5-hydroxytryptamine (5-HT). Treatment with cyproheptadine caused a documented response in the patient's debilitating diarrhoea and also produced symptomatic improvement in her muscular power. We suggest that the myopathy is due to circulating 5-HT or is a non-metastatic complication of the carcinoid tumour.
Observer-blind, randomized, intrapatient comparison of a novel 1% coal tar preparation (Exorex) and calcipotriol cream in the treatment of plaque type psoriasis
Authors: S. Tzaneva, H. Honigsmann, A. Tanew
Journal: British Journal of Dermatology (2003)

Summary Background In a recent pilot study a novel, patented fatty acid-based 1% coal tar preparation (Exorex) has been found to be similar in efficacy to calcipotriol in the treatment of psoriasis. Objectives Our aim was to investigate the therapeutic efficacy, safety and cosmetic acceptability of the new 1% coal tar preparation in comparison with calcipotriol cream in a larger patient cohort. Patients and methods Forty patients with chronic plaque type psoriasis were included in this randomized, observer-blind, intrapatient comparison trial. In each patient two comparable target plaques were treated twice daily with 1% coal tar preparation or calcipotriol cream. At the onset of therapy and at weeks 2, 4, 6 and 8, the response to treatment was determined by the psoriasis severity index (PSI) that assesses the degree of erythema, infiltration and scaling of the psoriatic lesions on a five-point scale. In addition, all treatment-related side-effects were recorded and cosmetic acceptability of both treatments was rated every second week by the patients. After complete or near complete clearing the patients were followed up until relapse or for a maximum period of 18 months. Results Thirty-eight patients completed the study. At termination of the trial the mean ± SD baseline PSI score of 9·2 ± 1·5 was reduced to 3·0 ± 2·9 by 1% coal tar preparation and to 2·8 ± 2·7 by calcipotriol. The mean PSI reduction between baseline and final assessment did not differ significantly between 1% coal tar preparation and calcipotriol (P = 0·77). The mean intraindividual difference in reduction of PSI score between 1% coal tar preparation and calcipotriol was 0·1 score points (95% confidence interval − 0·84 to + 0·63). No difference between either preparation was observed with regard to time until relapse. Itching was caused by 1% coal tar preparation in four patients and by calcipotriol in one patient. Unpleasant odour or staining of the 1% coal tar preparation was reported by six patients, whereas one patient complained about the smell of the calcipotriol cream. Conclusions The novel 1% coal tar preparation was found to be comparably as effective as calcipotriol in treating psoriasis. Tolerability and cosmetic acceptability was better for calcipotriol. Taking into consideration that the coal tar preparation is considerably less expensive than calcipotriol this new product appears as a very useful topical medication for chronic plaque type psoriasis.
Practice Makes Perfect
Authors: M. J. Friedrich
Journal: JAMA (2002)

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Eosinophilia associated with adult t-cell leukemia: Role of interleukin 5 and granulocyte-macrophage colony-stimulating factor
Authors: Masao Ogata, Yuko Ogata, Kazuhiro Kohno, Noritaka Uno, Eiji Ohno, Eiichi Ohtsuka, Yoshio Saburi, Perparim Kamberi, Masaru Nasu, Hiroshi Kikuchi
Journal: American Journal of Hematology (1998)

To clarify the mechanism of eosinophilia in adult T-cell leukemia (ATL), we studied three ATL patients having marked eosinophilia. Eosinophil-predominant colony-stimulating activity was detected in the serum of one patient and in the conditioned media (CM) from cultured ATL cells from two patients. Soluble interleukin 5 (IL-5), but no interleukin 3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF), was detected in sera from all patients. On the other hand, GM-CSF was produced in vitro by ATL cells from all cases, whereas detectable IL-3 and IL-5 was produced by cells from only one, suggesting that in the other two cases, the serum IL-5 was produced by the normal reacting lymphocytes. The fact that no patient showed marked neutrophilia supports the possibility that IL-5 may have a leading role in the development of eosinophilia, with GM-CSF produced by ATL cells playing a complementary role. Am. J. Hematol. 59:242–245, 1998. © 1998 Wiley-Liss, Inc.
Bacterial catabolism of nonulosonic (sialic) acid and fitness in the gut
Authors: Salvador Almagro-Moreno, E. Fidelma Boyd
Journal: Gut Microbes (2010)

The term nonulosonic acid or sialic acid encompasses a varied group of nine-carbon amino sugars widely distributed among mammals and higher metazoans. Among bacteria, the ability to synthesize sialic acid was first examined in a small number of human pathogenic species that deposit sialic acid residues on their outer surface. New phylogenomic data suggest that the ability to synthesize sialic acid and sialic acid-like compounds is not a novel bacterial innovation but a much more widespread ancient trait. In contrast, the genes required for the catabolism of sialic acid are found only among pathogenic and commensal bacterial species. This ability to utilize sialic acid as a carbon source is correlated with bacterial virulence, especially, in the sialic acid rich environment of the gut. In this article, we present the most recent findings in sialobiology with a focus on sialic acid catabolism.
Effect of angiotensin receptor blockade and antihypertensive drugs on diastolic function in patients with hypertension and diastolic dysfunction: a randomised trial
Authors: Scott D Solomon, Rajesh Janardhanan, Anil Verma, Mikhail Bourgoun, William L Daley, Das Purkayastha, Yves Lacourcière, Stephen E Hippler, Harold Fields, Tasneem Z Naqvi, Sharon L Mulvagh, J Malcolm O Arnold, James D Thomas, Michael R Zile, Gerard P Aurigemma
Journal: The Lancet (2007)
Abstract 5146: The histone demethylase KDM2A is a new promoter of tumorigenesis, drug target and negative prognostic biomarker for non-small cell lung cancer
Authors: Klaus W. Wagner, Hunain Alam, Shilpa S. Dhar, Uma Giri, Na Li, Yongkun Wei, Tina Cascone, Dipak Giri, Jae-Hwan Kim, Yuanqing Ye, Asha Multani, Chia-Hsin Chan, Baruch Erez, Babita Saigal, Hui-Kuan Lin, Xifeng Wu, Mien-Chie Hung, John Heymach, MinGyu Lee
Journal: Cancer Research (2014)

Abstract The molecular etiology of non-small cell lung cancer (NSCLC) is heterogeneous and mostly dominated by alterations in kinase signaling pathways (i.e. KRAS, EGFR, EML4-ALK, PI3K, MEK1). Epigenetic modifiers, including histone methyltransferase and demethylases, have emerged as important regulators of oncogenic phenotypes in a small but growing number of tumor types, but the pathogenic role of histone methylation modifiers in NSCLC is largely unknown. We found that the histone H3 lysine 36 (H3K36) demethylase KDM2A is a novel oncogenic promoter of NSCLC. In our analysis KDM2A is frequently overexpressed in NSCLC cell lines and patient samples (≥14% in NSCLC tumors), and high expression levels of KDM2A correlate with poor prognosis in three independent patient populations from the USA and Asia. KDM2A knockdown by RNAi in KDM2A overexpressing cell lines inhibits proliferation and invasiveness of NSCLC cells in vitro and in three mouse xenograft models (subcutaneous, intravenous, and orthotopic models). Consistently, KDM2A overexpression promotes these cellular characteristics in NSCLC cell lines with low endogenous KDM2A levels. Rescue experiments using KDM2A-depleted cells showed that ectopic expression of wild-type KDM2A, but not its catalytic mutant mKDM2A, restored proliferation and invasion. These results indicate that the effect of KDM2A on oncogenic phenotypes is largely dependent on its catalytic activity and validate it as drug target for development of small molecule inhibitors. Mechanistically, we uncovered, that KDM2A activates the MAPK signaling pathway (ERK1/2) by transcriptionally repressing the MAPK phosphatase DUSP3. In summary, these novel findings indicate that KDM2A overexpression promotes NSCLC tumor growth and invasion. Our results provide new insights into how the dysregulation of an epigenetic enzyme can be coupled to activation of the ERK1/2 signaling pathway to promote NSCLC tumorigenesis and suggest that KDM2A is a promising anti-cancer therapeutic drug target for KDM2A-overexpressing NSCLC patients. Citation Format: Klaus W. Wagner, Hunain Alam, Shilpa S. Dhar, Uma Giri, Na Li, Yongkun Wei, Tina Cascone, Dipak Giri, Jae-Hwan Kim, Yuanqing Ye, Asha Multani, Chia-Hsin Chan, Baruch Erez, Babita Saigal, Hui-Kuan Lin, Xifeng Wu, Mien-Chie Hung, John Heymach, MinGyu Lee. The histone demethylase KDM2A is a new promoter of tumorigenesis, drug target and negative prognostic biomarker for non-small cell lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5146. doi:10.1158/1538-7445.AM2014-5146
High Blood Pressure Reduction Reverses Angiotensin II Type 2 Receptor–Mediated Vasoconstriction Into Vasodilation in Spontaneously Hypertensive Rats
Authors: Dong You, Laurent Loufrani, Celine Baron, Bernard I. Levy, Robert E. Widdop, Daniel Henrion
Journal: Circulation (2005)

Background— We have previously shown that angiotensin II type 2 receptor (AT 2 R) stimulation causes endothelium-dependent vasodilation that does not desensitize after chronic angiotensin II type 1 receptor (AT 1 R) blockade, suggesting a role for AT 2 R in antihypertensive treatment. Methods and Results— We recorded mean arterial pressure (MAP) and investigated AT 2 R by Western blot analysis, immunohistochemistry, and function in isolated mesenteric resistance arteries (205 μm in diameter) from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) receiving the following for 4 weeks in drinking water: placebo, AT 1 R blockade (candesartan; 2 mg/kg per day), ACE inhibitor (perindopril; 3 mg/kg per day), nonselective vasodilator (hydralazine; 16 or 24 mg/kg per day), or candesartan plus hydralazine (16 mg/kg per day). In precontracted isolated arteries, AT 2 R stimulation (angiotensin II in the presence of candesartan) caused vasodilation in WKY rats (MAP=118 mm Hg) and vasoconstriction in SHR (MAP=183 mm Hg). In SHR treated with candesartan (MAP=146 mm Hg) or hydralazine (16 mg/kg per day; MAP=145 mm Hg), AT 2 R-induced contraction was reduced by 50%. In SHR treated with perindopril (MAP=125 mm Hg), AT 2 R stimulation induced vasodilation. In SHR treated with hydralazine (24 mg/kg per day; MAP=105 mm Hg) and in SHR treated with hydralazine (16 mg/kg per day) plus candesartan (MAP=102 mm Hg), an AT 2 R-mediated vasodilation was restored. Immunochemistry and Western blot analysis showed that AT 2 R expression, lower in SHR than in WKY rats, was restored to normal levels by treatments reducing arterial pressure in SHR. Conclusions— Our results suggest that in resistance arteries of SHR, (1) AT 2 R is downregulated by hypertension, and (2) specific and nonspecific antihypertensive treatments restore AT 2 R expression and vasodilator functions.
THE PATHOGENESIS OF INFECTION WITH A VIRULENT (CG 179) AND AN AVIRULENT (B) STRAIN OF NEWCASTLE DISEASE VIRUS IN THE CHICKEN
Authors: David T. Karzon, Frederik B. Bang
Journal: The Journal of Experimental Medicine (1951)

Circulating antibody appeared in the convalescing NDV-infected chicken concomitantly with the disappearance of virus from the tissues. The antigenic response to the CG 179 and B strains was demonstrated to be approximately equal. The neutralization test in the embryo and the hemagglutination inhibition technique yielded parallel results in the measurement of antibody early in convalescence, but late in convalescence the hemagglutination inhibition titers were relatively lower. This disparity indicates the possible duality of the antibodies. There was a wide ratio between the neutralizing antibody titers found in the brain and in the serum after an asymptomatic infection with NDV. The antibody level in the brain appeared to be related to the extent of virus growth and damage in the central nervous system. It appeared likely that a major factor in determining the virulence of the CG 179 strain was the more rapid attainment in the central nervous system of high virus concentration which outstripped the defense mechanisms of the host.