tbuckley/cabot-search huggingface dataset:
Antibodies to carbonic anhydrase and IgG4 levels in idiopathic chronic pancreatitis: relevance for diagnosis of autoimmune pancreatitis
Authors: L Aparisi
Journal: Gut (2005)

<h3>Abstract</h3> Proximal-tubule-cell EGFR activation mediates tubule cell proliferation and repair early after kidney injury, while sustained EGFR activation causes kidney fibrosis. Inflammation is a key driver of AKI-to-CKD transition and fibrosis, but mechanisms of EGFR-driven profibrotic responses are not well understood. In a mouse model of AKI-to-CKD transition and CKD progression, we show that EGFR-inhibition significantly reduced kidney expression of many immunoregulatory molecules already by day two after injury, including the potent inflammatory cytokine tumor-necrosis-factor (TNF). Single nuclei RNA-sequencing analysis showed that macrophages were among the main early cellular sources of TNF in the injured kidney. <i>In vitro</i>, EGFR activation in macrophages increased macrophage TNF expression, while EGFR inhibition <i>in vivo</i> reduced kidney macrophage accumulation, as early as two days after injury. Thus, profibrotic EGFR signaling increases kidney TNF levels both directly and indirectly. TNF inhibition did not alter tubule EGFR activation and in contrast to EGFR inhibition did not reduce early macrophage accumulation in the kidney, suggesting that TNF does not promote early infiltration of immune cells in the kidney, but rather regulates profibrotic functions of kidney and/or immune cells. TNF inhibition with etanercept <i>in vivo</i> in AKI-injured mice downregulated a number of cytokines, including TNF itself. This cytokine downregulation overlapped with EGFR inhibition, and additional non-overlapping downregulated cytokines shared the same functions, predicting that TNF inhibition would prevent AKI-to-CKD transition like EGFR inhibition. Indeed, TNF-inhibition with etanercept reduced AKI-induced fibrosis to the same degree as the EGFR-inhibition, while the combination of both treatments showed no additive effect. In conclusion, our results identify TNF as a downstream effector of profibrotic EGFR activation and motivate the examination of TNF pathway inhibition in human AKI or CKD. <h3>Translational statement</h3> Proximal tubule epidermal-growth-factor (EGFR) activation in mice and likely also in humans drives inflammation in the kidney after acute-kidney-injury (AKI) and causes chronic-kidney-disease (CKD) with fibrosis in a process termed AKI-to-CKD transition. Recent retrospective data shows that patients treated with TNF inhibitors show decreased incidence and progression of CKD. Our current work shows that TNF inhibition in mice is equally as effective as EGFR inhibition in preventing AKI-to-CKD transition and fibrosis. Thus, our results have translational potential and may stimulate examination of short-term TNF inhibition in AKI to prevent AKI-to-CKD transition or possibly of longer-term TNF inhibition in CKD to prevent CKD progression.
Vascular-Resident CD169-Positive Monocytes and Macrophages Control Neutrophil Accumulation in the Kidney with Ischemia-Reperfusion Injury
Authors: Kazunori Karasawa, Kenichi Asano, Shigetaka Moriyama, Mikiko Ushiki, Misa Monya, Mayumi Iida, Erika Kuboki, Hideo Yagita, Keiko Uchida, Kosaku Nitta, Masato Tanaka
Journal: Journal of the American Society of Nephrology (2014)

Monocytes and kidney-resident macrophages are considered to be involved in the pathogenesis of renal ischemia-reperfusion injury (IRI). Several subsets of monocytes and macrophages are localized in the injured tissue, but the pathologic roles of these cells are not fully understood. Here, we show that CD169+ monocytes and macrophages have a critical role in preventing excessive inflammation in IRI by downregulating intercellular adhesion molecule-1 (ICAM-1) expression on vascular endothelial cells. Mice depleted of CD169+ cells showed enhanced endothelial ICAM-1 expression and developed irreversible renal damage associated with infiltration of a large number of neutrophils. The perivascular localization of CD169+ monocytes and macrophages indicated direct interaction with blood vessels, and coculture experiments showed that the direct interaction of CD169+ cell-depleted peripheral blood leukocytes augments the expression levels of ICAM-1 on endothelial cells. Notably, the transfer of Ly6Clo monocytes into CD169+ cell-depleted mice rescued the mice from lethal renal injury and normalized renal ICAM-1 expression levels, indicating that the Ly6Clo subset of CD169+ monocytes has a major role in the regulation of inflammation. Our findings highlight the previously unknown role of CD169+ monocytes and macrophages in the maintenance of vascular homeostasis and provide new approaches to the treatment of renal IRI.
Idiopathic haemarthrosis with chondrocalcinosis.
Authors: C J Menkes, J Rondier
Journal: Annals of the Rheumatic Diseases (1987)

IgA serum levels and diseaseIdiopathic haemarthrosis with activity in ankylosing spondylitis chondrocalcinosis SIR, I read with considerable interest the report by Franssen and associates of a prospective study of IgA serum levels and disease activity in ankylosing spondylitis (AS).'In their comparative trial of phenylbutazone and
The Role of Host‐derived Dentinal Matrix Metalloproteinases in Reducing Dentin Bonding of Resin Adhesives
Authors: Shan‐chuan Zhang, Matthias Kern
Journal: International Journal of Oral Science (2009)

Dentin matrix metalloproteinases (MMPs) are a family of host‐derived proteolytic enzymes trapped within mineralized dentin matrix, which have the ability to hydrolyze the organic matrix of demineralized dentin. After bonding with resins to dentin there are usually some exposed collagen fibrils at the bottom of the hybrid layer owing to imperfect resin impregnation of the demineralized dentin matrix. Exposed collagen fibrils might be affected by MMPs inducing hydrolytic degradation, which might result in reduced bond strength. Most MMPs are synthesized and released from odontoblasts in the form of proenzymes, requiring activation to degrade extracellular matrix components. Unfortunately, they can be activated by modern self‐etch and etch‐and‐rinse adhesives. The aim of this review is to summarize the current knowledge of the role of dentinal host‐derived MMPs in dentin matrix degradation. We also discuss various available MMP inhibitors, especially chlorhexidine, and suggest that they could provide a potential pathway for inhibiting collagen degradation in bonding interfaces thereby increasing dentin bonding durability.
Arthrographic study of the rheumatoid knee. Part 2. Articular cartilage and menisci.
Authors: K Fujikawa, Y Tanaka, T Matsubayashi, F Iseki
Journal: Annals of the Rheumatic Diseases (1981)

The changes of the articular cartilage and of the menisci in 129 knee joints with classical rheumatoid arthritis have been investigated by an improved arthrographic technique. The changes of the intra-articular components on the arthrograms coincided well with direct views at arthroscopy and surgery. The changes of the articular cartilage on the arthrograms were graded as normal, deposit and pooling, thinning, filling defect, destruction, and disappearance, and those of the menisci as normal, degeneration, tear, and disappearance. The results showed that: (1) The radiographs did not always reflect the changes of those intra-articular components in the early stages; especially in stage 2 they showed various conditions from intact to destruction. (2) The changes of the menisci were less advanced than those of the articular cartilage in the early stages. (3) The changes in those components progressed almost symmetrically in both compartments. It is necessary to appreciate not only the pathological condition of the bones of the knee joints but also that of the intra-articular components to devise more careful programmes of treatment for rheumatoid knees.
Assortative Mating Drives Linkage Disequilibrium between Sperm and Egg Recognition Protein Loci in the Sea Urchin Strongylocentrotus purpuratus
Authors: Andres Plata Stapper, Peter Beerli, Don R Levitan
Journal: Molecular Biology and Evolution (2015)

Sperm and eggs have interacting proteins on their surfaces that influence their compatibility during fertilization. These proteins are often polymorphic within species, producing variation in gamete affinities. We first demonstrate the fitness consequences of various sperm bindin protein (Bindin) variants in the sea urchin Strongylocentrotus purpuratus, and assortative mating between males and females based on their sperm Bindin genotype. This empirical finding of assortative mating based on sperm Bindin genotype could arise by linkage disequilibrium (LD) between interacting sperm and egg recognition loci. We then examine sequence variation in eight exons of the sea urchin egg receptor for sperm Bindin (EBR1). We find little evidence of LD among the eight exons of EBR1, yet strong evidence for LD between sperm Bindin and EBR1 overall, and varying degrees of LD between sperm Bindin among the eight exons. We reject the alternate hypotheses of LD driven by shared evolutionary histories, population structure, or close physical linkage between these interacting loci on the genome. The most parsimonious explanation for this pattern of LD is that it represents selection driven by assortative mating based on interactions among these sperm and egg loci. These findings indicate the importance of ongoing sexual selection in the maintenance of protein polymorphisms and LD, and more generally highlight how LD can be used as an indication of current mate choice, as opposed to historic selection.
A Century of Pulmonary Hemodynamics
Authors: Alfred P. Fishman
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

At the start of the twentieth century, studies of pulmonary hemodynamics were largely confined to measurements of pulmonary arterial pressures in anesthetized, open-chest animals undergoing artificial respiration (1). By then, pressure recording was fairly well standardized, and pressures recorded in animals by different manometric systems were generally accurate and similar in form (2). Outflow pressures, for the calculation of pulmonary vascular resistance and the measurement of left arterial measures, became available at midcentury (3). A leading figure in setting standards for pressure recording was Otto Frank (1865‐1944), a distinguished German physiologist and physician, whose name is well known to circulatory physiologists as one of the discoverers of the Frank-Starling law of the heart. Less familiar, but seminal for the study of hemodynamics, was his role in setting standards for the accurate recording of vascular pressure pulses (4). These standards featured prominently in the subsequent design and application of cardiac catheters for
Antineoplastic Mechanisms of Niclosamide in Acute Myelogenous Leukemia Stem Cells: Inactivation of the NF-κB Pathway and Generation of Reactive Oxygen Species
Authors: Yanli Jin, Zhongzheng Lu, Ke Ding, Juan Li, Xin Du, Chun Chen, Xiaoyong Sun, Yongbin Wu, Jing Zhou, Jingxuan Pan
Journal: Cancer Research (2010)

NF-kappaB may be a potential therapeutic target for acute myelogenous leukemia (AML) because NF-kappaB activation is found in primitive human AML blast cells. In this report, we initially discovered that the potent antineoplastic effect of niclosamide, a Food and Drug Administration-approved antihelminthic agent, was through inhibition of the NF-kappaB pathway in AML cells. Niclosamide inhibited the transcription and DNA binding of NF-kappaB. It blocked tumor necrosis factor-induced IkappaBalpha phosphorylation, translocation of p65, and expression of NF-kappaB-regulated genes. Niclosamide inhibited the steps TAK1-->IkappaB kinase (IKK) and IKK-->IkappaBalpha. Niclosamide also increased the levels of reactive oxygen species (ROS) in AML cells. Quenching ROS by the glutathione precursor N-acetylcysteine attenuated niclosamide-induced apoptosis. Our results together suggest that niclosamide inhibited the NF-kappaB pathway and increased ROS levels to induce apoptosis in AML cells. On translational study of the efficacy of niclosamide against AML, niclosamide killed progenitor/stem cells from AML patients but spared those from normal bone marrow. Niclosamide was synergistic with the frontline chemotherapeutic agents cytarabine, etoposide, and daunorubicin. It potently inhibited the growth of AML cells in vitro and in nude mice. Our results support further investigation of niclosamide in clinical trials of AML patients.
An Open-Label Dose Escalation Study to Evaluate the Safety of Administration of Nonviral Stromal Cell-Derived Factor-1 Plasmid to Treat Symptomatic Ischemic Heart Failure
Authors: Marc S. Penn, Farrell O. Mendelsohn, Gary L. Schaer, Warren Sherman, MaryJane Farr, Joseph Pastore, Didier Rouy, Ruth Clemens, Rahul Aras, Douglas W. Losordo
Journal: Circulation Research (2013)

Rationale: Preclinical studies indicate that adult stem cells induce tissue repair by activating endogenous stem cells through the stromal cell-derived factor-1:chemokine receptor type 4 axis. JVS-100 is a DNA plasmid encoding human stromal cell-derived factor-1. Objective: We tested in a phase 1, open-label, dose-escalation study with 12 months of follow-up in subjects with ischemic cardiomyopathy to see if JVS-100 improves clinical parameters. Methods and Results: Seventeen subjects with ischemic cardiomyopathy, New York Heart Association class III heart failure, with an ejection fraction ≤40% on stable medical therapy, were enrolled to receive 5, 15, or 30 mg of JVS-100 via endomyocardial injection. The primary end points for safety and efficacy were at 1 and 4 months, respectively. The primary safety end point was a major adverse cardiac event. Efficacy end points were change in quality of life, New York Heart Association class, 6-minute walk distance, single photon emission computed tomography, N-terminal pro-brain natruretic peptide, and echocardiography at 4 and 12 months. The primary safety end point was met. At 4 months, all of the cohorts demonstrated improvements in 6-minute walk distance, quality of life, and New York Heart Association class. Subjects in the 15- and 30-mg dose groups exhibited improvements in 6-minute walk distance (15 mg: median [range]: 41 minutes [3–61 minutes]; 30 mg: 31 minutes [22–74 minutes]) and quality of life (15 mg: –16 points [+1 to –32 points]; 30 mg: –24 points [+17 to –38 points]) over baseline. At 12 months, improvements in symptoms were maintained. Conclusions: These data highlight the importance of defining the molecular mechanisms of stem cell-based tissue repair and suggest that overexpression of stromal cell-derived factor-1 via gene therapy is a strategy for improving heart failure symptoms in patients with ischemic cardiomyopathy.
Efficacy and safety of ascending methotrexate dose in combination with adalimumab: the randomised CONCERTO trial
Authors: Gerd-Rűdiger Burmester, Alan J Kivitz, Hartmut Kupper, Udayasankar Arulmani, Stefan Florentinus, Sandra L Goss, Suchitrita S Rathmann, Roy M Fleischmann
Journal: Annals of the Rheumatic Diseases (2014)

Objective CONCERTO was a randomised, double-blind, parallel-armed study of methotrexate (MTX) in combination with adalimumab to assess whether an increasing trend of efficacy and decreased safety exists when increasing MTX dose in patients with early rheumatoid arthritis (RA). Methods Early, biologic and MTX-naive RA patients (N=395) were evenly randomised to open-label adalimumab (40 mg every other week) plus weekly blinded 2.5, 5, 10 or 20 mg MTX for 26 weeks. Clinical, radiographic and functional outcomes were analysed using two-sided linear trend tests or one-way analysis of covariance. Results Statistically significant increasing trends were observed in the proportion of patients achieving the primary endpoint, 28-joint count disease activity score with C reactive protein (DAS28(CRP)) &lt;3.2 (42.9%, 44.0%, 56.6% and 60.2% for 2.5, 5, 10 or 20 mg/week MTX, respectively), DAS28(CRP) &lt;2.6 and American College of Rheumatology 50/70/90 responses with increasing doses of MTX in combination with adalimumab. No statistical differences in minimal clinically important differences in physical function were detected. Statistically significant trends for achieving low disease activity and remission were demonstrated with increasing MTX dose by validated clinical indices; differences comparing 10 and 20 mg MTX were minimal. Adalimumab serum concentrations increased with ascending dose up to 10 mg MTX. More patients experienced infectious adverse events with increasing MTX dose. Conclusions Increasing doses of MTX in combination with adalimumab demonstrated a statistically significant trend in improved clinical outcomes that mimicked the adalimumab pharmacokinetic profile. In early RA patients initiating adalimumab combination therapy, efficacy of 10 and 20 mg/week MTX appeared equivalent.
Chronic eosinophilic pneumonia after radiation therapy for breast cancer
Authors: Vincent Cottin, R. Frognier, H. Monnot, Avraham Levy, P. Devuyst, Jean-François Cordier, . Groupe d'Etudes Et de Recherche Sur Les Maladies "orphelines" Pulmonaires (germop)
Journal: European Respiratory Journal (2003)

The priming of bronchiolitis obliterans organising pneumonia by radiation therapy (RT) to the breast is now a well recognised syndrome. This study describes the occurrence of chronic eosinophilic pneumonia following RT after surgery for breast cancer in five female patients, with a mean age of 68 yrs (range 49–77). All patients had a history of asthma and/or allergy. At the onset of eosinophilic pneumonia, all patients were symptomatic. Chest radiograph showed pulmonary infiltrates, unilateral and limited to the irradiated lung in three patients, and bilateral in two. Pulmonary opacities were migratory in one patient. All patients had blood eosinophilia &gt;1.0 10 9 ·L −1 and/or eosinophilia &gt;40% at bronchoalveolar lavage differential cell count. The median time interval between the end of radiation therapy and the onset of eosinophilic pneumonia was 3.5 months (range 1–10). All patients rapidly improved with oral corticosteroids without sequelae. Relapse occurred in two patients after treatment withdrawal. Priming of alveolitis by radiation therapy to the breast might promote either bronchiolitis obliterans organising pneumonia or chronic eosinophilic pneumonia, with the latter depending on genetic or acquired characteristics of patients and/or further stimulation that may trigger a T‐helper cell type 2 form of lymphocyte response, especially in patients with asthma or other atopic manifestations.
Characterization of a Novel Tumor-Suppressor Gene <i>PLCδ1</i> at 3p22 in Esophageal Squamous Cell Carcinoma
Authors: Li Fu, Yan-Ru Qin, Dan Xie, Liang Hu, Dora L. Kwong, Gopesh Srivastava, Sai Wah Tsao, Xin-Yuan Guan
Journal: Cancer Research (2007)

Abstract Deletion of 3p is one of the most frequent chromosomal alterations in many solid tumors, including esophageal squamous cell carcinoma (ESCC), suggesting the existence of one or more tumor-suppressor genes at 3p. Recently, our loss of heterozygosity study revealed that 3p22 was frequently deleted in ESCC and a candidate tumor-suppressor gene (TSG), phospholipase C-δ1 (PLCδ1), was identified within the 3p22 region. In this study, absent expression of PLCδ1 was detected in 26 of 50 (52%) primary ESCCs and 4 of 9 (44.4%) ESCC cell lines, which was significantly associated with DNA copy number loss and promoter hypermethylation (P &amp;lt; 0.05). Functional studies showed that PLCδ1 was able to suppress both in vitro and in vivo tumorigenic ability of ESCC cells, including foci formation, colony formation in soft agar, and tumor formation in nude mice. The tumor-suppressive mechanism of PLCδ1 was associated with its role in the cell cycle arrest at the G1-S checkpoint by up-regulation of p21 and down-regulation of phosphorylated Akt (Ser473). In addition, down-regulation of PLCδ1 protein was significantly correlated with ESCC metastasis (P = 0.014), which was associated with its function in increasing cell adhesion and inhibiting cell mobility. Taken together, our results suggest that PLCδ1 plays an important suppressive role in the development and progression of ESCC. [Cancer Res 2007;67(22):10720–5]
The Annals of the Rheumatic Diseases becomes the EULAR journal
Authors: T. L VISCHER
Journal: Annals of the Rheumatic Diseases (2000)

EULAR (European League against Rheumatism), the umbrella organisation of the European professional societies dealing with rheumatic diseases has undergone many changes in the past years. This was necessary as Europe has changed and the practice of medicine has evolved. Medicine now …
Pressure-flow relationships and vascular impedance in man
Authors: C. J. Mills, I. T. Gabe, J. H. Gault, D. T. Mason, J. Ross, E. Braunwald, J. P. Shillingford
Journal: Cardiovascular Research (1970)

Journal Article Pressure-flow relationships and vascular impedance in man Get access C. J. Mills, C. J. Mills 1 From the Cardiology Branch, National Heart Institute, National Institutes of Health, Bethesda, Maryland, U.S.A. and M.R.C. Cardiovascular Unit, Hammersmith Hospital, London 1M.R.C. Cardiovascular Unit, Royal Postgraduate Medical School, Ducane Road, London, W.12. Search for other works by this author on: Oxford Academic PubMed Google Scholar I. T. Gabe, I. T. Gabe 1 From the Cardiology Branch, National Heart Institute, National Institutes of Health, Bethesda, Maryland, U.S.A. and M.R.C. Cardiovascular Unit, Hammersmith Hospital, London 1M.R.C. Cardiovascular Unit, Royal Postgraduate Medical School, Ducane Road, London, W.12. Search for other works by this author on: Oxford Academic PubMed Google Scholar J. H. Gault, J. H. Gault From the Cardiology Branch, National Heart Institute, National Institutes of Health, Bethesda, Maryland, U.S.A. and M.R.C. Cardiovascular Unit, Hammersmith Hospital, London Search for other works by this author on: Oxford Academic PubMed Google Scholar D. T. Mason, D. T. Mason From the Cardiology Branch, National Heart Institute, National Institutes of Health, Bethesda, Maryland, U.S.A. and M.R.C. Cardiovascular Unit, Hammersmith Hospital, London Search for other works by this author on: Oxford Academic PubMed Google Scholar J. Ross, Jr., J. Ross, Jr. From the Cardiology Branch, National Heart Institute, National Institutes of Health, Bethesda, Maryland, U.S.A. and M.R.C. Cardiovascular Unit, Hammersmith Hospital, London Search for other works by this author on: Oxford Academic PubMed Google Scholar E. Braunwald, E. Braunwald From the Cardiology Branch, National Heart Institute, National Institutes of Health, Bethesda, Maryland, U.S.A. and M.R.C. Cardiovascular Unit, Hammersmith Hospital, London Search for other works by this author on: Oxford Academic PubMed Google Scholar J. P. Shillingford J. P. Shillingford 1 From the Cardiology Branch, National Heart Institute, National Institutes of Health, Bethesda, Maryland, U.S.A. and M.R.C. Cardiovascular Unit, Hammersmith Hospital, London 1M.R.C. Cardiovascular Unit, Royal Postgraduate Medical School, Ducane Road, London, W.12. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 4, Issue 4, October 1970, Pages 405–417, https://doi.org/10.1093/cvr/4.4.405 Published: 01 October 1970 Article history Accepted: 21 January 1970 Published: 01 October 1970