tbuckley/cabot-search huggingface dataset:
Estrogen-Mediated, Endothelial Nitric Oxide Synthase–Dependent Mobilization of Bone Marrow–Derived Endothelial Progenitor Cells Contributes to Reendothelialization After Arterial Injury
Authors: Atsushi Iwakura, Corinne Luedemann, Shubha Shastry, Allison Hanley, Marianne Kearney, Ryuichi Aikawa, Jeffrey M. Isner, Takayuki Asahara, Douglas W. Losordo
Journal: Circulation (2003)

We hypothesized that estrogen-induced acceleration of reendothelialization might be mediated in part by effects involving mobilization and incorporation of bone marrow-derived endothelial progenitor cells (EPCs).Carotid injury was induced in ovariectomized wild-type mice receiving either 17beta-estradiol or placebo. Estradiol treatment significantly accelerated reendothelialization of injured arterial segments within 7 days and resulted in a significant reduction of medial thickness 14 and 21 days after the injury. Significant increases in circulating EPCs 3 days after the injury were observed in the estradiol group compared with placebo-treated mice. These data were further supported by fluorescence-activated cell sorting analysis, which disclosed a significant increase in Sca-1/Flk-1-positive cells in estradiol versus control mice. To evaluate the effects of estradiol on bone marrow-derived EPC incorporation at sites of reendothelialization, carotid injury was established in ovariectomized wild-type mice transplanted with bone marrow from transgenic donors expressing beta-galactosidase transcriptionally regulated by the Tie-2 promoter. Significantly greater numbers of X-gal-positive cells were observed at reendothelialized areas in the estradiol group 3 days after injury as compared with placebo. Fluorescent immunohistochemistry 14 days after the injury documented a marked increase in cells expressing both beta-gal, indicating bone marrow origin and Tie-2 expression, and isolectin B4, also indicating endothelial lineage, in the estradiol group compared with control. In contrast, estradiol did not accelerate reendothelialization or augment EPC mobilization into the peripheral circulation after injury in endothelial nitric oxide synthase-deficient mice (eNOS-/-). Furthermore, estradiol exhibited direct stimulatory effects on EPC mitogenic and migration activity and inhibited EPC apoptosis.Estradiol accelerates reendothelialization and attenuates medial thickening after carotid injury in part by augmenting mobilization and proliferation of bone marrow-derived EPCs and their incorporation into the recovering endothelium at the site of injury.
Close association between interleukin 2 receptor mRNA expression and human T cell leukemia/lymphoma virus type I viral RNA expression in short-term cultured leukemic cells from adult T cell leukemia patients.
Authors: H Umadome, T Uchiyama, T Hori, S Tamori, T Motoi, K Araki, H Uchino
Journal: Journal of Clinical Investigation (1988)

Human T cell leukemia/lymphoma (T-lymphotropic) virus type I (HTLV-I) infection has been considered to be closely associated with the leukemogenesis of adult T cell leukemia (ATL), in which interleukin 2 (IL-2) receptors are abnormally expressed. In this study, however, Southern blot analysis revealed no gross rearrangement or obvious amplification of the IL-2 receptor gene in ATL leukemic cells, indicating that abnormal IL-2 receptor expression in ATL is not due to the structural change of its gene. Hence, we studied the expression of the IL-2 receptor and HTLV-I at the RNA level during short-term cultures of leukemic cells from 9 ATL patients. Cytoplasmic dot hybridization and Northern hybridization revealed that fresh leukemic cells from seven of nine patients expressed a small amount of IL-2 receptor mRNA but HTLV-I RNA was undetectable in all cases. After cultures for up to 7 d, both IL-2 receptor mRNA and HTLV-I RNA (including pX message) expression concomitantly increased, whereas the amounts of other cellular genes, except for beta-actin, did not. The increases in their RNA expression were inhibited by early addition (within 12 h after the beginning of the culture) of cycloheximide, indicating that these increases are mediated by newly synthesized protein(s). These results strongly suggested that IL-2 receptor expression is closely associated with HTLV-I expression in leukemic cells from ATL patients.
AN ANTIVIRAL SUBSTANCE FROM PENICILLIUM FUNICULOSUM
Authors: Richard E. Shope
Journal: The Journal of Experimental Medicine (1966)

Helenine, NDV, and statolon, all known inducers of interferon in mice, all exerted a marked antiviral effect against Semliki Forest virus. This AV effect was, so far as can be demonstrated, mediated through, the induced interferon. The same three materials also exerted a marked antipassive immunity effect. All the evidence that can be brought to bear indicates that this API effect like the AV effect is mediated through interferon known to be induced by the three materials. If the API effect does indeed have interferon as its basis, this represents a new and totally unsuspected action of interferon.
Impact of cane use on pain, function, general health and energy expenditure during gait in patients with knee osteoarthritis: a randomised controlled trial
Authors: A Jones, P G Silva, A C Silva, M Colucci, A Tuffanin, J R Jardim, J Natour
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objective</h3> To assess the impact of daily cane use during gait in relation to pain, function, general health and energy expenditure among patients with knee osteoarthritis. <h3>Method</h3> Sixty-four patients were randomly assigned to an experimental group (EG) or control group (CG). The EG used a cane every day for 2 months, whereas the CG did not use a cane in this period. The first outcome was pain and the second were function (Lequesne and WOMAC), general health (SF-36) and energy expenditure (gas analysis during the 6-minute walk test (6MWT) with and without a cane). Evaluations were performed at baseline, 30 and 60 days. <h3>Results</h3> The groups were homogeneous for all parameters at baseline. Compared with the CG, the EG significantly improved pain (ES 0.18), function - Lequesne (ES 0.13), some domains of SF-36 (role physical, ES 0.07 and bodily pain, ES 0.08) and distance on the 6MWT with the cane (ES 0.16). At the end of the 6MWT with the cane, the EG significantly improved energy expenditure (ES 0.21), carbon dioxide production (ES 0.12) and metabolic equivalents (ES 0.15) compared with the CG. <h3>Conclusion</h3> A cane can be used to diminish pain, improve function and some aspects of quality of life in patients with knee osteoarthritis. The prescription of a cane should take into account the substantial increase in energy expenditure in the first month of use, whereas energy expenditure is no longer a factor for concern by the end of the second month due to adaptation to cane use. The trial was registered in clinicaltrials.gov (NCT00698412).
Lead Contamination in Cocoa and Cocoa Products: Isotopic Evidence of Global Contamination
Authors: Charley W. Rankin, Jerome O. Nriagu, Jugdeep K. Aggarwal, Toyin A. Arowolo, Kola Adebayo, A. Russell Flegal
Journal: Environmental Health Perspectives (2005)

In this article we present lead concentrations and isotopic compositions from analyses of cocoa beans, their shells, and soils from six Nigerian cocoa farms, and analyses of manufactured cocoa and chocolate products. The average lead concentration of cocoa beans was </= 0.5 ng/g, which is one of the lowest reported values for a natural food. In contrast, lead concentrations of manufactured cocoa and chocolate products were as high as 230 and 70 ng/g, respectively, which are consistent with market-basket surveys that have repeatedly listed lead concentrations in chocolate products among the highest reported for all foods. One source of contamination of the finished products is tentatively attributed to atmospheric emissions of leaded gasoline, which is still being used in Nigeria. Because of the high capacity of cocoa bean shells to adsorb lead, contamination from leaded gasoline emissions may occur during the fermentation and sun-drying of unshelled beans at cocoa farms. This mechanism is supported by similarities in lead isotopic compositions of cocoa bean shells from the different farms (206Pb/207Pb = 1.1548-1.1581; 208Pb/207Pb = 2.4344-2.4394) with those of finished cocoa products (206Pb/207Pb = 1.1475-1.1977; 208Pb/207Pb = 2.4234-2.4673). However, the much higher lead concentrations and larger variability in lead isotopic composition of finished cocoa products, which falls within the global range of industrial lead aerosols, indicate that most contamination occurs during shipping and/or processing of the cocoa beans and the manufacture of cocoa and chocolate products.
Mechanism of T-cell help in the immune response to soluble protein antigens II. Reconstitution of primary and secondary in vitro immune responses to dinitrophenyl-carrier conjugates by T-cell-replacing factor.
Authors: T H Hünig, A Schimpl, E Wecker
Journal: The Journal of Experimental Medicine (1977)

Spleen cells of dinitrophenyl keyhole limpet hemocyanin (DNPKLH) primed and boosted mice produced a nonantigen-specific helper factor upon in vitro challenge with DNPKLH. This helper factor displays all of the biological characteristics so far described for TRF produced by allogeneic or Concanavalin A stimulation of mouse spleen cells. It restores the primary anti-SRBC response in nude spleen cultures following the same kinetics of action as T-cell-replacing factor (TRF). Conversely, TRF restores the primary in vitro immune response of nude spleen cultures to DNPKLH. TRF also restores the secondary anti-hapten IgG response of T-cell-deprived spleen cell cultures derived from DNPKLH primed and boosted mice. Here the need for carrier specificity is fully overcome. The data therefore suggest that TRF, as a nonantigen-specific maturation signal, is involved in the primary and secondary immune responses to both particulate and soluble antigens.
The responsiveness of the Shoulder Disability Questionnaire
Authors: D. A W M van der Windt, G. J M G van der Heijden, A. F de Winter, B. W Koes, W. Deville, L. M Bouter
Journal: Annals of the Rheumatic Diseases (1998)

To evaluate the responsiveness of the Shoulder Disability Questionnaire (SDQ).The study was conducted within the framework of an observational study on shoulder disorders in primary care. After first presentation of their complaints to the general practitioner and after one and six months, participants completed the SDQ, a single question on functional status (FSQ), and an ordinal 11 point scale for the severity of pain (PSS). Responsiveness of the SDQ was evaluated compared with that of the FSQ and PSS, by calculating responsiveness ratios and by plotting receiver operating characteristic (ROC) curves. Recovery according to the patient was used as an external criterion for clinically relevant improvement (complete recovery or much improved on a six point Likert scale was denoted as clinically relevant improvement).A total of 349 consecutive patients with shoulder disorders were enrolled in the observational study. Response rates ranged between 96% and 89%. Responsiveness ratios were slightly higher for the PSS compared with the SDQ (2.53 versus 2.22 at one month, 2.24 versus 1.89 at six months). The area under the ROC curve was 0.84 for both the SDQ and the PSS, and 0.72 for the FSQ.The results of this study confirm the responsiveness of the SDQ, making it a useful instrument to assess functional disability in longitudinal studies.
Prevalence, clinico-pathological value, and co-occurrence of PDGFRA abnormalities in diffuse gliomas
Authors: A. Alentorn, Y. Marie, C. Carpentier, B. Boisselier, M. Giry, M. Labussiere, K. Mokhtari, K. Hoang-Xuan, M. Sanson, J.-Y. Delattre, A. Idbaih
Journal: Neuro-Oncology (2012)

PDGFRA is a critical gene in glioma biology. Similar to EGFR, PDGFRA has been shown to be overexpressed, amplified, mutated, or truncated in gliomas, particularly glioblastomas. In addition, PDGFRA has been recently shown to be rearranged in glioblastoma. However, the frequency, cooccurrence, and clinical value of PDGFRA abnormalities in diffuse gliomas remain unclear. We investigated PDGFRA abnormalities and their clinical impact on 619 primary diffuse gliomas, including 167 grade II, 168 grade III, and 284 grade IV gliomas, with use of BAC-aCGH and validated our findings by quantitative polymerase chain reaction (PCR). We studied PDGFRA expression using reverse-transcription quantitative PCR in 84 gliomas and 12 non-tumor samples. In 138 samples, we also screened PDGFRA point mutations in exons 5, 7, 8, 9, 10, 11, and 23; presence of KDR-PDGFRA fusion gene; and PDGFRA truncation. PDGFRA was amplified and gained in 5.2% and 1.9% of samples, respectively. In addition PDGFRA was point-mutated, rearranged, and truncated in 2.9%, 0%, and 0.7% of cases, respectively. PDGFRA point mutations were observed exclusively in grade IV gliomas and in 12.5% of PDGFRA-amplified tumors. High-level PDGFRA amplification was associated with PDGFRA overexpression, high malignancy grade, and older patient age. Of interest, high-level PDGFRA amplification has an independent negative prognostic value for progression-free survival and overall survival among patients with grade III tumors. PDGFRA is altered through various genetic mechanisms in a subset of high-grade gliomas in patients who might be ideal candidates for PDGFRA inhibitor treatment, and PDGFRA gene amplification could be used as a prognostic biomarker in anaplastic gliomas.
Nongenomic β Estrogen Receptors Enhance β1 Adrenergic Signaling Induced by the Nicotine-Derived Carcinogen 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone in Human Small Airway Epithelial Cells
Authors: Mourad Majidi, Hussein A. Al-Wadei, Takashi Takahashi, Hildegard M. Schuller
Journal: Cancer Research (2007)

Abstract Women are at higher risk for the development of lung adenocarcinoma than men; however, the mechanisms responsible for this are poorly understood. In lung adenocarcinoma cells, the estrogen receptor β (ERβ) is the predominating form. We found that 17β-estradiol enhanced proliferation of the putative cells of origin of lung adenocarcinoma, small airway epithelial cells (HPLD1), in response to the nicotine-derived nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Reverse-phase protein microarrays combined with Western blotting revealed that NNK induced phosphorylation of ERβ, an effect that involved stimulation of the adrenergic receptors β1 (β1AR). In transiently transfected cells, β1AR coprecipitated with ERβ, which increased with NNK treatment. ERβ enhanced NNK-induced cyclic AMP accumulation as well as Gαi-mediated mitogen-activated protein kinase/extracellular signal–regulated kinase (ERK) 1/2 activation. Coexpression of β1AR and ERβ activated NNK-mediated ERK1/2 cooperatively. ERβ gene knockdown, as well as coexpression of the dominant negative Ras and Raf, reduced stimulation of ERK1/2 by NNK. Whereas NNK phosphorylated Akt at Thr308 and Ser473, ERβ had no effect on this activity. Luciferase reporter assays showed that, in response to NNK, ERβ stimulated transcription of serum responsive element (SRE) but had a very small effect on the activity of estrogen responsive element (ERE). Together, the phosphorylation of ERβ, the dependence on Gαi proteins, the activation of ERK1/2, and the preferential targeting of SRE over the classic ERE pathway support a role for nongenomic ERβ in the development of smoking-associated lung cancer. This novel cooperation between β1AR and ERβ signaling may contribute to the prominence of lung adenocarcinoma in women. [Cancer Res 2007;67(14):6863–71]
EBV Latent Membrane Protein 1 Up-regulates Hypoxia-Inducible Factor 1α through Siah1-Mediated Down-regulation of Prolyl Hydroxylases 1 and 3 in Nasopharyngeal Epithelial Cells
Authors: Satoru Kondo, So Young Seo, Tomokazu Yoshizaki, Naohiro Wakisaka, Mitsuru Furukawa, Irene Joab, Kyung Lib Jang, Joseph S. Pagano
Journal: Cancer Research (2006)

Abstract Hypoxia-inducible factor 1 (HIF1) is up-regulated in most malignant tumors usually via interruption of ubiquitination and proteasomal degradation of its subunit α. Recently, we have shown that the principal EBV oncoprotein, latent membrane protein 1 (LMP1), activates HIF1α and subsequently expression of HIF1-responsive genes in epithelial cells. Here, we explore the mechanism for HIF1α activation by LMP1 in nasopharyngeal epithelial cells: LMP1 up-regulates the level of Siah1 E3 ubiquitin ligase by enhancing its stability, which subsequently induces proteasomal degradation of prolyl HIF-hydroxylases 1 and 3 that normally mark HIF1α for degradation. As a result, LMP1 prevents formation of von Hippel-Lindau/HIF1α complex, as shown by coimmunoprecipitation analyses. Thus, Siah1 is implicated in the regulation of HIF1α and is involved in a recently appreciated aspect of EBV-mediated tumorigenesis, namely, the angiogenesis process triggered by LMP1. (Cancer Res 2006; 66(20): 9870-7)
The Role of the Vascular Endothelial Growth Factor–Delta-like 4 Ligand/Notch4-Ephrin B2 Cascade in Tumor Vessel Remodeling and Endothelial Cell Functions
Authors: Patricia Hainaud, Jean-Olivier Contrerès, Aude Villemain, Lang-Xia Liu, Jean Plouët, Gérard Tobelem, Evelyne Dupuy
Journal: Cancer Research (2006)

Abstract Vascular endothelial growth factor (VEGF) and Delta-like 4 ligand (DLL4) are the only genes whose haploinsufficiency results in vascular abnormalities. Although many common pathways are up-regulated in both vascular development and tumor angiogenesis and in vascular remodeling, the role of the Delta/Notch pathway has not been clearly defined in tumor angiogenesis. In this study, we assessed the expression of DLL4, Notch4, and ephrin B2 in transgenic mice developing hepatocarcinoma characterized by a strong remodeling of the tumor sinusoids. We also investigated the role of VEGF in the expression and biological functions of these molecules on human venous endothelial cells. In transgenic livers, we showed that DLL4, active Notch4, and ephrin B2 were gradually up-regulated within the hepatocarcinoma progression and expressed on tumor sinusoidal endothelial cells. In venous endothelial cells, we showed that VEGF up-regulates DLL4 and presenilin, and increased the activation of Notch4, leading to an up-regulation of ephrin B2 with a down-regulation of Eph B4. We also showed that the activation of Notch4 is required for VEGF-induced up-regulation of ephrin B2 and the differentiation of human venous endothelial cells in vitro. Accordingly, the disruption of Notch4 signaling by pharmacologic inhibition of presenilin or addition of soluble DLL4 inhibited the effect of VEGF on human venous endothelial cell migration and differentiation. Our study strongly suggests that a coordinated activation of DDL4/Notch4 and ephrin B2 pathways downstream of VEGF plays a key role in the abnormal remodeling of tumor vessels. (Cancer Res 2006; 66(17): 8501-10)
Treatment of homosexuality during apartheid
Authors: Robert M Kaplan
Journal: BMJ (2004)

the self. 10The investigation of out of body experiences and related mechanisms at the temporo-parietal junction might thus allow us to improve our neuroscientific models of self and corporeal awareness.Although many other cortical areas are involved in self processing, recent neuroimaging studies indicate a key role for the temporo-parietal junction.This is not only true for out of body experiences but also for many aspects of body and self processing, such as the integration of multisensory bodily information, the visual perception of the body, the perception of biological motion, and the distinction between self and other. 3 11 12 The experimental investigations of these multisensory and cognitive mechanisms in out of body experiences and related illusions, in combination with neuroimaging and behavioural techniques, will further our understanding of the central mechanisms of self and corporeal awareness-much as previous research was successful with respect to understanding the central mechanisms of phantom limbs. 9
An optical and microPET assessment of thermally-sensitive liposome biodistribution in the Met-1 tumor model: Importance of formulation
Authors: E.E. Paoli, D.E. Kruse, J.W. Seo, H. Zhang, A. Kheirolomoom, K.D. Watson, P. Chiu, H. Stahlberg, K.W. Ferrara
Journal: Journal of Controlled Release (2009)
Rituximab Targets Podocytes in Recurrent Focal Segmental Glomerulosclerosis
Authors: Alessia Fornoni, Junichiro Sageshima, Changli Wei, Sandra Merscher-Gomez, Robier Aguillon-Prada, Alexandra N. Jauregui, Jing Li, Adela Mattiazzi, Gaetano Ciancio, Linda Chen, Gaston Zilleruelo, Carolyn Abitbol, Jayanthi Chandar, Wacheree Seeherunvong, Camillo Ricordi, Masami Ikehata, Maria Pia Rastaldi, Jochen Reiser, George W. Burke
Journal: Science Translational Medicine (2011)

Rituximab treatment in high-risk patients with focal segmental glomerulosclerosis directly affects podocyte function and is linked to reduced incidence of recurrent proteinuria after kidney transplantation.
Chronic disease care
Authors: E. H Wagner
Journal: BMJ (2004)

Chronic disease careInsights from managed care in the United States will help the NHS T wo papers in this issue of BMJ examine developments in the management of chronic illness in the United States and explore their potential relevance to recent NHS initiatives and policies. 1 2A new King's Fund study of the care of chronically ill people in five leading US managed care organisations, summarised in the paper by Dixon et al (p 220), provides several observations and insights of relevance to new NHS initiatives targeting care of chronic illness. 1 The authors conclude that the success of these organisations relates to five factors, which serve as the basis for their recommendations for NHS action.With some minor exceptions, I believe that their observations and recommendations are on target and worthy of serious consideration by policy makers in the United Kingdom.
A novel pathogenic role of the ER chaperone GRP78/BiP in rheumatoid arthritis
Authors: Seung-Ah Yoo, Sungyong You, Hyung-Ju Yoon, Dong-Ho Kim, Hyun-Sook Kim, Kyungho Lee, Jin Hee Ahn, Daehee Hwang, Amy S. Lee, Ki-Jo Kim, Yune-Jung Park, Chul-Soo Cho, Wan-Uk Kim
Journal: The Journal of Experimental Medicine (2012)

An accumulation of misfolded proteins can trigger a cellular survival response in the endoplasmic reticulum (ER). In this study, we found that ER stress–associated gene signatures were highly expressed in rheumatoid arthritis (RA) synoviums and synovial cells. Proinflammatory cytokines, such as TNF and IL-1β, increased the expression of GRP78/BiP, a representative ER chaperone, in RA synoviocytes. RA synoviocytes expressed higher levels of GRP78 than osteoarthritis (OA) synoviocytes when stimulated by thapsigargin or proinflammatory cytokines. Down-regulation of Grp78 transcripts increased the apoptosis of RA synoviocytes while abolishing TNF- or TGF-β–induced synoviocyte proliferation and cyclin D1 up-regulation. Conversely, overexpression of the Grp78 gene prevented synoviocyte apoptosis. Moreover, Grp78 small interfering RNA inhibited VEGF165-induced angiogenesis in vitro and also significantly impeded synoviocyte proliferation and angiogenesis in Matrigel implants engrafted into immunodeficient mice. Additionally, repeated intraarticular injections of BiP-inducible factor X, a selective GRP78 inducer, increased synoviocyte proliferation and angiogenesis in the joints of mice with experimental OA. In contrast, mice with Grp78 haploinsufficiency exhibited the suppression of experimentally induced arthritis and developed a limited degree of synovial proliferation and angiogenesis. In summary, this study shows that the ER chaperone GRP78 is crucial for synoviocyte proliferation and angiogenesis, the pathological hallmark of RA.