tbuckley/cabot-search huggingface dataset:
Adiponectin Inhibits the Production of CXC Receptor 3 Chemokine Ligands in Macrophages and Reduces T-Lymphocyte Recruitment in Atherogenesis
Authors: Yoshihisa Okamoto, Eduardo J. Folco, Manabu Minami, A.K. Wara, Mark W. Feinberg, Galina K. Sukhova, Richard A. Colvin, Shinji Kihara, Tohru Funahashi, Andrew D. Luster, Peter Libby
Journal: Circulation Research (2007)

Obese individuals often have low plasma adiponectin and concomitant chronic inflammation with a predisposition to metabolic and cardiovascular diseases. The present study reports a novel antiinflammatory action of adiponectin in human monocyte-derived macrophages (MPhi) suppressing T-lymphocyte accumulation in atherogenesis. RNA profiling of lipopolysaccharide-stimulated human MPhi identified CXC chemokine ligands (CXCLs), such as IP-10 (interferon [IFN]-inducible protein 10) (CXCL10), I-TAC (IFN-inducible T-cell alpha chemoattractant) (CXCL11), and Mig (monokine induced by IFN-gamma) (CXCL9), T-lymphocyte chemoattractants associated with atherogenesis, among the top 14 transcripts suppressed by adiponectin. Real-time quantitative RT-PCR and ELISA verified that adiponectin inhibited expression of these chemokines at both the mRNA and protein levels in a concentration-dependent manner. Adiponectin reduced the release by lipopolysaccharide-stimulated MPhi of chemoattractant activity for CXC chemokine receptor 3-transfected (receptor for IP-10, Mig, and I-TAC) lymphocytes. Adiponectin decreased lipopolysaccharide-inducible IP-10 promoter activity in promoter-transfected THP-1 MPhi but did not change IP-10 mRNA stability. In lipopolysaccharide-stimulated MPhi, reduction of IFN-beta by adiponectin preceded inhibition of IP-10 mRNA expression. Immunoblot and chromatin immunoprecipitation analyses demonstrated that adiponectin attenuated activation of the transcription factor IFN regulatory factor 3, involved in the MyD88-independent pathway of Toll-like receptor 4 signaling, and subsequent IFN regulatory factor 3 binding to IFN-beta promoter. In vivo studies further demonstrated that apolipoprotein E/adiponectin double-deficient (apoE-/-APN-/-) mice had increased plasma IP-10 levels, accelerated T-lymphocyte accumulation in atheromata, and augmented atherogenesis compared with apoE single-deficient (apoE-/-APN+/+) mice. This study establishes that low levels of adiponectin associated with obesity, the metabolic syndrome, and diabetes favor T-lymphocyte recruitment and contribute to adaptive immune response during atherogenesis.
Changes in bronchoalveolar lavage inflammatory cells in asthmatic patients treated with high dose inhaled beclomethasone dipropionate
Authors: M Duddridge, C Ward, DJ Hendrick, EH Walters
Journal: European Respiratory Journal (1993)

Using serial bronchoalveolar lavage (BAL), we have studied changes in the airway inflammatory cell populations in 20 asthmatic patients, before and after treatment with inhaled beclomethasone dipropionate (BDP), 2,000 micrograms daily in an uncontrolled study. There was a significant improvement in asthma severity, as measured by symptom score and airways responsiveness, and there were significant reductions in the total BAL eosinophil, epithelial cell and mast cell counts, with a significant increase in the percentage BAL lymphocyte count. No significant correlations were found between the changes in airway inflammatory cell numbers and the reduction in asthma severity. In contrast, the fall in ROS generation by the pulmonary macrophage and granulocyte populations was nonsignificant, but the improvement in airways responsiveness was positively correlated to the reduction in the unstimulated pulmonary macrophage activity. Although these data are uncontrolled, the results are compatible with previous studies in suggesting an effect of steroids on the eosinophil, mast cell and epithelial cell in asthmatic airways. They also highlight the probable importance of the luminal lymphocyte population and pulmonary macrophage activation within the asthmatic airway, the beneficial modulatory effect of inhaled BDP treatment upon them, and the relative steroid-resistance of pulmonary inflammatory cell activity.
Behavioral Training With and Without Biofeedback in the Treatment of Urge Incontinence in Older Women
Authors: Kathryn L. Burgio, Patricia S. Goode, Julie L. Locher, Mary G. Umlauf, David L. Roth, Holly E. Richter, R. Edward Varner, L. Keith Lloyd
Journal: JAMA (2002)

ContextPrevious research on urge urinary incontinence has demonstrated that multicomponent behavioral training with biofeedback is safe and effective, yet it has not been established whether biofeedback is an essential component that heightens therapeutic efficacy.ObjectiveTo examine the role of biofeedback in a multicomponent behavioral training program for urge incontinence in community-dwelling older women.DesignProspective, randomized controlled trial conducted from April 1, 1995, to March 30, 2001.SettingUniversity-based outpatient continence clinic in the United States.PatientsA volunteer sample of 222 ambulatory, nondemented, community-dwelling women aged 55 to 92 years with urge incontinence or mixed incontinence with urge as the predominant pattern. Patients were stratified by race, type of incontinence (urge only vs mixed), and severity (frequency of accidents).InterventionsPatients were randomly assigned to receive 8 weeks (4 visits) of biofeedback-assisted behavioral training (n = 73), 8 weeks (4 visits) of behavioral training without biofeedback (verbal feedback based on vaginal palpation; n = 74), or 8 weeks of self-administered behavioral treatment using a self-help booklet (control condition; n = 75).Main Outcome MeasuresReduction in the number of incontinence episodes as documented in bladder diaries, patients' perceptions and satisfaction, and changes in quality of life.ResultsIntention-to-treat analysis showed that behavioral training with biofeedback yielded a mean 63.1% reduction (SD, 42.7%) in incontinence, verbal feedback a mean 69.4% reduction (SD, 32.7%), and the self-help booklet a mean 58.6% reduction (SD, 38.8%). The 3 groups were not significantly different from each other (P = .23). The groups differed significantly regarding patient satisfaction: 75.0% of the biofeedback group, 85.5% of the verbal feedback group, and 55.7% of the self-help booklet group reported being completely satisfied with treatment (P = .001). Significant improvements were seen across all 3 groups on 3 quality-of-life instruments, with no significant between-group differences.ConclusionsBiofeedback to teach pelvic floor muscle control, verbal feedback based on vaginal palpation, and a self-help booklet in a first-line behavioral training program all achieved comparable improvements in urge incontinence in community-dwelling older women. Patients' perceptions of treatment were significantly better for the 2 behavioral training interventions.
Cryptogenic obliterative bronchiolitis in adults.
Authors: C W Turton, G Williams, M Green
Journal: Thorax (1981)

Patients referred for assessment of severe chronic airflow obstruction over a three-year period were reviewed, and when all smokers and ex-smokers, those with asthma, chronic bronchitis, emphysema, and other specific pulmonary diagnoses were excluded 10 patients remained. Their clinical, lung function, and bronchographic features were consistent with obliterative bronchiolitis. Nine were women, five had rheumatoid arthritis, and five had survived for more than 10 years after first symptoms. Obliterative bronchiolitis has not previously been considered as a cause of chronic airflow obstruction but the distinctive features suggest that it is a true disease entity.
IFN-gamma and IL-12 are increased in active compared with inactive tuberculosis.
Authors: R A Taha, T C Kotsimbos, Y L Song, D Menzies, Q Hamid
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Cytokine-mediated immune responses to Mycobacterium tuberculosis infection are important determinants of M. tuberculosis disease development and pathology. However, the distinction between changes in cytokine profile attributable to M. tuberculosis infection and those associated with active pulmonary tuberculosis is unclear. We have compared T cells and their subsets, macrophages, and cytokine messenger RNA (mRNA) profile in the bronchoalveolar lavage (BAL) of patients with active pulmonary tuberculosis with inactive tuberculosis subjects. Ten patients with microbiologically confirmed active pulmonary tuberculosis and 25 subjects with inactive tuberculosis were recruited. Bronchoscopy with BAL was undertaken in all cases and BAL cytospins were examined using the techniques of immunocytochemistry and in situ hybridization. There was a significant increase in the percentage of BAL cells that were CD8+ T cells in active tuberculosis compared with inactive tuberculosis (mean +/- SEM: 7.2 +/- 0.9 versus 2.1 +/- 0.4, p < 0.001), but not CD3+ or CD4+ T cells nor macrophages. There were significant increases in the percentage of BAL cells expressing mRNA for interferon-gamma (IFN-gamma) and interleukin-12 (IL-12) in active versus inactive pulmonary tuberculosis subjects (8.0 +/- 0.6 versus 3.7 +/- 0.4 and 28.4 +/- 2.3 versus 10.2 +/- 1.0, p < 0.001, respectively). There were no significant differences between the active and inactive groups in the number of cells expressing mRNA for IL-2, tumor necrosis factor-alpha (TNF-alpha), IL-4, and IL-5. In conclusion, active pulmonary tuberculosis is associated with increased numbers of CD8+ cells and marked increases in the expression of IL-12 and IFN-gamma mRNA in the BAL, both of which may be useful markers of disease activity.
Pharmacological Inhibition of Leukotrienes in an Animal Model of Bleomycin-Induced Lung Fibrosis: Role of the Cysteinyl and B4 Leukotrienes
Authors: M. Failla, S. Cuzzocrea, T. Genovese, E. Gili, C. La Rosa, E. Mazzon, N. Crimi, C. Vancheri
Journal: Journal of Allergy and Clinical Immunology (2006)
A 73-Year-Old Woman With Abdominal Pain in the Right Lower Quadrant
Authors: Jeffrey R. Bond
Journal: JAMA (1987)

<h3>History</h3> A 73-year-old woman presented with a sixday history of abdominal pain that had started in the epigastrium, but recently had become more intense in the right lower quadrant. She denied experiencing nausea, vomiting, diarrhea, or gastrointestinal bleeding. Peptic ulcer had been diagnosed three years prior to presentation and had been managed medically. Hysterectomy and left oophorectomy had been performed in the remote past. On physical examination, epigastric tenderness as well as guarding and rebound tenderness in the right lower quadrant were present. Mild leukocytosis was reported. Computed tomography (CT) of the abdomen was performed (Figure). Computed tomography demonstrated a 5-cm retrocecal mass with low attenuation (fluid content) surrounded by an irregularly thickened uncalcified wall (Figure). Multiple areas of tissue debris were seen extending into the mass, but no true septation was present. No other abnormality was observed in the abdomen or pelvis. <h3>Diagnosis</h3> Malignant appendiceal mucocele with acute inflammation.
Outcomes After Aortic Valve Replacement in Patients With Severe Aortic Regurgitation and Markedly Reduced Left Ventricular Function
Authors: Hari P. Chaliki, Dania Mohty, Jean-Francois Avierinos, Christopher G. Scott, Hartzell V. Schaff, A. Jamil Tajik, Maurice Enriquez-Sarano
Journal: Circulation (2002)

Background— Left ventricular dysfunction is an indication for aortic valve replacement (AVR) in patients with severe aortic regurgitation (AR). However, the postoperative outcome of patients with severe AR and a markedly low ejection fraction (EF) is not known. Methods and Results— The study group consisted of a total of 450 patients who had AVR for isolated AR between 1980 and 1995. Patients with markedly reduced left ventricular function (EF &lt;35%, LoEF, n=43) were compared with those with moderate reduction in left ventricular function (EF 35% to 50%, MedEF, n=134) and those with normal left ventricular function (EF ≥50%, Nl EF, n=273). The operative mortality rate was higher with LoEF (14%) than with MedEF and Nl EF (6.7% and 3.7%, respectively, P =0.02). At 10 years, 41%±9% of LoEF patients had survived compared with 56%±5% and 70%±3% of MedEF and Nl EF patients, respectively ( P &lt;0.0001). Congestive heart failure occurred at 10 years in 25%±9% with LoEF compared with 17%±4% and 9%±2% with MedEF and NL EF, respectively ( P &lt;0.003). Postoperative EF improved by 4.9%±13.8% in the LoEF group and by 4%±11.9% in the MedEF group compared with −2.3%±10.9% in the Nl EF group ( P &lt;0.002 and P &lt;0.0001, respectively). Conclusions— Patients with severe AR and markedly low EF incur excess operative mortality rates, postoperative mortality rates, and congestive heart failure after AVR. However, postoperative EF improves markedly, and most patients enjoy a long postoperative survival without recurrence of heart failure after AVR; thus they should not be denied the benefits of AVR.
Evaluating efficacy of plasmapheresis for patients with pemphigus using desmoglein enzyme-linked immunosorbent assay
Authors: T. Nagasaka, Y. Fujii, A. Ishida, M. Handa, A. Tanikawa, M. Amagai, T. Nishikawa
Journal: British Journal of Dermatology (2008)

Pemphigus is an autoimmune bullous disease caused by circulating IgG autoantibodies against cell-cell adhesion molecules between keratinocytes: desmoglein (Dsg) 3 and Dsg1. Plasmapheresis is often used to treat severe cases of pemphigus. Enzyme-linked immunosorbent assays (ELISAs) against recombinant Dsg3 and Dsg1 have recently become available, allowing us to quantify IgG autoantibodies against Dsg3 and Dsg1.Using ELISA against recombinant Dsg3 and Dsg1, to evaluate the efficacy of plasmapheresis in pemphigus.Sera obtained from 10 patients with pemphigus vulgaris and one with pemphigus foliaceus following a total of 16 cycles of centrifugal plasmapheresis and 12 effluents from the plasmapheresis were subjected to ELISA against Dsgs. The percentage of IgG autoantibodies removed was calculated using two different formulae: one used serum titres before and immediately after plasmapheresis and the other used the absolute amounts of IgG autoantibodies in the effluents. The percentage fall of anti-Dsg antibody level was also calculated using the serum titres 1 day after plasmapheresis.Using serum titres immediately after plasmapheresis, there was a mean fall per treatment in anti-Dsg 3 antibody level of 43.0% (n = 12) and in anti-Dsg1 antibody level of 48.4% (n = 7). By contrast, calculated from the effluents, on average one treatment removed only 14.6% of anti-Dsg3 antibodies (n = 12) and 16.4% of anti-Dsg1 antibodies (n = 7). This should reflect the correct percentage as it is based on the absolute amounts of IgG autoantibodies removed. Using serum titres 1 day after plasmapheresis, there was a mean fall per treatment in anti-Dsg 3 antibody level of 12.9% (n = 2) and in anti-Dsg1 antibody level of 8.4% (n = 4). The percentage of IgG autoantibodies removed 1 day after plasmapheresis was lower than that found to be removed immediately after plasmapheresis (n = 6).One centrifugal plasmapheresis procedure eliminates about 15% of the IgG autoantibodies from the whole body. The percentage fall of anti-Dsg IgG antibody level differed depending on when the serum samples were obtained after plasmapheresis. The change in the percentage fall of anti-Dsg antibody level within 1 day after plasmapheresis is thought to be attributable to the passive diffusion of the IgG autoantibodies from the extravascular space to the intravascular space. Therefore, removal of IgG autoantibodies calculated using serum titres only should be evaluated carefully considering the equilibration of the IgG autoantibodies between the different body spaces.
A phospholipase C 1-activated pathway regulates transcription in human vascular smooth muscle cells
Authors: I. Hunter, K. S. Mascall, J. W. Ramos, G. F. Nixon
Journal: Cardiovascular Research (2011)

AimsGrowth factor-induced repression of smooth muscle (SM) cell marker genes is an integral part of vascular SM (VSM) cell proliferation. This is partly regulated via translocation of extracellular signal-regulated kinase 1/2 (ERK1/2) to the nucleus which activates the transcription factor Elk-1. The mediators involved in ERK1/2 nuclear translocation in VSM cells are unknown. The aim of this study is to examine the mechanisms which regulate growth factor-induced nuclear translocation of ERK1/2 and gene expression in VSM cells.
Molecular genetics of lipoprotein disorders.
Authors: J L Breslow
Journal: Circulation (1984)

These types of studies lay the foundation for understanding the human apolipoproteins at the genetic level. In addition, through a few specific examples, we have already shown evidence at the DNA level that lesions in apolipoprotein genes can play a role in human atherosclerosis. This work is in its infancy, but we hope it will have a major impact on our ability to understand genetic susceptibility to atherosclerosis in the general population.
Inhibition of glutathione synthesis in the liver leads toS-adenosyl-L-methionine synthetase reduction
Authors: Fernando Corrales, Pilar Ochoa, Carmen Rivas, Manuel Martin-Lomas, José M. Mato, Maria A. Pajares
Journal: Hepatology (1991)

The hepatic levels of glutathione in rats treated with buthionine sulfoximine (4 mmol/kg), an inhibitor of glutathione synthesis, were 72.5% +/- 4.9% of those determined in control animals. This decrease in glutathione concentration was prevented by the administration of glutathione monoethyl ester (7.5 mmol/kg). S-Adenosyl-L-methionine-synthetase activity in the liver of rats treated with buthionine sulfoximine was 39.4% +/- 6.5% of that determined in control animals. Again, glutathione monoethyl ester prevented the effect of buthionine sulfoximine on S-adenosyl-L-methionine-synthetase activity. There was a close correlation (r = 0.936) between the hepatic levels of glutathione and S-adenosyl-L-methionine-synthetase activity. The hepatic concentration of S-adenosyl-L-methionine in buthionine sulfoximine-treated animals was 59.7% +/- 3.7% of that measured in control rats. Contrasting with the protective effects mentioned above, glutathione monoester had no preventive action on buthionine sulfoximine-induced S-adenosyl-L-methionine depletion. Electron microscopic examination of liver samples of rats after buthionine sulfoximine administration showed evidence of liver degeneration, which was attenuated by glutathione monoethyl ester treatment. Glutathione (7.5 mmol/kg) treatment was less effective than glutathione monoethyl ester in attenuating buthionine sulfoximine effects on hepatic S-adenosyl-L-methionine metabolism and morphology. The reduction of S-adenosyl-L-methionine-synthetase activity observed after treatment with buthionine sulfoximine and its prevention by glutathione monoethyl ester, as well as the correlation between the activity of this enzyme and glutathione levels, indicate that glutathione plays an important role in maintaining S-adenosyl-L-methionine-synthetase activity in the liver.
Childhood pulmonary sarcoidosis
Authors: Güzin Cinel, Nural Kiper, Diclehan Orhan, Ebru Yalçin, Deniz Dogru, Ugur Özçelik, Berna Oguz, Mithat Haliloglu, Gülsev Kale
Journal: European Respiratory Journal (2013)

Sarcoidosis is a chronic inflammatory disease leading to granulomatous lesions in many organs, especially in the lungs. It’s very rare in children and lung involvement is a subgroup of childhood diffuse parenchymal lung diseases.  In this study, we present clinical, laboratory, radiological and histopathological findings and follow-up of 18 children who had been diagnosed as sarcoidosis with lung involvement. The most common symptoms are cough, cervical lymphadenopathies and constitutional symptoms as anorexia and weight loss. Besides lung involvement, 16% of patients had skin, 11% had eye involvement; 1 patient had bone involvement. The most common radiological findings are bilateral mediastinal lymphadenopathies and reticulonodular infiltrations in the lung parenchyma. Spirometry was compatible with restrictive lung disease in 53% of patients. Only 4 patients had hypercalciuria and 8 patients had elevated ACE levels on admission. Histopathological investigations revealed numerous sarcoid granulomas consisting of epitheloid histiocytes and multinuclear giant cells; 3 of them had necrosis also. All patients were treated with systemic steroids. On the long term follow up 12 patients improved, 3 patients are still on steroid therapy, and 1 patient is clinically stable. We observed that inhaled steroids used when tapering systemic steroid therapy did not prevent relapses.  In conclusion, clinical and laboratory findings are non-specific in childhood sarcoidosis. Radiological findings are very helpful in the diagnosis; but the exact diagnosis must be done with the histopathological examination. Sarcoidosis responds well to systemic steroid therapy in this age group.
Comprehensive Biomarker Analysis and Final Efficacy Results of Sorafenib in the BATTLE Trial
Authors: George R. Blumenschein, Pierre Saintigny, Suyu Liu, Edward S. Kim, Anne S. Tsao, Roy S. Herbst, Christine Alden, J. Jack Lee, Ximing Tang, David J. Stewart, Merrill S. Kies, Frank V. Fossella, Hai T. Tran, L. Mao, Marshall E. Hicks, Jeremy Erasmus, Sanjay Gupta, Luc Girard, Michael Peyton, Lixia Diao, Jing Wang, Suzanne E. Davis, John D. Minna, Ignacio Wistuba, Waun K. Hong, John V. Heymach, Scott M. Lippman
Journal: Clinical Cancer Research (2013)

To report the clinical efficacy of sorafenib and to evaluate biomarkers associated with sorafenib clinical benefit in the BATTLE (Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination) program.
Repolarization of the mammalian heart action potential is modulated by changes in osmotic strength
Authors: U. Banderali, M. Fink, W. R. Giles
Journal: Cardiovascular Research (2011)

This editorial refers to ‘Osmotic modulation of slowly activating I Ks in guinea-pig ventricular myocytes’ by S. Missan et al ., pp. 429–436, this issue. 

Repolarization of the mammalian heart action potential is a very important physiological variable. It sets action-potential duration and thus strongly modulates contractility and refractoriness in both the atria and the ventricles. Repolarization is initiated and controlled by the time- and voltage-dependent onset of a variety of different outward potassium (K+) currents, some of which are highly non-linear.1 One of these currents, the so-called slow outward delayed rectifier, or I Ks, is expressed in the human ventricle. Its activation adds to the safety factor for repolarization (the so-called repolarization reserve) through its intrinsic time and voltage dependence. This is prominent following augmentation of I Ks by sympathetic nerve stimulation.2

A paper in this issue from the McDonald laboratory3 confirms and extends what is known about the modulation of I Ks in response to changes in osmotic strength of the external medium. A significant change in osmotic strength (±20–30%) may take place in the setting of ischaemia–reperfusion of the heart. This paper demonstrates relatively rapid (3–5 min to steady state) changes in I Ks in single ventricular myocytes obtained from the hearts of adult guinea pigs in response to alterations in osmotic strength: reductions result in reversible increases in I Ks and vice versa. These changes appear to be quite selective as judged by the reported lack of effect on a selected K+ current denoted HERG.

The context for these findings and some aspects of their interpretation is aided …