tbuckley/cabot-search huggingface dataset:
Erythrocyte membrane proteins reactive with human (warm-reacting) anti-red cell autoantibodies.
Authors: J P Leddy, J L Falany, G E Kissel, S T Passador, S I Rosenfeld
Journal: Journal of Clinical Investigation (1993)

Immunoglobulin G (IgG) autoantibodies of 20 patients with autoimmune hemolytic anemia (AHA) were used in immunoaffinity assays with surface-radioiodinated human red blood cells (RBCs), and detergent-solubilized products were analyzed by SDS-PAGE/autoradiography. Four membrane proteins were identified as candidate autoantigens: a nonglycosylated polypeptide with an apparent molecular mass of 34 kD (p34) that was expressed in all available RBC phenotypes except Rhnull but differed consistently in apparent molecular mass from the 32-kD Rh(D) polypeptide co-isolated by IgG allo-anti-D; a heterogenous 37-55-kD glycoprotein, also deficient in Rhnull RBCs, which disappeared after deglycosylation by N-glycanase, with the appearance of a sharp, new approximately 31-kD band distinct from p34 and from Rh(D) polypeptide; a approximately 100-kD major membrane glycoprotein identified by immunoblotting as the band 3 anion transporter; and glycophorin A (GPA), also confirmed by immunoblotting. GP37-55 was not seen in the absence of p34, and both proteins are likely to be members of the Rh family. Indeed, a 34-kD polypeptide band and 37-55-kD poly-disperse "smear," isolated concurrently from the same labeled RBCs by IgG allo-anti-e, were indistinguishable from their autoantibody-isolated counterparts and may well be the same protein identified at different epitopes by the auto- and allo-antibodies. Individual AHA patients' autoantibodies isolated p34 and gp37-55, alone or in combination with band 3 (nine cases); strong band 3 alone (five cases); and combinations of band 3 with GPA (six cases). The autoantibodies of three additional patients whose AHA had been induced by alpha-methyldopa also isolated p34 and gp37-55.
Measurement of albumin reflection coefficient with isolated rat glomeruli.
Authors: V J Savin, R Sharma, H B Lovell, D J Welling
Journal: Journal of the American Society of Nephrology (1992)

Macromolecular permeability of the glomerular capillary has been inferred from the clearance of endogenous protein or infused macromolecules. Permeability is increased after treatment with polycations as well as after renal injury. It has previously been shown that the capillaries of glomeruli isolated from normal mammals expand or collapse in response to transcapillary albumin gradients and that the magnitude of the changes in capillary volume and in total glomerular volume are directly proportional to the applied oncotic gradients. In the experiments presented here, the volume responses of control glomeruli and of glomeruli treated with protamine (100 to 600 micrograms/mL for up to 60 min) were used to calculate the albumin reflection coefficient, sigma albumin, and the convectional permeability, P convectional albumin = (1 - sigma albumin), of the capillary wall. Sigma albumin for normal glomeruli was about 1 (P convectional albumin = 0); sigma albumin fell to a minimum of 0.2 +/- 0.1 (P convectional albumin = 0.8 +/- 0.1) after incubation with protamine sulfate (600 micrograms/mL) for 30 min. Retraction and fusion of podocyte foot processes and denudation of the underlying matrix was seen on scanning electron micrographs of protamine-treated glomeruli. These results confirm that it is possible to study macromolecular permeability of the glomerular capillary in vitro and to calculate sigma albumin independent of hemodynamic and systemic humoral influences. This method will permit the assessment of the effects of individual mediators of glomerular injury and the study of glomeruli from kidneys affected by experimentally induced or naturally occurring renal diseases.
Unusual presentation of localized gingival enlargement associated with a slow-growing odontogenic myxoma
Authors: Jaume Miranda Rius, Alfons Nadal, Eduard Lahor, Beatus Mtui, Lluís Brunet
Journal: International Journal of Oral Science (2013)

Unusual presentation of localized gingival enlargement associated with a subjacent tumoural pathology is reported. The patient was a 55-year-old black male, whose chief complaint was a progressive gingival overgrowth for more than ten years, in the buccal area of the anterior left mandible. According to the clinical features and the radiological diagnosis of odontogenic keratocyst, a conservative surgery with enucleation and curettage was performed. Tissue submitted for histopathological analysis rendered the diagnosis of odontogenic myxoma. After 12-month of follow-up, no evidence of recurrence was found. Clinicians should be cautious when facing any gingival enlargement to avoid diagnostic pitfalls and to indicate the appropriate treatment.
Lower limb amputation in England: prevalence, regional variation and relationship with revascularisation, deprivation and risk factors. A retrospective review of hospital data
Authors: Naseer Ahmad, G Neil Thomas, Paramjit Gill, Colin Chan, Francesco Torella
Journal: Journal of the Royal Society of Medicine (2014)

We describe the prevalence of major lower limb amputation across England and its relationship with revascularisation, patient demography and disease risk factors.Retrospective cohort study.England 1 April 2003 to 31 March 2009.Patients aged 50-84 years.Age standardised prevalence rates were calculated using Hospital Episode Statistics as the numerator with census data as the denominator. The outcome measure 'amputation with revascularisation' was created if an amputation could be linked with a revascularisation. Logistic regression determined the odds of having an amputation with a revascularisation across England. Regression was performed unadjusted and repeated after controlling for demographic (age, sex, social deprivation) and disease risk factors (diabetes, hypertension, coronary heart disease, cerebrovascular disease, smoking).There were 25,312 amputations and 136,215 revascularisations, and 7543 cases were linked. The prevalence rate per 100,000 (95% confidence intervals) for amputation was 26.3 (26.0-26.6) with rates significantly higher in Northern England (North: 31.7; 31.0-32.3, Midlands: 26.0; 25.3-26.7, South: 23.1; 22.6-23.5). The revascularisation rate was 141.6 (140.8-142.3) with significantly higher rates again in Northern England (North: 182.1; 180.5-183.7, Midlands: 121.3; 119.8-122.9, South 124.9; 123.9-125.8). The odds of having an amputation with a revascularisation remained significantly higher in the North (OR 1.22; 1.13-1.33) even after controlling demographic and disease risk factors.There is a North-South divide in England for both major lower limb amputation and revascularisation. The higher odds of having an amputation with a revascularisation in the North were not fully explained by greater levels of deprivation or disease risk factors.
Effect of different asthma treatments on risk of cold-related exacerbations
Authors: H. K. Reddel, C. Jenkins, S. Quirce, M. R. Sears, E. D. Bateman, P. M. O'Byrne, M. Humbert, R. Buhl, T. Harrison, G. G. Brusselle, A. Thoren, U. Sjobring, S. Peterson, O. Ostlund, G. S. Eriksson
Journal: European Respiratory Journal (2011)

Common colds often trigger asthma exacerbations. The present study compared cold-related severe exacerbations during budesonide/formoterol maintenance and reliever therapy, and different regimens of maintenance inhaled corticosteroids (ICS), with or without long-acting β<sub>2</sub>-agonists (LABA), and with as-needed short-acting β<sub>2</sub>-agonists (SABA) or LABA. Reported colds and severe exacerbations (defined by oral corticosteroid use and/or hospitalisation/emergency room visit) were assessed for 12,507 patients during 6–12 months of double-blind treatment. Exacerbations occurring ≤14 days after onset of reported colds were analysed by a Poisson model. The incidence of colds was similar across treatments. Asthma symptoms and reliever use increased during colds. Budesonide/formoterol maintenance and reliever therapy reduced severe cold-related exacerbations by 36% <i>versus</i> pooled comparators plus SABA (rate ratio (RR) 0.64; p=0.002), and for individual treatment comparisons, by 52% <i>versus</i> the same maintenance dose of ICS/LABA (RR 0.48; p&lt;0.001); there were nonsignificant reductions <i>versus</i> higher maintenance doses of ICS or ICS/LABA (RR 0.83 and 0.72, respectively). As-needed LABA did not reduce cold-related exacerbations <i>versus</i> as-needed SABA (RR 0.96). Severe cold-related exacerbations were reduced by budesonide/formoterol maintenance and reliever therapy compared with ICS with or without LABA and with as-needed SABA. Subanalyses suggested the importance of the ICS component in reducing cold-related exacerbations. Future studies should document the cause of exacerbations, in order to allow identification of different treatment effects.
Cutaneous tuberculosis diagnosis in an inhospitable Amazonian region by means of telemedicine and molecular biology
Authors: Diana I. Angel, Rosalba Alfonso, Michel Faizal, Orlando Ricaurte, Julio A. Baez, Andres Rojas, Paola Barato, Manuel E. Patarroyo, Manuel A. Patarroyo
Journal: Journal of the American Academy of Dermatology (2005)
Advances in Antifungal Therapy
Authors: Carole A. Sable, Kim M. Strohmaier, Jeffrey A. Chodakewitz
Journal: Annual Review of Medicine (2007)

The prevalence of invasive fungal infections (IFIs) has increased over the past three decades owing to the increasing numbers of immunocompromised hosts. These infections are associated with significant morbidity and mortality. Recent significant advances in antifungal therapy include the broad-spectrum triazoles (voriconazole and posaconazole) and a new class of antifungals, the echinocandins (caspofungin, micafungin, and anidulafungin). New treatment strategies, such as combination therapy and pre-emptive therapy, are being investigated. There have also been significant improvements in diagnostics; the galactomannan enzyme immunoassay and the beta-glucan test are now part of the EORTC/MSG criteria for diagnosis of IFI. Despite these advances, there remain a number of unanswered questions regarding optimal management of serious fungal infections, and research continues to discover and develop new therapies and evaluate new management strategies.
Mitochondrial N-formylmethionyl proteins as chemoattractants for neutrophils.
Authors: H Carp
Journal: The Journal of Experimental Medicine (1982)

Mitochondria synthesize several hydrophobic proteins. Like bacteria, mitochondria initiate protein synthesis with an N-formylmethionine residue. Because N-formylmethionyl peptides have been found to be chemotactic for polymorphonuclear leukocytes (PMN), mitochondria isolated from cultured human cells and purified bovine mitochondrial proteins were tested for PMN chemotactic activity in vitro. Nondisrupted mitochondria were not chemotactic. However, intact mitochondria that had been incubated with a lysosomal lysate did stimulate PMN migration. Antibodies directed against two mitochondrial enzymes, cytochrome oxidase and ATPase, (both of which contain mitochondrially synthesized subunits) but not anti-C3 or anti-C5 decreased mitochondrially derived chemotactic activity. In addition, purified bovine mitochondrial N-formylmethionyl proteins stimulated PMN migration in vitro, whereas nonformylated mitochondrial proteins did not. Furthermore, the chemotactic activity of purified mitochondrial proteins and disrupted mitochondria was decreased by the formyl peptide antagonist butyloxycarbonyl-phenylalanine-leucine-phenylalanine-leucine-phenylalanine. Finally, disrupted mitochondria and purified mitochondrial proteins stimulated PMN-directed migration (chemotaxis), according to accepted criteria. In addition to other chemotactic factors, release of N-formylmethionyl proteins from mitochondria at sites of tissue damage, may play a role in the accumulation of inflammatory cells at these sites.
Chronic bronchitis: an objective diagnosis of exclusion
Authors: Alexandros G. Mathioudakis, Victoria Chatzimavridou-Grigoriadou, Efstathia Evangelopoulou, Georgios A. Mathioudakis
Journal: European Respiratory Journal (2012)

Chronic bronchitis: an objective diagnosis of exclusionTo the Editors:In their recent, very interesting study, MONTES DE OCA et al. [1] suggested that chronic bronchitis is associated with increased morbidity and poorer general health status in both chronic obstructive pulmonary disease (COPD) and non-COPD subjects.Although the term ''chronic bronchitis phenotype'' is mentioned in the title, we feel that the differentiation between the phenotype and the actual diagnosis should be highlighted.Chronic bronchitis is a diagnosis of exclusion, while its phenotype could include patients with congestive heart failure (CHF), asthma, tuberculosis, lung cancer, bronchiectasis or other respiratory diseases.All these possible diagnoses were insufficiently investigated in this study.As a result, the overwhelming majority of non-COPD subjects with chronic bronchitis phenotype presented in this study are expected to match one of these diagnoses, with the well-established levels of morbidity and quality of life burden.We believe that the CHF diagnosis should have at least been inquired from all the subjects.In the COPD group, the same confounding factor should have been taken into account.
Interleukin 10 (Tenovil) in the prevention of postoperative recurrence of Crohn's disease
Authors: J-F Colombel
Journal: Gut (2001)

<h3>BACKGROUND AND AIMS</h3> New lesions of Crohn9s disease occur early after ileal or ileocolonic resection and ileocolonic anastomosis. We performed a double blind controlled trial to evaluate the safety and tolerance of recombinant human interleukin 10 (IL-10; Tenovil) in subjects operated on for Crohn9s disease. We also assessed the effect of Tenovil in preventing endoscopic recurrence 12 weeks after surgery. <h3>METHODS</h3> Patients with Crohn9s disease who underwent curative ileal or ileocolonic resection and primary anastomosis were randomised within two weeks after surgery to receive subcutaneous Tenovil 4 μg/kg once daily (QD) (n=22) or 8 μg/kg twice weekly (TIW) (n=21), or placebo (QD or TIW) (n=22). An ileocolonoscopy was performed after 12 weeks of treatment. <h3>RESULTS</h3> Compliance was excellent. The most frequently observed adverse events were mild and moderate in severity and equally distributed across treatment groups. Thirty seven patients in the pooled Tenovil group and 21 patients in the pooled placebo group were evaluable by endoscopy. At 12 weeks, 11 of 21 patients (52%) in the placebo group had recurrent lesions compared with 17 of 37 patients (46%) in the Tenovil group (ns). The incidence of severe endoscopic recurrence was similar in both groups (9%). <h3>CONCLUSION</h3> Tenovil treatment for 12 consecutive weeks in patients with Crohn9s disease after intestinal resection was safe and well tolerated. No evidence of prevention of endoscopic recurrence of Crohn9s disease by Tenovil was observed.
Inhibition of ATP-sensitive potassium channels of adult rat heart cells by antiarrhythmic drugs.
Authors: R A Haworth, A B Goknur, H A Berkoff
Journal: Circulation Research (1989)

We have investigated the effect of antiarrhythmic drugs on the increased potassium conductance induced in isolated adult rat heart cells by ATP depletion. The rate of 86Rb uptake in the presence of ouabain was used as a measure of potassium conductance. Treatment of cells with rotenone plus p-trifluoromethoxyphenylhydrazone (FCCP) rapidly depleted ATP levels and strongly stimulated the rate of 86Rb uptake. The stimulated uptake and the ATP depletion were inhibited by oligomycin; thus, the uptake was not induced by rotenone plus FCCP directly. The stimulated uptake, but not the ATP depletion, was inhibited potently by glyburide (IC50, 38.3 nM), quinidine (IC50, 2.7 microM), verapamil (IC50, 4.5 microM), and amiodarone (IC50, 19.1 microM). The stimulated uptake was also inhibited by tetraethylammonium ion and by 4-aminopyridine but not by tetrodotoxin or manganese. We conclude that 1) the stimulated 86Rb uptake is measuring ATP-sensitive potassium channel activity, 2) the ATP-sensitive potassium channel is strongly inhibited by quinidine, verapamil, and amiodarone, and 3) this inhibition may contribute to the antiarrhythmic action of these drugs.
SKI-606, a Src/Abl Inhibitor with<i>In vivo</i>Activity in Colon Tumor Xenograft Models
Authors: Jennifer M. Golas, Judy Lucas, Carlo Etienne, Jonathan Golas, Carolyn Discafani, Latha Sridharan, Erwin Boghaert, Kim Arndt, Fei Ye, Diane H. Boschelli, Fangbiao Li, Craig Titsch, Christine Huselton, Inder Chaudhary, Frank Boschelli
Journal: Cancer Research (2005)

Src up-regulation is a common event in human cancers. In colorectal cancer, increased Src levels are an indicator of poor prognosis, and progression to metastatic disease is associated with substantial increases in Src activity. Therefore, we examined the activity of SKI-606, a potent inhibitor of Src and Abl kinases, against colon tumor lines in vitro and in s.c. tumor xenograft models. SKI-606 inhibited Src autophosphorylation with an IC(50) of approximately 0.25 micromol/L in HT29 cells. Phosphorylation of Tyr(925) of focal adhesion kinase, a Src substrate, was reduced by similar concentrations of inhibitor. Antiproliferative activity on plastic did not correlate with Src inhibition in either HT29 or Colo205 cells (IC(50)s, 1.5 and 2.5 micromol/L, respectively), although submicromolar concentrations of SKI-606 inhibited HT29 cell colony formation in soft agar. SKI-606 also caused loosely aggregated Colo205 spheroids to condense into compact spheroids. On oral administration to nude mice at the lowest efficacious dose, peak plasma concentrations of approximately 3 micromol/L, an oral bioavailability of 18%, and a t(1/2) of 8.6 hours were observed. SKI-606 was orally active in s.c. colon tumor xenograft models and caused substantial reductions in Src autophosphorylation on Tyr(418) in HT29 and Colo205 tumors. SKI-606 inhibited HT29 tumor growth on once daily administration, whereas twice daily administration was necessary to inhibit Colo205, HCT116, and DLD1 tumor growth. These results support development of SKI-606 as a therapeutic agent for treatment of colorectal cancer.
Role of free fatty acids and insulin in determining free fatty acid and lipid oxidation in man.
Authors: L C Groop, R C Bonadonna, M Shank, A S Petrides, R A DeFronzo
Journal: Journal of Clinical Investigation (1991)

Plasma FFA oxidation (measured by infusion of 14C-palmitate) and net lipid oxidation (indirect calorimetry) are both inhibited by insulin. The present study was designed to examine whether these insulin-mediated effects on lipid metabolism resulted from a decline in circulating FFA levels or from a direct action of the hormone on FFA/lipid oxidation. Nine subjects participated in two euglycemic insulin clamps, performed with and without heparin. During each insulin clamp study insulin was infused at two rates, 4 and 20 mU/m2.min for 120 min. The studies were performed with indirect calorimetry and 3-3H-glucose and 14C-palmitate infusion. During the control study plasma FFA fell from 610 +/- 46 to 232 +/- 42 to 154 +/- 27 mumol/liter, respectively. When heparin was infused basal plasma FFA concentration remained constant. During the control study, FFA/lipid oxidation rates decreased in parallel with the fall in the plasma FFA concentration. During the insulin/heparin study, plasma 14C-FFA oxidation remained unchanged while net lipid oxidation decreased. In conclusion, when the plasma FFA concentration is maintained unchanged by heparin infusion, insulin has no direct effect on FFA turnover and disposal. These results thus suggest that plasma FFA oxidation is primarily determined by the plasma FFA concentration, while net lipid oxidation is regulated by both the plasma FFA and the insulin level.
Functional Efficacy of Tendon Repair Processes
Authors: David L. Butler, Natalia Juncosa, Matthew R. Dressler
Journal: Annual Review of Biomedical Engineering (2004)

▪ Abstract Despite various attempts to repair and replace injured tendon, an understanding of the repair processes and a systematic approach to achieving functional efficacy remain elusive. In this review the epidemiology of tendon injury and repair is first examined. Using a traditional paradigm for repair assessment, the biology and biomechanics of normal tendon, natural healing, and repair are then explored. New treatment strategies such as functional tissue engineering are discussed, including a functional approach to treatment that involves the development of in vivo functional design parameters to judge the acceptability of a repair outcome. The paper concludes with future directions.
Decongestion in acute heart failure
Authors: Robert J. Mentz, Keld Kjeldsen, Gian Paolo Rossi, Adriaan A. Voors, John G.F. Cleland, Stefan D. Anker, Mihai Gheorghiade, Mona Fiuzat, Patrick Rossignol, Faiez Zannad, Bertram Pitt, Christopher O'Connor, G. Michael Felker
Journal: European Journal of Heart Failure (2014)
MHC class I chain related gene A (MICA) modulates the development of coeliac disease in patients with the high risk heterodimer DQA1*0501/DQB1*0201
Authors: A Lopez-Vazquez
Journal: Gut (2002)

Background and aims: Coeliac disease (CD) is an enteropathic disorder characterised by a strong association with major histocompatibility complex (MHC) heterodimer HLA-DQ2. It has been suggested that other HLA class I genes in combination with DQ may also contribute to CD susceptibility. The aim of this study was to investigate whether other candidate genes modify the risk of developing different clinical forms of CD. Patients and methods: We studied 133 Spanish coeliac patients, divided according to their clinical presentation into typical and atypical groups, and 116 healthy controls. All were typed by polymerase chain reaction-sequence specific primers (PCR-SSP) at HLA-B, DRB1, DQA1, and DQB1 loci and for exon 5 of the MHC class I chain related gene A (MICA). Results: No differences were found in the frequency of the DQA1*0501/DQB1*0201 heterodimer in either group. The risk of typical CD was significantly associated with the DR7/DQ2 haplotype (p<sub>c</sub>=0.02, odds ratio (OR)=3.4, ethiological fraction (EF)=0.4). Extended haplotype (EH) 8.1 (B8/DR3/DQ2) was found to be overrepresented in the atypical form compared with the typical form (p<sub>c</sub>=0.001, OR=4.19, EF=0.56). The trinucleotide repeat polymorphism MICA-A5.1 was found to be increased in the atypical group of patients compared with the typical group (p<sub>c</sub>=0.00006, OR=8.63, EF=0.81). This association was independent of linkage disequilibrium with EH8.1 as this was also found to be increased in EH8.1 negative atypical patients compared with the typical group (p<sub>c</sub>=0.004, OR=6.66, EF=0.56). Conclusions: Our results showed that the risk of developing typical forms of CD was associated with DR7/DQ2 haplotype, and the presence of B8/DR3/DQ2 was significantly increased in atypical patients. In these, the MICA-A5.1 allele confers an additive effect to the DR3/DQ2 haplotype that may modulate the development of CD.