tbuckley/cabot-search huggingface dataset:
Calcium Carbonate as a Phosphate Binder in Patients with Chronic Renal Failure Undergoing Dialysis
Authors: Eduardo Slatopolsky, Carol Weerts, Silvia Lopez-Hilker, Kathryn Norwood, Mary Zink, David Windus, James Delmez
Journal: New England Journal of Medicine (1986)

Phosphate binders that contain aluminum are frequently prescribed to treat hyperphosphatemia in patients with chronic renal failure, but an accumulation of aluminum can lead to osteomalacia. To evaluate the efficacy of calcium carbonate as an alternative phosphate binder, we studied 20 patients maintained on dialysis during three consecutive periods. In period 1, the patients took aluminum hydroxide for a month (mean dose, 5.6 g per day; range, 1.5 to 14.0). In period 2, they took no phosphate binders for a month, and in period 3, they took calcium carbonate (Os-Cal) for two months (mean dose, 8.5 g per day; range, 2.5 to 17). The mean (±SE) serum calcium level during period 1 was 9.6±0.2 mg per deciliter; this decreased slightly (to 9.3±0.1) during period 2 and increased to 10.0±0.2 during period 3. The mean (±SE) serum phosphorus level during period 1 was 4.8±0.1 mg per deciliter; this increased to 7.3±0.3 during period 2, but returned to the control value (4.8±0.2) during period 3. Six of the 20 patients continued to need aluminum hydroxide during period 3 for satisfactory control of hyperphosphatemia. Calcium carbonate successfully lowered serum phosphorus levels and raised serum calcium levels in the majority of our patients, thereby confirming that this agent may be a satisfactory substitute for traditional phosphate binders that contain aluminum. The possibility that long-term treatment could cause such side effects as metastatic calcification will require further investigation. (N Engl J Med 1986;315:157–61.)
Abstract 372: Endothelial epsin deficiency decreases tumor growth by enhancing VEGF signaling.
Authors: Hong Chen, Pasula Satish, Xiaofeng Cai, Yunzhou Dong, Baojun Chang
Journal: Cancer Research (2013)

Abstract To examine the angiogenic role of endothelial epsins, a family of ubiquitin binding endocytic clathrin adaptors, we generated mice with constitutive or inducible deletion of epsins 1 and 2 in vascular endothelium. These mice exhibited no abnormal phenotypes under normal conditions, suggesting that lack of endothelial epsins 1 and 2 does not affect normal blood vessels. However, adult mice lacking endothelial epsins 1 and 2 exhibited highly disorganized tumor vasculature, significantly increased vascular permeability, and markedly retarded tumor growth. Mechanistically, we show that VEGF promotes binding of epsin to ubiquitinated VEGF receptor 2 (VEGFR2). Loss of epsins 1 and 2 specifically impairs endocytosis and degradation of VEGFR2 which results in excessive VEGF signaling that compromises tumor vascular function by exacerbating non-productive leaky angiogenesis. This suggests that tumor vasculature requires a balance in VEGF signaling to provide sufficient productive angiogenesis for tumor development, and that endothelial epsins 1 and 2 negatively regulate the output of VEGF signaling. Thus, promoting excessive VEGF signaling within tumors via a block of epsin 1 and 2 function, may represent a strategy to prevent normal angiogenesis in cancer patients who are resistant to anti-VEGF therapies. Citation Format: Hong Chen, Pasula Satish, Xiaofeng Cai, Yunzhou Dong, Baojun Chang. Endothelial epsin deficiency decreases tumor growth by enhancing VEGF signaling. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 372. doi:10.1158/1538-7445.AM2013-372 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
P388Reduced pressure overload-induced myocardial remodeling in K201-treated mice with the R4496C cardiac ryanodine receptor mutation
Authors: S Sedej, M Matovina, A Schmidt, S Ljubojevic, FR Heinzel, S Negri, C Napolitano, MA Vos, SG Priori, B Pieske
Journal: Cardiovascular Research (2014)

Purpose: Spontaneous sarcoplasmic reticulum (SR) Ca2+ release through defective cardiac ryanodine receptor (RyR2) promotes contractile dysfunction and myocardial remodeling in response to pressure overload. We tested the hypothesis that RyR2 stabilizer K201 attenuates the SR Ca2+ leak and ameliorates pressure overload-induced cardiac remodeling in mice carrying RyR2 gain-of-function mutation. Methods: RyR2R4496C+/- knock-in mice (R4496C) and their wild-type (WT) littermates underwent surgery without (Sham) or with transaortic banding (TAB). Changes in Ca2+ spark frequency (as a measure for the SR Ca2+ leak) were monitored by means of confocal Ca2+ imaging (Fluo-4/AM, linescan mode) in isolated ventricular cardiomyocytes (1 week post-surgery) under control conditions and after the pre-incubation (≥ 1-hour) with 300 nmol/L K201 or 1 mmol/L dantrolene (positive control). K201 (12 mg/kg/day) or DMSO (vehicle) was administered in R4496C-TAB mice for 4 weeks via osmotic minipumps. K201 plasma concentration was determined by using high performance liquid chromatography. Structural dimensions and function of the left ventricle (LV) were assessed by transthoracic echocardiography 1 and 3 weeks after surgery. Data are shown as mean±S.E.M. Results: K201 markedly reduced the increase in Ca2+ spark frequency at matched SR Ca2+ load in R4496C-TAB (83.9±8.6 pL-1s-1 vs. 332.7±42.9 pL-1s-1) and WT-TAB cells (82.2±6.5 pL-1s-1 vs. 190.1±27 pL-1s-1) as well as R4496C-Sham cells (72.1±7.5 pL-1s-1 vs. 173.6±20.9 pL-1s-1, all P<0.05 versus control, respectively). The RyR2 stabilizing effect was more pronounced in the presence of K201 than dantrolene. Chronic infusion of K201 resulted in a mean K201 plasma concentration of 163±25 nmol/L. In R4496C-TAB mice, K201 prevented the decline in fractional shortening (1 week: 24.5±2.6% vs. 17.9±1.8%; 3 weeks: 21.3±2.6% vs. 15.2±2.4%, both P<0.05 versus vehicle-treated R4496C-TAB, respectively), restored an increase in the relative wall thickness (1 week: 0.44±0.02 mm vs. 0.40±0.01 mm; 3 weeks: 0.46±0.02 mm vs. 0.36±0.03 mm) and largely ameliorated LV dilatation (LV end-systolic diameter, 1 week: 3.10±0.15 mm vs. 3.75±0.26 mm; 3 weeks: 3.35±0.19 mm vs.4.23±0.31 mm, all P<0.05 versus vehicle-treated R4496C-TAB, respectively). K201 treatment reduced mortality over 6 weeks after TAB: 83% of K201-treated R4496C-TAB mice were alive vs. 31% treated with the vehicle (P<0.05). Conclusions: Pharmacological stabilization of SR Ca2+ release by K201 ameliorates the development of heart failure, preserves systolic function and improves survival in R4496C-TAB mice.
Toxicokinetic and Toxicodynamic Influences on Endocrine Disruption by Polychlorinated Biphenyls.
Authors: S Soontornchat, MH Li, PS Cooke, LG Hansen
Journal: Environmental Health Perspectives (1994)

Polychlorinated biphenyl (PCB) mixtures and individual chlorobiphenyl (CB) congeners have various endocrine-disrupting effects, but ultimate responses may be altered by concurrent effects on enzyme levels and enzyme activities. The toxicodynamics of estrogenic PCBs and metabolites have been studied in vitro, but nonlinear dose-response relationships in vivo suggest that tests must integrate toxicokinetic parameters to explain whole-animal responses. To determine if any such interactions occurred, relatively large doses were subdivided into different treatment regimens for immature female Sprague-Dawley rats. Aroclor 1242 was uterotropic when 120 mg/kg (total) was administered (intraperitoneally) in two, three or five doses. CB 47 (2,2',4,4'-tetraCB) and CB 153 (2,2',4,4',5,5'-hexaCB) increased absolute uterine weights at 30 mg/kg on days 20 and 21. Results at 25 days in rats that received zero, two, three or five doses between days 20 and 24 were much more variable due to changes in tissue responsiveness and/or toxicokinetic interactions. In rats receiving treatment for 5 days, pentoxyresorufin O-dealkylase (PROD) activity was inversely related to CB serum residues; in rats receiving CB 153 for 2 days, PROD activity was directly related to serum residues. It was not clear whether PROD activity was the cause of or a reflection of lower serum residues; however, nonplanar CBs are better substrates for PROD than are planar CBs, and the longer-term dosing may enhance metabolism and excretion, changing the biological effects observed.
False Positive Tests for HIV in a Woman with Lupus and Renal Failure
Authors: R. Jindal, M. Solomon, L. Burrows
Journal: New England Journal of Medicine (1993)

To the Editor: We recently encountered the uncommon situation of a false positive test for human immunodeficiency virus type 1 (HIV-1) during the pretransplantation evaluation of a 32-year-old Haitian woman with systemic lupus erythematosus and end-stage renal disease. Her condition had been stable with the use of hemodialysis for the previous 6 years, and she had resided in the United States for 15 years. Serologic tests were negative for cytomegalovirus, Epstein-Barr virus, herpes, toxoplasmosis, and hepatitis. Screening tests for syphilis were also negative. Both she and her husband were monogamous, with no history of drug abuse or blood transfusions. She . . .
Role of radiation induced ß1 – integrin expression in trastuzumab resistance in Her-2 positive breast cancer.
Authors: J Thoms, S Sabri, D Lesniak, D Murray, B Abdulkarim
Journal: Cancer Research (2009)

Abstract Abstract #2014 Problem Statement: Radiation therapy followed by Trastuzumab-based therapy is the standard of care for Her-2 positive breast cancer (BC) patients, but the molecular basis of this sequential treatment has not been investigated. Fifty percent of early BC patients show primary resistance to Trastuzumab (Tz) and 70% of metastatic breast cancer patients develop Tz resistance within one year. Our in vitro pre-clinical data suggests the role of ß1-integrin, a cell adhesion molecule involved in cell survival, invasion and drug resistance, in Tz resistance. Because ionizing radiation (IR) increases the expression of several integrin subunits in endothelial and tumor cells, we hypothesized that radiation induced ß1-integrin expression could be a potential mechanism of Tz resistance in Her-2 positive BC patients.&amp;#x2028; Methods: We use Her-2 positive Tz-senstive BC cell lines, SKBR-3 and BT474, which express lower levels of ß1- integrin, than the Tz-resistant cell line JIMT-1.&amp;#x2028; We analyzed by Immunoblotting the expression of ß1-integrin, phosphorylation and expression of Her-2 and common downstream signaling pathways, PI3-K/Akt and Erk1/2 before and after exposure to IR.&amp;#x2028; Results: Exposure to IR increased ß1-integrin expression in SKBR-3 and BT474 cells, but not in JIMT-1. Increased ß1-integrin expression in BT474 cells was associated with a substantial increase in phosphorlyation of Her-2, suggesting that ß1-inetgrin may induce transactivation of Her-2. Phosphorylation of Erk 1/2 and Akt, important signal transducers for cell proliferation and survival were also increased.&amp;#x2028; We will further, investigate Tz sensitivity of SKBR-3 and BT474 following exposure to IR using a blocking antibody for ß1-integrin, and clonogenic survival and XTT assays to evaluate cellular viability and proliferation.&amp;#x2028; Conclusion: Our results show that IR increased ß1-integrin expression and activation of the PI3-K/Akt pro-survival pathway and suggest that increased b1-integrin expression by IR may confer resistance to Trastuzumab in Her-2 positive cell lines. The physiological relevance of radiation-induced ß1-inetgrin expression in Trastuzumab resistance needs to be further investigated in vivo. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2014.
A new attachment hood (Nanoshooter) for transnasal endoscopic submucosal dissection of the hypopharynx
Authors: Masakatsu Nakamura, Hisakazu Shiroeda, Tomomitsu Tahara, Tomoyuki Shibata, Tomiyasu Arisawa
Journal: Endoscopy (2013)

Endoscopic submucosal dissection (ESD) in the pharyngeal region is considered difficult. When ESD is carried out transorally for a tumor in the pharynx, the patient must be sedated [1]. However, we have carried out, without sedation, ESD with a transnasal endoscope and our novel endoscopic attachment hood for this area. There is evidence that our method may be associated with reduced incidence of hemorrhage and perforation [2]. Here, we report on the use of ESD in the treatment of pharyngeal dysplasia.
INITIAL FEASIBILITY RESULTS OF A GROUP COPING AND RESILIENCE PROGRAM FOR ADULTS WITH CONGENITAL HEART DISEASE
Authors: Adrienne H. Kovacs, Amanda C. Kentner, Sherry L. Grace, Robert Nolan, Candice Silversides, Mimi Bandyopadhyay, Jane Irvine
Journal: Journal of the American College of Cardiology (2015)
BASELINE RED CELL DISTRIBUTION WIDTH INDEPENDENTLY PREDICTS POST-OPERATIVE ATRIAL FIBRILLATION
Authors: Joseph G. Akar, Georges El-Hachem, Bassem Ayyash, Anis Kadado, Rim Al Nabbout, Nader Lamaa, Haikun Bao, Bassam Abou Khalil
Journal: Journal of the American College of Cardiology (2016)
1182 THE LIVER LYMPHOCYTE INTRA-HEPATIC ACTIVITY IS DIFFERENT BETWEEN HEPATITIS B VIRUS AND HEPATITIS C VIRUS BUT DEPENDENT OF IL28B POLYMORPHISM
Authors: J.P. Zarski, M.A. Thélu, H. Marche, E. Fugier, A. Marlu, N. Sturm, V. Leroy, P. Marche, E. Jouvin-Marche
Journal: Journal of Hepatology (2013)
Primary Osteogenic Sarcoma of the Breast Demonstrated by Tc-99m MDP Scintigraphy
Authors: JONG-KANG LEE, SUN SHUNG-SHUNG
Journal: Clinical Nuclear Medicine (1998)

A 40-year-old woman with a large right breast mass underwent Tc-99m MDP scintimammography and a whole-body bone scan. Both images showed intense uptake of Tc-99m MDP in the right breast tumor. A modified radical mastectomy was performed, and histopathologic examination revealed the tumor to be a primary osteogenic sarcoma of the breast.
Frequency of alcohol-associated injury in adults presenting to a Ghanaian emergency department
Authors: Paa Kobina Forson, Andrew Gardner, George Oduro, Joseph Bonney, Eno Akua Biney, Chris Oppong, Eszter Momade, Ronald F Maio
Journal: The Lancet Global Health (2016)

Background Injuries are the cause of almost 6 million deaths every year, with 15–20% of these associated with alcohol use. However, the frequency of alcohol-associated injury varies widely between countries, but is unknown in Ghana. In this cross-sectional chart review, we aimed to measure the frequency of alcohol-associated injury in adults who presented to an emergency department in Kumasi, Ghana.
Successful Clinical Use of an Anti-HLA-DR Monoclonal Antibody for Autologous Bone Marrow Transplantation
Authors: G. Kvalheim, S. Funderud, S. Kvaloy, G. Gaudernack, K. Beiske, E. Jakobsen, A. B. Jacobsen, A. Pihl, O. Fodstad
Journal: JNCI Journal of the National Cancer Institute (1988)

It has been widely assumed that anti-HLA-DR antibodies react with pluripotent stem cells and cannot be used in bone marrow purging. We report a case of non-Hodgkin's lymphoma in which an anti-HLA-DR antibody (AB4) was used for immunomagnetic purging and the subsequent autologous bone marrow transplantation resulted in rapid marrow engraftment with no serious complications. The results indicate that the AB4 antibody, which binds to an antigen encoded by the B3 gene of the DR region, can be safely used in the clinic in the purging of bone marrow from patients with AB4-positive tumors (non-T-cell acute lymphocytic leukemia, nonHodgkin's lymphoma, and some cases of acute myelogenous leukemia).
Abstract 465: Alternatively activated bone marrow-derived macrophages enhance tumor growth and metastasis in a 4T1 mammary cancer model
Authors: Han Jin Cho, Do Young Lim, Jae In Jung, Song Her, Jung Han Yoon Park
Journal: Cancer Research (2011)

Abstract Tumor microenvironment consists of a number of components including malignant cells, stromal cells, endothelial cells, infiltrating immune cells, and extracellular matrix. Because inflammation plays an important role in cancer development and progression, tumor-associated macrophages (TAMs) can be one of key regulators of tumor microenvironment. Recent evidence has shown that TAM is associated with poor prognosis in a variety of cancers, including breast, lung, and pancreatic cancer. TAMs account for up to 50% of the total tumor mass, resemble M2-macrophages, and exhibit a number of pro-tumoral functions, including the expression of growth factors and matrix proteases, the promotion of angiogenesis, and the suppression of adaptive immunity. In the present study, we examined the effect of M2 macrophages on the development of and metastasis of mammary cancer using a 4T1-orthotopic tumor model. Monocytes were isolated from mouse bone marrow and treated with IL-4 to induce differentiation into an M2 phenotype. In order to determine whether or not M2 microphages stimulate mammary cancer growth and progression, 4T1 mammary carcinoma cells were injected into the inguinal mammary fat pad of syngeneic BALB/C mice, either alone or coupled with bone marrow-derived alternatively-activated macrophages (BMDAM). Co-injection of 4T1 cells with BMDAM increased solid tumor volumes (at 2 weeks after inoculation) and lung metastasis (at 3 weeks after inoculation). We prepared 4T1-luc cells that stably express firefly luciferase which allows for direct examination of tumor growth in animals by estimating the luciferase activity of 4T1 cancer cells via an in vivo imaging system. Luminescence was quantified, and the results demonstrated that the accumulation of 4T1-luc cells was significantly more pronounced when 4T1 cells were co-injected with BMDAM. Immunohistochemical staining of tumor tissues revealed that the proportion of Ki67 (proliferation index)-positive cells was increased in tumor tissues when 4T1 cells were co-injected with BMDAM. We also observed that co-injection of BMDAM with 4T1 cells increased the expression of hypoxia-inducible factor-1α and CD31 (a glycoprotein expressed on endothelial cells and in platelets)-positive cells. These results indicate that TAM increases the proliferation of mammary tumor cells, which may lead to the stimulation of lung metastasis in the 4T1 mammary carcinoma model. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 465. doi:10.1158/1538-7445.AM2011-465
A10.14 Inhibition of sclerostin accelerates TNFα-mediated bone destruction
Authors: C Wehmeyer, S Frank, D Beckmann, M Böttcher, C Cromme, U König, M Fennen, A Held, P Paruzel, C Hartmann, A Stratis, A Korb-Pap, T Kamradt, I Kramer, W van den Berg, M Kneissel, T Pap, B Dankbar
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Wnt-inhibitor sclerostin has anti-anabolic effects on bone formation by negatively regulating osteoblast differentiation. Loss of sclerostin expression results in high bone mass and bone strength in patients with sclerosteosis and sclerostin knockout mice. Therefore, antibody-mediated inhibition of sclerostin is currently evaluated for the treatment of osteoporosis in humans. Since it has been shown that sclerostin is upregulated by TNFα, we studied its impacton inflammatory arthritis using RA mouse models such as the human TNF transgenic (hTNFtg) model, the G6PI-induced arthritis model and the K/BxN serum transfer-induced arthritis model. <h3>Materials and methods</h3> Sclerostin knockout (<i>sost</i><sup>-/-</sup>) mice were crossed with hTNFtg mice to generate <i>sost<sup>-/</sup></i><sup>-</sup>/hTNFtg. Mice with serum transfer-induced arthritis were generated by injection of arthritogenic serum collected from K/BxN mice in <i>sost</i><sup>-/-</sup> and wild type (WT) mice. Arthritis was induced in DEREG mice by immunisation with recombinant glucose-6-phosphate isomerase (G6PI). To switch to the non-remitting G6PI-induced arthritis, Foxp3<sup>+</sup> regulatory T-cells were depleted by diphtheria toxin. hTNFtg and G6PI-induced arthritis mice were treated with a neutralising antibody against human and murine sclerostin. Clinical disease severity, bone erosion, cartilage destruction and pannus formation were evaluated by histomorphometric, x-ray and micro-CT analysis. Sclerostin expression and p38 activation was assessed by immunohistochemistry, western-blot-analysisor RT-PCR. Knockdown of LRP5 and LRP6 was performed by transfection of fibroblast-like synoviocytes (FLS) with siRNA. <h3>Results</h3> This study showed for the first time that TNFα induces sclerostin expressionin RA-FLS. Surprisingly, the lack of sclerostin and its antibody-mediated inhibition led to deterioration of RA-like disease in hTNFtgmice with enhanced pannus formation and joint destruction. Suggesting a specific role for sclerostin in TNFα&nbsp;signalling, inhibition of sclerostin also failed to improve clinical signs and joint destruction in the partially TNFα-dependent G6PI-induced arthritis, but ameliorated disease severity in K/BxN serum transfer-induced arthritis,in which&nbsp;TNFα&nbsp;plays only a minor role. FLS from <i>sost<sup>-/-</sup></i>/hTNFtg mice displayed increased TNFα-mediated p38 activation, a key step in arthritis development. In turn, sclerostin effectively blocked TNFα-induced but not IL-1-induced activation of p38 with participation of the canonical Wnt receptor LRP6. <h3>Conclusion</h3> Collectively, these data demonstrated that sclerostin appears to have a protective function in TNF-mediated chronic inflammation.
Endolumenal full-thickness colon-wall resection using an over-the-scope-clip: three techniques compared in a porcine survival study
Authors: E Rieder, I Mesteri, JE Bolton, MF Connor, BG Timmel, HM Whiteford, LL Swanström
Journal: Endoscopy (2012)

Objective: Reliable endoscopic full-thickness resection (EFTR) of the GI-tract would be a desirable adjunct to GI-cancer care. We have recently described an appealing technique for EFTR, using T-tag sutures for accurate tissue retraction and the over-the-scope-clip for pre-resection tissue closure. The aim of this animal survival study was to compare this technique in an either hybrid or purely endolumenal fashion, with a modified method using solely endoscopic suction for retraction.
Women's Health Trial on Trial
Authors: Kara Smigel
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Women's Health Trial on Trial Get access Kara Smigel Kara Smigel Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 5, 6 March 1991, Pages 321–323, https://doi.org/10.1093/jnci/83.5.321 Published: 06 March 1991