tbuckley/cabot-search huggingface dataset:
Mutual upregulation of endothelin‐1 and <scp>IL</scp>‐25 in atopic dermatitis
Authors: M. K. Aktar, M. Kido‐Nakahara, M. Furue, T. Nakahara
Journal: Allergy (2015)

Endothelin-1 (ET-1) has been reported to evoke histamine-independent pruritus in mammals. However, its association with pruritus or inflammation of atopic dermatitis (AD) has not been clarified. We sought to investigate the role of ET-1 in the skin inflammation of AD.To examine the role of ET-1 in AD, we investigated the expression of ET-1 and IL-25 in the skin of an AD mouse model and patients with AD and examined the mutual regulatory relationship between ET-1 and IL-25, one of the important cytokines in AD, using the human HaCaT keratinocyte cell line.We immunohistochemically confirmed the upregulation of ET-1 and IL-25 expression in the epidermis of both the AD mouse model and patients with AD. In vitro, IL-25 upregulated ET-1 mRNA and protein expression in a concentration- and time-dependent fashion in HaCaT cells. This IL-25-induced ET-1 expression was inhibited by ERK1/2 or JNK inhibitor. In a reciprocal manner, ET-1 also induced IL-25 upregulation. The enhancing effect of ET-1 on IL-25 was inhibited by an endothelin A receptor antagonist, ERK1/2 inhibitor, or p38 inhibitor, but not by an endothelin B receptor antagonist or JNK inhibitor.These findings suggest that mutual upregulation of ET-1 and IL-25 takes place in the epidermis of AD, which may be a future target for antipruritic agents.
Mechanisms of sudden cardiac death
Authors: Michael Rubart, Douglas P Zipes
Journal: Journal of Clinical Investigation (2005)

Despite recent advances in preventing sudden cardiac death (SCD) due to cardiac arrhythmia, its incidence in the population at large has remained unacceptably high. Better understanding of the interaction among various functional, structural, and genetic factors underlying the susceptibility to, and initiation of, fatal arrhythmias is a major goal and will provide new tools for the prediction, prevention, and therapy of SCD. Here, we review the role of aberrant intracellular Ca2+ handling, ionic imbalances associated with acute myocardial ischemia, neurohumoral changes, and genetic predisposition in the pathogenesis of SCD due to cardiac arrhythmia. Therapeutic measures to prevent SCD are also discussed.
Enzalutamide in Metastatic Prostate Cancer before Chemotherapy
Authors: Tomasz M. Beer, Andrew J. Armstrong, Dana E. Rathkopf, Yohann Loriot, Cora N. Sternberg, Celestia S. Higano, Peter Iversen, Suman Bhattacharya, Joan Carles, Simon Chowdhury, Ian D. Davis, Johann S. de Bono, Christopher P. Evans, Karim Fizazi, Anthony M. Joshua, Choung-Soo Kim, Go Kimura, Paul Mainwaring, Harry Mansbach, Kurt Miller, Sarah B. Noonberg, Frank Perabo, De Phung, Fred Saad, Howard I. Scher, Mary-Ellen Taplin, Peter M. Venner, Bertrand Tombal
Journal: New England Journal of Medicine (2014)

Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer in whom the disease has progressed after chemotherapy. New treatment options are needed for patients with metastatic prostate cancer who have not received chemotherapy, in whom the disease has progressed despite androgen-deprivation therapy.
MesomiR 1: A Phase I study of TargomiRs in patients with refractory malignant pleural mesothelioma (MPM) and lung cancer (NSCLC)
Authors: N. van Zandwijk, N. Pavlakis, S. Kao, S. Clarke, A. Lee, H. Brahmbhatt, J. Macdiarmid, S. Pattison, F. Leslie, Y. Huynh, A. Linton, G. Reid
Journal: Annals of Oncology (2015)
ACC/AHA guidelines for coronary angiography11“ACC/AHA Guidelines for Coronary Angiography” was approved by the American College of Cardiology Board of Trustees in October 1998 and by the American Heart Association Science Advisory and Coordinating Committee in December 1998.22When citing this document, the American College of Cardiology and the American Heart Association request that the following format be used: Scanlon PJ, Faxon DP, Audet AM, Carabello B, Dehmer GJ, Eagle KA, Legako RD, Leon …
Authors: Patrick J Scanlon, David P Faxon, Anne-Marie Audet, Blase Carabello, Gregory J Dehmer, Kim A Eagle, Ronald D Legako, Donald F Leon, John A Murray, Steven E Nissen, Carl J Pepine, Rita M Watson, James L Ritchie, Raymond J Gibbons, Melvin D Cheitlin, Kim A Eagle, Timothy J Gardner, Arthur Garson, Richard O Russell, Thomas J Ryan, Sidney C Smith
Journal: Journal of the American College of Cardiology (1999)
Effects of 12-<i>O</i>-Tetradecanoylphorbol-13-acetate (TPA) in Combination with Paclitaxel (Taxol) on Prostate Cancer LNCaP Cells Cultured <i>In vitro</i> or Grown as Xenograft Tumors in Immunodeficient Mice
Authors: Xi Zheng, Richard L. Chang, Xiao-Xing Cui, Gina E. Avila, Vidya Hebbar, Mark Garzotto, Weichung Joe Shih, Yong Lin, Shou-En Lu, Arnold B. Rabson, Ah Ng Tony Kong, Allan H. Conney
Journal: Clinical Cancer Research (2006)

Abstract Purpose: To investigate the effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) in combination with paclitaxel (Taxol) on prostate cancer cells cultured in vitro or grown as tumors in immunodeficient mice. Experimental Design: Human prostate cancer LNCaP cells in culture were treated with TPA alone or in combination with paclitaxel. NCr immunodeficient mice with well-established LNCaP tumors received i.p. injections with vehicle or with TPA, paclitaxel, or TPA in combination with paclitaxel. The animals either received daily treatment for 5 consecutive days followed by a 2-day intermission, which was repeated for a total of 28 days (experiment 1), or continuous daily treatment for 28 days (experiment 2). Results: Treatment of LNCaP cells with a combination of TPA and paclitaxel synergistically inhibited the growth and induced apoptosis in cultured LNCaP cells, and this treatment also induced a marked increase in phosphorylated c-Jun-NH2-kinase (JNK). In animal experiments, tumor growth occurred in all mice treated with vehicle. When treated with TPA alone, the percentage of animals with some tumor regression was 33% in experiment 1 and 100% in experiment 2. Treatment of animals with paclitaxel alone caused some tumor regression in 17% and 57% of the animals in experiments 1 and 2, respectively. All animals treated with TPA + paclitaxel in both experiments had some tumor regression. Conclusions: TPA and paclitaxel in combination had a stronger inhibitory effect on the growth of LNCaP cells in culture or as xenograft tumors in immunodeficient mice than either agent alone. Clinical trials with TPA alone or in combination with paclitaxel in patients with prostate cancer may be warranted.
A case of idiopathic portal vein thrombosis?
Authors: R D Johnston, C Chang, R K Singh, A Austin, E. El-Omar
Journal: Gut (2009)

A 21-year-old Caucasian male presented with a short history of epigastric pain and weight loss. Physical examination revealed splenomegaly only. Renal biochemistry and full blood count were normal. There were minor elevations in liver enzymes. A contrast-enhanced abdominal CT scan identified splenomegaly with infarcts, and portal and splenic vein thrombosis without cavernoma formation (figs 1 and 2). A thrombophilia screen comprising anticardiolipin immunoglobulin G (IgG) and lupus anticoagulant, factor V Leiden and prothrombin gene mutation analysis, protein C and S quantification and screening for paroxysmal nocturnal haemoglobinuria was normal. Bone marrow architecture was normal, with a non-significant increase in megakaryocyte count. The BCR-ABL oncogene was absent.



Figure 1 
Contrast-enhanced axial CT scan of the abdomen in portal venous phase. The arrows indicate …
Transdermal Selegiline in Major Depression: A Double-Blind, Placebo-Controlled, Parallel-Group Study in Outpatients
Authors: J Alexander Bodkin, Jay D Amsterdam
Journal: American Journal of Psychiatry (2002)

The authors investigated the efficacy and safety of transdermal selegiline in adult outpatients with major depressive disorder.Following a 1-week placebo lead-in, 177 adult outpatients with major depressive disorder were randomly assigned to receive transdermal selegiline (20 mg applied once daily by means of a 20-cm(2) patch) (N=89) or placebo (N=88) for 6 weeks. The patients followed a tyramine-restricted diet during the medication trial and for 2 weeks after completion of treatment. Response to medication or placebo was measured by using the 17-item and 28-item versions of the Hamilton Depression Rating Scale, the Montgomery-Asberg Depression Rating Scale, and the Clinical Global Impression (CGI) severity and improvement measures.Greater improvement was observed after 6 weeks in patients treated with transdermal selegiline than in those given placebo according to all measures. A statistically significant difference between drug and placebo was seen in Hamilton depression scale and Montgomery-Asberg Depression Rating Scale scores as early as week 1 of treatment. There were no differences in the adverse event profile of the patients given selegiline and those given placebo with the exception of application-site reactions, which were more common with the selegiline transdermal system. No orthostatic hypotensive or hypertensive reactions were observed.Transdermal selegiline (20 mg applied once daily by means of a 20-cm(2) patch) administered for 6 weeks was an effective and well-tolerated treatment for adult outpatients with major depression. The typical side effects commonly seen with traditional monoamine oxidase inhibitor antidepressants were not observed.
In-Vitro Studies of Myocardial Asynchrony and Regional Hypoxia
Authors: JOHN V. TYBERG, WILLIAM W. PARMLEY, EDMUND H. SONNENBLICK
Journal: Circulation Research (1969)

Ten pairs of cat papillary muscles were arranged in tandem to study their individual and combined length-tension and force-velocity relationships. Physiologic asynchronous contraction (up to 60 msec) of the pair of muscles produced a change in the individual force-velocity relations of each muscle which was characteristic of a change in muscle length; i.e., there was an alteration of tension developed without a change in the maximum measured velocity of shortening. On the ascending limb of the length-active tension curve, asynchronous stimulation (average time interval 32 msec) increased the force developed (5.3 ± 1.4%) by the tandem pair, as compared to synchronous stimulation. When one muscle was made hypoxic for 20 minutes, its force development was reduced by 64 ± 3%, and paradoxical motion occurred. After 2 minutes of reoxygenation, the time to peak tension was slightly prolonged, while the time for isometric tension to relax to one-half its peak value was increased to 234±27% of control. During this period the contraction pattern of the tandem pair was out of phase (asynergic), even though they were stimulated synchronously. Thus transient asynergy associated with regional myocardial ischemia may be explained in part by these observed alterations in the time course of contraction and relaxation.
Idiopathic diffuse pulmonary ossification
Authors: C F Ryan
Journal: Thorax (2004)

Idiopathic diffuse pulmonary ossificationA 51 year old man presented with a 1 year history of fatigue and night sweats, cough with clear sputum, central chest discomfort, and mild exertional dyspnoea.A detailed exposure history was negative.Laboratory investigations including tuberculin skin test, white cell count, ESR, C-reactive protein, urea, creatinine and electrolytes, protein electrophoresis, rheumatoid factor, antinuclear antibody, calcium, alkaline phosphatase and liver function tests were all normal.Urinalysis and 24 hour urine calcium excretion were normal.Echocardiography was normal.Detailed pulmonary function tests and arterial blood gases were normal except for an isolated reduction in the transfer factor (73% predicted).The chest radiograph showed a reticulonodular pattern involving mainly the lower lobes.A high resolution chest CT scan showed a fine nodular pattern with foci of calcification (figs 1A and B).Transbronchial biopsy specimens were nondiagnostic.Thoracoscopic open lung biopsy was performed.Light microscopic examination revealed multiple foci of bone in a branching pattern randomly located within the alveolar airspaces.Bone marrow was identified within some fragments (fig 2).There was associated mild subpleural and focal small nodular interstitial scarring but no honeycombing or other features to suggest pulmonary fibrosis.There was no evidence of venous congestion or iron deposition.Congo red stains were negative and electron microscopy revealed no evidence of amyloid.There was no evidence of granulomas or malignancy.
Prevalence of the Metabolic Syndrome Among Patients Receiving Clozapine
Authors: J. Lamberti
Journal: American Journal of Psychiatry (2006)

Objective: This study compared the prevalence of the metabolic syndrome among outpatients with schizophrenia and schizoaffective disorder receiving clozapine with a matched comparison group from the National Health and Nutrition Examination Survey. Method: Ninety-three outpatients and a matched group of 2,701 comparison subjects were compared according to National Cholesterol Education Program criteria. Outpatient data were obtained through physical assessments, laboratory testing, and reviews of medical records. Results: The prevalence of the metabolic syndrome was significantly higher among clozapine patients (53.8%) than among the comparison group (20.7%). For clozapine patients, logistic regression analysis revealed significant associations with age, body mass index, and duration of clozapine treatment. Only age and body mass index were associated with the prevalence of metabolic syndrome in both groups. Conclusions: Patients receiving clozapine are at significantly increased risk for developing the metabolic syndrome. Psychiatrists and other providers should consider performing regular physical health monitoring to prevent long-term adverse health consequences.
Rapid and reversible inhibition by low density lipoprotein of the endothelium-dependent relaxation to hemostatic substances in porcine coronary arteries. Heat and acid labile factors in low density lipoprotein mediate the inhibition.
Authors: T Tomita, M Ezaki, M Miwa, K Nakamura, Y Inoue
Journal: Circulation Research (1990)

The effects of hemostatic substances on the vascular tone in porcine coronary arteries and the influence of low density lipoprotein on tension were investigated. Thrombin induced a marked concentration-dependent relaxation in prostaglandin F2 alpha-precontracted strips with intact endothelium, whereas it produced a modest constriction in endothelium-denuded arteries. Methylene blue abolished the relaxation, but indomethacin did not affect it significantly. An exposure of the intact strips to low density lipoprotein resulted in a marked inhibition of the relaxation to thrombin but did not interfere with vasodilation by sodium nitroprusside. The inhibition by low density lipoprotein was reversed completely by washing. In contrast, high density lipoprotein lacked such inhibitory effects. Adenosine diphosphate, calcium ionophore A23187, and platelet-activating factor also produced relaxation in the intact strips. An exposure of the strips to low density lipoprotein almost abolished relaxation to these substances. The inhibition was also reversible. Heat treatment or acid treatment of low density lipoprotein resulted in a complete loss of the inhibitory effects, but diisopropyl fluorophosphate treatment did not alter the effect. It is concluded that low density lipoprotein may play a new pathological role in promotion of coronary vasospasm through rapid and reversible inhibition in endothelium-dependent relaxation to hemostatic substances.
The localization of target antigens and autoantibodies in linear IgA disease is variable: correlation of immunogold electron microscopy and immunoblotting
Authors: None Zhou, None Ferguson, None Allen, None Wojnarowska
Journal: British Journal of Dermatology (1998)

Linear IgA disease (LAD) of adults and children is a dapsone-responsive, autoimmune subepidermal blistering disease characterized by linear IgA deposits at the basement membrane zone (BMZ) of the skin and mucosa. Circulating IgA antibodies to BMZ components are often present. In this study we investigated the ultrastructural localization of the antigens and autoantibodies in six patients with LAD (five adults and one child). Using a direct postembedding immunogold electron microscopy (EM) technique, three different patterns of IgA antibody deposition were seen in the skin of four patients with LAD. The IgA deposits localized within the uppermost part of the lamina lucida and to the basal surface of the hemidesmosome in two patients, to the lamina lucida in one, and to the lamina densa in the fourth patient. Using an indirect immunogold EM technique and serum or purified blister fluid from two additional LAD patients, we showed that the serum autoantibodies of one patient bound to the hemidesmosome of the BMZ, while the autoantibodies in the blister fluid of the other patient bound to the lamina densa and sublamina densa including the anchoring fibrils in a labelling pattern similar to that of the monoclonal antibody (LH7.2) to collagen VII. All the autoantibodies binding to the hemidesmosome or lamina lucida recognized a protein in epidermal extracts of molecular weight 180 kDa or its breakdown product of 97 kDa, 200 kDa or 230 kDa. The antibodies binding to the lamina densa recognized proteins of 180 and 285 kDa. The antibodies that bound to the lamina densa and anchoring fibrils recognized collagen VII. In this immunogold EM study we have shown four patterns of IgA labelling in six patients with LAD, associated with five different antigens as recognized by immunoblotting. These results, together with our previous immunofluorescence and immunoblotting findings add support to the contention that LAD is a heterogeneous disease as regards both the target antigens and epitopes.
Predicting Treatment Response of Malignant Gliomas to Bevacizumab and Irinotecan by Imaging Proliferation With [<sup>18</sup>F] Fluorothymidine Positron Emission Tomography: A Pilot Study
Authors: Wei Chen, Sibylle Delaloye, Daniel H.S. Silverman, Cheri Geist, Johannes Czernin, James Sayre, Nagichettiar Satyamurthy, Whitney Pope, Albert Lai, Michael E. Phelps, Timothy Cloughesy
Journal: Journal of Clinical Oncology (2007)

Purpose Evaluation of treatment effects in malignant brain tumors is challenging because of the lack of reliable response predictors of tumor response. This study examines the predictive value of positron emission tomography (PET) using [ 18 F] fluorothymidine (FLT), an imaging biomarker of cell proliferation, in patients with recurrent malignant gliomas treated with bevacizumab in combination with irinotecan. Patients and Methods Patients with recurrent malignant gliomas treated with biweekly cycles of bevacizumab and irinotecan were prospectively studied with FLT-PET at baseline, after 1 to 2 weeks, and after 6 weeks from start of treatment. A more than 25% reduction in tumor FLT uptake as measured by standardized uptake value was defined as a metabolic response. FLT responses were compared with response as shown by magnetic resonance imaging (MRI) and patient survival. Results Twenty-one patients were included, and 19 were assessable for metabolic response evaluation with FLT-PET. There were nine responders (47%) and 10 nonresponders (53%). Metabolic responders survived three times as long as nonresponders (10.8 v 3.4 months; P = .003), and tended to have a prolonged progression-free survival (P = .061). Both early and later FLT-PET responses were more significant predictors of overall survival (1 to 2 weeks, P = .006; 6 weeks, P = .002), compared with the MRI responses (P = .060 for both 6-week and best responses). Conclusion FLT-PET as an imaging biomarker seems to be predictive of overall survival in bevacizumab and irinotecan treatment of recurrent gliomas. Whether FLT-PET performed as early as 1 to 2 week after starting treatment is as predictive as the study indicates at 6 weeks warrants further investigation.
Regulation of mitochondrial function by PINK1, Parkin and DJ-1
Authors: Emilie Giaime, Jie Shen
Journal: Molecular Neurodegeneration (2013)

Loss-of-function mutations in PTEN-induced kinase 1 (PINK1), Parkin and DJ-1 genes have been linked to recessively inherited forms of Parkinsonism.PINK1 is a putative serine-threonine kinase containing a mitochondrial localization signal, whereas Parkin and DJ-1 function as E3 ubiquitin-protein ligase and scavenger for reactive oxygen species (ROS), respectively.Interestingly, all three of them have been implicated in the control of the mitochondrial function.In this study using primary mouse embryonic fibroblasts (MEFs), primary neurons and mice brain, we investigated how the mitochondrial respiration is affected by the loss of PINK1, Parkin and DJ-1.We found that intact mitochondria in PINK1-/and Parkin-/-cells recapitulate all the defects in mitochondrial respiration observed previously in isolated mitochondria from PINK1-/-and Parkin-/-mouse brains, suggesting that these cells are a valid experimental system to study the underlying mechanisms.Our data showed that these defects are not induced by changes in expression levels and activities of all individual complexes composing the electron transport system in PINK1-/and Parkin-/-.In parallel, we found that loss of DJ-1 does not affect mitochondrial respiration in intact and permeabilized DJ-1-/-MEFs and in isolated mitochondria from the cerebral cortex of DJ-1-/-mice at 3 months or 2 years of age.Interestingly, the mitochondrial transmembrane potential in MEFs cells is reduced in absence of PINK1, Parkin or DJ-1.We first discovered that this reduction is linked to an increase of the opening of the mitochondrial permeability transition pore in PINK1-/-, Parkin-/-and DJ-1-/-cells.Consistent with earlier reports, production of ROS species is increased in DJ-1-/-MEFs.The accumulation of ROS seems linked to the decreased mitochondrial transmembrane potential and to
Abdominal coarctation increases insulin-like growth factor I mRNA levels in rat aorta.
Authors: K A Fath, R W Alexander, P Delafontaine
Journal: Circulation Research (1993)

We have previously demonstrated specific insulin-like growth factor I (IGF I) mRNA transcripts in cultured endothelial and vascular smooth muscle cells and postulated an important role for IGF I in blood vessel growth responses. The purpose of this study was to characterize IGF I gene expression in a model of aortic coarctation hypertension in the rat. This high-renin model of hypertension is associated with hyperplastic vascular responses. Northern analysis of rat aorta demonstrated four specific IGF I mRNA transcripts sized 7.6, 4.6, 1.8, and 0.9-1.2 kb. Quantitation of aortic IGF I mRNA levels by solution hybridization/RNase protection assay demonstrated induction of IGF I transcripts in the hypertensive aorta; levels more than doubled at 7 days and were still significantly elevated 21 days after coarctation. In situ hybridization analysis indicated that IGF I transcripts were localized primarily to adventitial surfaces in normotensive aorta, with minimal signal detected over vascular cells. In hypertensive aortas, there was an increase in IGF I transcripts primarily over vascular smooth muscle cells. Thus, vascular IGF I gene expression is induced in this model of high-renin hypertension. IGF I may play an important role in autocrine/paracrine-mediated vessel wall remodeling in hypertension.