tbuckley/cabot-search huggingface dataset:
Cutaneous abnormalities in rheumatoid arthritis compared with non-inflammatory rheumatic conditions
Authors: K M J Douglas
Journal: Annals of the Rheumatic Diseases (2006)

Cutaneous abnormalities are common in rheumatoid arthritis, but exact prevalence estimates are yet to be established. Some abnormalities may be independent and coincidental, whereas others may relate to rheumatoid arthritis or its treatment.To determine the exact nature and point prevalence of cutaneous abnormalities in patients with rheumatoid arthritis compared with those in patients with non-inflammatory rheumatic disease.349 consecutive outpatients for rheumatology (205 with rheumatoid arthritis and 144 with non-inflammatory rheumatic conditions) were examined for skin and nail signs by a dermatologist. Histories of rheumatology, dermatology, drugs and allergy were noted in detail.Skin abnormalities were reported by more patients with rheumatoid arthritis (61%) than non-inflammatory controls (47%). More patients with rheumatoid arthritis (39%) than controls (10%) attributed their skin abnormality to drugs. Cutaneous abnormalities observed by the dermatologist were also more common in patients with rheumatoid arthritis (76%) than in the group with non-inflammatory disease (60%). Specifically, bruising, athlete's foot, scars, rheumatoid nodules and vasculitic lesions were more common in patients with rheumatoid arthritis than in controls. The presence of bruising was predicted only by current steroid use. The presence of any other specific cutaneous abnormalities was not predicted by any of the variables assessed. In the whole group, current steroid use and having rheumatoid arthritis were the only important predictors of having any cutaneous abnormality.Self-reported and observed cutaneous abnormalities are more common in patients with rheumatoid arthritis than in controls with non-inflammatory disease. These include cutaneous abnormalities related to side effects of drugs or to rheumatoid arthritis itself and other abnormalities previously believed to be independent but which may be of clinical importance.
Correlation of regional myocardial blood flow and function with myocardial infarct size during acute myocardial ischemia in the conscious pig.
Authors: R M Savage, B Guth, F C White, A D Hagan, C M Bloor
Journal: Circulation (1981)

Regional myocardial function and blood flow were determined for 48 hours after permanent occlusion of the left circumflex coronary artery in conscious swine. Systolic wall thickening and end-diastolic wall thickness (EDWTh) were correlated with regional myocardial flow (RMBF) at 15 minutes, 24 and 48 hours after occlusion. Both regional function and blood flow were compared with the extent of myocardial necrosis (determined histologically) after 48 hours in functionally distinct zones. Group 1 (control zones) was characterized by increased systolic wall thickening, EDWTh, RMBF and had no necrosis. Group 2 (marginal zones) had depressed systolic wall thickening (35 +/- 3% [mean +/ SEM] of preocclusion level at 48 hours) and RMBF (64 +/- 6% of preocclusion values), transiently decreased EDWTh and 46 +/- 5% necrosis. In Group 3 (ischemic zones), all values were greatly reduced: systolic wall thickening was 3.6 +/- 1.2%, EDWTh 76 +/- 8% and RMBF 25 +/- 9% preocclusion values; necrosis was 90 +/- 5%. Groups 2 and 3 had increased RMBF at 24 and 48 hours from that at 15 minutes after occlusion; however, in neither case was systolic wall thickening greater than that at 15 minutes after occlusion. We conclude that there is close correlation between RMBF, systolic wall thickening and the extent of necrosis present after 48 hours of coronary artery occlusion in the conscious swine; subsequent increases in RMBF to the marginal zone after occlusion are not accompanied by improved regional function.
Erythema nodosum and arthritis with Salmonella enteritidis enteritis
Authors: A. Shrivastava, D. Thistlethwaite
Journal: British Journal of Dermatology (1993)

Journal Article Erythema nodosum and arthritis with Salmonella enteritidis enteritis Get access A. Shrivastava, A. Shrivastava Department of Paediatrics, Royal Manchester Children's Hospital, Pendlebury, Manchester M27 1HA, U.K. Search for other works by this author on: Oxford Academic Google Scholar D. Thistlethwaite D. Thistlethwaite Department of Paediatrics, Burnley General Hospital, Burnley BB10 2PQ, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 128, Issue 6, 1 June 1993, Page 704, https://doi.org/10.1111/j.1365-2133.1993.tb00274.x Published: 01 June 1993
Histone deacetylase inhibitors suppress rheumatoid arthritis fibroblast-like synoviocyte and macrophage IL-6 production by accelerating mRNA decay
Authors: Aleksander M Grabiec, Olexandr Korchynskyi, Paul P Tak, Kris A Reedquist
Journal: Annals of the Rheumatic Diseases (2011)

Background Histone deacetylase inhibitors (HDACi) display potent therapeutic efficacy in animal models of arthritis and suppress inflammatory cytokine production in rheumatoid arthritis (RA) synovial macrophages and tissue. Objectives To determine the molecular mechanisms contributing to the suppressive effects of HDACi on RA synovial cell activation, using interleukin 6 (IL-6) regulation as a model. Methods RA fibroblast-like synoviocytes (FLS) and healthy donor macrophages were treated with IL-1β, tumour necrosis factor (TNF)α, lipopolysaccharide or polyinosinic:polycytidylic acid (poly(I:C)) in the absence or presence of the HDACi trichostatin A (TSA) or ITF2357 (givinostat). IL-6 production and mRNA expression was measured by ELISA and quantitative PCR (qPCR), respectively. Protein acetylation and the activation of intracellular signalling pathways were assessed by immunoblotting. The DNA-binding activity of nuclear factor κB (NFκB) and activator protein 1 (AP-1) components was measured by ELISA-based assays. Results HDACi (0.25–1.0 μM) suppressed RA FLS IL-6 production induced by IL-1β, TNFα and Toll-like receptor ligands. Phosphorylation of mitogen-activated protein kinases and inhibitor of κBα (IκBα) following IL-1β stimulation were unaffected by HDACi, as were AP-1 composition and binding activity, and c-Jun induction. TSA induced a significant reduction in nuclear retention of NFκB in FLS 24 h after IL-1β stimulation, but this did not reduce NFκB transcriptional activity or correlate temporally with reductions in IL-6 mRNA accumulation. HDACi significantly reduced the stability of IL-6 mRNA in FLS and macrophages. Conclusions Our study identifies a novel, shared molecular mechanism by which HDACi can disrupt inflammatory cytokine production in RA synovial cells, namely the promotion of mRNA decay, and suggests that targeting HDAC activity may be clinically useful in suppressing inflammation in RA.
Translocation of β-catenin into cytoplasm during TGFβ-induced EMT is negatively regulated by phosphorylation of the PTEN C-terminus in lung cancers
Authors: Naozumi Hashimoto, Daisuke Aoyama, Masaaki Kusumose, Yoshinori Hasegawa
Journal: European Respiratory Journal (2013)

Rationale: Transforming growth factor β (TGFβ)-induced translocation of β-catenin into cytoplasm is a critical step to induce de novo transcription of epithelial-mesenchymal transition (EMT) target genes. Although we demonstrate that modulation of phosphorylation sites in the PTEN C-terminus blunt TGFβ-induced EMT in lung cancers, whether TGFβ can induce translocation of β-catenin via phosphorylation of the PTEN C-terminal tail remains elusive.  Objective: We determined the underlying mechanisms, by which modulation of phosphorylation sites in the PTEN C-terminus tail could rescue EMT.  Methods: Immunofluorescence of β-catenin was performed for the lung cancer cells with mutation of phosphorylation sites in the PTEN C-terminal tail (PTEN4A).  Main Results: H358ON cells with either GFP or GFP-PTENWt protein showed TGFβ-induced β-catenin translocation into the cytoplasm when treated by Doxycycline. In contrats, only de novo GFP-PTEN4A protein completely inhibited β-catenin translocation induced by TGFβ stimulation. This finding was supported by the data that ectopic PTEN4A, not PTENWt, protein in H1299 cells completely inhibited β-catenin translocation induced by TGFβ stimulation.  Conclusion: Our data suggest that modulation of phosphorylation sites in the PTEN C-terminus inhibits TGFβ-induced EMT via blockade of β-catenin translocation. Our study is first to demonstrate the underlying mechanisms, by which phosphorylation sites in the PTEN C-terminal tail might be a promising therapeutic target to negatively regulate TGFβ-induced EMT in lung cancers.
Comparison of gallium scan, computed tomography, and magnetic resonance in patients with mediastinal Hodgkin's disease
Authors: L. Devizzi, L. Maffioli, V. Bonfante, S. Viviani, L. Balzarini, M. Gasparini, P. Valagussa, E. Bombardieri, A. Santoro, G. Bonadonna
Journal: Annals of Oncology (1997)
Clinical implications of scapular dyskinesis in shoulder injury: the 2013 consensus statement from the ‘scapular summit’
Authors: W Ben Kibler, Paula M Ludewig, Phil W McClure, Lori A Michener, Klaus Bak, Aaron D Sciascia
Journal: British Journal of Sports Medicine (2013)

The second international consensus conference on the scapula was held in Lexington Kentucky. The purpose of the conference was to update, present and discuss the accumulated knowledge regarding scapular involvement in various shoulder injuries and highlight the clinical implications for the evaluation and treatment of shoulder injuries. The areas covered included the scapula and shoulder injury, the scapula and sports participation, clinical evaluation and interventions and known outcomes. Major conclusions were (1) scapular dyskinesis is present in a high percentage of most shoulder injuries; (2) the exact role of the dyskinesis in creating or exacerbating shoulder dysfunction is not clearly defined; (3) shoulder impingement symptoms are particularly affected by scapular dyskinesis; (4) scapular dyskinesis is most aptly viewed as a potential impairment to shoulder function; (5) treatment strategies for shoulder injury can be more effectively implemented by evaluation of the dyskinesis; (6) a reliable observational clinical evaluation method for dyskinesis is available and (7) rehabilitation programmes to restore scapular position and motion can be effective within a more comprehensive shoulder rehabilitation programme.
The association between lung function and arterial stiffness in young childhood
Authors: Jacobien B. Eising, Cornelis K. van der Ent, Annemieke M.V. Evelein, Cuno S.P.M. Uiterwaal
Journal: European Respiratory Journal (2014)

The association between lung function and arterial stiffness in young childhoodTo the Editor:Several studies have shown that reduced lung function is a risk factor for cardiovascular morbidity and mortality [1].Precursors for cardiovascular diseases, like hypertension and arterial stiffness, are also associated with lower lung function, independent of sex or anthropometrics [2][3][4][5][6].Currently, there is no explanation for these relationships.Systemic inflammation or traditional cardiovascular risk factors, such as smoking and serum cholesterol, could not fully explain this relationship [4,5].Recent findings support the hypothesis that a common pathway exists between a decline in lung function and, subsequently, the development of arterial stiffness or hypertension [3,6].Suggested explanations were shared factors, like infections during childhood or postnatal growth, which could influence both lung function and arterial stiffness.However, little is known about the association between arterial stiffness and lung function, or about the influence of anthropometrics and environmental factors in early life.In this study, we aimed to assess whether an association between lung function and common carotid artery stiffness is already present in young healthy children.
Kinetics of the bile acid transporter and hepatitis B virus receptor Na+/taurocholate cotransporting polypeptide (NTCP) in hepatocytes
Authors: Alexander König, Barbara Döring, Christina Mohr, Andreas Geipel, Joachim Geyer, Dieter Glebe
Journal: Journal of Hepatology (2014)

The human liver bile acid transporter Na(+)/taurocholate cotransporting polypeptide (NTCP) has recently been identified as liver-specific receptor for infection of hepatitis B virus (HBV), which attaches via the myristoylated preS1 (myr-preS1) peptide domain of its large surface protein to NTCP. Since binding of the myr-preS1 peptide to NTCP is an initiating step of HBV infection, we investigated if this process interferes with the physiological bile acid transport function of NTCP.HBV infection, myr-preS1 peptide binding, and bile acid transport assays were performed with primary Tupaia belangeri (PTH) and human (PHH) hepatocytes as well as NTCP-transfected human hepatoma HepG2 cells allowing regulated NTCP expression, in the presence of various bile acids, ezetimibe, and myr-preS1 peptides.The myr-preS1 peptide of HBV inhibited bile acid transport in PTH and PHH as well as in NTCP-expressing HEK293 and HepG2 cells. Inversely, HBV infection of PTH, PHH, and NTCP-transfected HepG2 cells was inhibited in a concentration-dependent manner by taurine and glycine conjugates of cholic acid and ursodeoxycholic acid as well as by ezetimibe. In NTCP-HepG2 cells and PTH, NTCP expression, NTCP transport function, myr-preS1 peptide binding, and HBV infection followed comparable kinetics.Myr-preS1 virus binding to NTCP, necessary for productive HBV infection, interferes with the physiological bile acid transport function of NTCP. Therefore, HBV infection via NTCP may be lockable by NTCP substrates and NTCP-inhibiting drugs. This opens a completely new way for an efficient management of HBV infection by the use of NTCP-directed drugs.
Interferon-alpha restores the deficient expression of the cytoadhesion molecule lymphocyte function antigen-3 by chronic myelogenous leukemia progenitor cells.
Authors: G Upadhyaya, S C Guba, S A Sih, A P Feinberg, M Talpaz, H M Kantarjian, A B Deisseroth, S G Emerson
Journal: Journal of Clinical Investigation (1991)

Hematopoietic cells from the malignant clone in chronic myelogenous leukemia (CML) maintain and expand a proliferative advantage over normal hematopoietic cells within the bone marrow. This advantage is often ameliorated or reversed in vivo by IFN alpha. Based upon earlier studies suggesting decreased adhesiveness of CML progenitor cells, we asked whether CML progenitor cells are deficient in their expression of the cytoadhesion molecule lymphocyte function antigen-3 (LFA-3, CD58) which is normally expressed on hematopoietic progenitors. Progenitor cells from untreated CML patients showed greatly reduced or absent LFA-3 expression, whereas progenitors from patients treated with IFN alpha in vivo or in vitro expressed surface LFA-3 at more normal levels. LFA-3-deficient CML progenitor cells were unable to stimulate normal regulatory proliferative responses in autologous T cells. We hypothesize that IFN alpha-sensitive LFA-3 deficiency reflects a cell surface cytoadhesion defect which may help explain adhesive abnormalities of CML progenitor cells in vitro and clonal proliferation in vivo.
Measuring β-Cell Function Relative to Insulin Sensitivity in Youth
Authors: Lindsey Sjaarda, SoJung Lee, Hala Tfayli, Fida Bacha, Marnie Bertolet, Silva Arslanian
Journal: Diabetes Care (2012)

To compare β-cell function relative to insulin sensitivity, disposition index (DI), calculated from two clamps (2cDI, insulin sensitivity from the hyperinsulinemic-euglycemic clamp and first-phase insulin from the hyperglycemic clamp) with the DI calculated from the hyperglycemic clamp alone (hcDI).Complete data from hyperglycemic and hyperinsulinemic-euglycemic clamps were available for 330 youth: 73 normal weight, 168 obese with normal glucose tolerance, 57 obese with impaired glucose tolerance, and 32 obese with type 2 diabetes. The correlation between hcDI and 2cDI and Bland-Altman analysis of agreement between the two were examined.Insulin sensitivity and first-phase insulin from hcDI showed a hyperbolic relationship. The hcDI correlated significantly with 2cDI in the groups combined (r = 0.85, P < 0.001) and within each group separately (r ≥ 62, P < 0.001). Similar to 2cDI, hcDI showed a declining pattern of β-cell function across the glucose-tolerance groups. Overall, hcDI values were 27% greater than 2cDI, due to the hyperglycemic versus euglycemic conditions, reflected in a positive bias with Bland-Altman analysis.β-Cell function relative to insulin sensitivity could be accurately evaluated from a single hyperglycemic clamp, obviating the need for two separate clamp experiments, when lessening participant burden and reducing research costs are important considerations.
Immunochemical studies on blood groups LXII. Fractionation of hog and human A, H, and AH blood group active substance on insoluble immunoadsorbents of Dolichos and Lotus lectins.
Authors: M E Pereira, E A Kabat
Journal: The Journal of Experimental Medicine (1976)

The purified lectins from Lotus tetragonolobus and Dolichos biflorus were coupled to Sepharose 2B to make insoluble adsorbents for purification and fractionation of blood group A and H active glycoproteins. With both adsorbents, hog gastric mucin A + H blood substance (HGM), purified by phenol-ethanol precipitation, yielded fractions showing only A, only H, or AH activities. The AH fraction was obtained when the adsorbent column was overloaded with HGM and its A and H specificities seem to be carried on the same molecules since they were not separable by chromatography on either column. However A and H specificities of blood group substance from the stomach of a presumably heterozygous individual hog were both on the same molecules as they too could not be fractionated on either column. Analytical properties of the isolated fractions were generally similar to those of the unfractionated material, the purfied A substances had a higher galactosamine/fucose ratio than did the H substances. Although the original A + H showed very little specific optical rotation, the separated A and H substances rotated positively and negatively, respectively. The lectin-Sepharose adsorbents have also proven useful in isolating A or H substances directly from the crude commercial hog gastric mucin. Blood group A2 substance from a human ovarian cyst yielded two fractions on the Lotus-Sepharose column; the effluent did not interact with the Lotus lectin but precipitated the Ulex and Dolichos lectins and anti-A, and appears to contain type 1 H determinants. The other fraction reacted with Lotus and Ulex lectin as well as with Dolichos and anti-A.
The current status of small bowel transplantation in the UK and internationally
Authors: S J Middleton
Journal: Gut (2005)

Small intestinal transplantation should now be routinely considered for patients with irreversible intestinal failure and complications of parenteral nutrition (PN). Although technically possible for a century,1 and attempted in humans for more than 40 years,2 immunological graft intolerance presented an impenetrable barrier to successful engraftment until the development of the powerful calcineurin inhibitor immunosuppressive agents in the late 1970s. Their subsequent clinical use over the past 17 years has transformed small intestinal transplantation from a position of predictable failure to predominant success and routine clinical reality for a select group of patients

One year graft survivals for solid organs are now excellent and have been improving steadily since the introduction of ciclosporin to routine clinical practice in the early 1980s.3,4 In contrast, survival values for small intestinal transplantation have been slow to improve although are now comparable with those for lung, and the latest published values for one year survival approximate those for liver and kidney (table 1) Why then has progress with intestinal transplantation been so much more difficult?

View this table:

 Table 1  
 Patient and graft survival of patients receiving small intestinal and solid organ grafts



The technical feasibility of the procedure has been established for a century1 but immunological feasibility was far more difficult to establish. The high density of lymphoid tissue and the large mucosal surface area of the small intestine expressing class 2 major histocompatability antigens fuels the mutual intolerance between graft and host. As a hollow organ whose lumen is colonised by a multitude of bacteria and other micro-organisms, it behaves as a potent vector of infection to the host, a problem that is made worse by the precarious barrier from the lumen provided by the thin and vulnerable monolayer of mucosal epithelium. Here then is the fine balance between immunosuppression and infection that …
Blood Glucose Control by Intermittent Loop Closure in the Basal Mode: Computer Simulation Studies with a Diabetic Model
Authors: Stuart M Furler, M Biomed E, Edward W Kraegen, Robert H Smallwood, Donald J Chisholm
Journal: Diabetes Care (1985)

A semiclosed loop, bedside insulin infusion system using a simple basal infusion algorithm consisting of a linear transition between two insulin delivery rates as blood glucose (BG) increases has been developed. A theoretical study using computer simulation has now been undertaken to examine the effect of BG sampling frequency and algorithm parameters on BG control. A model for BG control by exogenous insulin in the individual with diabetes was developed from a model for healthy subjects and from clinical data in the literature. Results of computer simulation using this model showed a decrease in BG stability as the sampling interval increased from 1 to 4 h. Simulations also showed a decrease in BG stability as the sensitivity of the control algorithm increased. Choice of an appropriate basal control algorithm involved a compromise between stability, sampling interval, and metabolic control. We conclude that satisfactory metabolic control can be obtained using intermittent BG sampling in the basal state; sampling at intervals of 3 h combined with a basal control algorithm whereby insulin delivery rate increases linearly from 0.5 to 2.5 U/h over the BG range 2–12 mmol/L appears suitable for most diabetic persons. Three-hour sampling offers a good compromise between degree of metabolic control and clinical effort involved.