tbuckley/cabot-search huggingface dataset:
Bone Morphogenetic Protein-7 Improves Renal Fibrosis and Accelerates the Return of Renal Function
Authors: Jeremiah Morrissey, Keith Hruska, Guangjie Guo, Song Wang, Qing Chen, Saulo Klahr
Journal: Journal of the American Society of Nephrology (2002)

A prevention protocol has demonstrated that bone morphogenetic protein-7 (BMP-7) blunted the development of fibrosis in a rat model of unilateral ureteral obstruction. This prevention protocol also preserved, to an extent, renal function. The prevention protocol was extended and a treatment protocol used to examine if BMP-7 was beneficial at limiting fibrosis of the kidney when the BMP-7 was administered during the progression of fibrotic disease. Animals were distributed into four groups. Group 1 received vehicle, group 2 received enalapril (12.5 mg/kg body wt per d), group 3 received BMP-7 (50 or 300 microg/kg), and group 4 received both the enalapril and the high dose of BMP-7. Rats underwent reversible unilateral ureteral obstruction for 3 d, after which the obstruction was relieved. In the treatment protocol, 300 microg/kg BMP-7 was given after the release of obstruction. Seven days after release of the obstruction and the onset of treatment glomerular filtration rate (GFR), renal blood flow, and various histologic indexes of fibrosis were determined. On a consistent basis, BMP-7 treatment alone was found to be slightly but significantly (P < 0.04 to 0.007) better than enalapril alone or in combination with enalapril at decreasing interstitial volume or tubule atrophy. BMP-7 treatment was slightly but not significantly better (P < 0.09) than enalapril at restoring GFR in the prevention protocol. Treatment with BMP-7 significantly boosted GFR (P < 0.01) above that seen with vehicle treatment. These results suggest that BMP-7 treatment is capable of blunting the progression of fibrotic disease and of decreasing interstitial volume. Importantly, a return of renal function is accelerated by BMP-7 treatment. These results suggest that administration of BMP-7 may be an effective treatment to restore or preserve renal histology and renal function in this experimental model of renal disease.
Colorectal Screening after Polypectomy: A National Survey Study of Primary Care Physicians
Authors: Vikram Boolchand, Gregory Olds, Joseph Singh, Pankaj Singh, Amitabh Chak, Gregory S. Cooper
Journal: Annals of Internal Medicine (2006)

Background: Recommendations by primary care physicians for colorectal screening after polypectomy will influence rates of colonoscopy in open-access systems that do not require consultation by a gastroenterologist before colonoscopy. Objective: To determine the surveillance recommendations of primary care physicians after polypectomy and compare them with recommendations from the U.S. Multisociety Task Force on Colorectal Cancer. Design: Cross-sectional study of physicians. Setting: United States. Participants: A random sample of 500 physicians from the American College of Physicians and 500 physicians from the American Academy of Family Physicians, obtained by using a mail survey. Measurements: Physicians were asked when they would recommend repeated colonoscopy for a hypothetical 55-year-old man with no family history of colorectal cancer after the following 6 results on colonoscopy: hyperplastic polyp, one 6-mm tubular adenoma, two 6-mm tubular adenomas, one 12-mm tubulovillous adenoma, one 12-mm tubular adenoma with focal high-grade dysplasia, and no polyp but a previous tubular adenoma. Results: The overall response rate was 57% (568 physicians). Of the respondents, 48% were internists and 52% were family practitioners. Sixty-one percent of respondents would survey a hyperplastic polyp in 5 years or less, 71% would survey a single tubular adenoma in 3 years or less, and 80% would survey 2 tubular adenomas in 3 years or less. Limitations: The results are based on physicians' self-reported practices from clinical vignettes and may not match actual practice. Conclusion: Primary care physicians recommend postpolypectomy colonoscopic surveillance more frequently than is recommended by practice guidelines, especially if the colonoscopy showed a hyperplastic polyp or a single small adenoma.
Randomised controlled factorial trial of dietary advice for patients with a single high blood pressure reading in primary care
Authors: Paul Little, Jo Kelly, Jane Barnett, Martina Dorward, Barrie Margetts, Daniel Warm
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To assess the effect of brief interventions during the "watchful waiting" period for hypertension. <b>Design</b> Factorial trial. <b>Setting</b> General practice. <b>Methods</b> 296 patients with blood pressure &gt; 160/90 mm Hg were randomised to eight groups defined by three factors: an information booklet; low sodium, high potassium salt; prompt sheets for high fruit, vegetable, fibre; and low fat. <b>Main outcome measures</b> Blood pressure (primary outcome); secondary outcomes of diet, weight, and dietary biomarkers (urinary sodium:potassium (Na:K) ratio; carotenoid concentrations). Results Blood pressure was not affected by the booklet (mean difference (diastolic blood pressure) at one month 0.2, 95% confidence interval 1.6 to 2.0), salt (0.13; 1.7 to 2.0), or prompts (0.52; 1.3 to 2.4). The salt decreased Na:K ratio (difference 0.32; 0.08 to 0.56, P = 0.01), and the prompts helped control weight (difference 0.39 (0.85 to 0.05) kg at one month, P = 0.085; 1.2 (0.1 to 2.25) kg at six months, P = 0.03). Among those with lower fruit and vegetable consumption (&lt; 300 g per day), prompts increased fruit and vegetable consumption and also carotenoid concentrations (difference 143 (16 to 269) mmol/l, P &lt; 0.03) but did not decrease blood pressure. <b>Conclusion</b> During watchful waiting, over and above the effect of brief advice and monitoring, an information booklet, lifestyle prompts, and low sodium salt do not reduce blood pressure. Secondary analysis suggests that brief interventions—particularly lifestyle prompts—can make useful changes in diet and help control weight, which previous research indicates are likely to reduce the long term risk of stroke.
Gemcitabine Resistance in Pancreatic Cancer: Picking the Key Players
Authors: Michael P. Kim, Gary E. Gallick
Journal: Clinical Cancer Research (2008)

The diagnosis of pancreatic cancer confers a grim prognosis that has changed little over the last 30 years. Due to the lack of any efficacious screening or biomarkers for pancreatic cancer, presentation with advanced local disease is typical (classically, painless jaundice) and morbidity aside, 4%
Discrete Molecular Classes of Ovarian Cancer Suggestive of Unique Mechanisms of Transformation and Metastases
Authors: Nilesh L. Gardi, Tejaswini U. Deshpande, Swapnil C. Kamble, Sagar R. Budhe, Sharmila A. Bapat
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Tumor heterogeneity and subsistence of high-grade serous ovarian adenocarcinoma (HGSC) classes can be speculated from clinical incidences suggesting passive tumor dissemination versus active invasion and metastases. Experimental Design: We explored this theme toward tumor classification through two approaches of gene expression pattern clustering: (i) derivation of a core set of metastases-associated genes and (ii) resolution of independent weighted correlation networks. Further identification of appropriate cell and xenograft models was carried out for resolution of class-specific biologic functions. Results: Both clustering approaches achieved resolution of three distinct tumor classes, two of which validated in other datasets. Networks of enriched gene modules defined biologic functions of quiescence, cell division-differentiation-lineage commitment, immune evasion, and cross-talk with niche factors. Although deviant from normal homeostatic mechanisms, these class-specific profiles are not totally random. Preliminary validation of these suggests that Class 1 tumors survive, metastasize in an epithelial–mesenchymal transition (EMT)-independent manner, and are associated with a p53 signature, aberrant differentiation, DNA damage, and genetic instability. These features supported by association of cell-specific markers, including PAX8, PEG3, and TCF21, led to the speculation of their origin being the fimbrial fallopian tube epithelium. On the other hand, Class 2 tumors activate extracellular matrix–EMT–driven invasion programs (Slug, SPARC, FN1, THBS2 expression), IFN signaling, and immune evasion, which are prospectively suggestive of ovarian surface epithelium associated wound healing mechanisms. Further validation of these etiologies could define a new therapeutic framework for disease management. Clin Cancer Res; 20(1); 87–99. ©2013 AACR.
Platelet-Derived Growth Factor Receptor β Signaling Is Required for Efficient Epicardial Cell Migration and Development of Two Distinct Coronary Vascular Smooth Muscle Cell Populations
Authors: Amy M. Mellgren, Christopher L. Smith, Gregory S. Olsen, Banu Eskiocak, Bin Zhou, Michelle N. Kazi, Fernanda R. Ruiz, William T. Pu, Michelle D. Tallquist
Journal: Circulation Research (2008)

The epicardium plays an essential role in coronary artery formation and myocardial development, but signals controlling the development and differentiation of this tissue are not well understood. To investigate the role of platelet-derived growth factor receptor (PDGFR)β in development of epicardial-derived vascular smooth muscle cells (VSMCs), we examined PDGFR β −/− and PDGFR β epicardial mutant hearts. We found that PDGFR β −/− hearts failed to form dominant coronary vessels on the ventral heart surface, had a thinned myocardium, and completely lacked coronary VSMCs (cVSMCs). This constellation of defects was consistent with a primary defect in the epicardium. To verify that these defects were specific to epicardial derivatives, we generated mice with an epicardial deletion of PDGFRβ that resulted in reduced cVSMCs distal to the aorta. The regional absence of cVSMCs suggested that cVSMCs could arise from 2 sources, epicardial and nonepicardial, and that both were dependent on PDGFRβ. In the absence of PDGFRβ signaling, epicardial cells adopted an irregular actin cytoskeleton, leading to aberrant migration of epicardial cells into the myocardium in vivo. In addition, PDGF receptor stimulation promoted epicardial cell migration, and PDGFRβ-driven phosphoinositide 3′-kinase signaling was critical for this process. Our data demonstrate that PDGFRβ is required for the formation of 2 distinct cVSMC populations and that loss of PDGFRβ-PI3K signaling disrupts epicardial cell migration.
Small-Cell Cancers, and an Unusual Reaction to Chemotherapy
Authors: Jennifer R. Brown, Tad J. Wieczorek, Kitt Shaffer, Ravi Salgia
Journal: Journal of Clinical Oncology (2003)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.081.03 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12805344 Small-Cell Cancers, and an Unusual Reaction to Chemotherapy CASE 1. EXTRAPULMONARY SMALL-CELL CARCINOMA ARISING IN THE PROSTATE Jennifer R. BrownxJennifer R. BrownSearch for articles by this author , Tad J. WieczorekxTad J. WieczorekSearch for articles by this author , Kitt ShafferxKitt ShafferSearch for articles by this author , Ravi SalgiaxRavi SalgiaSearch for articles by this author Show More Dana-Farber Cancer Institute, Brigham & Women’s Hospital, and Harvard Medical School, Boston, MA https://doi.org/10.1200/JCO.2003.081.03 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
Users' Guides to the Medical Literature
Authors: Gordon H. Guyatt
Journal: JAMA (1993)

<h3>CLINICAL SCENARIO</h3> You are working as an internal medicine resident in a rheumatology rotation and are seeing a 19-year-old woman who has had systemic lupus erythematosus diagnosed on the basis of a characteristic skin rash, arthritis, and renal disease. A renal biopsy has shown diffuse proliferative nephritis. A year ago her creatinine level was 140 μmol/L, 6 months ago it was 180 μmol/L, and in a blood sample taken a week before this clinic visit, 220 μmol/L. Over the last year she has been taking prednisone, and over the last 6 months, cyclophosphamide, both in appropriate doses. You are distressed by the rising creatinine level and the rheumatology fellow with whom you discuss the problem suggests that you contact the hematology service to consider a trial of plasmapheresis. The fellow states that plasmapheresis is effective in reducing the level of the antibodies responsible for the nephritis and cites a number
CD30-positive cutaneous T-cell lymphoma with concurrent solid tumour
Authors: W.Y. Au, C.K. Yeung, H.H. Chan, R.W.M. Wong, T.W. Shek
Journal: British Journal of Dermatology (2002)

Summary Extranodal CD30+ T‐cell lymphomas seldom carry classical t(2;5) translocation and are usually anaplastic large cell lymphoma kinase protein negative. They cover a wide spectrum of histological and clinical behaviour. The prognosis of CD30+ cutaneous T‐cell lymphoma (CTCL) is good in the absence of nodal primary or disseminated disease. These lesions can undergo spontaneous regression, and overlap with the group of lesions of lymphomatoid papulosis. Although an increased incidence of solid tumours has been reported in patients with CD30+ non‐Hodgkin lymphoma of the skin, reports of concurrent malignancies are rare in CD30+ CTCL. We report two patients with CD30+ CTCL who, respectively, had concurrent disseminated gastric carcinoma and bilateral ovarian teratoma. Despite an aggressive clinical and histological appearance, both cases ran favourable clinical courses. The CTCL responded completely to chemotherapy in one patient, who eventually succumbed to gastric cancer. In the other patient, lesions regressed spontaneously after bilateral oophorectomy. A possible relationship between the lymphoma and the solid tumours is discussed.
Impact factor and its role in academic promotion
Authors: V. Brusasco, A. T. Dinh-Xuan, A. R. Leff, K. B. Adler, R. W. Glenny, J. A. Dempsey, M. L. Levy, R. Panettieri, H. K. Reddel, D. Singh, J. C. Virchow
Journal: European Respiratory Journal (2009)

shotgun fired at close quarters during military duty into the anterior lower thorax.The lower chest wall, liver, pericardium, base of right lung and heart were impregnated with shot pellets, giving the classical multiple ''star burst'' appearance.(fig.1a).Extensive debridement of the chest wall wound was performed, with the removal of numerous lead shots.Intracardiac and intrapulmonary shots were left in situ and successfully managed conservatively [5].He remained asymptomatic.Injuries were monitored by serial CT scans and echocardiograms, which later showed evidence of embolisation of multiple shots into the lung (fig. 1b).
Analysis of H-2 and Ia molecules by two-dimensional gel electrophoresis.
Authors: P P Jones
Journal: The Journal of Experimental Medicine (1977)

Mouse lymphocyte H-2 and Ia glycoproteins have been analyzed with a two-dimensional (2-D) acrylamide gel electrophoresis technique, in which proteins are separated first according to their charge in isoelectrofocusing gels and then according to their size in sodium dodecyl sulfate gels. Individual polypeptide chains from radiolabeled cells are resolved as discrete spots on autoradiograms of the gels, forming patterns which are characteristic of the proteins in the sample. 2-D gels of H-2K, H-2D, and Ia glycoproteins immunoprecipitated from 35S-methionine-labeled cells reveal that these proteins exist in the cells as complex arrays of molecules heterogeneous in both size and charge. Lactoperoxidase-catalyzed radioiodination of lymphocyte surfaces labels only subsets of the total H-2 and Ia molecules with 125I, indicating that some of the molecules may represent cytoplasmic precursors of the cell surface proteins. This theory is supported by the kinetics of labeling of various spots in 35S-methionine pulse-chase experiments. The 2-D gel patterns obtained for both H-2 and Ia antigens have also been shown to be haplotype-specific and independent of the genetic background.
CD40 Pathway Activation Status Predicts Response to CD40 Therapy in Diffuse Large B Cell Lymphoma
Authors: Bart Burington, Peng Yue, Xiaoyan Shi, Ranjana Advani, Jeffrey T. Lau, Jenille Tan, Susanna Stinson, Jeremy Stinson, Thomas Januario, Sven de Vos, Stephen Ansell, Andres Forero-Torres, Grazyna Fedorowicz, Teddy T. C. Yang, Kristi Elkins, Changchun Du, Sankar Mohan, Nancy Yu, Zora Modrusan, Somasekar Seshagiri, Shang-Fan Yu, Ajay Pandita, Hartmut Koeppen, Dorothy French, Andrew G. Polson, Rienk Offringa, Nancy Whiting, Allen Ebens, David Dornan
Journal: Science Translational Medicine (2011)

The primary function of B cells, critical components of the adaptive immune response, is to produce antibodies against foreign antigens, as well as to perform isotype class switching, which changes the heavy chain of an antibody so that it can interact with different repertoires of effector cells. CD40 is a member of the tumor necrosis factor superfamily of cell surface receptors that transmits survival signals to B cells. In contrast, in B cell cancers, stimulation of CD40 signaling results in a heterogeneous response in which cells can sometimes undergo cell death in response to treatment, depending on the system studied. We found an association between sensitivity to CD40 stimulation and mutation of the tumor suppressor p53 in a panel of non-Hodgkin's lymphoma cell lines. Consistent with p53's tumor suppressor role, we found that higher levels of intrinsic DNA damage and increased proliferation rates, as well as higher levels of BCL6, a transcriptional repressor proto-oncogene, were associated with sensitivity to CD40 stimulation. In addition, CD40 treatment-resistant cell lines were sensitized to CD40 stimulation after the introduction of DNA-damaging agents. Using gene expression analysis, we also showed that resistant cell lines exhibited a preexisting activated CD40 pathway and that an mRNA expression signature comprising CD40 target genes predicted sensitivity and resistance to CD40-activating agents in cell lines and mouse xenograft models. Finally, the gene signature predicted tumor shrinkage and progression-free survival in patients with diffuse large B cell lymphoma treated with dacetuzumab, a monoclonal antibody with partial CD40 agonist activity. These data show that CD40 pathway activation status may be useful in predicting the antitumor activity of CD40-stimulating therapeutic drugs.
Light- and electron-microscope studies of the effects of 4-aminopteroylglutamic acid (aminopterin) on the mucous membrane of the small intestine of the rat
Authors: A. W. Williams
Journal: Gut (1961)

Aminopterin, a cytotoxic agent, causes mitotic arrest by interfering with the catabolism of ribonucleoprotein. The effects on the small intestine are demonstrated. The resulting atrophy, with changes in the microvilli, is associated with severely impaired fat absorption.
Estrogen Receptor Mutations in Breast Cancer—New Focus on an Old Target
Authors: Corrinne V. Segal, Mitch Dowsett
Journal: Clinical Cancer Research (2014)

Abstract Recent studies have provided strong evidence for the emergence of substantial numbers of constitutively active ESR1 mutations in estrogen receptor–positive metastatic breast cancer that are undetected in primary disease. Some of these mutants remain partially sensitive to current anti-estrogen therapies but effective therapeutics targeted at them may require new approaches. Clin Cancer Res; 20(7); 1724–6. ©2014 AACR.
Aminooxypentane-RANTES Induces CCR5 Internalization but Inhibits Recycling: A Novel Inhibitory Mechanism of HIV Infectivity
Authors: Matthias Mack, Bruno Luckow, Peter J. Nelson, Josef Cihak, Graham Simmons, Paul R. Clapham, Nathalie Signoret, Mark Marsh, Manfred Stangassinger, Fréderic Borlat, Timothy N.C. Wells, Detlef Schlöndorff, Amanda E.I. Proudfoot
Journal: The Journal of Experimental Medicine (1998)

CCR5, a chemokine receptor expressed on T cells and macrophages, is the principal coreceptor for M-tropic HIV-1 strains. Recently, we described an NH2-terminal modification of the CCR5 ligand regulated on activation, normal T cell expressed and secreted (RANTES), aminooxypentane-RANTES (AOP-RANTES), that showed potent inhibition of macrophage infection by HIV-1 under conditions where RANTES was barely effective. To investigate the mechanism of AOP-RANTES inhibition of HIV infectivity we examined the surface expression of CCR5 using a monoclonal anti-CCR5 antibody, MC-1. We demonstrate that AOP-RANTES rapidly caused &amp;gt;90% decrease in cell surface expression of CCR5 on lymphocytes, monocytes/ macrophages, and CCR5 transfected Chinese hamster ovary (CHO) cells. RANTES also caused a loss of cell surface CCR5, although its effect was less than with AOP-RANTES. Significantly, AOP-RANTES inhibited recycling of internalized CCR5 to the cell surface, whereas RANTES did not. When peripheral blood mononuclear cells are cultured for prolonged periods of time in the presence of RANTES, CCR5 expression is comparable to that seen on cells treated with control medium, whereas there is no CCR5 surface expression on cells cultured in the presence of AOP-RANTES. Immunofluorescence indicated that both AOP-RANTES and RANTES induced downmodulation of cell surface CCR5, and that the receptor was redistributed into endocytic organelles containing the transferrin receptor. When RANTES was removed, the internalized receptor was recycled to the cell surface; however, the receptor internalized in the presence of AOP-RANTES was retained in endosomes. Using human osteosarcoma (GHOST) 34/CCR5 cells, the potency of AOP-RANTES and RANTES to inhibit infection by the M-tropic HIV-1 strain, SF 162, correlated with the degree of downregulation of CCR5 induced by the two chemokines. These differences between AOP-RANTES and RANTES in their effect on receptor downregulation and recycling suggest a mechanism for the potent inhibition of HIV infection by AOP-RANTES. Moreover, these results support the notion that receptor internalization and inhibition of receptor recycling present new targets for therapeutic agents to prevent HIV infection.