tbuckley/cabot-search huggingface dataset:
Chromosomal localization of the genes for the vitronectin and fibronectin receptors alpha subunits and for platelet glycoproteins IIb and IIIa.
Authors: D M Sosnoski, B S Emanuel, A L Hawkins, P van Tuinen, D H Ledbetter, R L Nussbaum, F T Kaos, E Schwartz, D Phillips, J S Bennett
Journal: Journal of Clinical Investigation (1988)

The integrins, a family of related membrane receptors involved in cell-cell and cell-matrix interactions, are heterodimeric complexes of alpha and beta subunits. To begin to understand the evolution of these complexes, we studied the genomic organization of several alpha and beta integrin subunits. Using both somatic cell hybrids and an in situ hybridization technique, we have determined the chromosomal location of the genes for the alpha subunits of the vitronectin receptor (VNR alpha), the fibronectin receptor (FNR alpha), and for the alpha subunit of the platelet glycoprotein IIb/IIIa complex, GPIIb. In addition, we have determined the chromosomal location of the gene for the beta subunit of the GPIIb/IIIa heterodimer, GPIIIa. Our studies indicate that the alpha subunits do not localize to a single locus, but that each is found on a different chromosome. The gene for VNR alpha is located on chromosome 2, the gene for FNR alpha is on chromosome 12q11----13, and the gene for GPIIb is on chromosome 17q21----23. In contrast to the chromosomal dispersion of the alpha subunits, the genes for GPIIb and GPIIIa are physically close, with the gene for GPIIIa also located on chromosome 17q21----23. These studies indicate that the genes for the alpha subunits of the integrin family have been dispersed during evolution while GPIIb and GPIIIa are in close physical proximity. This physical proximity of GPIIb and GPIIIa may be involved in the concurrent expression of these proteins by megakaryocytes, and may result in linkage disequilibrium between these two genes, which would limit the use of restriction length polymorphisms in linkage studies of GPIIb/IIIa abnormalities in small kindreds.
TIMP2 Deficiency Accelerates Adverse Post–Myocardial Infarction Remodeling Because of Enhanced MT1-MMP Activity Despite Lack of MMP2 Activation
Authors: Vijay Kandalam, Ratnadeep Basu, Thomas Abraham, Xiuhua Wang, Paul D. Soloway, Diane M. Jaworski, Gavin Y. Oudit, Zamaneh Kassiri
Journal: Circulation Research (2010)

Rationale : Myocardial infarction (MI) results in remodeling of the myocardium and the extracellular matrix (ECM). Tissue inhibitors of metalloproteinases (TIMPs) are critical regulators of ECM integrity via inhibiting matrix metalloproteinases (MMPs). TIMP2 is highly expressed in the heart and is the only TIMP that, in addition to inhibiting MMPs, is required for cell surface activation of pro-MMP2. Hence, it is difficult to predict the function of TIMP2 as protective (MMP-inhibiting) or harmful (MMP-activating) in heart disease. Objective : We examined the role of TIMP2 in the cardiac response to MI. Methods and Results : MI was induced in 11- to 12-week-old male TIMP2 −/− and age-matched wild-type mice. Cardiac function was monitored by echocardiography at 1 and 4 weeks post-MI. ECM fibrillar structure was visualized using second harmonic generation and multiphoton imaging of unfixed/unstained hearts. Molecular analyses were performed at 3 days and 1 week post-MI on flash-frozen infarct, periinfarct, and noninfarct tissue. Membrane type 1 (MT1)-MMP levels and activity were measured in membrane protein fractions. TIMP2 −/− -MI mice exhibited a 25% greater infarct expansion, markedly exacerbated left ventricular dilation (by 12%) and dysfunction (by 30%), and more severe inflammation compared to wild-type MI mice. Adverse ECM remodeling was detected by reduced density and enhanced disarray of fibrillar collagen in TIMP2 −/− -MI compared to wild-type MI hearts. TIMP2 deficiency completely abrogated MMP2 activation but markedly increased collagenase activity, particularly MT1-MMP activity post-MI. Conclusions : The MMP-inhibitory function of TIMP2 is a key determinant of post-MI myocardial remodeling primarily because of its inhibitory action on MT1-MMP. TIMP2 replenishment in diseased myocardium could provide a potential therapy in reducing or preventing disease progression.
Serum Amyloid A As a Prognostic Marker in Melanoma Identified by Proteomic Profiling
Authors: Peter Findeisen, Marc Zapatka, Teresa Peccerella, Heike Matzk, Michael Neumaier, Dirk Schadendorf, Selma Ugurel
Journal: Journal of Clinical Oncology (2009)

Currently known prognostic serum biomarkers of melanoma are powerful in metastatic disease, but weak in early-stage patients. This study was aimed to identify new prognostic biomarkers of melanoma by serum mass spectrometry (MS) proteomic profiling, and to validate candidates compared with established markers.Two independent sets of serum samples from 596 melanoma patients were investigated. The first set (stage I = 102; stage IV = 95) was analyzed by matrix assisted laser desorption and ionization time of flight (MALDI TOF) MS for biomarkers differentiating between stage I and IV. In the second set (stage I = 98; stage II = 91; stage III = 87; stage IV = 103), the serum concentrations of the candidate marker serum amyloid A (SAA) and the known biomarkers S100B, lactate dehydrogenase, and C reactive protein (CRP) were measured using immunoassays.MALDI TOF MS revealed a peak at m/z 11.680 differentiating between stage I and IV, which could be identified as SAA. High peak intensities at m/z 11.680 correlated with poor survival. In univariate analysis, SAA was a strong prognostic marker in stage I to III (P = .043) and stage IV (P = .000083) patients. Combination of SAA and CRP increased the prognostic impact to P = .011 in early-stage (I to III) patients. Multivariate analysis revealed sex, stage, tumor load, S100B, SAA, and CRP as independent prognostic factors, with an interaction between SAA and CRP. In stage I to III patients, SAA combined with CRP was superior to S100B in predicting patients' progression-free and overall survival.SAA combined with CRP might be used as prognostic serological biomarkers in early-stage melanoma patients, helping to discriminate low-risk patients from high-risk patients needing adjuvant treatment.
Hereditary angioneurotic oedema: an unusual case of recurring abdominal pain
Authors: E. J. Feller, H. M. Spiro, L. A. Katz
Journal: Gut (1970)

Two patients with hereditary angioneurotic oedema, a condition characterized by repeated episodes of abdominal pain and oedema, and by an absence of complement-1 esterase inhibitor activity in the plasma are presented in detail. Both underwent multiple surgical procedures before the diagnosis was established. Abdominal pain is often the presenting complaint, and although a complete history will usually lead to the proper diagnosis, cases in which the family history is not clear can present a diagnostic dilemma. Characteristic radiological demonstration of localized intestinal oedema will only be obtained if studies are performed early during the acute attack.
Complex, Not Monosomal, Karyotype Is the Cytogenetic Marker of Poorest Prognosis in Patients With Primary Myelodysplastic Syndrome
Authors: David Valcárcel, Vera Ademà, Francesc Solé, Margarita Ortega, Benet Nomdedeu, Guillermo Sanz, Elisa Luño, Consuelo Cañizo, Javier de la Serna, Maite Ardanaz, Victor Marco, Rosa Collado, Javier Grau, Julia Montoro, Mar Mallo, Teresa Vallespí
Journal: Journal of Clinical Oncology (2013)

Complex karyotype (CK) is the poorest risk factor in patients with myelodysplastic syndrome (MDS). It has recently been reported that monosomal karyotype (MK) worsens the prognosis of patients with CK. PATIENTS AND METHODS; We analyzed 1,054 adult patients with MDS with an abnormal karyotype from the Spanish Registry of MDS. The aim of the study was to describe the incidence, characteristics, and prognosis of MK; the main end points were overall survival (OS) and leukemia-free survival.MK was identified in 172 patients (16%), most of whom (88%) presented with CK. Variables significantly associated with OS were age (hazard ratio [HR], 1.90; P < .001), bone marrow (BM) blast percentage (HR, 1.05; P < .001), hemoglobin level (HR, 1.71; P < .001), platelet count (HR, 1.41; P < .001), karyotype complexity (CK [three abnormalities]: HR, 1.81; P = .003; very CK [> three abnormalities]: HR, 2; P < .001), and abnormalities of chromosome 5 and/or 7 (HR, 1.89; P < .001). Variables significantly related to the risk of transformation to acute myeloid leukemia (AML) were higher BM blast percentage (HR, 1.12; P < .001) and karyotype complexity (CK: HR, 2.53; P = .002; very CK: HR, 2.77; P < .001).After accounting for karyotype complexity, MK was not associated with OS or evolution to AML. In conclusion, these results demonstrate that the prognostic value of MK in MDS is not independent and is mainly the result of its strong association with number of chromosomal abnormalities.
Mast Cells Infiltrating Inflamed or Transformed Gut Alternatively Sustain Mucosal Healing or Tumor Growth
Authors: Alice Rigoni, Lucia Bongiovanni, Alessia Burocchi, Sabina Sangaletti, Luca Danelli, Carla Guarnotta, Amy Lewis, Aroldo Rizzo, Andrew R. Silver, Claudio Tripodo, Mario P. Colombo
Journal: Cancer Research (2015)

Mast cells (MC) are immune cells located next to the intestinal epithelium with regulatory function in maintaining the homeostasis of the mucosal barrier. We have investigated MC activities in colon inflammation and cancer in mice either wild-type (WT) or MC-deficient (Kit(W-sh)) reconstituted or not with bone marrow-derived MCs. Colitis was chemically induced with dextran sodium sulfate (DSS). Tumors were induced by administering azoxymethane (AOM) intraperitoneally before DSS. Following DSS withdrawal, Kit(W-sh) mice showed reduced weight gain and impaired tissue repair compared with their WT littermates or Kit(W-sh) mice reconstituted with bone marrow-derived MCs. MCs were localized in areas of mucosal healing rather than damaged areas where they degraded IL33, an alarmin released by epithelial cells during tissue damage. Kit(W-sh) mice reconstituted with MC deficient for mouse mast cell protease 4 did not restore normal mucosal healing or reduce efficiently inflammation after DSS withdrawal. In contrast with MCs recruited during inflammation-associated wound healing, MCs adjacent to transformed epithelial cells acquired a protumorigenic profile. In AOM- and DSS-treated WT mice, high MC density correlated with high-grade carcinomas. In similarly treated Kit(W-sh) mice, tumors were less extended and displayed lower histologic grade. Our results indicate that the interaction of MCs with epithelial cells is dependent on the inflammatory stage, and on the activation of the tissue repair program. Selective targeting of MCs for prevention or treatment of inflammation-associated colon cancer should be timely pondered to allow tissue repair at premalignant stages or to reduce aggressiveness at the tumor stage.
Smoldering multiple myeloma requiring treatment: time for a new definition?
Authors: Angela Dispenzieri, A. Keith Stewart, Asher Chanan-Khan, S. Vincent Rajkumar, Robert A. Kyle, Rafael Fonseca, Prashant Kapoor, P. Leif Bergsagel, Arleigh McCurdy, Morie A. Gertz, Martha Q. Lacy, John A. Lust, Stephen J. Russell, Steven R. Zeldenrust, Craig Reeder, Vivek Roy, Francis Buadi, David Dingli, Suzanne R. Hayman, Nelson Leung, Yi Lin, Joseph Mikhael, Shaji K. Kumar
Journal: Blood (2013)
SCLEROSING PERITONITIS AND PRACTOLOL
Authors: A Hensen, P.E.R Rhemrev, J.TH.L Oeberius Kapteyn, G.H Dunstone, F.A Ive, R.K Mallya, M.D.R Morris, M Minton, A Newland, G Knowles, A Turnbull
Journal: The Lancet (1975)
Identification and characterization of the rabbit angiotensin II myocardial receptor.
Authors: K M Baker, C P Campanile, G J Trachte, M J Peach
Journal: Circulation Research (1984)

The octapeptide, angiotensin II, elicits a positive inotropic response in myocardial tissue by activating slow calcium channels. Pharmacological studies suggest that the inotropic action of angiotensin II is receptor mediated. The current investigation was performed to characterize the binding of 125I-angiotensin II to the putative receptor in a plasma membrane-sarcoplasmic reticulum preparation of the rabbit left ventricle. In experiments performed at 18 degrees C, steady state binding occurred at 45 minutes and saturable binding was 80-85% of the total binding. Analysis of the binding data indicated that the 125I-angiotensin II interacted with a single class of sites with a Kd = 4.5 +/- 0.8 nM and exhibited a binding capacity of 53.5 +/- 8 fmol/mg protein. The potency order for the competitive binding of analogues and antagonists of angiotensin II paralleled that observed for in vitro contractile force development in bioassay systems utilizing left atrial tissue. The binding of 125I-angiotensin II was stimulated 2-fold in the presence of the divalent cations of calcium and magnesium (10 mM). Guanine nucleotides modified the binding of 125I-angiotensin II to the rabbit myocardial particulate fraction. Guanine triphosphate and nonhydrolyzable analogues of guanine triphosphate increased the dissociation rate of the bound 125I-angiotensin II and decreased hormone binding to the receptor at equilibrium. In the absence of magnesium, guanine nucleotides had no effect on the dissociation rate of 125I-angiotensin II. 125I-Angiotensin II binding to a rabbit myocardial particulate fraction was found to have high affinity, to be saturable, reversible, specific, and modulated by guanine nucleotides.(ABSTRACT TRUNCATED AT 250 WORDS)
Triglyceride-rich lipoproteins prevent septic death in rats.
Authors: T E Read, C Grunfeld, Z L Kumwenda, M C Calhoun, J P Kane, K R Feingold, J H Rapp
Journal: The Journal of Experimental Medicine (1995)

Triglyceride-rich lipoproteins bind and inactive bacterial endotoxin in vitro and prevent death when given before a lethal dose of endotoxin in animals. However, lipoproteins have not yet been demonstrated to improve survival in polymicrobial gram-negative sepsis. We therefore tested the ability of triglyceride-rich lipoproteins to prevent death after cecal ligation and puncture (CLP) in rats. Animals were given bolus infusions of either chylomicrons (1 g triglyceride/kg per 4 h) or an equal volume of saline for 28 h after CLP. Chylomicron infusions significantly improved survival (measured at 96 h) compared with saline controls (80 vs 27%, P &amp;lt; or = 0.03). Chylomicron infusions also reduced serum levels of endotoxin, measured 90 min (26 +/- 3 vs 136 +/- 51 pg/ml, mean +/- SEM, P &amp;lt; or = 0.03) and 6 h (121 +/- 54 vs 1,026 +/- 459 pg/ml, P &amp;lt; or = 0.05) after CLP. The reduction in serum endotoxin correlated with a reduction in serum tumor necrosis factor, measured 6 h after CLP (0 +/- 0 vs 58 +/- 24 pg/ml, P &amp;lt; or = 0.03), suggesting that chylomicrons improve survival in this model by limiting macrophage exposure to endotoxin and thereby reducing secretion of inflammatory cytokines. Infusions of a synthetic triglyceride-rich lipid emulsion (Intralipid; KabiVitrum, Inc., Alameda, CA) (1 g triglyceride/kg) also significantly improved survival compared with saline controls (71 vs 27%, P &amp;lt; or = 0.03). These data demonstrate that triglyceride-rich lipoproteins can protect animals from lethal polymicrobial gram-negative sepsis.
The ERK MAP kinase-PEA3/ETV4-MMP-1 axis is operative in oesophageal adenocarcinoma
Authors: Richard Keld, Baoqiang Guo, Paul Downey, Christian Gulmann, Yeng S Ang, Andrew D Sharrocks
Journal: Molecular Cancer (2010)

Abstract Background Many members of the ETS-domain transcription factor family are important drivers of tumourigenesis. In this context, their activation by Ras-ERK pathway signaling is particularly relevant to the tumourigenic properties of many ETS-domain transcription factors. The PEA3 subfamily of ETS-domain transcription factors have been implicated in tumour metastasis in several different cancers. Results Here, we have studied the expression of the PEA3 subfamily members PEA3/ETV4 and ER81/ETV1 in oesophageal adenocarcinomas and determined their role in oesophageal adenocarcinoma cell function. PEA3 plays an important role in controlling both the proliferation and invasive properties of OE33 oesophageal adenocarcinoma cells. A key target gene is MMP-1 . The ERK MAP kinase pathway activates PEA3 subfamily members and also plays a role in these PEA3 controlled events, establishing the ERK-PEA3-MMP-1 axis as important in OE33 cells. PEA3 subfamily members are upregulated in human adenocarcinomas and expression correlates with MMP-1 expression and late stage metastatic disease. Enhanced ERK signaling is also more prevalent in late stage oesophageal adenocarcinomas. Conclusions This study shows that the ERK-PEA3-MMP-1 axis is upregulated in oesophageal adenocarcinoma cells and is a potentially important driver of the metastatic progression of oesophageal adenocarcinomas.
Incidence and Prevalence of Idiopathic Pulmonary Fibrosis
Authors: Ganesh Raghu, Derek Weycker, John Edelsberg, Williamson Z. Bradford, Gerry Oster
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Idiopathic pulmonary fibrosis is a chronic interstitial lung disease of unknown etiology; its epidemiology in the United States has not been well characterized.To estimate the annual incidence and prevalence of idiopathic pulmonary fibrosis in the United States.Retrospective cohort design utilizing a large health care claims database spanning the period January 1996 through December 2000.Persons with idiopathic pulmonary fibrosis were identified based on diagnosis and procedure codes. Using broad case-finding criteria, prevalence was estimated to range from 4.0 per 100,000 persons aged 18 to 34 yr to 227.2 per 100,000 among those 75 yr or older; annual incidence was estimated to range from 1.2 to 76.4 per 100,000. Using narrow case-finding criteria, prevalence ranged from 0.8 to 64.7 per 100,000 persons; comparable figures for incidence were 0.4 to 27.1 per 100,000 persons. Extrapolating these rates to the overall United States' population, prevalence was estimated to be 42.7 per 100,000 (incidence, 16.3 per 100,000) using broad criteria; with narrow criteria, prevalence was estimated to be 14.0 per 100,000 (incidence, 6.8 per 100,000).Our results suggest that idiopathic pulmonary fibrosis is probably more common in the United States than previously reported.
Abstract B39: Activated B cells infiltrate lung cancer.
Authors: Tullia C. Bruno, Jeffrey Kern, Jill E. Slansky
Journal: Cancer Research (2013)

Abstract Lung cancer is the leading cause of cancer death in men and women, both in the United States and the world. The current 5-year survival rate for lung cancer in the United States is 16%, which can be attributed to the fact that the majority of lung cancer subjects present with late-stage disease that is not curable by current therapies i.e. chemotherapy and radiation. However, in the last several years, novel therapies have emerged to make lung cancer therapy better tolerated and more effective. We are particularly interested in developing an immunotherapy that will help to engage the immune system in targeting and destroying tumor cells. In a comprehensive survey of the immune infiltrate in non-small cell lung cancer (NSCLC) patients, we found that the frequency and total numbers of B cells (TIL-Bs) in the tumor versus the tumor-adjacent tissue was increased in comparison to other immune subsets, specifically, CD4, CD8, and regulatory T cells as well as NK and NKT cells. Further, these TIL-Bs were activated (CD21lo and CD69+), proliferated, and acquired a memory phenotype (CD27+). To test the function of the TIL-Bs, we are determining the types of cytokines they produce, their ability to secrete total IgG, and their potential to present antigen to CD4 T cells. Preliminary studies indicate that these cells generate activation cytokines (IFN-γ and IL-12) rather than suppressive cytokines, which suggests that the TIL-Bs have an effector phenotype that could aid in targeting the tumor. In addition, we are exploring why the TIL-Bs migrate to the site of the tumor. Preliminary data suggest that the common B cell chemokine receptors (CXCR3, CXCR4, CXCR5, CXCR7) are not elevated in TIL-Bs in the tumor compared to tumor adjacent tissue. However, normal peripheral blood B cells migrate toward tumor cell supernatant compared to tumor adjacent cell supernatant, which leads to the hypothesis that the tumor microenvironment generates more chemokines that attract TIL-Bs to the site of the tumor. Ultimately, we aim to identify a novel target for an immunotherapy clinical trial in lung cancer patients. Citation Format: Tullia C. Bruno, Jeffrey Kern, Jill E. Slansky. Activated B cells infiltrate lung cancer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B39.
Changes in bone sodium and carbonate in metabolic acidosis and alkalosis in the dog
Authors: James M. Burnell
Journal: Journal of Clinical Investigation (1971)

Metabolic acidosis and alkalosis were produced in adult dogs over 5- to 10-day periods. Midtibial cortical bone was analyzed for calcium, sodium, phosphorus, and carbonate. In acidosis bone CO(3)/Ca decreased 9.5% and bone Na/Ca decreased 6.3%. In alkalosis bone CO(3)/Ca increased 3.1% and bone Na/Ca increased 3.0%. Previous attempts to account for changes in net acid balance by summation of extra- and intracellular acid-base changes have uniformly resulted in about 40-60% of acid gained or lost being "unaccounted for." If it is assumed that changes in tibial cortex reflect changes in the entire skeletal system, changes in bone CO(3) (=) are sufficiently large to account for the "unaccounted for" acid change without postulating changes in cellular metabolic acid production.
Lack of Association Between Pertussis Vaccination and Symptoms of Asthma and Allergy
Authors: L. Nilsson, N.-I. M. Kjellman, J. Storsaeter, P. Olin
Journal: JAMA (1996)

<h3>To the Editor.</h3> —Previous reports<sup>1</sup>suggesting that pertussis vaccination considerably increases the risk for bronchial asthma in schoolchildren prompted us to add a structured interview to all the families in a double-blind study of per tussis vaccines to assess whether pertussis vaccination might influence symptoms in early childhood consistent with later development of allergic disease. Pertussis immunization elicits an IgE response in animals.<sup>2</sup>Children may also show pertussis IgE after pertussis infection and vaccination, but clinical consequences are unclear.<sup>3</sup>Retrospective data support a weak effect of pertussis infection on development of sensitization.<sup>4</sup> Since 1979, pertussis vaccination has not been included in the Swedish vaccine program. The Swedish Pertussis Vaccine Efficacy Trial 1<sup>5</sup>recruited 9829 infants born in 1992. The study was approved by the Human Research Ethics Committee of Karolinska Institute, Stockholm, Sweden. The study was performed double-blind, and three fourths of the infants were