tbuckley/cabot-search huggingface dataset:
Stimulators of soluble guanylate cyclase (sGC) inhibit experimental skin fibrosis of different aetiologies
Authors: Clara Dees, Christian Beyer, Alfiya Distler, Alina Soare, Yun Zhang, Katrin Palumbo-Zerr, Oliver Distler, Georg Schett, Peter Sandner, Jörg H W Distler
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objectives</h3> Stimulators of the soluble guanylate cyclase (sGC) have recently been shown to inhibit transforming growth factor-β signalling. Here, we aimed to demonstrate that riociguat, the drug candidate for clinical trials in systemic sclerosis (SSc), is effective in experimental fibrosis and to compare its efficacy to that of phosphodiesterase V inhibitors that also increase the intracellular levels of cyclic guanosine monophosphate. <h3>Methods</h3> The antifibrotic effects of riociguat and sildenafil were compared in the tight-skin 1 model, in bleomycin-induced fibrosis and in a model of sclerodermatous chronic graft-versus-host-disease (cGvHD). Doses of 0.1–3 mg/kg twice a day for riociguat and of 3–10 mg/kg twice a day for sildenafil were used. <h3>Result</h3> Riociguat dose-dependently reduced skin thickening, myofibroblast differentiation and accumulation of collagen with potent antifibrotic effects at 1 and 3 mg/kg. Riociguat also ameliorated fibrosis of the gastrointestinal tract in the cGvHD model. The antifibrotic effects were associated with reduced phosphorylation of extracellular signal-regulated kinases. Sildenafil at doses of 3 and 10 mg/kg exerted mild antifibrotic effects that were significantly less pronounced compared with 1 and 3 mg/kg riociguat. <h3>Conclusions</h3> These data demonstrated potent antifibrotic effects of riociguat on experimental skin and organ fibrosis. These findings suggest a role for riociguat for the treatment of fibrotic diseases, especially for the treatment of SSc. A phase II study with riociguat in patients with SSc is currently starting.
Immunophenotyping on simultaneously occurring plaques and tumours in mycosis fungoides and Sezary syndrome
Authors: A.H. PREESMAN, J. TOONSTRA, S.C.J. PUTTE, W.A. VLOTEN
Journal: British Journal of Dermatology (1993)

Skin biopsy specimens from 15 patients with mycosis fungoides and Sézary syndrome, with simultaneously occurring plaques and tumours, were examined to assess phenotypic deviation. We focused on immunophenotypic differences between the two types of lesions with respect to the T-cell markers CD2, CD3, CD4, CD5 and CD8. In six patients (40%) loss of one or more T-cell markers occurred in at least one of the lesions. Three of the patients studied (20%) showed a difference in immunophenotype between plaques and tumours, with an additional loss of one of the T-cell markers in the tumours (respectively, CD5, CD2 and CD4). All three of these patients showed a larger number of blast cells in the tumour compared with the plaque. No correlation between this loss of antigenicity and the prognosis was observed. The results of this study show that different immunophenotypes can occur simultaneously in an individual patient. Furthermore, we were able to confirm a relationship between the number of intraepidermal CD1+ cells in plaque lesions and the prognosis.
Coronary sinus blood flow determination by the thermodilution technique: Influence of catheter position and respiration
Authors: J. P BAGGER
Journal: Cardiovascular Research (1985)

By measuring the coronary sinus blood flow using the thermodilution technique the influence of "thermodilution catheter" withdrawal from the great cardiac vein to the ostium of the coronary sinus was investigated in 41 patients. In addition, the influence of normal and forced respiration on coronary sinus blood flow was measured in 16 of the patients. Mean great cardiac vein flow was measured to 54 +/- 25 ml X min-1. Catheter withdrawal revealed coronary sinus blood flows of 80 +/- 32, 103 +/- 35, 145 +/- 39 and 213 +/- 61 ml X min-1 when the catheter was moved by steps of 1 cm towards the coronary sinus ostium. The coronary sinus blood flow changed between 116 +/- 34 ml X min-1 and 128 +/- 41 ml X min-1 on expiration or inspiration during normal respiration, respectively, when the catheter was placed in a mid-coronary sinus position. Forced respiration changed the coronary sinus blood flow from 98 +/- 41 ml X min-1 during expiration to 196 +/- 76 ml X min-1 during inspiration. The data show that coronary sinus blood flow changes from 23 to 68 ml X min-1 per cm catheter movement, the nearer the ostium the greater the change. Therefore comparison of coronary sinus blood flow between groups of patients would be a comparison between different catheter positions. Normal respiration moves, as judged by the coronary sinus blood flow, the thermodilution catheter by less than 0.5 cm while forced respiration moves the catheter up to 2 cm within the coronary sinus.
Abstract 3799: HTS performance and high-content analysis of antimigratory compound phenotypes using the Oris Pro 384 cell migration assay.
Authors: Jennifer Fronczak, Laura Vollmer, Gopal Krishnan, Andreas Vogt
Journal: Cancer Research (2013)

Abstract The discovery of anti-metastatic agents that inhibit cancer cell motility has been hindered by a dearth of high-throughput screening (HTS) -compatible cell motility assays. The Oris™ Pro 384 well cell migration assay, developed by Platypus Technologies, is an innovative cell motility assay designed to enable HTS of potential anti-cancer compounds and wound healing agents on adherent tumor and endothelial cell lines. The assay utilizes a centrally located, non-toxic, biocompatible gel (BCG) to form a uniformly sized, cell-free detection zone into which cells migrate. The assay is logistically simple and does not require any mechanical processing steps, such as cell wounding or removal of physical barriers. The assay is fully compatible with laboratory automation, including robotic liquid handlers, plate washers, and high-content screening (HCS) readers. A formal investigation of the accuracy, robustness, and HTS performance of the assay was conducted following guidelines in place at the University of Pittsburgh Drug Discovery Institute (UPDDI). Using MDA-MB-231 human breast cancer cells, the assay was optimized for migration kinetics, cell seeding density, and DMSO tolerance. In multi-day variability studies, the assay delivered signal-to-background ratios &amp;gt; 10 and Z-factors above 0.5 on three consecutive days, was insensitive to process errors or edge-effects, and passed UPDDI Assay Protocol Approval Committee (APAC) criteria. The assay delivered equal HTS performance on two different HCS platforms – the Thermo Scientific Cellomics ArrayScan II and the Molecular Devices ImageXpress®Ultra point scanning confocal reader. Screening of a test cassette of 1280 compounds with known biological activities identified several agents with mechanisms associated with cell motility. The multiparametric nature of the HCS assay permitted correlation of antimigratory activity with cellular toxicity. Our results validate the Oris™ Pro 384 cell migration assay as a logistically simple and information-rich cell motility analysis platform that meets the demands of large scale compound screening. Citation Format: Jennifer Fronczak, Laura Vollmer, Gopal Krishnan, Andreas Vogt. HTS performance and high-content analysis of antimigratory compound phenotypes using the Oris Pro 384 cell migration assay. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3799. doi:10.1158/1538-7445.AM2013-3799
THE “SMOKER'S PARADOX:” IS IT INFLUENCED BY THE DIFFERENT TYPES OF TOBACCO USED? FINDINGS FROM THE 2ND GULF REGISTRY OF ACUTE CORONARY EVENTS (GULF RACE)-2
Authors: Jassim M.S. Al Suwaidi, Khalid F. AlHabib, Ahmad Hersi, Khalid Al Nemer, Shukri Al Saif, Walid M. Ali, Nidal Asaad, Mohammad Zubaid, Ahmad Al-Motarreb, Wael Al Mahmeed, Nizar Al Bustani, Jawad Al-lawati, Khadim Souliman, Norah Q. AL-Sagheer, Haitham Amin
Journal: Journal of the American College of Cardiology (2011)
Serial studies of autologous antibody reactivity to melanoma. Relationship to clinical course and circulating immune complexes.
Authors: D R Vlock, J M Kirkwood
Journal: Journal of Clinical Investigation (1985)

The low titer and incidence of autologous antibody to melanoma has hampered its evaluation. Through acid dissociation and ultrafiltration of serum, we have been able to augment the autologous immune response in 9 of 10 patients studied. This result suggests that autologous antibody is present in most patients with melanoma, but is obscured by circulating antigen and the formation of immune complexes. Because native antibody and antibody derived from circulating immune complexes are produced by the host against physiologically relevant antigens, correlations can be made to clinical course. Serological studies of three patients with melanoma were performed with serum samples obtained over many months; these studies demonstrated correlations with tumor progression and clinical course. Serial serologic studies may yet provide one of the better ways to evaluate these relationships. They have the advantage of detecting transient events that may occur with the inception of metastatic disease or autoimmune phenomena, and of avoiding the difficulties encountered in comparing antibody responses between different individuals.
Primary radiotherapy showed favorable outcome in treating extranodal nasal-type NK/T-cell lymphoma in children and adolescents
Authors: Zhao-Yang Wang, Ye-Xiong Li, Wei-Hu Wang, Jing Jin, Hua Wang, Yong-Wen Song, Qing-Feng Liu, Shu-Lian Wang, Yue-Ping Liu, Shu-Nan Qi, Hui Fang, Xin-Fan Liu, Zi-Hao Yu
Journal: Blood (2009)
Chronic Draining Fistula of the Chin
Authors: Edward F. Rosenfeld
Journal: JAMA (1972)

To the Editor.—  Whenever a persistent facial fistula is seen, dental causes must be considered in the differential diagnosis. 1 Drainage to the surface of the chin from a focus of infection in the mandibular incisor area is uncommon. Most often the infection will drain intra-orally following the path of least resistance. 2   Bernick and Jensen 3 recently reported a case in which a fistula of 32 years' duration was unsuccessfully treated by repeated local excision of the sinus tract. A cure was effected by endodontic therapy with apicoectomy.  Such a patient may present to a physician initially for treatment. Treatment will be unsuccessful if the dental etiology is overlooked. This is most often the case when the tooth is asymptomatic. A thorough evaluation must routinely include an intra-oral examination, radiographs, and vitality tests whenever an extra-oral fistula is seen.  The following case report illustrates the fact that a sinus
GW25-e4290 Efficacy and Safety of limus-eluting stent versus paclitaxel-eluting stent in patients with diabetes mellitus undergoing percutaneous coronary intervention: A meta-analysis
Authors: Liu Yuqi, Lei Gao, Yanqiu Song, Qiao Xue, Yu Wang, Yundai Chen, Chen Yundai
Journal: Journal of the American College of Cardiology (2014)
DIAGNOSTIC IMPORTANCE OF TUBERCULOUS LESIONS OF THE ORAL CAVITY
Authors: ROBERT H. IVY
Journal: JAMA (1923)

Tuberculosis of the oral mucous membrane occurs in two principal forms—lupus and tuberculous ulceration proper. In lupus, the mouth involvement is nearly always an extension of the disease from the skin of the face. The lesions are superficial and slowly progressive, and have little tendency to ulceration and extensive tissue destruction, tending rather to the formation of scar tissue. Of 964 cases of lupus seen by Sequeira, 1 ninety-five, or about 10 per cent., presented oral lesions.  Tuberculous ulceration proper is characterized by the breaking down of miliary tubercles, with the formation of one or more points of ulceration of the mucous membrane. Almost any part of the mouth may be involved, but especially the tongue, the gums, and the hard and soft palate. The ulcer is irregular in shape, not as a rule deep, with slightly undermined but not elevated margins, and with little or no induration. The surface
Possible mechanism for mianserin induced neutropenia associated with saturable elimination kinetics.
Authors: J L O'Donnell, J R Sharman, E J Begg, B M Colls, P W Moller
Journal: BMJ (1985)

Two cases of mianserin induced neutropenia associated with prolonged elimination of the drug were studied. In each case the pharmacokinetic profile suggested saturable elimination kinetics, and the temporal relation of mianserin concentrations and the neutrophil count suggested a direct toxic effect of mianserin on the bone marrow. Until further studies are carried out the plasma mianserin concentration and neutrophil count should be measured in any patient who develops an infection while taking this drug.
Basic isoforms of Par o 1, the major allergen of <i>Parietaria officinalis</i> pollen
Authors: M. R. Coscia, A. Ruffilli, U. Oreste
Journal: Allergy (1995)

We describe a group of basic isoforms of Par o 1 (cumulatively referred to as Par o lb), purified by anion‐exchange chromatography. The allergenic activity of Par o lb was compared with that of the acidic isoform (Par o la) by RAST inhibition. Par o lb showed a cathodic mobility in crossed immunoelectrophoresis. It was found to be homogeneous in SDS‐PAGE and SE‐HPLC (14.5 kDa), and heterogeneous in PAG‐IEF, yielding five IgE‐binding bands with pi ranging between 7.9 and 9.6. PAG‐IEF individual components were isolated by cation‐exchange HPLC. The N‐terminal amino acid sequence of the main component (pI 8.8) was determined and found to be similar to that of Par o la.
Toxoplasma gondii possesses a superantigen activity that selectively expands murine T cell receptor V beta 5-bearing CD8+ lymphocytes.
Authors: E Y Denkers, P Caspar, A Sher
Journal: The Journal of Experimental Medicine (1994)

To investigate early immune responses to the intracellular parasite Toxoplasma gondii, we examined the capacity of nonimmune splenocytes to respond in vitro to intact tachyzoites and soluble tachyzoite antigen (Ag). Both types of stimuli induced high levels of proliferation as well as interferon gamma (IFN-gamma) secretion. Based on several key criteria, the response appeared to be driven by a superantigen present in the parasite. Thus, stimulation of C57BL/6 spleen cells with T. gondii resulted in a preferential threefold expansion of a T cell population expressing the V beta 5 chain of the T cell receptor, and a survey of different inbred mouse strains revealed an inverse correlation between Ag-induced proliferation and genetic deletion of V beta 5. Moreover, proliferation was induced using irradiated Ag-pulsed and infected splenic adherent cells, and was blocked by a major histocompatibility complex class II-specific monoclonal antibody. Furthermore, paraformaldehyde-fixed IAb-, IAk-, and IEk-transfected fibroblast lines were able to specifically bind T. gondii Ag and drive proliferation of T lymphocytes, demonstrating that the response can be mediated by allogeneic class II molecules, and that it does not require cellular Ag processing. It is interesting to note that after 1 wk of culture with Ag, up to 70% of the expanded V beta 5-expressing cells were CD8+. These results provide the first description of a superantigen activity in a protozoan pathogen. In the case of T. gondii, superantigen-driven expansion of IFN-gamma-secreting CD8+ lymphocytes may play a role in the development of the dominant IFN-gamma-dependent, cell-mediated immunity characteristic of infection with this parasite.
AN UNUSUAL DISEASE OF THE BONE MARROW (OSSEOMYELODYSPLASIA)
Authors: CLIFFORD G. GRULEE
Journal: JAMA (1933)

The clinical and anatomic characteristics of the disease of the bone marrow (osseomyelodysplasia) in a white boy, aged 7 years, to be described herein are of interest chiefly because we have been unable to correlate it with any of the distinctive bone marrow diseases. Myeloma, at first glance, seems to be the group that might possibly include our case because of the marked destruction of bone and the wide dissemination of the bone marrow alterations. Yet, as will be noted from its characteristics, this disease differs greatly from myeloma so far as the general characteristics of neoplasms are concerned. Of the diseases now included under the group name myeloma, erythroblastoma would be worthy of the most consideration; but this disease has nothing really in common with our case. The absence of hyperplasia of the usual potential accessory myeloid depots in the liver and spleen, together with the absence of an
Carcinogenicity of saccharin.
Authors: M D Reuber
Journal: Environmental Health Perspectives (1978)

Saccharin is carcinogenic for the urinary bladder in rats and mice, and most likely is carcinogenic in human beings. The neoplasms of the urinary bladder are malignant and invade and metastasize. Male rats are more susceptible to urinary bladder carcinogenesis than female rats. Rats exposed as fetuses develop neoplasms more readily than rats exposed as weanlings. The lesions in the urinary bladder go through the stages of hyperplasia, hyperplastic nodules, and later carcinomas. The male of the human species ingesting saccharin, as for rats, is more susceptible to carcinogenesis of the urinary bladder than the female. Neoplasms of the urinary bladder in rats were not caused by stones, parasites, sodium, or impurities. There is a cocarcinogenic effect between saccharin and methylnitrosurea for the urinary bladder. Even through carcinomas of the urinary bladder are present in rats given the higher doses of saccharin, one was observed in a female rat given 0.5%. Chronic renal disease develops in rats ingesting saccharin. The disease is more advanced at the lower doses than at the higher doses, suggesting that saccharin at the lower doses does not reach the urinary bladder. Early neoplasms are seen in the renal pelvis of rats given the higher doses of saccharin. The risk ratios for urinary bladder carcinomas in human beings increase with both frequency andduration of saccharin usage. Benign and malignant neoplasms at all sites are significantly increased in mice and rats ingesting the higher doses of saccharin. These neoplasms are present in the reproductive and hematopoietic systems, and to a lesser extent in the lungs, vascular system and squamous epithelium. Neoplasms in some organs develop with the lower doses of saccharin. Lymphosarcomas of the lung are significantly increased in rats given 0.01% saccharin. Chronic renal disease in rats given saccharin interferes with the health and life span and consequently with development of neoplasms. Saccharin initiates neoplasms of the skin when its application is followed by croton oil. Epidemiological studies have not been done for neoplasms other than the urinary bladder in human beings.
Recurrence rate of atrial fibrillation in patients after the first relapse: A comparison between metoprolol CR/XL, sotalol, and amiodarone
Authors: Karlheinz Seidl, Margit Vater, Monika Rameken, Andreas Brandt, Axel Droegemueller, Jochen Senges
Journal: Journal of the American College of Cardiology (2003)
A soluble suppressor T cell factor protects against experimental intraabdominal abscesses.
Authors: D F Zaleznik, R W Finberg, M E Shapiro, A B Onderdonk, D L Kasper
Journal: Journal of Clinical Investigation (1985)

This paper describes a suppressor T cell factor which protects mice against intraabdominal abscesses caused by Bacteroides fragilis. This soluble cell-free factor (ITF) is derived from splenic T cells from mice immunized with capsular polysaccharide (CP) of B. fragilis. Mice receiving ITF are protected from developing abscesses caused by B. fragilis to the same degree as animals receiving intact immune splenic T cells. The factor appears to be small in molecular size as protective activity is dialyzable through a 12,000-mol wt exclusion dialysis membrane and is present in fractions intermediate between the bed and void volumes of a P2 Biogel column. The protective effect of ITF is antigen-specific to B. fragilis alone. Mice given a complex inoculum of B. fragilis, enterococcus, and another anaerobe develop abscesses even after receiving column-purified ITF. The activity of ITF also is eliminated after adsorption with B. fragilis CP coupled to sheep erythrocytes but not with an unrelated CP coupled to sheep erythrocytes. ITF, therefore, appears to have a binding site for B. fragilis CP. ITF is heat-labile and loses efficacy after protease digestion, suggesting that the active material is a protein. These studies define a suppressor cell factor with activity in a model system resembling human disease and offer promise for increased understanding of the diversity of cell-mediated immune systems.
Pill-Induced Esophageal Injury: Endoscopic Features and Clinical Outcomes
Authors: S. Abid, K. Mumtaz, W. Jafri, S. Hamid, Z. Abbas, H. A. Shah, A. H. Khan
Journal: Endoscopy (2005)

Pill-induced esophageal injury is a common but under-reported problem. The purpose of this study was to explore the clinical and endoscopic features, and the outcome of pill-related esophageal injury.Endoscopy records for the period from January 1997 to June 2003 were searched for reports of esophageal pathology. The records of patients with pill-induced esophageal injury were evaluated.A total of 92 patients with pill-induced esophageal injury were identified (33 men, 59 women; mean age 59, range 25-87). Common symptoms were odynophagia (n = 69, 75 %), chest pain (n = 55, 60 %), vomiting (n = 53, 58 %), dysphagia (n = 31, 33 %), and hematemesis (n = 14, 15 %). The endoscopic findings in the esophagus were: erythema in 76 patients (83 %), erosions in 53 patients (58 %), ulcers in 24 patients (26 %), seven of which were "kissing" ulcers, esophageal ulcer with bleeding in 17 patients (18 %), and esophageal strictures in seven patients (8 %). The causative pills were nonsteroidal anti-inflammatory drugs in 38 patients (41 %), tetracyclines in 20 patients (22 %), potassium chloride tablets in nine patients (10 %), alendronate in eight patients (9 %), and other drugs in 17 patients (18 %). Underlying diseases included diabetes in 60 patients (65 %), ischemic heart disease in 39 patients (42 %), and hypothyroidism in four patients (4 %). The mean hospital stay was 1.94 days; 14 patients (15 %) required injection of epinephrine 1 : 10,000 to control bleeding; and two patients died.Pill-induced injury may present as erosions, kissing ulcers, and multiple small areas of ulceration with bleeding, mainly in the middle third of the esophagus. Advanced age, female gender, diabetes, and ischemic heart disease were common associations. The majority of patients made an uneventful recovery.