tbuckley/cabot-search huggingface dataset:
Accumulation of Segmental Alterations Determines Progression in Neuroblastoma
Authors: Gudrun Schleiermacher, Isabelle Janoueix-Lerosey, Agnès Ribeiro, Jerzy Klijanienko, Jérôme Couturier, Gaëlle Pierron, Véronique Mosseri, Alexander Valent, Nathalie Auger, Dominique Plantaz, Hervé Rubie, Dominique Valteau-Couanet, Franck Bourdeaut, Valérie Combaret, Christophe Bergeron, Jean Michon, Olivier Delattre
Journal: Journal of Clinical Oncology (2010)

Neuroblastoma is characterized by two distinct types of genetic profiles, consisting of either numerical or segmental chromosome alterations. The latter are associated with a higher risk of relapse, even when occurring together with numerical alterations. We explored the role of segmental alterations in tumor progression and the possibility of evolution from indolent to aggressive genomic types.Array-based comparative genomic hybridization data of 394 neuroblastoma samples were analyzed and linked to clinical data.Integration of ploidy and genomic data indicated that pseudotriploid tumors with mixed numerical and segmental profiles may be derived from pseudotriploid tumors with numerical alterations only. This was confirmed by the analysis of paired samples, at diagnosis and at relapse, as in tumors with a purely numerical profile at diagnosis additional segmental alterations at relapse were frequently observed. New segmental alterations at relapse were also seen in patients with segmental alterations at diagnosis. This was not linked to secondary effects of cytotoxic treatments since it occurred even in patients treated with surgery alone. A higher number of chromosome breakpoints were correlated with advanced age at diagnosis, advanced stage of disease, with a higher risk of relapse, and a poorer outcome.These data provide further evidence of the role of segmental alterations, suggesting that tumor progression is linked to the accumulation of segmental alterations in neuroblastoma. This possibility of genomic evolution should be taken into account in treatment strategies of low- and intermediate-risk neuroblastoma and should warrant biologic reinvestigation at the time of relapse.
Portal vein thrombosis with ruptured oesophageal varices as presenting manifestation of hereditary protein C deficiency.
Authors: D Valla, M H Denninger, J M Delvigne, B Rueff, J P Benhamou
Journal: Gut (1988)

The protein C system is essential in limiting the activation of coagulation in vivo. We report the case of a 45 year old man with portal vein thrombosis complicated by ruptured oesophageal varices. Low concentration of plasma protein C was found in the patient and subsequently in one brother with a history of venous thromboembolism, and also in one son and one nephew who were asymptomatic. Hereditary protein C deficiency should be considered in patients with portal hypertension due to portal vein thrombosis.
Toll-like Receptor 4 Mediates an Antitumor Host Response Induced by <i>Salmonella choleraesuis</i>
Authors: Che-Hsin Lee, Chao-Liang Wu, Ai-Li Shiau
Journal: Clinical Cancer Research (2008)

We have shown tumor-targeting and antitumor activities of an attenuated Salmonella choleraesuis in various tumor models. Meanwhile, host factors, including innate and adaptive immune responses, play roles in Salmonella-induced antitumor activity. Toll-like receptor 4 (TLR4) is identified as a signaling receptor for lipopolysaccharide derived from Gram-negative bacteria. However, the detailed mechanism of the S. choleraesuis-induced antitumor immune response via TLR4 remained uncertain.Herein, we used wild-type C3H/HeN mice and TLR4-deficient C3H/HeJ mice to study the role of TLR4 in the antitumor immune responses induced by S. choleraesuis.The amounts of S. choleraesuis were cleared more rapidly from the normal organs in C3H/HeN mice than those in C3H/HeJ mice. Tumors in C3H/HeN mice treated with S. choleraesuis were significantly smaller than those treated with PBS. By contrast, in TLR4-deficient mice, there was a slight difference in inhibition of tumor growth. Meanwhile, we found that S. choleraesuis significantly up-regulated IFN-gamma, IFN-inducible chemokines CXCL9 (MIG), and CXCL10 (IP-10) productions in C3H/HeN mice, but not in C3H/HeJ mice. Furthermore, immunohistochemical staining of the tumors revealed less intratumoral microvessel density, more infiltration of macrophages, neutrophils, CD4(+) and CD8(+) T cells, and cell death in C3H/HeN mice after S. choleraesuis treatment compared with those in C3H/HeJ mice. The interaction between TLR4 and S. choleraesuis seemed to polarize the T-cell response to a T helper 1-dominant state.These results suggest TLR4 may play an important role in the molecular mechanism of S. choleraesuis-induced host antitumor responses.
Association of clinical features with HLA in chronic pulmonary thromboembolism
Authors: N. Tanabe, A. Kimura, S. Amano, O. Okada, Y. Kasahara, K. Tatsumi, M. Takahashi, H. Shibata, M. Yasunami, T. Kuriyama
Journal: European Respiratory Journal (2005)

The aetiology of chronic thromboembolic pulmonary hypertension (CTEPH) is largely unknown and may be heterogeneous, because there are several ethnic differences in the clinical characteristics of CTEPH. Female predominance and a higher ratio of chronic to acute pulmonary thromboembolism have been reported in Japan as compared with the USA. Because such ethnic differences may be controlled by genetic factors, the current study investigated HLA polymorphisms in Japanese patients with CTEPH. HLA typing by serological and/or DNA typing methods was performed (for HLA-A, B, DPB1, DRB1) in 80 patients and 678 controls, and the association of clinical characteristics with HLA alleles was studied. The frequencies of HLA-B*5201 (40 versus 24%) and DPB1*0202 (19 versus 6%) were significantly higher in the patients. HLA-B*5201 positive patients showed a significant female predominance. Total pulmonary vascular resistance and mixed venous oxygen tension were better in the HLA-B*5201 positive patients. In contrast, cardiac index and gas exchange parameters were worse in the HLA-DPB1*0202 positive patients. In the patients carrying HLA-B*5201 and/or -DPB1*0202, the frequency of deep vein thrombosis was significantly lower than the other patients. These observations suggested that both the susceptibility and clinical characteristics of chronic thromboembolic pulmonary hypertension were controlled in part by the HLA-B and -DPB1 loci.
Unipolar Depression and the Progression of Coronary Artery Disease: Toward an Integrative Model
Authors: Johan Ormel, Peter de Jonge
Journal: Psychotherapy and Psychosomatics (2011)

&lt;i&gt;Background:&lt;/i&gt; Despite extensive research on the relationship between depression and coronary artery disease (CAD) after an acute coronary syndrome (ACS), causal interpretations are still difficult. This uncertainty has led to much confusion regarding screening and treatment for depression in CAD patients. &lt;i&gt;Method:&lt;/i&gt; A critical and conceptual analysis of the pertinent literature, which elaborates the implications of the heterogeneity in symptom pattern, etiology, and course of depression in CAD patients. &lt;i&gt;Results:&lt;/i&gt; We propose an integrative dynamic model of the depression-CAD relationship. The model rests on three core hypotheses: (1) Depression in CAD patients consists of mixtures of two types of depression, denoted as ‘cognitive/affective’ and ‘somatic’ depression, each having a somewhat characteristic symptom expression and etiology. (2) Effects of depression on CAD depend on the type and duration of depression. The dynamic aspect of the model indicates that post-ACS depression shifts, when it persists, from a marker of the severity (somatic type) and meaning (cognitive/affective type) of the ACS to a largely indirect causal factor in the progression of CAD. (3) The most plausible pathways mediating the effects of persistent/recurrent depression, irrespective of type, on cardiac prognosis are behavioral and act by making depressed CAD patients more susceptible to other CAD risks. The model offers testable predictions and explanations for a variety of apparently unrelated or inconsistent findings. &lt;i&gt;Conclusion:&lt;/i&gt; The proposed model may have potential for integrating findings regarding the depression-CAD relationship, contributing to the clarification of discords on screening and treatment of depression, and guiding future research.
Evaluation of Impermeable Covers for Bedding in Patients with Allergic Rhinitis
Authors: Ingrid Terreehorst, Eelko Hak, Albert J. Oosting, Zana Tempels-Pavlica, Jan G.R. de Monchy, Carla A.F.M. Bruijnzeel-Koomen, Rob C. Aalberse, Roy Gerth van Wijk
Journal: New England Journal of Medicine (2003)

Encasing bedding in impermeable covers reduces exposure to house-dust mites, but the clinical benefit of this intervention as part of mite-avoidance measures for patients with allergic rhinitis is not known. We performed a multicenter, randomized, placebo-controlled trial of one year of use of impermeable bedding covers in the bedrooms of patients with rhinitis who were sensitized to house-dust mites to determine the effects on the signs and symptoms of disease.Three participating university medical centers enrolled 279 patients with allergic rhinitis who were randomly assigned to receive impermeable or non-impermeable (control) covers for their mattress, pillow, and duvet or blanket. At the start of the study, all participants received information on general allergen-avoidance measures. The severity of rhinitis was measured on a rhinitis-specific visual-analogue scale and by means of a daily symptom score and nasal allergen provocation testing. We also measured the concentrations of Dermatophagoides pteronyssinus (Der p1) and D. farinae (Der f1) in dust from patients' mattresses, bedroom floors, and living-room floors at base line and after 12 months as a measure of the efficacy of the intervention.A total of 232 patients completed the study. There was a significant reduction in Der p1 and Der f1 concentrations in the mattresses of the impermeable-cover group, whereas there was no significant reduction in the control group. However, there was no significant effect on the clinical outcome measures. Analyses of subgroups defined according to age, level of exposure, type and severity of sensitization, or characteristics of the patient's home had similar results.Mite-proof bedding covers, as part of a structured allergy-control program, reduced the level of exposure to mite allergens. Despite the success of the intervention, this single avoidance measure did not lead to a significant improvement of clinical symptoms in patients with allergic rhinitis.
Cisapride-Induced Transmural Dispersion of Repolarization and Torsade de Pointes in the Canine Left Ventricular Wedge Preparation During Epicardial Stimulation
Authors: José M. Di Diego, Luiz Belardinelli, Charles Antzelevitch
Journal: Circulation (2003)

Cisapride, a gastrointestinal prokinetic agent, was recently withdrawn from the market because of its propensity to induce torsade de pointes (TdP) arrhythmias. The present study examines the electrophysiological actions of cisapride in the isolated arterially perfused canine left ventricular wedge preparation.Transmembrane action potentials from epicardial and M regions and a pseudo-ECG were simultaneously recorded. Cisapride (0.1 to 5 micromol/L) was added to the coronary perfusate. Cisapride prolonged the QT interval and increased transmural dispersion of repolarization (TDR) at relatively low but not at high concentrations. TdP could be induced with programmed electrical stimulation only at a low concentration of drug (0.2 micromol/L), when TDR was maximally prolonged. Moreover, TdP could only be induced during epicardial (but not endocardial) activation of the wedge, which was found to augment TDR. At higher concentrations of cisapride, QT was further prolonged, TDR was diminished, and TdP could no longer be induced. Tpeak-Tend interval and Tpeak-Tend area provided reasonable electrocardiographic indices of TDR.Our data (1) demonstrate a biphasic concentration/response relationship for the effect of cisapride to induce long-QT syndrome and TdP, (2) show the value of the left ventricular wedge preparation in identifying drugs that pose an arrhythmic risk, (3) support the hypothesis that risk for development of TdP is related to the increase in TDR rather than to prolongation of the QT interval, and (4) indicate that epicardial activation of the left ventricle, as occurs during biventricular pacing, can facilitate the development of TdP under long-QT conditions.
Continuous or Intermittent Dosing With Sertraline for Patients With Severe Premenstrual Syndrome or Premenstrual Dysphoric Disorder
Authors: Ellen W Freeman, Karl Rickels, Steven J Sondheimer, Marcia Polansky, Sha Xiao
Journal: American Journal of Psychiatry (2004)

The authors compared the efficacy and acceptability of continuous versus intermittent treatment with a selective serotonin reuptake inhibitor in women with severe premenstrual syndrome and determined the effects of postmenstrual symptom severity and depression history as covariates of the treatment response.Patients who met symptom criteria and reported impaired functioning after three screening cycles were randomly assigned to three cycles of double-blind, placebo-controlled treatment with continuous (full-cycle dosing) or intermittent (luteal-phase dosing) sertraline. The design was stratified for severity of postmenstrual symptoms and history of major depression. Flexible sertraline dose was 50-100 mg/day. Outcome measures were the Daily Symptom Rating Form score and patient global ratings of functioning.Both sertraline groups improved significantly more than the placebo group as assessed by total premenstrual Daily Symptom Rating Form scores for 3 treatment months. Daily Symptom Rating Form factors that were significantly more improved in the sertraline groups were mood and physical symptoms. Sertraline improvement occurred swiftly in the first month of treatment. Gradual placebo improvement was similar to sertraline in the third month. Subjects with higher postmenstrual symptoms before treatment remained more symptomatic regardless of the dosing regimen. A history of major depression was not associated with treatment response. More sertraline-treated subjects reported improved functioning in the domains of family relationships, social activities, and sexual activity.Premenstrual dosing does not differ from continuous dosing with sertraline in premenstrual syndrome treatment. Higher levels of postmenstrual symptoms limit treatment response and are important to define in treatment of premenstrual syndrome.
Tamm-Horsfall Protein Regulates Granulopoiesis and Systemic Neutrophil Homeostasis
Authors: Radmila Micanovic, Brahmananda R. Chitteti, Pierre C. Dagher, Edward F. Srour, Shehnaz Khan, Takashi Hato, Allison Lyle, Yan Tong, Xue-Ru Wu, Tarek M. El-Achkar
Journal: Journal of the American Society of Nephrology (2015)

Tamm-Horsfall protein (THP) is a glycoprotein uniquely expressed in the kidney. We recently showed an important role for THP in mediating tubular cross-talk in the outer medulla and in suppressing neutrophil infiltration after kidney injury. However, it remains unclear whether THP has a broader role in neutrophil homeostasis. In this study, we show that THP deficiency in mice increases the number of neutrophils, not only in the kidney but also in the circulation and in the liver, through enhanced granulopoiesis in the bone marrow. Using multiplex ELISA, we identified IL-17 as a key granulopoietic cytokine specifically upregulated in the kidneys but not in the liver of THP−/− mice. Indeed, neutralization of IL-17 in THP−/− mice completely reversed the systemic neutrophilia. Furthermore, IL-23 was also elevated in THP−/− kidneys. We performed real-time PCR on laser microdissected tubular segments and FACS-sorted renal immune cells and identified the S3 proximal segments, but not renal macrophages, as a major source of increased IL-23 synthesis. In conclusion, we show that THP deficiency stimulates proximal epithelial activation of the IL-23/IL-17 axis and systemic neutrophilia. Our findings provide evidence that the kidney epithelium in the outer medulla can regulate granulopoiesis. When this novel function is added to its known role in erythropoiesis, the kidney emerges as an important regulator of the hematopoietic system.
Update on basic and clinical aspects of eosinophilic oesophagitis
Authors: Alex Straumann, Alain Schoepfer
Journal: Gut (2014)

The identification of a distinct syndrome, designated eosinophilic oesophagitis (EoE), with its own clinical and histopathological characteristics, was first described in the early 1990s. Meanwhile intense research has uncovered many molecular, immunological and clinical aspects of this chronic-inflammatory disorder. This article focuses exclusively on basic and clinical insights of EoE gathered during the last few years. Regarding aetiopathogenesis it has become clear that EoE is a food-triggered disease with milk and wheat as the dominant culprit food categories. However, it is still debated whether a disturbed mucosal integrity allowing allergens to cross the mucosal barrier, or changes in wheat and milk manufacturing might induce these inflammatory responses. Furthermore, basic science and clinical studies have accordingly confirmed that a chronic eosinophilic inflammation leads to a remodelling of the oesophagus with micro- and macro-morphological alterations, ending in a strictured oesophagus with impaired function. Fortunately, long-term therapeutic trials, using either topical corticosteroids or dietary allergen avoidance, have demonstrated that this sequela can be prevented or even reversed. This finding is of clinical relevance as it supports the initiation of a consistent anti-inflammatory therapy. Nevertheless, EoE is still an enigmatic disease and the long list of unanswered questions will certainly stimulate further research.
Epimorphin Is a Novel Regulator of the Progesterone Receptor Isoform-A
Authors: Jamie L. Bascom, Derek C. Radisky, Eileen Koh, Jimmie E. Fata, Alvin Lo, Hidetoshi Mori, Neda Roosta, Yohei Hirai, Mina J. Bissell
Journal: Cancer Research (2013)

Epimorphin/syntaxin-2 is a membrane-tethered protein localized extracellularly (Epim) and intracellularly (Stx-2). The extracellular form Epim stimulates morphogenic processes in a range of tissues, including in murine mammary glands where its overexpression in luminal epithelial cells is sufficient to drive hyperplasia and neoplasia. We analyzed WAP-Epim transgenic mice to gain insight into how Epim promotes malignancy. Ectopic overexpression of Epim during postnatal mammary gland development led to early side-branching onset, precocious bud formation, and increased proliferation of mammary epithelial cells. Conversely, peptide-based inhibition of Epim function reduced side branching. Because increased side branching and hyperplasia occurs similarly in mice upon overexpression of the progesterone receptor isoform-a (Pgr-a), we investigated whether Epim exhibits these phenotypes through Pgr modulation. Epim overexpression indeed led to a steep upregulation of both total Pgr mRNA and Pgr-a protein levels. Notably, the Pgr antagonist RU486 abrogated Epim-induced ductal side branching, mammary epithelial cell proliferation, and bud formation. Evaluation of Epim signaling in a three-dimensional ex vivo culture system showed that its action was dependent on binding to its extracellular receptor, integrin-αV, and on matrix metalloproteinase 3 activity downstream of Pgr-a. These findings elucidate a hitherto unknown transcriptional regulator of Pgr-a, and shed light on how overexpression of Epim leads to malignancy.
TCT-517 Effects Of Intravenous Human Atrial Natriuretic Peptide On Left Ventricular Function In Patients With Reperfused Acute Myocardial Infarction: An Assessment By Cardiac Magnetic Resonance Imaging
Authors: Takayuki Onishi, Yuko Onishi, Shigeo Umezawa, Isshi Kobayashi, Hirofumi Otani, Keiko Tachibana, Ken Kujiraoka, Hirotaka Muramoto, Yasutoshi Nagata, Akihiro Niwa
Journal: Journal of the American College of Cardiology (2012)
Advancements in the Treatment of Epilepsy
Authors: B.A. Leeman, A.J. Cole
Journal: Annual Review of Medicine (2007)

Diagnostic tools and treatment options for epilepsy have expanded in recent years. Imaging techniques once confined to research laboratories are now routinely used for clinical purposes. Medications that were unavailable a few years ago are now first-line agents. Patients with refractory seizures push for earlier surgical intervention, consider treatment with medical devices, and actively seek nonpharmacologic alternatives. We review some of these recent advances in the management of epilepsy.
Increased nitrotyrosine in exhaled breath condensate in cystic fibrosis
Authors: B. Balint, S.A. Kharitonov, T. Hanazawa, L.E. Donnelly, P.L. Shah, M.E. Hodson, P.J. Barnes
Journal: European Respiratory Journal (2001)

Exhaled nitric oxide (ENO), a marker of inflammation in airway diseases is decreased in cystic fibrosis (CF) patients, perhaps because nitric oxide (NO) is metabolized to oxidative end-products. A stable product, 3-nitrotyrosine, may indicate local formation of reactive nitrogen species. Whether NO metabolites in exhaled breath condensate may be increased in CF patients was investigated. The fractional concentration of ENO ( F eno ), nitrotyrosine and oxides of nitrogen in exhaled breath condensate from 36 stable CF patients were compared to 14 normal subjects using an enzyme immunoassay and fluorescence assay. Nitrotyrosine levels in breath condensate were increased significantly in stable CF patients, compared with normal subjects (25.3±1.5 versus 6.3±0.8 ng·mL −1 , p&lt;0.0001). There was an inverse correlation between the levels of nitrotyrosine and the severity of lung disease. F eno levels were significantly lower in CF patients than in normal subjects (4.4±0.3 versus 5.6±0.4 (parts per billion), p&lt;0.05). No correlation was found between nitrotyrosine and F eno levels in CF. There was no significant difference in the levels of nitrite and nitrate between CF patients and normals. The elevation in nitrotyrosine may reflect increased formation of reactive nitrogen species such as peroxynitrite or direct nitration by granulocyte peroxidases, indicating increased oxidative stress in airways of cystic fibrosis patients.