tbuckley/cabot-search huggingface dataset:
Autocrine Bone Morphogenetic Protein-9 Signals through Activin Receptor-like Kinase-2/Smad1/Smad4 to Promote Ovarian Cancer Cell Proliferation
Authors: Blanca Herrera, Maarten van Dinther, Peter ten Dijke, Gareth J. Inman
Journal: Cancer Research (2009)

Bone morphogenetic proteins (BMPs) act as central regulators of ovarian physiology and may be involved in ovarian cancer development. In an effort to understand these processes, we characterized transforming growth factor beta/BMP receptor and Smad expression in immortalized ovarian surface epithelial cells and a panel of ovarian cancer cell lines. These studies prompted us to evaluate the potential role of BMP9 signaling in ovarian cancer. Using small interfering RNA, ligand trap, inhibitor, and ligand stimulation approaches, we show that BMP9 acts as a proliferative factor for immortalized ovarian surface epithelial cells and ovarian cancer cell lines, signaling predominantly through an ALK2/Smad1/Smad4 pathway rather than through ALK1, the major BMP9 receptor in endothelial cells. Importantly, we find that some ovarian cancer cell lines have gained autocrine BMP9 signaling that is required for proliferation. Furthermore, immunohistochemistry analysis of an ovarian cancer tissue microarray reveals that approximately 25% of epithelial ovarian cancers express BMP9, whereas normal human ovarian surface epithelial specimens do not. Our data indicate that BMP9 signaling through ALK2 may be a novel therapeutic target in ovarian cancer.
Heterogeneity in hepatic transport of somatostatin analog octapeptides
Authors: Gert Fricker, Valerie Dubost, Dietmar Schwab, Christian Bruns, Christoph Thiele
Journal: Hepatology (1994)

Hepatic transport of the synthetic somatostatin analog octreotide-SMS 201-995, (D)Phe-Cys-Phe-(D)Trp-Lys-Thr-Cys-Throl--and its novel derivative N-alpha-(alpha-D-glucosyl(1-4)-1-deoxy-D-fructosyl)-octreotide--SD Z CO-611, N-alpha-(alpha-D-glucosyl(1-4)-1-deoxy-D-fructosyl)-(D)Phe-Cys-Phe- (D)Trp-Lys-Thr-Cys-Throl--was studied. In rats SMS 201-995 showed a plasma elimination half-life of 1.2 +/- 0.2 hr; that of SDZ CO-611 was 1.9 +/- 0.3 hours. Within 120 min 66% of a mesenterically injected 4.4-nmol dose of SMS 201-995 was excreted in bile, but only 5.3% of SDZ CO-611 was excreted in bile. Biliary concentration of SMS 201-995 showed a maximum enrichment of 540-fold +/- 75-fold over peripheral blood concentration, indicating hepatic transport mechanisms different from simple diffusion. Comparison of plasma profiles of both peptides after mesenteric and femoral administration demonstrated the relative importance of hepatic extraction for SMS 201-995 but not for SDZ CO-611. The mode of extraction was studied by means of multiple-indicator dilution in isolated perfused rat liver, with inulin as nonpermeable marker. Ratio plots, ln([inulin]/[peptide]) vs. time, exhibited decreasing slopes for SMS 201-995, suggesting very rapid binding to hepatocyte membranes. The slope of the ratio plot of (inulin/SDZ CO-611) was almost zero even at low doses (down to 0.2 microgram), implying mainly extracellular distribution and nonhepatic elimination. Binding assays indicated the absence of somatostatin receptors in sinusoidal hepatocyte membranes. However, SMS 201-995 and SDZ CO-611 bound with high affinity to somatostatin receptors in rat cortical membranes. Multiple-indicator dilution experiments in presence of increasing cholyltaurine concentrations suggested an interaction of SMS 201-995 with sinusoidal bile salt transport. In isolated hepatocytes, uptake of SMS 201-995 was saturable and showed mutual inhibition with cholyltaurine. The results indicate that SMS 201-995 transport is different from receptor mediated endocytosis as known for peptide hormones and elimination pathways of SDZ CO-611 other than biliary excretion.
Effects of alpha adrenergic blockade and tissue catecholamine depletion on pulmonary vascular response to hypoxia
Authors: Eric D. Silove, Robert F. Grover
Journal: Journal of Clinical Investigation (1968)

The highly reactive pulmonary vascular bed of the neonatal calf was utilized to determine whether the hypoxic pulmonary pressor response is modified by α-adrenergic blockade with phenoxybenzamine (Group A) or by tissue catecholamine depletion with reserpine (Group B). In addition, in Group A, the effects of hypoxia on the pulmonary circulation were compared and contrasted with those of l-norepinephrine (α-receptor stimulator) and isoproterenol (β-receptor stimulator).
Localization of glucocorticoid uptake in normal and ischemic myocardial tissue of isolated perfused cat hearts.
Authors: M Okuda, K R Young, A M Lefer
Journal: Circulation Research (1976)

We studied the uptake of labeled dexamethasone (3H-Dex) or methylprednisolone (3H-MP) in isolated perfused cat hearts during the first hour of acute myocardial ischemia. Considerable amounts of 3H-Dex and 3H-MP were taken up by the plasma membrane (F1) fraction in control, border zone, and ischemic myocardial tissue. Lesser amounts were incorporated into the remaining cell fractions. A gradient of glucocorticoid uptake was observed that decreased from control tissue to ischemic tissue in all subcellular fractions (i.e., F1 to F5). Accordingly, supernatant fraction (S) to particulate (P) ratios of labeled glucocorticoid uptake increased from control to ischemic tissue, indicating that myocardial cell damage resulted in a decrease in glucocorticoid-binding capacity in subcellular fractions obtained from ischemic tissue. The activity of 5'-nucleotidase (5'ND), a plasma membrane marker in myocardial cells, also decreased from normal to ischemic tissue. Furthermore, we found that uptake of 3H-MP and 3H-Dex was associated with the retention of 5'ND activity in F1 fractions of both border zone and ischemic tissue. Similar protection of plasma membrane integritg occurred in the supernatant fraction as determined by changes in S/P ratios of 5'ND activity. These data provide support for the concepts that (1) plasma membrane changes occur soon after acute myocardial ischemia, and (2) the mechanism by which glucocorticoids exert a protective effect in myocardial ischemia may be related to membrane stabilization.
Drug reaction with eosinophilia and systemic symptoms and severe involvement of digestive tract: description of two cases
Authors: G. Do-Pham, A. Charachon, T.A. Duong, A.W. Thille, N. Benhaiem, M. Bagot, O. Chosidow, J.C. Roujeau, P. Wolkenstein, L. Valeyrie-Allanore
Journal: British Journal of Dermatology (2011)

Journal Article Drug reaction with eosinophilia and systemic symptoms and severe involvement of digestive tract: description of two cases Get access G. Do‐Pham, G. Do‐Pham Department of Dermatology, Referral Centre for Toxic and Autoimmune Blistering Diseases Search for other works by this author on: Oxford Academic Google Scholar A. Charachon, A. Charachon Department of Gastroenterology Search for other works by this author on: Oxford Academic Google Scholar T.A. Duong, T.A. Duong Department of Dermatology, Referral Centre for Toxic and Autoimmune Blistering Diseases Search for other works by this author on: Oxford Academic Google Scholar A.W. Thille, A.W. Thille Department of Medical Intensive Care Unit Search for other works by this author on: Oxford Academic Google Scholar N. Benhaiem, N. Benhaiem Department of Anatomopathology, Hôpital Henri Mondor, Assistance Publique – Hôpitaux de Paris, Paris XII University, 94010 Créteil Cedex, France Search for other works by this author on: Oxford Academic Google Scholar M. Bagot, M. Bagot Department of Dermatology, Referral Centre for Toxic and Autoimmune Blistering Diseases Search for other works by this author on: Oxford Academic Google Scholar O. Chosidow, O. Chosidow Department of Dermatology, Referral Centre for Toxic and Autoimmune Blistering Diseases Search for other works by this author on: Oxford Academic Google Scholar J.C. Roujeau, J.C. Roujeau Department of Dermatology, Referral Centre for Toxic and Autoimmune Blistering Diseases Search for other works by this author on: Oxford Academic Google Scholar P. Wolkenstein, P. Wolkenstein Department of Dermatology, Referral Centre for Toxic and Autoimmune Blistering Diseases Search for other works by this author on: Oxford Academic Google Scholar L. Valeyrie‐Allanore L. Valeyrie‐Allanore Department of Dermatology, Referral Centre for Toxic and Autoimmune Blistering Diseases Laurence Valeyrie‐Allanore. E‐mail: laurence.allanore@hmn.aphp.fr Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 165, Issue 1, 1 July 2011, Pages 207–209, https://doi.org/10.1111/j.1365-2133.2011.10293.x Published: 01 July 2011
Phase III Trial of Two Investigational Schedules of Ifosfamide Compared With Standard-Dose Doxorubicin in Advanced or Metastatic Soft Tissue Sarcoma: A European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study
Authors: Paul Lorigan, Jaap Verweij, Zsuzsa Papai, Sjoerd Rodenhuis, Axel Le Cesne, Michael G. Leahy, John A. Radford, Martine M. Van Glabbeke, Anne Kirkpatrick, Pancras C.W. Hogendoorn, Jean-Yves Blay
Journal: Journal of Clinical Oncology (2007)

Single-agent doxorubicin remains the standard treatment for advanced soft tissue sarcomas. Combining doxorubicin with standard-dose ifosfamide has not been shown to improve survival and is associated with a significantly increased toxicity; it is not known whether higher dose single-agent ifosfamide is superior to doxorubicin.This randomized prospective multicenter phase III trial was designed to compare progression-free survival of patients with advanced soft tissue sarcoma receiving either regimen of standard doxorubicin 75 mg/m2 every 21 days, ifosfamide 9 g/m2 over 3 days continuous infusion, or ifosfamide 3 g/m2 per day in 3 hours over 3 days. The primary end point was progression-free survival. Secondary end points included overall survival, response rate, and toxicity.The study included 326 patients. Grade 4 leukopenia, neutropenia, febrile neutropenia, and encephalopathy were more frequent in the ifosfamide arms. Progression-free survival, overall survival, and response rates were not significantly different between the three arms. An independent data monitoring committee reviewed the interim data and recommended early closure of the trial for futility (ie, no significant difference would be shown).Single-agent doxorubicin remains the treatment of choice for patients with advanced soft tissue sarcoma.
TRANSFORMATION OF A HISTOCOMPATIBILITY IMMUNOGEN INTO A TOLEROGEN
Authors: Stephen H. Nimelstein, Allan R. Hotti, Halsted R. Holman
Journal: The Journal of Experimental Medicine (1973)

H-2 antigens on spleen cell membranes absorb antibody to H-2 antigens and induce both humoral and cellular responses. Liver cell membrane H-2 antigens by contrast also absorb antibody but do not influence cellular response and are tolerogenic for the humoral response. This paper demonstrates that syngeneic liver cells contain a substance which can transform the properties of allogeneic spleen cell membranes into those of allogeneic liver cell membranes, i.e., transform a humoral immunogen into a humoral tolerogen. The process appears to be accompanied by cleavage of an antigen component from the spleen membrane and hence to result in a structural change in the H-2 antigen.
Ignition of Calcium Sparks in Arterial and Cardiac Muscle Through Caveolae
Authors: Matthias Löhn, Michael Fürstenau, Victoriya Sagach, Marlies Elger, Wolfgang Schulze, Friedrich C. Luft, Hermann Haller, Maik Gollasch
Journal: Circulation Research (2000)

Abstract —Ca 2+ sparks are localized intracellular Ca 2+ events released through ryanodine receptors (RyRs) that control excitation-contraction coupling in heart and smooth muscle. Ca 2+ spark triggering depends on precise delivery of Ca 2+ ions through dihydropyridine (DHP)-sensitive Ca 2+ channels to RyRs of the sarcoplasmic reticulum (SR), a process requiring a very precise alignment of surface and SR membranes containing Ca 2+ influx channels and RyRs. Because caveolae contain DHP-sensitive Ca 2+ channels and may colocalize with SR, we tested the hypothesis that caveolae are the structural element necessary for the generation of Ca 2+ sparks. Using methyl-β-cyclodextrin (dextrin) to deplete caveolae, we found that dextrin dose-dependently decreased the frequency, amplitude, and spatial size of Ca 2+ sparks in arterial smooth muscle cells and neonatal cardiomyocytes. However, temporal characteristics of Ca 2+ sparks were not significantly affected. We ruled out the possibility that the decreases in Ca 2+ spark frequency and size are caused by changes in DHP-sensitive L-type channels, SR Ca 2+ load, or changes in membrane potential. Our results suggest a novel signaling model that explains the formation of Ca 2+ sparks in a caveolae microdomain. The transient elevation in [Ca 2+ ] i at the inner mouth of a single caveolemmal Ca 2+ channel induces simultaneous activation and thus opens several RyRs to generate a local Ca 2+ release event, a Ca 2+ spark. Alterations in the molecular assembly and ultrastructure of caveolae may lead to pathophysiological changes in Ca 2+ signaling. Thus, caveolae may be intimately involved in cardiovascular cell dysfunction and disease.
Preventive effect of carbocysteine on exacerbation of asthma, GAIA randomised, placebo-controlled multi-centre study
Authors: Hiroyuki Sano, Yuji Tohda, Mitsuru Adachi, Takeshi Fukuda, Ken Ohta, Shunsuke Shoji, Terumasa Miyamoto
Journal: European Respiratory Journal (2012)

Background : Management of exacerbation is clinically very important in asthma control. Carbocysteine, which improves airway mucus clearance and has anti-inflammatory effects, including antioxidant effect, is expected to prevent asthma exacerbation in addition to COPD exacerbation.   Objective : To evaluate the preventive effect of carbocysteine (C) on exacerbation in asthma patients using placebo (P) as a control.   Methods : A total of 286 patients with mild to moderate asthma were randomly assigned to receive either C (1500mg/day) or P for 48 weeks. Patients were allowed to use long-term asthma control medications. The primary endpoint was annual frequency of exacerbations, and the secondary endpoints were pulmonary function and asthma control by ACQ.   Results : At the time of enrollment, the disease type (atopic or non-atopic asthma) was significantly different (p = 0.02) between the two groups (C, n = 140; P, n = 140), but no statistically significant differences were observed in any other baseline characteristics of patients. The frequency of asthma exacerbations, the primary endpoint, was 5.40 /year in the C group and 8.04 /year in the P group, showing a significant decrease in the C group compared with the P group. The risk ratio of exacerbation was 0.658 (95% CI, 0.595-0.727; p    Conclusion : C significantly reduced the frequency of asthma exacerbations and thus provides a new therapeutic concept for long-term asthma management.
Decreased atrial natriuretic peptide binding in renal medulla in rats with chronic heart failure.
Authors: K Tsunoda, F A Mendelsohn, P M Sexton, S Y Chai, G P Hodsman, C I Johnston
Journal: Circulation Research (1988)

The relations between atrial natriuretic peptide (ANP) binding sites in the renal medulla, plasma ANP concentration, and ventricular dysfunction have been studied in rats 4 weeks after myocardial infarction induced by left coronary artery ligation. Plasma ANP concentration was measured by radioimmunoassay, and quantitation of receptors was performed by computerized in vitro autoradiography with 125I-labeled alpha-rat ANP (1-28) as the radioligand. When compared with controls, rats with myocardial infarction had markedly elevated plasma immunoreactive ANP concentrations (462 +/- 82 versus 124 +/- pg/ml, p less than 0.01) and reduced densities of ANP binding in the inner renal medulla (2.93 +/- 0.19 versus 3.53 +/- 0.22 fmol/mg protein, p less than 0.01). Extensive myocardial infarction was associated with a significant decrease in receptor numbers in the inner medulla (33.6 +/- 5.7 versus 95.6 +/- 9.6 fmol/mg protein, p less than 0.01) without significantly altering the affinity constant (1.76 +/- 0.51 versus 1.03 +/- 0.15 x 10(9) M-1, p greater than 0.05). Right ventricular weight increased in proportion to infarct size (r = 0.71, p less than 0.01), and both were correlated with plasma immunoreactive ANP levels (r = 0.74, p less than 0.01 and r = 0.75, p less than 0.01, respectively). Binding densities in the inner medulla of rats with infarcts were negatively correlated with right ventricular weight, plasma immunoreactive ANP concentrations, and also with infarct size (r = -0.92, p less than 0.001; r = -0.78, p less than 0.001; r = -0.77, p less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Application of color Doppler flow mapping to calculate effective regurgitant orifice area. An in vitro study and initial clinical observations.
Authors: P M Vandervoort, J M Rivera, D Mele, I F Palacios, R E Dinsmore, A E Weyman, R A Levine, J D Thomas
Journal: Circulation (1993)

BACKGROUND Analogous to stenotic valve area in the assessment of valvular stenosis, regurgitant orifice area (ROA) represents a fundamental parameter to assess valvular insufficiency. However, this parameter has not been routinely available up to now. In this study, we introduce the concept and provide the methodology to calculate regurgitant orifice area noninvasively, based on the analysis of the proximal flow convergence zone. METHODS AND RESULTS In an in vitro study, we showed the feasibility and the accuracy of calculating effective ROA by the proximal flow convergence method throughout a range of driving pressures. The calculated and true ROA showed an excellent correlation with r = .992, delta ROA = -1.4 +/- 2.9 mm2. We then applied this concept clinically in 77 patients with mitral regurgitation and showed a very good correlation between effective ROA calculated by the proximal flow convergence method and calculated by the Doppler echocardiographic method: r = .95, delta ROA = -0.2 +/- 3.9 mm2. The ROA also correlated very well with Doppler echocardiographic-derived regurgitant stroke volume (r = .93) and regurgitant fraction (r = .82). In a subgroup of 20 patients who underwent invasive evaluation, the calculated effective ROA also correlated well with the angiographic grade of mitral regurgitation (rho = .81). CONCLUSIONS We conclude that effective ROA represents unique information on the severity of a regurgitant lesion and can easily be calculated by the proximal flow convergence method. This new parameter should enhance our understanding and improve the serial assessment of valvular regurgitation.
Long-term oxygen therapy in COPD patients with moderate hypoxaemia: does it add years to life?
Authors: J Zielinski
Journal: European Respiratory Journal (1998)

In this issue of the Journal, an ANTADIR group from France presents interesting data on survival of chronic obstructive pulmonary disease (COPD) patients receiving long-term domiciliary oxygen treatment [1]. ANTADIR is a not-for-profit organization delivering respiratory home therapy in France. This includes long-term oxygen therapy (LTOT) and mechanical ventilation for patients with chronic respiratory failure and continuous positive airway pressure (CPAP) treatment for patients with obstructive sleep apnoea syndrome. Thirty-three regional associations creating ANTADIR are responsible for the care of around 70% of all patients with chronic respiratory problems treated at home in France. Data are collected centrally resulting in the so called ANTADIR observatory. This observatory comprises thousands of patients followed up for many years. The great advantage of analyses done by ANTADIR is that they are based on large populations of nonselected patients treated by primary care physicians giving an evaluation of how home respiratory care is applied on a national scale [2].
Differences in airway responsiveness to acetaldehyde and methacholine in asthma and chronic bronchitis
Authors: F Sánchez-Toril, L Prieto, R Peris, J A Pérez, M Millan, J Marín
Journal: European Respiratory Journal (2000)

Inhaled acetaldehyde may induce bronchoconstriction in asthmatic subjects and provides a new method to investigate airway responsiveness. The objective of the study was to determine whether acetaldehyde was a more specific stimulus than methacholine in differentiating asthma from chronic bronchitis with or without airflow limitation. Bronchial provocation challenges with methacholine and acetaldehyde were performed in 62 asthmatics and in 59 smokers with chronic bronchitis (32 with chronic bronchitis alone and 27 with chronic bronchitis and coexisting chronic obstructive pulmonary disease (COPD)). The response to both bronchoconstrictor agents was measured by the provocative concentration required to produce a 20% fall in forced expiratory volume in one second (FEV1; PC20). The two types of challenge yielded a similarly high level of sensitivity (100% for methacholine and 92% for acetaldehyde) in revealing airway hyperresponsiveness in asthma. However, bronchoprovocation with acetaldehyde yielded considerably greater specificity (95%) than bronchoprovocation with methacholine (24%) in separating asthma from chronic bronchitis. In subjects with asthma, methacholine and acetaldehyde responsiveness were weakly but significantly correlated (r=0.42, p=0.001) but no correlation was found between airway responsiveness to acetaldehyde and baseline FEV1 (r=0.13, p=0.33). These findings suggest that the demonstration of bronchoconstriction in response to acetaldehyde may be a more specific test than methacholine in the differentiation of asthma from chronic bronchitis. Furthermore, methacholine and acetaldehyde hyperresponsiveness are not reflecting the same pathophysiological process in the airways.
C-C Chemokine Receptor 5 Gene Variants in Relation to Lung Disease in Sarcoidosis
Authors: Paolo Spagnolo, Elisabetta A. Renzoni, Athol U. Wells, Susan J. Copley, Sujal R. Desai, Hiroe Sato, Jan C. Grutters, Atiyeh Abdallah, Anne Taegtmeyer, Roland M. du Bois, Kenneth I. Welsh
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Genetic factors are likely to influence the clinical course and pattern of sarcoidosis, a granulomatous disease of unknown origin.We tested this hypothesis for C-C chemokine receptor 5 (CCR5), a molecule involved in recruitment and activation of mononuclear cells.In addition to the known CCR5 Delta 32 insertion/deletion, we evaluated a further eight single-nucleotide polymorphisms in 106 British patients and 142 British unaffected subjects, and second-setted the results in 112 Dutch patients and 169 healthy Dutch control subjects.In the British population, the frequency of one of the identified haplotypes (HHC) was strongly associated with the presence of parenchymal disease (radiographic stage >or= II versus stages 0 and I) at presentation (odds ratio [OR], 5.2; 95% confidence interval [CI], 1.96-13.7; corrected p = 0.02), at 2 (OR, 6.6; 95% CI, 2.5-17.6; corrected p = 0.006), and at 4 years follow-up (OR, 6.8; 95% CI, 2.5-18.0; corrected p = 0.0045). In the Dutch population, the same association was seen at 2 (OR, 6.7; 95% CI, 2.8-16.4; corrected p = 0.002), and 4 years follow-up (OR, 9.0; 95% CI, 3.5-23.1; corrected p = 0.0009).No association between the CCR5 haplotype HHC and susceptibility to sarcoidosis was observed, indicating that this relevant gene only operates after disease induction. In summary, we report a strong association between CCR5 haplotype HHC and persistent lung involvement in sarcoidosis.