tbuckley/cabot-search huggingface dataset:
Macrophage inflammatory protein-1 alpha activates basophils and mast cells.
Authors: R Alam, P A Forsythe, S Stafford, M A Lett-Brown, J A Grant
Journal: The Journal of Experimental Medicine (1992)

Macrophage inflammatory protein-1 (MIP) is a recently cloned cytokine that causes neutrophilic infiltration and induces an inflammatory response. We studied the effect of MIP-1 alpha on histamine secretion from basophils and mast cells. Leukocytes from allergic and normal subjects were studied. MIP-1 alpha caused dose-dependent release of histamine from basophils of 14 of 20 allergic donors at concentrations of 10(-9)-10(-7) M, and the mean release was 13.50 +/- 2.9% at the highest concentration. In the same experiments, the mean histamine release by anti-immunoglobulin E and monocyte chemotactic and activating factor (MCAF) (10(-7) M) was 32 +/- 7% and 31 +/- 3%, respectively. The cells from only 2 of 10 normal subjects released histamine in response to MIP-1 alpha. Histamine release by MIP-1 alpha was rapid, and almost complete within the first 3 min. MIP-1 alpha-induced degranulation was a calcium-dependent noncytotoxic process. MIP-1 alpha showed chemotactic activity for purified basophils that was comparable to MCAF. Both MIP-1 alpha and MCAF at 10(-7) M concentration elicited a chemotactic response that was 40% of the maximal response to C5a (1 microgram/ml). Murine MIP-1 alpha induced histamine release from mouse peritoneal mast cells in a dose-dependent manner. Thus, we have established that MIP-1 alpha is a novel activator of basophils and mast cells.
Chondroitin and keratan sulphate epitopes, glycosaminoglycans, and hyaluronan in progressive versus non-progressive osteoarthritis
Authors: F. Fawthrop, R. Yaqub, C. Belcher, M. Bayliss, J. Ledingham, M. Doherty
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVE</h3> To determine if a single time point estimation of chondroitin sulphate (CS) or keratan sulphate (KS) epitopes, hyaluronan (HA), or total glycosaminoglycans (GAG) in knee synovial fluid at time of hospital referral can predict subsequent radiographic progression of knee osteoarthritis. <h3>METHODS</h3> Two groups of hospital referred patients with knee osteoarthritis were compared: (1) a "progressive" group (n = 45), showing further reduction in radiographic joint space of at least one grade (0-3) in at least one compartment; and (2) a "non-progressive" group (n = 25) in whom radiographs showed no change during the mean follow up period of 2.3 years (median 2, range 1 to 5 years). Knee synovial fluid obtained at the first visit was examined by elisa for: CS epitopes, using monoclonal antibodies 3B3 and 7D4; KS epitope, using monoclonal antibody 5D4; and HA, using biotinylated HA binding region of cartilage proteoglycan. Total sulphated GAG were measured by dye binding with 1:9 dimethylmethylene blue. <h3>RESULTS</h3> In patients with bilateral synovial fluid data right and left knee values were closely correlated for all variables. There were no significant differences between CS and KS epitopes, HA, total sulphated GAG, or ratios of individual CS or KS epitopes to total GAG, between progressive and non-progressive groups. <h3>CONCLUSIONS</h3> Single time point estimation of CS, KS, HA, or total GAG in synovial fluid does not distinguish radiographically progressive and non-progressive knee osteoarthritis patients followed for two years.
Murine hemopoietic colonies in culture containing normoblasts, macrophages, and megakaryocytes
Authors: Hiroshi Hara, Makio Ogawa
Journal: American Journal of Hematology (1978)

Murine marrow cells, when incubated in methylcellulose culture in the presence of erythropoietin and conditioned medium for two weeks, produced large macroscopic bursts containing normoblasts, macrophages, and often megakaryocytes. The clonal nature of these mixed colonies was supported by linearity studies and analysis of the percentages of constituent cells in different plating conditions. Time course observations and studies of the effects of L-cell-conditioned medium revealed that colony-forming cells for the mixed colonies (CFU-mix) are at earlier stages of hemopoietic development than burst-forming units (BFU-E). The mean of the modal sedimentation velocities of CFU-mix was 3.4 mm/hr and was in close agreement with that reported for the spleen colony-forming units. Almost none of the CFU-mix was in a DNA synthetic phase as measured by short-term exposure to tritiated thymidine. These results strongly indicate that CFU-mix represent a population of pluripotent hemopoietic stem cells in murine marrow.
S9 Cluster Analysis Reveals a Distinct Small Airway-Predominant Phenotype of Asthma
Authors: S Gonem, S Natarajan, R Hartley, S Gupta, D Desai, S Corkill, A Singapuri, P Bradding, P Gustafsson, CE Brightling, S Siddiqui
Journal: Thorax (2012)

<h3>Introduction and objectives</h3> Asthma is an inflammatory disease that is treated with inhaled corticosteroids, but some patients manifest persistent symptoms despite this. Small airway dysfunction may account for treatment resistance in asthma. We hypothesised firstly that small airway disease is characterised by multiple and independent domains, and secondly that small airway biomarkers define a distinct phenotype of asthma with altered clinical disease expression. <h3>Methods</h3> Ninety-six patients with asthma and eighteen healthy control subjects were recruited. Participants undertook spirometry, body plethysmography, single breath determination of carbon monoxide uptake in the lung, multiple breath inert gas washout and impulse oscillometry. Factor analysis was used to reduce multiple physiological variables to a smaller number of independent components. Hierarchical and k-means cluster analysis was used to classify asthma patients into groups based on physiological biomarkers. <h3>Results</h3> Factor analysis showed that the measured physiological biomarkers could be reduced to three independent components, corresponding to abnormal lung mechanics (R5-R20 and reactance area), airflow obstruction (FEV1 [% pred.] and FVC [% pred.]) and ventilation heterogeneity (lung clearance index and Sacin). Cluster analysis classified the asthma patients into two groups. Patients in Cluster 1 exhibited multiple physiological abnormalities suggestive of small airway disease, including air trapping, ventilation heterogeneity and abnormal lung mechanics, as well as significant expiratory flow limitation. In contrast, patients in Cluster 2 had largely normal physiology. Patients in Cluster 1 exhibited increased clinical disease expression compared to patients in Cluster 2, with significantly worse median Asthma Control Questionnaire-6 (1.33 vs 1.17, p&lt;0.05), Asthma Quality of Life (5.16 vs 5.97, p&lt;0.01), visual analogue score (VAS) breathlessness (38.5 vs 19.5, p&lt;0.05) and VAS wheeze (33.0 vs 12.0, p&lt;0.05) scores. <h3>Conclusion</h3> Small airway biomarkers define a distinct phenotype of asthma with multiple physiological abnormalities and increased disease expression. Future studies should examine the utility of screening for small airway disease at an early stage as a possible means of stratifying asthma therapy.
Effect of Nitric Oxide-cGMP-Dependent Protein Kinase Activation on Advanced Glycation End-Product–Induced Proliferation in Renal Fibroblasts
Authors: Jau-Shyang Huang, Lea-Yea Chuang, Jinn-Yuh Guh, Chorng-Jia Chen, Yu-Lin Yang, Tai-An Chiang, Min-Yuan Hung, Tung-Nan Liao
Journal: Journal of the American Society of Nephrology (2005)

Renal interstitial fibrosis is believed to play a key role in the development of diabetic nephropathy (DN), and advanced glycation end-products (AGE) may contribute importantly to this. Recent reports have shown that nitric oxide (NO) is closely linked to the renal interstitial fibrosis of DN. In this study, the mechanisms by which NO and its downstream signals mediate the AGE-induced proliferative response in normal rat kidney fibroblasts (NRK-49F) are examined. AGE decreased NO production, cyclic guanosine 5'monophosphate (cGMP) synthesis, and cGMP-dependent protein kinase (PKG) activation time- and dose-dependently. These effects were not observed when cells were treated with nonglycated BSA. NO and inducible nitric oxide synthase (iNOS) stimulated by NO donors S-nitroso-N-acetylpenicillamine (SNAP)/sodium nitroprusside (SNP) and PKG activator 8-para-chlorophenylthio-cGMP (8-pCPT-cGMP) prevented both AGE-induced proliferation and Janus kinase 2 (JAK2)-signal transducers and activators of transcription 5 (STAT5) activation but not p42/p44 mitogen-activated protein kinase (MAPK) activation. The ability of NO-PKG to inhibit AGE-induced cell cycle progression was verified by the observation that SNAP, SNP, and 8-pCPT-cGMP inhibited both cyclin D1 and cdk4 activation. Furthermore, induction of NO-PKG significantly increased p21Waf1/Cip1 expression in AGE-treated NRK-49F cells. The data suggest that the NO-PKG pathway inhibits AGE-induced proliferation by suppressing activation of JAK2-STAT5 and cyclin D1/cdk4 and induction of p21Waf1/Cip1.
Chylothorax as a complication of oesophageal sclerotherapy.
Authors: S D Nygaard, H A Berger, R B Fick
Journal: Thorax (1992)

Chylothorax is an unusual complication of sclerotherapy for oesophageal varices. A patient is described in whom a massive chylous effusion followed sclerotherapy with repeated injections of 1.5% sodium tetradecyl sulphate. The thoracic duct traverses the posterior mediastinum in close proximity to the oesophagus, and may be disrupted by injections at mid oesophageal level.
A phase II study of the 5-lipoxygenase inhibitor, CV6504, in advanced pancreatic cancer: Correlation of clinical data with pharmacokinetic and pharmacodynamic endpoints
Authors: D.R. Ferry, M. Deakin, J. Baddeley, S. Daryanani, S. Bramhall, D.A. Anderson, M.J.O. Wakelam, J. Doran, G. Pemberton, A.M. Young, J. Buckels, D.J. Kerr
Journal: Annals of Oncology (2000)
Late Stent Malapposition After Drug-Eluting Stent Implantation
Authors: Myeong-Ki Hong, Gary S. Mintz, Cheol Whan Lee, Duk-Woo Park, Kyoung-Min Park, Bong-Ki Lee, Young-Hak Kim, Jong-Min Song, Ki-Hoon Han, Duk-Hyun Kang, Sang-Sig Cheong, Jae-Kwan Song, Jae-Joong Kim, Seong-Wook Park, Seung-Jung Park
Journal: Circulation (2006)

Late stent malapposition (LSM) after drug-eluting stent (DES) implantation has not been evaluated sufficiently in real-world practice.We evaluated the incidence, mechanisms, predictors, and long-term prognosis of LSM after DES implantation in 557 patients (705 native lesions; sirolimus-eluting stent in 538 lesions and paclitaxel-eluting stent in 167 lesions) in whom intravascular ultrasound was performed at index and 6-month follow-up. LSM occurred in 82 patients with 85 lesions (12.1% overall, 95% CI 9.7% to 14.5%, 71 lesions (13.2%) in sirolimus-eluting stents and 14 lesions [8.4%] in paclitaxel-eluting stents, P=0.12]; the incidence was 25.0% (4/16) after directional coronary atherectomy before stenting, 27.5% (14/51) in chronic total occlusion lesions, and 31.8% (7/22) after primary stenting in acute myocardial infarction (P=0.13, P<0.001, and P=0.001, respectively, versus elective stenting with conventional balloon predilation, 9.7% [60/616]). There was an increase of external elastic membrane area (from 17.1+/-3.6 to 21.4+/-4.8 mm2, P<0.001) that was greater than the increase in plaque area (from 9.3+/-2.5 to 10.5+/-2.7 mm2, P<0.001). Independent predictors of LSM were total stent length, primary stenting in acute myocardial infarction, and chronic total occlusion lesions. Except for 1 death in the non-LSM group, there were no major adverse cardiac events in either LSM or non-LSM patients during a mean 10-month follow-up after detection of LSM.LSM occurs in 12% of cases after DES implantation. The predictors of LSM are total stent length, primary stenting in acute myocardial infarction, and chronic total occlusion lesions. LSM after DES implantation was not associated with any major adverse cardiac events during a subsequent 10-month (mean) follow-up.
Nuclear Factor-κB-Mediated Transforming Growth Factor-β-Induced Expression of Vimentin Is an Independent Predictor of Biochemical Recurrence after Radical Prostatectomy
Authors: Qiang Zhang, Brian T. Helfand, Thomas L. Jang, Lihua J. Zhu, Lin Chen, Ximing J. Yang, James Kozlowski, Norm Smith, Shilajit D. Kundu, Guangyu Yang, Adekunle A. Raji, Borko Javonovic, Michael Pins, Paul Lindholm, Yinglu Guo, William J. Catalona, Chung Lee
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Transforming growth factor-β (TGF-β)-mediated epithelial-to-mesenchymal transition (EMT) has been shown to occur in some cancers; however, the pathway remains controversial and varies with different cancers. In addition, the mechanisms by which TGF-β and the EMT contribute to prostate cancer recurrence are largely unknown. In this study, we elucidated TGF-β-mediated EMT as a predictor of disease recurrence after therapy for prostate cancer, which has not been reported before. Experimental Design: We analyzed TGF-β-induced EMT using nuclear factor-κB (NF-κB) as an intermediate mediator in prostate cancer cell lines. A total of 287 radical prostatectomy specimens were evaluated using immunohistochemistry in a high-throughput tissue microarray analysis. Levels of TGF-β signaling components and EMT-related factors were analyzed using specific antibodies. Results were expressed as the percentage of cancer cells that stained positive for a given antibody and were correlated with disease recurrence rates at a mean of 7 years following radical prostatectomy. Results: In prostate cancer cell lines, TGF-β-induced EMT was mediated by NF-κB signaling. Blockade of NF-κB or TGF-β signaling resulted in abrogation of vimentin expression and inhibition of the invasive capability of these cells. There was high risk of biochemical recurrence associated with tumors that displayed high levels of expression of TGF-β1, vimentin, and NF-κB and low level of cytokeratin 18. This was particularly true for vimentin, which is independent of patients' Gleason score. Conclusions: The detection of NF-κB-mediated TGF-β-induced EMT in primary tumors predicts disease recurrence in prostate cancer patients following radical prostatectomy. The changes in TGF-β signaling and EMT-related factors provide novel molecular markers that may predict prostate cancer outcomes following treatment.
Small airways function and molecular markers in exhaled air in mild asthma
Authors: S Battaglia, H den Hertog, M C Timmers, S P G Lazeroms, A M Vignola, K F Rabe, V Bellia, P S Hiemstra, P J Sterk
Journal: Thorax (2005)

<b>Background:</b> Several studies suggest that the periphery of the lung is the major site of inflammation in asthma. Fractional exhaled nitric oxide (Feno) and 8-isoprostane have been proposed as biomarkers of inflammation and oxidative stress. We therefore hypothesised that small airway dysfunction in asthma is of inflammatory origin that can be detected by molecular markers in exhaled air. To test this hypothesis, we examined the relationship of Feno and 8-isoprostane in exhaled air with small airways function as assessed by the single breath nitrogen test. <b>Methods:</b> Sixteen patients (14 women) with mild atopic asthma (forced expiratory volume in 1 second &gt;80% predicted) of mean (SD) age 23.0 (5.5) years participated in a cross sectional study. Feno was recorded by chemiluminescence and 8-isoprostane was measured by ELISA in concentrated exhaled breath condensate. The slope of phase III (δN<sub>2</sub>) and the closing volume (CV) were assessed from the single breath washout curve. <b>Results:</b> The median Feno level was 30.4 ppb (range 10.1–82.8), the median 8-isoprostane concentration in exhaled breath condensate was 2.2 pg/ml (range 1.6–2.7), and the mean (SD) δN<sub>2</sub> value was 1.1 (0.4)% N<sub>2</sub>/l. Feno was positively associated with δN<sub>2</sub> (<i>r</i><sub>s</sub> = 0.54, p = 0.032) while 8-isoprostane was inversely correlated with FEV<sub>1</sub>% predicted (<i>r</i><sub>s</sub> = −0.58; p = 0.017) and CV as a percentage of vital capacity (<i>r</i><sub>s</sub> = 0.58; p = 0.019). <b>Conclusions:</b> Feno and 8-isoprostane in exhaled air are associated with small airways function in mild asthma. This suggests that these markers reflect small airway inflammation and favours a role for them as disease markers that is complementary to spirometry in the monitoring of patients with asthma.
MR-guided focused ultrasound surgery (MRgFUS) for the palliation of pain in patients with bone metastases—preliminary clinical experience
Authors: R. Catane, A. Beck, Y. Inbar, T. Rabin, N. Shabshin, S. Hengst, R.M. Pfeffer, A. Hanannel, O. Dogadkin, B. Liberman, D. Kopelman
Journal: Annals of Oncology (2006)
Knee pain in older adults: the latest musculoskeletal "epidemic"
Authors: D P M SYMMONS
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Introduction</h3> The prevalence of alcohol misuse has risen dramatically over the past decade with younger individuals (aged 16–44 years) and women increasingly affected.<sup>1</sup> In 2007 24% adults were classified as hazardous drinkers (33% men, 16% women).<sup>2</sup> Over a 15-year period hospital admission rates for alcohol-related disorders have doubled,<sup>3</sup> with significant social and economic consequences. Recently, The British Society of Gastroenterology and NICE recommended an Alcohol Care Team including an ASN in every District General Hospitals to ensure early and effective inpatient treatment of patients with alcohol misuse; maximising compliance and reducing relapse. Studies indicate that an ASN generates 400 fewer admissions per year with shorter durations of stay and lower mortality rates.<sup>4</sup> <h3>Methods</h3> We retrospectively audited the impact of the ASN on rates of inpatient referrals and medical detoxification regimes undertaken between 2004 and 2011 at Bassetlaw District General Hospital. Rates of commenced and completed detoxifications in addition to self-discharge data were obtained. Medical and surgical inpatients were included. Exclusion criteria: outpatient and A&amp;E attendances, telephone referrals. <h3>Results</h3> Between 2004 and 2011 the number of inpatient referrals for medical detoxification increased BY 657% (49–371 referrals per year). On average, the majority of inpatients were male (66%) and 48 years of age (range 17–90 years). Over a 7-year period the number of inpatient detoxifications commenced increased by 600% (24–168 detoxifications per year). Similarly, completed detoxifications increased by 517% (23 and 142 completed detoxifications in 2004 and 2011 respectively). On average 90.8% (714/786) detoxifications were completed prior to discharge. 9.2% (72/786) patients self-discharged prior to completing the detoxification regime. <h3>Conclusion</h3> The workload of the Alcohol Care Team and ASN has increased substantially over a 7-year period, reflecting the rising prevalence of alcohol misuse and alcohol-related disease. The ASN provides early recognition and implementation of medical detoxification regimes for inpatients, offering support and continuity of care to maximise compliance and efficacy of treatment. Greater recognition and investment in alcohol services is essential within all UK District General Hospitals to minimise the growing burden of alcohol misuse. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>BMA Board of Science</b>. Alcohol Misuse: Tackling the UK Epidemic. 2008. 2. <b>NHS Information Centre</b>. <i>Statistics on Alcohol</i>. 2010. 3. <b>Institute of Alcohol Studies</b>. <i>The Impact of Alcohol on the NHS</i>. 2009. 4. <b>NHS Evidence</b>. Alcohol Care Teams: To Reduce Acute Hospital Admissions and Improve Quality of Care. 2011.
MAGE-A Inhibits Apoptosis in Proliferating Myeloma Cells through Repression of Bax and Maintenance of Survivin
Authors: Tricia Nardiello, Achim A. Jungbluth, Anna Mei, Maurizio DiLiberto, Xiangao Huang, Ania Dabrowski, Valéria C.C. Andrade, Rebecca Wasserstrum, Scott Ely, Ruben Niesvizky, Roger Pearse, Morton Coleman, David S. Jayabalan, Nina Bhardwaj, Lloyd J. Old, Selina Chen-Kiang, Hearn Jay Cho
Journal: Clinical Cancer Research (2011)

The type I Melanoma Antigen GEnes (MAGEs) are commonly expressed in cancers, fueling speculation that they may be therapeutic targets with oncogenic potential. They form complexes with RING domain proteins that have E3 ubiquitin ligase activity and promote p53 degradation. MAGE-A3 was detected in tumor specimens from patients with multiple myeloma and its expression correlated with higher frequencies of Ki-67(+) malignant cells. In this report, we examine the mechanistic role of MAGE-A in promoting survival of proliferating multiple myeloma cells.The impact of MAGE-A3 expression on survival and proliferation in vivo was examined by immunohistochemical analysis in an independent set of tumor specimens segregated into two groups: newly diagnosed, untreated patients and patients who had relapsed after chemotherapy. The mechanisms of MAGE-A3 activity were investigated in vitro by silencing its expression by short hairpin RNA interference in myeloma cell lines and primary cells and assessing the resultant effects on proliferation and apoptosis.MAGE-A3 was detected in a significantly higher percentage of relapsed patients compared with newly diagnosed, establishing a novel correlation with progression of disease. Silencing of MAGE-A showed that it was dispensable for cell cycling, but was required for survival of proliferating myeloma cells. Loss of MAGE-A led to apoptosis mediated by p53-dependent activation of proapoptotic Bax expression and by reduction of survivin expression through both p53-dependent and -independent mechanisms.These data support a role for MAGE-A in the pathogenesis and progression of multiple myeloma by inhibiting apoptosis in proliferating myeloma cells through two novel mechanisms.
Glycine and L-proline Demonstrate Similar IgG Stabilization in Liquid Immunoglobulin Intravenous 10% (IGIV) Formulations
Authors: A.K. Sun, Y. Wu, G. Pot, E. Vandamme, W.J. Grossman, T. Wolfgang, H.P. Schwarz
Journal: Journal of Allergy and Clinical Immunology (2011)
Foundation trusts still do not enjoy full autonomy, MPs hear
Authors: A. O'Dowd
Journal: BMJ (2008)

Foundation trusts in England are still struggling to achieve the full autonomy they were promised by the government, despite having been operational for around four years now, MPs have been told.

MPs on the parliamentary health select committee heard evidence this week as part of a one-off session on foundation trusts and the body that regulates them, Monitor.

Foundation trusts, which are meant to be independent of central government control, still find it hard to be innovative and to adopt new models of care. Witnesses told the committee that boundaries had been set on what foundation trusts could do but that the review of the NHS published this week by the …
Chlamydia trachomatis Infections in the United States
Authors: A. Eugene Washington
Journal: JAMA (1987)

<i>Chlamydia trachomatis</i>has emerged as the most common sexually transmitted bacterial pathogen in the United States and is now recognized to cause substantial morbidity. To determine the economic consequences of chlamydial infections in the United States, we analyzed data from local, state, and national sources. We estimate that<i>C trachomatis</i>infections cost Americans over $1.4 billion per year in direct and indirect costs. Chlamydial infections in women account for 79% of this cost, although men and infants are also affected. Three fourths of the total cost is due to sequelae of untreated, uncomplicated infections. If the current rate of chlamydial infection persists, the projected annual costs will exceed $2.18 billion by 1990. Reducing the incidence of personal suffering and heavy economic burden imposed by<i>C trachomatis</i>infections requires establishment and maintenance of effective prevention/control programs. (<i>JAMA</i>1987;257:2070-2072)