tbuckley/cabot-search huggingface dataset:
Mast Cells Cause Apoptosis of Cardiomyocytes and Proliferation of Other Intramyocardial Cells In Vitro
Authors: Masatake Hara, Akira Matsumori, Koh Ono, Hiroshi Kido, Myung-Woo Hwang, Tadashi Miyamoto, Atsushi Iwasaki, Masaharu Okada, Kazuki Nakatani, Shigetake Sasayama
Journal: Circulation (1999)

Mast cells are multifunctional cells containing various mediators such as cytokines, proteases, and histamine. They are found in the human heart and have been implicated in ventricular hypertrophy and heart failure. However, their roles in pathogenesis of these diseases are unknown.Cultured cardiomyocytes from neonatal rats were incubated with mast cell granules (MCGs) for 24 hours. The highest concentration of diluted MCGs caused the death of approximately 70% of cardiomyocytes. This cell death was proved to be apoptosis, as quantified by electron microscopy and biochemical criteria. MCG-mediated cytotoxicity was prevented by pretreatment of MCGs with protease inhibitors or a neutralizing antibody against rat mast cell chymase 1 (RMCP 1). RMCP 1 by itself was proved to induce cell death of cardiomyocytes. These results suggest that RMCP 1 contained in MCGs causes the death of cardiomyocytes. In contrast, MCGs induced the proliferation of intramyocardial cells other than myocytes. RMCP 1 was also proved to induce their proliferation.Mast cells cause apoptosis of cardiomyocytes and proliferation of other intramyocardial cells via the activity of RMCP 1. Our results suggest that mast cell chymase may play a role in the progression of heart failure, because loss of cardiomyocytes and proliferation of nonmyocardial cells exaggerate its pathophysiology.
Benign and Malignant Breast Disease: Initial Study Results of Serum and Breast Fluid Analyses of Endogenous Estrogens&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: V L Ernster, M R Wrensch, N L Petrakis, E B King, R Miike, J Murai, W H Goodson, P K Siiteri
Journal: JNCI Journal of the National Cancer Institute (1987)

Design, methods, and study population of a long-term multidisciplinary investigation of benign and malignant breast disease were reported. This initial report focused on the relation of menstrual, reproductive, and other factors to serum and breast fluid estrogen measures [estradiol (E2), estrone (E1), percent free estrogen, and sex hormone binding globulin] among control women. After adjustment for the factors found to be related to the various estrogen measures, estrogen levels in women with benign and malignant disease were compared to those of controls. Findings were as follows: a) little evidence of any relation of most breast cancer risk factors with the various serum estrogen parameters studied; b) differences in breast fluid estrogen levels that may be relevant to the protective effect of parity on breast cancer risk; c) markedly higher levels of E2 and E1 in breast fluid than in serum and no evidence of a correlation of serum with breast fluid measures; d) no support for the hypothesis that breast cancer patients have higher serum percent free E2 than controls or women with benign breast disease; and e) higher breast fluid E2 and E1 levels in women with biopsied benign breast disease than in controls.
A cytotoxic analysis of topical antimicrobials on skin substitutes and autograft
Authors: A. Burd, L. Huang
Journal: British Journal of Dermatology (2008)

Journal Article A cytotoxic analysis of topical antimicrobials on skin substitutes and autograft Get access A. Burd, A. Burd Division of Plastic, Reconstructive and Aesthetic Surgery, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong E‐mail: andrewburd@surgery.cuhk.edu.hk Search for other works by this author on: Oxford Academic Google Scholar L. Huang L. Huang Division of Plastic, Reconstructive and Aesthetic Surgery, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong E‐mail: andrewburd@surgery.cuhk.edu.hk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 158, Issue 4, 1 April 2008, Pages 837–838, https://doi.org/10.1111/j.1365-2133.2007.08398.x Published: 01 April 2008
Role of YKL-40 in Bronchial Smooth Muscle Remodeling in Asthma
Authors: Imane Bara, Annaig Ozier, Pierre-Olivier Girodet, Gabrielle Carvalho, Jennifer Cattiaux, Hugues Begueret, Matthieu Thumerel, Olga Ousova, Roland Kolbeck, Anthony J. Coyle, Joanne Woods, Jose-Manuel Tunon de Lara, Roger Marthan, Patrick Berger
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: Bronchial remodeling, including increased bronchial smooth muscle (BSM) mass, contributes to bronchial obstruction in asthma. However, its mechanisms are complex and remain controversial. Recently, a role of the chitinase 3-like 1 protein (YKL-40) has been evoked in asthma. Indeed, YKL-40 concentration was increased in asthmatic serum, and correlated with asthma severity and subepithelial membrane thickness. Nevertheless, the role of YKL-40 on BSM cells remains to be investigated.Objectives: To evaluate whether YKL-40 altered the physiologic properties of BSM cells in asthma in vitro and ex vivo.Methods: We enrolled 40 subjects with asthma, 13 nonsmokers, and 16 smokers. BSM cells were derived from bronchial specimens obtained by either fiberoptic bronchoscopy or lobectomy. We assessed cell proliferation using BrdU, flow cytometry, and cell count; signaling intermediates using Western blot; cell migration using inserts, wound healing, and phalloidin staining; and cell synthesis using ELISA and Western blot. The involvement of protease activated receptor (PAR)-2 was evaluated using blocking antibody and dedicated lentiviral small hairpin RNA. We also determined the BSM area and the YKL-40 staining ex vivo using immunohistochemistry on biopsies from subjects with asthma and control subjects.Measurements and Main Results: We demonstrated that YKL-40 increased BSM cell proliferation and migration through PAR-2–, AKT-, ERK-, and p38-dependent mechanisms. The increased cell migration was higher in BSM cells of subjects with asthma than that of control subjects. Furthermore, YKL-40 epithelial expression was positively correlated with BSM mass in asthma.Conclusions: This study indicates that YKL-40 promotes BSM cell proliferation and migration through a PAR-2–dependent mechanism.
Regulation and Function of the Interleukin 13 Receptor α 2 During a T Helper Cell Type 2–dominant Immune Response
Authors: Monica G. Chiaramonte, Margaret Mentink-Kane, Bruce A. Jacobson, Allen W. Cheever, Matthew J. Whitters, Mary E.P. Goad, Anthony Wong, Mary Collins, Debra D. Donaldson, Michael J. Grusby, Thomas A. Wynn
Journal: The Journal of Experimental Medicine (2003)

Highly polarized type 2 cytokine responses can be harmful and even lethal to the host if they are too vigorous or persist too long. Therefore, it is important to elucidate the mechanisms that down-regulate these reactions. Interleukin (IL)-13 has emerged as a central mediator of T helper cell (Th)2-dominant immune responses, exhibiting a diverse array of functional activities including regulation of airway hyperreactivity, resistance to nematode parasites, and tissue remodeling and fibrosis. Here, we show that IL-13 receptor (R)alpha2 is a critical down-regulatory factor of IL-13-mediated tissue fibrosis induced by the parasitic helminth Schistosoma mansoni. IL-13Ralpha2 expression was induced after the onset of the fibrotic response, IL-10, IL-13, and Stat6 dependent, and inhibited by the Th1-inducing adjuvant IL-12. Strikingly, schistosome-infected C57BL/6 and BALB/c IL-13Ralpha2-deficient mice showed a marked exacerbation in hepatic fibrosis, despite displaying no change in granuloma size, tissue eosinophilia, or mastocytosis. Fibrosis increased despite the fact that IL-13 levels decreased significantly in the liver and serum. Importantly, pathology was prevented when IL-13Ralpha2-deficient mice were treated with a soluble IL-13Ralpha2-Fc construct, formally demonstrating that their exacerbated fibrotic response was due to heightened IL-13 activity. Together, these studies illustrate the central role played by the IL-13Ralpha2 in the down-regulation of a chronic and pathogenic Th2-mediated immune response.
Multiple Stress Signals Activate Mutant p53 <i>In Vivo</i>
Authors: Young-Ah Suh, Sean M. Post, Ana C. Elizondo-Fraire, Daniela R. Maccio, James G. Jackson, Adel K. El-Naggar, Carolyn Van Pelt, Tamara Terzian, Guillermina Lozano
Journal: Cancer Research (2011)

p53 levels are tightly regulated in normal cells, and thus, the wild-type p53 protein is nearly undetectable until stimulated through a variety of stresses. In response to stress, p53 is released from its negative regulators, mainly murine double minute 2 (Mdm2), allowing p53 to be stabilized to activate cell-cycle arrest, senescence, and apoptosis programs. Many of the upstream signals that regulate wild-type p53 are known; however, limited information for the regulation of mutant p53 exists. Previously, we showed that wild-type and mutant p53R172H are regulated in a similar manner in the absence of Mdm2 or p16. In addition, this stabilization of mutant p53 is responsible for the gain-of-function metastatic phenotype observed in the mouse. In this report, we examined the role of oncogenes, DNA damage, and reactive oxygen species, signals that stabilize wild-type p53, on the stabilization of mutant p53 in vivo and the consequences of this expression on tumor formation and survival. These factors stabilized mutant p53 protein which oftentimes contributed to exacerbated tumor phenotypes. These findings, coupled with the fact that patients carry p53 mutations without stabilization of p53, suggest that personalized therapeutic schemes may be needed for individual patients depending on their p53 status.
β-Adrenergic receptor blockade reduces endoplasmic reticulum stress and normalizes calcium handling in a coronary embolization model of heart failure in canines
Authors: Isaac George, Hani N. Sabbah, Kai Xu, Nan Wang, Jie Wang
Journal: Cardiovascular Research (2011)

Alterations in calcium homeostasis in the endoplasmic/sarcoplasmic reticulum (ER) cause ER stress that ultimately may affect ventricular function. However, the role of ER stress in β-blocker therapy for congestive heart failure (CHF) has not been studied. This study examined ER stress in CHF and evaluated its role in β-blocker therapy in a canine model of ischaemic CHF. CHF was created by daily coronary embolization in chronically instrumented dogs. After oral administration of β-blocker metoprolol or vehicle for 12 weeks, Ca2+ transport proteins including sarcoplasmic reticulum Ca2+-ATPase (SERCA), ryanodine receptor (RyR2), Na+–Ca2+ exchanger (NCX1), Ca2+ storage protein calreticulin (CRT), and phospholamban were evaluated by Western blot analysis. Cellular levels of ER stress marker, phosphorylated eukaryotic initiation factor 2α (eIF2α-P), were also examined. Compared with the vehicle-treated group, metoprolol caused significantly improved cardiac function, restored the proteins of SERCA2a, NCX1, and CRT, increased phosphorylated phospholamban, reversed protein kinase A hyperphosphorylation of RyR2, and resulted in normalized ER stress marker eIF2α-P and reduced DNA damage. Our results suggest that ER stress could be induced by abnormal Ca2+ homeostasis in CHF. The restoration of calcium-handling protein function and resultant decrease in ER stress might, in part, explain the beneficial effects of β-blockade observed in CHF. Whether this mechanism occurs in other animal CHF models or human CHF warrants further study.
Diffuse lung disease caused by cotton fibre inhalation but distinct from byssinosis
Authors: H Kobayashi
Journal: Thorax (2004)

A 66 year old man had inhaled cotton fibre for 50 years at his workplace. He did not have any respiratory symptoms. Chest CT scans revealed diffuse centrilobular and peribronchovascular interstitial thickening. Lung biopsy specimens confirmed the presence of string-like foreign bodies as well as granulomas and fibrosis in the peribronchial region. Infrared spectrophotometry confirmed that the foreign bodies were composed of natural cellulose. This is the first study to show directly by examination of biopsy samples that cotton fibre inhalation can cause diffuse lung disease. The clinical features of the disease were entirely different from those of byssinosis.
Toxin, toxin-coregulated pili, and the toxR regulon are essential for Vibrio cholerae pathogenesis in humans.
Authors: D A Herrington, R H Hall, G Losonsky, J J Mekalanos, R K Taylor, M M Levine
Journal: The Journal of Experimental Medicine (1988)

Isogenic mutant strains of V. cholerae O1 lacking elements of a genetic regulon controlled by toxR and implicated in virulence were tested in volunteers. A deletion mutation in ctxA, the gene encoding the A subunit of cholera toxin, markedly attenuated disease symptoms without affecting intestinal colonization. Deletion of toxR, the gene encoding the cholera toxin-positive regulatory protein resulted in a diminution in colonizing capacity. A deletion mutation in tcpA, encoding the major subunit of the toxin coregulated pilus (regulated by toxR), abolished the colonizing capacity of this strain. These results show for the first time the role of a specific pilus structure in colonization of the human intestine by V. cholerae O1 and exemplify the significance of a genetic regulon in pathogenesis.
A new design of clinical trial – use of nomograms – illustration with local treatment of T2 tumors in the SEER database.
Authors: R Rouzier, B Lesieur, C Coutant, S Uzan
Journal: Cancer Research (2009)

Abstract Abstract #4079 Background: Nomograms are more and more used as models in which known prognostic factors are combined and used to predict individuals outcomes. Their use as pivotal tools for conducting clinical trial without randomizing treatment allocation has never been reported. We sought to investigate if the use of a nomogram could mimic a randomized trial. In this report, we designed a study based on the use of nomograms to investigate the prognosis of patients with tumors measuring 2.1 to 5 cm according to local treatment.&amp;#x2028; Methods: The SEER registry provided data from 17 registries. A survival difference is observed according to surgical treatment (p=0.01) in this database. This difference may account for patient and tumor characteristics leading to the choice of local treatment and not to the local treatment itself. To investigate this hypothesis, we developed a nomogram to predict cause-specific survival in patients with T2 tumors treated with breast conservation therapy (BCT). To provide a more flexible model, we represented continuous variables using restricted cubic splines. We then applied this nomogram to patients treated with mastectomy. In this particular application, a nomogram can provide individual predictions of cause-specific survival taking into account several variables and their interaction. Patients treated with mastectomy were then grouped in deciles and predicted survivals for these subgroups were plotted against observed proportions of patients alive (calibration curve).&amp;#x2028; Results: The study population comprised 128,454 patients. The nomogram for predicting cause-specific survival included number of metastatic nodes, tumor size, age, grade, estrogen receptor status of the tumor, and use of radiation. This nomogram was perfectly well calibrated in an internal validation (bootstrap). In patients treated with mastectomy, the calibration curve was almost perfect with a maximal difference of 0.6% between predicted probabilities and observed proportions (figure). Discrimination was very good (area under the ROC curve = 0.73). This result suggests that the apparent survival difference between T2 patients treated with breast conservation and those treated with mastectomy in the SEER database, is related to tumor characteristics leading to the choice of local treatment and not to the local treatment itself.&amp;#x2028; Conclusion: Nomograms may be useful to test a new treatment or therapeutic strategy without randomization. They can provide theoretical individualized outcome with a reference treatment (taking into account multiple variables, and interaction) for patients receiving an alternative treatment. Any difference between predicted probability and observed proportion reflects that alternative treatment modifies outcome.&amp;#x2028; &amp;#x2028; Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4079.
Heterogenous Nuclear Ribonucleoprotein F Modulates Angiotensinogen Gene Expression in Rat Kidney Proximal Tubular Cells
Authors: Chih-Chang Wei, Deng-Fu Guo, Shao-Ling Zhang, Julie R Ingelfinger, John S D Chan
Journal: Journal of the American Society of Nephrology (2005)

An insulin-responsive element (IRE) in the rat angiotensinogen (ANG) gene promoter that binds to two nuclear proteins with apparent molecular weights of 48 and 70 kD was identified previously from rat immortalized renal proximal tubular cells (IRPTC). The present studies aimed to identify and clone the 48-kD nuclear protein and to define its action on ANG gene expression. Nuclear proteins were isolated from IRPTC and subjected to two-dimensional electrophoresis. The 48-kD nuclear protein was detected by Southwestern blotting and subsequently identified by mass spectrometry, revealing that it was identical to 46-kD heterogeneous nuclear ribonucleoprotein F (hnRNP F), a nuclear protein that binds to TATA-binding protein and associates with RNA polymerase II and also interacts with nuclear cap-binding complex. The hnRNP F cDNA was cloned from IRPTC by reverse transcriptase-PCR. Bacterially expressed recombinant hnRNP F bound to the rat ANG-IRE, as revealed by gel mobility shift assay. The addition of polyclonal antibodies against hnRNP F yielded a supershift in gel mobility. Transient transfer of sense and antisense hnRNP F cDNA in IRPTC inhibited and enhanced ANG gene expression, respectively. High glucose stimulated and insulin inhibited hnRNP F expression in IRPTC. Expression studies indicated that hnRNP F is present in the kidney, testis, liver, lung, and brain but not in the spleen. In conclusion, these studies demonstrate that hnRNP F binds to rANG-IRE and modulates renal ANG gene expression, implicating that dysregulation of hnRNP F might affect renin-angiotensin system activation and, subsequently, kidney injury in diabetes.
Airway smooth muscle: an architect of the lung?
Authors: E C Jesudason
Journal: Thorax (2009)

This review examines the rationale for increased study of the prenatal development of airway smooth muscle (ASM). With a critical role in asthma and airway remodelling, ASM has been extensively investigated. Nevertheless, there is a paucity of studies looking at prenatal ASM development and function. A working party report from the National Heart Lung and Blood Institute identified this issue and has recommended further investigation. The impetus for this call stems not only from an appreciation that childhood and adulthood disease may have their origins in fetal life, but also because recent studies indicate that prenatal ASM regulates lung development (via its phasic contractility and growth factor production). Moreover, recognition that phasic ASM contractility is the prenatal norm has raised interest in the idea that postnatal reactive airways disease may likewise be a periodic oscillatory phenomenon. Finally, bronchial thermoplasty represents an exciting new therapy for refractory asthma. However, the mechanism for its effects is unclear. Recent studies show that prenatal ASM contractility is governed by a hierarchy of pacemakers within proximal airways. If such a pacemaker arrangement persists postnatally, it is possible that bronchial thermoplasty achieves its distal airway effects via ablation of controlling proximal pacemaker centres. Hence, study of prenatal ASM may allow us not only to develop ways to stimulate prenatal lung growth, but also to understand and develop new therapies for reactive airways disease.
Homozygous variegate pophyria: revision of a diagnostic error
Authors: L. D'Alessandro Gandolfo, A. Macri, G. Biolcati, D. Griso, L. N. Phung, J. C. Deybach, V. Da Silva, Y. Nordmann, G. C. Topi
Journal: British Journal of Dermatology (1991)

Journal Article Homozygous variegate pophyria: revision of a diagnostic error Get access L. D'Alessandro Gandolfo, L. D'Alessandro Gandolfo Porphyria Center, Istituto S. Gallicano, Via S. Gallicano 25, 00153 Roma, Italy Search for other works by this author on: Oxford Academic Google Scholar A. Macri, A. Macri Porphyria Center, Istituto S. Gallicano, Via S. Gallicano 25, 00153 Roma, Italy Search for other works by this author on: Oxford Academic Google Scholar G. Biolcati, G. Biolcati Porphyria Center, Istituto S. Gallicano, Via S. Gallicano 25, 00153 Roma, Italy Search for other works by this author on: Oxford Academic Google Scholar D. Griso, D. Griso Porphyria Center, Istituto S. Gallicano, Via S. Gallicano 25, 00153 Roma, Italy Search for other works by this author on: Oxford Academic Google Scholar L. N. Phung, L. N. Phung Center Francais des Porphyries, Hopital Louis Mourier, 178 rue de Renouillers, Colombes Cedex 927012, France Search for other works by this author on: Oxford Academic Google Scholar J. C. Deybach, J. C. Deybach Center Francais des Porphyries, Hopital Louis Mourier, 178 rue de Renouillers, Colombes Cedex 927012, France Search for other works by this author on: Oxford Academic Google Scholar V. Da Silva, V. Da Silva Center Francais des Porphyries, Hopital Louis Mourier, 178 rue de Renouillers, Colombes Cedex 927012, France Search for other works by this author on: Oxford Academic Google Scholar Y. Nordmann, Y. Nordmann Center Francais des Porphyries, Hopital Louis Mourier, 178 rue de Renouillers, Colombes Cedex 927012, France Search for other works by this author on: Oxford Academic Google Scholar G. C. Topi G. C. Topi Porphyria Center, Istituto S. Gallicano, Via S. Gallicano 25, 00153 Roma, Italy Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 124, Issue 2, 1 February 1991, Page 211, https://doi.org/10.1111/j.1365-2133.1991.tb00441.x Published: 01 February 1991
Induction of idiotope suppression in the anti-azophenylarsonate response of T-depleted A/J mice.
Authors: T L Rothstein, R A Miller, D J Parker, E Kelly, A P Vastola, A Marshak-Rothstein
Journal: The Journal of Experimental Medicine (1984)

The homologous, monoclonal antiidiotope, MB, induced idiotope suppression that was remarkably stable and could be transferred by B lymphocytes. Marked depletion of T cell function, confirmed by limiting diluting analysis, did not affect the ability of MB to suppress the corresponding idiotope. Suppression induced by MB appears to result from direct interaction with idiotope-positive B cells, without the intervention of idiotope-specific T suppressor cells.
Increased Risk of Acute Myocardial Infarction and Stroke During Hemorrhagic Fever With Renal Syndrome
Authors: Anne-Marie Connolly-Andersen, Edvin Hammargren, Heather Whitaker, Mats Eliasson, Lars Holmgren, Jonas Klingström, Clas Ahlm
Journal: Circulation (2014)

We recently observed that cardiovascular causes of death are common in patients with hemorrhagic fever with renal syndrome (HFRS), which is caused by hantaviruses. However, it is not known whether HFRS is a risk factor for the acute cardiovascular events of acute myocardial infarction (AMI) and stroke.