tbuckley/cabot-search huggingface dataset:
Prevention of amputation caused by rheumatic diseases following a novel therapy of exposing bone marrow, occlusive dressing and subsequent epidermal grafting
Authors: Y. Yamaguchi, Y. Sumikawa, S. Yoshida, T. Kubo, K. Yoshikawa, S. Itami
Journal: British Journal of Dermatology (2005)

Journal Article Prevention of amputation caused by rheumatic diseases following a novel therapy of exposing bone marrow, occlusive dressing and subsequent epidermal grafting Get access Y. Yamaguchi, Y. Yamaguchi Department of Dermatology, Graduate School of Medicine Osaka University, 2‐2 Yamada‐oka, Suita‐shi, Osaka 565‐0871, Japan Search for other works by this author on: Oxford Academic Google Scholar Y. Sumikawa, Y. Sumikawa Department of Dermatology, Graduate School of Medicine Osaka University, 2‐2 Yamada‐oka, Suita‐shi, Osaka 565‐0871, Japan Search for other works by this author on: Oxford Academic Google Scholar S. Yoshida, S. Yoshida Department of Dermatology, Graduate School of Medicine Osaka University, 2‐2 Yamada‐oka, Suita‐shi, Osaka 565‐0871, Japan Search for other works by this author on: Oxford Academic Google Scholar T. Kubo, T. Kubo Department of Dermatology, Graduate School of Medicine Osaka University, 2‐2 Yamada‐oka, Suita‐shi, Osaka 565‐0871, Japan Search for other works by this author on: Oxford Academic Google Scholar K. Yoshikawa, K. Yoshikawa Department of Dermatology, Graduate School of Medicine Osaka University, 2‐2 Yamada‐oka, Suita‐shi, Osaka 565‐0871, Japan Search for other works by this author on: Oxford Academic Google Scholar S. Itami S. Itami Department of Dermatology, Graduate School of Medicine Osaka University, 2‐2 Yamada‐oka, Suita‐shi, Osaka 565‐0871, Japan Satoshi Itami. E‐mail: itami@derma.med.osaka‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 152, Issue 4, 1 April 2005, Pages 664–672, https://doi.org/10.1111/j.1365-2133.2005.06401.x Published: 01 April 2005 Article history Accepted: 10 August 2004 Published: 01 April 2005
Nlr of Pro-Cryoablation Can Predict the Prognosis of Patients with Advanced Hepatocellular Carcinoma
Authors: Juan Xiu Chang, Zhen Zeng, Ying Yin Lu, Hiu Jian Qu, Lin Gui Xu, Xudong Gao, Hong Wang, Min Lou, Chunping Wang, Yongping Yang
Journal: Annals of Oncology (2014)
Mutations in the TGF-β repressor SKI cause Shprintzen-Goldberg syndrome with aortic aneurysm
Authors: Alexander J Doyle, Jefferson J Doyle, Seneca L Bessling, Samantha Maragh, Mark E Lindsay, Dorien Schepers, Elisabeth Gillis, Geert Mortier, Tessa Homfray, Kimberly Sauls, Russell A Norris, Nicholas D Huso, Dan Leahy, David W Mohr, Mark J Caulfield, Alan F Scott, Anne Destrée, Raoul C Hennekam, Pamela H Arn, Cynthia J Curry, Lut Van Laer, Andrew S McCallion, Bart L Loeys, Harry C Dietz
Journal: Nature Genetics (2012)
TGFβ, cardiac fibroblasts, and the fibrotic response
Authors: A LEASK
Journal: Cardiovascular Research (2006)

The cytokine transforming growth factor β (TGFβ) is a major contributor to fibrogenic responses both in vitro and in vivo. TGFβ possesses many functions; thus, broadly targeting TGFβ signaling as an anti-fibrotic approach is anticipated to be problematic. Recent experiments, however, have begun to elucidate the signaling pathways through which TGFβ activates a fibrotic program. This review critically evaluates the evidence supporting TGFβ as a pro-fibrotic cytokine, with special attention to cardiac fibrosis, and suggests several possible points for selective drug intervention to combat chronic fibrotic disease.
Discovering the Role of the Major Histocompatibility Complex in the Immune Response
Authors: Hugh O. McDevitt
Journal: Annual Review of Immunology (2000)

[Formula: see text] The discovery that genes in the major histocompatibility complex (MHC) play an important role in the immune response depended on the chance interaction of several unrelated events. The first, and most important, was the decision by Michael Sela to synthesize a series of branched, multichain, synthetic polypeptides based on a backbone of poly-l-lysine. The prototype compound, (T,G)-A–L, was tipped with short random sequences of tyrosine and glutamic acid. This resulted in a restricted range of antigenic determinants composed of only two or three amino acids with a variable length—ideal for binding to the peptide binding groove of MHC class II molecules. The second was the decision by John Humphrey to immunize various strains of rabbits with this synthetic polypeptide. Two of these rabbit strains showed very large quantitative differences in antibody response to (T,G)-A–L. In transferring this system to inbred mouse strains, the third bit of good fortune was the availability at the National Institute of Medical Research, in Mill Hill (London), of the CBA (H2 k ) and C57 (H2 b ) strains. The H2 b haplotype is the only one mediating a uniform high antibody response to (T,G)-A–L. The fourth critical ingredient was the availability of numerous congenic and H2 recombinant inbred strains of mice produced earlier by Snell, Stimpfling, Shreffler, and Klein. A search for congenic pairs of mice expressing the responder and nonresponder H2 haplotypes on the same background revealed that these strains responded as a function of their H2 haplotype, not of their inbred background. Extensive studies in a variety of inbred strains carrying recombinant H2 haplotypes, as well as a four-point linkage cross, mapped immune response to (T,G)A–L within the murine MHC, between the K and Ss loci. The demonstration that stimulation in the mixed lymphocyte reaction (MLR) mapped to the same region quickly led to attempts to produce antisera in congenic H2 recombinant strain combinations. These antisera identified I-region associated (Ia) antigens. Immunoprecipitation and blocking studies showed that the gene products controlling specific immune responses, the mixed lymphocyte reaction, and the structure of Ia antigens were one and the same—now designated as the I-A MHC class II molecules. These antisera and inbred strains enabled Unanue to demonstrate the peptide binding function of class II MHC molecules.
A secreted protein (Canopy 2, CNPY2) enhances angiogenesis and promotes smooth muscle cell migration and proliferation
Authors: Jian Guo, Yuemei Zhang, Anton Mihic, Shu-Hong Li, Zhuo Sun, Zhengbo Shao, Jun Wu, Richard D. Weisel, Ren-Ke Li
Journal: Cardiovascular Research (2015)

Ischaemic heart disease is a leading cause of mortality. After ischaemic injury, tissue hypoxia induces the activity of angiogenic factors that promote revascularization. Increased understanding of hypoxia-responsive genes and their role in angiogenesis will lead to new therapies for ischaemic injury. We delineated the function of Canopy 2 (CNPY2), a newly discovered, hypoxia-regulated gene. We found CNPY2 in a screen for genes induced by low oxygen in human smooth muscle cells (SMCs). CNPY2 protein co-localized with the endoplasmic reticulum and the Golgi. Treatment with Brefeldin A, which destroys Golgi stacks, resulted in CNPY2 accumulation in the endoplasmic reticulum. Secreted CNPY2 was detected in the blood of healthy mice and humans, and the medium of cultured SMCs. SMCs under hypoxia or treated with a prolyl-4-hydroxylase inhibitor stabilized HIF-1α protein and up-regulated CNPY2, while CNPY2 induction was lost after HIF-1α silencing. Chromatin immunoprecipitation demonstrated that HIF-1α binds to a hypoxia response element (HRE-1157) upstream of the human CNPY2 promoter, which was verified by a luciferase reporter driven by HRE-1157-containing constructs. CNPY2 stimulation activated Cdc42, PAK1, and FAK in SMCs, resulting in enhanced proliferation and migration in vitro, and dramatic aortic ring sprouting ex vivo. CNPY2 significantly increased revascularization of the mouse retina after reperfusion injury. CNPY2 is a HIF-1α-regulated, secreted angiogenic growth factor that promotes SMC migration, proliferation, and tissue revascularization. This new target may have a broader profile than currently available proteins.
Pathogenesis of persistent lymphatic vessel hyperplasia in chronic airway inflammation
Authors: Peter Baluk, Tuomas Tammela, Erin Ator, Natalya Lyubynska, Marc G. Achen, Daniel J. Hicklin, Michael Jeltsch, Tatiana V. Petrova, Bronislaw Pytowski, Steven A. Stacker, Seppo Ylä-Herttuala, David G. Jackson, Kari Alitalo, Donald M. McDonald
Journal: Journal of Clinical Investigation (2005)

Edema occurs in asthma and other inflammatory diseases when the rate of plasma leakage from blood vessels exceeds the drainage through lymphatic vessels and other routes. It is unclear to what extent lymphatic vessels grow to compensate for increased leakage during inflammation and what drives the lymphangiogenesis that does occur. We addressed these issues in mouse models of (a) chronic respiratory tract infection with Mycoplasma pulmonis and (b) adenoviral transduction of airway epithelium with VEGF family growth factors. Blood vessel remodeling and lymphangiogenesis were both robust in infected airways. Inhibition of VEGFR-3 signaling completely prevented the growth of lymphatic vessels but not blood vessels. Lack of lymphatic growth exaggerated mucosal edema and reduced the hypertrophy of draining lymph nodes. Airway dendritic cells, macrophages, neutrophils, and epithelial cells expressed the VEGFR-3 ligands VEGF-C or VEGF-D. Adenoviral delivery of either VEGF-C or VEGF-D evoked lymphangiogenesis without angiogenesis, whereas adenoviral VEGF had the opposite effect. After antibiotic treatment of the infection, inflammation and remodeling of blood vessels quickly subsided, but lymphatic vessels persisted. Together, these findings suggest that when lymphangiogenesis is impaired, airway inflammation may lead to bronchial lymphedema and exaggerated airflow obstruction. Correction of defective lymphangiogenesis may benefit the treatment of asthma and other inflammatory airway diseases.
Generalized eczema craquele as a presenting feature of lymphoma
Authors: D.J. BARKER, J.A. COTTERILL
Journal: British Journal of Dermatology (1977)

Journal Article Generalized eczéma craquelé as a presenting feature of lymphoma Get access D.J. BARKER, D.J. BARKER Department of Dermatology, University of Leeds, The General Infirmary at Leeds Search for other works by this author on: Oxford Academic Google Scholar J.A. COTTERILL J.A. COTTERILL Department of Dermatology, University of Leeds, The General Infirmary at Leeds Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 97, Issue 3, 1 September 1977, Pages 323–326, https://doi.org/10.1111/j.1365-2133.1977.tb15190.x Published: 01 September 1977
American Thoracic Society Statement on Research Priorities in Respiratory Nursing
Authors: Janet L. Larson, Karen Ahijevych, Audrey Gift, Leslie Hoffman, Susan L. Janson, Dorothy M. Lanuza, Nancy K. Leidy, Paula Meek, Julie Roberts, Terri Weaver, H. Lorrie Yoos
Journal: American Journal of Respiratory and Critical Care Medicine (2006)
Involvement of BAFF and APRIL in the resistance to apoptosis of B-CLL through an autocrine pathway
Authors: Catherine Kern, Jean-François Cornuel, Christian Billard, Ruoping Tang, Danielle Rouillard, Virginie Stenou, Thierry Defrance, Florence Ajchenbaum-Cymbalista, Pierre-Yves Simonin, Sophie Feldblum, Jean-Pierre Kolb
Journal: Blood (2003)
Association Between Treated and Untreated Obstructive Sleep Apnea and Risk of Hypertension
Authors: José M. Marin, Alvar Agusti, Isabel Villar, Marta Forner, David Nieto, Santiago J. Carrizo, Ferran Barbé, Eugenio Vicente, Ying Wei, F. Javier Nieto, Sanja Jelic
Journal: JAMA (2012)

<h3>Context</h3>Systemic hypertension is prevalent among patients with obstructive sleep apnea (OSA). Short-term studies indicate that continuous positive airway pressure (CPAP) therapy reduces blood pressure in patients with hypertension and OSA.<h3>Objective</h3>To determine whether CPAP therapy is associated with a lower risk of incident hypertension.<h3>Design, Setting, and Participants</h3>A prospective cohort study of 1889 participants without hypertension who were referred to a sleep center in Zaragoza, Spain, for nocturnal polysomnography between January 1, 1994, and December 31, 2000. Incident hypertension was documented at annual follow-up visits up to January 1, 2011. Multivariable models adjusted for confounding factors, including change in body mass index from baseline to censored time, were used to calculate hazard ratios (HRs) of incident hypertension in participants without OSA (controls), with untreated OSA, and in those treated with CPAP therapy according to national guidelines.<h3>Main Outcome Measure</h3>Incidence of new-onset hypertension.<h3>Results</h3>During 21 003 person-years of follow-up (median, 12.2 years), 705 cases (37.3%) of incident hypertension were observed. The crude incidence of hypertension per 100 person-years was 2.19 (95% CI, 1.71-2.67) in controls, 3.34 (95% CI, 2.85-3.82) in patients with OSA ineligible for CPAP therapy, 5.84 (95% CI, 4.82-6.86) in patients with OSA who declined CPAP therapy, 5.12 (95% CI, 3.76-6.47) in patients with OSA nonadherent to CPAP therapy, and 3.06 (95% CI, 2.70-3.41) in patients with OSA and treated with CPAP therapy. Compared with controls, the adjusted HRs for incident hypertension were greater among patients with OSA ineligible for CPAP therapy (1.33; 95% CI, 1.01-1.75), among those who declined CPAP therapy (1.96; 95% CI, 1.44-2.66), and among those nonadherent to CPAP therapy (1.78; 95% CI, 1.23-2.58), whereas the HR was lower in patients with OSA who were treated with CPAP therapy (0.71; 95% CI, 0.53-0.94).<h3>Conclusion</h3>Compared with participants without OSA, the presence of OSA was associated with increased adjusted risk of incident hypertension; however, treatment with CPAP therapy was associated with a lower risk of hypertension.
Delayed Diaphragm Injury and Diaphragm Force Production
Authors: TIAN-XI JIANG, W. DARLENE REID, JEREMY D. ROAD
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

The present study was designed to examine the effect of delayed diaphragm injury produced by inspiratory resistive loading (IRL) on diaphragm force production. On Day 1, three groups of anesthetized and intubated NZW rabbits (n = 7 in each group) were subjected to moderate IRL (Pao ∼ 30 cm H2O), high IRL (Pao ∼ 45 cm H2O), or no load for 1.5 h. On Day 3, the baseline twitch transdiaphragmatic pressure (Pdi) and Pdi at 10 to 80 Hz were measured during bilateral phrenic stimulation and these measurements were repeated after another IRL (high level) in all three groups. Diaphragm injury was assessed by the point-counting technique. Marked diaphragm injury was observed in the high-IRL group (p < 0.01), but no significant diaphragm injury was observed in the moderate-IRL or control groups. The baseline twitch Pdi was maintained in both IRL groups, whereas the baseline Pdi– frequency values in the high-IRL group were significantly reduced at most frequencies (p < 0.05). The decreases in twitch and Pdi at different frequencies were more pronounced after the IRL on Day 3 in the high-IRL group compared with controls. Moderate IRL did not decrease diaphragm force either before or after the high IRL on Day 3. We conclude that the diaphragm injury induced by high IRL has a significant impact on diaphragm force production and the attendant force loss produced by IRL is dependent on the intensity of inspiratory loading.
Cardiovascular Actions of Insulin
Authors: Ranganath Muniyappa, Monica Montagnani, Kwang Kon Koh, Michael J. Quon
Journal: Endocrine Reviews (2007)

Insulin has important vascular actions to stimulate production of nitric oxide from endothelium. This leads to capillary recruitment, vasodilation, increased blood flow, and subsequent augmentation of glucose disposal in classical insulin target tissues (e.g., skeletal muscle). Phosphatidylinositol 3-kinase-dependent insulin-signaling pathways regulating endothelial production of nitric oxide share striking parallels with metabolic insulin-signaling pathways. Distinct MAPK-dependent insulin-signaling pathways (largely unrelated to metabolic actions of insulin) regulate secretion of the vasoconstrictor endothelin-1 from endothelium. These and other cardiovascular actions of insulin contribute to coupling metabolic and hemodynamic homeostasis under healthy conditions. Cardiovascular diseases are the leading cause of morbidity and mortality in insulin-resistant individuals. Insulin resistance is typically defined as decreased sensitivity and/or responsiveness to metabolic actions of insulin. This cardinal feature of diabetes, obesity, and dyslipidemia is also a prominent component of hypertension, coronary heart disease, and atherosclerosis that are all characterized by endothelial dysfunction. Conversely, endothelial dysfunction is often present in metabolic diseases. Insulin resistance is characterized by pathway-specific impairment in phosphatidylinositol 3-kinase-dependent signaling that in vascular endothelium contributes to a reciprocal relationship between insulin resistance and endothelial dysfunction. The clinical relevance of this coupling is highlighted by the findings that specific therapeutic interventions targeting insulin resistance often also ameliorate endothelial dysfunction (and vice versa). In this review, we discuss molecular mechanisms underlying cardiovascular actions of insulin, the reciprocal relationships between insulin resistance and endothelial dysfunction, and implications for developing beneficial therapeutic strategies that simultaneously target metabolic and cardiovascular diseases.
Pharmacology of Nonpeptide Angiotensin II Receptor Antagonists
Authors: R D Smith, A T Chiu, P C Wong, W F Herblin, P B Timmermans
Journal: The Annual Review of Pharmacology and Toxicology (1992)

Due to the massive data sets available for drug candidates, modern drug discovery has advanced to the big data era. Central to this shift is the development of artificial intelligence approaches to implementing innovative modeling based on the dynamic, ...Read More
Three-Dimensional Imaging and Quantification of Both Solitary Cells and Metastases in Whole Mouse Liver by Magnetic Resonance Imaging
Authors: Jason L. Townson, Soha S. Ramadan, Carmen Simedrea, Brian K. Rutt, Ian C. MacDonald, Paula J. Foster, Ann F. Chambers
Journal: Cancer Research (2009)

Abstract The metastatic cell population, ranging from solitary cells to actively growing metastases, is heterogeneous and unlikely to respond uniformly to treatment. However, quantification of the entire experimental metastatic cell population in whole organs is complicated by requirements of an imaging modality with the large field of view and high spatial resolution necessary to detect both single cells and metastases in the same organ. Thus, it is difficult to assess differential responses of these distinct metastatic populations to therapy. Here, we develop a magnetic resonance imaging (MRI) technique capable of quantifying the full population of metastatic cells in a secondary organ. B16F1 mouse melanoma cells were labeled with micron-sized iron oxide particles (MPIO) and injected into mouse liver via the mesenteric vein. Livers were removed immediately or at day 9 or 11, following doxorubicin or vehicle control treatment, and imaged using a 3T clinical magnetic resonance scanner and custom-built gradient coil. Both metastases (&amp;gt;200 μm) and MPIO-labeled single cells were detected and quantified from MR images as areas of hyperintensity or hypointensity (signal voids), respectively. We found that 1mg/kg doxorubicin treatment inhibited metastasis growth (n = 11 per group; P = 0.02, t test) but did not decrease the solitary metastatic cell population in the same livers (P &amp;gt; 0.05). Thus, the technique presented here is capable of quickly quantifying the majority of the metastatic cell population, including both growing metastases and solitary cells, in whole liver by MRI and can identify differential responses of growing metastases and solitary cells to therapy. [Cancer Res 2009;69(21):8326–31]
A CD4 T cell gene signature for early rheumatoid arthritis implicates interleukin 6-mediated STAT3 signalling, particularly in anti-citrullinated peptide antibody-negative disease
Authors: Arthur G Pratt, Daniel C Swan, Sarah Richardson, Gillian Wilson, Catharien M U Hilkens, David A Young, John D Isaacs
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> We sought clinically relevant predictive biomarkers present in CD4 T-cells, or in serum, that identified those patients with undifferentiated arthritis (UA) who subsequently develop rheumatoid arthritis (RA). <h3>Methods</h3> Total RNA was isolated from highly purified peripheral blood CD4 T cells of 173 early arthritis clinic patients. Paired serum samples were also stored. Microarray analysis of RNA samples was performed and differential transcript expression among 111 'training cohort' patients confirmed using real-time quantitative PCR. Machine learning approaches tested the utility of a classification model among an independent validation cohort presenting with UA (62 patients). Cytokine measurements were performed using a highly sensitive electrochemiluminescence detection system. <h3>Results</h3> A 12-gene transcriptional 'signature' identified RA patients in the training cohort and predicted the subsequent development of RA among UA patients in the validation cohort (sensitivity 68%, specificity 70%). STAT3-inducible genes were over-represented in the signature, particularly in anti-citrullinated peptide antibody-negative disease, providing a risk metric of similar predictive value to the Leiden score in seronegative UA (sensitivity 85%, specificity 75%). Baseline levels of serum interleukin 6 (IL-6) (which signals via STAT3) were highest in anti-citrullinated peptide antibodies-negative RA and distinguished this subgroup from non-RA inflammatory synovitis (corrected p&lt;0.05).Paired serum IL-6 measurements correlated strongly with STAT3-inducible gene expression. <h3>Conclusion</h3> The authors have identified IL-6-mediated STAT-3 signalling in CD4 T cells during the earliest clinical phase of RA, which is most prominent in seronegative disease. While highlighting potential biomarker(s) for early RA, the role of this pathway in disease pathogenesis awaits clarification.
Pseudoviral Inclusion Bodies in Acute Leukemia. A Report of Two Cases
Authors: Yasukazu Tanaka, William R. Bell, Darlene Brindley
Journal: JNCI Journal of the National Cancer Institute (1967)

Cytoplasmic inclusions in leukemic cells of the bone marrow and peripheral blood are described in one patient with acute lymphocytic leukemia and in one patient with blastic crisis of chronic myelogenous leukemia. The inclusions were 1–7 μ in diameter and visible in routinely stained preparations. On electron microscopy, they consisted of subunits, 500–700 A in diameter, which resembled incomplete virus particles. Histochemical studies suggested that the particles contained acid phosphatase and acid mucopolysaccharide, but no DNA or RNA. The presence of structurally and histochemically similar particles in many other benign and malignant mammalian cells militates against their viral nature and etiologic role, although they have not been described in normal marrow cells to date.