tbuckley/cabot-search huggingface dataset:
Effects of immunosuppressive treatment on microsomal prostaglandin E synthase 1 and cyclooxygenases expression in muscle tissue of patients with polymyositis or dermatomyositis
Authors: M Korotkova, S B. Helmers, I Loell, H Alexanderson, C Grundtman, C Dorph, I E Lundberg, P-J Jakobsson
Journal: Annals of the Rheumatic Diseases (2007)

To investigate the expression of microsomal prostaglandin E (PGE) synthase 1 (mPGES-1) and cyclooxygenase (COX) in muscle biopsies from patients with polymyositis or dermatomyositis before and after conventional immunosuppressive treatment.mPGES-1 and COX expression was evaluated by immunohistochemistry in muscle tissue from healthy individuals and from patients with polymyositis or dermatomyositis before and after conventional immunosuppressive treatment. The number of inflammatory cell infiltrates, T lymphocytes and macrophages was estimated before and after treatment. To localise the mPGES-1 expression double immunofluorescence was performed with antibodies against mPGES-1, CD3, CD68, CD163 and a fibroblast marker. A functional index was used to assess muscle function.In patients with myositis, mPGES-1, COX-2 and COX-1 expression was significantly higher compared to healthy individuals and associated with inflammatory cells. Double immunofluorescence demonstrated a predominant expression of mPGES-1 in macrophages. Conventional immunosuppressive treatment resulted in improved but still lower muscle function than normal. A decreased number of CD68-positive macrophages and reduced COX-2 expression in muscle tissue was also seen. By contrast, following the same treatment no significant changes were observed in muscle tissue regarding number of infiltrates, T lymphocytes, CD163-positive macrophages or mPGES-1 protein levels.Increased expression of mPGES-1, COX-1 and COX-2 at protein level was observed in muscle tissue from patients with myositis compared to healthy individuals. Conventional immunosuppressive treatment led to a significant downregulation of COX-2 in myositis muscle tissue. However, the expression of mPGES-1 and COX-1 remained unchanged indicating a role of these enzymes in the chronicity of these diseases.
Systemic and Local Regulation of the Growth Plate
Authors: B. C. J. van der Eerden, M. Karperien, J. M. Wit
Journal: Endocrine Reviews (2003)

The growth plate is the final target organ for longitudinal growth and results from chondrocyte proliferation and differentiation. During the first year of life, longitudinal growth rates are high, followed by a decade of modest longitudinal growth. The age at onset of puberty and the growth rate during the pubertal growth spurt (which occurs under the influence of estrogens and GH) contribute to sex difference in final height between boys and girls. At the end of puberty, growth plates fuse, thereby ceasing longitudinal growth. It has been recognized that receptors for many hormones such as estrogen, GH, and glucocorticoids are present in or on growth plate chondrocytes, suggesting that these hormones may influence processes in the growth plate directly. Moreover, many growth factors, i.e., IGF-I, Indian hedgehog, PTHrP, fibroblast growth factors, bone morphogenetic proteins, and vascular endothelial growth factor, are now considered as crucial regulators of chondrocyte proliferation and differentiation. In this review, we present an update on the present perception of growth plate function and the regulation of chondrocyte proliferation and differentiation by systemic and local regulators of which most are now related to human growth disorders.
Evaluation of a 30-Gene Paclitaxel, Fluorouracil, Doxorubicin, and Cyclophosphamide Chemotherapy Response Predictor in a Multicenter Randomized Trial in Breast Cancer
Authors: Adel Tabchy, Vicente Valero, Tatiana Vidaurre, Ana Lluch, Henry Gomez, Miguel Martin, Yuan Qi, Luis Javier Barajas-Figueroa, Eduardo Souchon, Charles Coutant, Franco D. Doimi, Nuhad K. Ibrahim, Yun Gong, Gabriel N. Hortobagyi, Kenneth R. Hess, W. Fraser Symmans, Lajos Pusztai
Journal: Clinical Cancer Research (2010)

Abstract Purpose: We examined in a prospective, randomized, international clinical trial the performance of a previously defined 30-gene predictor (DLDA-30) of pathologic complete response (pCR) to preoperative weekly paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide (T/FAC) chemotherapy, and assessed if DLDA-30 also predicts increased sensitivity to FAC-only chemotherapy. We compared the pCR rates after T/FAC versus FACx6 preoperative chemotherapy. We also did an exploratory analysis to identify novel candidate genes that differentially predict response in the two treatment arms. Experimental Design: Two hundred and seventy-three patients were randomly assigned to receive either weekly paclitaxel × 12 followed by FAC × 4 (T/FAC, n = 138), or FAC × 6 (n = 135) neoadjuvant chemotherapy. All patients underwent a pretreatment fine-needle aspiration biopsy of the tumor for gene expression profiling and treatment response prediction. Results: The pCR rates were 19% and 9% in the T/FAC and FAC arms, respectively (P &amp;lt; 0.05). In the T/FAC arm, the positive predictive value (PPV) of the genomic predictor was 38% [95% confidence interval (95% CI), 21-56%], the negative predictive value was 88% (95% CI, 77-95%), and the area under the receiver operating characteristic curve (AUC) was 0.711. In the FAC arm, the PPV was 9% (95% CI, 1-29%) and the AUC was 0.584. This suggests that the genomic predictor may have regimen specificity. Its performance was similar to a clinical variable–based predictor nomogram. Conclusions: Gene expression profiling for prospective response prediction was feasible in this international trial. The 30-gene predictor can identify patients with greater than average sensitivity to T/FAC chemotherapy. However, it captured molecular equivalents of clinical phenotype. Next-generation predictive markers will need to be developed separately for different molecular subsets of breast cancers. Clin Cancer Res; 16(21); 5351–61. ©2010 AACR.
Dissociated Spatial Patterning of Gap Junctions and Cell Adhesion Junctions During Postnatal Differentiation of Ventricular Myocardium
Authors: Brigitt D. Angst, Laeeq U.R. Khan, Nicholas J. Severs, Kate Whitely, Stephen Rothery, Robert P. Thompson, Anthony I. Magee, Robert G. Gourdie
Journal: Circulation Research (1997)

Nonuniformity in the spatial patterning of gap junctions between heart muscle cells is now recognized as an important determinant of electromechanical function in working myocardium. Breakdown of the normal geometry of electrical intercellular connectivity in diseased myocardium correlates with reentry, arrhythmia, and conduction disturbance. The developmental mechanism(s) that determines this precise spatial order in gap junction organization in normal myocardium is at present unknown. To examine this question, we have used immunoelectron and immunoconfocal microscopy to analyze the spatial distributions of gap junctional (connexin43), desmosomal (desmoplakin), and adherens junctional (N-cadherin) components during maturation of rodent and canine left ventricular myocardium. In rats, a striking divergence in the distribution of gap junctions and cell adhesion junctions emerged within the first 20 days of postnatal life. It was found that although gap junctions initially demonstrated dispersed distributions across myocyte cell membranes, desmosomes and adherens junctions showed more rapid polarization toward cell termini (ie, nascent intercalated disks) after birth. Over subsequent postnatal development (20 to 90 postnatal days), gap junctions became progressively concentrated in these cell adhesion junction-rich zones of membrane. Quantitative analyses of this process in a series of rats aged 15 embryonic and 1, 5, 10, 20, 40, 70, and 90 postnatal days indicated that significantly higher levels (P < .01) of N-cadherin and desmoplakin than of connexin43 were immunolocalized to cell termini by as early as postnatal day 5. Although all three junctions types showed increasing polarization to myocyte termini with development, variation between junctions remained significant (P < .05) at all times points between 5 and 70 postnatal days. Only at 90 postnatal days, when the animals were nearly full grown, did the proportions of gap junction, desmosome, and adherens junction at intercalated disks become statistically similar (P > .05). Examination of myocardium from 1- and 3-month-old canines revealed that related differential changes to the spatiotemporal distribution of intercellular junctions occurred during postnatal maturation of the dog heart, suggesting that the process was not rodent specific. It is concluded that this progressive change in the organization and pattern of association between gap junctions and cell adhesion junctions is likely to be an important factor in maturation of electromechanical function within the mammalian heart.
Interpreting screw displacement apparent motion as a self-organizing process
Authors: T. D. Frank, A. Daffertshofer, P. J. Beek
Journal: Behavioral and Brain Sciences (2001)

Based on concepts of self-organization, we interpret apparent motion as the result of a so-called non-equilibrium phase transition of the perceptual system with the stimulus-onset asynchrony (SOA) acting as a control parameter. Accordingly, we predict a significantly increasing variance of the quality index of apparent motion close to critical SOAs. [Shepard]
Characteristics and clinical outcome of T1 breast cancer: a multicenter retrospective cohort study
Authors: G. Houvenaeghel, A. Goncalves, J.M. Classe, J.R. Garbay, S. Giard, H. Charytensky, M. Cohen, C. Belichard, C. Faure, S. Uzan, D. Hudry, P. Azuar, R. Villet, P. Gimbergues, C. Tunon de Lara, M. Martino, E. Lambaudie, C. Coutant, F. Dravet, M.P. Chauvet, E. Chéreau Ewald, F. Penault-Llorca, B. Esterni
Journal: Annals of Oncology (2014)
International Union of Basic and Clinical Pharmacology. XCII. Urotensin II, Urotensin II–Related Peptide, and Their Receptor: From Structure to Function
Authors: Hubert Vaudry, Jérôme Leprince, David Chatenet, Alain Fournier, David G. Lambert, Jean-Claude Le Mével, Eliot H. Ohlstein, Adel Schwertani, Hervé Tostivint, David Vaudry
Journal: Pharmacological Reviews (2014)

Urotensin II (UII) is a cyclic neuropeptide that was first isolated from the urophysis of teleost fish on the basis of its ability to contract the hindgut. Subsequently, UII was characterized in tetrapods including humans. Phylogenetic studies and synteny analysis indicate that UII and its paralogous peptide urotensin II-related peptide (URP) belong to the somatostatin/cortistatin superfamily. In mammals, the UII and URP genes are primarily expressed in cholinergic neurons of the brainstem and spinal cord. UII and URP mRNAs are also present in various organs notably in the cardiovascular, renal, and endocrine systems. UII and URP activate a common G protein-coupled receptor, called UT, that exhibits relatively high sequence identity with somatostatin, opioid, and galanin receptors. The UT gene is widely expressed in the central nervous system (CNS) and in peripheral tissues including the retina, heart, vascular bed, lung, kidney, adrenal medulla, and skeletal muscle. Structure-activity relationship studies and NMR conformational analysis have led to the rational design of a number of peptidic and nonpeptidic UT agonists and antagonists. Consistent with the wide distribution of UT, UII has now been shown to exert a large array of biologic activities, in particular in the CNS, the cardiovascular system, and the kidney. Here, we review the current knowledge concerning the pleiotropic actions of UII and discusses the possible use of antagonists for future therapeutic applications.
Role of the Retinoblastoma Pathway in Senescence Triggered by Repression of the Human Papillomavirus E7 Protein in Cervical Carcinoma Cells
Authors: Amanda Psyrri, Rosa Anna DeFilippis, Anne P. B. Edwards, Kristin E. Yates, Laertes Manuelidis, Daniel DiMaio
Journal: Cancer Research (2004)

Abstract Repression of the endogenous human papillomavirus (HPV) type 18 E7 gene in HeLa cervical carcinoma cells by the bovine papillomavirus E2 transcription factor activates the retinoblastoma (Rb) pathway and induces cells to undergo senescence. To determine whether activation of the Rb pathway is responsible for senescence in response to HPV18 E7 repression, we tested the ability of wild-type and mutant E7 proteins to affect the activity of the Rb pathway and to modulate senescence in these cells. Enforced expression of the wild-type HPV16 E7 protein prevented Rb activation in response to E2 expression and impaired senescence. Importantly, there was an absolute correlation between the ability of mutant E7 proteins to inactivate the Rb pathway and to inhibit senescence in HeLa cells. Similar results were obtained in HT-3 cervical carcinoma cells. These results provide strong genetic evidence that activation of the Rb pathway is required for senescence in response to E7 repression. Hence, continuous neutralization of the Rb pathway by the E7 protein is required to maintain the proliferation of cervical carcinoma cells. Similarly, our results indicate that activation of the Rb pathway can prevent apoptosis induced by repression of the HPV18 E6 gene in HeLa cells.
The Mechanism of Appearance of Immunoglobulin A in Nasal Secretions in Man*
Authors: William T. Butler, Roger D. Rossen, Thomas A. Waldmann
Journal: Journal of Clinical Investigation (1967)

Experiments were done to investigate mechanisms of appearance of both 7 S and 11 S IgA in nasal secretions. Three IgA preparations, (a) 11 S IgA from nasal secretions, (b) 7 S IgA from homologous serum, and (c) 7 S IgA from autologous serum, were isolated, labeled, and injected intravenously into volunteers. The rate of disappearance from plasma and the extent and nature of their appearance in nasal secretions were examined in detail. After intravenous injection, 11 S IgA from nasal secretions disappeared rapidly from plasma. However, only negligible amounts of 11 S IgA were detected in nasal secretion, which suggested that rapid selective secretion of circulating 11 S IgA does not occur as a mechanism of IgA accumulation in nasal secretions. Both the homologous and autologous 7 S IgA preparations disappeared from plasma at a normal rate, and both appeared in nasal secretions unchanged in sedimentation behavior. The specific activity of IgA in nasal secretions, when related to the total IgA concentration, was about 30-fold less than that in serum. When related to only the 7 S IgA concentration of nasal secretions, the specific activity was about one-half that of serum. These studies are consistent with the following hypotheses: (a) circulating 7 S IgA is a source of part of the 7 S IgA found in nasal secretions. The remainder of the nasal secretion 7 S IgA may be synthesized locally in the tissues of the upper respiratory tract; (b) 11 S IgA in nasal secretions is not assembled from serum 7 S IgA components; and (c) 11 S IgA in nasal secretions is synthesized de novo in the tissues of the upper respiratory tract.
Theophylline–citric acid co-crystals easily induced by DSC–FTIR microspectroscopy or different storage conditions
Authors: Hong-Liang Lin, Po-Chun Hsu, Shan-Yang Lin
Journal: Asian Journal of Pharmaceutical Sciences (2013)

A simultaneous differential scanning calorimetry–Fourier transform infrared (DSC–FTIR) microspectroscopy was used to quickly investigate the co-crystal formulation between anhydrous theophylline (TP) and anhydrous citric acid (CA) in a one-step procedure. The raw materials of TP and CA, as well as the intact TP–CA co-crystal prepared by slow solvent evaporation were also respectively examined by this approach. The result indicates that the TP–CA co-crystal formulation was easily induced using this DSC–FTIR technique. The thermal-dependent changes in three-dimensional FTIR spectral contour profiles were started from 165 °C to induce the co-crystal formation of TP–CA, which was prior to the endothermic peak at 173 °C found in the conventional DSC curve. Beyond 165 °C, several new IR absorption peaks at 3515, 3124, 1730, 1710, 1677, 1648, 1552 and 1265 cm−1 corresponding to unique IR spectral peaks of intact TP–CA co-crystal were observed. The DSC–FTIR microspectroscopic results also evidenced the dimer–monomer transition of CA, but there were no markedly changes for TP or intact TP–CA co-crystal before its fusion. This strongly implies that the DSC–FTIR technique giving spectroscopic and thermodynamic information could simultaneously induce and identify the TP–CA co-crystal formation and phase transition of samples. Different storage conditions affecting the stability of both physical mixture and ground mixture of TP–CA were also determined. The physical mixture of TP–CA after storing at 55 °C/75% RH condition for one day was fast transformed to TP–CA co-crystal, indicating that TP–CA co-crystal was easily induced under accelerated storage condition. While the co-crystal formed from TP–CA ground mixture was stable in both 25 °C/75% RH and 55 °C/75% RH conditions.
Myocardial blood flow in patients with hibernating myocardium
Authors: P Camici
Journal: Cardiovascular Research (2003)

The debate on whether resting myocardial blood flow (MBF) to hibernating myocardium is reduced or not has attracted a lot of interest and has contributed to stimulate new research on heart failure in patients with coronary artery disease (CAD). Positron emission tomography with oxygen-15 labeled water (H215O) or nitrogen-13 labeled ammonia (13NH3) has been used for the absolute quantification of regional MBF in human hibernating myocardium. When hibernating myocardium is properly identified, i.e. a dysfunctional segment subtended by a stenotic coronary artery that improves function upon reperfusion, the following conclusions can be reached based on the available literature: (a) in the majority of these studies resting MBF in hibernating myocardium is not different from either flow in remote tissue in the same patient or MBF in normal healthy volunteers; (b) a reduction in MBF of ∼20% compared to MBF in remote myocardium or age matched normal subjects has been demonstrated in a minority of truly hibernating segments; (c) hibernating myocardium is characterized by a severely impaired coronary flow reserve which improves after revascularization in parallel with contractile function. Thus, the pathophysiology of hibernation in humans is more complex than initially postulated. The recent evidence that repetitive ischemia in patients with coronary artery disease can be cumulative and lead to more severe and prolonged stunning, lends further support to the hypothesis that, at least initially, stunning and hibernation are two facets of the same coin.
THE EFFECTS OF INTRAVENOUS INJECTIONS OF DICHLOROETHYLSULFIDE IN RABBITS, WITH SPECIAL REFERENCE TO ITS LEUCOTOXIC ACTION
Authors: Alwin M. Pappenheimer, Morgan Vance
Journal: The Journal of Experimental Medicine (1920)

1. The lethal dose of dichloroethylsulfide (distilled from a German yellow cross shell), when injected intravenously into rabbits is from 0.005 to 0.01 gm. per kilo. 2. Rabbits dying within 24 hours showed extensive hemorrhages, and edema of the lungs. 3. Severe lesions of the intestinal tract were present in about one-third of the rabbits. 4. Dichloroethylsulfide injected intravenously is specifically poisonous for the hematopoietic tissues. Severe lesions are caused in the bone marrow, and the number of circulating leucocytes is markedly deminished. In animals surviving the injection regeneration occurs. The granular cells of the bone marrow seem to be more sensitive than the lymphoid cells and the erythrocytes. 5. The effect upon the blood and hematopoietic tissues is not due to the admixture of nitrobenzene or chlorobenzene in the shell filling. Injection of these substances in animals in amounts many times greater than the total dose of dichloroethylsulfide used produced no changes in the blood picture, and the subsequent injection of dichloroethylsulfide free from these solvents produced a typical reaction.
One-Hour Postload Plasma Glucose in Middle Age and Medicare Expenditures in Older Age Among Nondiabetic Men and Women
Authors: Kiang Liu, Alan R. Dyer, Thanh-Huyen Vu, Amber Pirzada, Larry M. Manheim, Willard G. Manning, Muhammad S. Ashraf, Daniel B. Garside, Martha L. Daviglus
Journal: Diabetes Care (2005)

OBJECTIVE—To examine associations in nondiabetic individuals of 1-h postload plasma glucose measured in young adulthood and middle age with subsequent Medicare expenditures for cardiovascular disease (CVD), diabetes, cancer, and all health care at age 65 years or older using data from the Chicago Heart Association Detection Project in Industry (CHA). RESEARCH DESIGN AND METHODS—Medicare data (1984–2000) were linked with CHA baseline records (1967–1973) for 8,580 men and 6,723 women ages 33–64 years who were free of coronary heart disease, diabetes, and major electrocardiogram (ECG) abnormalities and who were Medicare eligible (65+ years) for at least 2 years. Participants were classified based on 1-h postload plasma glucose levels &amp;lt;120, 120–199, or ≥200 mg/dl. RESULTS—With adjustment for baseline age, cigarette smoking, serum cholesterol, systolic blood pressure, BMI, ethnicity, education, and minor ECG abnormalities, the average annual and cumulative Medicare, total, and diabetes- and CVD-related charges were significantly higher with higher baseline plasma glucose in women, while only diabetes-related charges were significantly higher in men. For example, in women, multivariate-adjusted CVD-related cumulative charges were, respectively, $14,260, $18,909, and $21,183 for the three postload plasma glucose categories (P value for trend = 0.035). CONCLUSIONS—These findings suggest that maintaining low glucose levels early in life has the potential to reduce health care costs in older age.
The influence of treatments in daily clinical practice on the Children’s Dermatology Life Quality Index in juvenile psoriasis: a longitudinal study from the Child-CAPTURE patient registry
Authors: A.M. Oostveen, M.E.A. de Jager, P.C.M. van de Kerkhof, A.R.T. Donders, E.M.G.J. de Jong, M.M.B. Seyger
Journal: British Journal of Dermatology (2012)

Background Juvenile psoriasis has a negative effect on the quality of life (QoL). The influence of treatments on QoL of these children has never been investigated before in a prospective observational study. Objectives To assess the Children's Dermatology Life Quality Index (CDLQI) in a cohort of patients with juvenile psoriasis and to evaluate the influence of treatments in daily clinical practice on CDLQI. Methods We conducted a prospective observational study of children with psoriasis from a registry containing daily clinical practice data. Before and after treatment, QoL was assessed by the CDLQI and disease severity was documented by the Psoriasis Area and Severity Index (PASI). Three clusters of treatments were analysed: topical, dithranol and systemic therapy. Results In total, 125 patients were enrolled in the registry. Cross‐sectionally, a mean ± SD CDLQI score of 7·5 ± 5·0 and a mean ± SD PASI of 7·0 ± 5·8 were recorded. Itching and problems with treatment had the highest impact on the children's QoL. Longitudinally, 85 patients were analysed with a total of 137 treatment episodes. All treatments contributed to a significant decline in total CDLQI score, with the largest decrease seen in dithranol and systemic treatments. A significant correlation was found between ΔCDLQI and ΔPASI for all treatment modalities. The highest positive impact of treatments was found in a decline of itch and sleep disturbance. Conclusions In this first prospective observational study on CDLQI in juvenile psoriasis, a positive influence of treatments in daily clinical practice on QoL was demonstrated.