tbuckley/cabot-search huggingface dataset:
557. A Study of AAV2/1/SERCA2a Delivered Via the V-Focus Cardiac Delivery System in an Ovine Pacing Model of Heart Failure
Authors: Melissa J. Byrne, David Kaye, John M. Power
Journal: Molecular Therapy (2006)

Background: The development of targeted molecular therapy for the treatment of heart failure (HF) has lead to the development of a novel percutaneous recirculation technique, the V-Focus system. This study investigated its use to deliver adeno-associated vius mediated gene transfer of SR Ca2+ ATPase (AAV2/1SERCA2a) in an ovine model of tachycardia induced heart failure. Methods/Results: The V-Focus cardiac delivery system was used to deliver AAV2/1SERCA2a (5×1012 drp) in an ovine model of right ventricular pacing induced heart failure (HF), n=6, six additional animals did not undergo therapy (control). Animals were continually paced for a further four weeks after delivery of AAV2/1SERCA2a at which time the animals were anaesthetised and an echocardiogram, left ventricular (LV) +dP/dtmax and LV tissue obtained. After four weeks of additional pacing there was a significant increase in both ejection fraction (EF; treatment 40.2±4.6% vs control 27.8±3.4%) and LV +dP/dtmax (treatment 1042±178 vs control 893±204) between animals receiving AAV2/1Serca2a and controls. There was minimal and no significant difference in degree of left ventricular fibrosis between the two groups (p>0.05). Conclusions: These results suggest that targeted molecular therapy using AAV2/1SERCA2a has successfully been applied in combination with the novel V-Focus delivery system in an animal model of tachycardia induced heart failure (HF) and has excellent potential for its treatment. The next valuable step will be to determine the dose-ranging efficacy of AAV2/1SERCA2a. John Power and David Kaye are founding members of V-Kardia Pty.
Examination of adduct formation in vivo in the mouse between benzo(a)pyrene and DNA of skin and hemoglobin of red blood cells.
Authors: L Shugart, J Kao
Journal: Environmental Health Perspectives (1985)

We are interested in devising techniques which will allow us to measure and quantitate exposure to chemical carcinogens and which eventually can be used in risk analysis with humans. Our recent research with HPLC/fluorescence has demonstrated that we can detect, identify, and quantitate the binding of benzo(a)pyrene (BaP) with DNA of mouse skin. The technique not only allows femtomole amounts of BaPDE associated with DNA isolated from a single mouse skin to be detected using conventional instrumentation, but also establishes the stereochemical origin of the adduct, and has been employed in the investigation reported here to estimate the concomitant binding of BaP to hemoglobin in vivo. The temporal existence of BaPDE/DNA adducts in mouse skin over a 5-week period showed that at 35 days after treatment, approximately 15% of the initial adducts were still detectable even though DNA turnover would predict that they should have been deleted from the genome. The concentration of the major covalently bound adduct, anti-BaPDE/deoxyguanosine, relative to the total BaPDE/DNA adduct population remained essentially constant during the 5-week period. It is known that topically applied BaP is absorbed, metabolized, and excreted by the mouse. Examination of hemoglobin of mouse RBCs 24 hr after BaP treatment revealed covalent adduct formation exclusively via anti-BaPDE. The dose response of adduct binding to hemoglobin and DNA appeared to be similar.
'Esophageal Angina' as the Cause of Chest Pain
Authors: Huw Alban Davies
Journal: JAMA (1982)

One hundred consecutive medical emergency patients with anterior chest pain were followed to their final diagnosis to discover the prevalence of esophageal disease as the cause of anginal pain. Seventy-seven of the patients had pain that was anginal in character, and one fifth of these (16 patients) had abnormalities demonstrated by the following esophageal investigations: endoscopy with biopsy, manometry, radiology, and acid perfusion. The 16 patients whose anginal pain was thought to be due to esophageal disease all performed normally on an exercise tolerance test, and in eight of them the association between the esophagus and their symptoms was demonstrated by a positive provocation test result: esophageal acid perfusion was the most useful investigation in this group.
MARIHUANA, AN INTOXICANT
Authors: HERBERT S. GASKILL
Journal: American Journal of Psychiatry (1945)

1. Marihuana does not produce addiction in the sense that opium and its derivatives do. Tolerance is not established and withdrawal symptoms do not occur. It is an intoxicant which temporarily produces euphona, distortion of time perception and impairment of intellectual and moral judgment. 2. Its habitual users are largely emotionally immature individuals who are constantly frustrated in their attempts to find adequate instinctual expression. The fundamental problem is the abnormal personality. 3. Marihuana smoking creates an important problem since it often acts as the determining factor, turning the balance in the direction of asocial behavior rather than permitting the poorly integrated social conscience of such an individual to remain in control.
Diffuse hepatic calcinosis and hypercalcemia in association with a B‐cell (centroblastic) lymphoma
Authors: Kostas Konstantopoulos, Ioanna Delladetsima, Christos Kosmas, Athina Androulaki, Kostas Stamatopoulos, Litsa Rekoumi, Stratos Patsouris, Dimitris Loukopoulos
Journal: American Journal of Hematology (1995)
Book Review Idiopathic Generalized Epilepsies: Clinical, experimental, and genetic aspects Edited by Alain Malafosse, Pierre Genton, Edouard Hirsch, Christian Marescaux, Dominique Broglin, and Raymond Bernasconi. 538 pp. London, John Libbey, 1995. £45. 0-86196-436-5
Authors: Jerome Engel
Journal: New England Journal of Medicine (1995)
RORγt+ innate lymphoid cells regulate intestinal homeostasis by integrating negative signals from the symbiotic microbiota
Authors: Shinichiro Sawa, Matthias Lochner, Naoko Satoh-Takayama, Sophie Dulauroy, Marion Bérard, Melanie Kleinschek, Daniel Cua, James P Di Santo, Gérard Eberl
Journal: Nature Immunology (2011)
Targeting Heat Shock Protein 90 in Pancreatic Cancer Impairs Insulin-like Growth Factor-I Receptor Signaling, Disrupts an Interleukin-6/Signal-Transducer and Activator of Transcription 3/Hypoxia-Inducible Factor-1α Autocrine Loop, and Reduces Orthotopic Tumor Growth
Authors: Sven A. Lang, Christian Moser, Andreas Gaumann, Dagmar Klein, Gabriel Glockzin, Felix C. Popp, Marc H. Dahlke, Pompiliu Piso, Hans J. Schlitt, Edward K. Geissler, Oliver Stoeltzing
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Inhibitors of heat-shock protein 90 (Hsp90) may interfere with oncogenic signaling pathways, including Erk, Akt, and hypoxia-inducible factor-1α (HIF-1α). Because insulin-like growth factor-I receptor (IGF-IR) and signal transducer and activator of transcription 3 (STAT3) signaling pathways are implicated in the progression of pancreatic cancer, we hypothesized that blocking Hsp90 with geldanamycin derivates [17-allylamino-geldanamycin (17-AAG), 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG)] would impair IGF-I– and interleukin-6–mediated signaling and thus reduce pancreatic tumor growth and angiogenesis in vivo. Experimental Design: Human pancreatic cancer cells (HPAF-II, L3.6pl) were used for experiments. Changes in signaling pathway activation upon Hsp90 blockade were investigated by Western blotting. Effects of Hsp90 inhibition (17-AAG) on vascular endothelial growth factor were determined by ELISA and real-time PCR. Effects of 17-DMAG (25 mg/kg; thrice a week; i.p.) on tumor growth and vascularization were investigated in a s.c. xenograft model and in an orthotopic model of pancreatic cancer. Results: 17-AAG inhibited IGF-IR signaling by down-regulating IGF-IRβ and directly impairing IGF-IR phosphorylation. Hypoxia- and IL-6–mediated activation of HIF-1α or STAT3/STAT5 were substantially inhibited by 17-AAG. Moreover, a novel IL-6/STAT3/HIF-1α autocrine loop was effectively disrupted by Hsp90 blockade. In vivo, 17-DMAG significantly reduced s.c. tumor growth and diminished STAT3 phosphorylation and IGF-IRβ expression in tumor tissues. In an orthotopic model, pancreatic tumor growth and vascularization were both significantly reduced upon Hsp90 inhibition, as reflected by final tumor weights and CD31 staining, respectively. Conclusions: Blocking Hsp90 disrupts IGF-I and IL-6–induced proangiogenic signaling cascades by targeting IGF-IR and STAT3 in pancreatic cancer, leading to significant growth-inhibitory effects. Therefore, we suggest that Hsp90 inhibitors could prove to be valuable in the treatment of pancreatic cancer.
Pattern of blood flow within the heart: a stable system
Authors: D. E. M. TAYLOR, J. D. WADE
Journal: Cardiovascular Research (1973)

Flow patterns within the cardiac ventricles during diastolic filling have been studied in dogs and sheep by cineradiography with fine stream dye injection, and by endoscopic cinephotography. The results show that stable flow patterns occur with little evidence of gross mixing or lateral dispersion. The major flow patterns are expanding vortex systems behind the cusps of the mitral and tricuspid valves. These vortex systems appear important in normal valve dynamics.
Protective Effect of Disodium Cromoglycate on Propranolol Challenge
Authors: G. H. Koëter, H. Meurs, J. G. R. de Monchy, K. de Vries
Journal: Allergy (1982)

The protective activity of cromoglycate in histamine and propranolol bronchial provocation tests was studied in seven asthmatic patients by inhalation of increasing doses of histamine and propranolol in the absence and presence of inhaled cromoglycate. Cromoglycate showed a significant protective effect on the propranolol challenge, whereas no protection against histamine challenge could be observed.
PSYCHOSIS WITH CARDIAC DECOMPENSATION
Authors: Joseph C. Michael
Journal: American Journal of Psychiatry (1937)

Attention is called to the various prevailing theories with reference to the pathogenesis of psychosis in patients suffering cardiac failure. The literature is reviewed to indicate widely differing viewpoints. The records of 2293 admissions to a public hospital during the last decade because of cardiac decompensation indicated that 23 patients were treated because of complicating psychosis. Data from these and one additional patient are reviewed. Incidence, sex, age, heart stimulants employed, cardiac complications, hypertension, liver edema, other complicating diseases and course are discussed. Comparatively rare incidence of psychosis in cardiac failure is indicated. Digitalis and other drugs were not found to cause psychosis in this series of patients. Associated syphilitic infection was found in three cases, but, excepting one of these subjects, syphilis apparently could not account for the development of psychosis. Alcoholism was an etiologic factor in one patient's psychosis. The status of arteriosclerosis was found to be inferential; 13, or 54 per cent, of the patients presented clinical signs of cerebral arterial degeneration. However, no one or series of causative factors were noted which were not also observed in the 99 per cent nonpsychotic subjects treated for cardiac decompensation.
NEUTROPHIL POLYMORPHONUCLEARS, MEDIATORS AND THE PATHOGENESIS OF PSORIASIS
Authors: M.W. Greaves
Journal: British Journal of Dermatology (1983)

Journal Article NEUTROPHIL POLYMORPHONUCLEARS, MEDIATORS AND THE PATHOGENESIS OF PSORIASIS Get access M.W. Greaves M.W. Greaves Institute of Dermatology, Homerton Grove, London E9 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 109, Issue 1, 1 July 1983, Pages 115–118, https://doi.org/10.1111/j.1365-2133.1983.tb04001.x Published: 01 July 1983
Implantable Devices for the Treatment of Atrial Fibrillation
Authors: Joshua M. Cooper, Michael S. Katcher, Michael V. Orlov
Journal: New England Journal of Medicine (2002)

Overdrive pacing can suppress premature beats and other triggers of atrial fibrillation. Dual-site pacing may help prevent atrial fibrillation. An implantable atrial defibrillator can be programmed and can deliver shocks to terminate atrial tachyarrhythmias and restore sinus rhythm.
Tuberculin Booster Reactions and Conversions
Authors: Robert Harrington
Journal: Annals of Internal Medicine (1994)

Letters1 September 1994Tuberculin Booster Reactions and ConversionsRobert Harrington, MDRobert Harrington, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-121-5-199409010-00023 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The most notable result from the recent study by Menzies and colleagues [1] was that 6 (10%) of 61 students with a second purified protein derivative-tuberculin (PPd-T2) reaction of 10 mm or greater had radiographic evidence of previous tuberculosis. This did not differ statistically from the 10 (14%) of 74 students with a positive initial PPD test (PPd-T1) result and a chest radiograph consistent with previous tuberculosis. This finding suggests that, even in the tested population with a low (or presumed low) prevalence of tuberculosis, a positive reaction to PPd-T2 is as significant as a positive PPd-T1.... References1. Menzies R, Vissandje B, Rocher E, St. Germain Y. The booster effect in two-step tuberculin testing among young adults in Montreal. Ann Intern Med. 1994; 120:190-8. Google Scholar Author, Article, and Disclosure InformationAuthors: Robert Harrington, MD PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 September 1994Volume 121, Issue 5 Page: 387-388 Keywords Proteins Thorax Tuberculin Tuberculosis Young adults ePublished: 15 August 2000 Issue Published: 1 September 1994 Copyright & PermissionsCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Successful Treatment of ECHOvirus Meningoencephalitis and Myositis-Fasciitis with Intravenous Immune Globulin Therapy in a Patient with X-Linked Agammaglobulinemia
Authors: Philip J. Mease, Hans D. Ochs, Ralph J. Wedgwood
Journal: New England Journal of Medicine (1981)

PATIENTS with X-linked agammaglobulinemia (X-LA) characteristically have recurrent bacterial infection; they generally have a normal response to viral infection, presumably because cell-mediated immunity is intact.1 , 2 A notable exception is the usually fatal echovirus-induced meningoencephalitis, which is often associated with a "dermatomyositislike" syndrome.3 4 5 6 7 8 9 10 We successfully treated such a patient, who recovered from this complication after prolonged intravenous therapy with high doses of modified immune globulin containing type-specific anti-echovirus antibody.Case ReportA 32-year-old man (Case 8 in an earlier report11) with well-documented X-LA, who had been treated at the University of Washington since 1969 with intramuscular immune globulin (100 mg . . .
Oral pimecrolimus in the treatment of moderate to severe chronic plaque-type psoriasis: a double-blind, multicentre, randomized, dose-finding trial
Authors: A.B. Gottlieb, C.E.M. Griffiths, V.C. Ho, M. Lahfa, U. Mrowietz, D.F. Murrell, J-P. Ortonne, G. Todd, R. Cherill, I. Marks, S. Emady-Azar, C.F. Paul
Journal: British Journal of Dermatology (2005)

Background There is a need for safe and effective alternative treatments for patients with moderate to severe psoriasis. Objectives Pimecrolimus is a calcineurin inhibitor that is being investigated in oral form for the treatment of psoriasis. Patients and methods A double‐blind, randomized, parallel‐group, dose‐finding study was performed. Healthy adult outpatients with moderate to severe chronic plaque‐type psoriasis (n = 143) were randomized to receive oral placebo or pimecrolimus 10 mg, 20 mg or 30 mg twice daily (b.d.) for 12 weeks. Main outcome measures: The Psoriasis Area and Severity Index (PASI) was used to assess clinical severity of psoriasis. Results were analysed at weeks 7 (primary endpoint) and 13. Safety was assessed by monitoring all adverse events, laboratory investigations (blood chemistry, urinalysis, haematology) and physical examinations. Results The change from baseline in PASI at week 7 showed a dose‐dependent effect. The differences between each of the two higher doses of pimecrolimus and placebo were statistically significant (P < 0.001; anova). The mean percentage decreases from baseline in PASI in the placebo group and pimecrolimus 10 mg, 20 mg and 30 mg b.d. groups at week 7 were 3.1%, 22.2%, 51.3% and 54.0%, respectively. Most adverse events were of mild or moderate severity. The only adverse event to show a dose–response relationship was a transient feeling of warmth. No clinically relevant effects on laboratory parameters were observed, and no increase in skin infection with pimecrolimus was seen. Conclusions Oral pimecrolimus produces a dose‐dependent reduction in psoriasis severity, with doses of 20 mg and 30 mg b.d. being the most effective and well tolerated.
Biological stress systems, adverse life events and the onset of chronic multisite musculoskeletal pain: a 6-year cohort study
Authors: Ellen Generaal, Nicole Vogelzangs, Gary J Macfarlane, Rinie Geenen, Johannes H Smit, Eco J C N de Geus, Brenda W J H Penninx, Joost Dekker
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objectives</h3> Dysregulated biological stress systems and adverse life events, independently and in interaction, have been hypothesised to initiate chronic pain. We examine whether (1) function of biological stress systems, (2) adverse life events, and (3) their combination predict the onset of chronic multisite musculoskeletal pain. <h3>Methods</h3> Subjects (n=2039) of the Netherlands Study of Depression and Anxiety, free from chronic multisite musculoskeletal pain at baseline, were identified using the Chronic Pain Grade Questionnaire and followed up for the onset of chronic multisite musculoskeletal pain over 6 years. Baseline assessment of biological stress systems comprised function of the hypothalamic-pituitary-adrenal axis (1-h cortisol awakening response, evening levels, postdexamethasone levels), the immune system (basal and lipopolysaccharide-stimulated inflammation) and the autonomic nervous system (heart rate, pre-ejection period, SD of the normal-to-normal interval, respiratory sinus arrhythmia). The number of recent adverse life events was assessed at baseline using the List of Threatening Events Questionnaire. <h3>Results</h3> Hypothalamic-pituitary-adrenal axis, immune system and autonomic nervous system functioning was not associated with onset of chronic multisite musculoskeletal pain, either by itself or in interaction with adverse life events. Adverse life events did predict onset of chronic multisite musculoskeletal pain (HR per event=1.14, 95% CI 1.04 to 1.24, p=0.005). <h3>Conclusions</h3> This longitudinal study could not confirm that dysregulated biological stress systems increase the risk of developing chronic multisite musculoskeletal pain. Adverse life events were a risk factor for the onset of chronic multisite musculoskeletal pain, suggesting that psychosocial factors play a role in triggering the development of this condition.
779. Oral Delivery of Non-Viral DNA Nanoparticles for Hemophilia A
Authors: Katherine Bowman, Rita Sarkar, Sanj Raut, Neelima Shah, Xuli Wang, Hai-Quan Mao, Kam W. Leong
Journal: Molecular Therapy (2005)

Hemophilia A is a defect in coagulation factor VIII, which is predominantly produced in liver and secreted into plasma at a level of 100-200 ng/ml. Hemophilia A is an attractive model for non-viral gene delivery since levels as low as 1-2% FVIII can affect bleeding. In addition, FVIII can be processed from non-liver cell types. While non-viral gene delivery has advantages of production and safety compared to viral gene therapy, the transient nature of gene expression makes re-administration necessary, therefore an oral route of administration highly desirable. We previously reported preliminary results in hemophilia A mice orally administered chitosan-FVIII DNA nanoparticles, including phenotypic bleeding correction in 4/5 mice given the highest DNA dose. Levels of functional FVIII by chromogenic assay were modest. However a thrombin assay revealed significantly greater thrombin generation in mice given chitosan-DNA nanoparticles as compared to naked DNA.
Elevated levels of matrix metalloproteinases in bronchoalveolar lavage fluid of emphysematous patients
Authors: G. A. Finlay, K. J. Russell, K. J. McMahon, E. M. D'arcy, J. B. Masterson, M. X. FitzGerald, C. M. O'Connor
Journal: Thorax (1997)

Matrix degradation in emphysema has long been attributed to the action of neutrophil elastase (NE). More recently a role for other proteases, particularly the matrix metalloproteinases (MMPs), in the pathogenesis of this disease has been proposed. To date, however, the presence of MMPs in the lungs of patients with emphysema has not been demonstrated.Samples of bronchoalveolar lavage (BAL) fluid from 10 patients with emphysema and from control subjects matched for sex and current smoking status were assessed for collagenase, gelatinase, and NE activity. Pulmonary function tests and computed tomographic (CT) scans were carried out on all study subjects.Collagenase activity was detected in BAL fluid samples from all emphysematous patients but in only one smoking control (p < 0.001). Gelatinase B was present in six patients and in two smoking controls (p < 0.03). The concomitant presence of gelatinase B in complex with lipocalin (NGAL) in the gelatinase positive samples suggests that the neutrophil is a significant source of the gelatinase B observed. NE was detected in six of the 10 patients with emphysema and in two smoking controls (p < 0.01), indicating that collagenase was more useful in discriminating between disease and control groups than either NE or gelatinase B. No relationship was observed between any of the enzymes measured and pulmonary function or CT density score.This study demonstrates, for the first time, the presence of increased levels of matrix metalloproteinases in the lungs of patients with emphysema and suggests that, in BAL fluid, collagenase activity may be a better indicator of the presence of emphysema than elastase.
Tracking Quality of Life Changes in Asthma Requires Disease-Specific Measure for Optimal Sensitivity
Authors: K.M. Shanovich, K.T. Sullivan Dillie, M.D. Evans, K.A. Roberg, E.L. Anderson, K.M. Hanson, R.A. Grabher, D.F. DaSilva, T.E. Pappas, L.E.P. Salazar, C.J. Tisler, R.E. Gangnon, J.E. Gern, R.F. Lemanske
Journal: Journal of Allergy and Clinical Immunology (2007)
Porphyria Cutanea Tarda and Chloracne
Authors: C. J. Watson
Journal: JAMA (1964)

To the Editor:—  An editorial with the above title, appearing inThe Journalfor July 6, 1964 (189:56), was based on a paper published by Bleiberg et al (Arch Derm[Chicago]89:793 [June] 1964). This was entitled Industrially Acquired Porphyria and described the association of porphyria cutanea tarda (PCT) and chloracne in individuals engaged in the synthesis of 2,4 di- and 2,4,5 trichlorphenols. These substances are related to hexachlorobenzene, the established cause of an epidemic of hepatic cutaneous porphyria in Turkey1and of experimental hepatic porphyria in rats2  In both the editorial and the paper of Bleiberg and co-workers there is an unfortunate confusion with respect to the use and significance of chemical diagnostic methods in cases of PCT, especially the acquired form due to chlorinated benzene ring compounds, as mentioned above. The editorial states: Overt cases are readily diagnosed clinically, and by examination of the