tbuckley/cabot-search huggingface dataset:
Endomucin, a CD34-like sialomucin, marks hematopoietic stem cells throughout development
Authors: Azusa Matsubara, Atsushi Iwama, Satoshi Yamazaki, Chie Furuta, Ryutaro Hirasawa, Yohei Morita, Mitsujiro Osawa, Tsutomu Motohashi, Koji Eto, Hideo Ema, Toshio Kitamura, Dietmar Vestweber, Hiromitsu Nakauchi
Journal: The Journal of Experimental Medicine (2005)

To detect as yet unidentified cell-surface molecules specific to hematopoietic stem cells (HSCs), a modified signal sequence trap was successfully applied to mouse bone marrow (BM) CD34−c-Kit+Sca-1+Lin− (CD34−KSL) HSCs. One of the identified molecules, Endomucin, is an endothelial sialomucin closely related to CD34. High-level expression of Endomucin was confined to the BM KSL HSCs and progenitor cells, and, importantly, long-term repopulating (LTR)–HSCs were exclusively present in the Endomucin+CD34−KSL population. Notably, in the yolk sac, Endomucin expression separated multipotential hematopoietic cells from committed erythroid progenitors in the cell fraction positive for CD41, an early embryonic hematopoietic marker. Furthermore, developing HSCs in the intraembryonic aorta-gonad-mesonephros (AGM) region were highly enriched in the CD45−CD41+Endomucin+ fraction at day 10.5 of gestation (E10.5) and in the CD45+CD41+Endomucin+ fraction at E11.5. Detailed analyses of these fractions uncovered drastic changes in their BM repopulating capacities as well as in vitro cytokine responsiveness within this narrow time frame. Our findings establish Endomucin as a novel cell-surface marker for LTR-HSCs throughout development and provide a powerful tool in understanding HSC ontogeny.
The Problem of a Psychosomatic Theory and the Mind-body-unity Model
Authors: Th. von Uexküll
Journal: Psychotherapy and Psychosomatics (1970)

A critical review of the premises of dualistic thinking–which still forms the base of most existing psychosomatic models–will lead to the insight that a new beginning has to be sought. Psychosomatic theory ought to start from the mind-body-unit, and not to try to construct it. The concept of body-image presents a possibility to develop models which could answer this requirement.
Generation of gaseous sulfur-containing compounds in tumour tissue and suppression of gas diffusion as an antitumour treatment
Authors: Kazue Yamagishi, Kazuo Onuma, Yota Chiba, Shinya Yagi, Shigenobu Aoki, Tomoyuki Sato, Yasushi Sugawara, Noriyasu Hosoya, Yasutake Saeki, Minoru Takahashi, Masayoshi Fuji, Takeo Ohsaka, Takeyoshi Okajima, Kenji Akita, Takashi Suzuki, Pisol Senawongse, Akio Urushiyama, Kiyoshi Kawai, Hirofumi Shoun, Yoshimasa Ishii, Hiroya Ishikawa, Shigeru Sugiyama, Madoka Nakajima, Masaru Tsuboi, Tateo Yamanaka
Journal: Gut (2011)

The mechanisms of cancer cell growth and metastasis are still not entirely understood, especially from the viewpoint of chemical reactions in tumours. Glycolytic metabolism is markedly accelerated in cancer cells, causing the accumulation of glucose (a reducing sugar) and methionine (an amino acid), which can non-enzymatically react and form carcinogenic substances. There is speculation that this reaction produces gaseous sulfur-containing compounds in tumour tissue. The aims of this study were to clarify the products in tumour and to investigate their effect on tumour proliferation.Products formed in the reaction between glucose and methionine or its metabolites were analysed in vitro using gas chromatography. Flatus samples from patients with colon cancer and exhaled air samples from patients with lung cancer were analysed using near-edge x-ray fine adsorption structure spectroscopy and compared with those from healthy individuals. The tumour proliferation rates of mice into which HT29 human colon cancer cells had been implanted were compared with those of mice in which the cancer cells were surrounded by sodium hyaluronate gel to prevent diffusion of gaseous material into the healthy cells.Gaseous sulfur-containing compounds such as methanethiol and hydrogen sulfide were produced when glucose was allowed to react with methionine or its metabolites homocysteine or cysteine. Near-edge x-ray fine adsorption structure spectroscopy showed that the concentrations of sulfur-containing compounds in the samples of flatus from patients with colon cancer and in the samples of exhaled air from patients with lung cancer were significantly higher than in those from healthy individuals. Animal experiments showed that preventing the diffusion of sulfur-containing compounds had a pronounced antitumour effect.Gaseous sulfur-containing compounds are the main products in tumours and preventing the diffusion of these compounds reduces the tumour proliferation rate, which suggests the possibility of a new approach to cancer treatment.
Protective Role of Endogenous Erythropoietin System in Nonhematopoietic Cells Against Pressure Overload–Induced Left Ventricular Dysfunction in Mice
Authors: Yasuhide Asaumi, Yutaka Kagaya, Morihiko Takeda, Nobuhiro Yamaguchi, Hiroko Tada, Kenta Ito, Jun Ohta, Takashi Shiroto, Kunio Shirato, Naoko Minegishi, Hiroaki Shimokawa
Journal: Circulation (2007)

Background— Erythropoietin (Epo) receptors (EpoRs) are expressed in the heart. We have recently demonstrated that the endogenous Epo-EpoR system plays an important protective role in myocardial ischemia in mice and humans. In the present study, we tested our hypothesis that the endogenous Epo-EpoR system in nonhematopoietic cells also plays a protective role against pressure overload–induced cardiac dysfunction in vivo. Methods and Results— Transgene-rescued EpoR-null mutant mice ( EpoR −/− rescued ) that express EpoR exclusively in the hematopoietic cells were subjected to transverse aortic constriction (TAC). At 1 week after TAC, left ventricular weight and lung weight were significantly increased in EpoR −/− rescued mice compared with wild-type mice, although the fibrotic area was comparably increased after TAC in the 2 genotypes. In the EpoR −/− rescued mice with TAC, left ventricular end-diastolic diameter was significantly increased, left ventricular fractional shortening was significantly decreased, and survival rate was significantly decreased compared with wild-type mice with TAC. Phosphorylation of STAT3 at 5 hours and 1 week after TAC and that of p38 at 5 hours after TAC were significantly increased in wild-type mice but not in EpoR −/− rescued mice. Vascular endothelial growth factor protein expression and capillary density in left ventricular myocardium were significantly decreased in EpoR −/− rescued mice with TAC compared with wild-type mice with TAC. Conclusions— These results suggest that the endogenous Epo-EpoR system in the nonhematopoietic cells plays an important protective role against pressure overload–induced cardiac dysfunction in vivo.
Towards Effective and Safe Thrombolysis and Thromboprophylaxis
Authors: Xiaowei Wang, Jathushan Palasubramaniam, Yannik Gkanatsas, Jan David Hohmann, Erik Westein, Ruchi Kanojia, Karen Alt, Dexing Huang, Fu Jia, Ingo Ahrens, Robert L. Medcalf, Karlheinz Peter, Christoph E. Hagemeyer
Journal: Circulation Research (2014)

Rationale: Fibrinolysis is a valuable alternative for the treatment of myocardial infarction when percutaneous coronary intervention is not available in a timely fashion. For acute ischemic stroke, fibrinolysis is the only treatment option with a very narrow therapeutic window. Clinically approved thrombolytics have significant drawbacks, including bleeding complications. Thus their use is highly restricted, leaving many patients untreated. Objective: We developed a novel targeted fibrinolytic drug that is directed against activated platelets. Methods and Results: We fused single-chain urokinase plasminogen activator (scuPA) to a small recombinant antibody (scFv SCE5 ), which targets the activated form of the platelet–integrin glycoprotein IIb/IIIa. Antibody binding and scuPA activity of this recombinant fusion protein were on par with the parent molecules. Prophylactic in vivo administration of scFv SCE5 –scuPA (75 U/g body weight) prevented carotid artery occlusion after ferric chloride injury in a plasminogen-dependent process compared with saline ( P &lt;0.001), and blood flow recovery was similar to high-dose nontargeted urokinase (500 U/g body weight). Tail bleeding time was significantly prolonged with this high dose of nontargeted urokinase, but not with equally effective targeted scFv SCE5 –scuPA at 75 U/g body weight. Real-time in vivo molecular ultrasound imaging demonstrates significant therapeutic reduction of thrombus size after administration of 75 U/g body weight scFv SCE5 –scuPA as compared with the same dose of a mutated, nontargeting scFv–scuPA or vehicle. The ability of scFv SCE5 –scuPA to lyse thrombi was lost in plasminogen-deficient mice, but could be restored by intravenous injection of plasminogen. Conclusions: Targeting of scuPA to activated glycoprotein IIb/IIIa allows effective thrombolysis and the potential novel use as a fibrinolytic agent for thromboprophylaxis without bleeding complications.
On the demystification of mental imagery
Authors: Stephen M. Kosslyn, Steven Pinker, George E. Smith, Steven P. Shwartz
Journal: Behavioral and Brain Sciences (1979)

Abstract What might a theory of mental imagery look like, and how might one begin formulating such a theory? These are the central questions addressed in the present paper. The first section outlines the general research direction taken here and provides an overview of the empirical foundations of our theory of image representation and processing. Four issues are considered in succession, and the relevant results of experiments are presented and discussed. The second section begins with a discussion of the proper form for a cognitive theory, and the distinction between a theory and a model is developed. Following this, the present theory and computer simulation model are introduced. This theory specifies the nature of the internal representations (data structures) and the processes that operate on them when one generates, inspects, or transforms mental images. In the third, concluding, section we consider three very different kinds of objections to the present research program, one hinging on the possibility of experimental artifacts in the data, and the others turning on metatheoretical commitments about the form of a cognitive theory. Finally, we discuss how one ought best to evaluate theories and models of the sort developed here.
Antitumoral actions of the anti-obesity drug orlistat (Xenical™) in breast cancer cells: blockade of cell cycle progression, promotion of apoptotic cell death and PEA3-mediated transcriptional repression of Her2/neu (erbB-2) oncogene
Authors: J.A. Menendez, L. Vellon, R. Lupu
Journal: Annals of Oncology (2005)
Mesenchymal Stromal Cells Expressing ErbB-2/<i>neu</i> Elicit Protective Antibreast Tumor Immunity <i>In vivo</i>, Which Is Paradoxically Suppressed by IFN-γ and Tumor Necrosis Factor-α Priming
Authors: Raphaëlle Romieu-Mourez, Moïra François, Amanda Abate, Marie-Noëlle Boivin, Elena Birman, Dana Bailey, Jonathan L. Bramson, Kathy Forner, Yoon-Kow Young, Jeffrey A. Medin, Jacques Galipeau
Journal: Cancer Research (2010)

It is unknown whether mesenchymal stromal cells (MSC) can regulate immune responses targeting tumor autoantigens of low immunogenicity. We tested here whether immunization with MSC could break immune tolerance towards the ErbB-2/HER-2/neu tumor antigen and the effects of priming with IFN-γ and tumor necrosis factor-α (TNF-α) on this process. BALB/c- and C57BL/6-derived MSC were lentivirally transduced to express a kinase-inactive rat neu mutant (MSC/Neu). Immunization of BALB/c mice with nontreated or IFN-γ-primed allogeneic or syngeneic MSC/Neu induced similar levels of anti-neu antibody titers; however, only syngeneic MSC/Neu induced protective neu-specific CD8(+) T cell responses. Compared to immunization with nontreated or IFN-γ-primed syngeneic MSC/Neu, the number of circulating neu-specific CD8(+) T cells and titers of anti-neu antibodies were observed to be decreased after immunizations with IFN-γ- plus TNF-α-primed MSC/Neu. In addition, syngeneic MSC/Neu seemed more efficient than IFN-γ-primed MSC/Neu at inducing a protective therapeutic antitumor immune response resulting in the regression of transplanted neu-expressing mammary tumor cells. In vitro antigen-presenting cell assays performed with paraformaldehyde-fixed or live MSC showed that priming with IFN-γ plus TNF-α, compared to priming with IFN-γ alone, increased antigen presentation as well as the production of immunosuppressive factors. These data suggest that whereas MSC could effectively serve as antigen-presenting cells to induce immune responses aimed at tumor autoantigens, these functions are critically regulated by IFN-γ and TNF-α.
Reprogramming of Skeletal Myoblasts for Induction of Pluripotency for Tumor-Free Cardiomyogenesis in the Infarcted Heart
Authors: Rafeeq P.H. Ahmed, Husnain K. Haider, Stephanie Buccini, Longhu Li, Shujia Jiang, Muhammad Ashraf
Journal: Circulation Research (2011)

Skeletal myoblasts (SMs) with inherent myogenic properties are better candidates for reprogramming to pluripotency.To reprogram SMs to pluripotency and show that reprogrammed SMs (SiPS) express embryonic gene and microRNA profiles and that transplantation of predifferentiated cardiac progenitors reduce tumor formation.The pMXs vector containing mouse cDNAs for Yamanaka's quartet of stemness factors were used for transduction of SMs purified from male Oct4-GFP(+) transgenic mouse. Three weeks later, GFP(+) colonies of SiPS were isolated and propagated in vitro. SiPS were positive for alkaline phosphatase, expressed SSEA1, and displayed a panel of embryonic stem (ES) cell-specific pluripotency markers. Embryoid body formation yielded beating cardiomyocyte-like cells, which expressed early and late cardiac-specific markers. SiPS also had an microRNA profile that was altered during their cardiomyogenic differentiation. Noticeable abrogation of let-7 family and significant up-regulation of miR-200a-c was observed in SiPS and SiPS-derived cardiomyocytes, respectively. In vivo studies in an experimental model of acute myocardial infarction showed extensive survival of SiPS and SiPS-derived cardiomyocytes in mouse heart after transplantation. Our results from 4-week studies in DMEM without cells (group 1), SMs (group-2), SiPS (group-3), and SiPS-derived cardiomyocytes (group 4) showed extensive myogenic integration of the transplanted cells in group 4 with attenuated infarct size and improved cardiac function without tumorgenesis.Successful reprogramming was achieved in SMs with ES cell-like microRNA profile. Given the tumorgenic nature of SiPS, their predifferentiation into cardiomyocytes would be important for tumor-free cardiogenesis in the heart.
Human acute stem cell leukemia with multilineage differentiation potential via cascade activation of growth factor receptors
Authors: Ugo Testa, Giovanni F. Torelli, Roberta Riccioni, Andrea Onetti Muta, Stefania Militi, Luciana Annino, Gualtiero Mariani, Anna Guarini, Sabina Chiaretti, Jerome Ritz, Franco Mandelli, Cesare Peschle, Robin Foa
Journal: Blood (2002)
CD3+ cells at the invasive margin of deeply invading (pT3–T4) colorectal cancer and risk of post-surgical metastasis: a longitudinal study
Authors: Luigi Laghi, Paolo Bianchi, Elena Miranda, Emanuela Balladore, Veronica Pacetti, Fabio Grizzi, Paola Allavena, Valter Torri, Alessandro Repici, Armando Santoro, Alberto Mantovani, Massimo Roncalli, Alberto Malesci
Journal: The Lancet Oncology (2009)
Prostaglandin I<sub>2</sub>Signaling and Inhibition of Group 2 Innate Lymphoid Cell Responses
Authors: Weisong Zhou, Shinji Toki, Jian Zhang, Kasia Goleniewksa, Dawn C. Newcomb, Jacqueline Y. Cephus, Daniel E. Dulek, Melissa H. Bloodworth, Matthew T. Stier, Vasiliy Polosuhkin, Rama D. Gangula, Simon A. Mallal, David H. Broide, R. Stokes Peebles
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Group 2 innate lymphoid cells (ILC2s) robustly produce IL-5 and IL-13, cytokines central to the asthma phenotype; however, the effect of prostaglandin (PG) I2 on ILC2 function is unknown.To determine the effect of PGI2 on mouse and human ILC2 cytokine expression in vitro and the effect of endogenous PGI2 and the PGI2 analog cicaprost on lung ILC2s in vivo.Flow-sorted bone marrow ILC2s of wild-type (WT) and PGI2 receptor-deficient (IP(-/-)) mice were cultured with IL-33 and treated with the PGI2 analog cicaprost. WT and IP(-/-) mice were challenged intranasally with Alternaria alternata extract for 4 consecutive days to induce ILC2 responses, and these were quantified. Prior to A. alternata extract, challenged WT mice were treated with cicaprost. Human flow-sorted peripheral blood ILC2s were cultured with IL-33 and IL-2 and treated with the PGI2 analog cicaprost.We demonstrate that PGI2 inhibits IL-5 and IL-13 protein expression by IL-33-stimulated ILC2s purified from mouse bone marrow in a manner that was dependent on signaling through the PGI2 receptor IP. In a mouse model of 4 consecutive days of airway challenge with an extract of A. alternata, a fungal aeroallergen associated with severe asthma exacerbations, endogenous PGI2 signaling significantly inhibited lung IL-5 and IL-13 protein expression, and reduced the number of lung IL-5- and IL-13-expressing ILC2s, as well as the mean fluorescence intensity of IL-5 and IL-13 staining. In addition, exogenous administration of a PGI2 analog inhibited Alternaria extract-induced lung IL-5 and IL-13 protein expression, and reduced the number of lung IL-5- and IL-13-expressing ILC2s and the mean fluorescence intensity of IL-5 and IL-13 staining. Finally, a PGI2 analog inhibited IL-5 and IL-13 expression by human ILC2s that were stimulated with IL-2 and IL-33.These results suggest that PGI2 may be a potential therapy to reduce the ILC2 response to protease-containing aeroallergens, such as Alternaria.
Humoral immune response against minor collagens type IX and XI in patients with cartilage graft resorption after reconstructive surgery.
Authors: J Bujia, S Alsalameh, A Naumann, E Wilmes, M Sittinger, G R Burmester
Journal: Annals of the Rheumatic Diseases (1994)

OBJECTIVES--The humoral immune response against a broad spectrum of cartilage antigens (cellular and matrix antigens) was studied in a group of patients who showed resorption and/or rejection of transplanted cartilage in nasal surgery. METHODS--Sera were obtained from patients with successful and unsuccessful cartilage grafting in the nose, from age and sex-matched healthy donors and from patients with rheumatoid arthritis. Antibodies to cartilage components were analysed by the following methods: (1) indirect immunofluorescence on cartilage sections, (2) ELISA using cultured human chondrocytes, isolated chondrocyte membranes and purified collagens type I, II, III, VI, IX and XI, and (3) immunoblotting with purified collagens and chondrocyte cell membranes. RESULTS--In the cartilage grafting group showing resorption problems, levels of anti-collagen antibodies were significantly higher against native collagen types IX (p &lt; 0.002) and XI (p &lt; 0.002) compared with the non-resorption group and the normal donors. Both transplantation groups revealed elevated reactivities against isolated chondrocytes in the ELISA. In contrast, no reactivity was detectable against collagens type II, III, and VI and chondrocyte cell membranes by both ELISA and immunoblotting. CONCLUSIONS--These data demonstrate for the first time the existence of a humoral immune response, primarily directed against the so called 9minor cartilage collagens9, in patients showing cartilage resorption. Autoreactivities to collagen which are typical of inflammatory rheumatic diseases may also play an important role in the repeated failure of cartilage grafting.
On is an ought: Levels of analysis and the descriptive versus normative analysis of human reasoning
Authors: Walter Schroyens
Journal: Behavioral and Brain Sciences (2009)

Abstract Algorithmic-level specifications carry part of the explanatory burden in most psychological theories. It is, thus, inappropriate to limit a comparison and evaluation of theories to the computational level. A rational analysis considers people's goal-directed and environmentally adaptive rationality; it is not normative. Adaptive rationality is by definition non-absolute; hence, neither deductive logic nor Bayesian probability theory has absolute normative status.
Inflammatory features of nasal mucosa in smokers with and without COPD
Authors: I Vachier
Journal: Thorax (2004)

To investigate whether nasal and bronchial inflammation coexists in chronic obstructive pulmonary disease (COPD), nasal and bronchial biopsy specimens from seven control subjects, seven smokers without COPD, and 14 smokers with COPD were studied.Nasal and bronchial biopsy specimens were taken from the same patients during bronchoscopy and squamous cell metaplasia and the thickness of the epithelium and basement membrane were measured. The numbers of eosinophils (EG2), neutrophils (elastase), macrophages (CD68), and CD8 T lymphocytes (CD8/144B) were assessed by immunohistochemistry.Smokers with and without COPD had squamous metaplasia in the nasal and bronchial epithelium. In all groups the thickness of the nasal epithelium was greater than that of the bronchial epithelium. The thickness of the basement membrane was similar in nasal and bronchial biopsy specimens from smokers with and without COPD, but was greater in the bronchi than in the nasal epithelium of controls. Eosinophil number was higher in the nasal and bronchial mucosa of smokers without COPD than in smokers with COPD or controls. Neutrophil number was higher in the nasal and bronchial mucosa of smokers with COPD than in smokers without COPD or controls. CD8 T lymphocyte numbers were similar in smokers with and without COPD and higher than in controls. There were fewer macrophages in nasal and bronchial biopsy specimens from smokers without COPD than in those with COPD.Nasal and bronchial inflammation coexists in smokers and is characterised by infiltration of CD8 T lymphocytes. In smokers without COPD this feature is associated with an increased number of eosinophils, while in those with COPD it is linked to an increased number of neutrophils in both nasal and bronchial biopsy specimens.